Professional Documents
Culture Documents
0hemist
Patt I
Sections I-IV
Section I
Section II
Structure Elucidation
Section III
Stereochemistry
$ection IV
Hydrocarbon Reactions
'll'te
K.lE. V. I. E. W
Speci alizing in II{CAT Preparation
@
Nomenclature
a)
b)
IUPAC Nomenclature
General Nomenclature
Section I
Structure,
tsonding,
and
Reactivity
"</
/V"
by Todd Bennett
HH
C-C.
HH
HH
7ffiV"
HH
f)
g)
i.
ii.
iii.
Single Bonds
Double Bonds
Triple Bonds
Molecular Structures
Octet Rule (HONC Shortcut)
Charged Structures
Hybridization
a)
b)
i.
ii'
iii'
Bond Energy
c)
Steric Hindrance
d) Aromaticity
Fundamental Reactivity
i.
ii.
iii.
Primary Effects
Secondary Effects
Values and Terminology
Electrophiles and Nucleophiles
Physical Properties
a) l-lydrogen-Bonding
b) Polarity
c) Van der Waals Forces
d) Solubility and Miscibility
RNKIIELEY
l)n.n-v.r)E.w'
Organic Chemistry
Molecular Structure
Introduction
The perfect place to start any review of organic chemistry is the basics of
molecular structure, which traditionally include bonding, hybridization, and
electronic distribution. We shall consider a chemical bond to be the result of
atomic orbitals overlapping to form molecular orbitais. We shall consider all
bonds involving carbon to be covalent in nature. A covalent bond is thought to
involve the sharing of electrons between two adjacent nuclei. According to the
rules of electrostatics, the region between two nuclei offers a highly favorable
environment for electrons, where they can be shared by neighboring atoms.
However, there are several other factors to consider in bonding. if bonding were
purely a matter of electrostatics, then all of the eiectrons would be found between
two neighboring nuclei, not just the bonding electrons. The sharing of electrons
may be either symmetric (when the two atoms of the bond are of equal
electronegativity) or asymmetric (when the two atoms of the bond are of unequal
electronegativity). Sharing of electrons occurs when the atoms of a bond lack a
compiete valence electron shell. By sharing electrons, each atom moves closer to
completing its shell This is the driving force behind the formation of stable
covalent bonds.
Organic Chemistry
Molecular Structure
Nomenclature
Prefix
Carbons
Prefix
Carbons
Prefix
meth-
pent-
non-
eth-
hex-
10
dec-
prop-
hept-
11
undec-
but-
oct-
12
dodec-
Table 1-1
Functionality
Compound Name
R-CH3
Alkane
R-O-R
Ether
Aldehyde
R-CO-H
Bonding
C-C
&
C-H
C-O-C
o
il
C-C-
R-CH2-OH
Alcohol
C-O-H
R-CO-R
Ketone
o
il
C_C-C
R-CO-OH
Carboxylic acid
o
il
C_C_
OH
Table 1-2
Formula
IUPAC Name
Structural Class
H3CCH2CH2CH3
Butane
Alkane
H3CCH=CHCH3
Butene
Alkene
H3CCH2CH2CHO
Butanal
Aldehyde
H3CCH2COCH3
Butanone
Ketone
H3CCH2CH2CH2OH
Butanol
Alcohol
H3CCH2CH(oH)CH3
2-butanol
Alcohol
H3CCH2CH2CH2NH2
Butanamine
Amine
H3CCH2CH2CO2H
Butanoic acid
Carboxylic acid
Table 1-3
Copyright
.ffi
:.,
fr
::r'ii'*lllil+iji*i:il$i:
:::l':: .:.
::ri:::;ni:iiliiii:ri:*iiiliffii
Organic Chemistry
Molecular Structure
Nomenclature
Figure 1-1 shows examples of IUPAC nomenclature for four organic compounds
with variable functional groups:
C1
4-chloro-S-methyl-3-heptanol
Longest chain: 7 carbons
3-methylpentanoic acid
Longest chain: 5 carbons
Carboxylic acid group
Alcohol group
Chloro substituent at C-4
Methyl substituent at C-5
3,3-dibromobutanal
3-ethylcyclopentanone
Ring of 5 carbons
Ketone group
Ethyl substituent at C-3
Aldehyde group
2 Bromo substituents at C-3
Figure 1-1
General Nomenclature (Common Naming Based on Substitution)
H CH.
HCH"HH
carbon \r)yn"t
r"'r,iu.y
carbon
.s
\
l}}i""oary
r_zt{
./'\ oH
./-\
-/-\ Cl
HgC
CHg H3CH2C
carbon
H3CH2C
Isobutane
(2-Methylpropane)
Sec-butanol
(2-Butanol)
n-Propyl chloride
(1-Chlropropane)
Figure 1-2
Nomenclature is an area of organic chemistry best learned through practice and
experience. We will deal with nomenclature throughout the course, as we
introduce each new functional group. Understanding nomenclature is especially
important in MCAT passages where names rather than structures are given. Be
sure to know the Greek prefixes for carbon chain lengths up to twelve carbons.
Copyright
Organic Chemistry
Molecular Structure
Example 1.1
V\4rat is the Lewis dot structure for HcBF?
A.
B.
:H-B-F:
t"
u
C.
H- S-'F
t"
.ry
D.
H-ri-r:
H- B-F
t"
t"
Solution
Boron has only three valence electrons, hence it can make only three bonds.
There is no lone pair on the boron atom, eliminating choices A and C. Hydrogen
has only one electron, which is in the bond to boron, so there is never a lone pair
on a bonded hydrogen. This eliminates choices A (already eliminated) and B.
Fluorine has a completed octet, so it makes one bond and has three lone pairs, as
depicted in choice D, the best answer.
Bonding Model
Bonding is defined as the sharing of electron pairs between two atoms in either
an equal or unequal manner. As a general rule, a bond is the sharing of two
electrons between two adjacent nuclei. The region between two nuclei is the
most probable location for an electron. In most cases, with the exception ol ligand
bonds (kaown also as Leruis ttcid-base bonds), one electron from each atom goes into
forming the bond. When electrons are shared evenly between two atoms, the
bond is said to be a coualent bond. Ylh,en electrons are transferred from one atom
to another, the bond is said to be an ionic bond. The difference between a covalent
and ionic bond is measured in the degree of sharing of the electrons, which can
be determined from the dipole. The more evenly that the electrons are shared,
the less the polarity of the bond. The relative electronegativity of two atoms can
be determined by measuring the dipole of tl-re bond they form. When the
difference in electronegativity between two atoms is less than 1.5, then the bond
is said to be covalent. When the difference in electronegativity between two
atoms is greater than 2.0, then the bond is said to be ionic. When the difference
in electronegativity between two atoms is greater than 1.5 but less than 2.0, then
the bond is said to be polar-covalent (or partially ionic).
:-,'
E.
l"t
Organic Chemistry
Molecular Structure
Example L.2
A. C-O
B. N-F
C. Li-H
D. Li-F
Solution
A bond is ionic when the difference in electronegativity between the two atoms
exceeds 2.0. This means that the bond that is most likely to be ionic is the one
between the two atoms with the greatest difference in electronegativity. Lithium
is a metal and fluorine is a halide, so they exhibit the greatest electronegativity
difference of the choices listed. The best answer is therefore choice D.
Covalent Bonds
Bonds can be classified in one of three ways: ionic, polar-covalent, and covalent.
A covalent bond occurs when electrons are shared between two atoms having
Iittle to no difference in electronegativity. As the difference in electronegativity
decreases, the covalent nature of the bond increases. There are two types of
:ovalent bonds: sigma bonds (o), defined as having electron density shared
betvr'een the nuclei of the two atoms; and pi bonds (n), defined as having no
electron density shared between the nuclei of the two atoms, but instead only
above and below the internuclear region. Sigma bonds are made from many
types of atomic orbitals (including hybrids), while pi bonds are made exclusively
of parallel p-orbitals. In almost all cases, the sigma bond is stronger than the pi
bond, with molecular fluorine (F2) being a notable exception. Figure 1-3 shows a
generic sigma bond. You may notice that within a sigma bond, only about eighty
to ninety percent of the electron density lies between the nuclei, not all of it.
.Nuclei.
o@o
Electron density
Figure L-3
Example 1.3
Solution
A sigma bond has its electron density between the two nuclei, which eliminates
choice D. The two atoms in the bond are identical, so the electron density should
be symmetrically displaced between the two nuclei. This eliminates choice B.
Most of electron density is between the nuclei, so choice A is a better answer than
choice C. These drawings are ugly, so focus on the concept, not the pictures.
Copyright
Organic Chemistry
Molecular Structure
Figure 1-4 shows a generic n-bond. Within a n-bond, there is no electron density
between the two nuclei. The electron density in a ru-bond results from electrons
being shared between the adjacent lobes of parallel p-orbitals.
Nuclei
Electron Densitv
J
Figure 1-4
In organic chemistry, covalent bonds are viewed. in great detail, taking into
or-rp3
orp2-rp2
osp3_sp3
Figure 1-5
Figure 1-5 confirms that most of the electron density lies between the two nuclei
in sigma bonds, no matter what the orbitals are from which the sigma bond
originates. In pi bonds, electron density does not 1ie between the two nlclei. The
length of a bond is defined as the distance between the nuclei of the two atoms
making the bond. Figure 1-6 shows an example of a n-bond between two Zprorbitals, which is typical for nearly all n-bonds encountered in organic chemistry,
because carbon, nitrogen, and oxygen have 2p-orbitals in their valence shells.
2p,-2p,
ffi
eo
Figure 1-6
Copyright
Organic Chemistry
Molecular Structure
Pi bonds are found as the second bond present in double bonds and the second
and third bonds present in triple bonds. The first type of bond to form between
atoms is usually the sigma bond. Once a sigma bond exists between two carbon
atoms, then pi bonds can form between the atoms. Fluorine gas is an exception
to the "sigma bond first" rule. Molecular fluorine (F2) has only one rc-bond, with
no o-bond present. This is attributed to the small size of fluorine and the internuclear repulsion associated with a typical single bond. This is why the bond
dissociation energy of F2 is less than the bond dissociation energy of Cl2, even
Molecular Orbitals
Molecular orbital is a fancy way of describing a bond or anti-bond that exists
between two atoms. An anti-bond is a molecular orbital that results in bondbreaking when coupled with a bonding orbital. It is important to recognize the
shape and location of electron density in molecular orbitals. Figure 1-7 shows the
common bonding and anti-bonding orbitals associated with organic chemistry.
.@.@o + cffi'c
sp
orp3-rp3
sp3
+
D@c@
D*.c@
,3
-3
'
sp"
,
sp"
.-3 .-i
oxsp--sp-
I I
p
frzp-zp
fB n tr=
r ffic
5+6
P
P
d6
lt*rr-r,
Figure 1-7
The shading of the lobes in each orbital represents the direction of spin for the
electron. h:r order for electron density to overlap, the electrons must have the
same spin. This is analogous to driving on the freeway. If you join a freeway in
the same direction as traffic is flowing, you can easily blend into traffic. This is a
favorable interaction. If you join a freeway in the opposite direction as traffic is
flowing, you cannot easily blend into traffic. This is an unfavorable interaction.
Organic Chemistry
Molecular Structure
l\lolecular Bonds
of
greater interest than the sigma-bonds and pi-bonds are the single, double, and
triple bonds present between atoms. single, double, and triple bond nature is
discussed more so than the sigma and pi nature of bonds. In trganic molecules,
there are only single, double, and triple bonds. Between like atoms, the
descending order of relative strengths of boncls is triple bond > double bond >
single bond. Another rule to consider is that for bonds between like atoms, the
ionger the bond, the less the electron density overlaps between nuclei, and thus
the weaker the bond. This is summarized as: longer ionds are rueaker bonds.
single Bonds: single bonds are composed of only one sigma bond between the
two atoms. single bonds are longer than double and triple bonds between two
atoms, even though fewe_r electrons are present. Ethane has sigma bonds only
and is shown in Figure 1-8 in both stick figures and with the rele')ant orbitals.
HH
/v"
C-C.
OC
ffi"p
orp3-5p3
HH
\"
Figure 1-8
Double Bonds: Double bonds are composed of one sigma bond and one pi bond
between two adjacent atoms. Ethene (czH+) has f6ur sigma bonds between
carbon and hydrogen, a sigma bond between the two carf,ons, and a pi bond
present between the two carbons to compiete the carbon-carbon double bond.
Ethene is shown in Figure 1-9 in both stick figures and with the relevant orbitals.
ftp^-p^
Illtt,,,
H7:
..rr\H
\n
osp2-roz
%o="#
@rffi%
Figure 1-9
Triple Bonds: Tripie bonds are composed of a sigma bond. and two pi bonds
between two adjacent atoms. Triple bonds are shorter than either iingte or
double bonds. Ethyne (CzHz) has two sigma bonds between carbon and
hydrogen, a sigma bond between the two carbons, and two pi bonds between the
two carbons to complete the carbon-carbon triple bond. Ethyne is shown in
Figure 1-10 in both stick figures and with the relevant orbitals.
fipv-pv
@.- .P
Figure 1-10
lo
Organic Chemistry
Molecular Structure
Example 1.4
\A/hat is the relative bond strength of carbon-carbon bonds in the molecule shown
below?
,rr..
bondaS\
bond c
_-_*/
ooloo
l, /
C*C
,r,
H
-\ ^CH^CH"
z r
.v
(H3.)2HC
""Y T
CHe
bond d
Solution
There strongest C-C bond is a double bond, bond b, so choices A and C are
-Bond
eliminated.
d is the weakest, because it is between two sp3 carbons. Bond
c is stronger than bond a, despite both sharing an sp2 and an sp3 carbon, because
bond c contains the more highly substituted carbon. Choice D is the best answer.
Molecular Structures
We shall continue from the fundamental concept that a valence electron can be
shared between two nuclei rather than being isolated to just one nucleus, because
the attractive force of two positive sites is greater than the attractive force of one.
This is the basic, perhaps oversimplified, perspective of a chemical bond. The
sharing of electrons is what characterizes a covalent bond. One of the first rules
of organic chemistry that you must understand is the octet rule. It is valid for
carbon, nitrogen, and oxygen atoms. To understand organic chemistry, it is
important that you recall VSEPR theory, which applies to bonding (in particular,
to the subgroups of covalent bonding like single, double, and triple bonds and
their component o-bonds and n-bonds). Table 1-4 shows the skeletal structures
of molecules that contain carbon, nitrogen, oxygen, and hydrogen.
Atom
Carbon (C)
Valence
Electrons
To Complete
Shell
.c.
4 e- needed
4.
Nitrogen (N)
Oxygen (O)
-tY'
3 e- needed
- .ct.
2 e- needed
1H.
1 e- needed
1H-
..
-L_
'";
- -''Y',
-N' \
.N.
5.
b
Hydrogen (H)
_-6-_
i5:
:O.
Table 1-4
Copyright
ll
Organic Chemistry
Molecular Structure
tt
H
\//
/tnt
L-L
-.
{j
:,:
::
::.
-a
r-
'-'
)-l
,CHZ
^-A
L-L
/\
HH
/\
HH
Good Structure
Bad Structure
HsC- C- CAll
C:
CH2CH2CH3
/CH3
H"C-C:
cH2cH3
Bad Strttctttre
Dn
:-..!i
tl__
:_
'\H
tra,
CH"
/-"3
1\-L
CHs
:_r
N-C
CHs
A11
Good Structure
Bad Structure
Figure 1-11
You can validate molecular structures by seeing whether they satisfy bonding
rules (HoNC-7234) and conventions with regard to the number of bonds and
lone pairs. If a structure does not satisfy the rules, then there must be a charge
present. Generally, having too many bonds in a molecule results in a cation and
too few bonds results in an anion, except with carbon. For instance, if oxygen
makes three bonds and has one lone pair, it carries a positive charge. wnu.t
nitrogen makes two bonds and has two lone pairs, it carries a negative charge.
\Alhen carbon makes three bonds, the charge depends on the presence or absence
of a lone pair (presence yields an anion, r,t'hile absence yields a cation).
Copyright
t2
_
_
-i!
Organic Chemistry
Molecular Structure
Charged Structures
Formal charges (charged sites on a molecule) occur when there is an excess, or
shortage of electrons on an atom. For instance, an oxygen atom typically has six
valence electrons and wishes to have eight. This means that oxygen makes two
bonds to complete its valence shell (and thus satisfy the octet rule). However, if
an oxygen atom had only five valence electrons, it would be short one electron
from its original six and would consequently carry a positive charge. Having
only five valence electrons, the positively charged oxygen would need to make
three bonds (one more than its standard two) to complete its octet. We can
conclude that oxygen with three bonds carries a positive charge. Table 1-5 shows
somecommon organic ions to commit to memory:
to Neutral Atom
3l
Carbon (C)
.c.
-/t\
Nitrogen (N)
? ..
-+
-'Y',-\
/--
r+-
Oxygen (O)
.o.
'-ij\,:t
1--
z\':N\-5+=
'N'
Anionic Atom
t'
Number of Bonds to
Number of Bonds to
Cationic Atom
Number of Bonds
-t-
:o*=
-p]'
Table 1-5
Molecular and
Structural Formula
c2H60
cH3cH2oH
3D Structure
Lewis Structure
HH
ll
H_C_C- Otl
HH
.C_C
\t\
H.;
HHH
c2H7N
cH3NHCH3
rtl
H_ C-N_ C_ H
t..l
HH
ll
H-C-C:
t..
II
^- rr
.v
"irH
:
N'
C_
.(
)Y
HtH
.C_H
HH
c2H50*
cH3cHo+H
liu
\it
.C-C
\\
O*- H
"'*
.g*-H
Figure 1-12
Copyright
l5
Organic Chemistry
Molecular Structure
Ilybridization
Hybridization
Hybridization of Atomic Orbitals
Hybridization entaiis relocating electron density in atomic orbitals prior to
bonding, in order to minimize the repulsion between electron pairs and thereby
allow for bonding between atoms. There are three main types bi nyuria orbitals
to consider: sp,sp2, and sp3 hybrids. Hybrid orbitals are atomic orbitals that are
involved in making bonds between atoms. Listed in Table 1-6 are some pertinent
facts and structural features for each of the three types of hybridization. lable 1-6
:r
represents general trends that are observed in neariy all molecules with
hybridized orbitals involved in their molecular orbitals.
Hybrid
sp
sp2
sp3
Atomic Orbitals
s+p
s+p+p
s+P+p+p
Angle
180'
720"
109.5'
Shape
linear
trigonal pianar
tetrahedral
r-bonds
i!
Table 1-6
The number of n-bonds in Table 1-6 is for typicai molecules that obey the octet
class of molecules that is an exception to the features in Table 1-6 is the
boranes, such as BH3, BF3, and BR3. In boranes, the boron atom has only three
valence electrons, so a neutral boron cannot satisfy the octet rule. The result is
that boron has sp2-hybridization for its three sigma bonds, but no pi bond.
rule' A
s,4
j-
,H
-hybrid,ized
S...'n,
BH: H-p-1
sp'-hybridized
cH+
0-n
H-- \,,,*-,
sp3-hybridized
NHe
,H
r-Ut'un
sp'-hybridized
Hzo
ql
"t
t4
*i
Figure 1-13
Organic Chemistry
Molecular Structure
Hybridization
The orbital shown for BH3 in Figure 1-13 is actually an empty p-orbital, while the
other orbitals depicted in Figure 1-13 are hybrid orbitals. The p2-orbital of BH3 is
devoid of electrons, so the hybridization is sp2. \Mhile an empty p-orbital does
not actually exist, we consider the region where an electron pair could be
accepted. The three hybrid orbitals are detailed in Figures I-1.4,1.-75, and 1-16.
.&.o,
Hybridizes
to become
@&r.@
Figure 1-14
sp2-hybrtdtzation is the result of the mixing of the s-orbital,
the pa-orbital, and the py orbital.
st'ayarialzation:
Py
s^
.CJ@.O r)
o..
Hybridizes
Three atomic orbitals
to become
Figure 1-15
sp3-hybtidi"ation is the result of the mixing of the s-orbital,
the pa-orbital, the py-orbital, and the p2-orbital.
tt'-nyAnalzation:
i'rery.
ffi'I'^^,
+@trb.e
,o3
sp3
Hybridizes
Four atomic orbitals
tobecome ,or.m
Figure L-16
Example 1.5
What is the hybridization of each carbon in propene (H2C=CH-CH3)?
There are three carbons in propene. The first two carbons are involved in a rcbond, so they are each sp2-ltybridized. This makes the best answer choice C. The
last carbon is not involved in any n-bonds, so it has sp3-hybridization.
Copyright
Organic Chemistry
Molecular Structure
Hybridization
used to explain bond lengths and bond angles. Figures r-r7,1.-rg, and 1-19 show
structures with their corresponding geometry and structural features.
Tetrahedral and
sp3
-nybridization
A central atom with four electron pairs (any combination of bonds and lone
pairs) has tetrahedral orientation of the electron pairs about the central atom.
This does not mean that the shape is tetrahedral, but that the orientation of
electron pairs about the central atom (geometry) is tetrahedral. Figure 1-17
shows different structures with tetrahedral geometry about the central itom, but
different molecular shapes.
Tetrahedral
Structure
l-/-
t-t-'Y.tt
-Hlu
H
4
atoms/0lone
------^..
------*
..
H/NY,H
H/NY'H
pairs
I
I
lengths
are equal./
I
C-H: 1.10A & < HCH: 109.5" /
-symmetry, all bond
and bond angles
Because of
N-H:
l
I Bent Structure
\\
\r'n'
rr
1o-ru
2 atoms/21one pairs
Because
104.5'
Figure 1-17
Trigonal Planar an d sp2 -Hybridization
A central atom with three other atoms, two olher atoms and one lone pair, or one
-of
other atom and two lone pairs attached has trigonal p?ur,ut geometry
th" th.""
substituents (or electron pairs) about the central atom. This does not mean that
the shape is trigonal planar, but that the orientation of electron pairs about the
central atom is trigonal planar. Figure 1-18 shows the planar structure and
spatial representation of the bonds in ethene. The stick and ball representation
shows the three-dimensional perspective for ethene.
C-opyright
l6
Organic Chemistry
Molecular Structure
Ilybridization
Spatial Representation
Planar Structure
sn2-hvbridization
\i \ /
H'/\'
t,-
/\
HH
3
Figure L-18
Line ar and sp-Hybridiz
ation
A central atom with two other atoms or one other atom and
attached has linear geometry of the two substituents (or electron pairs) about the
central atom, This does not mean that the shape is linear (although in most cases
it is), but that the orientation about the central atom is linear. Figure 1-19 shows
the linear structure and spatial representation of the bonds in ethyne. The stick
and ball representation shows the three-dimensional perspective for ethyne'
Linear Structure
Spatial Representation
sr-hvbridization
' tt'
/\
180.0"
k\,
t\
C::
2 atoms/0lone pairs
Each carbon in ethyne
has sp-hybridization.
Figure L-19
Example 1.6
A. 108.3'
B. 771.7"
c. 118.5'
D.
121.5'
Solution
oxygen/ the electron density repels the electrons in the two carbon-hydrogen
bonds. This forces the two bonds closer together, which compresses the
hydrogen-carbon-hydrogen bond angle. According to valence shell electron pair
repulsion (vsEPR) theory, the angle shouid be slightly less than 120". The best
answer is thus choice C.
_:
Copyright
t7
Organic Chemistry
llolecular Structure
Bond Energies
Bond Energy
Bond Dissociation Energy
chemistry, the energy required to cleave a bond in a homolytic fashion
is commonly used to compare reiative bond strengths. Homolytic cleivage refers
to the breaking of a chemicai bond into two fiee radical fiagments. This is
typically viewed in the gas phase or an aprotic, nonpolar solvenl, where ions are
too unstable to exist. It is important that you recall that energy is released when
a bond is formed and that energy must be absorbed by the ilolecule to break a
bond. By subtracting the energy released upon forming new bonds from the
energy required to break bonds, the enthaipy of a reaction can be determined.
This is shown in Equation 1.1.
L:r organic
(1.1)
If
the enthalpy of a reaction is known, then the bond dissociation energies for
bonds that are formed and broken during the course of a reaction can be
determined. It is this method that allows for the comparison of bonds between
identical atoms within different morecules. For instance, the theory of
aromaticity is supported by the excess energy that is reieased. upon the formation
of a n-bond that completes the aromatic iing. The release of excess energy
implies that the molecule is more stable than expected from the standard bond
dissociation energies, so some other factor must be involved. Table I-T lists some
bond dissociation energies for typicat bonds in some common organic molecules.
Bond Dissociation Energies for
A-B
Bonds (Kcal/mole)
B=H
Me
Et
i-Pt
t-Bu
Ph
OH
NHz
Methyl
105
90
89
86
84
102
93
85
Ethyl
101
89
B8
6/
85
101
95
85
n-Propyl
101
89
88
86
85
101
95
85
Isopropyl
98
89
87
B5
82
99
96
B5
f-Butyl
96
87
95
82
77
99
96
B5
Phenyl
111
702
100
99
96
115
111
702
Benzyl
88
76
75
/+
73
90
81
77
Allyl
86
74
70
70
67
N/A
7B
69
Acetyl
86
81
79
77
75
93,5
107
96
Ethoxy
L04
83
85
N/A
N/A
101
44
Vinyl
1I2
102
101
100
95
105
N/A
N/A
N/A
704.2
105
i01
98
96
111
IT9
1.07
Table 1-7
A greater value in Table 1-7 implies that the bond is stronger. you may note that
the weakest bond listed in Tabie 1-7 is an o-o single bond within a peroxide
molecule (Eto-oH). Because this bond is so r.r'eak, peroxides are highly reactive
species, often used to oxidize other compounds. The data in Table 7-7 also reveal
that the substitution of the carbon and the position of the bond within the
molecule affect the bond energy. The effect of hybridization can also be extracted
when comparing bond energies betl-een r-inr.l and methyl substituents.
la
Organic Chemistry
Molecular Structure
Bond Energies
Example 1.7
1.-7,
7 q1q2
-4"%
c
p
t-^rt
- v t 1z -
andto=
"
0.2\
8.85
x rcjP -C*.
N.m2
The greater the charge on the ion, the stronger the bond; and the closer the ions
are to one another, the stronger the bond. Ionic bonds are typically stronger than
covalent bonds. However, because ions can be solvated in a polar, protic solvent,
ionic bonds are often cleaved more readily than covalent bonds in a protic
environment. In other words, despite the strength of ionic bonds, they are easily
broken by adding water to the ionic lattice. This implies that the Coulombic
attraction of the ions to water is comparable to the attraction of the ions to one
another.
Copyright
l9
Organic Chemistry
Molecular Structure
Intramolecular Features
Intramolecular Features
Intramolecular features encompass anything that affects the stability of a
molecule and the sharing of electron density beyond the localized region
between two neighboring, bonding atoms. There are various factors that dictate
the chemical reactivity of a compound and explain the distribution of electron
density within a molecule. I like to call them the "five excuses" to explain organic
chemistry. They are reslnence, the inductiae effect, steric interactions, aromnticity,
and hybridization. I/y'e have already examined hybridization and seen the effect it
has on the structure of a molecule in terms of bond angles. Besides considering
the three-dimensional position of the atoms within a molecule, we will consider
electron density and thus establish reactive sites within a molecule. We shall
|r
t
a
I
{':
fi
,!
#'
fr
2.
3a. if
3b. If the molecule contains a positive charge, it is best placed on the least
electronegative atom.
Figure 1-20 shows two resonance forms for an amide compound that obey the
octet rule, and a resonance hybrid that shows the composite effect. The
resonance hybrid is an average of all the major resonance contributors.
oo-
o6-
,rr.A*rr.,r.4.**r,
form
Less stable form
More stable
.&-
t:
,rr.A'r'?",
Resonance
hybrid
.$r-
Figure 1-20
The resonance structure farthest to the left in Figure 1-20 is more stable than the
middle structure, because there is no separation of charge. You must be able to
Copyright
20
St
or
fl
*
f,
*
m
q
fi
I
fti
Organic Chemistry
Molecular Structure
Intramolecular Features
Figure 1-21 shows four examples of resonance structures and the arrow pushing
necessary to convert between resonance forms. To draw resonance structures
that are stable, it is often helpful to start with a lone pair and push those electrons
into a n-bond. The electrons from the adjacent n-bond turn into a new lone pair.
roi
(ot
H
ll
l^<-+ \lltq.z ts
I -*
g,Qfl*],. -
nil,.
H,C/t'lv'L'l
:ij:o
I
to
-
\
I
r-
r"
HHH
Resonance
Hvbrid:
6-
/C1.6;2
HsC
f
Ct
s-
NH
..
ioi o
o6ti
6zt-'dl
aoy'c:.ooResonance Hybrid
t'
CH"
-*
",P'q8
t'
CH"
t"
3r.-t\.,,,
,.liz't'l3;,
Resonance Hybrid
CH"
Hrc?5l,',
CH"
t"
CH"
{-*
l"
CH"
t"
*rr3-c\c*r,
"lll"'13.,
Resonance Hybrid
Figure 1-21
In Examples 1",2, and 3, shown in Figure 7-2I, the negative charge moves every
other atom between resonance forms. The lone pair becomes a n-bond, and the
n-bond becomes a lone pair two atoms away. This is true when the number of
total charged sites remains constant. In Example 1, there is only one charged
atom in each of the resonance forms. You must look for the all-octet resonance
structures. A11 of the resonance forms except the carbocations in Example 4 are
all-octet resonance forms. This satisfies Rule 1 on the list of resonance rules.
Neither structure in Example 4 satisfies the octet rule. The resonance hybrid is a
composite of the individual resonance contributors. The most stable resonance
structures (major resonance contributors as they are called) have the greatest effect
on reactivity and structure for a compound exhibiting resonance.
Copyright
2t
Organic Chemistry
Molecular Structure
Intramolecular Features
Example L.8
The C-O bond length is LONGEST in the compound on the:
5-"
*
o
Solution
For this question, the resonance forms of the lactam should be drawn first:
$-"
Partially
single bond
6-
The all-octet resonance form on the right has the carbonyl bond in single bond
form. The single-bond resonance is caused by the donation of a lone pair of
electrons by nitrogen. This means that the C-O bond is longer in the compound
on the left, because nitrogen donates electrons through resonance. The correct
answer is thus choice A. The effect of resonance outweighs the inductive effect.
The inductive effect predicts that the nitrogen would be electron-withdrawing,
because it is more electronegative than carbon.
Inductive Effect
The inductive effect, as the name implies, induces charge separation in a
molecule, just as induction in physics refers to the creation of charged sites
through induction. From a chemist's perspective, the inductive effect is the
delocalization of electrons induced by electronegative atoms. The inductive
effect involves the transfer of electron density through the sigma bonds. A
highly electronegative atom pulls electron density from its neighbor, which in
turn pulls electron density from its neighbor. The effect dissipates over distance,
but it can affect bonds between atoms up to three or four atoms away. We most
often consider the inductive effect when a molecule has a halogen.
The inductive effect increases with the electronegativity of the atom. Fluorine is
the most electronegative atom found in organic molecules, so it pulls electrons
from the carbon to which it is attached in a strong manner. This makes that
carbon electron-poor, so it in turn pulls electrons from its neighbor. Ultimately,
as we see with polarity, the electron density in the molecule is pulled towards the
most electronegative atom in the compound. An electronegative atom therefore
withdraws electron density and thus can increase a compound's acidity, increase
its electrophilicity, decrease its basicity, or decrease its nucleophilicity.
Copyright
22
Organic Chemistry
Molecular Structure
Intramolecular Features
t.
t-.a*l*,
t.
t:a"*-rt
I
Z-roftate=L44
HH
FF
Trifluoromethylamine
Methylamine
Figurel-22
The withdrawal of electron density by the fluorine atoms decreases the
nucleophilicity of the amine compound by pulling electrons away from the
nitrogen atom. As electron density is removed, the compound becomes electronpoor and thus a worse electron donor. This can be verified by the reaction rate in
a substitution reaction. As the negative log of the rate increases, the rate of the
reaction decreases.
Example L.9
-{. H3CCHFNH2
B. FH2CCH2NH2
C. H3CCHCINHz
D.
CIHzCCH2NH2
Solution
The greatest reaction rate (the fastest reaction) is observed with the best
nucleophile. Each answer choice has one halogen, so all the choices have slower
rates than ethyl amine. The question asks which experiences the least inductive
"-cithdrawal. Chlorine is less electronegative than fluorine (Fonclbrisch), so
choices A and B are eliminated. The inductive effect diminishes with distance, so
tFre least electron withdrawal is observed with choice D. You must consider both
proximity and electronegativity when looking at the inductive effect.
-\lthough not applicable in Example !.9, you must also consider whether the
inductive effect involves electron donation or electron withdrawal. For instance,
methyl amine is more nucleophilic than ammonia (NHg), because the methyl
group is electron-donating. Varying the R-group changes the inductive effect. It
also changes the size of the molecule, so steric hindrance can affect the reaction.
For instance, trimethyl amine ((H3C)3N) is less nucleophilic than dimethyl amine
(H3C)2NH), because the electron donation by the additional methyl group does
not compensate for the increase in molecular size.
Copyright
23
Organic Chemistry
Molecular Structure
Intramolecular Features
Steric Hindrance
Steric hindrance occurs any time two atoms attempt to be in the same place at the
sarne time. It is repulsive in nature and increases as the atoms draw closer. No
one is certain about the nature of the force, but it is believed to be electron cloud
repulsion. The effects are similar to what is observed in general chemistry with
VSEPR (valence shell electron pair repulsion) theory, except that it is considered
only when two separate atoms or functional groups interact. Electrons move to
be as far apart as possible, so lone pairs and bonds spread out to accommodate
the geometry that spaces the greatest distance between electrons. Figure 1-23
demonstrates the effects of steric hindrance on a couple of organic molecules.
Because the alkene is planar, the substituents on the alkene carbons have a
tendency to collide with one another.
H.C
CHs
/
/
/\
t
\,"/L-L_ \
HsC
CHe
H.C
/\
L-
LJ
'""/
HsC
^-^
HHH
H"C
CH.
\.-./
\'
{
\/
\.
H"C
-\__/ CHN
/"t\
H_H H
Reduced bond angle in dimethylbutene,
because the methyl group hydrogens repel.
Figure 1-23
Example 1.10
A.
B. -OCH3
C. -OCH2CH2CH2CH1
D. -OCH(CH3)CH2CH3
-oC(CH3)3
Solution
On cyclohexane, substituents with axial orientation experience greater steric
hindrance than substituents with equatorial orientation. Because of steric
hindrance, the substituent most likely to assume the equatorial orientation is the
bulkiest. The tert-butoxide substituent, choice D, has the most crowded alkyl
groups/ resulting in the greatest steric hindrance. This makes the best answer
choice D.
Copyright
Organic Chemistry
Molecular Structure
Intramolecular Features
Aromaticity
Aromaticity is stability generated from having 4n + 2 ru electrons in a continuous,
overlapping ring of p-orbitals, where n is any integer including 0. This is known
as the Hilckel rule. The stability is rooted in the molecular orbital model, where
an energy level is completely filled when there are 4n + 2 n-electrons in the cyclic
n-network. Figure 1-24 lists experimental values for the enthalpy of
hydrogenation of a series of alkenes. The large deviation associated with
benzene is attributed to its aromatic stability.
o#o
o#o
o#o
o#* o
ktul/.ol.
AH = -2g
ktul/*ol"
AH = -56
AH = -54
LH =
-49
ktul/-n,"
ktul/r',or"
kcal/mole per n-bond. The third entry shows that conjugation results in
stability, reducing the amount of heat released upon hydrogenation, but only by
about 2 kcals/mole. Based on -28 kcal/mole for each n-bond, benzene should be
expected to have a AH of approximately -84 kcal/mole. The difference of 35
kcal/mole (84 - 49) cannot be attributed to conjugation alone, hence it is said to
be due to aromatic stability.
)'lot all cyclic, conjugated polyenes show such a large deviation from the
expected value for the enthalpy of reaction. 1,3,5,7-Cyclooctatetraene (CgHg)
shows a deviation of only 8 kcal/mole from its expected value of -112 kcal/mole.
This implies that conjugation is useful for only a small fraction of the 35
kcal/mole difference observed with benzene between its expected and actual
va-lues. Because benzene has 6 n-electrons in a continuous n-cycle, it obeys the
Huckel rule (it has 4n + 2 n-electrons where n = 1), whiIe1",3,5,7-cyclooctatetraene
(CsHs) has 8 n-electrons in a continuous n-cycle and does not obey the Hrickel
rule. This lack of aromaticity results in a less stable reactant, so more heat is
generated in the hydrogenation reaction.
Organic Chemistry
Intramolecular Features
Molecular Structure
Example 1.1L
" '\
H"CH"C
f-v-v
/\/
HsC
in the
/a
a-
A. 108.3"
B. 711..7"
c. 118.5"
D. 121.5"
Solution
First we must consider the hybridization of carbon. It is involved in one n-bond,
so the hybridization is sp2. The bond angle about an sp2-hybtidized carbon is
predicted to be 120". The question heri: is whether the angle is slightly greater or
slightly less than 120". Because there are two alkyl groups on the other carbon of
the alkene, the electron density repels the electrons in the two carbon-hydrogen
bonds. This forces the two C-H bonds closer together, which compresses the
hydrogen-carbon-hydrogen bond angle. According to steric repulsion theory,
the angle should be slightly less than 120'. The best answer is thus choice C.
Example 1.L2
C.
D.
Solution
HH
H'
Six conjugated n-electrons in a continuous
planar arrangement of p-orbitals is aromatic.
Because it includes the word tesonance, choice B may at first seem apPealing. But
a proton, having no electron pair, cannot be involved in resonance. Be careful of
wording like this, because it is easy to pick resonance without thinking about it.
Organic Chemistry
Molecular Structure
Fundamental Reactivity
dffifitffi:xiRd#Ctffit$
bond is broken. No matter what the result, the reaction has the same
tundamental drive and mechanics. The reactions can be viewed as Lewis acidbase reactions, so organic chemistry starts with a thorough look at Lewis acids
and bases. Prior to that, we shall review Bransted-Lowry acid-base chemistry.
Proton Transfer Reactions (Brsnsted-Lowry Acid-Base Reactions)
Brsnsted-Lowry acid-base reactions involve the transfer of a proton (H+) from
I,
is
)r
rf
n
.e
the acid (defined as the proton-donor) to the base (defined as the protonacceptor). This means that to be a Brsnsted-Lowry acid, the compound must
have a hydrogen that can be lost as H+. A hydrogen like this is often referred to
as a protic hydrogen or proton. Throughout this section, we will be using the term
grotonation to describe the gain of an H+. A hydrogen atom has one proton in its
nucleus and one orbiting electron (in a 1s-orbital). when hydrogen loses an
electron to become H+, all that remains is a proton. This is to say that H+ is a
Flroton, and thus the gain of H+ can be referred to as protonation. Deprotonation is
the loss of H+.
trt,
..'
,N:'
N:,a-\
+ Hf-.Cl '
Hrc\\Y
=F-
...
N-
..O
+ :cl:
Bond
"
son;/;iins
Hrc'{,:*:,
-I formed
Base
Acid
Conjugate
Conjugate
(Proton-acceptor)
(Proton-donor)
Acid
Base
"\o
H"C
Bond forming
Bond breaking
broken
te
re
Figure 1-25
)t
is
it
is
lrt
of
ln the reaction in Figure 1-25, you should note that an arrow going from
a lone
pair to an atom becomes a bond in the product, and an arrow going from a bond
to an atom becomes a lone pair on that atom in the product. This is a standard
convention in drawing mechanisms. The reaction shown in Figure 1-25 is very
favorable, as indicated by the asymmetric equilibrium arrow. The favorability is
attributed to the fact that HCI is a strong acid. Proton-transfer reactions proceed
favorably (AG < 0) from the side with the stronger acid and stronger base to the
side with the weaker acid and weaker base. This is to say that a favorable
chemical reaction proceeds from the less stable species to the more stable species.
There are five strong acids used in organic chemistry that you should recognize:
H2SO4, HNO3, HCl, HBr, and HL An important fact to know is that as a
Bronsted-Lowry acid gets stronger, it loses a proton more readily, so its
conjugate base is less willing to gain a proton. The result is:
\Alhen comparing two conjugate pairs, the pair with
the stronger acid has the weaker conjugate base.
Organic Chemistry
Fundamental Reactivity
Molecular Structure
"'\o
H^C
Bond forming
H.C
.N:
H,CV
E:
eti:'
Base
Figure
Carboxylic acid
o*'=e-10
o-*Vt
PKa = 15
R-
Phenol
OH
Alkoxide
|x:=17'20
Carbonyl cr-proton
Figure L-27
.ffii;'...:
tr!
1,-26
Figure 1-27 shows some common organic acids and their pKu values.
.A';il"
l[
Acidity
Acidity is defined by three definitions: the Arrhenius definition, the BrsnstedLowry definition, and the Lewis definition. The Arrhenius definition is that an
acid yields HgO* when added to water. The Bronsted-Lowry definition is that
an acid is a proton (H+) donor. The Lewis definition is that an acid is an electron
pair acceptor. The strength of an acid depends on the effects of intramolecular
forces on the bond to the acidic proton. These are the electronic forces within a
molecule. They are responsible for the distribution of valance electrons, which
accounts for the chemical behavior (such as acidity) of the molecule. An acid is
stronger when an electron-withdrawing group is attached to the backbone of the
acid, because the molecule is electron-poor, and thus a better electron-pair
acceptor. An acid is weaker when an electron-donating group is attached to its
backbone, because the molecule is electron-rich, and thus a wolse electron-pair
acceptor. The primary task associated with evaluating organic acid strength is to
decide which groups are electron-donating and which are electron-withdrawing.
=10
ril
rrrt
The role of a base is essentially the same in both the Lewis and Bronsted-Lowry
definitions. A base donates a lone pair of electrons to form a bond to an acid,
whether the acid is a Brsnsted-Lowry acid or a Lewis acid. In organic chemistry,
the terminology varies, and Lewis bases are frequently referred to as nucleophiles.
Nucleophile means "nucleus loving", which implies that nucleophiles seek out
positively charged sites (referred to as electrophiles). The simple guide to
organic chemistry is that negative charges seek out and bond to positive charges.
PKu
il
Acid
,t
d
q
"r."'.?'13,"#;\..
H
.F:
OH
T
I
n
fl
il
.&.
4&
&t.
3
lSE
air
rve
?S,
vis
cal
r'\i
iS
Organic Chemistry
Molecular Structure
Fundamental Reactivity
Basicity
Basicity is most easily thought of as the opposite of
organic bases.
o
Jl prn =e-71
-/\
RO-
Carboxylate
Iry
id,
=4
Phenoxide
PKa= 4
PKu = -1
PKu=-6--a
o/*Y,'
R-O-:
RACH,-
Alkyl amine
Alkoxide
Anionic g-carbon
Figure 1-28
ry,
Ies.
)ut
to
es.
AJthough you are not required to memorize exact pK6 values, it is a good idea to
know the "-5-10-75-20 general rule" for organic acids. The pKn for i carboxylic
acid is about 5, for a phenol it's about 10, for an alcohol it's about 15, and for a
proton alpha to a carbonyl it's about 20. These are close enough for good
guessing.
3d-
an
hat
:on
ilar
na
ich
lis
the
rair
its
rair
;to
ng.
-20
Example 1.13
tr\hat is the pK6 for p-nitrophenoi and the pK6 for its conjugate base?
A. O2NC6H4OH has pKa = 7.2; O2NC6H4O- has pKU = t2.8
B. O2NC6HaOH has pKa = 11.6; O2NC6H4O- has pKU = 8.4
C. O2NC6HaOH has pKa = 7.2; O2NC6H4O- has pKb = 6.8
D. O2NC6H4OH has pKa = 11.6; O2NC6H4O- has pKb=2.4
Solution
Pick the perspective (acid or base perspective) that works best for you, and use
rvith these questions.
rew
it
Organic Chemistry
Molecular Structure
Fundamental Reactivity
oxygen
at
^r,o} tt
o*ysJl';"'
!/) <+
uuc-h
\i6-11
[.
//
oxygena
H.C"\
f
H3c-c
\
.g^-H
Oxygenb
oxygen u :p-
o:
i9-11
Protonation at
Oxygen b
H1C-u
"
//)
<-'>
\^
Oxygen t !g-- g
/
H
:'6:o
/
H"CCO
"
\^
Oxygen bi6;'/
11
B.
C.
D.
Copyright
readily"
The oxygen is larger than nitrogen, so its electron cloud attracts protons more
readily.
Oxygen carries a partial positive charge due to resonance withdrawal from
the nitrogen.
Oxygen caries a partial negative charge due to resonance donation from the
nitrogen.
30
Organic Chemistry
Molecular Structure
Fundamental Reactivity
Solution
As shown below, the nitrogen of the amide donates electron density to the
carbonyl oxygen through resonance. This places a partial negative charge on
oxygen (increasing its basicity), and a partial positive charge on nitrogen
'decreasing its basicity). Choice A is eliminated, because oxygen is more
electronegative than nitrogen. Choice B is eliminated, because oxygen is smaller
Jran nitrogen, not iarger. Because of resonance, oxygen carries a partial negative
:harge, while nitrogen carries a partial positive charge. This means that choice C
-: false and choice D is true. This explains the basicity of amides.
:
ll-l
^Ar,- NHz
R
' *ot"
Aa -NHzlessbasicduetoabsenceofelec{rons.
R-
it
;-
-.-:h dictate where the electron density within a molecule lies, and thus they
,:,::atethereactivityof acompound. weshalllookathowthesefeaturesaffect
--- electron distribution within a molecule, starting with the primary effects.
l,:r-e 1-B shows common acids and bases in organic chemistry, listed according
- :elative strength (in both the acids and the bases).
rt
rs
:e
Strong Acids
H2SOa >
i\-eak Acids
HF > HCO2H > H3CCO2H > H2CO3 > H3CSH > H3CNH3CI
H5C6OH > H3COH
: trong Bases
l\'eak Bases
)'
at
Table 1-8
:,, right
3l
Organic Chemistry
Fundamental Reactivity
Molecular Structure
HH
\r
PKa = 10'4
,AHS
CH:
Stronger Acid
PKu = 15.7
HO
CHg
Weaker Acid
Figure 1-30
You should understand that atomic size (polarizability of the conjugate base) can
be applied only when the protic hydrogen is directly bonded to the larger atom.
The atomic size argument is used to explain relative acidity for haloacids.
Relative haloacid strength for haloacids is: HI > HBr > HCI > HF, confirming that
size is more important than electronegativity for elements within the same
column of the periodic table. This contradicts what you would expect if you
were to apply the rules of electronegativity. The relative strength in the case of
haloacids is dictated by atomic size of the halogen. As mentioned before, it is
because the bond is longest between hydrogen and the largest halogen, thus
making it the weakest and most readily broken hydrogen-to-halogen bond. It
can also be considered that the conjugate base (halide) is more stable as it gets
larger, because of the greater space over which the negative charge is distributed.
In the halogen case, the less concentrated (more diffuse) negative charge on
iodide (i-) is not as readily shared as the negative charge on bromide (Br-),
chloride (Cl-), or fluoride (F-). The weaker the conjugate base, the stronger the
conjugate acid, This is to say that because I- is the most stable anion of the
halides, it is the weakest base of the halides. Therefore, HI (the conjugate acid of
I-) is the strongest of the haloacids. This theory is also applied when looking at
the relative reactivity of halogen containing organic compounds in reactions
where the halide is a leaving gfouP. The relative acidity of haloacids should be
familiar to you. The mathematics of acidity and basicity is important in general
chemistry, but we shall consider only values such as pK6 to compare the relative
strengths of acids. In organic chemistry, by quantifying acidity with pKa values,
we can support or disprove relationships.
Copyright
Organic Chemistry
Str ength D ep en dence on El ectr oneg atia
e
r
rt
e
t.
I
R
Molecular Structure
ity
Within a row of the periodic table, the strength of the acid is dictated by the
electronegativity of the atom to which hydrogen is bonded. Given that atoms
within the same row of the periodic table are approximately equal in size, the
bond strength depends more on the distribution of electrons within the bond
than it does on the length of the bonds. Because the electronegativity of the atom
bonded to hydrogen affects the distribution of electron density within a bond, the
electronegativity of the atom directly bonded to the acidic proton dictates the
acidity of the compound.
e
n
e
s
e
e
t-
The greater acidity associated with alcohols than amines of equal alkyl
substitution can be explained by invoking the fact that the electronegativity of
oxygen is greater than that of nitrogen and that oxygen and nitrogen have
roughly equivalent atomic sizes. Figure L-31 shows the relative acidity when
comparing a hydrogen bonded to fluorine, oxygen/ nitrogen, and carbon.
Because fluorine is more electronegative than oxygen, which is in turn more
electronegative than nitrogen, the following relationship holds true:
HH
t
H-F
n
L
i.
rt
Strongest Acid
PKu = 3'2
\r
tt
s
t.
,),
ui.io
ir<o =
il
e
CH:
Weakest Acid
pKa = 33
PKo= 49
cH.,
-rl
iro
= -r.s
PKu
= 10'8
Figure L-32
rf
CHg
HzN
\r
The same rationale used to explain relative acidity in Figure 1-31 can be used to
erplain relative basicity in the conjugate bases amines, alcohols, and hydrofluoric
add. Because nitlogen is less electronegative than oxygen and fluorine, it more
rcadiiy donates an electron pair to a proton, so the trend in basicity shown in
Figure 1-32 holds true:
It
\l
Figure 1-31
tl
s
HH
HH
HO.4. CHs
Amphoteric
pKa = t57
Fundamental Reactivity
Amides (RZN-) are some of the strong bases that are used in organic chemistry.
They are used to remove alpha protons (the protons bond to the carbon that is
alpha to a carbonyl) and the terminal hydrogen of an alkyne, both with pKu
values above 17.
s/
Copyright
.'.'
Organic Chemistry
Strength
Molecular Structure
D
ependence on
Fundamental Reactivity
Hybridization
>e:
The hybridization of an atom affects the bond length and the distribution of
electron density within a bond, so the hybridization of an atom directly bonded
to the acidic proton affects the acidity of the compound. The relationship is not
obvious in that it is not true that longer bonds lead to stronger acids, as is the case
with most other acids. In fact, the relationship between length and acid strength
is exactly the opposite. As the hybrid orbital gets smaller, the electrons are held
closer to the nucleus of the atom bonded to hydrogen, so the bond can be cleaved
in a heterolytic fashion more easily.
The result is that the more s-character in the hybrid orbital
of the atom bonded to hydrogen, the stronger the acid,
This results in the relative acidity being sp > sp2 > sp3. It is most commonly
observed with carbon acidity, but can also be observed with nitrogen and
oxygen. Figure 1-33 shows the comparison of acids where hybridization explains
the difference in acid strength.
-HCH"
sPL
pKa=26 H- C= C- CH3
o
ir":
::r
:
:r:-
:a
:*ii l
nt-:,:
r"ai:r:
*C*,
:
-*,
--.
re5
:,*rl"
/ '
\
^CrC:
Ca
CHs
PKo=36 H
spr
Stronger Acid
Weaker Acid
L*
: ::-
-{
oK"=26 H
PKo=33 H
^"\r'cH3
SP.N
I
H
Stronger Acid
SP"
tir
rr;N--.cu,
lz-
il-ril:
HH
Weaker Acid
l:.
Figure 1-33
i:.:.
:-?;
Example 1.15
STRONGEST
base?
A.
B.
C.
D.
34
* i
-!..-
Organic Chemistry
Molecular Structure
Flrndamental Keactivity
Trpical examples of organic acids that are affected by resonance include phenols
and carboxylic acids. Figure 1-34 shows the resonance effect of an electrondonating group (OCH3) on a carboxylic acid. It decreases the acidity, raising the
pKu only when it can delocalize n-electrons.
oH,
uuco:
FoH
Pf"=56
Figure 1-34
The methoxy substituent (OCH3) has a lone pair of electrons on the first atom
adjacent to the carboxylic acid. The oxygen atom of the methoxy group donates
eleckon density to the system, and thereby decreases the acidity of the carboxylic
acid. An electron withdrawing substituent has the opposite effect, because it
grakes hydrogen electron deficient, and thus more protic. Electron-withdrawing
substituents increase the acidity of a compound, as shown in Figure 1-35.
".$.{'"o_Q
o
o*Jo
pKa=10.0
Figure 1-35
t5
Organic Chemistry
Fundamental Reactivity
Molecular Structure
Noz
cl>
HH
HH
PKa = 1'58
HO
HH
PKa = 3.17
HH
HH
pKo = 2.88
PKo =2.59
oo
,"\"^o\,
PKa=2.92
Figure
HH
PKa= 4.74
1"-36
CHg
Cl
HO
CHe
PKa = 2'88
PKa=
Ho
HH
HH
HH
cH2cl
HO
PKa = 4'82
PKa = 4'51
4'07
Figure 1-37
It may seem strange, but alkyl groups are electron-donating. This is attributed to
the fact that hydrogen is less electronegative than carbon. When the substituent
is electron-donating, the inductive effect decreases the acidity. As a result, alkyl
groups reduce thJ acidity of a compound. In Figure L-38, the compounds
become less acidic due to the electron-donating methyl group'
HoA.r '
'no\'"nu
,to
H]
PKa = 3'78
PKa = 434
HH
PKa = 4'82
Figure 1-38
Copyright
itv
;of
ni.c
ed,
ron
the
rrd
lof
rair
ron
sic
of
his
rlic
.H
Organic Chemistry
Molecular Structure
Fundamental Reactivity
ou must also be able to use the qualitative concepts. A proton transfer reaction
;"rcs favorably from the side with the stronger acid to the side with the weaker
:cid; a favorable reaction proceeds from stronger acid to weaker acid. To
jetermine the K"O for a proton-transfer reaction, first decide which of the acids
:l conjugate bases) is stronger. From there, it is a matter of determining the
;rection of the equilibrium. If the equilibrium lies in favor of the reactants, the
K*" < 1. If the equilibrium lies in favor of the products, the K"q t 1.
Example 1.16
r\irich of the following compounds is the STRONGEST acid?
-4- H3CCH2OH
m.
the
'of
C
D.
H3CCO2H
F3CCH2OH
F3CCO2H
id.
S'olution
len
-::boxylic acids are stronger acids than alcohols, due to the withdrawing of
.!e;ton density by the carbonyl oxygen through resonance. This eliminates
::--..ices A and C. Fluorine is highly electronegative, so it withdraws electrons
ent
::n
the acidic hydrogen via the inductive effect, thus increasing the acidity.
::,e skongest acid is the carboxylic acid with fluorines attached, choice D.
H"J
Etample 1.17
Ito
ent
kyl
because chlorine
is
more
rds
iolution
F:-rcrine is smaller than chlorine, so choice A is eliminated. The acidic proton is
:rar :,onded to the halogen, so atomic size does not dictate the acid strength. This
rew
Organic Chemistry
Molecular Structure
Flrndamental Reactivity
Example 1.18
A.
B.
C.
D.
Solution
Regardless of the effect (whether it is resonance or the inductive effect), electronwithdrawing groups increase acidity and lower the pKu while electron-donating
groups decrease acidity and raise the pKu. This eliminates choices A, C, and D
and leaves choice B as the best answer. The effect of an electron-withdrawing
group can be seen in the following trend: H3CCO2H (pKa = 4.74) is less acid than
H2CICCO2H (pKa = 2.85), which is less acidic than HCI2CCO2H (pKa = 1.26),
which in turn is less acidic than CI3CCO2H (pKu = 0.64). As the amount of
electron-withdrawal increases, the acidity increases.
Example 1.19
b
d
NHz
NHz
A.
B.
C.
D.
Nitrogen a
Nitrogen b
Nitrogen c
Nitrogen d
Solution
The most basic nitrogen atom is the one most capable of sharing its lone pair with
a proton or electrophile, which means that the nitrogen where the lone pair is
least shared within the molecule is the most basic. Nitrogens a and b have
reduced basicity, because the electron pair on nitrogen is being donated to the
aromatic ring through resonance. Nitrogen d has reduced basicity, because the
electron pair is being donated to the carbonyl group through resonance. Only
Nitrogen c is free to share its electrons (which are not being delocalized
Copyright
5A
ty
Organic Chemistry
Molecular Structure
F-undamental Reactivity
Example 1.20
l\hat is observed when histidine is protonated on its side chain?
le
te
le
le
\a
IE
\a
/e
nrg
D
r8
an
6),
of
A.
B.
C.
D.
The imine nitrogen gets protonated, because it is less electronegative than the
amine nitrogen.
The amine nitrogen gets protonated, because the imine nitrogen shares its
lone pair of electrons with the n-bonds in the ring through resonance/ thus it
cannot be protonated.
The imine nitrogen gets protonated, because the amine nitrogen shares its
lone pair of electrons with the n-bonds in the ring through resonance, so it
cannot be protonated.
Solution
tsoth nitrogen atoms are equally electronegative, because neither carries a charge.
This eliminates choices A and B. One could argue that having different
:"'bridization makes the electronegativity different, but the goal here is to find
-ie best answer, and if it is necessary to stretch the definition of terms, you're
:etter off finding a better answer choice. The histidine is protonated on the imine
:rtuogen, because the lone pair on the amine nitrogen is being shared with the
:;clic rc-system through resonance. This makes the ring aromatic, so the lone
:air on the amine nitrogen is not available to be donated as a base. The best
ins\{,er is choice D, as shown below.
HeN
H.N
oor
CH,,
t-
4;,
Ax
)^,J
H*
lmine nitrogen
r\-j
->
\:'
CH"
t'*#,r'
Oil
HsN
Ir---
th
is
7;;"
\
ve
he
he
NT.I\-
Lly
l-H
7 Amine nitrogen
CH?
1x,^
\Jz
ed
:w
CH?
Copvright
Organic Chemistry
Molecular Structure
Fundamental Reactivity
pH = -log[H3O+]
(1.3)
(1.5)
PKa = -1og Ku
(1".7')
PKb = -1og K6
(1.e)
[HaO+] = 10-PH
25"C)
Ku = 16-PKu
pKa + pKb = 74 (at25"C)
pH + pOH = 14 (at
(1.4)
(1.6)
(1.8)
(1.10)
Given pKu values, the AG" and K"O for a proton transfer-reaction can be
calculated. Listed below are four equations that you should be able to work
with. Equation 1.11 is the Henderson-Hasselbalch equation. It is used to
determine the pH of buffered solutions and is derived from the fundamental acid
dissociation reaction. Equations 1.11 and 1.13 are common, and should be
committed to memory:
pH=pKu+logl{l
-
(1.11)
tHA]
(1.12\
IHA]
-:i+
H3O+ +
A- ro=[H:-O*]-[A]
(1.13)
tHAI
A- + HB, wirere
K".
tu;
miln$mfr
iMM
sMl
,m$Mfl
,rm&
dM
d!
ry
mhq$h'
ffi
ilbttrrd
ffi
ffi@
dQu
ry'F
ffi
flmr
ffi
'm
w
r4
ry
q0
ffi@
(1.1,4)
HA + B-
-{llrt
mmm
1o(Pu-pKu;- [A-]
ForHA + H2O
hfr
hu6
[HB][A-]
lHAttB-t
By definition:
Ka(HA)
t"i#it
'
= 1o-pKa(HB)
Using equilibrium:
,, =#F
tHBltA-l
tHAltB-l
tA l
tHAl
= Ka(HA) x
lHBl =[H3o+][A]
tB-l
tHAl
irll
lH3o+llB-l
1 - Ka(HA)
Ka(HB) Ka(HB)
nffinW
Thus:
Ka(HB)
1g-PKa(HB)
i#t,,
i$ii:r
rnffi
ffimr
rillld
il@iifrfl'fr
Organic Chemistry
Molecular Structure
Fundamental Reactivity
Reaction Types
'al
NS
re
,4)
,6)
,8)
Lr organic chemistry, there are a few fundamental reactions that describe the
najority of reactivity in organic chemistry. In addition to acid-base chemistry,
there are substitution and addition reactions. All of these reactions involve the
aCdition of an electron pair to an electron-poor site. If you are able to identify the
:lectron pair that can be shared and the electron-poor site within the reactants,
'"-ou will be successful at predicting chemical reactivity. Addition and
:ubstitution reactions are often further classified according to their nucleophile
,rl eiectrophile, but for now, we shall consider only a generic addition reaction to
::,iroduce reaction pathways, mechanistic logic, transition states, intermediates,
0)
be
rk
to
id
be
4)
:w
Organic Chemistry
Molecular Structure
Fundamental Reactivity
Example L.21
D.
as:
a catalyst.
Solution
A carbocation is an intermediate, because it is not stable enough to be present at
the completion of a reaction, eliminating choice C. It is not present at the start of
a reaction, and it does not form an activation energy-lowering complex during
the reaction, so it is not a catalyst. This eliminates choice D. It is present for a
finite period of time, so it is not a transition state, meaning choice B is eliminated.
It has a finite lifetime and is semi-stable, so the best answer is choice A.
Arrow-Pushing in Mechanisms
When drawing mechanisms, the atrow starts with the electron pair destined to
form a bond. If a bond is broken, then the arrow starts at the bond being broken
and finishes as either a new bond being formed, or as a lone pair on another
atom. Figure !-39 explains the arrow-pushing associated with the electrophilic
addition of hydrobromic acid, HBr, to a symmetric alkene, E-2-butene.
Step 1: There is no lone pair in the alkene, so the arrow starts from the
most available electron pair (the rc-electrons) and goes to the partially
positive hydrogen of HBr. The bond between H and Br is broken.
a^
*a^
"").l.iYg.fil -f{
,/n-Bond\
breaking CH3
Nucleophile
(e- Pair Donor)
"Jj:"3>"
H"C Bond H
/\
H
Bondbrbaking
..o
r,t.
CHs
Electrophile
(e- Pair Acceptor)
H.C
"
.i_
CHa
Bromide anion
Planar carbocation
(Carbon is electron-poor) (Bromine is electron-rich)
\^ ;f
":',J-'t.",
Alkyl bromide product
Figure 1-39
Copyright
at
Df
Organic Chemistry
Fundamental Keactivity
Competing Mechanisms
lVhen an asymmetric alkene reacts with hydrobromic acid, there are multiple
potential products. The reaction can produce either a secondary or tertiary alkyl
bromide product. The pathway leading to the tertiary alkyl bromide has a lower
activation energy, forms a more stable intermediate, and results in the more
stable product. The pathway leading to the more stable product yields the
lhermodynamic product. The pathway with the lower activation energy yields
fie kinetic product. Some reactions may involve a competition between the
pathway leading to the thermodynamic product versus the pathway leading to
the kinetic product. Figure 1-40 shows the treatment of an asymmetric alkene
rvith hydrobromic acid.
rg
a
Molecular Structure
Observed Reaction
(Leads to the More Stable Product by way of the More Stable Intermediate)
al.
H"C
!o
II
er
ic
H:C
CH:
HsC
Nucleophile
(Alkene ru-bond)
'\^ ;f
H.C
...
.I1f.
CHe
3" Carbocation
(Electron-poor)
A
+
/\
HeC
3'Carbocation Bromideanion
stability) (Leaving group)
Electrophile
(Strong haloacid)
H.CA
'J4.}H
CHg
L-
H.c\7
:
Bromide anion(Electron-rich)
Bi
\ CH:
S'
A
').L.1
\*s-;ry;t-
H"C
/\
H:C
HeC
CHs
Nucleophile
n-bond)
(Alkene
2'Carbocation Bromideanion
stability) (Leaving group)
Electrophile
(Strong haloacid)
Hsc.
H"C
...c-
H$t"/
H:C
/,
\
...+
CHs
2'Carbocation
(Electron-poor)
Bromide anion
(Electron-rich)
Figure
)w
CHs
Copyright
\_
H\t"'/
HsC
-..
2"
\H ..
lP'':
\,
CHs
1"-40
Organic Chemistry
Molecular Sllrrclrrre
Fundamental Reactivity
Energy Diagrams
An energy diagram accounts for the energy of the system as a reaction proceeds.
As energy is added to the system (to break bonds or reorient the molecule to a
less stable structure), the energy goes up. As energy is released from the system
(upon making bonds or reorienting to a more stable structure), the energy goes
down. The overall difference from start to finish represents the energy change
for the reaction (either AG or AH.) The diagram reaches an apex with a transition
state, and a localized nadir in the middle with an intermediate. The start
represents the energy of the reactants, and the end represents the energy of the
products. Each apex represents a transition state in the reaction, which results in
a step in the reaction, Figure 1-41 shows the two energy diagrams associated
with the two possible reactions when adding HBr to an asymmetric alkene.
T
2(3')
Products
2": (H3C)2CHCHBTCH3
3': (H3C)2CBICH2CH3
>'
bo
rr
Reactants
(H3C)2C=CHCHa + HBr
/
aGr(3") = -8.77kcar /
AG"12.;
AJ
O)
li
trr
= -7.63kcar
mole
mole
Reaction coordinate
Figure 1-41
Energetics and Kinetics
1.
as
follows:
Identify and label the reactants (in most cases as nucleophile and
electrophile).
2.
3.
Predict the products of the reaction. If the reaction occurs in multiple steps,
predict products for each step.
Show the flow of electrons in each of the steps. This is known as drawing the
mechanism.
4.
is the standard free energy. When negative (AG" < 0), the reaction is
favorable in the forward direction. When AG' is negative, Ksq (the
equilibrium constant measuring the ratio of products to reactants) is greater
than 1 (K"q > 1). Because AG" = AH'- TAS", and most organic reactions take
place in sblution where entropy is relatively unchanging, AH" can be
approximated from AG". In conclusion, to determine whether a reaction is
thermodynamically feasible, look at O6', KeO, and AH".
Copyright
44
ty_
Organic Chemistry
i.
s.
n
}S
!e
rn
rt
te
Molecular Structure
Fundamental Reactivity
Evaluate whether the reaction can proceed at the given temperature. There
are favorable reactions that never take place, because the activation energy
(E6s1) is too great. When looking at reactions, there is AGX to consider, the
activation free energy for each step. There must be enough free energy
present that a reasonable number of reactants can overcome the activation
barrier. This factor is hidden in the rate constant (k.*), which takes into
account the frequency of collision, the temperature, and the orientation of
molecules during collision. In conclusion, look at: T (high temperature
equals fast reaction), Eact (low Eagl equals fast reaction), and intermediates
(stable intermediates equal fast reaction).
d
Effect of Temperature on Reaction Rate
The rate of a reaction increases as temperatute increases, because there is more
energy available in solution for reaction. Temperature is part the rate
=ee
:onstant, kr*, mathematically expressed Equation 1.15.
k.* = A
-,q-here
(1.1s)
"-Eut'/RT
E661
The energy diagrams in Figure 1-42 show the change in energy level as the
:eaction proceeds and Figure 1-43 shows the molecular energy distribution
iroughout the entire system at two different temperatures (T1 and T2).
state
(f)
>'
bD
t+
q.)
rl]
Reaction coordiante
Figure
TztTr
1,-42
Minium
Eo.1
for reaction
Kinetic energy
tr
Figure 1-43
e
e
At T2, the average kinetic energy of the molecules is greater than it is at T1. Thus,
at T2, more molecules have enough energy to overcome the activation energy
'rarrier
of the reaction.
Copyright
4s
Organic Chemistry
Molecular Structure
Physical Properties
Physical,, Propefties,
Physical Properties and Intermolecular Forces
the attraction between temporary dipoles (a very weak force). They are the
weakest of the three intermolecular forces between molecules that we shall
consider. They are considered to be less than 1 kcal/mole.
The intermoiecular forces are the primary consideration when approximating
physical properties, when forces are not enough to determine ihe physical
properties such as boiling and melting point, then structural features such as
molecular mass and molecular rigidity become the determining factors. The
heavier the compound, the harder it is to remove it from a lower energy phase
and place it into a higher energy phase (i.e., liquid to gas). what is meJnt by
"molecular flexibility" is the ability to twist and conform to allow for more
surface area, and thus more intermolecular interactions. Van der Waals forces
are rarely used to explain anything except why there is not a complete absence of
intermolecular force. Figure L-44 shows the different forces.
Copyright
46
ft
W
O!
,*
Organic Chemistry
Molecular Structure
Physical Properties
Hydrogen-bonding:
gu
HeC
-?o
\
-rr.
H
I
CHs
/
Dip ole - Dip ole I nte ractio
F_
kry
H3CV'066+l
T.)a%'"
H
HaC
Tr--$T,{,
:-.$e?.
H
Figure L-44
F-xample 1.22
'ir{-hv
ethane
CII3CH3) is a gas?
3"
E-
D.
Solution
!fiethanol (CH3OH) is a liquid at room temperature, while ethane (CH3CH3) is a
Sas, so methanol has the greater boiling point. Ethane is a nonpolar molecule, so
Cpice A is eliminated. Methanol has a molecular mass of 32 grams/mole, while
e$lane has a molecular mass of 30 grams f mole, so methanol is only slightly (not
significantly) heavier than ethane, so choice B is eliminated. The van der Waals
rnEractions are roughly equal for all molecules, so choice C is eliminated.
hfiethanol has hydrogen-bonding, while ethane has no protic hydrogen and
Sr,erefore no hydrogen-bonding. The higher boiling point is due to the
hr-drogen-bonding of CH3OH, so choice D is all yours!
Organic Chemistry
Molecular Structure
Physical Properties
Hydrogen-Bonding
Hydrogen-bonding is the strongest of the common intermolecular forces. It can
be thought of as a weak covalent bond between a hydrogen that carries a partial
positive charge and the lone pair on a nearby atom. The strength of a hydrogen
bond varies between 4 and 8 kcals per mole. Hydrogen bonds are similar to the
interaction of a base with an acidic proton in the transition state of a proton
transfer reaction. This is where the term protic comes from, as a hydrogen
capable of hydrogen-bonding is also slightly acidic. The partial positive on
hydrogen is strong enough to form hydrogen bonds when the hydrogen is
bonded to either fluorine, oxygerL or nitrogen (highly electronegative atoms).
The strength of the hydrogen bond is best approximated by the acidity of the
proton and the basicity of the lone pair donor. The strongest hydrogen bond
exists between hydrogen on fluorine and a lone pair from nitrogen. Hydrogen
bonding in alcohols is stronger than in amines, as supported by the greater
boiling points of alcohols relative to amines with comparable mass. The best
explanation for this is the greater acidity of the protic hydrogen of an alcohol
than an amine. compounds that form hydrogen bonds are polar, so when a
compound has hydrogen-bonding, it also has dipole-dipole interactions. This
means that when you are asked to compare boiling points of compounds, you
should first look for hydrogen-bonding.
Figure 1-45 shows the structures and boiling points of butanol and butanal.
Butanol is capable of hydrogen-bonding, while butanal is not. For this reason,
the forces between butanol molecules are stronger than the forces between
butanal molecules. The result is that butanol molecules bind one another more
tightly, resulting in a higher boiling point. This comparison of the two is
reasonable, because the two molecules are of roughly equal mass.
OH
\//
Butanol (b.p. =
,,^-'At
717.4' C)
Figure 1-45
Example 1.23
C. (H3C)3CH
D. H3COCH3
Solution
Copyright
Organic Chemistry
gs
Molecular Structure
Folarity
?olarity is defined as an asymmetric distribution of electron density within a
:roiecule. Perhaps an easier way to think of this is as a tug-o-war for the
=-ectrons between atoms. The more electronegative atoms pull the electrons
::ore tightly. If the molecule has more of one atom on one side of the molecule
-:ra-n another--that is, if it is asymmetric about a ceniral point-- then it is polar.
:-:ure 1-46 shows a series of chlorinated methane derivatives that demonstrate
::-arity (or lack of polarity) based on structure.
ln
ai
ln
1e
)n
tn
)n
is
I
:IE
CI
rd
st
ol
l'--.npoiar
Polar
)u
il.
n/
ln
Polar
Polar
Nonpolar
Figure 1-46
a
ris
CI
'/Y,.'ct/V.
ln
er
Physical Properties
-. : --iar compound has a dipole, which for a1l intents and purposes is a line
:::,1 r'r form the positive side of the molecule to the negative side of the molecule
ri- : i".-av that sums up the polarity vectors of each bond in the molecule. The line
rL'-:ates the direction in which the electron density shifts. Figure 7-47 shows the
m:
from Figure 7-46, wlth dipoles now drawn in.
'e;ules
re
is
F{
f'
,r'"{'Jn H .ztyrn
'',,:
l:O1af
C1
CI/IV:, ct o./Y.,
Polar
Polar
Figure
Nonpolar
1,-47
-r,e :,:elaction of the dipoles between two nearby molecules accounts for a weak
r'ur,:: l-- shown in Figure 1-44. The alignment of dipoles is best when the partial
J,"$itr-- e of one molecule aligns near the partial negative of another molecule.
{x.mrnie 1.24
$uluruc.ou-r
-]ilu "L':t
:w
l*um-nr,,::.=--
49
Organic Chemistry
Molecular Structure
Physical Properties
Van der Waals forces are weak intermolecular forces that exist between all
molecules' These weak attractive forces account for the minimal attraction
between hydrocarbons. In biochemical discussions of hydrophobic interactions,
it is in fact van der Waals forces that are being considered.
Figure 1-48 shows why lard (a saturated fat) has a higher melting point than
vegetable oil (an unsaturated fat). Because the molecules in laid are more
flexible, they are better able to interact with another molecule (tie knots around
another molecule, if you will) than is vegetable oil. Perhaps it is easier to picture
lard as a pile of strings that can tie knots around themselves, while vegetible oil
is like a pile of straws. If you were to build two separate piles, one a pile of
strings and the other a pile of straws, then intertwine each within itself, from
which would it be easier to remove a piece? It would be far easier to remove a
straw from the straw pile, because the straws are not tangled up. Their rigidity
prevents interactions between the straws. This is why saturited fats 1*hose
molecules are flexible like strings) are solid at room temperature, while
unsaturated fats (whose molecules are rigid like straws) are llquid at room
temperature. The greater the number of rc-bonds in a compound, the lower its
melting point, and the greater the odds it is a liquid at room temperature. The nbonds in the fatty acids in a phospholipid bilayer affect the fiuidity of a cell
membrane.
t"
trg
Solub
Sneubd
brmscift
ln*e s[
maFrfff,
hu'}"e0
*oto,.{ Src
mrMl
lmaru
he$p
rwmnmrhi
lx.{ryd
dmpdl
ffir.mmm
tr
f,'*rmt
il
ill*
ffi-
ffig"-
,IMffi
Figure 1-48
@fu
s
Example 1.25
Solution
For the membrane to be rigid, there must be many interactions between the
chains. The maximum degree of interaction occurs with long, saturated
acids. Pick B and feel good yet again.
50
lipid
fitty
{a
*"n
il
mhi
mm
Organic Chemistry
Molecular Structure
Physical Properties
Type
Examples
H-bonding, dipole-dipole,
Water. Alcohols
and van der Waals
Polar, Protic
Polar, Aprotic
Ketones, Ethers,
Alkyl halides
Oils, Petroleum
Table 1-9
The followrng three solubility observations can be explained by the solubility
rules in Table 1-9.
Salts dissociate into water, because ions are stabilized by the protic
nature of water.
Sugar dissolves into alcohol, because of the large amount of hydrogen
bonding.
Wax dissolves into oil, because it is entropically favorable to randomize.
Individual van der Waals interactions are weak; but over a long
molecule, they quickly become significant.
How can a nonpolar particle dissolve into water? Soaps help to make a
nonpolar, aprotic species dissolve into water. For a soap (surfactant) to do this, it
must be both hydrophilic (water-soluble) and hydrophobic (water-insoluble)
simultaneously. Such molecules contain a polar (or charged) end (referred to as
the head) and a alkyl chain (referred to as the tnil). Originally, soaps were made
by treating animal fats with strong base to convert the ester to a carboxylic acid,
and then further convert the carboxyiic acid to carboxylate (its conjugate base), a
Copyright
5l
Organic Chemistry
Molecular Structure
Physical Properties
species with an organic tail and a charged head. soap molecules form micelles
when placed into water. Micelles are little pockets (spherical in shape) with an
organic core and polar heads sticking out from the core to interact with the
water. They are shuttle pods for nonpolar, aprotic species through water.
o
IUo
m_
melts to form an oil. The melting point for wax i.s greater than room
temperature, but less than the temperature of the flame. The oil and vapor that
form burn when exposed to heat from the flame and to oxygen. only the oil near
f,o
1*
the flame burns, so heat is not evenly distributed in the system. The workings of
a candle can be explained using fundamental principles in science. euite often,
the simplest things in life are organic chemistry in action,
Example 1..26
\Alhich of the foiiowing compounds would make the BEST micelle?
A. H3C(CHz)gCOzH
B. H3C(CH2)3CO2C. H3C(CH2)1aCO2H
D. H3C(CHz)tqCOzSolution
The best micelle has an ionic (charged) head and a long carbon chain for the
organic tail. Choices A and c are eliminated, because they have uncharged
heads. Although a carboxylic acid group is polar and protic, a charged site is
better, because it is more hydrophilic when charged. Choice D is better than
choice B, because it has a longer organic tail. Pick D to score big on this question.
At
L
E{
tn"-
52
C{
Organic Chemistry
Molecular Structure
Section Summary
-\omenclature
1. IUPAC Nomenclature (Names are assigned systematically based on functional
groups and carbon chain length)
a) Name Root (Assigned according to the longest chain)
b) Suffices (Assigned according to functional group--generally, the most
oxidized functional group gets top priority)
c) Prefixes (Assigned to note stereochemistry; i.e., R or S, E or Z, and a or B)
d) Common Nomenclature (Prefixes based on substitution and relative
positions of functional groups; i.e., geminal diol and secondary alcohol)
Bonding and Orbitals
1. Bonding (An attractive interaction between neighboring atoms)
a) Covalent Bond (The sharing of electrons between atoms; carbon makes
covalent bonds)
i.
Single bonds are made of a sigma-bond; they are weaker than both
double and triple bonds.
ii. Double bonds are made of one sigma-bond and one n-bond; they are
weaker than triple bonds, but stringer than single bonds.
iii. Triple bonds are made of one sigma-bond and two n-bonds; they are
stronger than both single and double bonds.
iv. Sigma-bonds share electron density between nuclei while n-bonds
share electron density in the plane above and below the nuclei.
b) Molecular Orbitals
i. Like atoms, bonds have electrons in regions of high probability, so
there are sigma and pi orbitals to describe molecular bonds.
ii. Sigma bonding orbitals are more stable than pi bonding orbitals, while
iii.
c)
i,
Hybridization
1. The mixing of atomic orbitals (s and p in organic chemistry) to form hybrid
orbitals capable of combining to make molecular orbitals.
a) sp-hybridrzation results in linear compounds, often with two ru-bonds, a
180" bond angle, and the shortest of all hybrid orbitals.
b) sp2-hybridi"ation results in trigonal planar compounds, often with one nbond, a 120" bond angle, and a medium sized hybrid orbital.
c) sp3-hybridlzation results in tetrahedral compounds, with no n-bond.s, a
109.5'bond angle, and the longest of all hybrid orbitals.
Bond Dissociation Energy
1. The energy required to break a bond in a homolytic fashion (into free radicals)
is the bond dissociation energy. Higher BE refers to a stronger bond.
a) BDE depends on the atoms, the substitution, and electron distribution
b) Ionic bonds, rare in organic chemistry, break in a heterolytic fashion.
Copyright O by The Berkeley Review
5t
Organic Chemistry
Molecular Structure
Section Summary
Intramolecular Features
a)
i, Most stable resonance structure has an octet for all atoms but
a)
Acid-Base Chemistry
i.
Bronsted-Lowry deals with proton transfer while Lewis deals with the
accepting and donating of electron pairs.
ii. Electron pair donors are Lewis bases and nucleophiles, while electron
pair acceptors are Lewis acids and electrophiles.
b) Determining Acid Strength (stronger acids have lower pKu values)
i. Primary factors affecting acid strength are the size, hybridization and
electronegativity of the atom to which H is bonded.
ii. Secondary factors affecting acid strength are resonance and induction.
iii. Base strength goes in the opposite fashion as an acid.
c) Acid and Base Terminology and Facts
t.
Acids: pH = -log[H3O+], [H3O+] = 10-PH, pKa = -log Ka, K6 = lQ-pK2
t1,
As acid strength increases: 1) acid dissociation increases, 2) Ku
increases, 3) pKu decreases, 4) pH in an aqueous solution decreases,
and 5) conjugate base strength decreases and stability increases
111.
Bases: pOH = -log [OH-], [OH-] = 10-POH, pKb = -Iog K6, K6 = 1g-pK6
iv.
KU
d)
Physical Properties
b)
Copyright
i.
54
Stmcture, Bonding,
and Keactivity
Passages
15 Passages
I OO
Questions
III:
,1fu
REKI{ELEY
L)R
E.v.r.n.w'
betn
engt
is to
and
I.
II.
III.
IV.
V.
VI.
VII.
VIII.
IX.
X.
XI.
XII.
XIII.
(l -8)
(e
- 14)
(rs - 2L)
Amide Protonation
(22 - 28)
(2e - 34)
(55 - 42)
Micelles
(43 - 4e)
IR Determination
(5o - 56)
carb
ofb
inao
bood
It'c
l"i
lnrc
fut
lEtr
l'"r.
PetroleumDistillation
(57 - 63)
(64 - 70)
(7r - 77)
(78 - 84)
(85 - el)
Thcrt
(92 - lOO)
ThErc
I,nrc
t**.
l'"r.
T
guury
@
wrqE
TanilE
0fbil
Kaw Score
MCAT Score
rm a&
84 - 100
l5 l5
10 l2
7 -9
lb'@
ilm ilE
66-43
47 -6s
34
46
t-53
4-6
t-3
&s,
Fassage
I
=
(Questions 1 - 8)
I.
.
B.
C.
D.
A
rr :ond
ffilJ:C-I
Bond
mole
88
(H3C)2CH-CH3
84
(H3C)3C-CH3
81
85
H2C=CH-CH3
91
HrC-H
t04
H5C2-H
(H:C)zCH-H
(H:C)rC-H
H2C=CH-H
H3CO-H
H5C2O-H
98
2.
A. Methyl
B. Primary
C. Secondary
D. Tertiary
95
91
108
3.
103
A.
,1111p
4.
H2C=CH2
than
larger atoms.
A. unsubstituted.
B. monosubstituted.
C. disubstituted.
D. trisubstituted.
iltltlltrNflrurgfl:r.tion
AH
than
larger atoms.
rflrilllfiHrHmr-i.
lteal;
-32.6
RHC=CHz
-30.2
cis-RHC=CHR
-28.s
R2C=CH2
-28.3
trans-RHC=CHR
-27.4
R7C=CHR
-26.1
R2C=CR2
-26.4
Table
@
t02
J;nrlght
Alkene
BElleel;
H3C-CH3
H5C2-CH3
Table
5.
A.
B.
C.
D.
resonance.
hybridization.
the electronegativity of carbon.
steric hindrance.
6.
Passage
ll
(Questions
I - 14)
.
B.
C.
D,
A
A. H3C-I
B. H3C-CI
C. (H3C)2CH-I
D. (H3C)2CH-C1
A.
B.
C.
D.
H3C-CH3
(H3C)3C-C(CH3)3
H2C=CH2
(HgC)zC=C(CHl)z
Acid salt
Freebase
HrC
.\
N
(
N
HrC
-\
'\*--CHr
*Ao
(
+N
CH:
Figure L
cl-
\*z
cH:
*Ao
I
cHr
following reagents?
A. HCI
B. NaCl
C. CaCO3
D. NaOH
Copyright O by The Berkeley Review@
0.
beans,
caffeine?
rpHat
A.
B.
c.
D.
or the
9SASA
)rages
nulant
racted
using
rrate
14.
A. acidanhydride.
B. acid ester.
C. ester.
D. lactone.
tp3
Nitrogen atoms do not exhibit hybridization.
of
way is
rrm of
n their
:xhibit
BEST
re acid
caffeine?
Jhasa
A . Perpendicular planar
B. Coplanar
C. Tetrahedral
D . Inverted planar
rid salt
rrm by
e freereating
ue the
cl-
CH3
'o
e
form,
{ of its
;
a PKa
B.
C
ll
:'
compound.
r weak
rHofT
om tea
tof the
) as the
cation
rrganic
rto the
l to the
of the
IAGE
.
B.
C.
D.
A
lll
Passage
(Questions 15 - 21)
6.
A. Propanone
B. Propanol
C. Propanal
D. Propanoic acid
17.
It
8.
.
B.
C
D
19.
.
.
A.
B.
C.
D.
soaps is sodium
dodecyl sulfate (SDS), found in many commercial shampoos
and hand soaps. Soaps can be made by treating animal lard
(fatty-acid triglycerides) with a strong base (such as NaOH).
One
CH
A. Nonionic acid
B. Decanoic acid
C. Undecanoic acid
D. Dodecanoic acid
paper.
CH3CH2CO2H
CH3CH2CO2Na
CH3 CH2CH2CH2CH 2CH2CH2CO 2H
CH3CH2CH2CH2CH2CH2CH2CO2Na
and
20.
in water?
A. CHqCHzCO2H
B. CH3CH2CO2K
C. CH3CH2CH2CH2CH2CO2H
D . CH3CH 2CH2CH2CH2CO 2K
15.
A11
femperature.
Copyright
21.
A. CH3CO2H + CH3MgCl
B. HCO2H + CH3MgCl
C. Ethanoic acid + NaOH
D . Propanoic acid + NaOH
GO ON TO THE NEXT PA
lV
Passage
(Questions 22 - 28)
23.
A.
,2H
B.
C.
D.
ao.n
o
o.H
H-ii
i
Ll
<+
--c\N-R
R,,\N-R
*-c\p.,R'
ttl
ound?
4.
o
lt
HT
HHH
on the
rlained
-C-. /H
water.
ible in
il
/R'
-c\
"N
H+
_>
No resonance
lt
*- \g,,R'
Figure
B.
/\
HH
A.
C. The carbon
D.
Support
for
l . Alich
I
2Na?
A.
B.
C.
D.
nbUr$sn'
Site a
Site b
Site c
Site d
molecule?
this
soluble
-.,:'"-risht
A.
B.
C.
D.
7.
A.
B.
*,.c-*.,R'
*,
C--**.
c.
o-
R'
D.
oI
R,,clN,,R
**..
(Questions 29 - 34)
o-
il
Passage
C-*,,R'
of a compound is defined
as the
molecule
28.
organic compounds.
A.
B.
C.
D.
Chemist
Chemist
Copyright
GO ON TO THE NEXT PA
theory EXCEPT:
the
A.
rund
s the
B.
lbe
with
oints
rced.
roint
H3CCH2OH.
A.
B.
H3CCO2H.
C. decreases,
H3CCH2OCH2CH3.
H
than
D.
H3C(CH2)6CH3.
xule
ltion
3.
because
the atmospheric
pressure
decreases, because
the atmospheric
pressure
increases.
decreases.
the
- the
3tt.
rious
terate
r. To
must
three
Itr. H3CCH2NH2
A. H3CCH2OH> H3CCH2NH2 > H3COCH3
B. H3CCH2OH> H3COCH3 > H3CCH2NH2
C. H3CCH2NHz > H3CCH2OH> H3COCH3
D. H3CCHzNHz > H3COCH3 > H3CCH2OH
the
the
rre
L H3CCH2OH
tr. H3COCH3
'ornts
r
r
cH3
cl
II.
ct
of
cules
ofa
rctive
The
ween
from
Ticult
rhase,
The
as the
When
:cules
ll.
ct
The hydrogenation of an eight-carbon diene has which
of the following effects on the physical properties of the
m.
ct-t
compound?
A.
B.
A.
B.
C.
D.
point increases.
decrease.
GI
s, and
:es is
Waals
.in the
rot all
According to Chemist 2, as intermolecular hydrogenbonding increases, which of the following trends should
be observed?
A.
:ohols
se the
gen of
accept
ble of
Ins arg
of
the
,AGE
pressure decreases.
D. Both
decrease.
63
Passage
Vl
(Questions 35 - 42)
8.
A.
B.
C.
9.
in an asymmetric
Stretching
in
an asymmetilc
a carbonyl bond in
symmetric
molecule
of Fe(NH3)aC12?
Nonpolar
Polar
0.
A. 1,1-dichloroethane
B. cis-1,2-dichloroethene
C. trans-1,2-dichloroethene
D. E-1-chloro-2-fluoroethene
35.
A.
B.
ArHF
D.
CO,I
C6H6
c. Nz
A.
B.
C.
D.
7.
A.
B.
C.
D.
41.
I,1,2,z-tetrafluoroethane
I ,I
B . 1,1,2,2-tetrafluoropropane
C . 1,1-difluoro-2,2-dichloroethane
-difluoro-2,2-dichloropropane
I.
II.
il.
A.
B.
C.
D.
I only
II only
I and II only
II and III only
GO ON
TO THE NEXT PA
pound
rlength
bonds
bonds
ius can
rw the
metric
metric
Passage
Vll
3.
of
A.
B.
C.
D.
two
4
4.
H3C(CH)nCO2H
H3C(CH)nCOz'
H3C(CHz)nNHz
H3C(CHz)nNH:+
Technique
: rensional
NS
49)
.,lnique
iecule
mlcture
(Questions 43
three-
Hydrophobic tails
Pol
lns
lil:l:l:
4
5.
Fizure
A.
B.
C.
D.
,lecule i
(H:C)zCHNHCH3
(HrC)zCHCH2NH2
(H3C)2CHOCH3
(H3C)2CHCH2OH
6.
B.
"\y::
D.
-:.
-:r right
b5
7.
Passage
A.
B.
C.
D.
H3C(CH2\CO2H
Vlll
(Questions 50 - 56)
H3C(CH)zCoz'
H3C(CH)13CO2H
H3C(CH)nCOz-
8.
A.
B.
C.
D.
An alcohol (RCH2OH)
A carboxylic acid (RCOZH)
An amine (RCHZNHZ)
An alkene (R2C=CR2)
3'Alcohol
9.
A.
'Van
B.
C.
D.
Polar attractions
VV
2'Alcohol
,01",,
Hydrogen-bonding
1" Alcohol
,oL.*,
3396crnl
Covalent bonding
Carboxylic acid
Figure
functional groups
Because the covalent bond is weakened by hydrogenbonding, the IR signal of a covalent bond between atoms
involved in hydrogen-bonding broadens as the degree of
hydrogen-bonding increases. Not all hydrogen bonds are
equivalent, so the signal becomes a range of absorbances that
the
increases, the
.
B.
C.
D.
A
66
g?
53.
5.
-{. Ammonia
B. Propylamine
C. Dipropylamine
D. Tripropylamine
A.
B.
C.
D.
.\
6.
I.
II.
m.
absorbance decreases.
B.
bonding.
absorbance increases.
A. I only
B. II only
C. I and II only
D. II and III only
.{. Aldehydes
B. Esters
C. Ketones
D. Primary amines
.
B.
C.
D.
A
ol
Passage
lX
(Questions 57 - 63)
2-Methvlbutane
Benzene
Octane Rating
Hydrocarbon
oil
are used
process
93
28'C
r06
80'c
n-Hexane
25
69"C
Toluene
120
104'c
2.2.3-Trimethvlbutane
t25
98'C
88'C
82'C
100
104"C
n-Heptane
2-Methvlhexane
12
Table
levels of refinement.
5
7.
6'1"
Boilins Point
has
A.
B.
C.
D.
Vapor
Petroleum
25"C-t]5'C
2-Methylheptane
n-Octane
2,2-Dimethylhexane
2,2,4-Trimethylpentane
----+-
8.
component of kerosene?
Kerosene
A. n-Octane
B. n-Decane
C. 2,2-Dimethyloctane
D, 2,2,4,4-Tetramethyldecane
175'C-280'C
___>
Heating oil
250'C-350"C
_+
Lubricating oil
300'c-375"C
5
9.
-------->Tar
Figure
n?
0.
A.
B.
fr}..
1.
A.
B.
C.
D.
enthalpy of combustion.
entropy of combustion.
ratio of CO2 to water in the exhaust.
r'ate o1'combustion.
Passage
(Questions 64 - 70)
2.
I.
II.
il.
A. I only
B. III only
C. I and II only
D. I and III only
oly
63
A.
B.
C.
D.
rp3 to sp2.
rp2 to sp3.
sp to sp3.
R-C:n'
__ .o +
R-C:C:
..@
H
sp3 to sp.
o-^E^.
a u.
to the
dense
righer
righer
non-
AGE
=:
in a homolytic
Copyright
sense.
64.
A.
B.
C.
D.
9.
A' H-c:c-H
Carbon-l
Carbon-2
Carbon-3
g.
H:..
Carbon-4
H/u
il
B. Hsc-cEc-cr-rs
D'
^.- Hs
^_ t-
'
fuc
otrErt
qiffiEr
K^('v-
\^-^.zH
t- tt^/
,
ThEB
fli:t$ fi
H
isau
gnhflGf,
from
6
"Go.
ur\o,
wmsm
70.
oG*,,
.\*.\
C.
B.
-NH
(,\*,
compounds
is
7.
8.
rerirj i
uquilil
&][!DeEl|
*sasti
Eq
lu0msh
Kq"
CH3CH2CH2CH2Na
CH3CH2CH=CHNa
CH3CH2CNa=CH2
,l\ r
CH3CH2C=CNa
cl'ick$
A.
B.
C.
D.
Tr
the
STRONGEST base?
A.
B.
C.
C.
mufu
tr lwt
ilfum
D.
G,"
66. Which of the following organic
H on carbon-l of 2-methyl-1-butene
H on carbon-2 of 2-methyl-1-butene
H on carbon-l of 2-methyl-1-butanol
H on oxygen of 2-methyl-l-butanol
Th
A. H- CE C"'*..-r
,/"
Ct-ls
D' H:^-
n-n./u3
'-
B. H-C= c-
o,
,/u:
i.r dEE
WurftlE
mesrmt
fuErudl
md rce
diiffieru
ryid cm
cqldliihi
^//H
t\
n
mfirm*
ffiuc rtpr
Passage
Xl
(Questions 71 - 77)
H3CCOCH2COCH3
tHAltBl
Ka (acid HA)
.
B.
C.
A
HB
Ka (acid HB)
D.
I04
an equilibrium
CI3CH + H3CCH2S-
-+
H3COH + H2CNO2- +
H3CCOCH3 + H3CO- *
C13C'+ H3CCH2SH
H3CO- + H3CNO2
H3CCOCH2COCH3 + C13C-
A. H3CCOCH3
B. H3CCH2SH
1,3-
C. H3COD. HzCNOz-
HA+CsHs-5+A-+C5H6
The structur"e
10-9
L:ure
104
H3CCOCHCOCH3- + CI3CH
Equation I
Reaction
H3CCOCH2-+H3COH
= tg(pKa
106
H* = tA-llFIBl '
x 10-i
Reaction
8.2
Table
A- +
8.0
H3CNO2
==::\
5.2
CI3CH
HA + B-
3.9
H3CCH25H
acid is a product).
added quantitatively
1.2
H3COH
:;r,l is
2.Ox1O4
H3CCOCH3
1,
3.
H3Co- --
H3CCH2S- + H3COH
Figure
1,3-Cyclopentadienyl anion
A.
B.
C.
D.
iat
7l
Passage
Xll
(Questions 78 - 84)
79.
hydrocarbons, because:
A.
B.
C.
it is aromatic.
it has an aromatic conjugate
base.
D. in the conjugate
5.
6.
^l
because they are less basic and thus less able to donate their
lone pair of electrons to an electrophile. To compare the
nucleophilicity of alkoxides and alkyl sulfides, Reaction 1 is
carried out with a range of combinations of one solvent and
one nucleophile.
-9"
tlrf
Nuc-
Tffi n.c4ff.
H:C
Reaction
.l
+r
Solvent
H3CO-
Ether
t.44
H3CS-
Ether
HO'
Ether
1.03
HS-
Ether
1.16
H3CO-
Ethanol
3.19
H3CS-
Ethanol
2.12
HO-
Ethanol
3.35
HS-
Ethanol
r.96
H3CO
Water
4.22
H3CCOCH3
H:CS
Water
CI3CH
HO-
'Water
5.62
H3COH
HS
Water
2.14
Lewis acid?
A. CI3CH
B. H3CNO2
C. NaCH3
D. BFr
A.
B.
C.
D.
H3CNO2
it
fr. tf
:F
ni{
-Log rate
9',7
1.
-\,r
fol
A.
B.
C.
D.
.t
^'7
Table I
ft'c
-{.
Se
attributable to differences
The
&
77.
B.
C.
D.
8.
)st
nd
I)
ise
tic
3.
A.
B.
C.
D.
A.
B.
C.
D.
An
An
An
An
3S,
eir
he
is
9.
nd
4. In comparing
the properties
A.
B.
1.05
.
B.
C.
D.
2.04
c. 3.09
D.
4.52
for
na
\ill
ied
for
would:
.
B.
C.
D.
A
the
.{. c-H
B. C-I
C. C-O
D. C-S
ton
rller
The
)lS
The
rs is
eto
The
A.
B.
C.
D.
the
r the
; the
:nt.
GE
Passage
Xlll
(Questions 85 - 91)
.
.
C,
D.
aqueous solution:
illi
B. H3CCH2CCO2CH3
C. H3CCH2CH2CONH2
D. H3CCH2CH2CH2NH2
ol,cur
o
.-------->
88.
NI
CH 1
Figure
Cl3CNH3+?
A.
B.
Deacylation of an ester
Compound
If
c.
17.3
12.3
8.3
D. 1.0
89. If the pKu for NH4+ is 9.25, then pK6 for NH3 must
be equal to which of the fbllowing?
Cornpound C
A.
B.
9.25
D.
4.15
7.00
c. 5.75
6.0
1.0
pH
Figure
8.0 6
pH
7.0
8.0 6
7.0
8.0
pH
A,
B.
C.
D.
.{,
B.
C.
D.
ol conipounds is tl.re
Primary alcohols
1.
Aniline
A.
B.
C.
D.
Benzylamine
primary amines.
aromatic amines.
conjugated amines.
nonalkyl amines.
Esters
Secondary amines
Teltiary thiols
@irqplifi
Questions
92
97.
through
boiling point?
descriptive passage.
2.
A. H3CCH2OCH2CH3
B. H3CCH2CH2OCH3
C. (H3C)2CHoCH3
D. H3CCH2CH2CH2OH
A. 2-pentene
B. Diethyl ether
C. Heptanal
D. Cyclohexanol
I
,1
8.
.
.
C.
D.
cis-1,3-dichlorocyclopentane
trans-
1 ,3-dichlorocyclopentane
E-1,4-dichloro-2-butene
1,2,2,3-tetrabromopropane
-\
A.\
.
.
C.
D.
A
2,4-diethyl-3,5-dimethylheptane
4-ethyl-3,5,6-trimethyloctane
3-ethyl-5,6-dimethylnonane
3,5,6-trimethyldecane
C.
exhibits
conjugation?
I. 1,4-cyclohexadiene
II. 3-ethylcyclohexene
m. 2-methyl-1,3-cyclopentadiene
A. I only
B. II only
C . III only
D . I and III only
'r
5.
.
B.
C.
D.
C2H5
2-methyl-l,3-pentadiene
1.S-hexadiene
L Z-1,4-dichloro-2-butene
II. E-1,4-dichloro-2-butene
m. cis-1,2-dichlorocyclopentane
A. Compound I only
B. Compound II only
C. Compound III only
D . Compounds I and III only
by The Berkeley Review@
groups is found in
3-methyl-1,4-pentadiene
CH(oCH:
A. Aldehyde
B. Ester
C. Ketone
D. Oxirane
2-methyl-I,4-pentadiene
Copyright
D.
/5
iCHEMICA ES FIN!
Choice A is correct. According to the bond dissociation energies listed in Table 1, iodine and chlorine both make
their strongest bonds to methyi carbons. It thus can be assumed that bromine would exhibit the same behavior
as these other halides, and that the strongest bond to bromine is formed by a methyl carbon. Choice A is best.
J.
Choice C is correct. Table 1 shows an increase in bond strength for bonds formed between equivalent carbons and
atoms of decreasing size (I, C1, ar-rd O). From this, it can be concluded that shorter bonds are generally stronger
than longer bonds, and that as atomic size decreases, the bond length to a neighboring atom decreases. No bondlength data are provided in the table, but this can be inferred from the passage. Choice C is best.
4.
Choice A is correct. The hydrogenation of an unsubstituted alkene yields the greatest energy (according to the
heats of reaction listed in Table 2). A less stable reactant yields a greater amount of heat upon reaction, so the
n-bond must be weakest in an unsubstituted alkene. The energy generated from oxidative cleavage, or any
reaction that breaks the n-bond, is greatest when the alkene is unsubstituted. The best answer is choice A.
5.
Choice D is correct. The difference in reactivity between the cis and trans geometrical isomers of an alkene is
attributecl to i.ntramolecular steric hindrance in the cis compound, because the substituents are on the same side
of the molecule. The resonance, hybridization, and electronegativity of carbon are the same in both
geometrical isomers of the alkene. This eliminates choices A, B, and C and makes the best answer choice D.
6.
Choice D is correct. This question should be a lvelcome freebie, relative to other questions in the passage.
Alkene carbons have sp2-hybridization, and alkane carbons have sp3-hybridization. Two of the three carbons
in the compound are alkene carbons, while tire other carbon is an alkane carbon. The best answer is choice D,
two sp2-hybriclized carbons and one sp3-hybtidized carbon. Pick choice D to get your point for correctness.
7.
Choice B is correct. Table 1 lists the bond dissociation energy for various bonds, which is the energy required to
break the bond in a homoiytic fashion. This in essence means that Table 1 lists the bond strength. The strongest
bond, according to that data listed in Table 1, is the bond with the highest bond energy. The highest value
among the answer choices is the bond between the methyl carbon and chlorine. The best answer is choice B.
Choice D is correct. Double bonds are stronger than single bonds, meaning that more energy is required to break
a double bond than a single bond. Choices A and B are thus eliminated. The lower heat of hydrogenation in
the second chart implies that the reactant alkene molecuie is more stable. The more stable the alkene
compound, the stronger its n-bond. This means that the double bond in the tetrasubstituted aikene is stronger
than the double bond in the unsubstituted alkene. The best answer is choice D.
Choice D is correct. To convert the acid form of a nitrogen-containilg compound (in this case, a protonated imine
species) into a neutral species, you must add a strong base (strong enough to deprotonate the iminium cation).
Choice A is eliminated, because it is a strong acid, which protonates rather than deprotonates the compound.
Choice B is eliminated, because it is inert and has no effect on caffeile. Choice C and choice D are both bases,
but the stronger base is NaOH, so choice D is the better choice. The carbonate base is not strong enough to fu111'
deprotonate ihu i*ir-ri.rrrr cation. For best results in a case like this, pick choice D.
76
Choice B is correct. We know that the nitrogen in questions has sp2-hybridization for three reasons: It is
involved in one rc-bond, it has three substituents attached and no lone pairs, and it is pianar with respect to the
adjacent atoms bonded to it, with bond angles of approximately 120'. For so many good chemistry reasons, the
nitrogen in question is sp2-hybridized,, so why choose anything but choice B?
E
r
the
Choice B is correct. Because of the delocalization of electron density throughout the n-network of the caffeine
molecule (achieved by the resonance between all adjacent non-hydrogen atoms), the compound must be planar to
allow the p-orbitals to overlap correctly. This means that all of the atoms in a caffeine molecule, and thus all
of the nitrogens, must be coplanar with respect to one another. Pick choice B for a whopping good answer.
tW'
'bon
ized
rices
role.
Choice A is correct. Because of the resonance donation of the lone pair of electrons on nitrogen to the carbonyl
carbon, the C=O bond takes on some single-bond properti"es, which makes it longer than a standard sprhybridized C=O bond that lacks any resonance effect. The best choice is therefore choice A. |ust as a side note,
the C=O bond in formaldehyde is longer than the C=O bond in carbon dioxide because of the varying
hybridization of carbon in the two compounds. In formaldehyde the hybridization of carbon is sp2,while in
carbon dioxide it is sp. The more s-character in the hybrid orbital, the shorter the orbital and thus the shorter
the bond. The stable resonance structures for an amide are shown below:
:the
Ihis
rake
vior
-t
,1,
..o
and
llger
lt
:nd-
\r.-/t\
N-
tl
the
r the
any
<----->
:9:
lF
\gZL\
N-
Choice D is correct. Ionic forces are stronger than polar forces, so the ionic compound (acid salt form) should
have both a higher melting and a higher boiling point than the polar uncharged compound (free-base form).
This makes choice D correct, and you want that which is conect. Follow society's infiuence and pick D.
Choice A is correct. If the N-CH3 group is replaced by an oxygen atom, the compound that remains has an
oxygen between two carbonyls. This is referred to as an acid nnhydride (from the fact that the compounds forms
when two acids combine in a dehydration reaction). The best answer is choice A. There is no such term as an
"acid ester", so choice B is elin-rinated. An ester inl,olves just one carbonyl, so choice C is eliminated. A lactone
is a cyclic ester, and given that the compound is not an ester at all, it can't be a lactone. Choice D is eliminated.
good soivent for dissolving a dye to form an ink is one that is a liquid at roorn
temperature, evaporates quickly, and exhibits a high degree of dye solubility. Having a high vapor pressure
impiies that it evaporates readily, so choice A is eliminated. If it has functional groups that are similar to
the dye, then the dye is like1y to be highly soluble in the solvent, so choice B is eiiminated. If the boiling
point is slightly above room temperature, then it is a volatile liquid, so choice D is eliminated. The solvent
should not react with paper (celluiose), so the correct answer is choice C.
reak
rn
in
-:"
Choice B is correct. Becar-rse like dissolves like, the best solvent for dissolving the dye should also have
hydroxyl groups attached to it, just as the dye does. The best choice is therefore the alcohol, The carboxylic
acid is not a good choice, because carboxylic acids are not as volatile as alcohols. If you have melting points
memorized, then yor-l may be aware that carboxylic acids that are three carbons or greater in length are solids
at room temperature. If yor-r don't have them memori.zed, like 99.999"/0 of us, that's okay too. Aldehydes and
ketones may work, but not as well as the aicohol. The best choice is B.
:-.
Choice B is correct. Determining the IUPAC name for the compound requires that you count the longest
continuous chain of carbon atoms in this straight chain compound, which yields a total of ten. Next, you must
identify all functional groups on the molecu1e, including alkyl groups that are not a part of the carbon backbone.
The only functional group on this compound is a carboxylic acid. If there were multiple functional groups, the
more oxidized functior-ral gror,rp gets higher priority in the name of the compound. For instance, if there were
also an OH group, then it would be namecl a hydroxy substituent, rather than an alcohol. Having ten carbons
and a carboxylic acid group makes the compound decanoic acid. Choice B is the best answer.
(ene
nger
q
nrne
ion).
und.
ases/
rully
-:ryright
77
18.
Choice C is correct. When water is spilled on paper, it diffuses across the surface of the paper. If the ink bound
to the paper is soluble in water, it dissolves into the water and spreads out, or runs. So if an ink runs, it must be
soluble in water. The colored portion of the ink is the dye, not the solvent. Running ink means ihat the ink dye
is water soluble. Pick choice C for best results.
19.
Choice D is correct. As stated in the last paragraph of the passage, a compound must contain at least eight
carbons in its chain to be a good soap. The best soap has a polar and nonpolar end associated with the molecule.
The negatively charged carboxylate is at one end and an organic tail is at the other end. Molecules with
charged and organic ends are optimal for making a soap. Choice D has both eight carbons and a charged end.
20.
Choice B is correct. To be soluble in water, a compound must be either charged or polar. Because choices B and D
are ionic, they are better in this regard than choices A or C. The organic tail is smaller in choice B, so it
dissolves into water more readily than choice D. Pick choice B, and feel the sensation of correctness.
21.
Choice C is correct. Carboxylates are formed when a carboxylic acid is deprotonated. The Grignard reagent in
A deprotonates the carboxylic acid to form the carboxylate, but the cation is not sodium, so choice A is
eliminated. Choice B is invalid, because the Grignard reagent deprotonates the carboxylic acid (formic acid),
and the carboxylic acid does not have enough carbons to make sodium acetate. Choice D is invalid, because it
has too many carbons (propanoic acid has three carbons). The H3CCO2Na molecule results from the
deprotonation of acetic acid by a base with a counterion of Na+. The best choice is therefore choice C.
choice
Choice A is correct. Because of the resonance donation from nitrogen, the carbonyl bond (C=O) of an amide has
some single-bond character. Since a single bond is longer than a double bond, the single-bond character of the
amide carbonyi bond results in a longer carbonyl bond than the unconjr-rgated carbonyl (as observed with the
ketone). This makes statement I a false (not true) statement. Because of the previously mentioned resonance,
the carbon-nitrogen bond has some double-bond character, making it shorter than a standard carbon-nitrogen
single bond (as seen with a primary amine). This makes statement II a true statement. Because of the
resonance, the carbonyl oxygen carries a partial negative charge. This makes the oxygen more basic than
typical carbonyl oxygens (such as the one in an aldehyde). Statement III is also a true statement. Only
statement I is ttot true, so choice A is the best answer.
23.
Choice D is correct. As emphasized in the passage, nitrogen donates electron density to oxygen through
resonance. This places a partial negative charge on oxygen (increasing its basicity) and a partial positive
charge on nitrogen (decreasing its basicity). Choice C is thus eliminated, and choice D is correct. Choice A
should be eliminated, because oxygen is more electronegative than nitrogen. Choice B should be eliminated,
because oxygen is smaller than nitrogen. If you want to do what you should do, pick D and gain incredible
satisfaction doing what you should do.
Choice D is correct. Because of the resonance donation from nitrogen, the nitrogen has sp2-hybridization.
Having sp2-hybridization results in trigonal planar geometry. The carbonyl carbon aiso has trigonal planar
geometry, so the central two atoms force the three hydrogens and one oxygen to assume a coplanar orientation.
Choices A, B, and C therefore ail must be eliminated as incorrect geometric descriptions, making choice D the
best answer. The two resonance forms and the resonance hvbrid are drawn below:
o-
il
25.
,.'C\
o6
sp2-Hybridizati,n
/H
n-----------*
H/ \N*-H
Trigonal planar
I'
li
-7 Cf. ./H
H
a]T---._
H
sp2-Hybridization
Trigonal planar
Choice C is correct. From the passage, we know that amides are protonated at the carbonyl oxygen, so choice D
is eliminated. Because nitrogen is less electronegative than oxygen, it donates more electron density to the
carbonyl oxygen (through resonance) than the ester oxygen donates to the ester carbonyl oxygen. This places a
larger partial negative charge on the amide carbonyl oxygen than or-r the ester carbonyl oxygen. The larger
negative charge makes Site c the most basic site. Choice C is therefore the best answer.
7a
=fll
Choice A is correct. The most stable hydrogen bond forms between the best lone-pair donor (most basic site) and
the hydrogen with the greatest partial positive charge. Because amides are protonated at the carbonyl oxygen
(as stated and drawn in the passage), the carbonyl oxygen is most basic and thus donates one lone pair of its
electrons. This eliminates both choice C and choice D, Of the answer choices remaining, the hydrogen on
nitrogen carries the partial positive charge, not the hydrogen on carbon. This means that the hydrogen bond
forms between the carbonyl oxygen and the hydrogen bonded to nitrogen, thus the best answer is choice A. If you
are unsure, think of the hydrogen-bonding in B-pleated sheets.
Choice D is correct. Choice A is the most stable resonance structure of the amide (all octet and no formal
charges are present). When nitrogen donates electron density to oxygen, choice B becomes the resonance
structure. This is a minor contributor due to the formation of charges on the molecule. The fact that it is an alloctet resonance structure is favorable. If the nitrogen were to pull its n-electrons back from the carbon in answer
choice B, the resonance structure represented by answer choice C would be formed. Because carbon does not have
a complete octet in this resonance structure, it is a very minor contributor, but it is none-the-less a resonance
structure of the amide. It is not possible to form a double bond to the R-group, because that would require five
bonds to carbon. In order for carbon to donate in that manner (and have only four bonds), it must have had a lone
pair (and thus a negative charge) in the original structure. R was not drawn as having a lone pair, so it is
assumed that the R represents a standard alkyl group. The best answer is therefore choice D.
/o
\il
r\
,. c5-R' ..1\
I
H
Choice A (major)
o-
o-
o.r\*,R'
lt
-* o-tlN.R
HH
Choice B (minor)
Choice A is correct. Given that the molecular masses of the three compounds are roughly equal (59 g/mol, 58
g/llrol, and 44 g/mol), the top consideration for determining their boiling points is the intermolecular forces. An
amide has hydrogen-bonding, while a ketone and a hydrocarbon do not. At room temperature, most amides are
solids, acetone is a volatile liquid, and propane is a gas. Based strictly on the phases, the best answer (and the
only answer that lists acetamide as the highest) is choice A, BP'sslnmide > BPacetor.,u > BPpropane. Acetone has
a higher boiiing point than propane, because it is polar and more massive.
Choice C is correct. Chemist 1 considers molecular mass to determine the relative boiling points of compounds.
We are looking for the exception, so the correct answer is the choice where the lighter compound has the
higher boiling point (or lower vapor pressure). A higher vapor pressure at room temperature corresponds with
a lower boiling point. In choice A, the heavier compound of the two has the higher boiling point, so choice A is
not an exception to Chemist 1's general rule. In choice B, the heavier compound of the two has the lower vapor
pressure (and thus higher boiling point), so choice B also follows the rule. In choice D, the heavier compound of
the two has the lower vapor pressure (and thus higher boiling point), so choice D follows the rule too. In choice
C, the heavier compound of the two has the lower boiling point, so choice C contradicts Chemist 1's theory.
Choice A is correct. Chemist 2 considers intermolecular forces to determine the boiling point of a compound.
The strongest intermolecular forces correspond to the highest boiling point. The passage states that alcohols
have stronger hydrogen-bonding than amines. This means that the alcohol (I) has the highest boiling point
(and thus is listed first), because ethanol has the strongest H-bonds of the three compounds. The ether (II) has
the lowest boiling point, because it cannot form hydrogen bonds with itself (due to its lack of an electropositive
hydrogen). The order of the boiling points is therefore: I > III > II, making choice A the best answer.
Choice A is correct. Hydrogenation is the addition of H2 gas to an alkene to break the n-bond and reduce the
compound to an alkane. For every n-bond that is lost by the alkene molecule, two hydrogens are gained. This
increases both the molecular weight of the compound and the molecular flexibility of the compound (the
product is both more massive and more flexible than the reactant). Both of these effects increase the melting
point of the compound, making the melting point of the product greater than the melting point of the reactant.
This makes choice A the correct answer. Pick A and you'il be an MCAT supernova.
79
32.
Choice B is correct. According to Chemist 2 (and as a general rule), the stronger the intermolecular forces, the
greater the boiling point for a compound. The greater the boiling point for a compound, the less of it there is
that evaporates, thus the lower its vapor pressure. Pick choice B, to correctly interpret the logic of Chemist 2.
33.
Choice D is correct. Higher elevation means fewer molecules of gas per volume of air, and thus a lower
atmospheric pressure. The elevation and atmospheric pressure have no effect on the intermolecular forces
between molecules. Flowever, the lower atmospheric pressure means that less energy (heat) is required to
rgach a temperature at which the vapor pressure (Prrupo.) is equal to the atmospheric p."rs.tte (Patmosph"ric),
the definition of the boiling point. The boiling point is therefore lowered as elevation increases. This'makes
choice D correct.
34.
Choice A is correct. The boiling points of Compounds I and II are directly comparable, because they are
geometrical isomers. Compound I (the cis isomer) is poiar, while Compound II (the trans isomer) is nonpolar.
This means that the boiling point of Compound I is greater than the boiling point of Compound II, which
eliminates choice C. Because Compound III is an alkane, it is flexible (whereas Compounds i and II are rigid,
due to the n-bond), so Compound III is able to rotate between conformers. The most stable conformation of
Compound III is nonpolar, but because it can assume polar conformations on occasion, the compound is slightly
polar. The boiling point of Compound III is less than the boiling point of Compound L Compound III shbuld
have the second highest boiling point, because it is slightly polar, while Compound II is non-polar. Thus, the
correct order is I > IiI > II, making choice A the best answer.
J5.
Choice A is correct. The greatest reduction in voltage is caused by the compound with the greatest dielectric
constant. The greatest dielectric constant is associated with the most polar compound. Choices B, C, and D are
all symmetric, so they are a1l nonpolar. This eliminates choices B, C, and D. Only ArHF (choice A) is polar,
meaning that ArHF has the greatest dielectric constant. Choice A is a fine choice in a situation like this.
36.
Choice C is correct. The hydrolysis of an alkene forms an alcohol. An alcohol is polar, so choice A is
eliminated. The halogenation of an alkane forms an alkyl halide. An alkyl halide is polar, so choice B is
eliminated. The hydrogenation of an alkene forms an alkane. An alkane is most often nonpolar, so the best
answer is choice C. Reduction of an amide forms a primary amine. An amine is polar, so choice D is eliminated.
J/.
Choice C is correct. Assuming that an alkyl iodide is polar to begin with, then replacing iodine with bromine
results in a more polar compound, because bromine is more electronegative than iodine, so that the difference in
electronegativity between the halogen and carbon has increased. A carboxylic acid is more polar than a
primary alcohol (or any alcohol, for that matter), so choice B results in a more polar compound. Alkenes are
typically nonpolar, so the addition of HBr forms an alkyl bromide, which increases the polarity, so choice D is
eliminated. Because fluorine is more electronegative than chlorine, replacing a fh,rorine substituent with a
chiorine substituent results in a compound that is less polar, making choice C the choice that does nof result in
increased poiarity. Pick choice C to be a star of chemistry.
38.
Choice C is correct. The dipole moment changes only when a compound's bonds are either stretched or bent, if
the compound is asymmetric. This makes choices A and B less likely to exhibit the least change in dipole
moment. The dipole moment does not change drastically (if at al1), when the chemical bonds of a symmetric
compound are either bent or stretched. Therefore, the least change in dipole is observed in a symmetric
molecule. Stretching a symmetric molecule often balances out, meaning that the electron density is shifted
uniformly in opposing directions, The result is that the dipole of the molecule does not change. The best answer
is choice C. Bending a symmetric molecule can make it asymmetric, so choice D is not as good as choice C.
39.
Choice B is correct. To be nonpolar, all of the ligands must pu1l in such a way that the vectors of each
individual bond cancel out. Tetrahedral structures are not possible with six ligands, so choices C and D are
eliminated. It is only when the two chlorine ligands are trans to one another that they cancel out one another
in terms of polarity. The best answer is therefore choice B.
40.
Choice C is correct. A dielectric constant of zero results from a nonpolar molecule. The only nonpolar molecule
among the answer choices is trans dichloroethene. Cis alkenes are polar, so choice B is eliminated. Choice D is
trans, but there are different substituents on each carbon, so it is polar. The best answer is choice C.
Copyright
80
ES
Choice D is correct. Choice A is nonpolar, because the vectors expressing the electron withdrawal of the
fiuorines cancel out, so choice A is eliminated. Fluorine is more electronegative than chlorine, so the
asymrnetric electron distribution is found n'ith choices C and D, which rules out choice B. In choices C and D,
the fluorine atoms withdraw the electron der-rsity, making the molecule asymmetric. In the propane molecule
(choice D), the methyl substituent donates eiectron density to the electron-poor central carbon, placing a
partial positive charge on the methyl groupi therefore, it increases the dipole moment. This makes the
to
propane molecule more polar than the ethane molecule. The structures are shown below:
1e
15
CI
:1,
:),
ES
re
rr.
,h
.1,
.'. nonpolar
of
lr.
td
1e
slightly polar
]C
.t,
Lc
is
St
Choice B is correct. For a tetrahedral structure, if the four ligands are not all equivalent, then the structure is
asymrnetric. If the compound is asymmetric, then it must be polar (have an asymmetric distribution of electron
der-rsity). This makes statement I true. Figure 1 shows an example of a 1,4-disubstituted cyclohexane molecuie
that is tlot polat, which means that statement Ii is rzol true. A11 optically active compounds must be
asymmetric in order to be optically active, so they must be at least slightly polar, This makes statement III
trtre. Only statement lI is not true, so choice B is the best answer.
'.e
tn
a
:e
is
_:1
Choice B is correct. A dication carries a +2 charge, so it must be coupled with an anion that is organically
soluble. The only organic anion among the answer choices is choice B.
Choice A is correct. A micelle turns inside out from its aqueous structure rt'hen it is added to an organic solvent
(as stated in the passage). Figure 1 shows a micelle as it appears in water, where the polar heads are exposed
to the liquid, and the organic tails are protected in the core. In a hydrophobic (organic) solvent, the organic
tails are exposecl, and the polar heads form a protective core. This is best illustrated in choice A. Choice C
may look familiar, in tl-Lat cell membranes arrange themselves in such a manner. Choice D is a "throw-away"
answer, because the tail and the head of the compound exhibit no attractive forces.
Choice A is correct. To be absorbed through respiration, a cornpouncl must be a gas or a vapor, because only gases
are absorbeci through respiration. This means that any compound intended to be taken into the lung must be
either a gas or a liquid r,r,ith a low boiiing (one with a high vapor pressure). There is hydrogen-bonding in
choices B, C, ancl D, but not in choice A. Hydrogen-bonding increases the boiling point and thus lowers the
vapor pressure. All of the compounds have roughly comparable masses (either 73 or 74 grams per mole). The
only factor to consider in approximating the relative boiting points is hydroger-r-bonding. The best answer is the
ether, choice A. As a point of trivia, it is estimated ihat the average human adult takes in approximately
3500 gallons of air a
1S
Choice B is correct. To be water-soluble, the compound should be able to form hydrogen bonds. Choices C and D
are eliminated immediately, because they are hydrophobic. Although choice A has an alcohol group, it is
primaril;z organic. Choice B has two hydroxyl groups and an amide group. All of these functional groups form
hvdrogen bonds, so choice B exhibits the greatest amount of hydrogen-bonding. The best answer is choice B.
8l
47.
Choice D is correct. The best micelle has an ionic (charged) head and a long carbon chain for its organic tail.
Choices A and C are eliminated, because they have uncharged heads. Choice D is a better answer than choice
B, because it has a longer organic tail.
48.
Choice D is correct. A micelle enhances the water solubility of a compound that is normally insoluble in water.
This question therefore is asking for the least watersoluble compound. An alcohol, a carboxylic acid, and an
amine all exhibit hydrogen-bonding (although within a tertiary amine, there is no protic hydrogen for
hydrogen-bonding), so they should all be water-soluble to some degree. Because an alkene has no hydrogenbonding (it has neither a lone pair nor an electropositive hydrogen), it is unlikely that it would be watersoluble at all. The best answer of the given choices is therefore choice D.
49.
Choice A is correct. The organic tails of micelles are held together by the weak attraction associated with van
der Waals forces (choice A). The organic tails are alkyl-based, so they are nonpolar, and they contain neither
nitrogen, oxygen/ nor fluorine. This means that choices B and C are both eliminated, because to form hydrogen
bonds, a compound must have an electropositive hydrogen bonded to either nitrogen, oxygen, or fluorine. Choice
D is eliminated, because covalent bonds are formed in chemicai reactions, and the organic tails in micelles
exhibit only attractive forces, nothing as strong as covalent bonding. The best answer, and thus choice to make,
is choice A.
50.
Choice D is correct. Hydrogen-bonding weakens the covalent bond to hydrogen and thus makes the bond easier
to vibrate. This means that as the degree of hydrogen-bonding to a protic hydrogen increases, the IR
absorbance for the bond decreases in energy (in terms of wave numbers) and the peak broadens (showing a
variety of strengths associated with the hydrogen-oxygen covalent bond). The greatest amount of hydrogenbonding is found with the carboxylic acid, as shown by the smallest wave number and broadest absorbance in
the IR. The best answer is choice D.
51.
Choice A is correct. The broadest peak is associated with the compound having the greatest amount of
hydrogen-bonding. As is observed in alcohols, the amine with the least steric hindrance exhibits the greatest
amount of hydrogen-bonding. The least steric hindrance is found in ammonia. The best answer is choice A. As a
point of interest, the tertiary amine has no N-H covalent bonds, so it has no hydrogen-bonding.
\)
Choice A is correct. The relationship between bond. strength and IR absorbance is that the lower the absorbance
value in the IR (as measured in cm-1), the lower the energy associated with the stretching vibration of the
bond. The lower the energy necessary to stretch a bond, the lower the energy necessary to break the bond, and
thus the weaker the bond. Longer bonds are usually weaker bonds. Thus, as bond length increases, the wave
number of IR absorbance decreases. This eliminates choices B and D. An increase in the degree of hydrogenbonding weakens and thus lengthens the bond. This eliminates choice C and makes choice A the best answer.
53.
Choice D is correct. Of the choices, only primary amines have a protic hydrogen, which means that only
primary amines exhibit hydrogen-bonding. The best answer is choice D.
54.
Choice B is correct. The strongest hydrogen bond comes from the more basic lone-pair donor (found on the
nitrogen atom, which is less electronegative than oxygen) being donated to the most protic hydrogen (found
covalently bonded to the oxygen). This makes choice B the best choice.
55.
Choice D is correct. The addition of dimethyl sulfide to solution reduces the degree of hydrogen bonding
exhibited by the alcohol, because less alcohols will be adjacent to one another to form hydrogen bonds. The
absorbance associated with a hydroxyl peak sharpens with the reduced hydrogen bonding. Associated with
reduced hydrogen bonding is a stronger covalent bond and thus an IR absorbance with a higher wave number.
Pick choice D for optimum correctness satisfaction.
56.
Choice A is correct. The IR absorbance of a covalent bond is affected by hydrogen-bonding as stated in the
true. As hydrogen-bonding increases, the covalent bond lengthens, so Statement II
is true. The acidity of a proton increases with hydrogen-bonding, because the covalent bond to hydrogen is
weakened. This is why acidity is higher in water than in other solvents. This makes Statement III true. The
only not true statement is Statement I. The best answer is thus choice A.
Copyright
a2
57.
Choice D is correct. From the data in Table 1, it can be seen that branching in a hydrocarbon increases its octane
rating. The greatest amount of branching is observed with 2,2,4-trtnethylpentane, choice D, which can be
inferred from reading that 2,2,4-trimethylpentane has an octane rating of 100, higher than the straight-chain
hydrocarbons. Don't be a dodo, pick D.
58.
Choice D is correct. According to Figure 1, kerosene has a boiling-point range of 175"C to 280"C, so the
component most likely to be found in kerosene should have a boiling point in that range. The four answer
choices are saturated hydrocarbons of eight, ten, ten, and fourteen carbons. The eight-carbon compound should
be found in the petroleum range, and the ten-carbon compounds are probably found in the petroleum-to-naphtha
range. You should use test-taking iogic to eliminate choices B and C, because their boiling points are simiiar,
given that their molecular masses are identical and their structures are similar. The best answer is choice D,
with the highest molecular mass (and thus the higher boiling point) of the choices. To make an estimate of
the boiling points for both n-octane and n-decane, you can use the trend in other straight-chain hydrocarbons,
where n-hexane has a boiling point of 69"C and n-heptane has a boiling point of 9B'C. Following this trend
predicts that n-octane has an approximate boiling point of I25"C - 130"C and n-decane an approximate boiling
point of 775'C - 180"C. The branching of Z,2-dimethyloctane reduces the boiling point from that of n-decane
(the straight-chain, ten-carbon alkane) to somewhere around 165"C to I70'C. The2,2,4,4-tetramethyldecane is
most likely to have a boiling point in the 175"C to 280"C range. Your job, should you accept it, is to pick D,
59.
Choice D is correct. From the data in Table 1, it can be seen that branching increases the octane rating of a
hydrocarbon. For example, as branching increases, so does octane rating for the seven-carbon aliphatic
hydrocarbons 2,2,3-trtmethylbutane > 2-methylhexane > n-heptane. This makes choice A a valid statement,
thus eliminating choice A. From the data in Table 1, it can be seen that as branching increases, the boiling
point decreases (for hydrocarbons of comparable mass). This can also be seen with the boiling points of the
seven carbon aliphatic hydrocarbons, which have relative boiling points of n-heptane > 2-methyihexane >
2,2,3-trrrnethyibutane. Choice B is a valid statement, so it is also eliminated. Due to branching, the
hydrocarbon with the greatest number of alkyl substituents has the greatest mass of compound occupying the
smallest volurne. This results in an increase in density with branching. Choice C is a valid staternent, so it is
r
,r
e
S
t,
T
tr
R
a
rf
)L
also eliminated. Hydrocarbons have no hydrogen-bonding, so regardless of the arnount of branching, hydrogenbonding neither increases nor decreases from hydrocarbon to hydrocarbon, This makes choice D an invalid
statement as to the effect of branching. You should smile brightly when you pick choice D.
:e
IC
60.
Choice B is correct. As density increases for a hydrocarbon (or any gas), it does not rise as easily. This means
that as density decreases, the ability of the vapor to rise (ascend the cracking column) increases. This
eliminates choice A. Choice D is eliminated, because as shown in the apparatus in Figure 1, the aromatic
hydrocarbons are not collected in the highest chamber of the cracking column. You could have immediately
deduced that the correct answer is either choice B or C, because they are opposites and the boiling point is
listed in the diagram. As indicated by the picture in Figure 1, the hydrocarbons with the lower boiling points
are collected towards the top of the cracking column, which makes choice B the best choice. You'd be sad if you
were to choose anything except choice B.
61.
Choice D is correct. Octane rating is based on the ability of a compound to distribute heat uniformly as it
combusts. This ability is found in compounds that are capable of reieasing their heat energy steadily over an
extentied period of tirne. The best answer is therefore choice D. Do what is best, and pick choice D. The octane
rating does not depend on the enthalpy or entropy of combustion, although the favorability of the combustion
reaction does. The ratio of carbon dioxide to water depends only on the number of carbons and hydrogens in the
fuel"
62.
Choice D is correct. Because toluene and benzene have octane ratings higher than the other six- and sevencarbon saturated hydrocarbons, it can be inferred that aromaticity increases octane rating. Statement I is
therefore a true statement. Because toluene (methylbenzene) has an octane rating of 120 and benzene has an
octane rating of 106, it is assumed that ethylbenzene should also have an octane rating in excess of 100.
Statement II is therefore a false statement. Because of the brar-rching associated wrth 2,2,3-trimethylbutane, it
has a high octane rating. A high octane rating is a quality associated with a good fuel additive, so a branched
hydrocarbon such as 2,2,3-trirnethylbutane is a good fuel additive. Statement IIi is therefore a true statement.
Because statements I and III are both true statements, the best answer is choice D.
Ld
,-e
n-
rd
irg
he
rth
er.
he
III
.is
he
83
63.
Choice D is correct. Because 2,2,4-ttimelhylpentane is a saturated hydrocarbon, all of its carbons have a
hybridization of sp3. In the final product, the carbons are all pr"r"r-,i in the form of carbon dioxide. The
hybridization of^ carbon in carbon dioxide (CO2) is sp. This means that in this reaction, the hybridization
changes from sp3 to sp. The best answer, and on- we highly recommend to all parties interested in success, is
choice D.
64.
Choice A is correct. The start of the third paragraph states that the closer the electrons within a carbonhydrogen bond are to the carbon nucleus, the more acidic the compound is. To determine the relative acidity,
you must make a decision about how close the electrons are to the nucleus. The passage also states that the
more p-character there is in the hybrid, the longer the bond is. Connecting the two concepts, you should reach
the conclusion that the shorter the bond, the closer the electrons are to the nucleus. This means that the less pcharacter there is in the hybrid, the more acidic the hydrogen. The most acidic hydrogen is thus found on an
sp-carbon. In 3-methyl-1-pentyne, carbons 1 and 2 are sp-hybridized, but only carbon t has a hydrogen
attached. Pick choice A for optimal results. Make a note from the conclusions that sp > sp2 > sp3 for uiiaity.
sphybridized
i\
H- C: C- Ct -
CH
2-
CH3
cll3
55.
Choice D is correct. The largest Ku is associated with the strongest acid. All of the choices are hydrocarbons,
so the most acidic proton is the one on an sp-hybridized carbon, as opposed to either an sp2-I.rybridized o, sp3hybridized carbon. Of the four answer choices, only choice D has a hydrogen bonded to an sp-hybridized
carbon, so choice D is the best answer.
66.
Choice A is correct. Al1 of the compounds are depro^tonated hydrocarbons (with a lone pair on carbon), so the
strongest base is the one with the lone pair on an spJ-hybridized carbon. The only choice with a lone pair of
electrons ot-t an sp3-hybridized carbon is choice A. The iation is irrelevant to the pioblem, because it is sodium
in each answer choice.
67.
Choice D is correct. NaNH2 is a base strong enough to deprotonate a hydrogen on an sp-hybridized carbon.
Although this is true, it is not critical information in solving this question. Only one answer choice can be
correct, so the correct choice must be the compound with the most acidic hydrogen. This means that this
question is reduced to asking "Which compound, of the choices listed, has the most acidic proton?" The most
acidic hydrogen is attached to the oxygen, so you had better pick D.
68.
Choice C is correct. The longest carbon-carbol bond is a single bond between the two largest orbitals. The
largest of the three possible hybrid orbitals is sp3 , so the longest carbon-carbon bond is formed between an sp3hybridized carbon and an spJ-hybridized carbon. Choices B and D are eliminated immed-iately, because they
contain no C-C single bond. Choice A is a bond between an sp-hybridized carbon and an sp3-ltybridized carbon,
while choice C is between an sp2-hybtidized carbon and an sp3-hybridlzed carbon. An sp2-6t6rid orbital is
longer than an sp-hybrid orbitai, so choice C is the best answer.
69.
Choice C is correct. The weakest carbon-carbon bond is associated with the longest carbon-carbon bond. Choice
A is eliminated, because the C-C bond is a triple bond, and triple bonds are the shortest of carbon-carbon bonds.
Choice B is between an sp-hybridized carbon and an sp3-hybridized carbon, choice C is between an sp2hybridized carbon and an sp3-hybtidi"ed carbon, and choice D is between an sp2-hybridized carbon and an sp2hybridized carbon. Choice C is the longest, so it would terrific if you would pick choice C.
70"
Choice A is correct. The iowest pK6 is associated with the strongest base. Because the most acidic proton is
found on an sp-hybridized atom, the strongest base must be a lone pair on un sp3-hybtidrzed atom. Choices C
and D are spz-hybridized nitrogens, so they are both eliminated. Choice A is better than choice B, because the
lone pair of electrons on nitrogen in choice B is tied into resonance r,r'ith the adjacent alkene n-bond. Electronwithdrawing resonance reduces a compound's basicity.
a4
Tt-
Choice D is correct. For a reaction to have an equiiibrium constant greater than 1.0, the reaction must be
favorable in the forward direction as written. A favorable acid-base reaction proceeds from stronger acid to
weaker acid in the forward direction as written. The larger the equilibrium constant, the more favorable the
reaction, so the strength of each acid can be inferred from the K"O values in the table. In choice A, the reaction
proceeds from the weaker acid (C13CH with KuO of 8.0 x 10-9) to the stronger acid (H3CCH2SH with K"O of 5.2
x t0a). This means that this reaction is unfavorable and thus has u Keg < 1. Choice A is therefore eliminated'
In choice B, the reaction proceeds from the weaker acid (H3COH witfi K"O of g.g x 10-1) to the stronger acid
(H3CNO2 with K"O of 8.2 x 104). This means that this reaction is unfavorable and th.y_s \a1 l Sgq < 1. Choice
B is therefore eliminated. In choice C, the reaction proceeds Jrom the weaker acid (H3CCOCH3 with Kg* of
2.0 x 10-4) to the stronger acid (H3COH with K"O of e.g x 10-1). This means that this reaction is unfavorable
and thus has a K"O < 1. Choice C is therefore elimlnated, It is only in choice D that the reaction proceeds from
a stronger acia 6IiCCOCH2COCH3 with Keq = 1.2 x 106) to a weaker acid (CI3CH with Kuo = 8.0 x tg-v;. The
correct answer is choice D.
Choice C is correct. Reaction 2, the experimental reaction from the passage, involves the protonation of CSHSto form CSHO. This question asks for the reverse reaction. This means that any acid that shows an equilibrium
constant less than 1.0 has a conjugate base that is strong enough to deprotonate C5H6. Choices A and B are
eliminated, because they are acids, not bases. Because only methanol (CH3OH) shows an equilibrium constant
less than 1.0, only methoxide anion (CH3O-) is strong enough to deprotonate C5H6. The best answer is choice C.
Choice D is correct. The reaction as drawn proceeds from the stronger acid to the weaker acid, therefore the
equilibrium constant is greater than 1.0. When the equilibrium constant is greater than 1.0, the products are in
higher concentration at equilibrium than the reactants. This means that H3CCH2S- is in higher concentration
than H3CO-. This eliminates choices A and C. To distinguish choice B from choice D, the initial
concentrations must be known. Because H3CCH2SH and H3CO- are mixed equally initially, they must be
equally concentrated at equilibrium, The best answer therefore is choice D'
Choice B is correct. The conjugate base of the 1,3-cyclopentadiene species has six n-electrons in a continuous
cyclic planat affay of p-orbitals. These conditions result in aromatic stability. The best explanation for the
relative ease with which the 1,3-cyclopentadiene loses its proton is the aromaticity associated with the
conjugate base ( 1,3-cyclopentadienyl anion). The more stable that the conjugate base is, the stronger the acid
is. Pick choice B and be satisfied.
L-
Choice A is correct. The weaker of the two acids has the larger of the two pKn values. This question is asking
for the weakest acid relative to the strongest acid. As the acid gets weaker, the reaction with CSHS- becomes
less favorable, so the equilibrium constant for the reaction gets smaller. C13CH shows the Iowest equilibrium
constant of the answer choices, so it is the weakest acid and thus has the highest pKo value. It is only in choice
A that CI3CH is listed as having the highest pK3 value, which makes choice A correct.
.S
Choice C is correct. A Lewis acid is an electron-pair acceptor. The classic example of a Lewis acid is choice D,
BF3, with highly electronegative fluorine atoms and an empty p-orbital that can readily accept electrons.
This makes the boron severely eiectron-deficient. Both CH3CI and CH3N 02 are listed as acids in the table, so
choices A and B are not good choices. NaCH3 cannot accept a lone pair, but instead readily donates a lone pair.
This means that choice C is not a Lewis acid, and in fact is a Lewis base. Pick C to be terrific.
'i\
Choice D is correct. Using Equation 1, the K"q for a reaction is found by taking L0 to the power of the product
acid pKu minus the reactant acid pKu. In the itandard reaction, C5H6 is the product acid andits^pKuvalue is
10 0)
= 195'
given as fS.0" If the pKu of the reactant acid is 10.0, then the equilibri.tm cor-rsiar-,t wouid be 10(i5'0-ihe question is thereiore: "Which acid in Table t has an equilibrium constant of roughly 105?" The best answer
is choice D, CH3NO2, with an equilibrium constant of 8.2. x 104 when it reacts with C5H5-.
.ls
iC
ire
rn-
-i.
Choice A is correct. Reading from Table 1, the fastest reaction rate corresponds to the lowest negative log
value. Of the answer choices, the slowest reaction is observed with an alkoxide in an aprotic solvent. The 1.44
makes it the fastest reaction rate of the choices offered to you. The best answer is therefore choice A.
-pyright
a5
79.
Choice B is correct. Ethyl sulfide would react with 2-iodopropane just slightly more slowly than methyl
sulfide, so the negative log of the reaction rate would be slightly higher tnai lsir for the ethyl sulfide. The
best answer is choice B, 2.04. Following the trend for ether s6lvent silows a negative 1og value for HSof I.76
and for H3CS- of 7.97. It can be conciuded from this that the negative log of-rate for "H3CCH2S- should be
greater than 7.97, but no iarger than about 2.2. The only choice in this .utlgJi, 2.04. The tact of linearity in the
trend is due to the fact that the change in steric hindrance from H3CS- to u3CCu2S- is less drastic than the
change from HS- to H3CS-. The difference il the change in steric hindrance can be seen in the smaller change
i1
negative log value for the reaction rate.
80.
Choice C is correct. Because bromine is smaller than iodine, bromine forms a stronger bond with carbon than
iodine, so bromine is a worse ieaving group than iodine. Tl-re rate of the reaction dJpends on the electrophile.
The worse the leaving group, the worse the electrophile, and the slower the nucleophilic substitution reaction.
The bromine leaving group wotild yield a slower reaction (a decrease in the ,"u.tior-, rate) than the iodine
leaving group, and consequer-rtly a larger negative log of the reaction rate. The best answer is thus choice C.
81.
Choice B is correct. The weakest bond is the one that would be broken in a nucleophilic substitution reaction,
such as Reaction 1. In Reaction 1, the bond that is broken is the one between carbon und iodi.,", thus the
C-I bond
must be the weakest of the choices. Pick choice B. Choice A should be eliminated, because the H is not the
leaving group in Reaction 1. Because a C-O bond and C-S bond are formed when a C-I bond is broken in
separate reactions listed in Table 1, it can be inferred that both the C-O and C-S bonds are stronger
than the
C-I bond. This eliminates choices C and D and further supports choice B as the best answer.
82.
Choice A is correct- As the solvent is changed from ether to ethanol and finally water, the degree of hydrogen
bonding in solution increases. It can be observed from the data in Table 1 that the reaction rate decreases. The
conclusion must be that hydrogen bonding decreases the reaction rate. Choices C and D are eliminated. The
rate must decrease due to hindrance of the nucleophile, not enhancement. Your answer is choice A"
83.
Choice D is correct. According to the data in Table 1, regardless of the solvent, the negative 1og of the reaction
rate is greater with H3CS- than HS-. This means that changing the nucleophile from HS- to H3CS- decreases
the reaction rate. Choice A is therefore eliminated. the negitive log values of the rate are lower with the
ether solvent than the water solvent, therefore water solvent must decrease the reaction rate. This eliminates
choice B. Decreasing the temperature always produces a clecrease in the reaction rate, so choice C is eliminated
too.
The negative log values of the rate are greater with the water solvent than the ethanol solvent,
iE
r!9lti
so
ethanol solvent must increase the reaction rate. That makes choice D the best answer. This question requires
determining the relationship between the reaction rate ancl negative 1og of the rate.
84.
Choice C is correct. In ether, aikoxides have lower negative 1og values for their reaction rates than alkyl
sulfides, so the alkoxides must react faster. This eliminates choices B and D. The passage states that the
difference in reactivity can be attributed to alkoxides being better bases than alkyl sulfides. The stronger the
base, the lower the pK6 value. Pick C and feel jovial for just a moment, at least until the next question stirts.
85.
Choice C is correct. The most basic species is the compound containi-ng nitrogen. In general, nitrogen compounds
are more basic than oxygell- and sulfur-containing co-mpounds of eqtr"at hybiidization. This eliminates choices A
and D. The degree of substitution is irrelevant. Esters have no lone pair of electrons that can be readihdonated to a proton, so choice B is not correct. The best answer is an amine, independent of whether it is
primary, secondary, or tertiary. This means that you really should pick C for the sensation of correctness.
86'
Choice C is correct. The rate referred to in Figure 2 is for a nucleop}rilic substitution reaction at a carbonyl site.
There is a direct corelation between nucleophilicity and the rate of reaction. The graphs show that above a
pH of 7, as the pH increases, so does the reaction rate. This mea11s that ihe nucleoptritcity increases. As pH
incteases, compounds are no longer cationic. This eliminates choices A ancl B. Size ls noi applicable here, so
choice D is eliminated. Afier eliminating the wrong choices, vou shor,rld settle for choice C as the best answer.
87.
Choice D is correct. At pH = 9.0, all of the compounds should be neutral (although the amine in choice D marhave a small fraciion that rernains protonated). Tl-re most reactive compound is the best nucleophile. For
nucleophilicity, an arnine is better than an ether, an ester, or an arnide. Foi this reason, pick D.
Copyright
dt
.il1
'-l
IE
-bt
te
1e
',e
Choice C is correct. The chlorine atoms are electron-withdrawing by the inductive effect (chlorine is more
electronegative than carbon). Electron-withdrawing groups make the compound more acidic and thus lower its
pKu value. Both choice C and choice D are lower than 10.3. Choice C is the better choice, because the
inductive effect is not so substantial that it will make the ammonium cation that acidic. For the pKu to drop
down to 1.0 would mean that the three chlorine atoms on the methyl group increased the acidity by a factor of
109'3 = 2 x 709 = 2,000,000,000 times. That is too much. Be conservative and pick C.
in
Choice D is correct. The sum of pKu + pKU for a conjugate pair in water is equai to 14.0 al25"C. This means that
pK6 for NH3 (the conjugate base of NH+*) is equal to 14.0 - 9.25 = 4.75. Pick D and score with the best of them
(whoever they are).
Choice A is correct. The hybridization of carbon in a carbonyl compound, such as an ester (which contains one 7[bond), must be sp2 1th" n-bond requires one p-orbital, so only two p-orbitals remain for hybridization). This can
also be deduced from the trigonal planar structure of the carbonyl compound. The hybridization of carbon in the
tetrahedral intermediate (which contains no lr-bonds) is spJ. The final product again has the carbonyl
functionaiity, only now with the nucleophile attached. Tl." carbonyl product still has trigonal planar
geometry. The hybridization therefore changes from spt to spJ and back to spt in the overall reaction, making
choice A your choice. Make that choice today!
Choice A is correct. In each case, there is a nitrogen with one alkyl group and two hydrogens. This defines a
primary amine , so both compounds are primary amines. It just so happens that the R-groups are aromatic rings/
but they are not aromatic amines per se, because the nitrogen atom is not a part of the aromatic system. The best
answer is choice A. Of the two amines, only one is conjugated (aniline), so choice C does not describe both
structures.
Choice D is correct. Alcohois exhibit hydrogen-bonding, which increases their intermolecular forces. The
stronger forces make it harder to move a molecule from the liquid phase into the gas phase. This raises the
boiling point of an alcohol compared to a molecule of comparable size, so choice D has the highest boiling
point. Molecular mass is of concern as well, but choice D is also the heaviest of the choices.
Choice B is correct. The longest chain is eight carbons, so based on that alone, you know that the best answer is
All you need to do is find the longest chain to decipher the correct answer choice.
choice B (octane).
L,.
.i._
Choice C is correct. Conjugation is defined as consecutive, alternating n-bonds. The structures are drawn below.
OnIy Compound III has conjugation, so choice C is correct.
:he
il
^ i-
rl.)'
_:- 1:
'ite,
\4,/
\,.
,.^
';H
Choice D is correct. Saying that a compound has a dipole that is not equal to zero is equivalent to saying that
the compound is polar. Cis compounds (both alkenes and cyclic structures) are aln'ays polar. This makes both
Compound I and Compound III polar. You need not even examine Compound II, because no answer choice includes
all three compounds. Pick choice D to score more MCAT points.
F..l
LOns
- :vright
97.
98.
Choice D is correct. All alcohols have hydrogen-bonding, which increases their intermolecular forces and thus
increases their boiling points, so choice D has the highest boiling point. Note that all of the compounds have
exactly the same formula (and thus the same molecular mass). This eliminates the need to accbunt for any
differences in molecular mass (which would also affect the boiling point). Because of the linear nature of
choice B and its asymmetry (which makes it more polar than the two remaining choices), it should have the
second-highest boiling point.
Choice C is correct. For a compound not to be polar, it must be s).'rnmetric. Cis compounds are asynunetric about a
point (although they may have mirror-plane symmetry, rather than point symmetry), and thus are always
polar, so choice A is eliminated. This leaves choices B, C and D as possible answers. An odd-numbered ring
must be polar when it has two substituents, so choice B is polar and thus ruled out. In choice D, the middle
carbon has varying substituents attached (not all four groups are identical), so it cannot be symmetric, thus it is
polar, too. By eliminating three choices, choice C must be the correct answer. Drawing choice C out shows that
the individual dipoles for the bonds cancel each other out, making the compound nonpolar.
E-1,4-dichloro-2-butene
The individual vectors cancel out, so there is
no net vector. The compound is nonpolar.
99.
Choice B is correct. The most heat is generated by the least stable compound; thus finding the least stable
compound is the task at hand. All of the choices have the same formula (C6Hg) so it comes down to structural
features. The four-membered ring is unstable, so choices A and B are good. Choice B has no conjugation, while
choice A does (conjugation is a stabilizing feature), so this makes B the least stable compound a*ot g the answer
choices. The bond angles are not the optimal 109.5", whether the n-bond is in the ring or not.
100.
Choice C is correct. Translating from the chemical formula into the structure yields the compound below:
H3CH2C
H3CO H H
CFI3
There is no aldehyde group (which would have been represented as CHO), so choice A is eliminated. There is
no ester group (which would have been represented as CO2R), so choice B is eliminated. There is a carbonyl
adjacent to two alkyl groups, so the compound has a ketone functionality. This eliminates choice D and makes
choice C the best answer.
Copyright
lsomerism
Section II
Structure
Elucidation
a)
b)
by Todd Bennelt
Isomers
i. Constitutional Isomers
ii. Stereoisomers
iii. Configurational lsomers
iv. Optical and Geometrical Isomers
Conformational Isomers
i. Eclipsed vs. Staggered Conformation
ii. Oauche vs. Anti position
Newmanprojections
!ii. Cycloalkanes
iv.
v. Cyclohexane
vi. Chair and Boat Conformations
vii. trquatorial vs. Axial Orientation
Structural trnsights
a) Structural Symmetry
b) Units of Unsaturation
H:C
a)
b)
c)
d)
Qeneral Spectroscopy
Infrared Spectroscopy
i. Theclry and Key Signals
ii. CommonAppplications
iil Hydrogen-Bonding
Ultraviolet Spectroscopy
l. I heory
ii" Common Appplications
NMR Spectroscopy
i. Theory
ii. Structural Symmetry
iii. Proton NIVIR
iv. Shift Values
v. Splitting Pattern
oi: Signal Integration
vii. Structural Features
RERI{EIEY
L)K.E'v.r.-b.wt
Speci ahzing
in MCAT Preparation
Structure Elucidation
Section Goals
Be able to identifv isomers from both their structure and their name.
There are several types of isomers. Be familiar with structural isomers (identified by different
connectivity), stereoisomers (identified bv asymmetry), optical isome-{s (and their ability to rotate
plane-polaijzed lieht), geometrical isom'ers (found #ith rings and alkenes), and conformational
isomers (identified"by ro-tation about bonds or ring-flips). You should know how the different types
of isomers are related to one another.
Be able to identify the more stable chair conformation for six-membered rings.
Cvclohexane and pyranose sugars involve three-dimensional ring structures. The most stable
conformation result3 in the leaEt steric hindrance. As a general rule, axial orientation results in
greater steric hindrance than equatorial orientation. Know the difference in stability between axial
Srientation and equatorial oriehtation. Recognize the steric repulsion associated *ith 7,2-diaxial,
1,3-diaxial, and 1,4-diaxial orientation.
@3
*t
,-11-
@3
Some auestions reouire vou to determine the potential functional groups of a molecule. The presence
of eithbr a n-bond'and 1 rine within a strucfure results in a uniFof dnsaturation, which manifests
itself as two fewer hvdroeefrs in the formula. A fullv saturated hvdrocarbon or carbohydrate has
a total of 2n + 2 hydrdgen itoms in the compouLnd, where n is the nurhber of carbons in the fompouLnd.
*I-
-:ii
rM':lT
:tr:I,
Jtll
I'L
[ht*
arLi:r:
ll l:-i,
t?
f,
JIl
Jllli.ru
l8,itr
lll
[.i
ri
slru
ItI l[
ffir*
;r Ii|]U
ryr*
rux
rllietu
1ll[ir'u
]L
LJ u
4$r
W,ot!,r
$mfigll
Organic Chemistry
Structure Elucidation
Introduction
In this section, lve shall address the concept of isomerism and the many
classes of
isomers. Isomers have the same atoms within the molecule, but they differ
in
some manner, so that the molecules are not superimposable on one
another. The
difference could result from different bonding *il-,ir-, the molecules,
similar
bonding but different three-dimensional distribution about a stereogenic
center,
or the same bonds and stereogenic syrnmetry with different conformational
orientation. A significant part of structure elucidation is determining the
exact
isomers that are formed in a chemical reaction.
about the
_symmetry
reatures. In its simplest application, NMR can show the carbon skeleton
of a
molecule. In its more sophisticated application, NMR can show the presence
of
stereoisomers and the exact positions of functional groups. we shall address
:roth carbon-13 and proton NMR. combining xvn data with uv-vis
spectroscopy and IR spectroscopy data allows for precise determination
of threelimensional molecular structure.
-t is best to review NMR with symmetry as your focus. The question ',How can
' ou distinguish compounds by NMR?" .ur-r b" reduced to ,,How many different
:r'pes of hydroge^s are there in each compound?" Multiple-choice NMR
questions can be answered easilv by predicting the spectra from
possible
:tructures. For instance, if you can narrow down the potential struciures to
(etones, then it's just a matter of systematically eliminating
ketones that do not fit
:he spectral data. This is the perspective from which w.-e will approach
NMR.
i he abiiity to predict spectra from structures is best attained thiough practice.
-\s you do the multiple-choice qtiestions il the spectroscopy sections,-pr"di.t th"
spectra for the structures in this same manner. the cliiference belween the
:pectra in each answer choice (A,8, c, or D) is what often answers the question.
Organic Chemistry
Isomerism
Structure Elucidation
Isomerism
Isomers
Isomers are structures with the same formula, meaning they are made of the
exact same atoms, but they differ in the location of each atom. The difference in
position can be the result of different connectivity (bonds), different spatiai
arrangement because of asymmetry in the structure, or different orientation
about a bond. The result is that there are several different types of isomers.
Figure 2-1 shows a flow chart for determining the type of isomers.
ISOMERS
Structures made of the same atoms
Constitutional (Structural)
Differ in connectivity (bonds)
Stereoisomers
Conformers
Di f fer by orieniaion in space
Optical
Differ by orientation in space
Can't rotate to become identical due to
asymmetry in the structure
Geometrical
Differ by orientation in space
Can't rotate to become identical due to
the presence of a ring or n-bond
(
(
qn
rt
Enantiomers
Nonsuperimposable mirror images
Diastereomers
Nonsuperimposable and not
mirror images
&
ffi
Figure
2-1
Copyright
92
ffi
m
Organic Chemistry
Structure Elucidation
Isomerism
B. Geometrical isomers
C. Structural isomers
D. Stereoisomers
S ol uti on
The two compounds have different IUPAC names, so they are structural isomers.
The two structures vary in the position of their alcohol and side chain methyl, so
:hey are also positional isomers. The question was not that specific, so the best
.rnswer is choice C. The two structures are drawn below:
3-methyl-2-pentanol
2-methyl-3-pentanol
Constitutional Isomers
-
HoM
Ho- cH2cH2cH2cH3
1-butanol
'l
LI
I{1C-
CH-
HICCH2
H3C-
-l-.-^-.
CH-
o-
cH2cH3
- CH CH2CHT
I
&
2-chloropentane
CHq
H3cH2c-
diethyl ether
CH2CH2CH3
cl
=/\
&
LI
m
C1
3-chloropentane
CH2CH2CH3
CHa
&
2-methyipentane
lt
CHs
CHI
CHr
I-
CHa
2,3-dimethylbutane
CHs
Organic Chemistry
Structure Elucidation
Isomerism
Example 2.2
How many possible constitutional isomers exist for a molecule with the
molecular formula CaHlg?
A. 1
8.2
c.3
D.4
Solution
The maximum number of hydrogen atoms possible on a four-carbon alkane is
ten, so there are no units of unsaturation in C4H1g. This means that there are no
Example 2.3
Which of the following pairs of molecules is NOT
A. 2-Methylpentane and 3-methyipentane
B. Cyclobutanol and tetrahydrofuran
a set
of constitutional isomers?
COH1+ and
different IUPAC
names, so they are constitutional isomers. In choice B, both compounds have the
formula CaHgO and different IUPAC names, so they are constifutional isomers.
In choice C, both compounds have the formula CaHgCl and different IUPAC
names, so they are constitutional isomers. In choice D, the first compound has
the formula C3H15C1, while the second compound has the formula C6H11Cl, so
they are not even isomers, let alone constitutional isomers. This makes choice D
the correct answer.
Ttu$
Shfls
0m!um
dnr:mrln
lrMffi
For a given formula, tirere is a finite number of possible structural isomers. The
htw
un
WillfieffiD
mfrems
mr{
dtfimd
ru[
-;.*-
@!-'0-
illifirrfnt
J;ut.E
nery:l
pirffiii
*
lllcmr
au]l
$riffwe
nUemr:
Copyright
i[r_,Mplilu
Organic Chemistry
C3H8 (1 total):
Structure Dlucidation
CaHro (2 total):
HsC
I
CH.
'\
./
H:rC'
Isomerism
Hr./cHt\ ,r{"'
CHg
"ra/tt-a",
3-Carbon chain
4-Carbon chain
CsHtz (3 total):
CHr
-\.f
HrC/
-CHz'-.ur,
S-Carbon chain
HqC
"\/
"rf
_CH
-CH3
Hrc/ -."i
-zc\
HSC
4-Carbon chain
CHr
CH:
3-Carbon chain
CeHr+ (5 total):
ur./cH'\.t'ttt'' .r{"t
5-Carbon chain
"l
CHr
--
HrC/
-CHz
an-
"rf
.zCH'
-zcH\-cH,
-c",
Hzc'
cH,
HsC
S-Carbon chain
t"\
;o
D
\e
a.
*r
AS
It
ES
1a
,4,
of
in
:w
"rl
"l
,t"'
"..-t"-
*C/t-.t'tt'
4-Carbon
,r('^u
CHs
chain
4-Carbon chain
Figure 2-3
C
IS
S-Carbon chain
95
Organic Chemistry
Isomerism
Structure Elucidation
Example 2.4
How many structural isomers are possible for the formula CaH9C1?
A.3
8.4
c.5
D.6
Solution
For a problem of this type, the possibilities for the carbon skeleton must be
determined first. The four carbons can either be aligned four in a row or three in
a row with the fourth carbon coming off of the second carbon of the three-carbon
u
ft
chain.
STEP 1: 2 possible carbon skeletons
fii
C-C-C
C-C-C-C
ni
o!
ffi
3-Carbon chain
4-Carbon chain
The second step is to determine how many unique carbons each chain contains.
STEP
Co-
Co
Cu
I
/i
Cu
ca
2 Unique carbons
Unique carbons
The last step requires placing a chlorine on each unique carbon one structure at
time and verifying your answer by checking to see if each structure has
a
a
C_C-C-C
C-C-C-C
I
C1
C1
1-chlorobutane
C_C-C
tl
CIC
2-chlorobutane
C-C-C
/\
CCl
1-chloro-2-methylpropane 2-chloro-2-methylpropane
The best choice is answer B, because there are four possible structural isomers.
This systematic procedure works every time. It is assumed that isomer problems
much beyond this example in terms of difficulty will be avoided on the MCAT
because of time constraints. The skills employed when deducing the number of
structural isomers can also be used when deducing structure from spectral data,
such as IR and NMR information.
Copyright
Organic Chemistry
Structure Dlucidation
Isomerism
Example 2.5
How many possible constitutional isomers have the molecular formula CaHg?
A.4
8.5
c.6
D.7
Solution
These questions are time-consuming, but unfortunately, there is not a convenient
rvay around
it.
Degreesof unsaturation
-2 -
=z(+)+?-(8) =8+2-8=10-8
2222
\Vith one unit of unsaturation, the structure must contain either a n-bond or a
ring. To get the correct answer, you must systematically consider each linear
connectivity and each cyclic connectivity. Be sure not to count stereoisomers
i'including geometrical isomers). The alkenes are listed first, followed by the
cvclic structures.
Possible alkene structures:
HzC: CHCH2CH3
1-Butene
H3CHC:
H.
CHCH3
,C=
2-Butene
Note that there are two possible
,CH'
C,,
CHs
Methylpropene
-tt
H?C- CH,
H2C-
CH2
CH"
/\'
H?C-\
CH
CHg
Cyclobutane
Methylcyclopropane
Because there are five total constitutional isomers in all, the best answer is choice
B.
97
Organic Chemistry
Structure Elucidation
Isomerism
I
(
Stereoisomers
Stereoisomers are molecules of the same formula that have the same bonds
(connectivity), but a different spatial arrangement of the atoms. included in
stereoisomers are configurational isomers (molecules that cannot be converted
into one another through rotation about a o'-bond) and conformational isomers
(caused by rotation and ring-flipping). Configurational isomers can be broken
down further into either geometrical isomers (associated with nonrotating
structures, such as rings and alkenes) and optical isomers (isomers that rotate
piane-polarized light differently). Not all configurational isomers rotate planepolarized light, as you have seen with meso compounds, but opticai isomers
differ in the magnitude and possible direction in which they rotate incident
plane-polarized light. Stereoisomers of all types are not superimposable (they
fi
ru
&
d[
m[
,0u
cannot be superposed onto one another.) Figure 2-4 shows the types of
stereoisomers. Rotamers are conformational isomers that vary in orientation in
space because of rotation about a sigma bond.
Stereoisomers; Same bonds,
\sC:.
HOH
\s--
HOH
&
(-
H^ccHz/
.z
H:C
at,
(S)-2-butanol
CH2CHl
(R)-2-butanol
,Q
Configurational isomers
(Optical isomers)
CH:
(cis)-4-methylcyclohexanol
,{F
.'rtl CH3
&
(trans)-4-methylcyclohexanol
Configurational isomers
(Geometrical isomers)
\r
HH
C:.
-z
H3CCH2CH2OH
&
H"CCH'
1-butanol
isC:.
H-z
CH2OH
1-butanol
Conformational isomers
(Rotamers)
Figure 2-4
Configurational Isomers
Configurational isomers are a subgroup of stereoisomers that have the same
bonds, but a different arrangement of their atoms in space, no matter how the
structures are twisted and rotated. Common examples with which you are
familiar include optical isomers and geometrical isomers.
Copyright
9a
Organic Chemistry
Structure Elucidation
Isomerism
Optical Isomers
optical isomers are molecules of the same formula and the exact same bonds
'connectivity), but a different spatial arrangement of the atoms due to asymmetry
-'r'ithin the structure. An optical isomer cannot
be rotated or manipulated tb
assume the structure of another isomer. They cannot be converted into another
cptical isomer without breaking a bond. Optical isomers rotate plane-polarized
light differently from one another. Figure 2-5 shows an example of a pair of
..ptical isomers.
",?l7t-
\
Ctrrrtt-
&
cH2cH2cH3
CH2CH2CHI
HaC-
(R)-2-chloropentane
(S)-2-chloropentane
Optical Isomers
Figure 2-5
:{orv can the relationship between the following two molecular structures BEST
::
described?
.\
\
CH2C\IZ -
CIH,CH?CH?C.
CH2CH2CH2CI &
.rut7t-
CH2CI
H
.4,. Identicalmolecules
B. Optical isomers
Ll. Skeletal isomers
f. Structural isomers
Solution
can start by naming each of the structures. Both have three chlorine atoms on
atoms are on carbons 7, 2, and 5, so each
rlecule has the IUPAC name 1,2,5-trichloropentane. To be skeletal or structural
',-e
-:-rmers requires that the two compounds have different IUPAC names, so
-:-oices C and D are eliminated. No matter how you rotate the first structure, it
:::rnot be superposed onto the second structure. This implies that they are not
:entical molecules, so choice A is eliminated. The left structure has s-
':ereochemistry at the second carbon, while the right structure has R:::reochemistry at the second carbon. This confirms that the two structures are
.:rical isomers, so the best answer is choice B.
-".pyright
99
Organic Chemistry
Structure Elucidation
Isomerism
Geometrical Isomers
Geometrical isomers, simply put, are the cis and trans forms of a rigid compound
(where rigid implies that it is not free to rotate between conformations). They are
sometimes referred to as cis/trans isomers, which applies to rings and alkenes.
They are nonsuperimposable, because they are locked into an orientation by the
cyclic structure or n-bond. If two substituents on a cyclic compound are on the
same side of the plane or if two substituents on alkene are on the same side of the
carbon-carbon n-bond, then they are said to be cls to one another. If two
substituents on a cyclic compound are on opposite sides of the plane or if two
substituents on alkene are on opposite sides of the carbon-carbon n-bond, then
they are said to be trans to one another. IUPAC convention does not use cis or
trans in the naming of alkenes; instead, the letters E and Z are employed. In
general nomenclature, the terms cis and trans are common. For geometrical
isomers, which have different spatial arrangement about a n-bond, the prefix of E
is given for trans orientation of the two highest priority groups, while Z is given
for cis orientation of the two highest priority groups. Figure 2-6 shows several
examples of pairs of geometrical isomers, both alkenes and cyclic structures.
Geometrical Isomers: Identical bonds with a different spatial
arrangement (found with double bonds and rings).
Alkenes
HH
\/
CH,CHTCH3
c:c
\/LL
&
/\
HsC
L-L
/\
HsC
CH2CH2CH3
Cis (Z)
Trans (E)
H?CO
CHg
&
HsC
CHe
Z ("Zis")
Cyclic Systems
cH"
(uP)
(up)
HrC-H-)
&
(up) /YcHs
HzC-_/--/
(down)
Trans
Cis
(up)
(up)
(t.tp)
Hrc\rA.rCH"
(down)
H3C\.n,.,rt\CH3
\J&
Trans
Cis
Figure 2-6
Copyright
loo
Organic Chemistry
Structure Elucidation
Isomerism
The term E is derived from the German word entgegen meaning "across from"
and refers to a compound where the two highest priority groups on each
respective alkene carbon are trans to one another. The term Z is derived from the
cerman word zusnmmen meanine "together" and refers to a compound where the
two highest priority groups on each respective alkene carbon are cis to one
another. Think of cis as "Zis", and you will always remember which is which.
Example 2.7
All of the following are true about geometrical isomers EXCEpT that:
A. the E designation for an alkene refers to the highest priority groups on each
alkene carbon in trans orientation.
Solution
To determine the geometry of an alkene, first locate the two carbons that
constitute the alkene. Determine the highest priority substituent on each of the
two alkene carbons, using the Cahn-Ingold-Prelog rules for assigning priorities to
substituents by sequentialiy looking at the atoms attached to the site of interest.
If the two highest priority groups are across from one another with respect to the
louble bond, then the compound is trans and thus is assigned the letter E. If the
:rvo highest priority groups are both on the same side of the double bond, then
'&e compound is cis and thus is assigned the letter Z. This makes choice A a true
,qtatement, so
it is eliminated.
Because the
are
lhe best answer. The structures of both an aikene and cyclic molecule are
relatively static and do not change drastically. The ring may flip-flop a littie, but
rotation is observed only for the substituents on the ring, and not observed for
Jee bonds in the ring. Because the structure is static, the molecular features are
lVe shall discuss stereoisomers oniy at this superficial 1evel for the time being. In
the stereochemistry and carbohydrate sections, stereoisomers will be discussed
in
greater detail.
lol
Organic Chemistry
lsomerism
Structure Elucidation
are molecules
stable conformation
hybridization,stericrepulsion,andVSEPR(ValenceShellElectronPair
because
nlpurcion) theory. Understanding conformational isomerism is vital,
shows
2-7
Figure
compound.
a
of
stability
anl
strlcture ii.tut", the reactivity
two pairs of conformational isomers'
spatial orientations
||
H-4
Hzc-=L--,/
t\
CH"
t"
.._
-
oH
OH
OH
H3
"--/--"
H\/t/cwzc
H:C
CHa
cH2cH3
Figure 2-7
molecule' Figure
Conformational isomers are different orientations of the same
for butane'
orientations)
2-8 shor"s six possible conformations (three-dimensional
temperature,
room
at
Conformational isomers are in dynamic equilibrium
energy available'
because rotation about sigma bonds is possible with the
in jusi one of
remain
not
does
Because molecules are consiantly rotating, butane
or another'
time
at
one
the conformations, but rather urrn*", all confirmations
that there
means
This
frequently'
It assumes the most stable conformation most
is a most favored and least favored conformation'
nT1.,,
V^
nrr/ Y;"
H
Structure #3
Structure #2
Structure #1
HeC
CHs
CH:
CHe
CHa
HsC
v^
H\ul
#4
Structure #4
Structure
#5
H\9)
HsC
ffo
btructure #6
Structure
Figure 2-8
another.Forinstance,al80"rotationabouttheCz-Czbondofbutaneconverts60'
six structures represent
Structure #1 in Figure 2-8 into Structure #4. The
incrementalrotationsabouttheC2_.Cgbond,acrossafull360"rotation.
Copyright
t02
Organic Chemistry
Structure Elucidation
Isomerism
Of the conformers in Figure 2-8, Structure #4 is the least stable, due to steric
hindrance between the two methyl substituents (the largest groups). Structure
#4 has hydrogens on carbon 1 and carbon 4 colliding with one another. Structure
#1 is the most stable, because repulsion is minimized. To maximize stability, the
largest groups on each carbon (CH3, in this case) need to be as far apart from one
another as possible (tn anti orientation), if they repel. This minimizes the steric
repulsion between the two groups. The least stable conformation (eclipsed, as it is
cailed) has the two largest groups colliding into one another. The different
orientations are referred to as confonnational isomers. Figure 2-9 shows a sider.iew of steric repulsion for the fully eclipsed butane molecule in Structure #4.
/\'H
HzC..
\-/
'.i.
H.
H\YZ
VN
HH
Figure 2-9
the
Eclipsed: Eclipsed refers to the orientation where from a front view of the
molecule, you are prevented from seeing all of the substituents on the rear
tarbon, because the substituents on the front carbon block the view of the rear.
Structures #2, #4, and #6 are exampies of the eclipsed orientation of butane,
Because of steric hindrance, the eclipsed conformations are less stable than the
staggered conformations. Figure 2-10 shows the eclipsed conformation of ethane.
Eclipsed Drawings of Ethane
HH
"Jy'-'Y';,.
Figure 2-10
Staggered: Staggered refers to the orientation where from a front view of the
rrolecule, you can see all of the substituents on the front and rear carbons. There
,s a 60" dihedral angle between neighboring substituents. Structures #1, #3, and
=5 are examples of the staggered orientation of butane. Staggered is the most
.:able conformation. Figure 2-11 shows the staggered conformation of ethane.
Staggered Drawings of Ethane
n
H
c-c
v"
H
Figure 2-11
-opyright
l03
Organic Chemistry
Structure Elucidation
Isomerism
Within staggered conformation, there are two terms used to describe the relative
position of substituents on adjacent atoms. These terms arc gauche and anti, and
they refer to the position of a substituent on one atom relative to the position of a
substituent on an adjacent atom. In the case of ethane, where each carbon has
three hydrogen atoms attached, each hydrogen has two hydrogens gauche to it
and one hvdrogen anti to it. Butane, having a methyl group on both carbon-2
and carbon-3, is a simplistic molecule to consider gauche and anti orientation.
Rotation about the bond between carbon-2 and carbon-3 of butane generates
conformational isomers where there is a methyl group on each carbon. We shall
demonstrate gauche and anti orientation by referencing the methyl substituent
on carbon-2 of butane relative to the methyl substituent on carbon-3 of butane.
m
L0
jj
il\
:[
5
CH,
Hfi!-cHr
'>("
H.C
C-
n'/
,/tn.
v"
C..
l
:
Figure 2-12
:.
t!,
Anti: Anti
anti to one another. This is the most stable structurel Three different
perspectives of the staggered conformation of butane, with carbons 1 and 4 anti
to one another, are shown in Figure 2-13.
Er
^1
ar
IC
-{
H
B.
C.
c-c. ,/'n'
H:C
\,"
Sc
CH:
L<
B"
br,
Figure 2-13
ar
st:
Cr
Organic Chemistry
Structure Elucidation
Isomerism
io
:!
0"
60"
180'
1.20'
240'
300'
360'
Degrees of rotation
Figure 2-14
Example 2.8
Ilow does the energy diagram for the complete rotation about a central bond of
an asymmetric (chiral) compound compare to the energy diagram for its
complete rotation about the CZ-CS bond of butane?
A. The energy diagram is symmetric like butane, but with higher energy values.
B. The energy diagram is symmetric like butane, but with lower energy values.
C. The energy diagram is asymmetric like butane, but wiih greater differences
D.
in energy values.
The energy diagram is asymmetric, with different energy values than butane.
Solution
Because the structure is asymmetric, the energy diagram depicting the rotation
associated with the molecule must also be asymmetric, eliminating choices A and
B. The energy diagram for the complete rotation about the C2--4.g bond of
butane is symmetric, so choice C is eliminated. Choice D must be the correct
answer. The three staggered conformations are of unequal energy.
The
Copyright
l05
Organic Chemistry
H,.
H3c<.^
L
-(.
HsC
HsC
HsC
Structure Elucidation
.cH.cH, H"C.
r&.- _/tn"n'
r-r.'c'32.^
^,/tn,t',
Hz9
.cH2cH3
^/
V"
n,c/'-
CH:
Isomerism
n)'- \:,t
CH2CH?
HgC
CHs
2 methyl/methyl and
1 ethyl/methyl interactions
\:,f
CHa
HgC\.
CH"J
H:C
H
H
CHs
methyl/methyl and
I ethyl/methyl interactions
Lowest Energy Conformation
1
1
2
methyl,/methyl and
ethyl/methyl interactions
Figure 2-15 shows the exact orientation of the atoms at various times during the
first 120" of rotation of ethane. The graph shows that at 20" and 100" the
structures are symmetric and thus of equal energy. This is also observed for the
conformers at 40" and 80".
C-C
bond of ethane
20
40
60
80
100
720
Figure 2-15
Copyright
Organic Chemistry
Structure Elucidation
Isomerism
Erample 2.9
.he best explanation for why the most stable orientation about the C2-C3 bond of
:i.e amino group and the carboxylic acid group in 3-aminopropanoic acid is
:auche is which of the following?
\. Gauche is the most stable, because it minimizes the steric hindrance between
the amino group and the carboxylic acid group.
B. The gauche conformation is always more stable than the eclipsed
conformation.
C. The carboxylic acid and amino groups form a hydrogen bond best from
gauche orientation.
D. The carboxylic acid and amino groups form a hydrogen bond best from anti
orientation.
Solution
il
the substituents attract one another, then the most stable conformation is
s:aggered with the two attracting groups gauche with respect to one another.
I-re best choice is C, because gauche has the amino and hydroxyl groups close
.nough to form a hydrogen bond. Hydrogen-bonding is a stabilizing force. The
:lrongest hydrogen bond is formed by the lone pair of nitrogen with the acidic
:,r'drogen of the carboxylic acid group.
n&J*n,
H
,o,-./
ll"
\:r:"
Anti orientation
U-
o-
(.
ta
^.'.4
"&_J
,'/
o?c
zHvdrogen bond-------
- ,,H-
u^xr.
\Hz
Y3"
Gauche orientation
Copyright
r07
Organic Chemistry
Structure Elucidation
Isomerism
Newman Projections
Understanding the nuances of conformational isomers requires good threedimensional viewing skills, so you may wish to dig out your molecular models if
you still have them. Be able to recognize structures from the stick figure view
(with dashed and bold wedges), as well as from Newman projections. Newman
projections are front views of a molecuie. In drafting, three views are given to
see the whole. It is no different in organic chemistry. The side view is a dashedand-bold wedge representation, the front view is a Newman projection, and a
top view is a Fischer projection. Figure 2-16 shows a pictorial explanation of the
conversion from a dashed-and-bold wedge drawing to a Newman projection,
CJ
q,)
,/
o. HsC
o
Y;,.",
o
L
9.
CHs
-o
Figure 2-16
Conversion from Newman projection to dashed-and-bold wedge drawing:
behind
HgC
H
CHs
+)
:f&1"'
OH
in front
of
plane ,/ L-\,
,/
H
behind
Y,::*,"
ln frontH
of piane
Figure 2-17
Cycloalkanes
Cyclic alkanes which contain only one ring have the chemical formula C.,H2.,
and contain no n-bonds. The stability of a given cycloalkane is rooted in its
ability to form bond angies of approximately 109.5', the norm for sp3-hybridized
carbons. The farther from 109.5" the angle is, the greater the reactivity of the
cycloalkane. For this reason, three- and four-membered rings are reactive, while
five- and six-membered rings are stable. When treated with hydrogen gas (H2),
cyclopropane and cyclobutane readily form straight chain alkanes (propane and
butane). Cyclopentane and cyclohexane do not undergo hydrogenation.
Copyright
loa
r,n
str
ery
drit
wT
trmr
I[tuP
MW
od
mft
Organic Chemistry
Structure Elucidation
Isomerism
The reactivity of three- and four-membered rings is attributed to ring strain. Rtng
T
:I
o
t-
a
e
strain is defined as the energy difference between the linear and cyclic alkanes of
equal carbon iength. Because the bond angle in cyclopropane is 60", vastly
different than 109.5' associated with a normal spr-hybridrzed carbon, there is a
great deal of ring strain. To relieve this angle problem, cyclopropane forms what
are referred to as bent bonds (sigma bonds in which the electron density does not
lie between the two nuclei). Because the electron density is not between the two
nuclei, the bond is much weaker and thus easier to break. Figure 2-18 shows the
orbital and bonding pictures for various cyclic alkanes.
I,
a
tI.
Cyclopropane
n
e
Cyclobutane
nole
Cyclopentane
H2C-
cH2
uri-."r-)rr,
Rrng strain 6.8 kcai/mole
Cyclohexane
HH
Figure 2-18
ln
its
ed
:le
t!.
lecause of their stability, most cyclic organic and bio-organic molecules are
=rther five-membered or six-membered rings. Six-membered rings are slightly
rore stable than five-membered rings. Given their frequent presence in
:iological molecules, five-membered and six-membered rings have a high
:robability of appearing on the MCAT.
-J
3I'{
-opyright
l09
Organic Chemistry
Structure Elucidation
Isomerism
Cyclopentane
Cyclopentane does not require much^distortion of its bonds and shape to
accommodate the 109.5" angle for the sf -hybrid. A perfect pentagon has angles
of 108', so there is only a small discrepancy from 109.5". This angle difference
does not account for the small ring strain of 6.8 kcals per mo1e. To achieve the
correct angle and alleviate this torsional strain, cyclopentane forms what is
referred to as an enaelope shape, where one of the carbons is not coplanar with the
other four. The major problem with cyclopentane is not the ring bond angles, but
the substituents on the ring that are in an eclipsed conformation as a result of the
near-planar ring structure. This eclipsing of hydrogen atoms causes further
contortion of the structure, which accounts for the ring strain energy. Still,
cyclopentane structures are relatively stable, Their stability makes them common
in such biological structures as ribose, deoxyribose and the purine ring of the
DNA bases adenine and guanine. Figure 2-19 shows a few other common fivemembered rings frequently encountered in the biological sciences.
ui"
lh
LU
lllln
m
il
rilm
COr-
"l
*H"N-
t-
t'
CH"
HN\---zN
OHH
B-D-Fructofuranose
L-Histidine
OH
OHH
HO
B-D-Ribofuranose
2-Deoxy-B-D-ribofuranose
Figure 2-19
lIo
L-l
Organic Chemistry
Structure Elucidation
Isomerism
Cyclohexane
Cyclohexane has the most stable ring structure of all of the cycloalkanes. This is
evident in biological molecules, which have multiple rings of six atoms. The
most stable form of cyclohexane is the chsir conformation. There are two
different chair conformations for cyclohexane. The two conformational isomers
can interconvert through a process referred to as ring-flipping. In interconverting,
the structure passes through the boat conformation. Because the two chair
conformations are equally stable, AGr* - 0. The interconversion between the two
chair conformations of cyclohexane requires 10.8 kcals/mole in activation
H
Cyclohexane showing equatorial Hs
axial (up)
equatorial (up)
(up)
eq (down)
eq (down)
eq (up)
eq (up)
axial (down)
equatorial (down)
axial (down)
axial (down)
Cyclohexane showing all substituents
Figure 2-20
Copyright
lll
Organic Chemistry
Structure Elucidation
Isomerism
il
ry
dffi
p1 H
tu
ro
Twist
ffi
mh
tu
@ry
ffi
ffim
il[m
HH
@M
Figure 2-21
Because molecules can readiiy rotate and contort
at room temperature, an
equilibrium exists between the two chair conformations of the cyclohexane
molecule. Either at low temperatures or'in cases where a substituent is too bulky
to orient itself in an axiai manner, one conformer is present exclusiveiy. The
proton NMR can be used to determine the more stable structure by focusing on
the different signals for the two orientations of hydrogen. You should be able to
determine the most stable conformation. The boat conformation is not as stable
as the chair conformation, because its substituents encounter high energy
eclipsed interactions its substituents encounter, while the substituents in the
chair conformation are staggered with lower energy gauche and anti interactions.
Monosubstituted Cyclohexane
The ring-flip process is the same when there is a substituent on the ring as it is for
cyclohexane, but the energetics are different. When a substituent is present, the
activation energy for interconversion increases, and the two chair conformations
differ in stability. Because the two chair conforrnations are no longer of equal
energy, the two twist forrns are also no longer of equal energy. The most stable
chair conformation is the structure r,r'ith the least steric repulsion. Substituents
with axial orientation on the same side of the ring are close enough to repel
(known as 1,3-diaxinl interactions), so axial orientation is less favorable than
equatorial orientation. This is indicatecl in Figure 2-22, where the two chair
conformations of both methylcyclohexane ar-rd cvclohexanol are shown. The two
chair conformations of methylcyclohexane differ in stabiliiy by 7.69 kcals,/mole.
Because a hydroxyl grorlp is smaller than a methyl group, the difference in
energy for the two chair conformations of cr-clohexanol is only 1.04 kcals/mole.
Copyright O by T'he Berkeley Review
tt2
Organic Chemistry
Structure Elucidation
H
Methylcyclohexane
Equatorial > Axial by 7.69 kcals/mole
Isomerism
oH
I
Cyclohexanol
Equatorial > Axial by 7.04 kcals/mole
Figwre 2-22
Disubstituted Cyclohexane
Disubstituted cyclohexane exhibits different dynamics than monosubstituted
cyclohexane. The greatest energy difference is observed when comparingT,3diaxial to 1,3-diequatorial, because the steric repulsion of 1,3-diaxial substituents
is the strongest repulsion encountered in cyclohexane. This is shown in Figure 222 for dimethylcyclohexane. When comparing 7,2-diaxial to 1,2-diequatorial,
there are no diaxial interactions of the bulkiest substituents, because the two
bulky substituents are trans to one another. This makes the energy difference
between chair conformations less than what would be observed with the 1,3cyclohexane. The energy difference between the 1,2-diaxial and 1,2-diequatorial
orientations is also less than the energy difference between 1,4-diaxial and 1.,4diequatorial (which is another compound having the two bulkiest substituents
trans to one another), because the 1,2-diequatorialcyclohexane species has gauche
CH"
l"
L;-/ :
"'[.\1-\
/-=--/4
H.c/114
CH.
"
Trans-7,2-dimethylcyclohexane
:- "''H*"
N
|
CHs
.r,
Cis-1,3-dimethylcyclohexane
9H:
F/Fcrr.
H:c-\/-\
CH,
"
Traus-7,4-dimethylcyclohexane
ll3
Organic Chemistry
Structure Elucidation
Isomerism
Table 2-1 lists the possible orientations for disubstituted cyclohexane. Trans
refers to substituents on opposite sides of the ring, equating to either up/down
or down/up. Cis refers to substituents on the same side of the ring, equating to
either up/up or down/down. Cis and trans do not refer to equatoriil or axial
orientations, but rather to whether the substituents are above or below the ring.
si
J:,
t.
Possible Orientations for Disubstituted Cyclohexanes
<+
e;
e>
7, -trans (upldown) or (down/up) e
\, -cis (up/up) or (down/down)
++
7,2-trans (upldown) or (down/up)
1,2-cis (uplup) or (down/down)
7,3-cis (uplup) or (down/down)
7,3-trans (upldown) or (down/up)
C-1
C-1
C-1
C-1
C-L
C-1
axial
axial
axial
axial
axial
axial
C-2
C-2
C-3
C-3
C-4
C-4
Table 2-1
It is essential that you be able to translate from nomenclature to the most stable
conformation. For instance, trnns-3-methylethylcyclohexane is a 1,,3-trans
compound. A compound with 7,3-trans orientation has both an axial and an
equatorial substituent. The ethyl group is larger than the methyl group, so the
ethyl group occupies the equatorial orientation in the most stable conformation
of trans-3-methylethylcyclohexane. This is shown in Figwe 2-24.
-:
rr.x
llhr
tl!
I"}ff
:lhu
ilIJI,
f__4
IIIIIII
b--_LcH:
:ilh,r
dlilrru
[]rgft
I[!r!
cH2cH3
Figure 2-24
You should take note that when you convert from one chair conformer to the
other, the axial substituents become equatorial (as seen with the ethyl group),
and the equatoriai substituents become axial (as seen with the methyl group).
The most stable conformation has the least steric repulsion.
Example 2.10
The most stable conformation of cis-L,2,4-trimethylcyclohexane has which of the
following orientations for the three methyl groups?
CHg
Copyright
ll4
Organic Chemistry
Structure Elucidation
Isomerism
Solution
The most stable conformation has as many methyls equatorial as possible. 7,2-cis
has one axial and one equatorial substituent, so there must be at least one axial
substituent. Answer B is best. Drawn below are the two chair conformations of
as
CH.
CH,
l"
r-)
H:.cd
l'
equatorial;2axial
-\
CH.
\-\4
1"".
WcH.,
2 equatorial; 1 axial
This covers the topics associated with isomerism. These topics are applicable in
both the physical and biological sciences areas, so know them well. To implant
this section as a working knowledge base, there are many passages with which to
work. From the very beginning, you want to emphasize the logic behind your
answers. The MCAT may not have passages that are verbatim duplicates of
what you see in here, but if you answer these questions using sound logic and
fundamental concepts, then you will slowly get acclimated to the MCAT way of
thinking. At this point, passages may seem like an absurd form of asking
questions, but hopefully you wiil take a liking to the style. Passages present
information that you must incorporate into your background knowledge, and
then using all the information you have, you must reach a conclusion concerning
their questions. Multiple-choice tests require that you find the best, most
reasonable answer. You are not required to solve detailed questions or derive
fundamental concepts. Just find the best answer, as fast as you can.
Copyright
I l5
Organic Chemistry
Structure Elucidation
Structural Insights
ffi#ffiilffit
Structural Symmetry
\A/hen deducing the molecular structure for an organic molecule, it helps to know
something about the symmetry of the compound and its units of unsaturation.
symmetry can be broken into plane symmetry and point symmetry. In plane
symmetry, the compound has two halves that are evenly displaced about an
HOH"C
H
'\r.-o1rY*'
cH20H
*--*oof''
HgC
-,H
"\..
CH2Q.H
thus twenty bonding electrons). There are three carbons with four bonding
electrons each. There are eight hydrogens with one bonding electron each.
This means that propane (C3Hg) has exactly the twenty bonding electrons
needed. There are no extra bonding electrons, so propane has a linear
rr6
Organic Chemistry
'1.
ie
n
rt
iJ
re
L-
re
rl
Structure Elucidation
Structural Insights
that every atom needs a minimum of two bonding electrons. Using this
perspective, we can determine the number of excess electrons per atom.
Hydrogen makes just one bond, so you subtract one for each hydrogen in the
molecule. Oxygen atoms are ignored, because they make the minimum two
bonds that are needed. Carbons are multiplied by two, because carbons
make four bonds, two beyond the minimum to propagate the chain. There
are two ends to every chain, so two is added to the total. The units of
unsaturation refer to bonds, rather than bonding electrons, so the sum of
excess electrons must be divided by two. This is summarized in Equation
2.7.
Units of unsaturation =
:\
)g
'D
a1
2(#C)+2-(#H)
l"lethod 3 works with other atoms, too. Nitrogen makes three bonds, which is
::-e more than the minimum needed, so you add 1 per nitrogen atom. Halogens
:-':ke one bond, which is one less than the minimum, so you subtract 1 per
. -:-,de. Equation 2.2 includes nitrogen and halogens.
Units of unsaturation =
to
:IC
1e
ls
ta
II1
-t\'
be
of
to
nt
.,J
(2.2)
0t
ls
(2.1)
Erample 2.11
:::",r' many units of unsaturation are present in a compound with the molecular
::::nula C7H9N3O2Cl2?
{.
8,2
:.3
1.4
1
t rlution
-:,s question is solved by applying Equation 2.2.
-. )+ (3)-(9)-(2)+2 =r4+3-9-2+2
2222
=72
-9 - B -
4Unitsof unsaturation
oi
:::ause there are four units of unsaturation, choice D is the best answer. With
could contain three n-bonds and one
::ng, meaning it is potentially a benzene derivative. When there are four units of
,:.saturation, you should immediately consider the possibility that the
. --mpound contains an aromatic ring. While there are other combinations of four
-::ts of unsaturation, there is a high probability of having an aromatic ring.
:*'
-:p.r'1i*1't,
ng
ln.
'l:s
lar
tt7
Organic Chemistry
Structure Elucidation
Spectro3bop$
Structural Insights
an Andysis
,il
Spectroscopy
unknown, you may also have to assign signals and peaks to an existing
compound. The spectra should be interpreted using the typical features you
have learned. To date, the test has emphasized only a few features that have
been stressed in course work. We shall start by reviewing the basic operations of
the IR and its applications to structure elucidation. From there we sha1l consider
ultraviolet,/visible spectroscopy, proton NMR, and carbon-13 NMR.
Infrared Spectroscopy
Er,'ery molecule produces a unique IR spectrum. Infrared spectroscopy starts by
adding a monochromatic beam of IR photons to either a thin oil suipension (if
the compound is a solid) or a neat solution (if the compound is a liquid) between
(recorded as 4000 cm-1 to 600 cm-1 on the graph). \A/hat we record is the change
in the intensity of the EM radiation from when it enters the molecule to when it
exits the molecule. This is compared to a reference beam that traverses a path of
identicai length but does not pass through the compound itself. If the compound.
absorbs a given wavelength of light (corresponding to some transition), then we
observe an absence of light exiting the sample tube. This is known as absorption
spectroscopy. The graph records transmittance as a function of wave number (cmr), so absorbances are represented by drops rn intensity.
The frequency at which light is absorbed is specific for each type of bond. As
you may have learned in physics, the frequency of light is directly proportional
to the masses of the two atoms in the bond and the bond strength. This is to say
that the potential energy in a resonating system (such as a spring that obeys
Hooke's law) is described by Equation 2.3
P.E. = 1 kx2
(2.3)
The k-term is the spring constant, which we can say describes the bond strength.
The x-term describes the distance from equillbrium that the bond has stretched.
The absorbance can be thought of as increasing the potential energy of the bond,
so the absorbance is proportional to the energy of the bond. As a resuit, the bond
Copyright
rr8
il
d
d
Jffi
tffi
mh
l@G
h
ffi
Organic Chemistry
Structure Dlucidation
For instance, a C=O boncl absorbs around 1700 cm -1, while a C-O bond absorbs
around 1300 cm -1. this is because a C=O bond is stronger than a C-O bond.
Carbonyl functional groups a-re common, so you should know the absorbance
value for a C=O bond. An sp3-C-to-H bond absorbs just below 3000 cm-1, while
an sp2-C-to-H bond absorbs just above 3000 cm-l, because an sf -C-to-H bond is
stronger than an sp3-C-to-H bond. This is because the sp2-hybrid, having more scharacter, is smaller than the sp3-hybtid. The result is that an sp2-C-to-H bond is
shorter and thus stronger than an sp3-C-to-H bond. The stronger bond, having a
higher bond dissociation energy, has a higher energy absorbance.
Although the molecule as a whole absorbs the EM radiation, we can use the
absorbances we measure to fingerprint particular functional groups and bonds
rvithin the molecule. The skill needed to make IR useful is an active process.
Scientists use IR not only to confirm the presence of certain functional groups,
but to also to help decide which functional groups are not there. IR is most
useful as a supplement to the moiecular formula and the NMR spectra for
molecules. Table 2-2lists several useful IR absorbances. The values are listed in
terms of wave numbers. Note that the absorbance of a given bond varies with
ihe compound in which the bond exists.
Stretching (cm-1)
Bond type
3640 - 3580 v)
C=C alkvnes
C=N nitrile
C=O ester
C=O aldehyde
C=O ketone
C=O acid
C=O amide
C=C alkene
C=C aromatic
C-O
C-N
amines, alkyl
Bending (cm-1)
1620 - 1590 (v)
3500 - 3350 m)
3450 - 3200 m)
3300 - 3220 s)
3100 - 3000 v)
880
3060 - 3020 m)
2980 - 2860 s)
660 (v)
w = weak absorption
v = variable absorption
s = strong absorption
m = medium absorption
Table 2-2
Copyright
ll9
Organic Chemistry
Structure Elucidation
using Table 2-2, you can evaluate IR data given in spectrum form to identify
structures. As for memorizing peaks, according to the MCAT student Maru,Lal you
are required to "know the important ones," which is open to interpretation. You
don't necessarily have to memorize all of the values, but if you do enough
problems, the values you repeatedly see should become second nature.
fr
I
(
$
T
oru
,&
lflr,
efl
mm
@u
on carbon one. This leaves only three possibilities, and they are:
1. H3CCOCH2CH3 (butanone)
2. H3CCH2CH2CHO (butanal)
3. H3CCH(CH3)CHO (2-methylpropanal)
Thus, we can reduce the choices from many types of compounds having one unit
of unsaturation and one oxygen (a cyclic ether, for example) to a few. Ketones
Example 2.12
Which of the following compounds with the formula C5H19O cannot have an IR
absorbance peak between 1700 cm-1 and 1750 cm-1?
A.
B.
C.
D.
An aldehyde
A ketone
A cyclic ether
A11
of the above have an IR absorbance between 1700 cm-1 and 1750 cm-1.
Solution
An IR absorbance between 1700 cm-1 and 1750 cm-1 implies that the compound
has a C=O in its structure. Because it has no absorbance between 1700 cm-1 and
1750 cm-1, it does not have a C=O bond. Choices A and B have a C=O in their
structure, so they can be eliminated. The best answer is choice C. The one
degree of unsaturation associated wlth the formula is used in the ring. The one
oxygen in the formula is in the ether, which contains carbon-oxygen single
bonds. Choice D is also eliminated, because choices A and B are eliminated.
Copyright
TM
w
ffi
&
h
tu
Organic Chemistry
Structure Elucidation
Example 2.13
How many structural isomers of C4H3O2 are possible that have an IR absorbance
peak between 7735 cm-1 and 1750 cm-1, u p"ik around 1200 cm-1 and no broad
peaks above 2500 cm-1
4.2
B.3
c.4
D.5
Solution
The absence of a broad peak above 2500 cm-1 indicates that the compound does
not have an o-H bond, which eliminates the possibility of it being an alcohol or
carboxylic acid. It is most likely an ester, although it could have both a carbonyl
and ether functionality. According to Table 2-2, the peak betweenIT35 cm-1 and
1750 cm-1 indicates ihat there ;s a c=o bond of an ester and not a ketone or
aldehyde. The compound must be an ester, so the question now becomes, "How
many esters are there that contain only four carbons in their structure?" There
are only four four-carbon esters, as drawn below, so the best answer is choice C.
1)o2)
o
lt
H,/-\
il
OCH"CH2CH3
3)o
H3CH2C/C-
Oarr,
4)o
il
H,ZC\
il
OCH(CH3)2
nrC/
toarrra*ru
"tttt"a
;
f
1r
te
te
ie
t2l
Organic Chemistry
Structure Elucidation
l""o"Tro"*
\ ts
I .$
j"''-.'"
Stronger hydrogen-bot-td
HH
\""0
o/t\ o/\n
o/c\
st.ong", cluut"r,t
bond
\,.s
*t
\I
i ' '\
o<n
s
c<H
I
Given that molecules are in continuous random motion within a liquid, some
alcohols have strong hydrogen bonds, while others have no hydrogen-bondingThis means that the solution has a random distribution of hydrogen bonds and
therefore a random distribution of covalent bonds. The result is a distribution of
signals in infrared spectroscopy. To see each individual peak for each different
covalent bond requires a high resolution IR spectrophotometer. It is unlikely you
used such an instrument, so the signal with which your are familiar is a broad
composite signal covering the range of the individual signals. Figute 2-27 s
a high-resolution IR signal and the standard-resolution equivalent.
3440
3320
3440
Figure 2-27
Copyright
t22
The Berkeley
3320
l5
0rganic Chemistry
Structure Dlucidation
Example 2.14
',"hat
is true for the compound associated with the following IR spectra?
te
1457
cm-l ll
3317 cm-l
2903 cm1
2987
cn-l
Solution
- he compound represe-nted by the lR spectrum above in the question has a broad
:-eak around 3300 cm-l and no peak near 1700 cm-]. These are the first areas to
:onsider when looking at IR spectra. The compound has a hydroxyl group, but
ro carbonyl group. This makes choice B incorrect and choice C correct. Because
:t has the hydroxyl group, it can exhibit hydrogen-bonding. This eliminates
;hoice A. Because of the peaks in the 1300-1400 cm-1 range, we know the
:ompound has a carbon-carbon bond, so it must have at least two carbons. The
Lightest compound with two carbons is ethyne (HC=CH), which has a molecular
nass of 26 grams per mole. However, because there is an oxygen present, the
compound must have a molecular mass greater than 30 grams per mole. Choice
D is eliminated.
Ultraviolet/Visible Spectroscopy
spectroscopy. \A4rile infrared photons (in the 3-to-10 kcals/mole region) affect
the vibrational energies of a molecule, ultraviolet (in the 70-to-300 kcals/mo1e
region) and visible (in the 40-to-70 kcals/mole region) photons affect the
electronic energy levels. when uv or visible photons are absorbed by a
molecule, an electron is said to be excited from the ground state to an excited
state. Because o-bonds are so much stronger than n-bonds, the lowest energy
absorbance for alkanes is significantly higher than the lowest energy absorbance
for alkenes. To excite an electron from the o-level (sigma bonding orbital) to the
o*-level (sigma anti bonding orbital), photons of approximately 140 nm to 120 nm
are necessary. However, because molecules in the air readily absorb energy in
this region, the spectra must be obtained in a vacuum, Because this constraint is
rather impractical, uv-visible spectra typically range from 200 to 800 nm, where
air does not interfere. As a result, we typically use only UV-visible spectroscopy
to analyze molecules with n-bonds, especially conjugated systems. uv-visible
spectroscopy in organic chemistry focuses on transitions between the n and n*
energy levels. For systems with conjugation, there are several n-levels, but we
care about only the lowest energy transition.
3W
Copyright
t23
Organic Chemistry
Structure Elucidation
l
r75nm
'r3
iI
t/\Arl
H2C:
H"C:
CF{2
{m
M
t/V\-l
@M
,tE.
rc1
H,C:
--
CH
CH:
r@
lrillt[
ir1
-r-
ryr
Tn4
-I.
z58nm
l*ln3
n2
TE
J]iL
dffi.
fuil
V\nrl
217nm
F[
mm
_Tn
Il*
CH
-cn
ll
CHZ
H2C:
/C'
CH
Md
'tlllllillF
ffie
ffiar
@m
mry
,ilmhm
muil
mum
,m
Figure 2-28
{ffrol
Because the energy gap between n and n* decreases as the conjugation increases,
I-u, = 270 nm
H^cD ^r.W
-t fi*
I,,'u* = 324nm
-->
I-u,
-t
I-u*
Tl
-\
HsC
n -+ 7tn
TE
-)
1l*
o
CHs
= 187 nm
Tl*
= 219 nm
7t*
I*u*
= 368 nm
Figure 2-29
Copyright
124
The Berkeley
mru
rym
Organic Chemistry
Structure Elucidation
terms of what is absorbed. The energy levels that are affeited are for the spin of a
nucleus in the presence of an external magnetic field. Normally all of the nuclei
have spins of the same energy. However, when an external magnetic field is
applied, spins can either align with the field or align against the fie[, so multiple
energy states are possible. In the case of 1H, theie or"u t*o energy levels: o
line
one aligned with the external magnetic field), and G (the one aligned against the
external magnetic field.) The B energy level is defined as higher tlian the cx
energy level. The energetics of the two levels depends on the strength of the
erternal magnetic field and the magnetogyric ratio of a particular nucieus. This
:neans that the energy gap between the two levels also clepends on the strength
of
:-'' the moving electrons, they do not require exactly the same amount of energy
excite the nucleus to a higher-energy spin state. This can also be viewed is
::
-
cal magnetic fields altering the strength of the apptied external magnetic field
(spin-flip) at a set frequency for the EM radiation. NMR
:-achines can be designed to vary the frequency of the radiation or vary the
.::ength of the magnetic external field. The NMR graph we observe typically
:=:ords changes in the magnetic field strength along the x-axis, so we tnint or
l,\lR in terms of varying external magnetic field strength.
l:oton NMR (which uses the 1H nucleus) is the most common form of NMR and
rkes advantage of the magnetic spin associated with the hydrogen nucleus. The
l.:cAT test-writers focus on analyztng the graphs produced uy lumran. There is
:,lrimal 13cxuR on the MCAT. rn"e scaie rot tuNvn is set from 0 to 10 parts
: =r million (pp*) of the total magnetic field of the machine.
Just as an inchls an
..;h because someone made it a standard unit of measurement, NMR is
:easured in ppp of the external magnetic field, because that is the arbitrary
.::.ndard. All lHNMR shift values are relative to a standard compounj,
=:ramethylsilane ((H3c)4si). All twelve of the hydrogens on tetramethylsilane
.:e equivalent, so they absorb at the same value. This value is arbitrarily
';signed to be 0 ppm, and all shift values are referenced against it. Rather than
.-
- Lnto other intricacies of NMR, we shall concentrate on how to read the graphs.
125
Organic Chemistry
Structure Elucidation
H,Ct t-
cHrC'
a"
oarr"cHrcH)cH1"
H^Ct 'a"
b- c
d--
a-dina3:2:7:6ratio.
ffim
dh
tH^Ct
M
m
aandbinal,:3ratio.
oc1arr.,;.
' b'''
at
Two unique hydrogens labeled
ocHrcH(cHj)?
m!
@!
lt
lt
l!..
ffi
mh
o
/-
tu
[M
&,r
oarrlcH?)cH2cH3
-
e"
b'
d
Five unique hydrogens labeled
a-e in a 3 : 1 : 3 : 2 : 3ratio.
h' c'd-
a'
&
MM
il
il
m
@
Figure 2-30
dM
The first two esters, n-butyl acetate and sec-butyl acetate, each have six unique
1HNMR
carbons, of which five hav-e hydrogens. gach exiribits five signals in its
13CNMR
spectrum. Isobutyl acetate has five
spectrum and six signals in its
unique carbons, but only four contain hydrogens. This means that isobutyl
acetate exhibits four signals in its I HNMR spectrum and five signals in its
13CNUR spectrum. Tertbutyl acetate has four unique carbons, but only two
contain hydrogens. This means that tertbutyl^acetate exhibits only two signals in
its 1HNMR spectrum and four signals in its IsCNMR spectrum. The presence o{
only two signals in an NMR spectrum makes it easy to identify tertbutyl acetate.
ffim
q q
OCH?
OCH"
H
f
l"'
H
b
.T,
CHs
ina3:2:2:3ratio.
1""
CHs
b
H
c
H
d
Iabeled a-f
labeled a-f
ina3:1:3:1:1:1ratio.
ina3:3:1:1:1:1ratio.
Figure 2-31
t26
]b,fr
qm
Organic Chemistry
Structure Elucidation
therefore four signals in its proton NMR. Meta-methylanisole has eight unique
carbons, of which six contain hydrogens. This means that meta-meiirylanlstle
has six types of hydrogens and therefore six signals in its proton NMR.
ortho-
methylanisole also has eight unique carbons, of wtrich six contain hydrogens.
This means that ortho-methylanisole also has six types of hydrogens"and
therefore six signals in its proton NMR. The structures in Figur e-2-Br"are para-,
meta-, and ortho-methylanisole, respectively.
You may have noticed that many problems are often just variations on a single
theme. In Figure 2-32, compounds with comparable i\MR readings are shoirn
hydrogens. Figure 2-32 shows two sets of three isomers that can be distinguished
irom one another using IHNMR by simply looking at the number of "signals.
Butanol and pentanal each have five unique types of hydrogens. The hydrigens
are in exactly the same ratio on both compounds, so thelr lHNMR spectra
strong similaritie^s. Each has five signals in its 1HNMR spectrum, ilthough
"r,f,6it
they
iave different 13cxMR spectra arie to a different nrr-L", of unique ciruor,r.
rhe HNMR spectra of the two compounds can be distinguished from one
.1
another by the shift values of the respective signals. Methylpiopyl ether and.2lentanone each have four unique types of hydrogens. rhe hydrogens are in
exactly the same ratio on both compounds, so their 1HNMR spectra exhibit
strong similarities. Each has four signals with the same relative area in their
-HNMR spectra, but at different shift values. Diethyl ether and 3-pentanone
each
have mirror symmetry and thus have similar carbons and similar hydrogens due
io this symmetry. There are two unique types of hydrogens in both diettyl ether
:ld 3-pentanone. This means that diethyl ether and 3-pentanone have only two
1HNVn.
'ignals in their
Butanol
./o--CH,-CF:.
. CH;-CHz
e-
H
.r
b-
il
T-t-.f {'!'-cu1cF:
d-
Methylpropyl ether
H,C/
dr
o-a*t,-tF'b.
2-Pentanone
o
il
a".
-;'j
-C.
H'rCt - CHr'
CH.
t '\
CH.
b'
d'
Four unique hydrogens labeled
a"
a-dtna3 2:2:3ratio.
a-dina3:2:2:3ratio.
Diethyl ether
3-Pentanone
fl
T"- c+{c-ctlr-cYu
bb
Pentanal
aandbina3:2ntio.
aandbina3:2rctto.
Figure 2-32
127
Organic Chemistry
Structure Elucidation
lrer,
-i
illl
f,*::
You must be able to identify unique hydrogens and then determine their
respective features. This is where we shall start our analysis. The features we
shall focus on primarily are the integration of the peak, the splitting pattem
(shape) of the peak, and the shift value (measured i. pp*) of the peak. Be sure
that you understand the importance of each of these features and the factors that
can produce changes in them.
lnteg:
-ra
'^''
---
tL
-^-!
_.AL
!:
L
: ack-r,
_5OU:
either
shou-li
hvdro,
Copyright
Copr:
Organic Chemistry
Structure Elucidation
P-":iy::
lHNMR
r)
tra\
ll
zc\
CH.
a'
.zCHz
CH"
h'
ppm
pp-
Figure 2-33
The zero reference is ignored for analytical purposes, because it is there just to set
lhe scale correctly. The integral is not drawn on the spectrum in this example. In
ntost cases, you will be provided with the relative areas of the peaks, or you will
:e given a summation line to evaluate the relative areas. Either way, you must
:e able to apply the relative areas of the peaks to the quantity of hydrogens that
each peak represents. This is the start of NMR analysis.
Spectrum Analysis
iVe shall start off with how to anaryze the three basic components of the graph:
:'r.tegral (determined by the number of hydrogens making up a signal), splitting
:attern (derived from the coupling between hydrogen neighbors), and shift aalue
determined by the local magnetic field caused by either lone pair electrons in
rrotion or the electronic density associated with electronegative atoms). Each
piece is equally important. At times, one piece of information may be a little
more enlightening than the rest, but on the whole, every bit of data counts.
Integral
for a signal can be integrated, meaning that the area under the curve
:an be summed up, and set directly proportional to the number of hydrogens
:hat the signal represents. For instance, a CH3 group has a signal with a relitive
area of 3 compared to a CH2 group with a signal of relative area 2, working
rackwards from the integration to the structure, it is possible to deduce the
Sroup from the integration. For instance, a relative area of 5 can be attributed to
either 2 equivalent CH3 groups or 3 equivalent CH2 groups. Further inspection
should reveal which of the two scenarios is responsible for the six equivalent
The peaks
hydrogens.
11
129
Organic Chemistry
Structure Elucidation
Splitting Pattern
)r_
t'
rl:
'1:
:-
:lll,::
::,L
iir:
It"
yril
rit,r
liI
up/down or down/up CHZ group has a normal signal, because the opposite
spins cancel each other. The result is that one out of every four times, the CH3
'llri
signal is slightly higher, two out of every four times the signal is unaffected, and
one out of every four times the signal is slightly lower. This is why the CH3
signal in 3-pentanone occurs as a triplet (in a 1 : 2 : 1 ratio).
Likewise, the CH2 group of 3-pentanone is next to a CH3. The three hydrogens
of the CH3 have eight possible spin combinations: up / up / up, down/down/ up,
dow n / up / down, up / down/ down, up / up / down, up,/ down / up, down / up / ap,
or down/down/down. If all three spins are up (up/up/ up), then the net spin is
+3/2. If only two spins are up, then the net spin is +7/2. There are three
-*
It
tl
rt
li'
fr,
This is why the CH2 signal in 3-pentanone occurs as a quartet (1 ; 3 : 3 : 1). There
are eight outcomes, but three of them share one value and three of them share
another value, so we see only four different outcomes. Working from a spectrum
to a structure, it is possible to say that a 1 : 3 : 3 : 1 quartet is the result of the
hydrogens on a carbon being next to three equivalent hydrogens, often due to the
presence of a CH3 group as the neighbor. To determine the ratio of the peaks
within an overall signal (like the 1 : 3 : 3 : 1 value for the quartet), you can use
Pascal's triangle for binomial expansion to get the relative area of each peak
:-.
j'.
i'
Neighbors
Signal Shape
Pascal's Triangle
0Hs
Sinslet
1H
Doublet
11
2Hs
3Hs
4Hs
5Hs
6Hs
Triplet
Quartet
Quintet
Sextet
Septet
peak
2peaks:L:1ratio
t27
1331
74641
1 5 1010 5
1 6 152075 6
:r:
:2: 1 ratio
4peaks:1:3:3:lratio
3 peaks: 1
1, : 4: 6: 4 : 1 ratio
6peaks: 1 : 5 : 10 : 10 : 5 : 1 ratio
5 peaks:
1
1
-:
Tpeaks: 1 : 6 : 15 : 20 : 15 : 6 : 1 ratio
.-
:.-
Table 2-3
Copyright
ir
Organic Chemistry
Structure Elucidation
Shift Value
The shift value is a diagnostic tool for assessing the locai electronic environment.
it is measured in parts per million (ppm) relative to the magnetic field necessary
(ppm)
Hydrogen Atom
d (ppm)
RCHc
0.8 - 1.0
R2C=CH2
5.0 - 5.8
RCH2R (acyclic)
1.3 - 1.5
RCH=CRz
5.2 - 6.4
RCH2R (cyclic)
1.5
R3CH
r.5 - 2.0
RNHCH3
2.0 - 3.2
R2C=C(R')CH3
1.8 - 2.2
ArNH2
3.5 - 5.0
RCOCH3 (ketone)
,\rCH3
2.2 - 2.5
ROH (alcohol)
1 - 5 (broad)
RC=CH
2.5 - 2.6
AIOH (phenol)
4 - 7 (broad)
R.OCH3 (ether)
3.5 - 4.0
ArH
3.0 - 3.8
RCOH (aidehyde)
9.0 - 9.8
RCO2CHa (ester)
3.5 - 4.0
RCO2H (acid)
10
1.8
_)
1-3
RNH2
RCONHR (amide)
(benzene)
5-9
7.0 - 7.4
-72
Table 2-4
Erample 2.15
lentanal can be distinguished from 2-pentanone by what lgNIrrtR feature?
\. A 3H triplet at 1.5 ppm
B. A 2H multiplet at 1.8 ppm
C. A 2H triplet at 2.3 ppm
D. A 1H triplet
at9.7 ppm
Solution
lentanal has an aidehyde hydrogen, while 2-pentanone does not. The shift value
:-r an aldehyde hydrogen is found between 9.0 and 9.8 ppm. The peak shape is a
:rp1et, because there are two equivalent alkyl hydrogens on carbon 2. The two
- .'-drogen
nerghbors couple with the aldehyde hydrogen to split it into a triplet in
:e lHNMR spectrum. This makes choice D the best choice. 2-pentanone could
:e distinguished by the singlet of relative integration 3 caused by the isolated
:'.ethyl group adjacent to the carbonyl. Because the carbonyl carbon has no
:.','drogens attached, the methyl group of carbon one is not coupled to any other
l5r
Organic Chemistry
Structure Elucidation
hydrogens, which makes it appear as a singlet in the 1HNMR spectrum. The two
structures are drawn below, along with their proton NMR features.
lt
il
(-
&
A
(-
.-/*\
^
H:C
CH2CH2CH2CH3
cl
CH2CHzCH3
,./-\
1HNMR.
1HNMR.
r(
Il
f,
lfi
ffin
GT
gM
Example 2.16
\A/hat signals are present in the
lIlUVn
spectrum of chloroethane?
ffim
lffi
ft
Solution
Chloroethane has two unique types of hydrogens. This results in two signals in
its 1HNMR spectrum. The two hydrogens on carbon 1 are split into a quartet bv
the three hydrogens on carbon 2. Equally, the three hydrogens on carbon 2 are
split into a triplet by the two hydrogens on carbon 1. The lines split according to
the neighboring hydrogens and project down to the spectra. The quartet is
farther downfield than an ordinary alkyl group due to the electron density on the
chlorine atom. This means that the triplet is upfield, making choice D the best
answer.
lL
n
n
rf
lfr
l[
ffi
tfrr
1HNMR
ag
signals.
ffir
CIH
\^
-.Lu
n:
l[r
fi.
nttuTt-t\
H
fl,
n"
F{t
iii
,II
iiI
&
on carbon 1, resulting in
triplet upfield.
i
mM
ilhs
l]lt
tttt
tu
ffi
fiF
Actual srectrum
1
Copyright
132
Organic Chemistry
Structure Elucidation
Erample 2.17
lentanol can best be distinguished from ethyl propyl ether by which of the
:,rllowing features in the lHNMR spectrum?
',',hich
retones?
\,
B.
C.
D,
A
A
A
A
Soiution
methyl ketone has an isolated methyl group neighboring the carbonyl carbon
'.;hich has no hydrogens). Having no neighboring hydrogens makes the peak a
.nglet. The protons on a carbon alpha to a carbonyl are found between 2.0 and
I 5 ppm. The signal has a relative integration of 3 hydrogens. The only answer
:hat fits this is choice D, a 3H singlet at 2.1 ppm. The best choice is choice D.
Example 2.19
-- monosubstituted benzene has which of the following in its IUXVIR spectrum?
\.
of certain peaks and features that occur over and over. For instance,
,vhenever you see a triplet and quartet in a 3: 2ratio, you should conclude that
there is an isolated ethyl group (H3CCH2-) in the molecuie somewhere.
Be aware
Copyright
r33
Organic Chemistry
Structure Elucidation
molecule. Rather than looking at molecules to determine the spectra (going from
structure to spectrum), it is important to work problems from the spectrum to the
structure. By recognizing the combination of peaks, you will save time in
determining the unknown structure. This is very conunon in NMR spectroscopy.
We will use symmetric structures at first and then move on to more difficult
examples. The MCAT has traditionally asked simple questions about this topic,
but it's better to be safe than sorry, so we will present examples that are harder
than the questions they have given on previous exams. In the following few
questions are sample spectra from which you must determine the corresponding
structures. It helps to solve for the units of unsaturation first. Once these are
known, deduce possible functional groups that fit both the heteroatoms in the
formula and the calculated units of unsaturation. For instancet zero units of
unsaturation and one oxygen can be an aliphatic ether or an aliphatic alcohol.
Take advantage of the multiple-choice format by eliminating wrong answers as
you come across them. In the case of a compound with zero units of
unsaturation and one oxygen, an answer choice of a ketone is eliminated
immediately. Any structures with rings or n-bonds should be eliminated. This
ability to eliminate wrong answers can be very useful in the multiple-choice
format. To gain both insight and experience, try the following spectral problems:
ft
I
(
Tffi
ffi
&
&
fr
il"
l.
c.
D.
Example 2.20
\A/hat is the name of the compound that has the following 1I-nuraR spectrum, and
whose formula is C7H14O?
&
tu
ffi
:-
fr
mm
ffiF
A. 2,4-dimethyl-3-pentanone
B. 2,2,4,4-tettamethyl-3-pentanone
C. 1,1,3,3-tetramethyl-2-propanone
D.
2,2- dimethyl-3-pentarone
Solution
The septet and doublet in a 1 : 5 ratio are a dead give-away for an isopropd
group. Choice D is eliminated, because it does not have an isopropyl group"
Choice B is eliminated, because it contains too many carbons (nine instead od
seven). Choice C is eliminated, because the structure is misnamed. The bes,t
answer and only remaining choice is A.
134
Organic Chemistry
Example 2.21
s-hape-of the signal at 2.3 ppm
best described as:
.The
Structure Elucidation
A. a quartet.
B. a sextet.
C. a septet.
D.
an octet.
Solution
lve counting seven apexes within the signal at2.3 ppm, and seven apexes (peaks)
is referred to as a septet. check to see whether the ratio is 1 : 6 :rs :20: 15 : 6 : 1
to be sure. This seems reasonable, so the best answer is choice C. If you already
know the structure, then you can see that the septet results from six equivalent
hvdrogen neighbors on the methyl groups neighboring the alpha carbon.
Example 2.22
The ratio of the areas under the peaks
within
a quartet is:
-{.7:2:2:1..
B. 1 :3:3: 1.
C. 2:5:5:2.
D. 1:4:4:'J..
Solution
Bv using Pascal's triangle, you can easily determine the ratio. It is a good idea to
know the ratios of the more common peaks such as a doublet, a triplet, and in
--}'ris case a quartet. A
quartethas a ratio of 1 : 3 : 3 : 1. Choice B is correct.
Example 2.23
'r\'hat is the IUPAC name of the compound represented by the following
spectrum, whose molecular formula is C4H3O?
lHNltR
c4H8o
-{.. Butanal
B. Butanone
C. Ethyl ethanoate
D. Methyl propanoate
Solution
Because the formula has only one oxygen, the two esters (choices C and D) are
135
proton NMR between 9.0 and 9.8 ppm. There is no peak in that range, so choice
A is eliminated. Only choice B remains. To be certain, butanone
(CH3COCHZCHS) has three types of hydrogens and thus three peaks in its
proton NMR spectrum. The peaks are a singlet (3H), a quartet (2H), and a triplet
(3H). This is what the spectrum shows, so choice B is correct.
-.
Organic Chemistry
Structure Elucidation
Example 2.24
\iVhat is the IUPAC name of the compound represented by the following lHirll,tR
spectrum, whose molecular formula is C4H3O2?
E"r
:n
"4t
ffi
C.
lL-il
50
-.
][jr:
ta
t
l,/{1/,1
A.
B.
C.
D.
ppm
:-:
ppm
Butanal
Butanone
Ethyl ethanoate
Methyl propanoate
Solution
This question is similar to the previous question, except the ketone and aldehyde
are eliminated, because there are two oxygen atoms in the molecular formula.
Choices C and D show identical peak shapes and integrals in their 1HNMR
spectra" The distinguishing feature is the shift value of each signal. The ethyl
ethanoate (structure shown on the left below) exhibits a quartet near 4.0 ppm,
making choice C correct. The structure of methyl propanoate is shown on the
right below.
OO
T,t-.-A o/'\,
o
Singlet
2.1
ppm
2H Quartet 3H
at - 3.8 ppm at -
"0,
ffi
Srntr
-_E
,.4.,/tT'---,,
o
at
Triplet
1.0 ppm
3H
at
Triplet
2H
1.0
at
ppm
Quartet 3H Singlet
2.3 ppm at - 3.5 ppm
fri j
trr0g:
*Ltxn:
I.EI
:I:
-*
l_:
a.
=!
JIl
Organic Chemistry
Structure Elucidation
Example 2.25
Hydrogens on a carbon adjacent to two equivalent CH2 groups show which type
of signal in a IHNMR spectrum?
A. A1:3:3:lquartet
B. A1:4:4:lquartet
C. A1:3:5:3:lquintet
D. A1:4:6:4:Lquintet
Solution
Having two equivalent CH2 groups adjacent to the site of interest results in a
total of four equivalent hydrogen neighbors. Four equivalent hydrogens split a
signal into a total of five (4 + 1,) peaks. This makes the signal a quintet, which
according to Pascal's triangle (or binomial expansion of any sort) has a ratio of L :
1:6:4: 1. The best answer is choice D.
Example 2.26
eliminated.
Copyright
r37
Organic Chemistry
Structure Elucidation
ftm
mm
ffio
.f'
du
al
fu@
ffi
,fillfl
3H
3H
3H
m.
oHa
o
b 11H
2H
c
12
1H
2H
d
A1H
ppm
10
ppm
ppm
6 PPm
4 ppm
PP*
ppm
Figure 2-34
Be certain that you can match the peaks in the spectrum to the hydrogens in the
structure drawn above it in Figure 2-34. This can be done on the exam using a
chart of values if one is given, but it is not a bad idea to know the values from
memory.
Example2.27
\A/hat is the IUPAC name of an unknown compound with the molecular formula
C3H6O, an IR absorption at 1722 cm-l, and three 1HNVR peak,; one at 9.7 ppm
(1H), one at 2.3 ppm (2H), and one at 1.4 ppm (3H)?
A. Propanoic
B. Propanal
C.
D.
acid
Propanone
Methyloxyrane
Solution
There is an excess of information in this question beyond what is needed to
aswer it. The one and only piece of information you need is the peak at9.7 ppm,
which makes the compound an aldehyde. Pick choice B and move on quickly.
Copyright
Organic Chemistry
Structure Elucidation
;f.
X
Ha
Hb
Ha
U
rlb
Ha
Ha
Ha
Ha
Hb
different Hs
All
3 different Hs
in a 1 :2:lratio
inal:lratio
Case
Hb
Ha
Hd
Hc
{ different Hs in
a1:1:1:lratio
Hs are
equivalent
4 different Hs
in
2 different Hs
a1:1:1:lratio
inal:lratio
Figure 2-35
:rara substitution is the easiest arrangement to distinguish of the three possible
-.:uctural isomers, because it has a doublet of doublets. The dissimilar heights of
-:s peaks can be attributed to a mathematical phenomenon whereby peaks, as
--:.ev near one another, begin to coalesce. Figure 2-36 shows the aromatic region
Ha
Hb
Figure 2-36
-;.pyright
Organic Chemistry
Structure Elucidation
TE
Example 2.28
rL"AlI
what is the common name of the compound that has the formula C6Hgo, an IR
absorption at7722 cm-], and three notable lHNMR peaks at9.7 ppm (1H, s), 2.3
ppm (4H. dd), and 2.2ppm (3H, s)?
trs':
A.
B.
C.
D.
&e"r
Ortho-methylbenzoic acid
Para-hydroxyacetophenone
&,f,1r
rli J
*-"
Ortho-methylbenzaldehyde
J,ffi
Para-methylbenzaldehyde
Mfl
,ILfu.
Solution
The compound has only one oxygen, so neither a carboxylic acid (methylbenzoic
acid) nor a hydroxy ketone (hydroxy acetophenone) is possible. Choices A and B
are eliminated. we know that the compound must be an aldehyde from the
choices that remain, so the lriNvtR peak at 9.7 ppm and the lR absorption at
1722 crn-ldo not help our efforts to identify the compound. The trqrulan signal
at 7.3 ppm is a doublet of doublet (dd), which indicates para-substitution. This
makes choice D the best answer.
*."'
[i
*-
:mb{:.
tnlm
1me
$fft
Example 2.29
which of the following compounds does Nor lose a luNIvtR signal after D2o
has been added to a solution containing it?
A.
B.
C.
D.
Carboxylic acid
Cyclic ether
Primary amine
Secondary alcohol
Solution
If a compound contains a protic hydrogen, then it loses a peak from its 1HNMR
spectrum when D2o is added to the solution. Primary and secondary amines
have a hydrogen bonded to nitrogen, so thev are protic. This eliminates choice C.
All alcohols have a hydrogen bonded ,o s11:gen, so all alcohols are protic. This
eliminates choice D. A cirboxylic acid hasl dissociable proton, so it readily
exchanges with deuterated water. choice A is eliminated. An ether, whether
cyclic or not, has all of its hycirogens bonded to carbon, so it is aprotic. When
D2O is added to an ether, no exchange transpires. The best answer is choice B.
Copyright
,-
i,:,:
-:r:
Organic Chemistry
Structure Elucidation
13CNMR Spectroscopy
Carbon-13 NMR focuses on the carbons of a compound rather than the
hydrogens. The NMR cannot detect carbon-12, because it has no nuclear spin.
However, carbon-13 has an odd number of nucleons (particles in the nucleus), so
ii has a nuclear spin. For that reason, NMR can be used to detect carbon-13.
Because carbon-13 constitutes only about 1"/' of all carbon atoms, a 13CNMR
requires maly more scans to obtain a spectrum than 1HNMR. This is why the
'raseline
in 13CNMR spectra is noisy (scattered and messy). l3CNltR is used to
rdentify the number of unique carbons in a compound. A typical application of
t'hrs technique is to distinguish the substitution of disubstituted benzenes. Figure
l-37 shows the proton-decoupled (ali singlet spectrum) C-13 NMR spectra for
-,2-dimethylbenzene, 1,3-dimethylbenzene, and 1,4-dimethyibenzene. What is
:reant by "proton-decoupled" is that the compound is irradiated constantly
similar in concept to Dolby noise^reduction) with the coupling energy, so that
iere is no coupling between the IJC and IH atoms. This makes all of the peaks
=inglets, as drawn.
80
#
CH"
ppm
140
120
100
BO
60
40
20
Figwe 2-37
llhe shift values for 13CNMR are simple to recall. They come in blocks of 50
rpm. An sp3-hybridized carbon next to a carbon has a shift value between 0 and
50 ppm. An sp3-hybridized carbon next to an electronegative atom has a shift
Copyright
t4t
Organic Chemistry
Structure Elucidation
value between 50 and 100 ppm (usually less than 75 ppm). An sp2-hybidized,
carbon next to a carbon has a shift value between 100 and 150 ppm. A carbonyl
carbon with sp2-hybridization has a shift value between 180 u"a zso ppm. The
shift value increases as the substitution increases, meaning that 3' > 2" > f in
shift value. Quaternary carbons do not show up on the 13cruvR very well, due
to their long relaxation times. \44-rat is meant by a "long relaxation time" is that
the excited energy state of carbon takes longer than a few seconds to dissipate the
energy into solution and relax back to a lower energy level. We will not focus on
relaxation times, but instead will focus only on the application of information
tr:
In the three spectra shown in Figure 2-37, you'lrnote that the number of peaks in
each spectrum corresponds to the number of unique carbons in the compound
the spectrum represents. For the ortho compound, there are four carbons in a 1 :
1:1:1ratio. Thespectrumshows fourpeaks ina 1:1:1:1ratio. Three of the
peaks are from sp2-hyb.idized carbons and one is from an sp3-hybridized
carbon. For the meta-substituted and para-substituted compounds, a similar
relationship between spectrum and unique carbons in the structure is observed.
using spectroscopy data, you should be able to solve any problem following a
systematic procedure. It is best to use l3ctlVR to get-the symmetry oI a
structure and to identify selected functional groups (in a manner similar to IR
spectroscopy). Don't make much more out of i3cNun spectroscopy than this.
Be sure to use your degrees of unsaturation in structure elucidation problems!
Stn
1.
Sper
1.
Copyright
t42
copl
Organic Chemistry
Structure Elucidation
Section Summary
1.
Isomers (compounds with the same type and number of atoms but different
spatial arrangement due to bonding, connectivity, or molecular contortion)
ii.
because of
b)
i.
ii.
iii. Conformational isomers are formed by rotating or contorting
1.
Structural symmetry
a) Plane symmetry (mirror plane in molecule splits molecule into equal
halves)
b)
c)
1.
d)
Key peaks: C=O around 1700 cm-1, O-H around 3400 cm-1 (broad), and
C-H around 3000+ cm-1 (varies with hybridization-- ,p > ,p2 > ,p3j
Copyright
t43
Organic Chemistry
e)
Structure Dlucidation
2.
c)
conjugated systems
Peak intensity and wavelength increase as the amount of conjugation
increases
3.
of
d)
e)
Copyright
of 0 ppm
1HrultR special features (effects of deuterium and structural symmetry)
i. Exchanging of deuterium for protons (peak disappearance)
ii. Para substitution pattern (symmetric benzenes have unique spectra)
iii. Solvent choice (solvent must be invisible)
13CXUR and symmetry
i. The number of signals in 13CNVR spectrum is equal to the number
of unique carbons in the molecule
ii. Alkene carbons have signals between 100 ppm and 150 ppm, while
carbonyl carbons have signals between 180 ppm and 230 ppm
iii. 13C is a rare isotope, so 13CNMR spectra require more scans and
have more noise in their baseline than IUXVn spectra
r44
Stnrcture
Elucidation
Passages
14 Passages
l OO Questions
Suggested schedule:
I: After reading this section and attending lecture: Passages I, V, VI, VIII, & XI
Qrade passages immediately after completion and log your mistakes.
II: Following Task I: Passages III, IV XII, & Xlll (27 questions in 55 minutes)
Time yourself accurately, grade your answers, and review mistakes.
III: Review: Passages II, VII, IX, X, XlV, & Questions 98 - lOO
Focus on reviewing the concepts. Do not worry about timing.
REru{ffiNY
l)n.n.v.r.-E.w'
Speci altztng
in MCAT Preparation
rsftfficffirrui1ii1iruffiilil#tflff
{tndh
lil
mm@{
@m)
r,Mm
I. Chair Conformation
II. Rotational Energy Diagrams
III. Deuterated Cyclohexane
IV. Infrared Spectroscopy
V. Unknown Alkene Determination
VI. Structure Elucidation
VII. NMR and IR Spectroscopy
VIII. NMR Data Table
IX. Alkene-Coupling Experiment
X. Unknown Compound Identification
XI. Carbon-l5 NMR
XII. Distinguishing Isomers Using lnnmR
XIII. Structure Elucidation Using lHnMn and IsCNMR
XIV. Proton NMR of an Unknown
Questions not Based on a Descriptive Passage
MCAT Score
84 - 100
15-15
66
B5
lo-12
47
65
7 -9
34-46
4-6
t-33
t-3
(r -7)
(B
14)
ry
ttAmrl
mc
lffi,Gdli'r
lhm
(r5 - 22)
(23 - 2e)
dffi
,t5m
,@mo
(50 - 56)
(37 - 43)
(44 - so)
(5r - 57)
(58 - 64)
(65 - 71)
(72 - 78)
(7e - 84)
(B5 , eO)
(er - e7)
(eB
- l oo)
qn*
fr
Passage
(Question 1 - 7)
A. 0
B.
1
to
c.2
D.
to
3
-/--_/
t\eq = ll'J
A.
B.
c.
D.
nttt
4,
H,c{{\
0.0029
2.16
4.31
345
A.
B.
C.
D.
*-H.
9H..
CH3/H gauche
CH3/H anti
CH3/CH3 gauche
H/H anti
s,cG4,
'
K"o+ +.Zl
\--l-{/'cH\
5
.l:
,
"
dimethylcyclohexane?
Hence,
6.
The value of K"O for the conversion of cls-1,3dirnethylcyclohexane from its diaxial conformation to
,
B.
C.
D.
.
B.
C.
D.
-:pyright
147
1.
7.
Passage
ll
(Questions 8 - 14)
qlr"'
H
&F
OH
ffi*f=,"
D.
at
Figure
bo
b
+.1
l8o
360
Figure
it
Which
of the following
of the time.
1?
B.
H.C
CH.
Hf{,,cH:oH
D.
C.
H:C.
\CH2OH
sr,'HH
J\
H
Copyright
CHr
TF{::""
9.
3.
butene is that:
A.
B.
C.
room temperature.
14.
represents the
1?
A.
B.
C.
D.
B.
9Hr
Dipropyl ether
2-butanone
2,3-butanediol
Methylcyclopentane
H
CHzOH
HOH2C
CH2OH
H
CHc
l.
H:C
A.
B.
C.
D.
2.
A.
B.
C.
D.
A
A
A
A
-opyright
149
Passage
lll
(Questions 15 - 22)
6.
H2
of equatorial hydrogens to
axial
A.6:5
8.5:2
C.3:2
D. 2:3
A IHNMR
.
B.
C.
D.
A
A. 90'
B. 109.5'
c. 120'
D. 180"
19.
A.
15,
B.
Hsc
that:
A.
B.
C.
D.
ctl
0.
Passage
A. 3
B. 4
(Questions 23 - 29)
c. 5
D.
lV
A.
orientation.
B. are larger
C.
pref'erence
orientation.
D.
A.
cH:
B.
H,CN
' >'--L
CH:CH-1
CH2CHj
4000 3600 3200 2800 2400 2000 1800 1600 1400
D.
HCh
CH2CH3
Figure
CH2CH3
1200
1000
CH:
23, An
cm-1
A. ethyl propanoate.
B. butanal.
C. 2-pentanone.
D. diethyl ether.
l5l
24.
A.
B.
C.
D.
8.
A. 2-methylpropanal
B. Butanal
C. Butanone
D. Tetrahydrofuran
3300 cm-l.
2980 cm-l.
2300 cm-1.
1715 cm-1.
eill@
']rMt,"[
m!&m
:6r1ttlriu
{@fu
ifi'mrrrrlrm
qnmliftr
tfupr
2
5.
A.oB.
29.
"oA.H2cH3
c.o
H3co
A.
B.
C.
D.
cHs
D'
,4..
oo
H,cnrcoAn
6.
.
.
C.
D.
27
8 ppm?
.
B.
C.
D.
Copyright
152
WMffi
ilil&,m
Ml
,6&Lm
Passage
(Question 30 - 36)
3
mass
of
122.2
A. 12.0 ppm
B. 9.7 ppm
C. 7.5 ppm
D. 5.5 ppm
absorbances would
A. 1125 cm-1
B . 2200 cm-l
C. 1620 cm-l
D. 3550 cm-l
3.
A. C9H14
B. C9H16
C. C9H1s
D. C9H26
Figure
A.
B.
C.
D.
-rfound A
Shilt(cm-11
absorbance values is
indicative of an alkene?
3550 cm-l
2200 cm-1
1"725 cm-l
1620 cm-1
Inrensir.y
2962
2912
2106
1126
1212
strong
medium
mediurn
strong
strong
structures corresponds
Compound A?
A.oB.
Table
1 IR absorbances
of Compound A
t,"A.r,
HicH2c
A,,
-r
C.
be:
A. a cyclic ketone.
B. a cyclic ether.
C. acarboxylicacid.
D. an ester.
: . right
153
CHr
6. Which of
the
Compound B?
A.
'{x:,
.o
oA
to
Passage
Vl
(Questions 37 - 43)
shift
Integration
Shape
J-Value
1H
triplet
3Hz
6 = 3.1 ppm
1H
singlet
NA
6 = 4.3 ppm
2H
doublet
3Hz
Table
l3CNtvtR spectrum
is also the
number
of
carbons
ii
Compound T.
37.
A. an ether.
B. an ester.
C. a carboxylic acid.
D. an alcohol,
Copyright
,#!
"
38.
A.
B.
C.
D.
39.
alkane.
alkene.
43. the
A. CofaC=O.
B. CofaC-O.
C.
D.
alkyne.
alcohol.
H next to C=O.
H next to C-O.
.
B.
C.
D.
A
tt).
Cofanketone
A. 3.
B. 4.
c. 7.
D.
1.
14.
A.
B.
C.
D.
shift value.
peak integration.
area under theirpeaks.
same J-value.
A.
H-
B.
C: C- Ct-te
\
OH
H- C= C- Chtz
'\ ,/.H
c
il
c.
HO-
-:'pyright
C=
"-
o\
D.
- cH,
H-C=C-cH^
\o,
Passage
Vll
(Questions 44 - 50)
6.
Fa
From the leaves of a tree that grows wild along the coast
A. Methyl ethanoate
B. Methyl propanoate
C. Ethyl methanoate
D. Propyl methanoate
7.
Compound I
i'"
4
ppm
8.
2 ppm
Compound
A.
lm
ppm
C.
2 PPm
Compound
III
4.
2 ppm
C.
B.
o*.
4
5. It
llil{:
Oclr*"
III
49.
..A,,/ocH.
D.
o"oYo'
0.
A. CDC13 (chloroform)
B. C6D6 (benzene)
C. D3CD2COD (ethanol)
D. D2CO (formaldehyde)
order to:
:1
,T!*
llr
'r t]
rll
Copyright
rl-
gj,
ctl
D.
1 ppm
.o
ill
3 pDm
Figure
ilr
o
ocH 2cH 3
cH2cH3
d:,.
lr"
il,'"
B.
oa
il
DDm
II
ll2H
illi
I.
A. 3500 cm-1
B. 2980 cm-1
C. 1685 cm-1
D . 1300 cm-1
CaHs02.
lrr
6 pom
r56
*.!n-:'
i,]"
.i[[,u:-
Passage
Vlll
(Question
5t - 57)
53.
A.
B.
C.
D.
Hydrogen
Shift
0.8
RCH2R,
0.9
-COCH3
2.1
-COCH2R
2.3
-OCH3
3.5
-OCH2R
-CH=CH2
5.5
-CH=CHr
\H
7-8
-CH2CH=CH2
CH=O
9.7
-CO2H
Table
4.
B.
D.
2.3
to-12
5
hyclrogen types
because a
i.,-:on-carbon single bond is weaker than a carbon-carbon
A.
B.
C.
D.
NMR
]-Methyl-3-pentanoneconrains:
ratio"
6.
1.0
an
ppm (6H)?
Tetrahydrofuran
2-methylpropanal
Butanal
Butanone
7. A
A.
B.
C.
D.
disappears.
5.3
--
il"
be best
grows.
-:e
i l.
it would
peak disappears.
"
peak grows.
A.
l:;
to add:
(ppm)
-RCH3
a ketone.
an aldehyde.
an alkene.
cyclic.
Passage
lX
(Question 58 - 64)
A 1HNMR was run for the cis and trans isomers of the
molecule shown in Figure 1 below. The spectra obtained for
the two geometrical isomers are also shown in Figure 1. The
cis compound can be distinguished from the trans compound
using the coupling constants for the vinylic hydrogens. The
trans species has a larger coupling constant due to better
transfer of magnetization in the trans orientation. The shift
values on the spectra are listed in parts per million (ppm) of
B. A meta substituted
cH- cH-
Spectrum I
]H
.A
. A para substituted
substituents
benzene
substituents
ocHj
7.25
5.37
4.88
3.76
2.25
substituents
n,.-G
P@
61.
ppn (4 H)
pptn (l H)
ppm (1 H)
ppm (3 H)
ppm (3 H)
rllr
ilfl
llLl
]l]i
PPmz65432lo
Spectrum
II
6
3
3H
4H
7.25
5.37
4.88
3.76
2.25
2.
ppm (4 H)
ppn
(l
A.
B.
C.
D.
H)
ppm (l H)
ppm (3 H)
ppnt (3 H)
IHIH
rllr
ilil
iltiltil
rn
3500 cm-l
2220 cm-l
1120 cm'l
1640 cm-l
PPmz6s432lo
Figure
63.
8.
9.
A. 1 :1
B. 1 :3
C" 1:2:l
D. 1:1:1:1
A.
B.
C.
D.
FitE'ru
64.
7.25 ppm.
B. -5.37 ppm.
C. 3.76 ppni.
D. 2.25 ppm.
Copyright O by The Berkeley Review@
at:
"
ill:'tn:1
*"'"
iu.
I Jr
lrl
intmr
i:
)illi;IlL,I
.i
ll,il T1:.
[:ifL
l[
1.i"
l:iiL'tt:ti
iud
t'
t,i
l,nr;'
,il]fiI'rl',':r:
pr|trnTI- '
r58
Passage
(Question 65 - 71)
5.
C=O of:
A. an aldehyde.
B. a carboxylic acid.
C. an ester.
D. a ketone.
of
-.96. ppm,
:tre
: l.
:lur
66.
A. 3:1
B. 6:2
C. 9:3
D. 12: 4
mpound B.
7.
B.
C.
D.
8.
A.
B.
C.
D.
Figure
lHNltn
B.
at
Review@
at
Methyl benzoate
3-methyl-2-hexanone
3-methyl-2-penranol
3-methylpentanal
,niur*orbance
69.
170.2
70. in IHNMR,
.
B.
C.
D.
1.
Passage
Xl
(Questions 72 - 78)
A.oR'
Hrc
CH:
HIC
H:C
CH:
CH:
"''K)rn .XY
D.
C.
HrC- - O-
HsC CH:
H:C CHr
Carbon
Carbon
ppm
R2C=O
205 - 220
.C-OH
RHC=O
185 - 200
R2C=CH2
t20 - 140
-C-CI
-C-NH2
R2C=CH2
r 10
120
-C-Br
85
F{3C-C=O
50-70
40-45
35-45
25-35
20-35
R2CH2
l0-30
RC=CH
12
RC=CH
65 -10
-CH-r
Table
ppm
1 l3cxltR shilt
values
It
spectrum. For peaks that represent rnore than one carbon, th:
intensity increases, but not in a way that is easily integrate;
Integration is generally not carried out on 13CNMR spectra.
A researcher used I3CNMR to distinguish two structur-isomcrs formed when toluene (methylbenzene) was acylate:
using acetyl chloride by comparing the I3CNMR spectra :t
the two compounds. The molecular tbrmula fbr both isome:i
is CgH160. Spectra fbr both compounds were recorded usi:'s
the same NMR instrument for the same period of time in lt:l':
same concentration. The only clifTerence between the t''n:
samples invoived the isomers themselves. The spectral d:-l
tbr the two isomers are listed below:
I:
lsonierll:
Ison-ier
2-1,34, 110,
ll1,
123, 130,206
Copyright
would be seen
in the carbon-l3
l3CNvtR spectra?
A. Four
B. Five
C. Six
D. Eight
77
isomers?
structure of Compound I?
A.
B.
C.
D.
ov.+t
d
il
B.
C. Isomer
I, because it
II,
and Isomer
II
unsaturation.
Gl3
78.
A. Carbon
B. Carbon 2
C. Carbon 3
D. Carbon 4
1
f,
Isomer
Isomer II.
Isomer
t!
II,
cH2cH
A. Aldehyde
B. Alkene
C. Ketone
D. Methyl
How can
it
B.
)pyright
attached show
l6l
Xll
Passage
(Questions 79 - 84)
9.
A. Ethyl acetate
B. Acetone
C. Methyl acerare
D. Isopropyl formate
A.
B.
C.
D.
t-be
hydrogens:
the lftNMR
the
Spectrum
H
8
of a CH2 group.
on a carbon next to a CH2 group.
of a CH3 group.
of a carbon next to a CH3 group.
A.
B.
C.
D.
82. A
An ethyl ester
A methyl ester
An ethyl ketone
A methyl ketone
4ppm
3ppm
2ppm
lppm
A.
B.
C.
D.
a hydroxyl proton.
an aldehyde hydrogen.
abenzenehydrogen.
a
[h
,ct-
A.
B.
C.
D.
2ppm
lppm
84.
of
f-p
,lU- s
each
Copyright
162
frdmmm
A-m
A. Two
B. Three
C. Four
D. Five
D-.
1.
4-heptanone?
Figure
il.
0-,
ratio of
3pp-
GO ON TO THE NEXT PA
Fassage
Xlll
(Question 85 - 90)
7.
Ltu.L
:-"pound I:
r-:CNMR'
:HNMR:
(i),
17
8.
A.
B.
,".iound II:
rCNMR:
HNMR:
13 ppm (2)
carbonyl.
:cLutd
III:
C.
D.
ppm
III?
9.
A.
B.
C.
D.
A, An alcohol
B. An ether
C . A ketone
D. An alkene
90.
Pentanal
2-Pentanone
3-Pentanone
3-Methylbutanone
.
B.
C.
D.
A
^arbon-13 NMR is
useful for determining all of the
'.llowing EXCEPT the:
.
.
C.
D.
A
right
163
91.
rhe
A.
B.
C.
D.
structure
92.
Phenylmethane
Toluene
Methylbenzene
Orthoxylene
A. 3 :2:3
B. 1:1 4
C. 2:3
D. 1:2
5
3
Spectrurl A
CzHrc
5H
ppm
3.
3H
Figure
ppm
ppm
ppm
0 pprn
94
A.
(H3C)2HC
cH2cH3
(H3C)2HCH2C
H3CH2C(H3C)2C
D.
C.
B.
CHe
H3CH2CH2C
Figure
5 pprn
o ppm
lUlltR
ha"'e
A. 2-methyl-1-pentanol
B. 3-methyl-1-pentanol
C. 4-methyl-1-pentanol
D. A11 isomers of methyl-1-pentanol
have double-;
:ne n.iolecuie.
'r
6.
A.
B.
C.
D.
8.
based on
a
--
Singlet
Doublet
Triplet
.
B.
C.
D.
A
Septet
NOT
descriptive passage.
9.
geomelrical isomers.
optical isomers.
the same molecule with altered spatial orientation.
.
B.
C.
D.
A
10
structural isomers.
0.
structural isomers.
geometrical isomers.
optical isomers.
the same molecule with altered spatial orientation.
A. 3
B. 4
c. 5
D.
Structure Elucidation
Passage Answers
L.
Choice B is correct. The most stable form of the cyclohexane ring is the chair conformation. The most
position on the chair form is referred to as equatorial. Combine these two facts and the result is choice B.
Choice C is correct. Because the three deuterium atoms are cis with respect to one another, they cannot all
axial nor all be equatorial. The most stable orientation (most stable chair confirmation) has as many deute
atoms with axial orientation as possible. However, because the deuterium atoms are all mutually cis to
another, the structure must have at least one deuterium with equatorial orientation. The best choice (
consequently your choice) is C, which is drawn below.
D
2 axial deuteriums and
1 equatorial deuterium
J.
D
1 axialdeuterium
2 equatorial deuteri
11
Choice D is correct. As the reaction is written, the value of Kgt-1,4 must be greater than 1, because the prod
more stable than the reactant. The reaction is favorable in the forward direction as written. This elimi
choice A, a value less tiran 1.
The question now focuses on whether the conformational change with Ksq-1,4 is more favorable than
conformational change with K"O-1,2, because the value of Kqq-1,2 is 4.31. In the case of the 1,2-disubstih
compound, there are both diequdtorial versus diaxial interactions as well as gauche versus anti interactions
consider. The diequatorial orientation is better than the diaxial orientation, because with diaxial there
eclipsed interactions with the axial hydrogens. Howevet, the anti orientation of the methyl groups is
than the gauche orientation.
Overall, diequatorial preference over diaxial is a more important factor than a preference for gauche over
so the value of Keq-l,Z is greater than 1. The 1,4-disubstituted compound has no gauche-versus-anti ini
between the methyi groups to consider, because the carbons are far apart. Thus, the conformational pre
purely an effect of the diequatorial orientation being preferred over the diaxial orientation. This makes
value of Keq-1,4 greater than the value of Keq-1,2, making choice D the best answer. Drawn below is one
worth (apprbximately equal to 1000 words worth) of explanation.
Methyl groups are apart from Methyl groups are close to one Methyl grouPs collide with
one another when diaxial. another when diequatorial. axial Hs when diaxial.
CH.
9Hs
I,CH1
rr3L
oiulgl
- = !,"guubtl
-H.C,
Anti > Gauche
cF{3
cFI3
4"
Choice C is correct. In order for substituents to be gauche or anti to one another, they must be bonded to ca
that are connected to one another. In the case of 1-4-dimethylcyclohexane, the methyl groups are not
adjacent carbons, so the two methyl groups cannot be gauche or anti to one another. This makes choice C
There are hydrogens on every carbon, so H can be gauche to methyl. For the H to be anti to a methyl, the
group must assume axial orientation. The oniy possible chair conformation of cis-1,4-dimethylcyclohexane
one methyl group axial and the other in an equatorial orientation. This makes choices A, B, and D valid.
Copyright
166
Choice C is correct. Both of the chair conformations possible for cis-1,2-dimethylcyclohexane are equivalent in
energy. In both of the chair conformations, one methyl substituent assumes axial orientation and the other
methyl substituent assumes equatorial orientation. The equilibrium constant for the ring-flip process is equal to
1, because the energy levei of the product is equal to the energy level of the reactant. This makes choice C
correct. Do the correct thing and pick C. As a point of interest, the value of KuO can never be less than or equal to
0 (products and reactants always have some positive quantity), so choice A is an absurd answer.
HsC
HsC
Both structures have one methyi equatorial and the other methyl axial
Choice
between the two methyl groups makes the diaxial orientation less stable than the trans-1,2-diaxial orientation.
This decrease in stability in the conformation drawn on the reactant side results in a greater value for Ksq as
written. This means that K"O-1,3 ,K"q_I,2, which is choice D.
Methyl groups are apart from
one another when diaxial.
Methyl grouPs are close to one Methyl groups collide with Methyl groups do not collide with
another when diequatorial. one another when diaxial. one another when diequatorial.
CH.
IJ
.r, a, fn,
In,
S^
cF{"
Choice B is correct. The key to this problem is drawing the two hydrogen atoms on the bridging carbons cis to one
another. When the hydrogens are cis to one another on adjacent carbons, one hydrogen assumes axial orientation,
while the other assumes equatorial orientation. As a consequence, the carbon-carbon bonds to the left ring must
also be axiai for one and equatorial for the other. The structure is drawn below with the hydrogens noted.
Choice B is the best answer.
Equatorial
OH
Axial
Equatorial--+11
Choice C is correct. Because 240' is at the nadir (low point) of the graph in Figure 1, it correlates with the
staggered structure. This eliminates choices A and B. The compound has R stereochemistry at carbon two which
makes the correct answer choice C and eliminates choice D, which has S stereochemistry.
Choice A is correct. Because 60" is at a local apex (high point) of the graph in Figure 1, it correlates with an
eclipsed structure. This eliminates choices C and D, which have the compound in its staggered confirmation.
The 60' point is not the highest point on the energy diagram, so it does not involve the largest groups (carbon 1
and carbon 4) interfering with one another. This eliminates choice B. The best answer is choice A, with the
two methyl groups eclipsing one another.
t67
10.
Choice A is correct. The 330" point on the graph is near (30" away from) the most stable conformation (nh:
has anti orientation of the CH2OH group and the CH3 group of carbon 4). This eliminates choices C and
Because of R stereochemistry, the correct choice is A. Stereochemistry is difficult to see in the Newrr
projection and can be seen more easily in other projections. Drawn below is a way to convert the Neu,c:
projection back to the stick-wedge drawing and a subsequent evaluation of stereochemistry.
CHs
H:9
H
cH2oH
11.
CH.OH
H\\"t"'
Choice A is correct. Conditioning may cause yoll to respond automatically that the best orientation is the ane
with the fewest repuisive interactions. This is often true, but it does not tell the entire story in this case. The,
most stable orientation can also be the result of the strongest attractive interactions. Hydrogen-bonding betn'
the hydroxyl and amine groups occurs only from gauche orientation, where the two gtorpi are close enough
bond. Hydrogen-bonding cannot occur between substituents with anti orientation. This *uk"r choice A correct.
1'
Choice D is correct. Hydrogen bonds have some acid-base character to them, so the most favorable pro::
transfer reaction is a good indicator of the strongest hydrogen bond. Because the amine is more basic than i
hydroxyl group, the nitrogen is the lone pair donor. Likewise, the hydroxyl is more acidic than the amine
the hydroxyl is the hydrogen donor. This makes choice D correct.
13.
Choice D is correct. Because of the planar nature of electron density in a n-bond, rotation about a double bc:
requires that the n-bond be broken. This is not observed under thermal conditions. To convert a cis n-bond int;
trans n-bond, UV light is needed. Pick D to tally big points. The drawing below shows that a 90' rotation abc
the C-C breaks the r-bond. It requires substantial energy to break a rc-bond.
ru-bond
R1
R,
90" rotation
----------------
R3
R2
1.4.
Choice D is correct. The only single bond about which rotation is not possible is a single bond between two ar
in a cyclic compound. The only cyciic compound of the answer choices is methylcyclopentane, choice D. The
answer is therefore choice D. One item of notable interest is that both n-bonds and rings lower the entropl
compound by lowering its degrees of freedom (i.e., its ability to rotate freely).
1.5.
Choice B is correct. The most stable form of cyclohexane is the chair conformation (as opposed to the i:
conformation), with the smallest substituents (determined by bond length) in the axial position. The inteq
from the proton NMR shows that the ratio of peaks for 1H is 1.12 : 1 in favor of the 6 = 7-.25 ppm shift, the
due to the equatorial hydrogen. This indicates that more hydrogens are located in the equatorial position=i
1.25 ppn) than the axial orientation (6 = 1.51 ppm). Consequently, the preferred conformation has deuteriu-cr
the axial position. For this reason, choose B. Drawn below are the two chair structures and their equilibriurc"
6 = t.st ppm ----->H
L{
D
6 = 1.25
ppm
--->H
,0
t[
rU
H
5
axialH:6equatorialH llUruVRintegral 1:
Actual ratio is I.1.2:1, rvhich shows H prefers the equatorial position, so the right structure is more stable.
Copyright @ by The Berkeley Review@
l6a
rfi
,fl
Choice C is correct. Using D2 gas rather than H2 gas would have produced C6H5D7. The addition of the D2 is
in syn addition for all 6 deuteriums that are added, producing two possible conformational isomers, one having
three hydrogens equatorial and two hydrogens axial (choice C) and the other having two hydrogens equatorial
and three hydrogens axial (choice D). Choice C is more stable, because hydrogens prefer the equatorial
orientation. Choose C if you want to be a star. The structure is drawn below:
.3 axialH:2 equatoriaiH
3axialH:2equatoriaiH
2axiaIH:3 equatorialH
H prefers the equatorial position, confirming that the structure on the right is
more stable. The K"O for this ring flip is > 1. The ratio is 2 axial: 3 equatorial.
This question could have also been answered without knowing the exact chemistry. The passage infers that
hvdrogen prefers the equatorial position over deuterium. This means that in the most stable orientation, there
are more hydrogens with equatorial orientation than axiai orientation. This eliminates choice D. Because
there are only five hydrogens present (you start with five on deuterobenzene), the sum of the two numbers must
be five. This eliminates choices A and B and makes choice C the best answer. Learn to answer questions as
quickly as you can, whether you use organic chemistry knowledge or common sense.
Choice D is correct. The addition of H2 gas to chlorobenzene results in the hydrogenation of the benzene ring
and the formation of CH11Cl (chlorocyclohexane). For chlorocyclohexane, there are two possible stable
conformational isomers, one having a ring structure in a chair conformation with the chlorine equatorial
(choice D) and one iraving a ring structure in a chair conformation with the chlorine axial (choice C). Chlorine
is larger than hydrogen, so it prefers to be in the equatorial orientation. Choice D is more stable so choose it.
Clroice B is correct. The hybridi zatron of carbon remains sp3, whether it is bonded to deuterium or to hydrogen'
The angle therefore should be around 109.5". It is stated in the passage that the bond angles are between 107.5"
and 111", which are both nearest to 109.5" of all the choices. Pick B for best results on this question.
Choice A is correct. The cis form of 1,3,5-trimethylcyclohexane allows for all three methyl groups to assume
identical orientation in terms of axial or equatorial. This means either choice A or choice D is the best answer.
Equatorial orientation is more stable than axial orientation, so choice A is the best answer. The conformation is
shown below:
H
H
Hsc
H
Choice B is correct. Like benzene, C6H5D has three n-bonds and one ring. The best answer is choice B. If you
recall the formula for units of unsaturation, (2(#C) - (#H) + 2)/2, you can calcuiate the units of unsaturation,
knowing that D behaves the same as H. This would also yield a total of 4.
Choice D is correct. A hydroxyl group, OH, is larger than a hydrogen, so choice A should be eliminated. The
axial orientation is -or" iritld"redin terms of sterics, so choice B is invalid. Choice C is a good explanation for
why the two hydroxyl groups would be found in a diequatorial orientation, but the question is looking for an
expianation foi why diaxiai, rather than diequatorial, is the preferred conformation. This eliminates choice
C. When the two hydroxyl groups are both in axial orientation, they can exhibit 1,3-diaxial interactions.
This is normally considered to be steric repulsion; but in the case of two hydroxyl grouPs, there exists the
ability to form hydrogen bonds. This makes choice D the best answer.
Revierv@
r69
,,
Choice D is correct. Only in choice C and choice D do the rings have their substituents with cis orientation.
Choices A and B are eliminated, because the substituents are trans to one another. The more stable conformer
has the larger substituent (the ethyl group) in the equatorial position. This describes choice D.
23.
Choice D is correct. An IR absorbance between 1700 cm-1 and 7740 cm-1 is the result of a carbonyl (C=O) group, as
stated in the passage. Of the choices, only the_ether doesn'tcontain a carbonyl group, so it is the ether thai
does not have an IR absorbance between 1700 cm-1 and.7740 cm-1. Pick D for best t"rrttr.
24.
Choice C is correct. A straight-chain monosaccharide has O-H groups, a C=O functionality and C-H bonds.
These groups have IR absorbances for bond stretching of 3300 cm-r,l7I5 cm-1, and 2980 cm-1 respectively. This
makes choice C the best choice. You are required to know common values for the IR absorbances. No commonvalue peak is found around 2300 cm-1, so thit should lead you to answer choice C.
25.
Choice A is correct. A broad signal near 2850 cm-1 indicates the hydroxyl group of a carboxyiic acid (O-H witin
hydrogen-bonding). A hydroxyl group exhibits hydrogen-bonding, so the signal is broad. Because the O-H
bond of a carboxylic acid is weak, its absorbance is lower than that of standard hydroxyl groups. Of the ansirer
choices, only choice A has a carboxylic acid functionality, let alone a hydroxyl gio,rp. plit a for happiness.
26.
Choice D is correct. The region between 7.0 and 8.0 ppm in the proton NMR can be attributed to hydrogens on
aromatic ring. This immediately eliminates choices A and B, which have no aromatic rings associated rri
them. The difference between ethylphenol and methylphenol can be demonstrated by eithei the total numb
of hydrogens (as shown in the integration) or by the coupling of the alkyl portion of the compounds. The
grouP exhibits a 2H quarter and a 3H triplet, while the methyl group exhibits a 3H singlet. The extra
group associated with the ethylphenol compared to methylphenol is found in the 2.0 to 2.5 ppm region, not
aromatic region. This eliminates choice C. To decide between the two compounds in choice D, one can look
the coupling of the hydrogens on the benzene ring, found in the range between 7.0 ppm and 8.0 ppm.
splitting for the hydrogens on a benzene ring with para-substitution is symmetric, while the splitting for
hydrogens on a benzene ring with meta-substitution is asymmetric. This is the distinguishing iactor betu
the para-substituted and meta-substituted phenols in choice D. The best choice is answer D.
,n
Choice A is correct. Because the broadness of hydroxyl peaks is associated with hydrogen-bonding,
decreased hydrogen-bonding of a tertiary alcohol is reflected as a narrower absorbance in the IR spectru-n:.
compared to a primary alcohol. The alcohol peak is found weli above 3000 cm-1, so the best answer ii choice
28.
Choice D is correct. An IR absorbance at 1775 cm-1 is rndicative of a carbonyl group (the stretching of a C
bond)' Aldehydes and ketones contain a carbonyl group, so choices A, B, and C are eliminated. Only the
(tetrahydrofuran) does not have a carbonyl functionality. Pick D and bask in the glow of correctness.
29.
Choice C is correct. The hydrolysis of an ester results in the formation of a carboxylic acid and an a
Both the ester and the carboxylic acid have carbonyl groups, so each has an IR absorbance around 1700 c
This means that both before and after hydrolysis, there is a signal around 1700 cm-1, eliminating choices A
B. An ester has no hydroxyl group, so initially there is no signai around 3300 cm-1. Following hydrolysis,
an alcohol and carboxylic acid are formed, so a signal for the hydroxyl group appears. In particular"
hydroxyl group of an alcohol shows an absorbance around 3300 cm-1. This means that during the course cdhydrolysis of an ester, an IR signal appears around 3300 cm-1, making the best answer choice C.
30.
Choice A is correct. Because a ring takes one degree of unsaturation and a carbonyl takes one d
unsaturation, a cyclic ketone has two degrees of unsaturation. The compound has only one
unsaturation, so it cannot be a cyclic ketone. The correct answer is choice A. A cyclic ether has one ring and
bonds, so it has one degree of unsaturation. This eliminates choice B. A carboxylic acid has no rings and
bond, so it has one degree of unsaturation. This eliminates choice C. An ester has no rings and one n-bond.
has one degree of unsaturation. This eliminates choice D.
t70
,ii
iu
fr
'@
rffi
Choice B is correct. Ozonolvsis cieaves the double bond of an aikene, converting it into two carbonyl compounds
(either an aldehyde or a ketone). In this reaction, the products formed are aldehydes, as mentioned in the
passage. Aldehvdes can be identified by their peak around 9.7 ppm in the 1HNMR. Choose B for best results.
it
shows an IR
Choice A is correct. Compound A has one degree of r-rnsaturation (due to the carbonyl), and Compound B has two
degrees of unsaturation (one due to the carbonyl and the other due to a ring). The second degree of unsaturation
has to be from a ring, because there can be no double bond in the product from ozonolysis (had there been a nbond, the ozone would have reacted with it.) This means that the original alkyne must have had a ring and a
triple bond, which in turn means that the original alkyne had three degrees of unsaturation. The alkyne had
nine carbons (the sum of the carbons from Compounds A and B). A nine-carbon compound with no units of
unsaturation has the formula CSHZO. For every unit of unsaturation, two hydrogens are removed from the
formula, so a hydrocarbon with three units of unsaturation must have the formula C9H1.4, choice A. You can
verify tlris with the molecuiar mass, which is roughly 122 g/mole, as stated in the passage.
Choice D is correct. An alkene is distinguishable by an IR absorbance between7620 cm-1 and 1660 cm-1 for the
stretching of the C=C bond. You should know that i carbonyl C=O bond absorbs at around 1700 cm-1, and being
that a C=C bond is slightly weaker than a C=O bond (they are both double bonds, but a carbonyl bond is
slightly shorter), it takes siightly iess energy to stretch the C=C bond than the C=O bond. This means that a
C=C bond has an absorbance slightly less ihar-r 1700 cm-1. Only choice D is less than 1700.*-1, so choice D is
tl-re best answer. The test requires that you have some iR peaks in your memory; but for ones you don't recali,
estimate them by comparison to the values you know. Choose D in this question for the feeling of correctitude.
Choice ll is correct. The products from the ozonolysis of the alkene are both aldehydes, so Compound A must be
an aldehvde, which makes choice B the best answer. All of the choices have the correct units of unsaturation,
so the bcst answer rnust be determir-red from the presence of the aldehyde proton.
Choice C is correct. As stated in the passage, Compound B must be an aldehyde, which eliminates choice A.
The con'rpound cannot contair a double bond (the product from ozonolysis cannot have a double bond between
carbons), so choice B is eliminated. The lHXVR integration shows a peak ratio of 7:1:4:4, which indicates
that there are no methyl groups in the compound. A methyl group would have shown a relative ratio in the
integrai of 3. This eliminates choice D. Choice D can also be eliminated, because it contains too many carbons.
This narrows it down to choice C, which does in fact show four nonequivalent hydrogens in a ratio of 1:1:4:4. It
is vital that you solve this question by a muitiple-choice elimination process rather than structural deduction,
because in a multiple-choice format, eliminatir-rg invalid structures is faster than elucidating the correct one.
Choice D is correct. The question here is not what type of bond is causing the shift, because all four answer
choices are C-O bonds. The question is: "What type of molecule is Compound T?" Because of the broad IR
absorbance at 3350 cm-1, tire compound has H-bonding, so it must be an alcohol. The correct answer is therefore
choice D. Choices B and C should be elimilated, because the passage states there is no carbonyl. Choice A can
be eliminated, because ethers exhibit no hydrogen-bonding.
Choice C is correct. An absorbance at 2\76 cm-1 implies that the compound is an alkyne. This is trivial
knowledge for the most part, but the passage provided the information, in case you don't have carbon-to-carbon
triple-bond IR data committed to memory. You can deduce the IR absorbance vaiue for an alkyne knowing that
a C-C boncl has an IR absorbance between 1100 cm-1 and 1300 cm-1, and that a C=C bond has an IR absorbance
between 1620 cm-1 and 1680 cm-1. As the bor-id strength increases (or bond length decreases), the IR shift value
incre;rses. Choices C is the best answer. The answer is given at the end of the tl-rird paragraph in the passage.
Choice A is correct. A doublet in the 13CNMR is due to a carrbon with one hydrogen attached to it. Because a
ketone carbon and an internarl alkyne carbon do not have hydrogens attached to them, they would be singlets
rather than doublets. This eli.mi.nates both choice B ancl choice D. There is no peak in the IR spectrum,
inciicating that there is a C=O present (no peak around 1700 cm-1), so choice C is eliminated. The only choice
left is choice A, the best choice.
t7l
40.
Choice C is correct. If a compound has no symmetry, then thereis a 13CNMR peak for every carbon in -*-*
compor-rnd. The number of carbons in a compound exhibiting seven 13CWR peaks is therefore r"rr"rr. pick C :.r
best results.
47.
Choice D is correct. When hydrogens are coupled to one another, they have the same coupling constants :
values)' This makes choice D the best answer. Two different hydrogen groups have different shift values, .,:
choice A is eliminated. Choices B and C are the same answer, so they shouldboth be eliminated. This lear'=
only choice D as the best answer.
42.
Choice A is correct. From tl-re NMR data, we know that Compound T has three carbon atoms and four hydrog.:
atoms, so the structure must contain only three carbons. Choices B, C, and D al1 have four carbonr, ,o thuy .-,=
eliminated without involving the spectroscopic data. The only choice that fits the formula is choice A. Or^.::
this question is resolved, it can help to solve some of the other questions. This happens often on the MCAT.
43.
Choice B is correct. The 13CNMR peak at 50 ppm is due to a carbon, not a hydrogen. This eliminates choices
and D. A carbonyl shows a 13CNMR peak around 200 ppm, so choice A is eliminafed. Only choice B remains,
you sl-rould pick it. The absence of an IR peak around 1700 cm-1 should reaffirm that a carbonyl is not present '.,:
Compound T. This means that choice B is the best answer.
Choice B is correct. The total number of hydrogens in the compound, according to the NMR is eight, of whr::
five are on the benzene ring. This eliminates choice C. The pisug" states thal the compound is an ester,:.
choice A, a ketone, is eliminated. The best answer is choice B, because the methyl shift is around 4.0 ppm. Th,is tough to know without an NMR chart. In the passage, it is mentioned that the alkoxy group hai a shift :
the 1HNMR between 3.5 and 4.0 ppm. if you can'f recali a fact, search for it in the passage.
45.
Choice C is correct. The three separate IUXMR spectra are to be compared to determine the compounds :
solution. It is important that nothing varies between samples, so the same solvent should be used i1 each ca.s=
Any impurity peak wouid be common to all of the spectra and thus could be eliminated. This makes choice C
the best answer. A common solvent has no effect on the pH or the behavior of a protic species in the lF{Nlt:
Although lHUltR invokes an externai magnetic field, the solvent has no bearing on the iielcl.
46.
Choice B is correct' This question is typical of spectra-to-structure-to-name questions. There are four carbons :
Compor,rnd III, so choices A and C are elj.minated, bec;ruse they have only three carbons, according to t:nomcnclature. Translating the narrles of cl-roices B and D yields the following two structures:
H3CH2C
ocH3
Methyl propanoate
H:C
OCH2CH3
Ethyl ethanoate
Both A anci C would have identical peaks of a 2H quartet, 3H triplet, and a 3H singlet. The key feature is ti.
3H singlet at approximately 3.5 ppm. This indicates that the methyl group is attached to the ester oxygen :i
in choice B. You should pick B to score.
47.
Choice A is correct. The four answer choices are the result of the following bonds: O-H (3500
sp3C-"^-t),
(2980 cm-l), C=O (1685 cm-1;, and C-O (1300 cm-1). An ester contains an sp3-f-g bond, a C=O bond,
and a C-i
bond, but it does not contain an O-H bond. This means that there will be no O-H stretcl-r (thus no IR peak at i:
near 3500 cm-1; associatecl with the IR spectra of an ester. Cl-roose A and be a stellar achiever at choosr-r.:
correct answers^
48.
Choice B is correct. Compound II has two oxygerls in its formula, so choices A ancl C are out immediately. T:'.
question here is reciuced to placing the a1ky1 group either on the ox\1gen (as in choice B) or on the carbon., carbon (as in choice D)" Because the peak for the two hydrogens is around 4.0 ppm, the ethyl group must'r=
attached to the oxygen, making choice B the best answer. You should note that when there is a jH quartet ar.:
a 3H tripiet in the spectra, there is an isolatec-l ethyl group ir-i the n-rolecule.
Copyright
172
m
hllL.
+Y.
Choice D is correct. Taken sequentially, the signals are a singlet (one apex), a quartet (four apexes), and a
triplet (three apexes). This makes choice D the correct choice. The shape of a peak, you should recall, is due
to the presence of hydrogens on the neighboring carbon.
Choice C is correct. An NMR solvent should be inert and show no peaks in the spectra. All of the compounds are
deuterated, (contains 2H rather than 1H) so they show no peaks in the 1HNMR spectrum. The most reactive
solvent listed is the alcohoi. The problem with an alcohol is that when it is heated or given enough time, it
can undergo a transesterification reaction and change the ester. This makes choice C the best choice. An ester
should be soluble in all four of the solvents. It is a general rule that protic solvents are bad choices for the
NMR, because they exchange for hydrogens and are typically more reactive than aprotic solvents.
Choice C is correct. 2-methyl-3-pentanone has four nonequivalent hydrogens, according to the symmetry of the
molecule. The structure of 2-methyl-3-pentanone is drawn below:
H*C
"l
bl
6 a hydrogens
c
'll
A../tt\ ,/t'=-.ff,
b hydrogen
2 c hydrogens
3 d hydrogens
o
This resuits in a ratio of 6:3:2:l for the four nonequivalent hydrogens, which makes choice C the best answer.
Choice A is correct. An isolated isopropyl group has two equivalent methyls groups (six hydrogens total)
adjacent to a CH group (one hydrogen). The six hydrogens of the methyl groups are expressed as a doublet
(being adjacent to one hydrogen), and the one hydrogen of CH are expressed as a septet (being adjacent to six
equivalent hydrogens). This results in a proton NMR with a septet (1H) and a doublet (6H). This is choice A,
so choice A is the best of all possible choices,
Choice B is correct. An alcohol hydrogen is rnildly acidic. This means that when a base is added to an alcohol,
ihe protic H on oxygen can be removed. If the alkoxide formed is placed in deuterium-labeled water, then the
alkoxide can remove deuterium from water to form a deuterium-labeled alcohol. Deuteriums do not appear in
the 1HNMR, so the peak for the H on oxygen disappears, making choice B the best answer.
R_d:\
r\ "\/
e
+oo1
H----/
D-dl"\/
u
e
+on1
D-\
--
D---/
+Ro
H
+DO
D
Choice A is correct. A methyl ketone has an isolated CH3 group adjacent to a carbonyl. Because the methyl
group has no hydrogen neighbors, it has no coupling, and thus is a singlet between 2.0 and 2.5 ppm. Pick A.
-::r-right
173
56.
57.
Choice B is correct. A 1HNMR peak at 9.7 pprr- indicates that the compound is an aldehyde. This eliminat.s
choice A (an ether) and choice D (a ketone). The ratio of 1,:7:6 lor theirea of the signali indicates that the::
are two equivalent methyl groups (that accounts for six equivalent hydrogens) and two unique hydrogens on +;,:
compound. Only choice B has two equivalent methyl groups, so choice B is the best answer. Theie are fc::
unique types of hydrogens on butanal, so butanal would show four signals in its 1HNMR, not just three signals.
Choice D is correct. Having no IR absorbance between 1600 cm-1 and 1750 cm-1 indicates that the compound h.:-.
neither a C=C bond nor a C=O bond in its structure, both of which have IR signals between 1600 cm-1 and 1li,
cm-1' This eliminates all of the choices except choice D. The compound ,rr.rit b" cyclic to account for the o:*
degree of unsaturation.
Choice C is correct. In Spectrum I, the distance between the peaks in the aikene region (coupling constant :;
59.
Choice D is correct. The methyl group has three hydrogens, so the signai for the methyl group on benze:.
cannot be the peak at either 7.25 ppm and 5.37 ppm, because neither of those peaks contains three hydroge:-This eliminates choices A and B. The alkoxy methyl group on the oxygen is found farther downfield than f *
methyl on benzene. Thus from the values on the spectra, the methyl on benzene (3H singlet) comes at 2.25 pp::
which is choice D.
60.
Choice C is correct. In order for the disubstituted benzene compound to have the same number of peaks in -:*
carbon NMR as it has carbons, the compound must not have symmetry. Symmetry results in equivallnt carbc:-.
resulting in fewer 13CXUR signals. the only asymmetric iompound u-orlg tire answer choices is the n.-:.l
substituted benzene with two different substituents. Choice C is correct. The choices are drawn below:
B.X
A.
C.X
D{
cc /Cb,'
c,/cu.-
il
i-'
?Cr
CcX
C.\
au
1"
t Cr--.
^
udY
'iiT"'f.
c.1 lzC.
$'
6 Carbons
3
61.
l3cltttR
peaks
6 Carbons
13CNMR
peaks
Carbons
13CNMR
peaks
Carbons
13CNMR
peaks
Choice B is correct. The 1H peaks (the vinylic hydrogens) in the spectrum fall between 4.88 and 5.37 py=".
implying that the hydrogens on the alkene are found in this range. Hydrogens on an alkene are referred tc m
vinylic hydrogens. This means that vinylic hydrogens are found in the range of 4.5 ppm to 7.0 ppm. This ma..:s
choice B the best choice.
Choice D is correct. The compound contains a C=C double bond, which has an IR absorbance between 1620 c::'')
and 1660 cm-1. The best choice is 1640 cm-l, choice D. An IR absorbance of 3500 cm-1 is due to a O-H bond, ar. Ji
absorbance of 2220 cm-1 is d"ue to a C=C bond, and an IR absorbance of 7720 cn-7 is due to a C=O bond.
63.
Choice D is correct. With meta-substitution, all of the benzvlic hydrogens would be different, because --:*
benzene compound would be asymmetric. There would thus be four nonequivalent hydrogens in a 1:1:1:1 ra-r:,
Picking D is a beautiful thing on this question.
64.
Choice D is correct. An ethyl group on benzene is composed of a CH3 group next to two equivaient hydrogi--r,.,
(making it a 3H triplet) and a CH2 group next to three equivalent hvdrogens (making it a 2H quartet). I:
describes choice D.
t74
ry
tr5.
Choice C is correct. Because the compound contains two oxygen atoms, choice A (an aldehyde) and choice D (a
ketone) are both eliminated. There is no peak in the IR spectrum that is indicative of an O-H bond, so the
compound is not a carboxylic acid. This eliminates choice B. The only choice left is choice C.
,ffi.
Choice C is correct. The molecular ratio of hydrogens cannot be 3:1 in that region of the proton NMR spectrum,
given the shift values. In order for there to be only one hydrogen on a carbon, there must be other groups
ittached to that carbon. If the other group was caibot'r-based, ihere would be more signals in the IHNVIR
spectrum than two and more signals in the 13CNMR spectrum than four. If the groups contained no hydrogen,
then they would affect the shift value, making it farther downfield than 2.0 ppm. They are alkyl hydrogens,
so the ratio is most likely 9:3, caused by the presence of equivalent methyl groups. Any alkyl group besides
methyl would show coupling and not singlets. The structure must therefore have a tertiary butyl group (nine
equivalent hydrogens forming a singlet) and an isolated methyl group (three equivalent hydrogens forming a
singlet). Choose C for best results.
Choice D is correct. A 13CNMR peak is for carbon, not hydrogen, which eliminates choices A and B. The
passage states that the carbon of the C=O bond is found at170.2 ppm., which eliminates choice C. The best
answer is choice D. Carbons bonded to an electronegative atom that arc spJ-hybridized typically show a
signal between 60 and 90 ppm.
tr!"
Choice C is correct. As stated in the passage, the peak at 170.2 ppm is attributed to a carbonyl carbon.
Carbonyl carbons are found between 770 and220 ppm in the 13CNMR. Choice A is an ester, choice B is a ketone,
and choice D is an aldehyde, of which all three contain a carbonyl group. This means that choices A, B, and D
can be eliminated, because they all exhibit a signal in the l3CNltR that is greater than 100 ppm. An alcohol
has a peak around 70 ppm to 80 ppm for the alcohol carbon, but not greater than 100 ppm. The best answer is
choice C.
Choice A is correct. The shift value for hydrogens on an alpha carbon (the carbon adjacent to a carbonyl) is
found to be between 2.0 ppm. and 2.5 ppm. The alpha hydrogens are described in the answer choices as
hydrogens on a carbon adjacent to a carbonyl (C=O) bond. This is choice A; your choice for a question like this.
Choice D is correct. A singlet in a 1HNMR spectrum occurs when there is an isolated hydrogen (or group of
equivalent hydrogens), with no hydrogens on the neighboring atoms. This eliminates choices A, B, and C, and
makes choice D the best answer.
Choice D is correct. Compounds A and C are eliminated, because they do not contain two oxygen atoms, as is
stated in the passage. Choice B is eliminated, because the CH3 of the methoxy group would show a shift value
between 3.5 ppm and 4.0 ppm. The peak for the lone methyl group is found near 2.0 ppm, which indicates that
the methyl group is adjacent to the carbonyl. The correct structure is choice D.
:a
Choice C is correct. The oxidation of a secondary alcohol to a ketone results in a carbon that goes from a
i3CIrIptR signal of roughly 75 ppm to a signal of roughly 200 ppm. This conversion can be monitored.easily by
13CNMR, so choice A is valid. Nitration of ethylbenzene results in a carbon that changes from a TTCNMR
signal of roughly 115 ppm to a signal of roughly 140 ppm,.lecause the nitro group changes the immediate
chemical environment. This conversion can be monitored by 13CNVR, so choice B is valid. Deprotonation of a
carboxylic acid. does not change the immediate environment (adjacent atoms) of any carb.oSr so no drastic change
in change in any l3CNltR sifral is observed. This conversion cannot be monitored Uy isg*tR, so choice C is
invalid, and thus is the best choice. Reduction of an alkene to an alkane results in a carbon that goes from a
13CNMR signal of roughly 100 ppm to a signal of roughly 20 ppm. This conversion can be monitored by
l3CNVln, so choice D is valid.
:i
Choice C is correct. According to the reaction in the passage, the compound is an aromatic ketone. The peak at
206 pprn, according to the data in Table 1, confirms that Isomer I is a ketone. Choice D (the aldehyde) is thus
eliminated.. Becau-se there are only seven peaks for the 13CNMR, the compound must have symmetry, so
choices A and B are eliminated. The best answer (one that contains only seven unique carbons) is choice C.
Review@
175
74.
Choice A is correct. An aldehyde, according to Table 1, is found between 185 and 200 ppm, and no peak is fou_i.:
in this range for either structural isomer. Choice A may be the corect choice. It stated in the pu5ug" that c,:
occasion, the shift may not fall exactly in the range given. An alkene, according to Table 1, is found beiween 1- and 140 ppm, and there are peaks found in this range for both structural isomers. Choice B can thus i.
eliminated. A ketone, according to Table 1, is found betr.r'een 205 and 220 ppm, and peaks are found in this rans=
for both compounds. Choice C is thus eliminated. A methyl group, according to Table 1, is found between 10 a-r;
35 ppm, and there are peaks found in this range for both structural isomers. Choice D is thus eliminated. Tf.best answer is choice A.
/J.
Choice D is correct. According to the passage, the least intense peak is caused by a carbon with no hydroge:,.
attached. This makes choice D the best answer. The carbons with no hydrogens attached in a disubstitute:
benzene derivative with a carbonyl are two of the benzene carbons (the beniene carbons with a substituer:
attached) and the ketone carbon. It has sp2-hybtrdization, not sp3-hybridization, and
it is achiral.
Th-"
eliminates choices B and C. While it has sp2-hybridization, that is not the cause of its low intensity. Chor.:
D is a better answer than choice A. This is a question that rewarded the test taker who sifted through t:information in the passage. This will happen on occasion, because even the science sections are reading u*u*..
76.
Choice C is correct. Para-methoxybenzaldehyde has a total of eight carbons in its structure, but the molecu-.
contains a mirror plane that reflects two pairs of equivalent carbons. Using symmetry, this means that the:=
are only six unique carbons, so the best answer is six signals, choice C. The structure is shown below:
o\^-t
!u
I
CD
.c/-\
ilt
oC-..
-Z
c.
Cd
eC
lr
ocH3
Choice D is correct. Because the two compounds are isomers, they have the same molecular formula. Havrr:
the same molecular formula results in having the same units of unsaturation. This eliminates choices A and E
Each compound has a benzene ring and a carbonyl group. The benzene ring has three n-bonds and the one rir-r:
There are four ur-rits of unsaturation due to the benzene ring alone, so choice C is eliminated. When the carbor.-.
n-bond is accounted for, there are five units of unsaturation in the molecule, so the best answer is choice D.
-
78.
Choice B is correct. It is stated in the second paragraph of the passage that quaternary and carbonyl carbor..
generate peaks of low intensity. There is no carbonyl in the compound, but carbon 2 of 2,2-dimethylbutane ha-.
four other carbons attached, making it a quaternary carbon. The best answer is choice B, carbon 2.
79.
Choice A is correct. Spectrum I contains a quartet (2H), a triplet (3H) (this combination is a dead give-an-a:
for an isolated ethyl group), and a singlet (3H) (a dead give-away for an isolated methyl group)- The t',=
question here is whether the ethyl group or methyl group is attached directly to the oxygen of the ester grou;
The degrees of unsaturation (1) and number of oxygens (2) tell you the compound must be either an ester or :
carboxylic acid. The lack of a broad peak between 10 - 12 ppm eliminates the possibility of the compound bef :
a carboxylic acid, so the compound must be an ester. Because the quartet is so far ciownfield (at a higher sh,:value), the ethyl group is attached to the oxygen. This makes the best choice an ethyl group on the meth'. ester, whose common name is ethyl acetate. Choose A for best results.
80.
Choice B is correct. A triplet is the result of coupiing to the neigl-rboring hydrogens (there are two hydrogens c.
the adjacent carbon in the case of a triplet). The integral (quantitr. of hvdrogens for the signal) has no effect c:
the shape of the signal, meaning that the peak shape does not tell vou any information about the hydrogens cthe signal, only about the neighboring hydrogens. This eliminates choices A and C. A triplet is therefore th=
result of neighboring a CH2 group. Choose B for a grade A, genuine, altogether correct, best answer.
176
E
&F
Choice B is correct. Spectrum II contains a quartet (2H), a triplet (3H) (this combination is a dead give-away
for an isolated ethyl group), and a singiet (3F{) (a dead give-away for an isolated methyl group). Because the
3H singiet is found around 4.0 ppm, the methyl group is attached to the oxygen. This makes the best choice a
methyfgroup on an ethyl ester. Choose B for the happiness of another correct answer. The drawing below lists
how the name and structure are determined for the compound.
Singlet in the 3.5 to 4.0 PPm range
/il
H;C-.
methyl
--J
cHzcHj
propanoate
Nomenclature rules state that the alkyl group on oxygen is named first, followed by the ester chain' This
makes this compound methyl propanoate.
Choice C is correct. This is one of those trivial facts that you should know. A peak in the neighborho od ol 7
ppm is indicative of aromatic hydrogens, which are found in benzene compounds. Pick C, to score bigl
Choice A is correct. A carboxylic acid has one proton that forms a broad peak between 10 ppm and 12 ppm in the
1nruVtR. The hydrogen in question is the acidic proton of the carboxylic acid. Because there is only one proton,
the peak between 10 ppm and 12 ppm has an integration value of one hydrogen, so choices C and D are
eliminated. An ester nui at'r alkyl group attached to the noncarbonyl oxygen of the ester. Protons on the first
carbon from the oxygen have a peak between 3.5 ppm and 4.0 ppm. This eliminates choice B, leaving only
choice A as the possible answer. The peak between 2.0 ppm and 2.5 ppm is the result of alpha hydrogens,
which ot" preser-ri in both an ester and a carboxylic acid. 'lhis means that a peak between 2.0 ppm and 2.5 ppm
cannot be used to distinguish an ester from a carboxylic acid. The correct answer is choice A'
Choice B is correct. 4-Heptanone is a seven-carbon ketone with the carbonyl directly in the middle- The
structure is symmetric, so there are many equivalent carbons and hydrogens. There are four unique carbons, of
which tl-iree contain hydrogens. This resulti in three signals in the 1HNMR for 4-heptanone. The best answer
is choice B.
Choice A is correct. For Compound II, the absence of a 13CNMR signal between 180 ppm and 230 ppm supports
rHNMR spectrum
the idea that it has no C=O group. This eliminates choice C. No peak above 5 pp* in the
in the
unsaturation
confirms that there is no double bond. This eiiminates choice D. This means that the unit of
1HNMR
idea
suPPorts,the
spectrum
compound must be the result of a ring. The presence of a broad peak in the
IrCNMR
The
al1swer.
that the compound is an alcohol, eliminating choice B and making choice A the best
spectrum shows that there is great symmetrv in the structure. The choices are either cyclopentanol or 2,3dlmethylcyclopropanol. The integral of the proton NMR says that there are mostly CH2 groups present,
which iurro., ryclopentanol over 2,3-dimethylcyclopropanol. Cyclopentanol is drawn below:
H<\ /
Broad------>1tO
(1H)
,zt\
H"C
42c-
(1H)
CH"
\,2
Tripiet (4H)
Copyright
Multiplet
MuitiDiet
13cNMR,
There is a mirror planecutting throughthe
molecule, so there are three unique carbons,
resulting in three different signals.
(4FU
86.
Choice D is correct. Each unique carbon within a molecule exhibits a unique signal in the 13CNMR spectrum, so
choice A is valid. This eliminates choice A. A carbonyl carbon has a slgnaiaround 180 ppm in a 13CNVR
spectrum, which b d+lf:=llom other signals in the 13CNMR spectru-. ih" presence of a carbonyl group can
be identified using l3CNl'tR spectroscopy, so choice B is valid and thus elirninated. The substitution of a
benzene ring affects the symmetry of the molecule. For instance, if the substitution is para, then there is a
mirror plane in the molecule. This results in fewer unique carbons, which is seen with 13CNMR spectroscopy.
This makes choice C a valid statement, and therefore it is eliminated. The geometry about a doulle bond, cis
versus trans, does not express itself in l3CNltR spectroscopy. Typicaily, geJmetry is determined by looking at
constants of the vinyiic hydrogens in 1HNMR spectroscopy. bhoice D cannot be determined using
ll:::_"-p_t*g
87.
Choice C is correct. According to the data in the passage, only Compound I has a UV absorbance above 175 nm.
This means that only Compound I has a r-bond. There is only one unit of unsaturation, so Compound I can have,
at most, one n-bond. This means that Compound I cannot be a conjugated diene, which eliminites choice A. If it
were a conjugated diene, there would be a UV absorbance above 200 nm for the n to rc* transition. Compounds II
and III cannot be carbonyl compounds, according to their UV data. If there was a carbonyl gro.rp on the
molecule, there would be a n-to-n* transition around 190 nm and an n-to-n* transition around jOO n*. this
eliminates choice B. Because Compound I has two UV absorbances and only one n-bond, it must be a carbonyl
species of some sort, While it is not possible to decide between an aldehyde and ketone based on this
information, choice C is a solid answer. Because Compounds II and III show no UV absorbance above 1,75 nm,
there is no n-bond present. However, choice D refers to Compounds I and II, not II and III, so choice D is
eliminated. Choice C is the best answer.
88.
Choice D is correct. For Compound III, the absence of a broad peak in its 1HNMR spectrum confirms that there
is no alcohol in the compound. This makes choice A a valid statement, and thui the incorrect choice. The
absence of a peak around 180+ ppm in its 13CNMR spectrum confirms there is no C=O present. This makes choice
B a valid statement, which eliminates it. The absence of an absorbance above 180 nm in the UV-visible
spectrum implies that there is no n-bond ir-r the compound, confirming that the structure must be cyclic to account
for the one unit of unsaturation. This makes choice C a valid statement, which eliminates it. The I3CNIrAR
shows very few signals (only three), which implies that there is great symmetry in the structure. It must be a
symmetric cyclic ether. This makes choice D an invalid statement, making it the best answer.
89.
Choice B is correct. Key features from each spectrum must be extracted. From the molecular formula, we know
there is one unit of unsaturation and one oxygen. This means that the compound must contain either a ring, a
C=C bond, or a C=O bond. All of the answer choices fit these criteria, so we must use the spectroscopic dita.
the l3CNVtR data show a peak at 211 ppm (1), and that no two carbons are alike. This means that the
compound is a carbonyl, which does nothing to eliminate any choices. If the compound were 3-pentanone, it
would show only three signals in the 13CNVR due to its symmetry, which eliminates choice C. The fact that
no two carbons are alike also eliminates choice D, which has two equivalent methyl groups. the 1HN\4R data
shows a 3H singlet at 2.08 ppm, and no peak between 9 and 10 ppm. This means that the iompound is a methyl
ketone and not an aldehyde, which elj.minates choice A and choice C. The ratio of the hydrogen signals in the
lHNltn (3 :2 :2: 3) supports choice B. The structure is shown below:
ll
n"r/'T-.r'/
1HNMR,
13CNMR,
t' I t'
rrJptet
(3H)
tV',.
v,,rlipturrrlpt"t
(2H) (2H)
:v-vis:
18e
CNMR:
nm and 268 nm
21 1
PPm
t
silgr"t
(3H)
are different, so there are five different signals.
There can be no branching, because the proton NMR shows that the integral values are 3,2,2,3. This implies
Copyright
t7a
E
91"
90.
Choice D is correct. Integration is used to determine the reiative quantity of hydrogens within a signal by
looking at the area of the signal. Integration does not change with magnetic environment, so choice A is
eliminated. The neighboring hydrogen atoms affect the splitting, not the integral, so choice B is eliminated.
Integration does nothing to determine the presence of atoms other than hydrogen, so choice C is eliminated.
The best answer is choice D.
91.
Choice C is correct. Five hydrogens constituting a singlet with a shift value between 6.0 and 8.0 ppm indicates
that the compound is a monosubstituted benzene. The three remaining hydrogens make up a methyl group. This
now becomes a nomenclature question, rather than a spectroscopy question. The correct name for a methyl group
attached to benzene is methylbenzene. The common name for methylbenzene is toluene. Choose C for optimal
results.
92.
Choice D is correct. The formula contains six hydrogens in all, so the sum of the ratio values must equal 6. The
first peak is shortest, the middle peak is the second tallest, and the last peak is the tailest. This means that
the values must be ascending. The only combination of ascending values adding to 6 is 1:2:3. Choice D is the
best answer.
93.
9'1.
Choice D is correct. The compound 2-bromopropane has two unique types of hydrogens, so it has two peaks in its
IUNUn spectrum. The two terminal methyl groups are equivalent, so they are seen as one signal with an
integration of 6. The middle carbon (carbon 2) has one hydrogen, so it has a signal with an integration of 1. The
peak shape is determined by adding 1 to the number of hydrogens on the adjacent carbons. The six equivalent
hydrogens have one hydrogen neighbor, so there is a doubiet of integration 6. The one hydrogen has six
hydrogen neighbors, so there is a septet of integration 1. Choice D is the best ansr.ver.
Choice C is correct. A quartet is the result of the observed hydrogens being coupled to three equivalent
hydrogens. This is often the result of hydrogens that are adjacent to a methyl group on one side and no other
protons on the other. The quartet hydrogens are in bold face, and the neighboring three hydrogens are boxed in
the drawing below. Choice C is the oniy structure that shows no quartet in its proton NMR spectrum.
A.
(H3C)2HC
A cHr@
C.
(H3C)2HCH2C
cHg
B.
fnrburclHrcyrc
D.
o
H3CH2CH2 C
CH:
A cHr@
95.
Choice D is correct. A doublet is the result of hydrogens on a carbon that neighbors a carbon with only one
hydrogen attached (most easily recognized as a tertiary carbon). In each of the first three answer choices, the
methyl group attached to the interior of the carbon chain is bonded to a carbon with only one hydrogen (a
tertiary carbon), which results in every compound having a doublet with an integration of three hydrogens.
This leaves choice D as the best answer.
q5.
Choice
A is correct. A positive iodoform test, as stated in the question, is caused by a compound with three
aipha hydrogens on one carbon. This means that the iodoform test is positive for a methyl ketone, which
would have a CH3 group adjacent to a carbonyl (there are no hydrogens on a carbonyl). With no hydrogens on
the neighboring carbon (carbonyl), there is no coupling and thus a the peak is a singlet. Pick A for the pleasure
of correctness. The iodoform test works by removing an alpha hydrogen to form an anion. The anion
subsequently attacks iodine, adding an iodide to the alpha carbon. This is repeated two more times, until there
are three iodides bonded to the alpha carbon. The CI3 group is a great leaving group, and it forms a yellow,
oily compound when protonated.
-opyright
97.
Choice D is correct- The hydrogen responsible for the broadness is the carboxylic acid proton. It is bondecl to an
oxygen, making choice A an incorrect answer. The couphng to eight or more other hvdrogens would result in a
multiplet made of many sharp peaks, not a broadened signal, which eliminates ciroice B. Choice C can be
eliminated, because hydrogens on carbon do not form hydrogen bonds. the hydrogen forming the hydrogen bond
in this molecule is bonded to oxygen. This makes choice D the best answer.
Choice B is correct. Because the compound on the left has cis orientation about ttrre internal double bond, while
the compound on the right has trans orientation abor-rt the internal doubie bond, the two compouncls must be
geometrical isomers of one another. Pick choice B, and you won't be sorry. In case you were considering choice
C, the two compounds have the same absolute configuration, so they cannot be optical isomers.
99.
Choice C is correct. Both double bonds are trans, so choice B is immediately eliminated. Both have the same
connectivity, so that eliminates choice A. The last thing to check is the chiral centers, and each has just one
chiral center. The compound on the left has R chirality, while the compound on the right has S chiralitr.
This makes the two structures optical isomers, choice C. If you flip the structure on the right to align with the
structure on the left, it can be seen that the chirai center has changed" A change in a chiral center results in an
optical isomer.
,ars".s
100. Choice A is correct. The best way to do this probiem is the systematic counting of carbon backbones, starting
with the iongest carbon chain possibie (five carbons). The tally for each possible carbon backbone is drar,r,r
beiow. There are only three possible structures: pentane, 2-methylbutane, and 2,2-dimethylpropane. Tlr-c
structures that are in fact structural isomers must have different IUPAC names. Pick A to be a correct anst'e:
picker person.
C
I
I
C-C
I
Section III
Stereochemistry
by Todd Bennett
TIEBITEIEY
l) g. p- y.1.-6. u/'
&
Ntrt,,,-
ct/
-i,n_^_^
cl
CI
a?
Be able to
and
stereoisomers.
Youmustunderstandthedifferencesbetweenenantiomersu''da
op.tica] inactivity and structure. iL"
9"*""*.'.fl_1":"_.::Tf?.yf:ji9T
lh"toanh epimerscasesinvol,vi"g
such as anomers
M<ist importantly, when
:"g?.t:
be able to identify
@?
Be able to use
rotation data to i
an unknorun
JustIiketheboilrngpointandthemeltingpoint,theopticalrotationi'upnyffi
uyrrldr rurdr.rurr ls d pftyslcal pl.opeftv tnat can
l"'""';
_"': :"'::.,6
Deused to Identlty a molecule. The
Ihe opti"cal,rotation
optical rotation is a measurement df
of t'he
the rotation
rotalion ol
o1,.r nlan,,d
pti""J
::,T:9P,i1""l,ilt:
i?],"jq"
p,."hlt::1,!,qht bi a solution of the cipticatly active .o*po.rtld. A;.-;;;;;ppli;"ti;"'il;h;
ldentrtlcatron an unknown susar.
sugar.
rrrL rrrcrrrrrS PUrrrr, .rrE
Be able to disti
ish
ic substitution mechanisms.
There are two mechanisms for nucleophilic-substitution that you must know. fft" fitst ir tt-r" Slryf
ancl the second is the S1x2.
and
Sg2. They are
aredefined
deTined bv the number of leactants
ieactants in the rate cletermininc,
sfen
determining step
of the mechanism. You.must 6e able io predict the reaction from the l.ltiri.."ailio"s, t"co"g"ir'"
the reaction from the intermediate or trahsition state, and identify the reaction it;;ih6 p;;f,;;r.
The differences include solvent, strength.of leaving group, sterii hindrance, ability to slabilize a
carbocation intermedia te, and stereoch"emistry.
llili:li
ilit i:
)il[*
lh*:
:!*
iX!:tlt
nucleophile.
it"y;;;l";ih;;;"dil;l
:tLlt
tllgli
r*
&r&
-[gfi!
$Ima:
|]t&i0![
ilUMll'r
tumrrn
Organic Chemistry
Stereochemistry
Introduction
molecule, but they differ in some manner so that the molecules are not
superimposable on one another. No matter how a compound is rotated or
contorted, it is not superimposable on its configurational isomer. As a
consequence of their different configurations, one configurational isomer may
have the correct arrangement of atoms to offer minimal steric hindrance in a
chemical reaction with another asymmetric molecule, while another
configurational isomer proves to be too stericaily hindered on one side to
undergo reaction. This is frequently seen with enzymatic chemistry, where
enzymes have several stereogenic centers and are highly specific about which
configurational isomer can bind and undergo a reaction.
Copyright
r85
Organic Chemistry
Stereochemistry
Configurational Isorners
Configurational Isomers
Configurationai isomers have identical bonds, but they have a different spatial
arrangement of their atoms, no matter how the structures are contorted.
Common examples, with which you are familiar, are optical isomers. Opticat
isomers, due to their asymmetry, rotate piane-polarized light. This is used as a
diagnostic test to identify a specific configurational isomer. We shall first look at
asymmetry and chirality, as configurational isomers are based on chirality.
Asymmetry
A molecule with asymmetry has a site about which there is uneven distribution
of the bonded atoms. Analyzing symmetry is critical, because at least one of two
stereoisomers must be asymmetric in some manner if the two structures are not
superimposabie. To understand stereoisomers, it helps to be familiar with mirror
plane symmetry and chirality (molecular asymmetry). Figure 3-1 shows the
asymmetry of carvone and the symmetry of 2,2-dichloropropane.
C1
-H5
Hsc
CHs
Plane of symmetry, so
the compound is achiral.
No plane of symmetry, so
the compound is chiral.
Figure 3-1
Chirality
Chiral is the term assigned to a molecuie with no plane of symmetry, therefore a
chiral molecule has an asymmetric structure. Simply put, chirality is the "left
and right handedness" of a molecule. From our perspective (keeping at the leve1
of this test), a chiral molecule has at least one stereogenic center present. A
stereogenic center is an atom within the chiral compound^that has asymmetrrabor.rt it. For our needs, chiral (asymmetric) carbons are sf -hybridized carbons
with four unique substituents attached. Within 2-chloropentane there is one
stereocenter (chirai carbon), as emphasized in Figure 3-2 below. Figure 3-2
shows the two configurational isomers (enantiomers) of 2-chloropentane in such
a manner that the two structures are mirror images of one another. The plane
mirror reflects a configurational isomer as its image.
-;---plane
mlrror
-'CHTCH2CH3
I '
I
-_____;;__.v,1:
I-ug" cl
sp3-hyb.idirotitor-t
Figure 3-2
'tLl
:tl
&n
-;
Organic Chemistry
Stereochemistry
Configurational Isomers
What makes this important is that an atom with four unique substituents
attached has two possible ways that the substituents may be connected (which
ate mirror images of one another). The two structures, mirror images that have
identical bonds, are stereoisomers that may exhibit different chemical properties
despite identical physical properties as one another. The biological ramifications
of chirality are important. For instance, humans digest only D-sugars (D refers to
one of the two possible stereogenic orientations associated with the penultimate
carbon within a sugar backbone), because enzymes bind and react only with Dsugars. If this seems unclear, the following everyday analogies may help:
a) A soew with right-handed threads does not fit into a left-handed nut.
b) Your right hand does not fit rnto a left glove.
:) A key with a groove on only one side and its mirror image do not open the
same iock.
Exampie 3.1 shows some examples of pairs of butane moiecules that have four
'l1ique substituents on carbon two. The goal of the question is to develop skills
:or quickly recognizing when two structures represent conformational isomers
ciscussed in section II) versus when they represent configurational isomers.
Example 3.1
,ihich of the following structurai pairs represents the same molecule and not a
:air of configurational isomers?
\.
&
F{3CH2C
F{rCHrC&I
H
D
D.
OH
&
irL
cH2cH3
""-&rx,.,,,
!Br
i
-,./YcHrcH3&
cH2cH3
CHg
D.
cH.cH"
l'J
:ul2clY/H
CH"Cl
&
t-
H3cH2clY/H
! olution
- :u must decide whether the compournds are either enantiomers or the identical
,:r-Lpound with different spatial orientation. Rotate the molecules in your mind
' - see if the atoms overlay. If you do this successfully, then you will see that they
=:e identical only in choice C. However, if this is hard for you to visualize, try a
.=: of models. A shortcut you may recognize is that when two of the substituents
':e interchanged, the chirality of that stereocenter changes. In choices A, B, and
l' two substituents have interchanged, making them enantiomeric pairs.
-:pyright
r85
Organic Chemistry
Stereochemistry
Confi
gurational Isomers
The molecules in choice C in Example 3.1 are identical. If the left structure is
rotated counterclockwise by 120" about the carbon 2 - carbon 3 bond (as shown in
Figure 3-3), the identical structure and orientation are formed. Note that when a
structure is rotated by 720" about a bond, the three other substituents interchange
their locations on the molecule. The conclusion from this is that when three
substituents are different from one structure to another, those two structures
represent different conformational isomers (orientations) of the same compound.
C1
I
BrlYcH2cH3
zGH:-
Figure 3-3
Rotating molecuies in your mind becomes easier with practice, although if the
ski11 is never fully developed, you can stil1 answer stereochemistry questions br
following a few simple rules. If two groups are interchanged and the rest of the
molecr,rle remains in place, then the two structures are configurational isomers. If
there is a mirror plane between two molecules and no mirror plane within the
molecule, then the two structures are configurational isomers.
lx
;
1i
lr
llr
:tr"r
1) First, you must prioritize (from heaviest to lighiest) the substituents that
$."
2)
3)
are
attached to the carbon of the stereocenter according to the atomic mass of the
atom directly bonded to the chiral carbon. (Get it from the periodic table)
Second, you must orient the molecule in such a way that the substituent wil;.
priority number four points behild the plane of the molecule'
Third, you must draw a circular arc from substituent 1 through 2 and on to l
If the arc is clockwise, it is referred to as R. If the arc is counterclockwise, it r.
referred to
as S.
ra6
"i
'11
l:t
lill lr ,
iut!1,
zu.
;i.*
'l,r
Organic Chemistry
Stereochemistry
Configurational Isomers
R is from the word rechts, which is right in Latin, while S is from the word sinister
which is left in Latin. If you point your thumb in the direction of substituent
number four on a compound with R-stereochemistry, the fingers of your right
hand will curl from one to two and on to three. Thus, R-chirality can be thought
of as right handedness. The same holds true for your left hand with an s-center.
Reposition by
Redraw to
see
chirality
_______>
Clockwise: R
3
Reposition by
rotating by 90' about
C.51.o1-C1 bond
Redraw to
see
chlrality
---------->
Counterclockwise:
Figure 3-4
-\ carbon center that when you look down the bond from the chiral carbon to the
:ourth priority substituent (usually a C-H bond) in a way that you can't see the
iourth priority substituent, the remaining substituents form a clockwise arc
,r-hen moving from priority one to priority two and on to priority three according
io the priority rules. This can be thought of as a right-handed molecule when
llacing your thurnb in the direction you're looking and curling your fingers to
natch your right hand to the structure.
S-center:
carbon center that when you look down the bond from the chiral carbon to the
:ourth priority substituent (usually a C-H bond) in a way that you can't see the
:ourth priority substituent, the remaining substituents form a counterclockwise
:rc when moving from priority one to priority two and on to priority three
:ccording to the priority rules. This can be thought of as a left-handed molecule
'";hen placing your thumb in the direction you're looking and curling
-1,
your
Copyright
ta7
Organic Chemistry
Configurational Isomers
Stereochemistry
23
Tt'
f',
Ir
n4$'r
sI
n,
"r'*'it
!n'
T"'
I>Br>C>H O>C>D>H
Br>C=C>H
t CHs
CH2CH3
C-C-C-C
C{
>
C-H
Figure 3-5
Shortcut to Determine R and S
As with so many other topics in organic chemistry, such as nomenclature, R and
S questior-rs become easy and redundant with time. Once they become easy,
there are useful quick tricks to help you to identify chiral centers as being either
R or S. For instance, when the fourth-priority substituent is sticking out from the
rnolecule, the molecule must be rotated. To save time, it is easiest to first solve
for the arc using the structure as it is, and then take the opposite chirality for the
center. In the interest of saving time, this works well for use on tl're MCAT.
Substituent number four can either be behind the plane, in front of the plane or
in the plane. In each case, there is a technique to apply to arrive at the chiral
center easily. Many techniques shall be presented, so choose your favorite.
Figure 3-6 shows how to get the chirality easily when the structure is drawn irr
the conventional manner.
'(')t4
,l,.i(f-},.t-,,
t, Ho
H"
H?CH2
H
H in front of plane
.'.
H3CH
iY)
HO
CHs
H in plane close to back group
.'.
Figure 3-6
Copyright
L{._
Organic Chemistry
Stereochemistry
Configurational Isomers
Example 3.2
The following molecule has what type of chiral
- orientation?
H"C
,\
Ho$tyc
cH2cH3
A.R
B.S
C. The molecule has no chiral center.
D. The compound is meso.
Solution
The compound has one chiral center, so it cannot be meso (to be meso requires an
even number of chiral centers). The compound is chiral, because carbon two has
Priority#1
HO\\)
H
Counterclockwise = R
Priority
#4
Example 3.3
CH"OH
OH
{.
OH
2R,35,45,6R
B. 2R,3R,4R
C. 2R,3R,43
D. 2R,35,45
Solution
larbon six is not a chiral center, because there are two methyl groups present
lhis eliminates choice A. The chiral centers are 2R, 35, 45 (choice D), as shown.
oH oH
cH2oH
4S
CHs
-,:pvright
CH"OH
V<
ra9
Organic Chemistry
Stereochemistry
Confi
gurational Isomers
Example 3.4
Which of the foilowing compounds have R orientation?
C1
HgN*
nrcnrc4/;cn,
HOH
CH2OH
Compound II
Compound I
A.
B.
C.
D.
HOH2C
Compound III
Compound T only
Compound II only
Compound III only
Compounds I and III only
Solution
Hydrogen points out in each of the compounds. Whichever arc is seen from this
view must be reversed to get the arc that would be seen from the correct view.
The priorities in Compound I are: Ci > CH2CHg > CHe > H. Compound I has an
R chiral center. The priorities in Compound iI are: NH3+ > COZ- > CH2OH > H.
Compound iI has an S chiral center. The priorities in Compound III are: OH >
CHO > CH2OH > H. Compound III has an R chiral center. Choice D is best.
Compound I
Compound II
(2-chlorobutane)
(Serine)
tcl
H3CH2
Compound III
(D-Glyceraldehyde)
o
HOH2
o-
H3
Example 3.5
What is the stereochemical orientation of the foilowing molecule?
"\-
.CH,
Eil
r,.J)y'-'a.,
A.
B.
C.
D.
2R,3R
2R,35
23,3R
2S,3S
Solution
For the first chirai center (carbon 2), the fourth priority (hydrogen) is in the plane
close to the group in back (a reversing position). An arc from priority one to two
and on to priority three is counterclockrvise. However, because H is in a reverse
position, the chirality is R. The second chiral center (carbon 3) has H in front of
the plane, so it is in a reversing position too. An arc from priority one to two and
on to priority three is clockwise. Horr-ever, because H is in a reverse position, the
chirality is S. The best answer is thus 2R, 35 which makes choice B correct.
:i
-s
lt*
i,:
Il
lr:
r90
Organic Chemistry
Stereochemistry
Configurational Isomers
Figure 3-7 shows a summary of the tricks presented in Figure 3-6 and applied in
Examples 3.2 through 3.5.
If Priority #4 is in front,
If Priority #4 is in back,
Figure 3-7
HOH2C<
cHs
HoH2r<
'@
Priority #4 not in back
lHtz
'HO
Priority
...
#4
H.J
H*
.'.
CH"OH
H2OH
...
Hgcl
Hscj
HOH2C
Priority #4 not in back
1oH
HOH2c
Priority #4 now in back of plane .'.
New structure has a clockwise arc, so it is R
The original compound must be S
.'.
Figure 3-8
These are two-dimensional tricks that may be done on
a molecule.
l9r
Organic Chemistry
Stereochemistry
Confi
gurational Isomers
Optical Rotation
Optical rotation is a physical measurement of the rotation of plane polarized light
by a solution with a chiral molecule. A soiution containing a pure compound of
known concentration (dissolved into solvent) in a standardized cuvette rotates
piane-polarized iight the same amount each time. Consequently, the specific
rotation (optical rotation under specific condiiions) is a physical measurement
(like melting point and boiiing point) that may be used as a diagnostic test for the
identity of a compound. This is common with sugars which have multiple chiral
centers. The direction of the rotation is signified by either (+) or (-) orientation
foliowed by the degrees of rotation. The (+) denotation describes clockwise
rotation of light while the (-) denotation describes counterciockwise rotation of
light by the molecule. If the R-enantiomer of a compound lotates the light in a
positive direction by X", then the S-enantiomer of the cornpound rotates light by
X' in the negative direction. The measurement is taken with a polarimeter which
is made from a sample tube sandwiched between two polarizing plates' The
plates are rotated in a manner to allow for the greatest amount of iight to pass
through. If the plates are rotated 90' away from the orientation with highest
intensity, then the new orientation of the plates does not allow for any light to
pass through. A sample polarimeter is shown in Figure 3-9 below.
Solution of Chiral Compound
light enters
light rotates
^nd
z porarlzet
Figure 3-9
Chiral molecules may be assigned a "+" or "-" preceding their name to indicate
the direction that the compound r,r'il1 rotate plane polarized light. For instance.
(+)-2-butanol rotates tight in a clockwise direction while its mirror image, (-)-2butanol, rotates light in a counterclockr.r'ise direction. There are compounds with
R-stereochemistry that rotate plane polarized light in a clockwise fashion anC
other compounds with R-stereochemistry that rotate plane polarized light in a
counterclockwise direction. Consequently, R stereochemistry does not
necessarily correspond to either (+) or (-) rotation of plane polarized light. Ir
biochemistry, the designation of D and L is based on threose, where (+) was
originally assigned to D-threose and (-) rvas assigned to L-threose. Flowever.
because of the vast multitude of sr-rgars, there is no correlation between D and L
designation and (+) or (-) rotation oi pl3ns polarized light.
Copyrighi O by The Berkeley Review
t92
Organic Chemistry
Stereochemistry
Configurational Isomers
Having chiral centers does not always result in the rotation of plane polarized
light. Meso compounds have opposing chiral centers that cancel one another out,
resulting in no net rotation of plane polarized light. Meso compounds are
therefore opticnlly innctiue, meaning they have a specific rotation of zero.
Polarimeters measure the optical rotation of a soiution. The specific rotation of a
compound, [a]p, is calculated from the optical rotation using Equation 3.1.
[o]5
ItuTt)
(3.1)
mL
r93
Organic Chemistry
Configurational Isomers
Stereochemistry
These modified definitions should prove to be easier to use than the traditional
definitions. Recall how these definitions were derived and they will be easy to
remember and apply. Figure 3-10 shows two pairs of enantiomers and Figure 311"
HgC.
\J
cH2cH3
HsC
/cF{2cH3
8,,'f Vott
Enantiomeric pair because both'of the chiral centers are different
rl
&
H'v
ffi
{m
Figure 3-10
lt
cH2cH3
&
Diastereomers, because only one of the chiral centers (the left one) is different
ocH2cH?
OCH"CH"J
-.--
Ht
Diastereomers, because only one of the chiral centers (the right one) is different
Figure 3-1L
After practice (and thus on your exam), you should be able to just scan structures
to look for interchanged substituents (chiral centers that are different.) First, look
for any chiral centers (sf-carbons with four unique substituents). From that
point, compare the comparabie chiral centers in the two structures. If ttr
structure is oriented in a similar fashion, but two substituents are in differsfr
positions, then the chiral center is different between the two compounds. If ttrc
structure is oriented in a similar fashion, but three substituents are in differeril
positions, then the chiral center is the same between the two compound.*
Finally, it is a matter of deciding i-f a1l, some, or none of the chiral centers on tlu
two molecules are different and then determining their relationship.
Copyright
t9,4
A,
rt
Organic Chemistry
Stereochemistry
Configurational Isomers
Example 3.5
cl.
as
H1C
"
\___./
\-J
H.,c$\'/ Yrort
c(cH3)3
\r"
"v
HH
Ci
A. Diastereomers
B. Enantiomers
C. Identical achiral compounds
D. Identical chirai compounds
C(CH.):
'
OH
Solution
\Vhen the orientation of the molecule remains constant and three substituents
:hange their location, this implies that the compound has been rotated about that
chiral center. The left chiral center is just rotated between the two compounds,
thus it has the same chirality. When two substituents interchange their location,
this implies that the chiral center changed. The right chiral center has changed,
because the H and aldehyde group have interconverted. This means that only
one out of the two chiral centers has changed its orientation between the two
structures. The two compounds are therefore diastereomers of one another,
CHs
-{. Diastereomers
B. Enantiomers
C. Identical achiral compounds
D. Identical chiral compounds
Solution
ln this example, the mirror plane between the two molecules can be seen easily
as
lhey are drawn. So without rotating or counting chiral centers, the two
:ompounds can be identified as enantiomers of one another. Enantiomers are
HO
HHO.H
\-,)cH,
Hrcrsf \
H
&
f",.",
ocH3
OCH3
A. A pair of anomers
B. A pair of constitutional isomers
C. A pair of diastereomers
D. A pair of enantiomers
Copyright
r95
Organic Chemistry
Confi
Stereochemistry
gurational Isomers
Solution
The two structures are not aligned in an equivalent fashion, so one of the trt'o
structures must be rotated into a structure equivalent to the other structure.
H\
#'
J";
"t.&--J"
/ poc",
OCH?
H
H"C
-z
ro'&_/-
\ao.tt,
CHs
CHe
&
H
ocH3
After rotating the structure, it is easier to see that the left chiral center has tn'c
substituents thut huu" interchanged between the two structures, thus it ha-'
changed chirality. The same is true for the right chiral center after rotation, thus
it toJhas changed chirality. This means that both chiral centers have changed, sc
the compoundi are e.rut iio*"ts. There is no need to determine the chiralitv c:
the stereocenters (R or S) within molecules to determine whether they are
enantiomers or diastereomers. Deciding whether two molecules are enantiomers
or diastereomers is as easy as asking whether aII of the stereocenters or just sonr
of the stereocenters have changed their orientation between the two compounds'
(All centers differ = enantiomers; Some centers differ = diastereomers)
(I
r(
Example 3.9
The following molecules are best described as:
Hsc
HeC
CHs
Br
CI
&
CHs
Br
C1
CHc
A. diastereomers.
B. enantiomers.
C. identical achiral comPounds.
D. identical chiral comPounds.
Solution
The structures are drawn as Fischer projections, which represent the top vierr
the all eclipsed form of the molecule. In a Fischer projection, the side gloups
coming olrt ut you in the three dimensional perspective,. The two isomers h
two c(iral ."r-tiuru. Only the chiral center with the chlorine is different r'r'
comparing the two compounds. The chiral carbon with bromine has
changed, t".urrr" the subitituents have not moved' Only one out of the
chiraf centers di{fers, so the compounds are diastereomers. This makes choice
the best answer.
Copyright
r96
The BerkeleY
Organic Chemistry
Configurational Isomers
Stereochemistry
Example 3.10
cH?oH
H.c{ou
CH:
Br-+H
CH:
&
CHs
CH3 and OH are interchanged. The chiral center on carbon 3 is not different
:etween the two structures, because the H, CH3 and the Br have all
,nterconverted. When three substituents interconvert, the chiral center is not
:hanged. This means that one out of two chirai centers differ, so the two
:ompounds are diastereomers. Diastereomers have different physical properties
rcluding melting point, boiling point, and density. Pick C for best results.
Example 3.11
lhe following pair of isomers is best described by which of the following terms?
H:cr'''1)''\$oH
r,.r,"'Q
\.
",tt
aH
Anomers
Diastereomers
rl. Enantiomers
D. identical meso compounds
B.
Solution
-ne two compounds are mirror images of one another, so they are enantiomers,
:.::oice C. To see the mirror plane relationship, one of the compounds must be
::tated 180'. The drawing below shows the right structure berng rotated.
nr.r,,O..rr\oH
"r@
t""O"rr\oH
"or'O".,,tCHg
I
nirror ima
Organic Chemistry
Stereochemistry
Confi
gurational Isomers
Meso
Meso compounds are individual structures which contain a mirror plane slicing
through the middle of the compound and an eaen number of chiral centers
symmetrically displaced about the mirror plane. The net optical rotation of a
meso compound is 0". It is zero, because the opposing chiral centers on each haU
of the molecule cancel one another out, Ieaving no net rotation of plane polarized
light. Meso compounds are referred to as optically inactiae. Remember the
phrase, "Me so inactive", a high-energy rap lyric that describes your physicai
state while studying for the MCAT. Figure 3-12 shows a meso compound (it has
been rotated into a side view to see the mirror plane more easily).
side view
top view
Figure 3-12
CHa
I!
Figure 3-13
Example 3.12
The reflection of a meso compound can be classified as which of the following?
Solution
"u"l H
HOO
,[
5
'n
"aI
.i:
\,/
ln
tr
mirror plane
--t
Copyright
198
Organic Chemistry
Configurational Isomers
Stereochemistry
Stereoisomerism
As mentioned before, stereoisomers are compounds that have identical bonds
but their atoms differ in spatial orientation. \Mhen a molecule contains more than
one chiral center, the maximum number of stereoisomers increases exponentially
with each new chiral center according to the equation 2n, where n is the number
of chiral carbons in the molecule. There are less than 2n stereoisomers, if one of
the possible structures is meso. If there are an odd number of chiral centers, the
structure cannot be meso, so there is exactly 2n possible stereoisomers. For
example, consider the compound 3,4,5-trimethyloctane, which has three chiral
centers and thus eight possible stereoisomers. 3R, 4R, SR-trimethyloctane is just
one of the eight possible stereoisomers. Table 3-1 shows the possible
stereoisomers for compounds with a variable number of chiral centers.
Chiral Centers
Maximum
Stereoisomers
Stereoisomers
RorS
R& RS, SR, or
SS
OT SSS
Table 3-1
lVe are most concerned with stereoisomers when a molecule contains more than
rne chiral center. If there is only one chiral center, there cannot be diastereomers.
Stereoisomerism is important in biological sciences, because only a very few
riological compounds have just one chiral center (some amino acids being
amongst of these few) with some proteins having in excess of 200 chiral centers.
E-xample 3.13
o
-\.
c.
72
OH
CHs
CH:
ts.8
D.
16
Solution
lhe molecule is drawn in a way to make you mistakenly see four chiral centers if
- ou don't pay close attention, but the number of chiral centers is only three.
larbon five is not a chiral center, because there are two methyl substituents
::'iached to it (one that is drawn as a methyl substituent and the other that is
j:awn as carbon six of the longest chain). By having two methyl groups
.::ached, it does not have four different substituents attached, thus it is not a
::riral carbon. This means that only carbons two, three, and four are chiral. The
:-aximum number of stereoisomers is derived using the equation 2n, which is
::rs case is 23. Because there is an odd number of chiral centers, the compound
::mot be meso, so there are eight stereoisomers. The correct answer is choice B.
-:,:vright
r99
Organic Chemistry
Stereochemistry
Configurational Isomers
Example 3.14
The relationship of the following pair of compounds is best described as:
CHs
A.
B.
C.
D.
OH
Anomers
Diastereomers
Enantiomers
Structural isomers
Solution
The hydroxyl group is attached to different carbons in the two structures. In the
left structure the hydroxyl group is on carbon 4 while in the right structure, the
L 2R,3S-dibromopentane
II. 2S,3R-dichlorobutane
III. 1R,2R-diiodocyclopentane
A. Compound I only
B. Compound II only
C. Compound III only
D. Compounds I and III only
Solution
To be optically inactive, the compound must either be achiral or meso. All of the
compounds iisted have stereocenters, so achiral is not a possibility. The questio:.
Copyright
:
T]f
1l!18
mrt
,&-
il"
C.
l!i't
Organic Chemistry
Stereochemistry
Stereochemistry in Reactions
Stereoisomer Formation
The
ll
,rrc'c\nrcr,,
j*",
t,to\
.. O
l"o
O..
t\ St",
&
,C-.
.rC-.
HsC CH2CH3
CH2CH3
HsC
Planar carbonyl
I
I
HO. OCH,
""\ c-.ft
z
HsC
&
cH2cH3
\l'._-,
HsC
,rC-.
nocu"
"
cH2cH3
Enantiomers
Figure 3-14
Example 3.16
The addition of alkyl magnesium bromide (RMgBr) to a carbonyl in ether adds a
B. Two diastereomers
C. Two enantiomers
D. Two epimers
,opyright
Organic Chemistry
Stereochemistry
Stereochemistry in Reactions
Solution
In this reaction, the methyl group can add to either the top or bottom of the
planar carbonyl group. This results in a new chiral center that can be either R or
S. However, there is already a chiral center present in the reactant that is not
involved in the reaction, which retains its original chirality. The chiral center
present in the reactant does not change during the course of a reaction, so the
products cannot be enantiomers. This eiiminates choice C. The compound is not
eliminated. It is not meso, so choice A is eliminated. One
of the two chiral centers differs between the two stereoisomer products, so thev
are diastereomers. Choice B is correct. Due to steric hindrance from the ethll
group on carbon two, the product mixture of the two diastereomers is not 50/50.
a sugar, so choice D is
HO
.*rCHe
+ HrCMgBr
.'rrCHs
----->
.,tfCHe
When two enantiomers are formed, they are formed in equal quantity, and the
product mixture is said to be rncemic. When the two enantiomers are equalhpresent, there is no net rotation of plane poiarized light. When tu'o
diastereomers are formed, they are formed unequally, so the product mixture has
a major and a minor product. When the two diastereomers are present ir.
:i:
.4_
Example 3.17
\Atrich of the following reactions produces no optically active compounds?
A.
B.
C.
D.
ffi
,I
i:
::i
Solution
For a compound to be optically inactive, it must either be meso or achiral. In
choice A, NaBH4 adds a hydrogen to the carbonyl carbon from either side,
resulting in a racemic mixture of alcohols. Choice A is eliminated. In choice B,
KMnO4 adds a pair of hydroxyl groups to ihe alkene carbons to from a syn
vicinal diol. Because the alkene is svmmetric to begin with, symmetric addition
results in a symmetric product. The product is a meso diol, so choice B is the
best answer. In choice C, LiAIH4 adds a hydrogen to the imine carbon from
either side, resulting in a racemic mixture of ami.nes following workup. Choice C
is eliminated. In choice D, a good nucleophile attacks an alkyl halide, resulting in
inversion of stereochemistry. One chiral species is formed, so choice D is out.
Choice
B\
\-*/
Copyright
+ KMnOr
Symmetric -+
additioi-r
-t'
OH
OH
HO
Symmetric product: meso vicinal diol
HO
Organic Chemistry
Stereochemistry
Stereochemistry in Reactions
The only way to get a meso compound from an addition to an alkene, is to have a
percentage between the more abundant enantiomer and the less abundant
enantiomer.
700% (3.2)
Example 3.18
if
=75%
= 67.h
= 75%
=ZS%
Solution
"/oee
=+13'6 x
27.2
100%
=!x
2
100%
50'/oinfavorof the(+)-enantiomer
Copyright
203
Organic Chemistry
Stereochemistry
Nucleophilic Substitution
Nubledphiliru1i;$fib$$.flfi ffi,bn
Nucleophilic Substitution
One application of stereochemistry is in nucleophilic substitution reactions.
Nucleophilic substitution involves the attack of an electropositive carbon by a
nucleophile (Lewis base) to dislodge an atom or functional group (referred to as
the leaving group). This is a recurring reaction in organic chemistry and it
involves the substitution of one functional group for another. Nucleophilic
substitution can proceed by more than one reaction pathway. It can proceed bv
the two-step 51111 mechanism, or it can proceed by the one-step 5512 mechanism.
Nucleophilic substitution reactions are based on the fundamental chemistrv
concept that negative charge seeks positive charge. The electron pair of the
nucleophile hunts for an electron deficient carbon to attach to. It will be
important to understand the steps of the reaction for both mechanisms, as
reactants proceed to products. Figure 3-15 shows an example of a nucleophiJic
substitution reaction.
fi
lli
ri[
rl
..-..o
.1.
H.CO
,M
d
Figure 3-15
will discuss the mechanism of this reaction shortly, but for now, there are
some fundamental definitions with which to be familiar. Listed below are the
most important definitions. Each definition is followed by some generecomments about the relative reactivity of the species and how to discern i5
We
reactive strength.
Nucleophile
ffii
.Lq
I
(
f,
Organic Chemistry
Stereochemistry
Nucleophilic Substitution
Electrophile
'+ product mixture that has an even distribution of enantiomers, 507u of each
=nantiomer, in the product mixture. A racemic mixture is the observed product
-'""hen the mechanism
involves an intermediate where the reactive site is'an sp2-^,., bridized carbon (like a carbonyl or carbocation) and
the molecule is symmeiric
-:ras r-lo other chiral centers). There is no such thing as a racemic mixture
of
..iastereomers, because diastereomers have at least two chiral centers associated
''ith them, and a chirai center present in the reaction hinders attack of one side of
-: e electrophiie relative
to the other, causing the distribution to not be fifty-fifty.
;:oup.
Erample 3.19
-, iavorable nucleophilic substitution reaction has all of the following EXCEpT:
d. a good leaving group.
l. a reactant with a weak bond to the leaving group.
:. a strong Lewis base as the nucleophile.
f . a weak Lewis base as the nucleophile.
nvright
20s
Organic Chemistry
Stereochemistry
Nucleophilic Substitution
Solution
A favorable nucleophilic substitution reaction is one that forms a stronger bond
than the one broken. A good nucleophile is one that forms a stronger bJnd with
carbon than the bond between carbon and the leaving group. A good leaving
group is one that forms a weak bond with carbon, thus minimal eneigy is needeJ
to break the bond between it and carbon. when the leaving group ii strong, ihe
reaction is said to be favorable, so choice A is a valid statemet-,i. choic" e is
eliminated. A weak bond to the leaving group makes it a good leaving group, so
choice B is also a valid statement. This eliminates choiie B. The n.t"t"optl1t"
should be a strong Lewis base, so choice C is a valid statement and choice Dls an
invalid statement. This eliminates choice C and makes choice D the best answer.
You might note that to determine the favorability of a nucleophilic substitution
,
"".rt"", t"" """,
,i
sru2
In an sjr]2 reaction, the nucleophile attacks prior to the ieaving group leaving. lru:1"1.9, the nucleophile comes in from the backside and pushes ine teaving gio.rp
off of the electrophile. An important factor to consider is the transition state tha:
forms during the reaction. Transition states cannot be viewed directly (thei:
lifetimes are too short), but evidence in the product (inversion of configuration ai
a chirai carbon) infers they exist. Backside attack by a nucleophile causes thr-.
inversion at the chiral carbon. Certain features in the reactants (nucleophile an;
electrophile) and the product (if it is chiral) indicate that the reaction proceedec
by an slr]2 mechanism. These are idiosyncrasies of the reaction, and they dictatr
the pathway the reaction chooses. Each property favors one of the trr l
mechanisms. They can be used to distinguish an slr]2 reaction from an slreaction. Figure 3-16 shows a generic mechanism for an sl.I2 reaction.
Trigonal bipyramidal
Transition state
R+
L'G'--+
s,
.G.
------> Nuc
L.G.-
l'==
HH
Figure 3-16
The reaction takes place in one step, so the rate of an sry2 reaction depend.s
.-mr
206
II
&
Nuc---f---'L
rm
,&riil
Nuc:
The Berkeley
ln"
Organic Chemistry
Product Features
Reactant Features
An
51112
Nucleophilic Substitution
Stereochemistry
-{n
S11i2
ln
-l
5512 mechanism is favored Steric forces destabilize the Sl12 reactions are one-step
poiar, aprotic solvents such transition state by forcing bond reactions, so they have fast
rates of formation
ethers and ketones
angles to values less than 109,5'
Table 3-2
H"C
,\
NC:@ +
Good
\ucleophile
H'''y
CH"
r --+
Et2O NC-J-
D
1" Electrophile
Y,o"
D
+I@
Stable
Anion
Inversion Product
Figure 3-17
E"xample 3.20
Copyright
Organic Chemistry
Stereochemistry
Nucleophilic Substitution
sp1:
Lr an s|J1 reaction, the leaving group leaves before the nucleophile attacks. Lr
essence/ the nucleophile waits until the leaving group has left, allowing it more
room to attack. The slr]1 reaction rate does not depend on nucleophile
concentration. once the leaving group has dissociated, a planar caiionic
intermediate forms. Evidence for the intermediate comes from kinetics data as
well as stereochemicai evidence provided by the products. The carbocation
intermediate has a long enough lifetime to be detected using spectroscopy. Both
rearrangement (hydride shifts and alkyl shifts) and a mixture of stereoisomers
(formed from the spl-intermediate) are observed with sNI1 reactions. The
nucleophiie is free to attack from either side of the carbocation intermediate, if
the carbocation is symmetric. As a result, a racemic mixture of enantiomers is
formed as the product mixture. Figure 3-18 shows a generic mechanism for an
5111
reaction.
,onf"$G"
R"
->
Nuc attacks
720'A
,."(
fromrhe,9r__ Nuc
Vf ffi;=-.
R,,
R,
from the
right
Trigonal planar
Carbocation Intermediate
'[r
R>..
109
109.5"
-R;
L.c.
R"
Figure 3-18
The reaction takes place in two steps, where the first step is the slowest. In the
first step, the bond between the carbon and the leaving group breaks. As the
leaving group begins to leave, the substituents on the carbon foia in the direction
of the less hindered side of the molecule, allowing the-bond-angles to increase
from 109.5' to 120" as the carbon re-hybridizes from ry3 to sp2. ihis results in a
slight increase in stability, accounting for the intermediate being at a lower
energy level than the first transition state in the energy diagram. In addition to
re-hybridization, the planar cation is solvated, which also increases the stability
of the intermediate. The nucleophile can attack the carbocation intermediate and
displace the solvent from either side of the carbocation intermediate. This
displacement of solvent and the re-hybridization from sp2 back to sp3 causes a
decrease in stability from the intermediate to the second transition state. Finally,
as the new bond is formed, the energy level decreases until it reaches the level of
the products. Bond formation is an exothermic process. The hybridization of the
central carbon finishes atsp3. Table 3-3 lists features associited with the sx11
reaction. Like in Table 3-2, the features are iisted according to observation order.
Reactant Features
The preference for an 5511
mechanism is 3" > 2' > 7"
in terms of electrophiles
Product Features
An
An
Table 3-3
-:pvright
Ll
.:
-,':
.q,.
Organic Chemistry
Nucleophilic Substitution
Stereochemistry
'\
H3c\f
H?CH2CH2C
H3N:
Average
Nucleophile
NH3
H3CH2C
tr.o'YF
*Io
I+&
gH2cH2cH.
' '
|
H3CH2C
ol
,,*_\,,.,r,
3" Electrophile
stable
Anion
cH2cH3
Racemic Mixture of Products
Figure 3-19
The reaction is favorable, because the leaving group is a good leaving group and
the nucleophile forms a stronger bond with carbon than the leaving group.
Example 3.21
Solution
First, we must determine whether the reaction proceeds by an S1r11 or 51..12
mechanism. The electrophile (R-3-iodo-3-methylhexane) is tertiary, so the
reaction proceeds by an S1'tr1 mechanism. The chiral center is lost with the
formation of the carbocation intermediate, because the intermediate is pianar
with symmetric sides. This results in a racemic product mixture of two
enantiomers. Choice C is a swell answer for this question.
Copyright
209
Organic Chemistry
Stereochemistry
Nucleophilic Sutistitution
H,.C
"l
H.C
"\
\'
,,L--r
Hv
(H3C)2HC
-([t
"-c H
hydride
"l
shift
"'h
c*
/\
HsC CHs
2'carbocation
HlCH,C
" 'l
/\
HsC
CHe
3" carbocation
H3CH2C
HAN:
\-
urcsf.NH'
li,-
HsC
H"C
CHa
HsC
achiral product
3" carbocation
Figure 3-20
Rearrangement is rapid, because it is an intramolecular process. L:r the example
in Figure 3-20, the secondary carbocation rearranges to form a more stable
If the electrophile has a chiral center at a site other than the electrophilic carbon,
an Str11 reaction will form both a major and minor product. The major product
results from the transition state with least steric hindrance.
CHICH?
YYYY
OCI
-.>
CH,,CH"
e.'C*
CH,CH"
ry.s
CH.CH,
O'"?:il; Ort:il;
Major
Product
Minor
Product
Figure 3-21
In the example in Figure 3-27, the ethyl group in front of the plane interferes with
the attack by the nucleophile, which results in an uneven distribution of
diastereomers as the product mixture. The major product is formed when
ammonia attacks the less hindered face of the carbocation (backside attack in this
example). The minor product is formed when ammonia attacks the more
hindered face of the carbocation (front side attack in this example).
2to
Organic Chemistry
Nucleophilic Substitution
Stereochemistry
If rate data are given, then the mechanism can be inferred without ambiguity.
The rate law associated with an 5111 mechanism is shown in Equation 3.3, while
the rate iaw associated with an Sp2 mechanism is shown in Equation 3.4.
S1.tr1
5512 Rate =
Rate = k [Electrophile]
(3.3)
k [Nucleophile][Electrophile]
(3.4)
The energy diagrams for the two mechanisms also differ. There is no
intermediate associated with an 51112 reaction, only a transition state. There is ar"t
intermediate and two transition states associated with an 5511 reaction. Figure 322 shows the energy diagrams for the one-step S52 reaction (on the left) and the
Transition state
Intermediate
Reactant
bo
H
G)
F]
Product
Reaction co-ordinate
-+
Figure 3-22
Copyright
2tl
Organic Chemistry
Stereochemistry
Nucleophilic Substitution
The energy level increases at the start of each energy diagram, because a bond is
being broken. In the case of the S1r11 reaction, the intermediate is of lower energy
than the transition state, because the carbocation can rehybridize to the leil
crowded sp2-center rather than an sp3-center and the intermediate can be
solvated in a protic solvent. The increase in energy from the intermediate to the
second transition state is associated with rehybridization to the more crowded
sp3-center and the intermediate losing solvition to allow the nucleophile to
A.
B.
C.
D.
Solution
First, we must determine whether the reaction proceeds by an sIrI1 or sry2
+ H,CCHTBT -----+ H3CCH2SCHTCH, + BrA. The reaction rate increases in a linear fashion with increasing nucleophile
H?CCH2S-
concentration.
Solution
The reaction has a primary electrophile and a good nucleophile, which favors an
s512 mechanism. The rate equation associated with a reaction proceeding by an
s}..J2 mechanism is rate = k lElectrophile][Nucleophile]. The equation shows that
Copyright
212
Organic Chemistry
Stereochemistry
Nucleophilic Substitution
Example 3.24
A. H3CCHZO- + H3CCH2BT ----t> H3CCH2OCH2CH3 + BrB. H3CCH2OH + (H3C)3CBr ------> H3CCH2OC(CHa)3 + HBr
C. (H3C)3CSH + (H3C)2CHOHz* +
@3C)3CS+HCH(CH3)2 + H2o
D. NH3 + (H3CH2C)3CBr --.> (H3CCH2)3NH3+ + BrSolution
As shown in Figure 3-27, no intermediate is associated with an sx12 mechanism,
so we must find the reaction most likely to proceed by an sN2 mechanism. The
reaction most likely to proceed by an Sl.]2 mechanism should have a good
nucleophile and ideally a primary electrophile. A low temperature is important
here so that there will be little to no E2 product formed. Choice C is the ieaction
of a secondary electrophile with a poor nucleophile, so it will likely proceed by
an S51 reaction mechanism. This eliminates choice C. Choices B and D involve
tertiary electrophiles, therefore they definitely will proceed by an SlrJ1 reaction
mechanism. This eliminates both choice B and choice D. Choice A has a primary
electrophile and a good nucleophile, which makes it the most likely to proceed
by an sg2 mechanism, and therefore makes it the best answer. The ethoxide
anion is also a strong base, so elimination is possible in choice A. Despite the
competition with the E2 reaction, choice A is still the best answer.
Reaction Kinetics
The rate'of a reaction depends on several factors. The rate depends on the
available energy for the molecules to collide, orient, and break the necessary
bonds. The rate depends on the likelihood of the molecules colliding. For an
sirl2 reaction, the rate depends on the availability of nucleophile, while it does
not depend on the nucleophile concentration in an Sry1 reaction. Consider the
5512 reaction shown in Figure 3-23 with an ethoxide concentration, [CH3CH2O-],
of 0.01 M a 2-bromopropane concentration, [CH3CHBTCH3], of 0.01 M and a k1*
of 2.53 x 10-2 L.mol-1.s1 at 2gBK.
HqCH?CO:
Figure 3-23
The concentrations are low, so the reaction is very slow. Plugging the values into
Equation 3.4 yields a rate of 2.53 x 70-6 M per second. The reaction rate may be
increased by increasing the reactant concentrations, increasing the temperature,
or by adding a catalyst. A catalyst stabilizes the transjtion state complex and
lowers Eu.1. Transition states are short-lived complexes. In the course of the
reaction, reactants collide with the correction orientation (from backside attack)
to form the transition state complex, when eventually splits io generate the
products. Figure 3-24 represents the species of the S5tr2 reaction in Figure 3-23 at
different stages in chronological order over the duration of the reaction.
213
Organic Chemistry
Stereochemistry
Nucleophilic Substitution
CH"
..4- | - ..5
----+----Bri
H,cH"co
H.C
..6- '\
H3cH2co.
;f
---
CH3
Transition State
..6Br!
..5-
..6Bri
H3CH2CO.- - - /::'
\"
HsC
CHs
Cl"t.
Ceurly
H.CH"CO
J
L
..
Reaction co-ordinate
Yg"
-/'n'
Figure 3-24
Physical Properties of Stereoisomers
Enantiomers have identical physical properties (boiling point, melting point, and
density to name a few), while diastereomers have slightly different physical
Chirality
CTD
Boiling Point
Density
Index of Refraction
(+)
+ 13.5"
99.4'C
0.808
1.398
(-)
-t-J.5
99.4'C
0.808
1.398
(r)
R/S
0'
t01.2"c
0.840
1..442
Table 3-4
lrom the data in TabIe 3-4, it can be seen that a racemic mixture allows the
molecules to get closer together. This can be thought of when considering your
hands, where a left and right hand fit together nicely. It is common that a
racemic solid mixture has a higher melting point and greater density than either
enantiomer.
Organic Chemistry
Stereochemistry
Nucleophilic Substitution
Separating Stereoisomers
One of the most chailenging tasks a synthetic organic chemist faces is the
separation of stereoisomers. If a reaction generates a new chiral center in the
product, then it will be complicated by stereoisomerism. To generate a pure
stereoisomer as a product, chirality must be invoked at some point. From
biochemical examples, we know that enzymes (chiral polypeptides) orient
molecules in a specific fashion, allowing just one stereoisomer to form, The
chirality of the enzyme helps to select for the desired product. In organic
chemistry, there are compounds known as chiral nuxiliaries, which introduce
chiraiity to, or exaggerate existing chirality within, a reactant molecule. Chiral
auxiliaries serve in a similar fashion to an enzyme. When aiming for one specific
stereoisomer, it is often easiest to select for it in the reaction. If not, a mixture of
stereoisomers is formed and chirally selective separation techniques must be
applied.
Chirally selective separation techniques come in two types. The first involves
employing an enzyme (or chirally selective molecule) to react specifically with
one stereoisomer within the mixture. By reacting and therefore introducing a
new functional group to only one stereoisomer, the two enantiomers now have
different physical properties and can easily be separated. Once separated, the
same enzyme can be employeci to return the compound back to its original form.
An example of such an enzyme ts porcine renal acylase, which selectively acylates
the N-terminal of L-amino acids. By acylating the L-amino acid, it is no longer a
zwitterion at neutral pH, while the D-amino acid is a zwitterion. Because one
carries a net charge, it is easily separated from the other.
The second chiraily selective separation technique involves invoking chirality in
an existing separation technique. For instance, a column chromatography gel can
be made from a pure stereoisomer. If the column is made with an R-alcohol for
instance, then when a racemic mixture of alcohols is added, the S-enantiomer has
a greater affinity for the column and thus has a greater elution time. This is the
basic principle behind affinity chromatography in biochemistry, where an
antibody is bound to the column so that it can selectiveiy bind an antigen. Chiral
columns in organic chemistry are not as specific as enzyme columns and they
hinder solutes, but do not actualiy bind them. In theory, chiraiity could be
invoked in any organic chemistry separation technique, including distillation,
but only it is chiral columns that are commonly used.
Copyright
215
Organic Chemistry
Stereochemistry
Summary
Summary
This section involved a few basic concepts. From this particular section, you
should be able to identify R and S chirality, determine the relationship between
stereoisomers, understand the nuances of nucleophilic substitution, distinguish
between the slri1 and sIN2 reactions, and apply stereochemistry to organic lab
techniques and biochemistry.
Determining R and S: When a structure is drawn in dash-and-wedge style, if
priority number four is in back or two substituents away from the substituent in
back, then take the arc as is and assign the corresponding chirality (Clockwise =
R; Counterclockwise = S). If priority number four is one substituent away from
the substituent in back, then determine the arc and assign the opposite chirality
of the arc.
Enantiomer: Enantiomers are stereoisomers which are nonsuperimposable
mirror irnages (reflections that you can't overlay). They have the same bonds,
but they have a different orientation of atoms in space, as do all stereoisomers.
Enantiomers can be thought of as stereoisomers in which all of the chiral centers
have different orientation between the two molecules. Enantiomers have
The rate of an
reaction are referred to as major and minor, because they do not occur in a fiftvfifty ratio. Separating one diastereomer from another is easier than separatirrg
one enantiomer from another. To separate enantiomers, chirality must b.
incorporated into the separation technique.
216
Organic Chemistry
Stereochemistry
Nucleophilic Substitution
1.
Chiral Molecules
a) Have asymmetry within their structure due to atoms that are unevenly
substituted
i. Stereogenic carbons are sp3-hybridized carbons with four unique
substituents
ii. Chiral moiecules are predominant in many organic reactions
b)
iii.
c)
in
S-
stereogenic centers.
To determine whether a center is R or S, you can place your thumb in
the direction of substituent #4 and curl your fingers from priority #1,
through priority #2, and on to priority #3. Only one of your hands
can do this. If it is a right hand that does this, the stereogenic carbon
has R-chirality. If it is a left hand that does this, the stereogenic
carbon has S-chirality.
ii.
Configurational Isomers
1.
i.
ii.
iii.
b)
ii.
iii.
iv.
217
Organic Chemistry
Stereochemistry
Section Summary
Stereochemistry in Reactions
7.
a)
b)
ii.
iii.
c)
invoke chirality.
Enzymatic reactions use a chirai catalyst to cause the reaction to
drastically favor the formation of one stereoisomer over all other
possible stereoisomer products
When two enantiomers are present in unequal amount, there is said
to be an enantiomeric excess. Enantiomeric excess is used to describe
the success in a stereoselective synthesis
Nucleophilic Substitution
Proceeds by either an Sp1-mechanism or Sp2-mechanism
1.
a)
b)
51
Copyright
2ta
Stereochemistry
Passages
15 Passages
I OO
Questions
Suggested schedule:
I: After reading this section and attending lecture: passages I, II, vll & x
Grade passages immediately after completion and log your mistakes.
II:
III:
Keview: Passages III, VI, VIII, XI, XII, & Questions 92 - IOO
Focus on reviewing the concepts. Do not worry about timing.
#fi
il
rtffi-iffit
:lffiffings.
(r -7)
(B
14)
(15 - 21)
(22 - 28)
(2e - 35)
(36 - 42)
(43 - 4e)
(5O - s6)
(s7 - 63)
(64 - 70)
(7r -77)
lI:r
lll.r:
(78 - 84)
.lr-:
el)
illl:,"
(Bs -
(e2 - lOO)
rlltut
rLllJ
Passage
(Questions
'1
- 7)
::n
Isoleucine is one
A.
B.
CH 2CH
. If L-isoleucine
A.
B.
-62'
D.
+31'
+62'
c. -31'
o-
B. -CH(oH)CH3
C. -CH2CH2OH
D. -CH2OH
L-Isoleucine
(-) 32'
Figure
(.+)32'
c. 0'
A.
B.
C.
D.
2. If
2R. 3R
3.
A.
B.
of synthetic
C. In synthesizing isoleucine,
2R, 35
25,3R
25, 35
D. In synthesizing isoleucine,
.
B.
C.
D.
An enantiomer of isoleucine.
A diastereomer of isoleucine.
An epimer of isoleucine.
ldentical lo isolcucine.
A. R
B. S
C.
D.
Copyright
Passage
ll
(Questions 8
10.
14)
A. 35, 45
B. 3R, 45
C.
D.
35, 4R
3R, 4R
P,
Red-Eared
HOH
;"
cH 2cH
H H HO
A. It is an enantiomer of Compound P
B . It is a diastereomer of Compound P
C. It is identical to Compound P
D . It is a meso structural isomer of Compound P
OH
Figure
Compound P
12.
A.
B.
C.
D.
:Ft
15, 25
lR,
25
15,2R
lR,
*'it:r:
2R
lEri
A.
B.
C.
D.
-i:r':
14.
chiral speciiic.
L:,
size specific.
A.
B.
C.
D.
";
lf-:r:
EXCEPT:
3R., 4R
:.;
-"&
3R, 45
35, 4R
A. E.
B. Z.
C. Either, the reaction has no stereoselectivity.
D . Neither, the reaction has no stereoselectivity.
"1::r'
lr:
35, 45
c,-
- i'
A.
B.
C.
D.
assignments?
*rt
jr-
-!:
::i*.
Ct-12CHs
I.lrr"
lll
Passage
(Questions 15 - 21)
16.
types
of
as
in
4.4
B. 3
c.2
D.
the
A. rl
B. 1
c.
D.
6
5
centers
C.
D.
5. The pure R
A.
B.
C.
D.
A. 2R, 3R
B. 2R, 35
,pyright
5Vo
50Vo
25Va
optical
isomers?
25, 35
25, 3R
.
B.
C.
D.
A
223
L.
4.32
B. 64
c.
(oH)
128
(oH)
D.256
o
Figure
Tartaric Acid
m.p.
(+)
168-170
(-)
0D
Density
g/l00ml
12"
1.7598
139
168-170
12'
1.7598
139 g/100ml
meso
t46-148
0"
r.5996
125
(t)
205-207
0'
1.7880
Table
g/l}0mL
2l g/l}0mL
Figure
L-Dopa
A. Melting point.
B. Density.
C . Molecular mass.
D. Specific rotation.
Copyright @ by The Berkeley Review@
NHz
HO
22
{
ts
-{"
E"
D"
6.
B.
value
of the optical
D.
D.
D_
27
^vo
u-f
cHs
oH
so-FH
I
H-1-
oH
-1-
oH
CH:
A. 0
B. I
c.2
D.
CH2OH
D_Glucose
28. Which of
B.
H'coc6Hsl/
I
,h.y
A.
8,2
c" 4
t\a.r,
-CHr
co2H
compounds.
another.
D.
D.
:vright
31.
32.
A. Boiling point
B. Density
C. Alcohol solubiiity
D. Optical Rotation
3.
^"-&""&
R-limonene?
lemon
odor
Figure
orange odor
ca
Enantiomers of Limonene
29.
"-u\.4
of
p,
n-u-=A
an
enantiomeric mixture?
A.
B.
C.
D
34
A.
B.
30.
D.
A.
B.
C.
D.
c-rmum
chiral solvent.
chiral catalyst.
Carrying the reaction out at a lower temperature.
Carrying the reaction out at a higher concentration.
;:anr
226
GO ON TO THE NEXT P{
HrC Br
.
B.
C.
D.
A
IJ
O
HrC
CHroH'
Li
O
&
major
product
Reaction
"'u''
OCHr
minor
product
attempted
reaction?
A.
B.
Syl
D.
Ez
S52
c. Er
7.
B.
C.
D.
:r'right
221
8.
42.
.
B.
C.
D.
A
HrC
t/
su'
":
:::::
cHroH
.->
maJor
"'ry,
.F--
.
B.
A
\,
."
MI;:
minor
tr:
D.
0.
":ira
J:i
"tr
.
B.
C.
D.
-u
'fui:
9. To
::[:
:rtu:
CHr
\,)
Pas
_:_
",u,s.",
compound.
L,'e
r,:
\r
A.
B.
C.
D.
by
llllus
.,:
unit;
urrTI
ill"ri-ullJ
41.
.
B.
C.
D.
(1R,2S)-2-Methylcyclopentanol
(1R,2R)-2-Methylcyclopentanol
(1S,2R)-2-Methylcyclopentanol
(1S,2S)-2-Methylcyclopentanol
228
GO ON
TO THE NEXT P{
f,assage
Vll
(Questions 43
49)
45.
of
Reaction
. (2S,3S) 2-amino-3-methylpentane
B. (2R,3S) 2-amino-3-methylpentane
C. (2S,3R) 2-amino-3-methylpentane
D . A racemic mixture of A and C.
A
A.
B.
C.
D.
NH:
H3CSH
H3COH
8.2
Table
\ ucleophile
10-3 M/sec
SNr2
S5E1
SpE2
H3CNH2
3.3
x l0-4 M/sec
NH:
3.6
H3CSH
H3COH
3.5
Table
47
Sp1
10-4 M/sec
10-4 M/sec
H:C-o
.
B.
C.
D.
A
{r'"""'
(R)-2-chlorobutane
(S)-2-chlorobutane
(R)-2-aminobutane
(S)-2-aminobutane
48. Which of
the following graphs BEST represents the Clconcentration as a function of time for the reaction of
ammonia with 1-chloropropane?
A. H3CNH2
B. NH3
C. H3CSH
D. H3COH
1
Time
Time+
-->
. A nucleophilic substitution
A.
B.
2"
D.
c.
1'
3'
substitution.
rvright
Time
---------_->
Time
---+
49.
Passage
tz-
HjCH2CH2C
(Questions 50 - 56)
Br
HjCH2C
Vlll
+ HqCSH -+
-/
CH:
nucleophilic attack of the carbocation intermediate. In S.,reactions, the nucleophile attacks the electrophilic carb':i
------->
Time
NaOEt
Time
OEt
----------------
HOEr.0'
Reaction
Time
I: ,
L-l--->HOEI
_-_=>
pH=5,0"
Reaction
Reaction
Rate (M/s)
ICH3CH2ONa]
1.32
10-2
0.05 M
0.0-5
2.63
10-2
0.10 M
0.05 M
5.25 x l0-2
0.10 M
0.10 M
Table
IC6H11Cl]
Reaction
ICHTCHzOHI
lCoHrrCll
x l0-3
0.20 M
0.05 M
x l0-3
3.83 x 10-3
0.40 M
0,0.5
0.40 M
0.10 M
Rate (M/s)
1.93
1.95
Table
230
GO ON TO THE NEXT
PAG.M
0.
reactions
type of reactions?
A.
B.
C.
D.
A. H3CO- + (H3C)3CBr -+
B. H3COH + (H3C)3CBr -+
Reaction
Reaction
Reaction
Reaction
1. All of
C.
D.
.
B.
C.
D.
to
H3CO- + (H3C)2CHCHBTCH3 -+
H3COH + (H3C)2CHCHBTCH3 -+
EXCEPT:
is most likely
carbocation intermediate.
6.
A.
B.
2. A
Rxn Coordinate
Rxn Coordinate
A.
B.
C.
D.
Rxn Coordinate
3. If
.
B.
The
Spl
would decrease.
C.
D
A.
B.
C.
D.
tteCOH3COH
ClHCI
Passage
lX
(Questions 5Z - 63)
::::tive electrophile,
::re
A. HCN
B. CN.
C. H3CCH2SD. H3CCH2SH
electrophile.
.
B.
C.
D.
A
Equation
Acid
pKa
HI
-r0.5
Acid
PKa
HCN
9.1
HBr
-8..5
C6H5OH
10.0
HCI
-1.0
H3CCH2SH
10.5
HF
3.3
Hzo
15.1
compounds
electrophile'l
(CH3)3CI
B.
C.
D.
slightly favorable.
slightly unfavorable.
Lll a
very unfavorable.
t\,,
62.
A.
B.
C.
D.
Very favorable.
Slightly favorable.
Slightly unfavorable.
Very unfavorable.
a_
is the
BEST
B.
C
D.
hinde::,rr
r iir"i:
LLtt]tri
as alcohol, F- exhibits : I
hydrogen bonding, so it cannot migrate as we1l.
In an aprotic solvent such as ether, F- exhibirs - I
hydrogen bonding, so it cannot migrate as we11.
(CH3)jCBr
(CH3)3CCI
(CH3)3CF
li:
Table I
A.
B.
C.
D.
61.
Table
If C >
is the MOST
A. CH3CH2F
B. CH3CH2OC6H5
C. CH3CH2SCH3
D. CH3CH2BT
compounds
GO ON TO THE NEXT
PACM
r.4
65
A.
B.
C.
D.
to
experiment is
D.
\x
\
-+
electrophile.
OSO3CH3
CI
OCHr
H:N
-3.82
-3.31
-4.11
No Rx
CN.
1.39
1.tl
L92
No Rx
No Rx
No Rx
)JucJ
H3CS-
-2.16
1.92
)Aa
H3COH
-5.21
-4.80
-5.10
Table
68. Which of
.
B.
C.
D.
observed
A.
B.
C.
D.
A.
B.
C.
D.
as which
of
the
following?
A.
B.
C.
D.
ALewisacid.
A Lewis base.
An oxidizing agent.
A reducing agent.
233
Xl
Passage
(Questions 71 - 77)
2.
A.
B.
c.
D.
Sp1
S1q2
Er
Ez
has
3.
H$\l
H:C
+ Nuc
--->
C. 25, 3R
D. 25, 35
Product
CH:
Reaction
Trial
Temperature
l0'c
Trial II
60"c
Trial III
Trial IV
Trial V
l0'c
NaOH
-38"
60'c
r0"c
60'c
NaOH
0"
NaNH2
0'
NaNH2
0'
Trial VI
Table
It is fbund that
deuterium is less acidic than a proton due to the cleuterium
isotope effect rooted in the shorter bond length associated
with the deuterium-carbon bond. An E1 r.eaction can
compete if the leaving group is a good leaving group and it
is situated on a tel'tiary carbon.
product when elimination is observed.
A.
B.
Spl
D.
Ez
is
produ:::t
present.
D.
Based
Trial I
71.
a.
A. 2R, 3R
B. 2R, 35
Br
5.
:u
B.
::r'c
ur
5512
c. Er
GO ON TO THE NEXT
P.{GM
A.
B.
c.
D.
+24'
0"
-24'
-42'
Passage
Xll
(Questions 78
84)
l,
drawn below,
CH2CHj
CH2CHj
---->
2'fuoz
,'r/CH3
cHs oH (aq)
A. Carbon2only
B. Carbon 3 only
C. Both calbon 2 and carbon 3
D. Carbons l, 2 and 3
..t\OH
1. BHr(etrO)
+48'
[o]o = +48'
[cr]o
Reaction
A and Compound B,
[cr]l = +18"
are
Oobs=xacxa+(l -xu)cx6
Equation
NHr
.$\
:NH:
...'St'
___l-
[s]o = +62'
Reaction
lulo = +30"
.
.
C.
D.
:yright
9.
if
A. 48'
B. 42"
c. 33"
D. 18'
0.
carbons) at:
rPa
A. 0
B.
1
c.2
D.
.
B.
C.
D.
A
enantiomers.
epimers.
diastereomers.
identical.
Tlll_t
L\.
1.
.
B.
C.
D.
A
82.
specific rotation.
melting point.
retention time on a GC.
IR spectroscopy.
A'
B'Hn
ay
M.o/>cHt ""#
,GH.CH3
HrcH2i
C.
OH
CH2CHj
9Hr
cH2cH3
3.
A.
B.
C.
D.
S,R,S
R,R,S
S,S,S
R,S,S
Passage
Xlll
(Questions 85 - 91)
85
lhe first
A.
B.
C.
D.
oo
q"ri,.
"..\.
o
Compound
Compound 1 Compound 2
6.
Br2(l)/CCla(l)
Hz(e)/Pd(s)
cold KMnO4(aq) at pH =
l0
NH3(l)
A.
Reaction I
B.
..rr(
,,,,,(
o
..r(
o
HeC
HgC
o
D.
C.
HsC
o
Compound 3a
In the second step, Reaction 2, Compound 3a is treated
rth meta-chloro peroxybenzoic acid, mcpba, in ether to form
!ompound 4.
,'.
87
A.
B.
HgC
Compound
Compound
4 then undergoes
o
Reaction
3 to
form
Compound 5.
-.:e("HicNH2H3;iq"
o
o
Compound
Compound 4
Reaction
gas
chromatography experiment.
8.
A.
HrC"
H3CHN
OH
OH
HO
Hec
Compound
237
EXCEPT:
A. Reaction I
B. Reaction 2
C. Reaction 3
D. Reaction 4
Questions 92 through
descriptive passage.
92
ocH3
-oH
excess
A.
A. 2R, 3R
B. 2R, 35
C.
D.
B.
25,3R
25, 35
H3CN
the
CHr
NCFI3
HsC
C.
H?CHN
ocH3
A. 2R, 3R
B. 2R, 35
HO
HsC
C. 25, 3R
D. 25, 35
D.
H"CHN
HO
NHCFL
NHCr-t
94.
HsC
CHr
t?a
HHO
91.
and
HOH
be described as:
A.
B.
C.
D.
CH2CH3
\ts
up = Q'.
a diastereomeric mixture with ap = Q".
a diastereomeric mixture with up * 0".
a meso mixture with up * 0".
cH2cH3
CH:
. Diastereomers
B . Enantiomers
C. Epimers
D. Anomers
A
f,r:
5.
4.2
A.
B.
C.
D.
B.
c.
D.
,6.
1,2,3-trifl uoropentane?
4
6
8
2R, 3R dibromobutane
2R, 35 dibromobutane
2R, 3R dibromohexane
2R, 35 dibromohexane
A.
B.
C.
D.
7.
Two diastereomers
Two meso compounds (not identical)
One meso compound
A.
B.
C.
D.
Two enantiomers
2R,3s-dibromobutane
2R,4s-dibromopentane
2R,4s-dibromohexane
cis-1,3-dichlorocyclohexane
compounds CANNOT be
optically active?
A. 2-chlorocyclopentanol
B. 2-chlorocyclohexanol
C. 3-chlorocyclohexanol
D. 4-chlorocyclohexanol
9.
.
B.
1.D
1.C
13. D
19. B
25. D
31. A
31. D
43. A
49. A
55. C
61. A
61. D
73. B
19. B
85. D
91. C
91. C
2.8
8.C
14. A
20. A
26. B
32. D
38. B
44. A
50. B
56. B
62. D
68. B
14. D
80. C
86. A
92. A
98. D
Stereochemistry
Choice D is correct. Using the Cahn-Ingold-Prelog rules for substituent priority and drawing
the appropria:.
arcs, the chiraiity for the two stereogenic carbons of isoleucine is determined as iollows:
H:9
*HrN
Priority #4 in back
(an as lsposition)
Countercloskwise Arc
.'. Chirality isS
Priority #4 in back
(an as isposition)
Countercioskwise Arc
CH2CFI3 ChiralitY isS
"'
CozIsoleucine
Both of the chiral carbons have S chirality, which makes the compound 2S,3S. It wouid be swell of you:D. The chiral center on carbon two of an amino acid must be S according to the rules discussed in :: .
Passage, so choices A and B could have been eliminated eariy. Regardless, the chiral center on the side cha-:
of the amino acid must be solved for. Determining R and S ii actuiily rather simple when you get the hang .:
it. The key is to find a method that works for you and hone it in by repeated .rr". '
choose
2.
Choice B is correct. If the side chain (carbon three of isoleucine) were to change the orientation of its chr.ot" o] the two chiral centers lyoL-:
differ between the two compounds. The two stereoisomers (isoleucine and the other compound) would ::
classified as diastereomers. The correct choice is B.
center while carbon 2 retained the orientation of its chiral center, then only
Choice B is correct. This question can be solved from straight memorization. Naturally occurring amino ac:-.,
are "L" as in life and natural. It is also stated in the passage that naturally occurring amino acids har'- :
stereoconfiguration and that S stereochemistry is associated with L-amino acids. The besi answer is choice B
4.
Choice C is correct. With H as the side chain, carbon two of glycine (the alpha carbon) has two hydrog..
-,
attached, thus there is no chiral center present on glycine. Neither of the two carbons in glycine have::-:
different substituents attached. The absence of a chiral center in glycine results in an opticai rotation o: ,
Choose C and be happy.
5.
Choice B is correct. Enantiomers are nonsuperimposable mirror images, thus ail of the chiral centers ,:.
different between the two structures. If all of the chiral centers are reversed, then the specific rotation shc*-:
be completeiy reversed, which would lead to a value of +62" rather than -62". It would be terrific if you \{e:- ::
choose B. Enantiomers always have the same absolute value for the specific rotation, only the sign (direc-* :
of rotation) differs.
6.
Choice B is correct. As stated in the passage, the side chain of threonine is an alcohol (eliminating cholct ..
and it is chiral (eliminating choices A, C, and D), all choices except answer B are eliminated. Only chor:t S
contains a carbon that is asymmetric (chiral center).
7'
Choice C is correct. Isoleucine contains two chiral centers, one for the alpha carbon and one in the side ch,*Plugging into the stereoisomer equation 2n where n is the number of chiral centers, there are four pos'-- -r
stereoisomers for the isoleucine structure. Because isoleucine contains two chiral centers that must have s1.;- -,orientation, only one of the four stereoisomers wili have the correct chirality to be biologically usable. Ti.,-" ,.
stated in the passage in two fragments. The best choice is C.
8.
Choice C is correct. PBr3 converts the OH group of an alcohol ir-rto a Br group through an S1.;2 reaction. Bec: --,o
the reaction is by way of an S52 mechanism, the chiral centers inverts. If you recall, chiral centers inr e ::
Sp2 reactions, but not S1l11 reactions. This means the product shows stereochemistry of 35, 4R. Choose C fc: --:':
sensation of correctness and satisfaction.
-Ln
240
STEREOCHEMISTRY EXPLANATIC,i\]$
9.
Choice B is correct. If you rotate the original structure so that the hydroxyl groups are syn, then the two alkyl
groups of the molecule also have syn orientation. The original alkene must therefore have the two alkyl
groups cis to one another, resulting in Z geometrical alignment. Pick B for best results.
HO
cH2cH3
h B{r
R"t"t
"
cH2cH3
cH2cH3
OH
So, utt
"rlu*ust
74
cH2cH3
Priority #4 in front
Clockwise =
This makes the compound 3R,45. Choose B for optimal correctness and the satisfaction that goes with it.
11.
Choice B is correct. On the third carbon, the OH and H groups have interchanged, so that chiral center has
changed. On the fourth carbon, the ethyl group, hydrogen and hydroxyl group have interchanged, so that
chiral center has not changed. When only one out of two (some, not all) chiral centers change, it is not a mirror
image, nor identical (superimposable), making the two compounds diastereomers. Pick answer B.
HOH
cH2cH3
e
il
?.,
HH
Compound
mt
12.
HO
H
P
Mystery Compound
H in front, so reverse
chirality from R toS
H3C
m!
H in back, so chirality
is S as shown
ile
:hr
[3.
&
for
hc
CH2CH3
Choice D is correct. The active site of an enzyme carries out a highly specific function (reaction), so they must
be highly selective in terms of reactivity. As implied by the passage, active sites are highly specific in terms
of chirality. This eliminates choice A. Although it is not stated in the passage, you should know that the
active site has specific dimensions, so it is size specific. This eliminates choice B. Active sites are highly
specific for the functional groups involved in a chemical reaction, so choice C is eliminated. Because isotopes
show the same chemical reactivity, enzymes are unable to distinguish isotopes. This means that enzyme
active sites are nof isotope specific, making choice D the best answer.
lopyright
241
STEREOCHEMISTRY EXPI,ANATIONS
't4.
Choice A is correct. Enantiomers have the exact same physical properties, such as boiling point,
melting point,
and density. This makes choice A correct and eliminates choices B and C. Enantiomers have the
same
magnitude for specific rotation, but with the opposite sign (in the opposite direction). This makes
choice D an
incorrect answer, and leave choice A as the best choice ini sea of many choices (weil maybe not
many, but four.)
15.
Choice B is correct. A specific rotation for an enantiomeric mixture that is positive means that there is an
of the enantiomer with the positive rotation (in this case the R enantitmer). If the two enantiomers
were present in a fifty-fifty ratio, then the specific rotation would be 0". This eliminates answer choice C.
Choice D is eliminated because an excess of th" S stereoisomer would result in an overall negative opticai
rotation, making choice D invalid. If the mixture were in fact 100% of the R enantiomer, thei the specific
rotation would be +32.2" ' This is not the case either, so choice A is eliminated. By the process of elimination.
choice B must be the correct answer. The problem could have been solved mathematically as follows:
excess
Thus2(%R-%S)=%R+%S
2%F.-2"k5=%R+%S
%R = 3 %S, so o/,R = 75oh and %S = 25"/o
16.
17.
Choice A is correct. Because one enantiomer aiways has the opposite optical rotation of the other enantiome:
(one is negative and one is positive with the same magnitude), li Uotn enantiomers are present in
solution, the
absolute value of the rotation must decrease from the absolute value of the pure enantiomer. The observec
optical rotation is an average of the enantiomers in solution. Therefore, choice A cannot account for an obser'ec
specific rotation greater than that of the pure species, because the mixture of the two enantiomers would cause
the value to be less than the literature value (given that the literature value is positive). Choices B and C
both lead to an increase in the observed rotation. The standard rotation is based orrmonochromatic light from;
sodium iamp. If monochromatic light from another source is used, it will interact differentlyiwith the
compound, resulting in a different optical rotation. Whether the rotation is greater or lower is uniertain, bu:
because it is possible that the rotation is greater, choice D is eliminated.
Choice C is correct. The formula for units of unsaturation is Units of unsat = 2(#C)+1(#N)+2-1(#H)
For
2(77)+7(7)+2-7(27)
22
- 4 -'
Pick C. Remember that oxygen is not included in the formula for degrees of unsaturation. Iflrou didn't rememte:
the formula, then count the bonding electrons for the compound (44 for the eleven carbons, 21 for the hydrogerr.
3 for the nitrogen, and 4 for the two oxygens). There are a total of 72 bonding electrons, so the compound has lr
bonds total. There are 35 atoms in the molecule, therefore only 34 bonds (minimum) are necessary to connect r;,e
atoms and form the molecule. There are 36 bonds when only 34 are needed, thus there are two extra bonds. Thlong-winded path still leads to answer choice C.
18.
Choice D is correct. The only way to do this problem is to count isomers systematically. Start with the longe=:
chain (6) and list all the possible isomers. Then look at chain lengths of one less carbon (5) and list all of thopossible isomers. This continues until the possible backbones are depleted. For this question, the carbi:
backbone is shown for all of the possible isomers. There are five isomers total, so pick D.
rongest chaln
= 6 carbons
c-c-c-c-c-c
Copyright @ by The Berkeley Review@
rnnnact chain
longest
^-,
^h.i- _
= 5< carbons
c-c-c-c-c
ccccc
llrtt
c-c-c-c_c
\l
c_c_c_c c_c_c_c
-
242
STEREOCHEMISTRY EXPLANATIO\5
19.
Choice B is correct. It is stated that the OH substituent is on carbon 2. The OH is attached to an R chiral center
while the Br is attached to an S chiral center. Pick B. The rationale is shown below:
I
Br
switched, the
compound would be R. Because they
are not switched, it must be an S.
Li\
,,F,,,Y
front, it reverses to R.
20.
Choice A is correct. A geminal diol has two hydroxyl groups on the same carbon (think of 'geminal' as being
equivalent to gemini, meaning that the two OH groups are twins.) Because the two hydroxyl groups are on the
same carbon, that carbon cannot be asymmetric. As a result, the molecule is achiral, so it cannot form optical
isomers. This makes choice A the best answer. A vicinal diol has two hydroxyl groups on neighboring carbons
(think of 'vicinal' as meaning vicinity or vicino, the Spanish word for neighbor). Because this ensures that the
second carbon has a hydroxyl group, the second carbon must be asymmetric. As a result, the molecule is chiral,
so it can form optical isomers. This eliminates choice B. Four carbon chains with a secondary functional group,
whether it is an amine or alcohol, have a carbon with four different substituents (H, CH3, CH2CH3, and the
group), so they are chiral. Being chiral, four carbon chains with a secondary functional group can form optical
isomers. This eliminates choices C and D. Choice A is the best answer.
21.
Choice B is correct. In polycyclic systems, if there is no plane of symmetr1z, then all tertiary and quaternary
carbons are stereogenic centers. In addition, any secondary carbons with a functional group are also stereogenic
centers. The compound has two quaternary carbons, three tertiary carbons, and one secondary hydroxyl group.
This means that there are six chiral centers. Given that there are two possible orientations at each chiral
center and the compound is not meso, the total possible number of unique stereoisome rs ts 26, which is 64, Pick B,
and feel the warmth of correctness.
22.
Choice C is correct. As indicated in Table 1 in the passage, diastereomers show different physical properties.
The melting points of diastereomers are different, because the molecules pack into their respective lattice
structures differently. The density is different between isomers, because the two diastereomers have different
conformations that also pack into their respective lattice structures differently. The optical rotation of
diastereorners must be different given the fact that they are identified by their differences in optical rotation.
This eliminates choices A, B, and D. Because diastereomers are isomers, and they have the same molecular
formula, thus they have the same molecular mass. The correct answer is therefore choice C.
23.
Choice B is correct. When using a polarimeter, an observed optical rotation of +233.0" and -1.27.0'would yieid
the same reading (given that a full circle is 360"). To discern one optical rotation from the other, the sample
should be diluted to reduce the rotation. If the actual optical rotation is in fact +233.0', then the lower
concentration would show a rotation less than +233.0' (less clockwise). If the actual optical rotation is in fact
-727.0", then the lower concentration wouid show a rotation less than -727.0" (less counterclockwise). If the
solution concentration were cut in half for instance, the rotation would be either +116.5" or -63.5". The change in
rotation can therefore determine the original rotation value. The only answer that indicates changing the
concentration is choice B.
24.
Choice A is correct. If D-glucose has an optical rotation of +52.6' , then the enantiomer of D-glucose (L-glucose)
must have an optical rotation of -52.6'. Mannose, the C-2 epimer of glucose (the diastereomer of glucose that
only differs at carbon two) is neither of these two structures (L or D glucose), thus it does not show an optical
rotation of either + 52.6' or -52.6". Mannose is chiral and not meso, so it cannot have an optical rotation of 0".
The best answer is choice A.
25"
Choice D is correct. The number of stereoisomers (assuming that there is no meso structure), can be determined
by raising 2 to the power of the number of chiral carbons (stereocenters). There are three chiral carbons
(stereocenters) associated wiih penicillin V, thus there will be eight (23) stereoisomers for the structure of
penicillin V. The 2n formula represents the maximum number of stereoisomers. For every meso structure, you
must subtract one frorn the total. Choice D is correct.
243
STEREOCHEMISTRY EXPLANATIONS
26.
Choice B is correct. The greater the density of a compound, the more tightly packed the compound
is in its
crystal lattice. This means that this question is a read-the-chart-to-fitr"a-tnu-d"r-rsity question.
The mesc
compound is less dense than the other compounds according to the data in the table, thus it
must pack least
tightly of all of the choices. The best answer is therefore choice B.
27.
Choice C is correct. Stereocenters can be identified quickly as sp3 carbons with four different
substituents
attached. In camphor, there are two carbons that fit this deicriptibn. The correct choice is answer
C. Dral'n
below is camphor with the two chiral carbons (stereocenters) labeled:
Top
Side
CH:
28.
Choice D is correct. If the hydrogen bonds in a pure compound were stronger than the hydrogen bonds in a
mixture of stereoisomers, then the intermolecular forces would be greate"r in the p,rr"- .orripound. As a
consequence, the pure compound would have the higher melting point, which is the exact opposite of the
premise. Choice A is an untrue statement, and thus it is eliminated. Physical properties, such as'melting point
result from intermolecuiar forces, not covalent bonds. Enantiomers are no
-ore lit ely to form covaleni bonds
with one another than diastereomers. Choice B is an untrue statement that
does not explain the observei
melting points. Choice B is eliminated. Covalent bonds are not affected when a .o*porr1d melts, so choice C
should be eliminated. The best explanation is choice D, because when the moleculei pack more tightly, ther
exert stronger forces on each other. Because the enantiomeric mixture (R with S) has a higher
-"itlng po*,
than the pure enantiomer (R with itself), the forces are in fact stronger in the enantiomeric mixture
than the
29.
]!
Choice B is correct. To separate enantiomers from one another, the medium must be chirally pure (be chiral
with only one enantiomer present). The best method is the use of chiral gei in colum. .hro^uiography. The
two enantiomers exhibit different migration rates down the column, because the two adhere to thJcoiumn to a
different extent. Choice A is a valid methocl. Distiilation r,vill nof separate the two enantiomers, so choice B
is the correct answer choice. The mixture can be selectively crystallized with a pure R or pure S compound. ThL
is often carried out with tartaric acid. Enzymes are chiral, so chiral .o-porrr.i, pass thiough an enzyme filter
at different rates. This makes choice C and D vaiid.
30.
Choice B is correct. To prevent the product mixture from being racemic, chirality must be present in the
transition state. A change in temperature does not affect the chirality of the products. Choice Cis eliminated.
The concentration does_not affect ihe alignment of the molecules in the transition state, only the frequency witi.
which the reactants collide to form the transition state. This eliminates choice D. The presence of a chiracenter in the solvent cloes not affect the chirality of the transition state unless the soivent is involved in the
transition state. Choice A cannot be eliminated yet, but it is not a likely choice. The only change that vr'i-definitely affect the distribution of enantiomers is the addltion of a chiral catalyst which affects the
transition state. This is the whole idea behind the activity and specificity of enzymes (chiral catalysts) i-r.
biological reactions. The best answer is therefore choice B.
31"
Choice A is correct' Both enantiomers have oniy one stereocenter, therefore choices C and D are eliminatec
The lemon fiavored extract is the structure on the left, which has its lone stereogenic center in R configgration
This eliminates choice B and makes choice A the correct answer.
.)At
STEREOCHEMISTRY EXPLANATIONS
Choice D is correct. The one physical property that definitely changes with the chiral center is the optical
rotation. The specific rotation of a product mixture measures its enantiomeric purity (percentage of each
enantiomer). The boiling point, density, and solubility in a given solvent does not vary between enantiomers.
These physical properties can vary between diastereomers, but enantiomers are identical in their packing and
intermolecular forces, unless the alcohol solvent is chiral and optically pure. The best answer is choice D.
Choice A is correct. The regio-chemistry is correct in all of the answer choices (the boron has attached to the
less hindered carbon of both alkenes). Hydroboration, you may recall, proceeds with anti-Markovnikov
regioselectivity. The reaction calls for the R enantiomer, which has the alkenyl group sticking out of the
plane (the structure on the left in Figure 2, labeled "lemon odor", has R stereochemistry). This eliminates
choices C and D. Because the boron and the hydrogen add syn to one another, the methyl substituent on the ring
must be trans to the bridging boron. This eliminates choice B and makes choice A the best answer.
nrC4,
First addition
of BH3(Et2O)
Second addition
of BH"(EI2O)
H-B
R stereocenter
->
Choice A
Choice B is correct. The two enantiomers have a different flavor (and thus different smell), so they must bind
the olfactory receptors differently. This eliminates choices C and D. Because they recognize the difference
between the two enantiomers, they too must be asymmetric (and thus chiral). The correct answer is choice B.
Choice A is correct. The isoprene molecule has no chiral centers, so the product is a racemic mixture. The
molecule listed in the question as an alternative reactant has a chiral center present that will influence the
orientation in the transition state. The product would contain three chiral centers (one new chiral center
formed and one each present in the two reactant molecules). The product would be present in a mixture of
diastereomers. Diastereomers cannot be present in a racemic mixture, therefore the product mixture would not
be racemic for the new reaction. The best answer is choice A.
Choice A is correct. The proposed product is a mixture of diastereomers formed from a nucleophilic substitution
reaction. Because two diastereomers are formed, the proposed reaction must have been predicted to proceed by
an Sp1 mechanism. The best answer is choice A.
Choice D is correct. Any nucleophilic substitution reaction that proceeds with either inversion of a chiral
center or retention of a chiral center remains chiral, and thus is optically active. This eliminates choices A, B,
and C. The product from elimination is an alkene, which has no chirality, and thus no optical activity. The
correct answer is elimination, choice D. The rearrangement clause, although true, has little bearing.
i8.
Choice B is correct. There are two chiral carbons present on each compound. The tertiary carbon retains its
chirality between stereoisomers, but the methoxy carbon has different chirality in the two stereoisomers. This
means that one out of two of the chiral centers differs, making choice B the best answer.
39.
Choice B is correct. To increase the amount of substitution product that forms, the amount of elimination
product that forms must be reduced. The elimination reaction is by way of an E1 mechanism, because no strong
base is present. To reduce the amount of E1 product, the amount of acid should be reduced, and the reaction
should be carried out at a lower temperature. This means that the temperature should decrease (elimination is
favored at higher temperatures) and the pH should increase. The best answer is choice B.
40.
Choice C is correct. There is a secondary electrophile, protic solvent, and a poor nucleophile present, so the
substitution reaction takes place by an SX11 mechanism. The presence of the methyl and methoxy groups on the
same carbon can be explained by rearrangement. There is a secondary carbocation formed when the leaving
group leaves. When the hydride shifts, a tertiary carbocation forms. This is a more favorable intermediate, so
the reaction proceeds via a hydride shift before the nucleophile attacks. The best answer is choice C.
245
STEREOCHEMISTRY EXPLANATIONS
41,
Choice B is correct. Given that the conversion of the hydroxyl group into a bromine goes with inversion o;
stereochemistry, the alcohol must have opposite chirality at carbon 1 as the bromoalkane in Reaction 1. The
passage states that the reactant is (1S,2R)-2-methylbromocyclopentane, so the alcohol precursor must har.e
chirality of 1R and 2R. The best answer is B. The reaction and chirality is shown below.
H in back on C-2,
so take as is: R
.)'rrOU
H in front on C-1,
so reverse it: R
42.
#
CFL
PBre
.,rrr\OH ______*
Br
Choice B is correct. The preference for the major product can be attributed to steric hindrance in the transition
state (the transition state is asymmetric). The carbocation is sp2-hybridized,, so it is planar. The only steri:
hindrance comes from the adjacent methyl group (which is above the ring). The adjacent methyl, by beir.e
above the ring, influences the nucleophile to attack from below the ring. The best answer is choice B.
44'
Choice A is correct. From the data in Table 1, the faster reactions are observed with 1-chioropropane an othe:
electrophiles, so it is a safe and valid assumption that the reaction with the primary aikyl halide proceed.
most rapidly. Choose A.
45.
Choice A is correct. The reaction can proceed by either an S511 or Sl112 mechanism with a secondary alk,,'halide as the eiectrophile. If the reaction were to proceed by an 51112 mechanism, then the product wouid be
the 25, 35 stereoisomer. Only the stereocenter from which the bromine substituent left underwent a change r,..
chirality (inversion), thus only that stereocenter will show a change in its orientation. If the reaction were tc
proceed by an S1r11 mechanism, then the intermediate would undergo rearrangement, and thus the ammoni"
wouid attack the third carbon leaving an achiral product. Given the answer choices, choices B and C car.:
form, and there is no achirai choice, therefore the reaction proceeded by an SNI2 mechanism. This means tha:
inversion of the second carbon will transpire to yield 25,35. Choose A.
46.
Choice A is correct. To have optical activity and lose it during the course of the reaction eliminates choice B
because the 51'12 reaction proceeds with inversion (thus an optically active product is formed). By definitior
the product mixture as described in the question is racemic. A racemic product mixture is associated with th.
51111
reaction. Pick A.
47,
Choice A is correct. The ether product has S stereochemistry as drawn and was formed by a substitutic:.
reaction using NaOCH3 as the nucleophile. Sodium methoxide (NaOCH3) is a strong base, and thus it is also a
good nucleophile. Because the nucieophile is good, the reaction must have proceeded by an 51112 mechanisn'.
Because the final product has S stereochemistry, the starting material (electrophile) must have had F.
stereochemistry to form the S product from inversion. This eliminates choices B and D. For the substitutior.
reaction to proceed, the electrophile must have had a good leaving group. Ammonia is not a leaving group
therefore the chlorine leaving group is the better choice. This makes the correct answer choice A.
48.
Choice A is correct. The reaction proceeds at the fastest rate during the first segment of the reaction becaus:
initially the concentration of L-chloropropane (a reactant in the rate determining step) is greatest and bot:r
reactants (nucleophile and electrophile) are depleted over time. Chloride anion is the leaving group, thus rls
concentration will increase over time. A11 of the graphs show increasing concentration. Over time, the
concentration of 1-chloropropane gradually decreases, thus the reaction rate decreases graduallyi this resulin a slower production of Cl- anion. Graph A best depicts this gradual decrease in reaction rate. Choose A anc
be a wunder sfudent.
246
STEREOCHEMISTRY EXPLANATIONS
I
illl'
49.
Choice A is correct. Because the electrophile is a tertiary alkyt halide, the reaction is an Sry1 reaction, which
with racemization. The optical rotation of the product mixture following an 5511 reaction is 0". This
eliminates choice B. Graph C (the schizophrenic graph) shows the correct final optical rotation, but no
reaction will proceed with the erratic change in rotation. Choice D shows that the reaction proceeds at a
constant rate until the reaction is complete. This would be seen with a zero order reaction, not a first order
reaction' The SIrI1 reaction is first otder, so answer choice D is eliminated. Graph A best depicts the gradual
loss of chirality. The optical rotation will never switch to the opposite sign unless there is inversion *hi"h it
not possible with an sI.I1, reaction. Choose A and make your support group proud.
proceeds
50.
Choice B is correct. The ether product shown in both Reaction 1, and 2 is the result of a substitution reaction, not
an elimination reaction, so choices C and D are eliminated. The data in Table 1 correlates to Reaction 1.
Because the rate of the reaction varies directly with both the concentration of the nucleophile and the
concentration of the electrophile, Reaction 1 must be an 5512 reaction. The data in Table 2 correlates to Reaction
2' Because the rate of the reaction varies directly with the concentration of the electrophile, but does not vary
with the concentration of the nucleophile, the reaction must be an 51111 reaction. The rate of an 51111 reaction
only depends on the concentration of the electrophile, and does not vary with the concentration of the
nucleophile. This means that you must choose B to live up to your potential.
Choice A is correct. Because the rate of Reaction 2 varies directly with the concentration of the electrophile,
but does not vary with the concentration of the nucleophile, Reaction 2 must be an St'tr1 reaction. an S51t
reaction undergoes racemization, not inversion, so choice A cannot apply to Reaction 2. In addition, Reaction 2
has no chirality, so choice A is invalid. The best answer is choice A. A carbocation intermediate corresponds
with an Sp1 reaction, so choice B is valid and thus eliminated. All nucleophilic substitution .eactions,
whether it is an 5111 or S1rJ2 rnechanism, have a rate that depends on the electrophile. Choice C is valid, and
thus eliminated. A protic solvent helps to stabilize the carbocation intermediate and the leaving group, so a
5511
it.
Choice
52.
Choice B is correct. If the reaction were to proceed purely by an 5512 mechanism, the product would be 100% R,
because the reactant is enantiomerically pure and the SNI2 reaction results in complete inversion. If the reaction
were to proceed purely by an S1r11 mechanism, the product mixture would be 50% R and 5Ao/" S, because the
reaction goes through a planar carbocation intermediate resulting in a racemic mixture. The mixture is 87% R
and 13% S, which is closer to the products of an 51'12 mechanism than the products of an 51111 mechanism. It is
not a pure reaction so the best answer is choice B.
53.
Choice A is correct. Because the carbon-bromine bond is weaker than the carbon-chlorine bond, it is more easily
broken. This makes the bromine a better leaving group than chlorine. An alkyl bromide is therefore a more
reactive electrophile than an alkyl chloride. With a better electrophile, the reaction is faster for both the
Sp1 and the Sir12 mechanisms, because they both depend on the electrophile. This makes choice A correct.
i4.
Choice A is correct. The strongest nucleophile is most willing to donate its lone pair to carbon. The answer
choices include two conjugate pairs. The conjugate base is the better nucleophile of the pair, so choices B and D
are eliminated. HCI is a strong acid while methanol is a weak acid, so methoxide is a stronger base than
chloride. This means that methoxide is more willing to donate electrons than chloride, and therefore
methoxide is the better nucleophile. Pick A and see your score improve.
f5.
Choice C is correct. An SNJ2 reaction favors a primary electrophile over second aty ot tertiary electrophile, and
a good nucleophile is required. Choices A and B can both be eliminated, because the electrophiles are tertiary
(and tertiary electrophiles proceed via the Sry1 mechanism). Choice C is better than choice D, because
methoxide is a better nucleophile than methanol. Pick C for optimal results.
56,
Choice B is correct. An
5512 reaction proceeds by way of a one-step mechanism, which eliminates choices A and
reaction has the products at a lower energy level than the reactants, which eliminates
choice D and leaves choice B as the correct answer. The apex of the graph represents the transition state, and
the absence of a valley on the graph implies that there is no intermediate for the reaction. Choice A is an
exothermic 5111 reaction, choice C is an endothermic Sp1 reaction, and choice D is an endothermic Sp2 reaction.
C. An exothermic
241
STEREOCHEMISTRY EXPLANATIONS
57.
Choice A is correct. The best electrophile is the compound with the best leaving group. The best leaving group
is the leaving group with the strongest conjugate acid. In this case, iodide is the best leaving group, beciuse HI
(hydroiodic acid) is the strongest conjugate acid of the choices listed. This makes choice A the best answer.
58.
Choice D is correct. This question requires that you identify the best electrophile. Again, the best electrophile
is the compound with the best leaving group. The best leaving group has the strongest conjugate acid, which rn
this question is the bromide leaving group. The ranking of the conjugate acids for the leaving groups are: HBr >
HF > HOC6H5 > HSCH3. It is in your best interest to choose D.
59.
Choice D is correct. A leaving group, once it has left an electrophile, must have at least one lone pair (as a
result of the heterolytic bond cleaving). This stipulation eliminates choice A, because the carbon of the cyanic
acid has no lone pair, and the nitrogen does not interact with a carbon to be a leaving group. The most stable
leaving #oup is the weakest base. Of the three choices left, CH3CH2SH has the strongest conjugate acic
(CH3CH2SH2+ is a stronger acid than CH3CH2SH and HCN), thus CH3CH2SH is a weaker base than
CH3CH2S- and CN-. CH3CH2SH is the weakest base of the choices remaining, therefore it is the best leaving
group. Choose D to score a point in this contest of point collecting.
60.
Choice D is correct. The difference between the two molecules is the alkyl group. According to the question, the
smaller molecule is the better nucleophile. The inductive effect would predict that the electron donating
methyl groups would make the larger alkyl group more electron donating and thus more nucleophilic. This is
the opposite of what is observed, so choice A is eliminated. Resonance is not a factor, because there is no rsystem. Choice B is eliminated. The hybridization is sp3 in both cases, so the difference in nucleophilicit',cannot be attributed to hybridization. This eliminates choice C. Steric hindrance predicts that the smaller
nucleophile has less interference in the transition state, thus iL is a better nucleophile. In this case, steric
hindrance plays a larger role than the inductive effect in the reactivity of the nucleophile. The correct ansn'er
is choice D.
61.
Choice A is correct. Sodium cyanide is a good nucleophile and iodide is a great leaving group, therefore thi.
reaction shouid be very favorable. The difference between their pKu values ts 79.6, which implies that the
Ksq for this reaction is near 1919'6 = 4v1919. This defines a reaction that goes completely to product, whic-i.
supports the evaluation that the reaction is very favorable. Do the correct thing, choose A.
62.
Choice D is correct. Hydroxyl groups are terrible leaving groups. Thiols are average to poor nucleophiles. The
reaction between a poor nucleophile and an electrophile with a poor leaving group should be very unfavorab:e
by intuitio.n. The difference between their pKu values is -5.2, which implies that the K"O for this reaction'.
near 10-5'2 = 6 x 10-6. This defines a reaction that stays predominanlly as reactant, rirhich supports the
evaluation that the reaction is very unfavorable. Choose D,
63.
Choice A is correct. In protic solvents, there is hydrogen bonding, so choice C is eliminated. Equally, in a:,
aprotic solvent, there is no hydrogen bonding, so choice B is eliminated. Hydrogen bonding affects fluoride an:
not iodide, so the fact that fluoride is a worse nucleophile than iodide in alcohol implies that hydroger,
bonding reduces the nucieophilicity of fluoride. This can be attributed to hindrance to migration caused t'i
hydrogen bonding. The best answer is choice A. Choice D can be eliminated, because if it were true, then the
opposite relative nucleophilicity would be observed for fluoride and iodide.
64.
Choice A is correct. The strength of a nucleophile can be measured by its reaction rate in a second-orde:
nucleophilic substitution reaction (an SX12 reaction). The nucleophiles are listed in the first column of Table 1
Any other column can be used to determine the relative strength of the nucleophiles, because all other factors i
the reaction are constant. The less negative the value in ihe table, the faster the reaction, and therefore th.r
better the nucleophile. The CN- has the lowest value in all three columns, so the best nucleophile is CN-. Thri
eliminates choices C and D. The question now is to determine whether the ammonia (NH3) or methanc(HOCH3) is the better nucleophile. The stronger nucleophile is ammonia, because in each column, the 1e..
negative value is associated with ammonia. The best answer is choice A, CN- > CH3S- > NHg > HOCH3.
STEREOCHEMISTRY EXPLANATIO\,(
55.
Choice C is correct. As mentioned in the passage, the methyl electrophile is chosen to avoid the complication
of the competing elimination reaction. It is not possible to form a dbuble bond with only one carbon in the
reactant (at least two carbons are required for the formation of a double bond). This makes choice C the best
answer. Steric hindrance increases when using the isopropyl electrophile in lieu of the methyl electrophile,
but that is not necessarily a difficulty. The effect should be uniform u"ross the reaction chart, so choices A and
B can be eliminated.
66.
Choice A is correct. The best leaving group is the functional group that takes electrons from carbon and retains
them to the greatest extent. Retaining electrons can also be viewed as not sharing electrons. By not sharing
electrons, an ion or molecule can be viewed as being a weak base. The strength of i leaving group is generally
correlated (in a linear fashion) to the strength of the conjugate acid of the leaving group. aJ un icid becomes
stronger, the conjugate base becomes weaker. This implies that it is valid to compare the strength of the
ieaving grouP in a linear fashion with weakening base strength. This makes choice A, "The less basic the
leaving group, the better it is as a leaving group,' the best answer. Choices B and C are essentially the same
answer, therefore they should both be eliminated.
67-
Choice D is correct. The strength of a nucleophile can vary with many reaction features. Depending on its
nature, a solvent hinders a nucleophile to a varying degree. For instance, if a solvent is capable of fbrming
hydrogen bonds, then it will hinder the attack of nucleophiles that are capable of forming hydrogen bonds-.
This can be seen in the differing nucleophilic strength of halides as they are observed in apiotic and protic
solvents. The fluoride is the strongest nucleophile of the halides in aprotic solvents whilelt is the weakest
nucleophile of the halides in protic solvents. This eliminates choice A. The nucleophilicity of a compound can
be correlated to its basicity in terms of a Lewis base. Generally, for a nucleopiile that is more basic than
another, it is the better nucleophile of the two, with steric hindrance responsible for most deviations from that
pattern. This eliminates choice B. The strength of a nucleophile reduces with increasing bulk. This implies
that nucleophilicity can vary with steric hindrance, which eliminates choice C. The only answer choice left is
choice D. The leaving group is independent of the nucleophile in nucleophilic substitution reactions. This
makes choice D the best answer.
68.
Choice B is correct. Because the rate of an Sp1 reaction depends only on the leaving group breaking free from
the electrophile in the rate-determining step, the nucleophile is irrelevant .to the reaction rate f-or an Sy1
reaction. The strength of a nucleophile cannot be determined by a rate study in which the nucleophile does not
influence the rate. The rate can vary with changes in the leaving group strength (which can be viewed as
changes in the electrophile), the temperature (temperature always affects the rate of a reaction), and solvent.
It is only the strength of the nucleophile that cannot be determined from the reaction rate data of an S1q1
reaction. Choose B for yet another chance to flash a happy "I just got another one right" smile.
59.
Choice D is correct. Choice B can be eliminated immediately, because NH3 is the nucleophile and not the
leaving group. Choice C can be eliminated immediately, because -OCH3 is the leaving group (if it were to
react) and not the nucleophile. The data in Table 1 shows that no reaction was observed each time that the
electrophile was dimethyl ether (CH3OCH3). O.t the other hand, the data in Table tr shows that ammonia
(NHg) is a reactive nucleophile with the other three electrophiles used in the experiment (CH3OSO3CH3,
CH3I, and CH3CI). This implies that the lack of reactivity can be attributed to the electrophile rather than
the nucleophile. The leaving group in the cases where dimethyl ether is the electrophile is a methoxide anion
(-OCH3). Pick D to prosper and score... well score at least.
70.
Choice B is correct. By definition, a nucleophile is a lone pair donor, which by yet another definition is
Lewis base. This makes this question a freebie and the correct answer choice B.
71.
Choice B is correct. From the low temperature of the reaction and the retention of optical activity in the
product, it can be inferred that the reaction proceeds by way of an 51112 mechanism. Elimination and S1g1
reactions produce products that lose their optical activity. Choices C and D can be eliminated because the
alkene products would show no optical rotation because they lose both stereocenters in the formation of the
alkene. The products from a reaction proceeding by an Sry1 mechanism in this case would be a mixture of
diastereomers (not enantiomers), which would lead to an optical rotation close to zero. Enantiomers are
obtained if the reactant is symmetric. The best (although not perfect) answer is choice B.
249
STEREOCHEMISTRY EXPLANATIONS
72.
Choice D is correct. At high temperature, the predominant reaction is elimination. This eliminates choices C
and D. Because a strong base (NaOH) was used, the mechanism must have been an E2 rather than an E1
mechanism. The best answer is choice D. This can be verified by looking at Trial IV in Table 1, which shou'
identical reaction conditions as the reaction in the question. The loss of optical rotation in the product impl,v
that the reaction was an elimination reaction. A substitution reaction would yield some sort of optical
activity. You have to know that base infers that the mechanism is E2.
/5.
Choice B is correct. There are two chiral centers in the reactant, located at carbons two and three. This can be
inferred from the answer selections. The number four priority is hydrogen on both chiral centers and
conveniently it is in the back in both cases. The first chiral center (carbon two) has priorities bromine > deutero
ethyl > methyl which form a clockwise arc. The first chiral center is thus R. The second chiral center (carbon
three) has priorities ethylbromide > methyl > deuterium which form a counterclockwise arc. The seconi
chiral center is thus S. The solution is drawn below:
I
u'\.
n"}V
2
H
carbon 3 =
carbon 2 = R
Choice D is correct. If the reaction proceeded purely by an SNI2 mechanism, then the optical rotation would b,e
the same as was observed for trial I(-36"), a purely 5512 reaction. This eliminates choice A. An eliminatior.
reaction would yield an optically inactive product so the optical rotation observed for an elimination reactio:.
would be zero. This eliminates choice B. The optical activity observed implies that an S52 reaction must har-e
been occurring to some degree. The reduction in optical activity must be attributed to the Presence of sone
impurities (from some side reaction). The best answer is choice D.
75.
Choice A is correct. Because the enantiomer is a mirror image of the reactant, it forms a transition state wher, -:
is eliminating that is a mirror image of the reactant's transition state. This means that the products are ali:
mirror images, but without stereogenic centers, they can be rotated to match as identical compounds. Th;
symmetry presents itself in the product as an identical geometric isomer. Because a diastereomer varies at on-i
one chiral center, it is not a mirror image of the reactant when it is eliminating. This asymmetry presents itse''
in the product as d"ifferent geometric isomers. This may not make sense in words so the drawing below shou s
the products.
BrH
Br
H$FT
HsC
CHs
rotation to correct
alignment
CH"
H$tjl
'
with
b"* - HEC
Elimnation
"
HsC
rtrr"g
CH:
Cis Methyls
Reactant
Br
"T,>+"
HsC
CHs
rotation to correct
---------=--+
alignment
H\ty
Elimnation
H:C
Diastereomer
-..,i';*"
H
CHs
with -
a strong base
><
CH.
HaC
D
Trans methyls
HeC
rotation to correct
aiignment
Cis Methyls
Enantiomer
The enantiomer forms the same products while a diastereomer forms geometric isomers, making the best ansl,:s"
choice A.
Copyright O by The Berkeley Review@
250
STEREOCHEMISTRY EXPLANATION$
76.
Choice B is correct. The elimination product would be optically inactive, because it will lose
both stereocenters
(chiral carbons) upon forming the alkene. This means that the specific rotation of the
alkene product is zero
making choice B the best answer.
77.
Choice C is correct. An E2 mechanism involves the removal of a proton alpha to the leaving
group which then
shifts the electrons into a n-bond forcing the leaving group off. The mechanism is concerted, iiplying
that both
events occur simultaneously. This results in very predictable geometry with respect to the
p.oirct a-lkene. To
support the operation of the E2 mechanism, both carbons that become involved rn the n-bond should
be chirally
labeled to trace the reaction. If the mechanism is specific, then the final product is a specific
geometrical
isomer. This is why the reactant is deutero labeled at iarbon three. Therefore-, the best answer is choice
C.
78'
Choice B is correct. Because the electrophile is a tertiary alkyl halide, Reaction 2 proceeds by way of an S.u1
mechanism. The two products have specific rotations of +62' and +30' respectiveiy as writtln. A fifty
/ fifty
mixture of the two products would yield an observed specific rotation of +46'" (the average of the values ior
the
two diastereomers). Because of steric hindrance from the bonds to the six membereJring, the nucleophile
(It{Hs) prefers to attack from the backside of the molecule. This makes the major product Lompound
A, the
first product in Reaction 1. The
product has a specific rotation of +62', thus'the specific rotution of the
-ujgt
mixture is closer to +62" than +30". The specific rotation is between 46' and 62', which
-ik", choice B the best
answer.
79'
Choice B is correct. The specific rotation for the mixture is found by taking a weighted average
of the specific
rotations for the components in the mixture, which is essentially what Equition 1 does. Becarise there
is more
of the component with an ct = +48" than the component with an o = +18', the averaged value should be
closer to
+48' than +18'. However, because it is not purely one component, the specific rotation for the mixture
must be
less than +48" (within the range of +33" to +48'). The best answer is therefore +42', choice
B. The exact
can be determined mathematically as follows:
'alue
oobs = 80% (+a8") + 20'/" (+18') = 38.4 + 3.6
= 42'
80'
Choice C is correct. The two products formed in Reaction 2 both have identical bonds to one another
and three
chiral centers each. In comparing the two sttuctures, only one of the three chiral centers differs, making
the
two structures diastereomers. If some, but not all, of the chiral centers differ between two stereoiso^"rr,1h"y
are not superimposable nor are they mirror images. This, by definition, makes them diastereomers.
The best
answer is choice
term epimers describes diastereomers that differ at one chiral center, but it applies
9
Jh"
specifically to the backbones of sugars.
81'
Choice D is correct. The two products for Reaction 1 are diastereomers of one another so they have different
specific rotations' This means that they can be distinguished by their different specific rotation values. This
eliminates choice A. Because they have different geometry (asymmetry), thef pack differently into their
respective solid lattices and thus they exhibit different melting points. Tiis eliminates choice B. Because of
their varying asymmetry, they bind a gas chromatography
differently (due to a difference in steric
"ot.,*n
hindrance) and thus they show different retention times on the
gas chromatogiapher (GC). It can be inferred
from the last sentence in paragraph two of the passage that the two products hurr" dlff"r"nt retention times on
the gas chromatographer (GC), since the concentration values can be d.etermined (and thus verified in this
example) using the GC. This eliminates choice C. Infrared spectroscopy measures the type of bonds in the
molecules, therefore it is difficult, if not impossible, to diitinguistr ihe two diaster"o*ers by infrared
spectroscopy' Diastereomers have identical bonds as one another. The best answer is choice D even if vou have
no idea what infrared spectroscopy does.
82"
Choice A is correct. The first product has the methyl and ethyl groups both up and the hydroxyl group down.
To retain the chiral integrity shown in Figure 1, the chair confoimatior,,
have ethyi and mjhyl Lp with
the hydroxyl down. This eliminates choices B and C, which have the -.rrt
exact opposite geometry (ethyl and
methyi are down and the hydroxyi group is up). The most stable conformer hai the least steric repulsion,
which idealiy occurs if the three substituents are in equatorial orientation rather than having the three
substituents in axial orientation. Because the substituents are on adjacent carbons, they alternate upTdown/up,
which allows all the substituents to be equatorial. This makes the best answer choice A.
251
STEREOCHEMISTRY EXPLANATIONS
83.
41
clockwise to
counterclockwise.
counterclockwise
chiral center S.
counterclockwise
chiral center S.
arc makes
the
Choice B is correct. In the alkene reactant in Reaction 1, only one carbon has four different substituent=
attached, therefore only one carbon is chiral. The best answer is choice B. The chirality is specified in th=
reactant for the ring carbon with the ethyl substituent attached.
85.
Choice D is correct. This question is asking to determine which reactions generate new chiral centers. Wher
treating an alkene with bromine, two bromides are added, one to each of the double bond carbons. The result that the two double bond carbons become new chiral centers. This eliminates choice A. When treating a:
alkene with hydrogen gas in the presence of a catalytic metal such as palladium, two hydrogen atoms aradded, one to each of the double bond carbons. The result is that the double bond carbon with the methyl grou:
becomes a new chiral center. This eliminates choice B. When treating an alkene with permanganate in bas-:
water, two hydroxyl groups are added, one to each of the double bond carbons. The result is that the two doub,i=
bond carbons become new chiral centers. This eliminates choice C. When Compound 3a is treated with a goc:
nucleophile like ammonia, the acid anhydride is cleaved. The result is that one carbonyl group becomes amide and the other becomes a carboxylic acid. Neither of these groups are chiral, so no new chiral centers a::
87.
88.
Choice A is correct. It is stated in the passage that Compound 3 represents a mixture of enantiomers, -: Compound 3b is the enantiomer of Compound 3a. Enantiomers are mirror images of one another, therefore ail --:
their chiral centers differ. There are two chiral centers in Compound 3, so Compound 3b must have the opposr::
chirality of Compound 3a at these two chiral centers. This is true in choice A, so choice A is the best answer.
Choice B is correct. To separate a compound from its enantiomer, the technique must select for one of the
t',"":
enantiomers. This requires that there is chirality (asymmetry) in the technique. If the mixture tra\ = j
through a column with one enantiomer attached, the other enantiomer is likely to adhere to the column as -:
travels. This means that one enantiomer r,r'ill migrate quickly while the other travels slowly. This ma-.choice B a strong answer. If the column has both enantiomers bound, then both of the free enantiomer: :
solution will be hindered by the column, slowing equally. This does not result in separation. Choice A '
eliminated. The same logic can be used to eliminate choice C . If the distilling column has beads with b - -:
enantiomers, then both of the free enantiomers in solution will exhibit the same affinity for the beads, a::
will not separate as well. Choice C is eliminated. The compounds do not interact with the carrier gas in ;*
chromatography to any notable extent. This means that choice D will do nothing to help separate --- {
enantiomers. Choice D is eliminated.
Choice B is correct. Reaction 2 converts Compound 3a into Compound 4, using a peroxyacid. The oxirane ::L:
form from either side of the n-bond. Flowever, because of the steric hindrance above the ring with the aLk.- *
(caused by the six-membered ring), it is preferential to form the epoxide on the back side. Both bonds to oxr-;*nl
in the epoxide must be on the same side, so choices C and D are eliminated. Because of steric hindrance, ci^ - -:*
B is a better structure than choice
A.
STEREOCHEMISTRY EXPLANATIO\$
89.
Choice A is correct. It is stated in the passage that Reaction 1 generates a mixture of enantiomers. When
enantiomers are formed, they are formed in a racemic mixture. The result is that the optical activity is zero,
because the two isomers cancel one another out. This means that Reaction 1 generates an optically inactive
product mixture. Once the enantiomer mixture is separated, isolating Compound 3a, the subsequent reactions all
start with an optically active starting material, resulting in optical activity in the end. Reactions 2 and 3 form
diastereomers and Reaction 4 cleaves the anhydride to retain the same chirality as the starting material.
Because the materiai is optically pure at the start, the product of reaction 4 is also optically purel The best
answer is choice A.
90.
Choice C is correct. Methyl antine, like all amines, is a good nucleophile. Tl-re first equivalent reacts with the
most reactive electrophile, which in this case is the epoxide ring. However, an anhydride is also highly
reactive. In the event excess amine is added, it can easily add to the carbonyi, cleaving the anhydride and
generating a carboxylic acid and amide. Choices A and B can be eliminated immediateiy, becar-rse the threemembered ring is highly unstable and will not reform once broken. The OH group is a bad ieaving group, so it is
not likely that an amine will substitute for the hydroxyl group, once the airhydride is cleaved, so choice D is
elimrnated. The result is that choice C is the best answer.
91.
Choice C is correct. In Reaction 2, a mixture of stereoisomers is formed that is never resolved. As a result, the
reactant in Reaction 4, Compottnd 5, represents a mixture of stereoisomers. Two of the chiral centers are the
same in all of the stereoisomers, so they cannot be enantiomers (where all of the chirai centers differ). This
eliminates choice A. The product is not meso, it does not have an internal mirror plane, so choice D is
eliminated. Because the mixture starts with optical activity, and Reaction 4 does nothing to affect the
chirality, the product mixture in Reaction 4, Compound 6, must be optically active. This makes choice C the
best answer.
92.
Choice A is correct. If you are well versed ir-r r-rsing the thumb technique, then you can place your thumb in the
direction of the C-H bond and curl your fingers from priorities 1-2-3 using a right hand for both stereocenters.
This makes both centers R. For some, it may be easier to rotate the molecule to the side view rather than using
the Newman projection to deterrnine the chirality. From the side perspective, it is much easier to see the three
dimensional orientation of the molecule. As shown in the determination below, the molecule has 2Ii., 3R
stereochemistry. Choose A; be a chem star.
CFI?
ocFi3
H in back; R stereocenter
OH
OH
H in back; R stereocenter
93-
Choice D is correct. With Fischer projections, you must remember that when an H is drawn on the side, it
represents an H coming out at you ln a three dimensional perspective. Hence, whatever arc you determine from
the Fischer projection must sutsequently be reversed to get the chirality of the stereocenter. in this example,
both chiral centers generate ciockwise circles in a two-dimensional perspective. But after reversing ihe
clockwise circles to counterclockwise becanse of the hydrogen atoms are in fiont, both centers have S chirility.
Choose D and be a scholar.
CH"
| '
1/l
rF+T-
\y
OH
-Fs.,,.
Clockwise arc r,r'ith H in front;
S stereocenter
ocF{3
Copyright O by The Berkeley Review@
253
STBREOCHEMISTRY EXPLANATIONS
94.
Choice A is correct. On the second carbon, the OH and H groups have interchanged, so that chiral center differs
between the two stereoisomers. On the third carbon, the OH and H groups have not interchanged, so tha:
chiral center is identical in the two stereoisomers. On the fourth carbon, the ethyl and methyl groups hale
interchanged, so that chiral center differs between the two stereoisomers. When two out of three (i.e., some
but not all) of the chiral centers differ, the two stereoisomers are neither superimposable, nor are they mirro:
images of one another, which defines diastereomers. Pick A and be jovial.
95.
Choice B is correct. In the molecule, carbons two and three are chiral centers. However, carbon one is not r
chiral center, because it contains two equivalent hydrogen atoms. The maximum number of stereoisomers i.
equal to 2n where n is the number of chiral centers in the molecule, which in this case is 2. This yields a total c:
fot.l (22) stereoisomers. Be stellar and choose B.
96.
Choice A is correct. Syn addition of equivalent to a trans double bond in an alkene results in the formation c:
two enantiomers (specifically the R,R and S,S enantiomers) as shown below. Choose A for best results. A mes:
compound can be obtained from syn addition to a cis alkene, where the aikyl groups are equal on the alkene.
H.C
\
Fi
/.,-, \
H
CFL
"
KMnOalaq)
__-+
pH=10
Syt-,addition
Trans reactant (asymmetric) (symmetric)
HO
\_J
OH
CFI"
. H:cr,l /-.,,,"H
c'
HrcY \"'*,
,,,Tt
H
HO
CH:
OH
As).rnmetric products
97.
Choice C is correct. If a compound has stereocenters but is not optically active, this implies that the compou:.:
must be meso. To be meso, a compound must have a mirror plane in the molecule about which the chiral centef.
are evenly displaced. This mirror plane slices the molecule into two equivalent halves. 2R,3S-dibromobuta:.=
and 2R,4S-dibromopentane each have equivalent mirror halves (thus mirror symmetry) so they are both me>:
compounds. Cis-1,3-dichlorocyclohexane has equivalent halves as wel1, thus it is a meso compound. Or-.
2R,4S-dibromohexane does not have two equivaient halves. The correct answer is thus choice C.
98.
Choice D is correct. 4-chlorocyclohexanol contains no stereocenters (chiral carbons), therefore it cannot rota.:=
plane polarized light. The result is that 4-chlorocyclohexanol is not optically active. Choose wisely ar.:
choose D. The other three compounds have two chiral carbons and therefore are all opticaily active. It:'
possible for the compound (4-chlorocyclohexanol) to exhibit isomerism in the form of geometrical isomers r.-'
and trans), but geometrical isomers do not rotate plane polarized light.
99.
Choice C is correct. Isoleucine contains two chiral centers, one for the alpha carbon and one in the side chaPlugging into the stereoisomer equation 2n, wl-rere n represents the number of chiral centers, there are tc..:
possible stereoisomers for the isoleucine structure. Because isoleucine contains two chiral centers that mu-.
have specific orientation, only one of the four stereoisomers has the correct chirality to be biologically use:...,
Choose C to be a successful point collector.
100.
Choice B is correct. For a compound with chiral centers to be optically inactive, it must be meso. and tt-.
contain an internal mirror plane of symmetry. The molecule must have R, S chiraiity to be meso. T-,-:
eliminates choices A ar-rd C. The mirror plane must be through the C2-C3 bond according to the chiral centers -:
the ansll'er choices. This mirror plane is possible only with butane, so the correct answer must be choice B.
Copr ri-sht O
STEREOCHEMISTRY EXPLANATIO\i
Section HV
Hydrocarbon
Reactions
by Todd Bennett
Alkanes
a)
b)
llydrocarbon R.eactions
a) Elimination Reactions
i. Ez Mechanism
ii" E1 Mechanism
iii. Carbocation Stability
iv" Electrophilic Addition
v. Regioselectivity
vi. Steneoselectivity
Geraniol
vii.
Stereoisomer Formation
Terpenes
a)
b)
c)
d)
Section Goals
aB
@?
base. Rearrangement can offer complications in an E1 reaction. E2 reactions require the acidic proton
and leaving group to be anti to one another.
"?
reaction is also found in sigmatropiclearrangements like the Cope and Claisen rearrangements.
You should have a basic understanding of n-systems.
Organic Chemistry
Introduction
features. Common
.reaction types incrude acid-base reactions (section 1),
nucleophilic substitution (section 3), free radical reactions (typically halogenation
of an alkane or polymerization of an alkene), elimination, electrophilic Jdditlon,
electrophilic aromatic substitution, electrocyclic reactions, oxidation-reduction
reactions, and carbonyl substitution reactions (section 5). There are other types
of reactions, name reactions, which we shall address by functiond grtlp.
However, in this section, we shall address the reactions of alkaner ur,a tt-r"
reactions of n-bonds, as classified by their mechanisms.
Free radical reactions follow three basic mechanistic steps: initiation,
synthesized.
Although the MCAT test writers do not require that you memorize the reactions
of alkenes, as they have required in the past, you are expected to know the
general classes of reactions that involve n-bonds. when the n-bond of an alkene
ac-ts- as a nucleophile by attacking an electrophile, this starts an
electrophilic
addition reaction. The ru-bond is not limited to being part of an alkene, u, lt .u1
also be part of a diene, triene, or any other conjugaied system of multiple rcbonds. V\4ren there is more than one n-bond in the system, we must consider the
possibility of the addition reaction occurring at different reactive sites. The
nucleophiiic n-bond can also be found on benzene, although the aromaticity of
the n-system drastically reduces the nucleophilicity of a r-bond. However, if the
electrophile is strong enough, the n-bond oi benrene can attack it and eventually
e>rqhange the electrophile for a hydrogen, retaining the aromaticity of the system.
This is known as an electrophilic aromatic substitulion. The last reaction we shall
consider for n-bonds is the Diels Alder reaction, an electrocyclic reaction
involving the addition of an alkene to a conjugated diene to form a cyclohexene
moiety.
From this section on, we shall focus on the reactivity of organic compound.s. To
best prepare for the MCAT, your goal shourd not be to memorize every reaction,
but instead, learn a few simple, common mechanisms and have a conceptual
picture of how they work. If you can summarize the contents of this secti,on in
terms of the nucleophilicity of a n-bond, no matter what compound contains the
rc-bond, then you have a solid grasp of the topic at the MCAr level. Reaction
details will be provided in the passage, so from this point on, know the general
reaction and work on your information extraction skills by reading graphs,
tables, and data charts,
257
Organic Chemistry
Alkanes
Alkanes
Alkane Structure
Alkanes contain only carbon and hydrogen atoms, and all of the carbons have
spr-hybridization. AII of the hydrogens in aikanes use s-orbitals to form bonds.
Alkanes are held together exclusively by o-bonds. In any alkane, there are only
two types of bonds present: C-C bonds (which are osD3-s'3) and C-H bonds
(which are oro3-r). Both types of bonds present in alkanis aie shown in Figure 4-
cffic
1 as molecular orbitals.
@.
orp3-tp3
os-sP3
Figure 4-1
CHa
Hexane
CoHra
Ethane
CzH.e
Heptane
CzHrc
Propane
csHs
Octane
CgHrs
Butane
C+Hro
Nonane
CsHzo
Pentane
CsHrz
Decane
CrcHzz
CsHo
Cycioheptane
CrF{u
Cyclobutane
C+Hs
Cyclooctane
CsHro
Cyclopentane
CsHro
Cyclononane
CsHra
Cvclohexane
CoHrz
Cyclodecane
CroHzo
Table 4-1
Copyright
258
Organic Chemistry
Alkanes
Alkane Properties
The physical properties of concern associated with an alkane are its solubility
features, its density, its melting point, and its boiling point. Alkanes are
hydrophobic, nonpolar molecules. They can also be defined as lipophilic, which
implies that they are highly soluble in oils such as the lipid membrane of a cell.
As with all compounds, their physical properties vary with mass and branching.
As the molecular mass increases, both the boiling point and melting points
increase. As the branching increases, the boiling point decreases. Table 4-2
shows the physical properties of several aliphatic alkanes. From the data in
Table 4-2, the effects of mass and branching on the physicai properties can be
observed.
Name
Isomer
Boiling
Point
Melting
Point
-762"C
-183"C
76.043
Density
Mass
(g/mL) (g/mole)
CH+
Methane
H3CCHe
Ethane
-89'C
-183'C
30.070
H3CCH2CH3
Propane
-42"C
-787'C
44.097
H3C(CH2)2CH3
Butane
0"c
-138'C
58.124
H3C(CH2)3CH3
Pentane
36'C
-130'C
0.557
72.151
H3C(CH2)aCH3
n-Hexane
69"C
-95.3'C
0.659
86.778
(HrC)zCH(CHD2CH3
2-Methylpentane
60'c
-754"C
0.654
86.1.78
H3CCH2CH(CH3)CH2CH3
3-Methylpentane
63'C
118"C
0.676
86.778
(H3C)3CCH2CH3
2,2-Dimethylbutane
50"c
-98"C
0.649
86.178
(H3C)2CHCH(CH3)2
2,3-Dimethylbutane
58'C
-729"C
0.668
86.778
H3C(CH2)5CH3
n-Heptane
98'C
-90.5"C
0.684
100.205
H3C(CH2)6CH3
n-Octane
126"C
-57"C
0.703
1.1.4.232
H3C(CH2)7CH3
n-Nonane
151"C
-54'C
0.778
128.259
H3C(CH2)sCH3
n-Decane
174'C
-30"c
0.7362
142.286
Table 4-2
Example 4.1
A, 228.21,grams,/mole
B. 266.51, grams/mole
C. 268.57 grams/mole
D. 280.54 grams/mole
Solution
First, we must determine the number of carbon atoms and hydrogen atoms.
Dimethyl accounts for two carbons, propyl accounts for another three, pentyl
accounts for another five, and nonane accounts for nine. The compound contains
19 carbon atoms totai. Because of the "cyclo" in the name, there is one unit of
unsaturation. The one unit of unsaturation implies that there are 38 hydrogens
(two less then the 40 that would be present in an aliphatic, linear alkane). The
molecular mass is thus 19(12) + 38 = 266, choice B.
259
Organic Chemistry
Alkanes
Alkane Reactivity
Alkanes undergo a minimal number of reactions, and the few they do undergo
involve free radical chemistry. The two reactions of concern are free radi&l
halogenation (more specifically bromination, using Br2, and chlorination, using
C12) and combustion. Reaction 4.1 is the free radical chlorination of methane.
CH+(g) + Cl2(g)
-il*
CH3CI(g)
+ CHrCtr(1) +
80%
70%
CHC13(I)
+ CCla(t) +
minor
C2Cl6(s)
minor
minor
Reaction 4.1
Free Radical Halogenation of Alkanes
A free radical halogenation reaction starts with the addition of activation energ\to cleave a halogen-halogen bond (the weakest bond in the reactants) to form two
free radical halogen atoms. A free radical is an atom, such as a halogen or
carbon, with one unpaired electron. According to the octet rule, most atoms wish
to have eight valence electrons. In a free radical, there are only seven, so free
radicals are highiy reactive. Figure 4-2 shows a 3-D perspective of four alkyl free
radicals with the p-orbital filled with one electron. The three substituents are
drawn slightly below the carbon atom, because the free radical molecule is
slightly trigonal planar due the electrostatic repulsion from the single electron.
Because the electron can exist in either lobe of the p-orbital, the substituents carr
be angied up or down, so the average of the two trigonal pyramidal forms is
planar' The stability of a free radical depends on its substitution. Tertiary free
radicals are more stable than secondary free radicals, which in turn are more
stabie than primary free radicals. Figure 4-2 shows the relative stability of the
alkyl free radicals.
o-6Xii.* '
"-6*gF
3" Free
radical
2' Free
radical
1' Free
>H.
Figure 4-2
Once a free radicai halogenation reaction has been initiated by the addition cr
light (activation energy), a free radical halogen atom then attacks an alkane anc
abstracts a hydrogen from the alkane to leave behind an alkyl free radical. The
halogen free radical abstracts the first hydrogen it encounters, but because alkr.
free radicals can react with other alkanes, over time the distribution favors the
formation of the more stable tertiary free radicals. The conversion from a
primary free radical into a tertiary free radical is shown in Figure 4-3 below.
t'.\
H*f
n,\
\-^*i
cH.cH,.
H:C
JQ_
HsC
cH"cH1----*
.,,,|
HaC
n,.\
cH"cH^
.|
cH^cH
HsC
The reaction in Figure 4-3 heavily favors the formation of product, because the
tertiary free radical is substantially more stable than the primary free radical.
Copyright
Organic Chemistry
Alkanes
ila
--------->
X.+.X
Reaction 4.2
Propagation:
tGi*
----->
R. + H-X
Reaction 4.3a
-c?a
-------> R-X +
.X
Reaction 4.3b
Termination:
n! *
'.R
------->
R-R
Reaction 4.4a
nli.x
------->
R-X
Reaction 4.4b
*li.*
Overall
--------> x-x
Reaction 4.4c
The sum of the propagation steps for a free radical halogenation reaction gives
the overall reactiort, Reaction 4.5. The initiation step is brief, for just a split
second at the start of a free radical reaction. However, the propagation steps
continue until the reaction is quencired or the free radicals are completely
consumed in termination reactions. There are always multiple termination steps
possible. One of the possible termination steps is the reverse of the initiation
reaction. A termination step is any reaction that combines two free radicals to
generate a stable compound. Termination steps are responsible for several minor
side products.
26r
Organic Chemistry
Alkanes
Example 4.2
A.
B.
C.
D.
+ Br. -) H3CCH2CH2BT
+ H3CCH2CH3 -+ H3CCH2CH3 +
Br2 -) H3CCHBTCH3 + Br.
HOBr --> HO. + Br.
H3CCHzCHz.
H3CCH2CH2.
(H3C)2CH. +
@3C)2CH.
Solution
In an initiation reaction, free radicais are generated, so the product side has more
radicals than the reactant side. Choice A is eliminated, because there are fewer
radicals on the product side, making it a termination reaction. In choices B and
C, there is the same number of radicals on both sides of the reaction, so they are
propagation reactions. This elimrnates choices B and C. In choice D, the reaction
goes from zero free radicals on the reactant side to two free radicals on the
product side, so it is an initiation reaction.
Example 4.3
In the free radical chlorination of ethane, butane is a minor side product. Horr'
can this best be explained?
A.
B.
C.
D.
Solution
An ethane molecule has neither a lone pair of electrons nor an available pair o:
bonding electrons to share (like a n-bond), so it is definitely not going to act as a
nucleophile. This eliminates choice A. An ethyl free radical can definitel,,'
remove a hydrogen from an ethane molecule. However, that does not resuit ir.
the formation of butane, it simply regenerates the same molecules.
ne\^.'
sigma bond between the two free radical carbons. Combining the two twocarbon fragments results in the formation of a four-carbon fragment. The resuL:
is that butane is formed from the termination reaction of two ethyl free radicals,
The best answer is choice C. Carbon-carbon bonds are not easily cleaved, so the
activation energy added in the initiation step is not high enough to cleave a
carbon-carbon bond. Even if it could cleave the carbon-carbon bond to forr.
methyl free radicals, there is iittle likelihood that four CH3 groups woulc
combine to form C+H1O. The loss of two hydrogen atoms would not occur.
262
Organic Chemistry
Alkanes
AHi.itiatic,n = 58 kcal
AH1 =
I ks.1
AH2 = -26kcaI
Figure 4-4 shows the energy diagram associated with propagation steps in
Reaction 4.1.
HCl + CH3
fr
overall AH = AHr
CJ
tr.l
CH3C1 +
OJ
Reaction Coordinate
Figure 4-4
X=F
Halogenation Reaction
kritiation; X2
-+
2X.
X. + CHa -+ HX + H3C.
H3C" + X2 --+ H3CX + X.
CH4 + X2 -+ H3CX + HX
X=Cl
X=Br
X=I
38
58
46
36
-32
+1
+76
+33
/t)
-26
-z+
-20
-102
-25
-8
+13
Table 4-3
Copyright
Organic Chemistry
Alkanes
Because tertiary free radicals are more stable than other free radicals,
halogenation occurs preferentially at tertiary carbons. When there is more than
one unique carbon in the alkane reactant, the product distribution is a result of
cl"
__>
$.,
hv
c+Hro
77.7"/o Secondary
28.3%
Primary
Br
Br,
hv
C+Hro
.t\-/
$Br
97.6"/o Seconda ty
2.4"h Prirnary
Figure 4-5
As a general rule, slower reactions are more selective than faster reactions,
because reactants have more time to select the best site for reacting. Chlorination
reactions are faster than bromination reactions, so bromination is more selective
>\+X2grb.hx
Reaction 4.6
Trial
Halogen
Temp (K)
Br2
II
III
IV
V
Clz
Btz
Clz
12
Product A
Product B
298
03%
89.40/"
70.1%
0.2%
298
29.1%
243%
32.00/"
t4.6%
0.4%
88.3%
1,L.1%
0.2%
aa ao/
LL.L
/O
27.8%
No Rxn
No Rxn
T6]%
No Rxn
J/J
J/J
373
JJ.J
70
No Rxn
Product C Product D
Table 4-4
Copyright
264
Organic Chemistry
Alkanes
The data in Table 4-4 confirms that bromination is more selective than
chlorination for tertiary over secondary over primary. Bromination is slower
than chlorination, but it should also be noted that bromination is more reversible
than chlorination, so it is more likely undergo a reverse reaction from an unstable
product to ultimately form the most stable product. The data in Table 4-4 also
shows that temperature has an effect on the reaction rate and therefore on the
selectivity. As the reaction temperature is increased, the reaction proceeds at a
faster rate, resulting in the formation of products based more on random
probability rather than selection for the most stable intermediate. In addition,
Boltzmann's law states that as energy is added to a system, the distribution of
compounds is shifted to the less stable compounds, to absorb the energy.
Actually, who reaily knows if Boltzmann said it, or if it's even a law. The key
thing is that as energy is added, less stabie compounds are formed.
Example 4.4
\44ry in Trial
II of Table
B?
A.
B.
c.
D.
Product A results from the more stable free radical, thus it is selected for.
Product B rearranges to form product A.
Product B is more stable, but there are more hydrogens that lead to product
A, so overall less Product B is formed.
Product A is more stable, but there are more hydrogens that lead to product
B, so overall less Product B is formed.
Solution
Product A results from a reaction at a primary carbon, so it proceeds via a
primary free radical. Product B results from reaction at a tertiary carbon, so it
proceeds via a tertiary free radical. This eliminates choice A. Rearrangement is
seen with carbocations, but not with free radicals or carbanions, so choice B is
eliminated. The best answer is choice C. It is often possible to answer a question
without fuil analysis. The reason for the substantial amount of Product A is
because there are six hydrogens that lead to Product A while there is only one
hydrogen that leads to Product B. Although tertiary reactivity with chlorination
is roughly four to five times greater than primary reactivity, the six-to-one
abundance ratio outweighs the four or five-to-one reactivity preference, making
the probability of forming Product A greater than the probability of forming
Product B. This is makes choice C the best answer. Choice D can be eliminated,
because there are more hydrogens available to form Product A than Product B.
Copyright
Organic Chemistry
Alkanes
Example 4.5
C.
D.
Solution
Because chlorine and bromine form free radicals, we can be assume that another
halogens, such as iodine, can also form a free radical. This eliminates choice A.
Iodine is lower in the periodic table than chlorine and bromine, so the iodineiodine bond is weaker than the chiorine-chlorine bond and the bromine-bromine
bond. Because Cl2 and Br2 are cleaved, it is safe to assume that 12 is even easier
to cleave. This eiiminates choice B. Iodine forms weak bonds to carbon and
hydrogen, so the products are less stable than the reactants. Because the
products of free radical iodination are less stable than the reactants, the reaction
is unfavorable, so there is no reaction observed with iodine. This makes
choice D
the best answer and eliminates choice C. Fluorine is not used for completely
opposite reasons. Fluorine forms strong bonds to carbon and hydrogen, and
th!
fluorine-fluorine bond is weak. The products are so much more stable than the
:j'"",,^"
t'""
",
Example 4.6
A.
B.
c.
D.
The acldition of the halogen makes the alkyl halide less acidic than the
alkane, so it is less reactive to subsequent halogenation reactions.
The addition of the halogen makes the alkyl halide more acidic than the
alkane, so it is more reactive to subsequent halogenation reactions.
After the first halogen is added to the alkane, the carbon-hydrogen bonds
grow weaker and thus more reactive.
After the first haiogen is added to the alkane, the weakest bond is a carbonhalogen bond and not the carbon-hydrogen bond. As a result, it is easier to
remove the halogen rather than the hydrogen from the mono-substituted
alkyl halide.
Solution
Halogens are electron-withdrawrng, so their presence on a molecule increases its
acidity. This eliminates choice A. Choice B is invalid, because an increase in
reactivity would imply that more poly-halogenated products would form, not
less. Choice C can be eliminated for almost the same reason. If the carbonhydrogen bond is weaker, and thus more reactive, then it would be easier to add
a_second halogen than the first, making poly-haiogenation preferable. once an
alkane is haiogenated, the weakest bond is the carbon-halogen bond, not a
carbon-hydrogen bond. If a second halogen free radical ruuit, with an alkvl
halide (rather than an alkane), it preferentiully r"rr,orr"s the halogen (breaking the
weakest bond), forming a non-halogenated alkyi free radical. this is because the
reverse halogenation reaction (in propagation) is more favorable than the
removal of a hydrogen and subsequent additional halogenation reaction. Choice
-1.
-j
-,1L
ts
(-
5-c
:._
:_
-:
"'*.
Iopyright O by The Berkeley Review
:f
Organic Chemistry
Alkanes
Example 4.7
A. Bromination at25"C
B. Chlorination at25'C
C. Bromination at 100"C
D. Chlorination at 100'C
Solution
Using the data listed in Table 4.3, what percent of the mono-halogenated
products is 2-bromo-2-methylbutane following the free-radical bromination of 2methylbutane at75"C?
A. 88.1%
B. 88.7%
c. 89.1%
D. 89.7%
Solution
To answer this question, you need to read Table 4-3. In trials I and III, product B
is 2-bromo-2-methylbutane. Therefore, we need to estimate how much Product B
is formed at75"C. At25'C, there is 89.4% product B formed, while at 100"C there
is 88.3% product B formed. This means that the amount of product B formed at
75'C should be between 88.3% and 89.4o/o, which eliminates choices A and D.
The amount formed at75'C should be closer to 88.3% than89.4"h, so choice B is
the best answer.
Example 4.9
How many mono-chlorinated structural isomer products are possible when 2,5dimethylhexane undergoes free radical chlorination?
A.3
8.5
c.6
D.8
Solution
This question is asking for how many structural isomers there are for chloro-2,Sdimethylhexane. Because of the mirror plane through the carbon 3-to-carbon 4,
bond, there are three unique carbons on 2,5-dimethylhexane. This means that
there are just three carbons that can be chlorinated, so there are only three monochlorinated structural isomers. If stereoisomers were included, the value would
increase to four, given that chlorination of the secondary carbon yields a
stereogenic center. The best answer is choice A.
Copyright
267
Organic Chemistry
Aydroiberbdh
tlydrocarbon Keactions
Radtiddb
,,-,,.,*,,,,,,r',i,,,t,,,,,,,f,,,,
Elimination Reactions
The reaction that forms an alkene from a substituted alkane is elimination. It is
named from the fact that a functionai group and a hydrogen on adjacent carbons
are eliminated in order to form a n-bond. The-reac-tion requires elevated
temperatures to help overcome the activation energy and to p.rsh the reaction in
the forward direction. Like the nucleophilic substiiution ,*u.tior,r, there are two
reaction mechanisms, appropriately named E1 and E2. As with nucleophilic
substitution, the two versions are named also for theiireaction orders (kinetic
rate dependence). E1 is similar to sry1 and E2 is similar to slr]2, except that the
product is an alkene. In an E1 elimination, the leaving gto.rp first ieaves and
there is a carbocation formed. The empty p-orbital of thi c"arbocation eventuallrbecomes one of the two p-orbitais in the new n-bond. In an E2 elimination,
a base
removes an alpha hydrogen to force the leaving group off of the neighboring
carbon. Elimination converts a functionarized alkyigroup into an alkenJ.
E2 Reaction (Carried out under Basic Conditions at High Temperature)
The E2 reaction is corrcerted (one-step) rike the sNI2 r;action, with one major
exception being that the E2 reaction occurs at higher temperatures (temperatuies
above ambient temperature) than the S52 reaction. An E2 reaction also requires
that the base be bulky. Because of the steric hindrance aisociated with a bulky
base, it is.less apt to act as a nucleophile and thereby minimlze in;;;;fi;;
Sp2 reaction. An important feature of the E2 reacti-on is that the substituenti
being eliminated must be onti to one another (have a dihedral angle of 1g0.). The
mechanism for an E2 reaction is shown in Figure 4-6.
(^
oR-
R:
o
I
-----+
H,CV
H
H
X-
H
H3Ctt,,)
HgC
(trrH
H
Figure 4-6
group must be oriented anti to the hydrogen being eliminated before the base
attacks the proton to start the reaction. whenever there are two alpha hydrogen,.
that can be eliminated from the starting reagent, there are two posiible prodicts.
The consequence is that when the starting material has a specific stereoChemistl'
268
r.:
Organic Chemistry
DH
\
LINR^
----1-
EJ
^/\ H:C
Bt
LiNR,
H.C
CH:
CH:
F<
--+
llydrocarbon Reactions
cHs
Figure 4-7
HH
><
HsC
CHs
CH:
Multiple products can result when their are multiple hydrogens available for
deprotonation. In Figure 4-7, onry the products with in iniernai n-bond are
drawn. The internal n-bond is more favorable then the terminal n-bond by about
1.5 kcals, making 1-butene a minor side product in the reaction
in Figure [-2. rn"
relative stability of substituted alkenes ii shown in Figure 4_9.
\_J
R'
R'''
\_-/
R''
Tetrasubstituted
R'
R''
Trisubstituted
HR
Disubstituted
\--/
H
Monosubstituted
Figure 4-9
Terms such as anti-periplanar orientatiott should sound familiar and immediately
make you think of an F2 reaction. Any time you see a strong bulky base, a
hydrocarbon with a leaving group, and high temperature, you should think
of an
E2 reaction.
Copyright
Organic Chemistry
tlydrocarbon Reactions
the sI.J1 reaction. In both the E1 and sNJ1 reactions, there is (1) a carbocation
intermediate formed after the leaving group leaves in the rate determining step
of the reaction and (2) the possibility of rearrangement with the carbocation
intermediate. A schematic for a typical E1 reaction is shown in Figure 4-10.
HsQ
OH
oHz
--+
-n
------>
+ Hro
,rg,
T'.';*1f\'" '
Hb\
-HA
HJ
H"C
Hb
i
CH,
><J
CHs
Ha
Figure 4-10
To recognize E1, as opposed io E2, it is easiest to look at the reaction conditions
E1 reactions are best carried out under acidic conditions while E2 reactions
.atll*
H-'-'--.-H
."O
'\)
HO:
s- ::.
..S"1:.t,
H3c$\'7-l -:
*r"au"R
HsC
HrC /,
\SH2CH3
CHs
1t
l,,rt\\
CH, cH2cH3
,?
_-H
r.3
Urclrr,,rp-W,
rrrttl CH2C
H,c7\ts-{./
/F.",
H.
CH:
Figure 4-11
Copyright
Organic Chemistry
Ilydrocarbon Reactions
Example 4.10
A.
B.
CHz
cHs
Solution
At an elevated temperature in the presence of a strong acid, the reaction proceeds
by an E1 mechanism, so the product is a highly substituted aikene. Choice A is
eliminated, because it is a terminal alkene. Choice B is eliminated, because it is
an alkane and not an alkene. Choice D is eliminated, because it is not the most
substituted alkene and it formed via a secondary carbocation, a less stable
intermediate than the tertiary carbocation. The best answer is choice C, because
the n-bond is highly substituted and it includes the tertiary carbon, implying that
it was formed via a tertiary intermediate.
Rearrangement is possible with carbocation intermediates, so E1 reactions are
susceptible to forming rearranged products. Hydride and alkyl shifts are rapid,
intramolecular processes that occur before the soivent can remove the
neighboring proton to form an alkene.
Carbocation Stability
Because carbocations are common intermediates,
".. 'slx:
3"
Carbocation
:6"'"
o:.
)@..,,,trtu
1'Carbocation MethylCarbocation
Figure 4-12
The conclusion that can be drawn from the relative stability of alkyl carbocations
is that methyl groups are electron donating to electron poor carbons, which can
be extrapolated to say that alkyl groups are electron donating. Figure 4-13 shows
three rearrangements where a less stable carbocation is converted into a more
Copyright
277
Organic Chemistry
llydrocarbon Reactions
)'w;*
----->
HI
"\_
o_,/cylH
'H
H2"
"Yt-t\r,
1'
CH"
H\ l''
-------->
.1--.n,
nf-.vn
HHHH
\/\/
H ------> c-c-\
H
/
o /'
/c-c \
3"H
o/
"YJt"
l"
,,f-'Y#.,
2"
Allvlic
Figure 4-13
A.
B.
C.
D.
(H3C)3C+
(H3C)2CH+
H3CH2C+
(H3C)2CHCH2+
Solution
Choice A is already a tertiary carbocation, so it has no reason to rearrange, least
of all to a primary carbocation. Choice A is eliminated. Choice B is a secondarr-
272
Organic Chemistry
flydrocarbon Reactions
----------tStep
Figure 4-14
After the electrons from the n-bond are donated to the electrophile, a positive
charge is situated on the most substituted carbon of the original alkene in the
carbocation intermediate. This is the first step in almost all electrophilic addition
mechanisms. In the second step of the mechanism, a nucleophile attacks the
carbocation formed in the first step of the electrophilic addition reaction. The
second step of a generic electrophilic addition reaction is shown in Figure 4-15.
H-Nu:J
\-/'
-----------.r>
\
SteP
H-Nuc
II
H-Nu
Figure 4-15
-\
\lll
L-#
\-/
\-,/t
----------.>
(workup)
Step
Solv represents any polar/protic solvent
Figure 4-16
A protic solvent is capable of forming hydrogen bonds and transferring protons.
Copyright
273
Organic Chemistry
tlydrocarbon Reactions
to
dienes and to recognize the class of reaction. Know how to diaw the reaction if
they describe the mechanism for the reaction in words. The MCAT doesn't focus
much on memorization. The focus is on conceptual understanding, so be certain
that the corresponding terms such as Markovnikov, syn and anti ire completeiy
Copyright
274
Organic Chemistry
llydrocarbon Reactions
H2C:
z- CH
-\
L
H:SOq{aq)o"c
HC_ CH2
H,c-.')ot
"r.\
HC-
ttr.CH2
62%
HC-
CH2OH
38%
1,2-AdditonProduct 1,4-Additonproduct
H
H.C.\
CH
HC-
H2SO,1(aq)
CHz
l-hLc)ot
'
H,c'r-\
cH
50"c
HC-
CH2
16%
HC-
CH2OH
84%
1,2-Additonproduct 1,4_Additonproduct
Figure 4-12
In the example in Figure 4-77, there are two possible carbocation intermediates.
The mechanism and both intermediates ur" ,ho*r, in Figure 4-1g.
To start the
reaction, the proton adds to the terminal carbon (least hiidered carbon)
leavi'g
the carbocation on carbon two (a secondary carbocation). The carbocation
is
allylic meaning it can resonate through tie n-network. It is in essence a
propylene cation that can have cationic density at either end of the rc-network.
What this means is that the carbocation can resonate to the terminal carbon
(carbon number four). This forms a primary carbocation, whicl-r is
not as stable
as a secondary carbocation. According to the Boltzmann distribution law,
as
temperature increases, the higher energy levels become more populated to
absorb this increase in energy. This means that at higher temperatures
there are
more primary carbocations than at lower temperatuies. This is why we see
the
product distribution favoring substitution of the alcohol at carbon two at lower
temperatures while we at higher temperatures we observe the substitution
of the
alcohol at the fourth carbon. Figure 4-18 shows the energy diagram and
mechanism associated with this reaction, which includes t*o poisiute
iuth*uyr.
275
Organic Chemistry
Pathway
Kinetic
Ilydrocarbon Reactions
Thermodynamic Pathway
HO
I
rirC=Cri :HrC-C^\
'
\
HC:CH2
-J
H3C-CH
o/,
.e
)^)^..
HC:CH2
1f.""
H@
HsC-.i""'
HC:
\HC-C@/H
'
1f.""
H?C"\o
CH
HC-
CH2
H*
1r
HeC"\
CH2OH2
1f".
>oH
H"C"\
C-
\
HC:
CH
HC-
CH2
CH2OH
Monosubstituted alkene
Disubstituted alkene
is least stable
is most stable
1" carbocation
Reaction Coordinate
*--*-+
Figure 4-18
The energy diagram shows the two possible pathways for the reaction and their
Organic Chemistry
Ilydrocarbon Reactions
Pericyclic Reactions
Pericyclic reactions involve the repositioning of both sigma-bonds and pi-bonds
through a cyclic transition state. These reactions are believed to be concerted,
meaning that the formation and breaking of all bonds occur simultaneously.
Pericyclic reactions include cycloaddition reictions,which most notably include the
Diels-Alder reaction, sigmatropic rearrnngement, and electrocyclic reactiors. We will
address only cycloadditions and sigrnatropic rearrangement. The significant
difference between a cycloaddition reaction and sigi-Latropic rearrangement
involves the number of molecules. In cycloaddition, two separate compounds
Diels-Alder Reaction
The Diels-Alder reaction, an electrocyclic addition reaction, involves the addition
of a conjugated diene (4 n-electrons) to an alkene (2 n-electrons) to from a six
membered cyclohexene ring. The transition state for a Diels-Alder reaction is
similar to the resonance of benzene, as shown in Figure 4-19.
49
_->
dieneophile
cyclohexene derivative
.A
(
22"
,(+
4
o
1
CHs
cH2cH2
2//\6
^*ll3\-/s l+
4
CHg
cH2cH3
Second: draw the rest of
the molecule connected
to the numbered carbons
Figure 4-20
Copyright
Organic Chemistry
Hydrocarbon Reactions
The six membered ring that is formed is cyclohexene. The carbons are numbered
to help identify the product, which will make large, polycyclic products easier to
evaluate. Figure 4-21 shows a more complex Diels-Alder reaction. Because both
the diene and dienophile have substituents, there is a chance that stereoisomers
can form. The stereoselectivity is driven by orbital overlap in the transition state.
The two stereoisomers products, diastereomers, are drawn for the reaction.
ro
^*:o:::;1"
no
Endo Product
Figure
Exo Product
4-21.
The last thing for us to consider is regioselectivity. when the diene and
dienophile have substituents, there exists the potential for different structural
isomers. Regioselectivity can be predicted using resonance, where the most
electron rich terminal carbon of the diene attacks the electron poor carbon of the
dienophile. The reaction is optimized when the dienophile has electron
withdrawing groups. Figure 4-22 shows the effect of electron donating and
electron withdrawing groups on the diene through resonance.
EWG
/)
EW G
t)
4
<:+
l-/
<)
l_-.-.
EDG
EDG
'a:
Figure 4-22
H?co
zl.
.s-
o
H
--+
6*
H3CO
Major
CHs
Figure 4-23
Copyright
Organic Chemistry
flydrocarbon Reactions
Example 4.12
\A/hich of the following Diels-Aider reactions is
fastest?
A.
2
l*
HrC\
4.", --+
ll\A
CHe
CHa
B.
2
l*
nrao\
4.". -^tlCHa
C.
CHa
H3CO
,4.',,
(+
Ar-
H.c^
H:C
CH:
-CHs
cHs
D.
2
I,
-^>
"r.o\
CHs
H3CO
Solution
The rate of a Diels-Arder reaction is increaseci by
the presence of an electron
donating_ group on the diene and an erectron
withdrawing group on the
dienophile. The rate of a Diels-Alder reaction is decreased
by the presence of
bulky groups in the transition state. Choices C and D are
eliminated because of
the two methyl groups on the dienophile. No matter
how the molecure aligns
entering the transition state, one of the methyl groups wiil
be in the way. In
choice B, there is a methoxy group on the diene, *-hil" ,^
choice A is just a methyr
Methoxy groups donate electron density through resonance, so choice
,grou.p.
B
has the more electron rich diene, resulting in a faster
reaction than choice A.
Cope Rearrangement
The Cope rearrangement is a sigmatropic rearrangement
i.vorving two pi-bonds
and one sigma-bond. Figure 4-24 shows a simpl"e Cope rearrangement
carried
out on a 1,S-diene. In more comprex examples, stereo.i-rerr-ristry
rnay be an issue,
because stereocenters can be both formed and rost
as hybridizaiior-, changes.
HaC
'G
-\g
A
--+
4
,-,,.4,
Figure 4-24
Copyright
279
Organic Chemistry
Hydrocarbon Reactions
The Cope rearrangement involves two pi-bonds and one sigma-bond aligned in
such a way that the terminal p-orbitals of the two pi-bonds are close enough to
overlap. The reaction requires the input of energy to overcome the activation
barrier. The structure of the product is dictated by the orbital overlap in the
transition state.
Claisen Rearrangement
The Claisen rearrangement is similar to Cope rearrangement, except that in a
Claisen rearrangement, the reactant is a vinylic allyi ether. The rearrangement
involves two pi-bonds and one sigma-bond and has a transition state that is
similar to the one observed with the Cope rearrangement. The difference is the
presence of an oxygen. Figure 4-25 shows a Claisen rearrangement.
as
o^
---l>
A
\,
Figure -l-25
when the ether is benzylic instead of vinylic, the cyclic ketone can quickly
tautomerize to form a phenol. The preference of a phenol over the cyclic ketone
is due to the aromaticity of the benzene ring.
Example 4.13
\z\4rich statement is
A.
B.
c.
D.
Solution
Choices C and D are eliminated immediately, because Cope rearrangement
results in the conversion of one 1,5-diene into another 1,5-diene, not an aidehyde.
The question is reduced to determining which carbon in the reactant forms the
carbonyl group following Claisen rearrangement. The reaction is shown be1ow.
H
vinylicT\
I
aidehyde
altvtic
etner
---l>
It is the vinylic ether carbon that becomes the carbonyl carbon, not the allylic
ether carbon. This means that the vinylic ether carbon must only have a
hydrogen, and no carbons, in order to form an aldehyde and not a ketone. The
best answer is choice B.
Copyright
Organic Chemistry
Terpenes
Terp,he$
Classification
Terpenes and terpenoids, btological molecules derived from terpenes, are
natural hydrocarbons found in plants and animals that are made from S-carbon
isoprene (2-methyl-1,3-butadiene) units. The five-carbon skeleton of isoprene can
be found in terpenes. Terpenes are classified by their number of carbon atoms.
Monoterpenes have ten carbon atoms, sesquiterpenes have fifteen carbons,
diterpenes have twenty carbons, sesterterpenes have twenty-five carbons and so
on, The in aitro synthesis of terpenes and terpenoids is called nstural product
synthesis. Some naturally occurring monoterpenes are shown in Figure 4-26.
CH,O
gH
Geraniol
(Oil of Germanium)
Myrcene
(Oil of Bay)
Citronellol
Citronellal
N"
r
Limonene
(or Limin)
tt
Y\oH
^
i
Carvone
(Oil of Spearmint)
(Oil of Lemongrass)
H"C. -CH"
"XJ
t'
u?
lS
."-\1./
Citral
y-Terpinene
(Oil of Coriander)
CH"
o,-Terpinene
(Oil of Coriander)
LR
HeC
CH:
Camphor
cr-Pinene
Menthol
CH.O
(Oil of Turpentine)
(Oil of Peppermint)
Figure 4-26
Studies in biogenesis show that the large terpenes are synthesized using
isopentenyi pyrophosphate rather than isoprene. Pyrophosphate adds across the
L,
Isoprene
o-
oo
ilil
P-
ll
o-
P-
oo-
o-
oH
oo
illt
P-
tl
o-
P-
oH
o-
oDimethylallyl pyrophosphate
Isopentyl pyrophosphate
Figure 4-27
These molecuies add to one another in a way where the n-bond of isopentyl
pyrophosphate is the nucleophile and pyrophosphate of another molecule is the
leaving group. A proton is lost from the nucleophilic moiety to regenerate a rubond. The reaction involves head-to-taii addition. When cyclizing, the bond that
is formed to complete the ring is rarely connected head-to-tai1. Figure 4-28 shows
the reaction of isopentenyl pyrophosphate and dimethylallyl pyrophosphate.
281
Organic Chemistry
oo
ll
il
Geranyl pyrophosphate
Isopentyl pyrophosphate
oo
ll
Terpenes
oo
ilil
ll
- r
HO- P- O- P- O- Y
HO- P- O- P- O
tt
o-
o-
Figure 4-28
Both plants and animals synthesize terpenes. Larger terpenes are built from
multiple additions of isoprene units, including both isopentenyl pyrophosphate
and dimethylallyl pyrophosphate. Geranyl pyrophosphate (a C-10 terpene
derived from the head-to-tail connection of two isopentenyl pyrophosphate
molecules) is the first monoterpene in many natural synthetic pathways.
Another isoprene unit can be added to geranyl pyrophosphate to form farnesyl
pyrophosphate (a C-15 terpene). These molecules can undergo further addition,
dimerization, or modification into other terpenes and terpenoids. Figure 4-29
shows a generic pathway for the biosynthesis of larger terpenes.
l"o
loo
I
4./\o-li-o-ll-o.,
tt
o-
o-
Isopentyl pyrophosphate
(3-Methyl-3-butenyl pyrophosphate)
,.^^o-ll_o_ll_on
or
,
I
Dimethylallr, Orr3pn"rf,i","
(3-Methyl-2-butenyl pyrophosphate)
Isopentyl
{PFophosthate
oMonoterpenes (C1s)
sesquiterpenes
+_
Farnesyl pyrophosphlt"
(C15)
(C,5-pyrophosphate)\
tt o- P- oH
O- OP-
tt
o-
o-
\
squalene
tsoPentYl
I
rr-"r--""r-."".I pyrophosphate
Diterpenes(C2s)
Geranyl pyrophosphate
(C1o-pyrophosphate)
oo
illt
C2g-pyrophosphate
I
Tetraterpenes (Ca6)
(c36)
Lanesterol (C36)
{
Chloesterol (C27)
Figure 4-29
Copyright
282
Organic Chemistry
Terpenes
oo
ilil O- P-
j.
-P-
OH
f"
Isopentenyl pyrophosphate
Figure 4-30
As a general rule, smaller terpenes are found primarily
,larger
terpenes,
larger terpenes.
Elemene
(oiiofCoral)
Farnesol
Z+
?or
G-Selinene
(Oil of Celery)
(Oil of Lemon)
"
Vitamin
HeC
.A,1
CH:
CHg
CHs
OH
Figure 4-31
Copyright
283
Organic Chemistry
Terpenes
One of the skills that you must deveiop to do well on terpene related
questions on the MCAT is to recognize terpenes and be able to identify the
isoprene subunits in the carbon skeleton. Figure 4-32 shows the analysis of some
terpenes for the isoprene units in the skeletal fragments.
^4{
Me
+Me
o,-Terpinene
^'r ,-
Me
ll t
,ll
t,,-=A'
Me
y-Bisabolene
"*A
+ix
^4;
Zingerberine
Patchouli Oil
Figure 4-32
Copyright
284
Organic Chemistry
Section Summary
Alkanes
1'
i.
ii.
iii.
b)
i.
ii.
iii.
a)
i.
ii.
iii.
b)
E1 reactions are
i.
ii.
iii'
c)
E2 reactions are
i.
ii.
iii.
2. ElectrophilicAddition
a) An electrophile can be added to a n-bond followed by nucleophilic attack
i. The n,bond is a weak nucleophile
ii. The reaction is driven by the strength of the electrophile
b) Electrophilic addition reactions exhibit regioselectivity
i' Steric hindrance and carbocation stability influence the site of attack
ii. when the electrophile attacks the ress substituted carbon, the
reaction is said to be a Markovnikov addition
iii. when the electrophile attacks the more substituted carbon, the
reaction is said to be an anti-Markovnikov addition
c)
Copyright
Organic Chemistry
3.
Section Summary
1,2-Additionversus 1,4-Addition
(kinetic
control)
temperatures
(thermodynamic controi)
4.
Diels-AlderReaction
a)
i.
ii.
iii.
iv.
5.
a)
Both sigma-bonds and pi-bonds are broken and formed via a cyclic
transition state
i. Cope rearrangement converts a y,8-unsaturated alkene into another
y,8-unsaturated alkene via a realignment of molecular orbitals
ii. Claisen rearrangement converts a vinylic allyl ether into another y,5unsaturated carbonyl via a realignment of molecular orbitals
iii. Sigmatropic rearrangement requires heat
Terpenes
1.
a)
b)
Copyright
286
(r -7)
(B
14)
(r5 - 2t)
(22 - 28)
(2e - 35)
(36 -
4t)
(42 - 48)
(4e - 54)
(s5 - 60)
(6r - 67)
(68 - 73)
(74 - BO)
(81 - 86)
(87 - e2)
Kaw Score
MCAT Score
84 - 100
l5-15
66-85
47 -65
10-12
7 -9
34-46
4-6
t-33
t-5
(e5 - loo)
Passage
(Questions 1 - 7)
4.2
B. 3
c. 4
D.
4.
of 2-methylbutane?
A.
B.
C.
D.
abundance
This means that the chlorination product ratio is six lchloropentane to ten 2-chloropentane to five 3-chloropentane.
1.07 2-chlorohexane
A.
A. 0
B.
C,2
D. 3
A. 5
B. 6
C.
D.
c.1
.
B.
C.
D.
A
D.
a ratio of
3-chlorohexane be
expected.
B.
to one
explarned?
compound C5H9C1?
1-bromo-3-methvlbutane
5.
2-bromo-3-methylbutane
1-bromo-2-methylbutane
2-bromo,2-methylbutane
A. 2:3
B. 5:3
c.2.5:1
D. 3:
primary. The
289
Passage
ll
(Questions 8 - 14)
9.
B.
I
bo
nE
Compound
F2
154
kJ
-483
mole
Clz
n9
kI
193
kJ
149
114
kJ
-33
kJ
mole
1
1.
A.
B.
C.
D.
Equation
Reaction Coordinate
t1'.. kJ
kJ
Table I
Reaction Coordinate
mole
mole
AHr^n =
Reaction Coordinate
A.XZ + R.
RX + X.
->
B. RH + X.
-> HX + R.
C.Xz
2X.
->
D. X. + R.
-> RX
kJ
mole
mole
I2
0.
mole
mole
Br2
AH.t
B.D.E.
Reaction Coordinate
12.
the monobromination
of (R)-3-methylhexane is best
A. RH + X.
RX + H.
B. XZ + R. -> RX + X.
->
C. RH + X.-> HX + R.
D. X. + R.
RX
->
described as:
A.
B.
C.
D.
primary.
seconclary.
tertiary.
quatefnary.
290
13.
Passage
I.
II.
bond strength.
A. II only
B. III only
C. I and II only
D. I and III only
Br
1
4.
'
-->
CHrCH'
><
CH2CHj
H:C
kJ
CHr
Reaction I
mole
C.
rbutOK
t-butOH
B.
HqC
CH"
A. - 483
III.
lll
-lt6 kJ
rnole
+116 kJ
mole
D. + +83 kJ
mole
15.
Trial
(H3C)3CBr
t-ButOK
Rate
0.25 M
0.25M
il
0.50 M
0.25M
9.29
III
0.40 M
0.50M
x t0-3 Mls
1.47 x 10-2 Mts
D.
291
16.
20.
A.
B.
A.
B.
C.
another.
D.
it
17. The
A.
B.
C.
21
the
and
A. 0
B. I
c.2
D.3
I
8.
Br
CH:
H$t),
H:C
A.
CHzCHT
",$.".
Br
B.
CH:
H
CH2CH3
CH2CHj
c.
Br
D.
Br
;"4; ;"V:
CH2CH3
CH2CH3
pru
rea{
reag
19.
)'t
A. 2R, 3R
B. 2R, 35
C. 25,3R
D. 25, 35
Copyright @ by The Berkeley Review@
292
copl:
Passage
lV
(Questions 22 - 28)
23.
A.
B.
C.
D.
24.
conc.
HrSOa
Major Product
(crp=6';
60-
CHr
A.
B.
C.
Yg
t-butOK
-----'+
D.
t-butOH,50"C
II:
&
&
CI
Reaction
II only
Reactions II and III only
Reaction III only
cH3
Reaction I:
CI
Reaction
Reaction I only
Reactions I and
25
t-butOK
-..+
rbutOH,50'C
I.
in Reaction I
II.
at
lower temperatures.
III:
OH
conc. HrSOa
_->
60'c
product. Among the minor side products for each of the three
reactions is the alkene products from one of the other two
2.
different major
B.
C.
involves
rearrangement?
A.
B.
C.
D.
II yield
A. Et
reactions.
2
and
products?
Reaction I only
the
II only
Reactions II and III only
Reaction III only
Reactions I and
if
and
293
27
B. spz to sp
C. sp3 to sp2
D. spi to sp
28. If diethyl
a'E,rN
Passage
(Questions 29 - 35)
o4.",
Oriental Fruit Moth sex attractant
[(E)-8-Dodecen-
HpCa
\J
/\
-yl acetare]
.CttHzt
HH
(Muscalure [(9Z)-Tricosenel)
Figure
A.
B.
C.
D.
Copyright @ by The Berkeley Review@
all of
the
conjugation.
30.
5.
A.
B.
C.
il
oA
A.
B.
C.
D.
cH.
a confbrmational isomer.
a geometrical isomer.
an optical isomer.
l3cNltR
spectrum
a structlu'al isomer.
1?
I.
II.
m.
be
classifled as a terpene.
A. I only
B. iII only
C. I and II only
D. i and III only
3
2.
34.
295
Passage
VI
(Questions 36 - 41)
-l 6
.
B.
C.
D.
A
7.
c'
.+ i.sd'u.":.:.
+CO+Ho-
- cat. Rh
,zt\
CHCH3
-tt
.cH,
D'
tt
HC-C
,/
CH.
H2C-O
.
B.
C.
D.
A
H2C= CHCHj
il
il
C
H2C-
COzCHT
B.o
HrC- C/
Reaction I:
II:
an oxidant.
CHz
Reaction
a nucleophile.
/\
HzC-
98%o vterd
an electrophile.
co2cHj
dienophile.
A.o
H:C
as:
CH:CHzCHr
III only
II only
Reactions I and III only
Reactions II and III only
Reaction
Reactions I and
Jt
CH(CHr)r
9.
.
B.
A
Pd, H2
Supercritical CO2
HrC
cHr
. Using solid-state
catalysts
1ar
equipment.
D.
Hrc
Syntheses
40.
A. reduction.
B. hydrogenation.
C. stereoselective.
D. regioselective.
41
Passage
lt
(Questions 42 - 48)
la" -:+
e(+
Vll
,\A
OH
A.
uo
o
Compound
ee("q"
C.
tu
oB'o
conc. HrSO,
A
Compound
Reaction
D.
II
OH
Compound IV
39.27n
60.\Vo
Compound
III
OH
Figure I
The percentage ofthe secondary alcohol formed increases
ofthe hydration reaction increases. This is
as the temperature
2.
I.
II.
I?
as an intermediate
in the reaction.
m.
A. I only
B. II only
C. I and II only
D . I and III only
Copyright @ by The Berkeley Review@
43. Which
8.
a. IHNlaR
B. Infraled
C. Ultraviolet
D. Visible
O[.",
A.
44.
Cornpound
A.
B.
C.
D.
IV is best described
75'C
-..>B' oH
d.,, d..,
as:
"G;
pair of diastereomers.
a pair of enantiomers.
a
H2O/H2SOa
^er* "ff*
'er-* 'er*
compounds
is an allylic
alcohol?
46.
A.
B.
C.
D.
7.
2,4-Hexadiene
2-methylcyclopentadiene
1,4-cycloheptadiene
1,3-cyclohexadiene
A^
\-ry
A'
tgr,
'eD
t;,,\--
Passage
Vlll
(Questions 49 - 54)
temperatures.
an
the
dienophile.
49
I is one of two
of the following
pairs of molecules represents the product mixture
formed in Trial 6?
A.
CH:
CH:
Reaction I
Trial
""1( CHr
&
CH:
cHr
Relative
rate
CH:
t.0
CH:
5.3
CH:
cHr
8.1
CH:
CH:
0.00s0
"J( CH:
CHr
&
cHs
CHq
"ff::,
&
CH:
CH:
'\'.
82
'$f;:
o
6
cHr
'Y'"',
4t1
o
cHr
CHr
T,"'
&
613
CH:
CH:
'1('"'
cHr
cHr
o
0.34
o
Table
299
dienophile?
A.
A.NB.
B.
C.
Io'""''
0.005.
D.
WORST
COCHzCHT
0.005.
species to
Trial
c.o
D'
A.
B.
C.
D.
(t
AICI3
CCla
("
KH
cHrCHe
()
LiAlHa
rather
y*,(/*,
c'
cHr oo
D'
cHq oo
53. How
A.
diene
Passage
lX
(Questions 55 - 60)
6.
.+.
I
7.
and
C.
D.
l+L^*
\
CompoundB
A.
In both Product A
OCH3
NHCH3
94Vo
6Vo
OCH3
CH:
88Vo
l2%o
CH:
NHCH3
87Vo
l3Vo
cHr
CH:
63Vo
37Vo
COCH3
NHCH3
lSVo
82Vo
COCH3
CH:
3lVo
69Vo
\,4
and
cH2cl
c.
H3CH2CO
CH2CI
D.
H3CH2CO
eq: Oq:
o
8.
,o
the
is
B.
''""44.
____>
150'C
^O:")
55. If
cHrcr
Table
based
)^.
B.
H3CH2CO
If
the
Compound A
Figure
A.
*ff..q.
o
c.
A.
B.
C.
D.
301
Passage
(Questions 61 - 67)
A.
B.
C.
D.
60.
H:Co
HrC
CH.
'----*
4.2
B.4
c.8
D.
A new 1,5-diene
1,5-diene
Claisen rearrangement
o/N
16
v
l)\
t3,31 _
Figure
A y,&unsaturated
carbonyl compound
64"
benzene ring, the ketone formed from the allyl phenylic ether
CH:
__>I
Hrc
Step
A
Step
II
Ia
OH
Step
<-
Hrc
III
65. rn
A.
CH:
cHr
302
B.
C.
D.
Copyright
61.
6.
substitution?
.
B.
C.
D.
A
are retained
are inverted
Several cross products are formed
.
B.
C.
62.
Step
A.
B.
C.
D.
.
63
B.
Heat serves what role in the Claisen rearrangement?
the activation
barrier
64
7.
D.
A.
5.
B.
A.
B.
C.
D.
303
Passage
Xl
(Questions 68 - 73)
il
1l
1i
i"'
H:C
-s
cHr
CH:
Caryophyllene
cr-Pinene
HSC CH:
cHr
CH:
OH
Vitamin.\
CHr
*o^
HO
Cholesterol
Citronellol
8.
A. Limonine (C16H16)
B. Geraniol (C16H1gO)
C. Patchouli alcohol (C15H26O)
D. Stearol (C1gH3gO)
known as terpenoids.
Studies in biogenesis show that the large terpenes are
synthesized starting from isopentenyl pyrophosphate. The
pyrophosphate adds across the diene of isoprene to form either
isopentenyl pyrophosphate or dimethylallyl pyrophosphate.
to one
another
69.
by way of
304
Passage
Xll
(Questions 74 - B0)
in isopentyl pyrophosphate?
il
il
o- P- o- PP
I
1.
Carbon
oH
()
o-
A.
B.
C.
D.
Carbon 2
Carbon
Carbon 4
o
il
I
HrC---.\ -
SCoA
Acetyl Coenzyme A
.
B.
C.
D.
A
1''
Limin
Carvone
Ethanol
Acetic acid
Isopropanol
Myrcene
units?
. Caryophyllene
B. Citronellol
C. a-Pinene
D. Vitamin A1
A
73.
A"
The biosynthesis
Camphor
4.
Bond d
.
B.
C.
D.
A
CH:
A. Bonda
B. Bond b
C. Bondc
D. Bondd
Oxidation of carbon
Reduction ofcarbon
Hydrolysis of
n-bond
Nucleophilic substitution
with 03?
A. Camphor
B. Carvone
C. I-imin
D. Myrcene
305
76.
A.
B.
C.
D.
77
Three
Six
natural
Nine
Diterpene
79.
Sesterterpene
0.
I only
II only
and II only
I and III only
I
A.
B.
C.
D.
oils.
as
Sesquiterpene
L
II.
m.
A.
B.
C.
D.
BG)
Monoterpene
Camphor
(Questions B1-
of terpene is fbrmed?
78.
Xlll
Two
A.
B.
C.
D.
Passage
soAn,
-oA*,
o
- oAo
R2 + H2o
Li'ases
-oA*.
1
Figure
[I
* HoAnu
o
HoAn,
Acid
Formula
Arachidic
CH3(CH2)1sCO2H
Arachidonic
CH
Behenic
CH3(CH2)2sCO2H
Lauric
CH:(CHz)roCO2H
Lignocaric
CH3(CH2)22CO2H
Linoleic
A.
B.
Linolenic
CH3CH2(CH=CHCHz): (CH2)6CO2H
Myristic
CHj(CH2)12CO2H
C)leic
CH 3 (C H2
Palmitic
CH3(CH2)1aCO2H
Palmitoleic
CH 3 (C H 2 ).5 CH =C H (CHz
Stearic
CH3(CH2)16CO2H
Carnphor
Carvone
" Limin
D.
Myrcene
(C Hz)+( CH =C HC
)7
0
H2) +(fH) zCO zH
CH =C H ( CHz
)7
CO
2H
0
)1
CO
2H
o1I
3.
of
acid, and 4Vo linolenic acid with the rest being made of other
saturated fatty acids. As the amount of unsaturation
increases, the melting point of the fatty acid decreases,
assuming that the number of carbons remains constant. For
this reason, many animal fats are solids while many
vegetable oils are liquids at room temperature. Fatty acids
can play one of three roles in biological systems. They are
found as the building blocks of cell walls as phospholipids
and glycolipids. Fatty acids form derivatives that serve as
hormones (intercellular messengers). Fatty acids are also
used for fuel through fany acid metabolism.
81.
A,7nro
B. One
C. Two
D. Four
4.
B.o
HO
85
A. Arachidic
B. Arachidonic
C. Linoleic
D. Linolenic
HO
D.
HO
86.
82. The n-bond of a fatty acid can be reduced via
hydrogenation when treated with hydrogen gas and a
catalytic metal or by FADH2. Treatment of linoleic
acid with FADH2 yields a product:
A. Myristic
B. Palmitic
C. Stearic
D. Arachidic
C. with
87
A. I
B. 2
'rr4<
1
(t)-Occidentalol
la"
A.
B.
C.
D.
-Cq
---+
Step I
CO2Me
Compound 2
Step 2
I l' HoaoH
| rrou. phH. A
z. LeH, eroEt
<-
Compound 4
Step
4ll
diterpenes.
triterpenes.
sesquiterpenes.
89. Which
A.
B.
C.
D.
Compound I
Compound 2
Compound
Compound 4
the
.
B.
C.
D.
A
SOj.Py, THF,0"C;
monoterpenes.
150'C,
Compound
A multistep
CO2Me
c. 3
D.4
88.
loH
Figure
A cyclohexadiene
A cyclohexene
An cr,B-unsaturated ketone
Alactam
NHCI. HOAc
MeLi?
EtO\ -jSMe
Eto_o
o
Compound
fr
Figure
B.
HMPA,
DME,62'C
---_->
Step 5
A.
Compound 6
oxygen.
Synthesis of Compound 6
.
B.
Carbon a
Carbon b
" Carbon c
D.
Carbon d
Questions
based on
descriptive passage.
93.
97, A
in which of
the
A.
B.
has
D.
necessary
cora
A.
B.
C.
is
A . Claisen rearrangement
B. Clemmensenreduction
C . Cope rearangement
D . Diels-Alder cycloaddition
conjugated diene
following reactions?
EXCEPT:
n't\.0$1,
Br.
__=+
t1cbHcH.,
o."*,.:,'rlT,
hv
I
B.
HTCCHCH3
D'
"'"r"
nrc
..,noTr
I
FIlCCHCH3
I!CCBTCHT
reactions
0.
H:C
I{TCCHCH3
L E-butene
II. CzHq
il. Z-butene
A. I only
B. II only
C . iII only
D. I and III only
is a propagation
reaction?
A.
B.
C.
D.
9
6.
A.
B.
C.
D.
1.B
1.8
13. c
19. c
2s. D
31. A
37. A
43. A
49. D
55. D
61. D
61. C
13. B
19. D
8s. B
91. B
91. D
2.D
8.C
14. A
20. A
26. C
32. D
38. A
44. D
50. A
56. A
62. D
68. D
14. A
80. C
86. B
92. A
98. C
6.B
12.A
18. D
24. C
30. D
36. A
42. D
48. A
54. D
60. C
66. A
12. C
78. B
84. D
90. B
96. A
_ 2(s)+2-(e)-(1)
_ 70
+2-9 -7 _12-10
22
_2_,
___
r
Choice D is correct. According to the molecular formula, there are no units of unsaturation
within the molecule,
so there are three linear carbon backbones to be considered. No other carbon backbones
are possible, because
they would be either on9_of the following structures, but drawn differently, violaie the
units of unsaturation, or
not be structurally possible.
C
(-C-CC-C
C-C
I
I
on each of the carbon backbones, the chlorine must be systematically placed to deduce the total number
of
structural isomers that are possible (stereoisomers do not count in this question).
There are three non-equivalent
carbons in the five carbon siraight chain, therefore there are three monochloro
isomers of pentane. There are
four non-equivalent carbons in the four carbon chain, therefore there are four monochloro
isomers of 2methylbutane. There are two non-equivalent carbons in the three carbon chain, but one
of the carbons (the
central carbon) already has for-rr bonds, therefore there is only one monochloro isomer
of 2,2-dimethylpropane.
This means that there are eight structural isomers total, so pict< o for greatest success.
C_C-C_C-C
C_C-C-C-C
tti
C_C-C_C-C
C1
1-chloropentane
C-C-C-C
C-C-C_C
C-C-C_C
2-chloro-2-methylbutane
CCi
2-chloro-3-methylbutane
CCI
clc
-chloro-2-methylbutane
3-chloropentane
C-C-C_C
/\
CCI
rl
C1
2-chloropentane
C_
lr
1-chloro-3-methylbutane
CI
C- C- C
7-chloro-2,2-dimethylpropane
total
C
J.
Choice C is correct. By symmetly, there are four unique carbons on methylcyclopentane, therefore
chlorination
can occur at a total of four different sites (four different carbons). This yields u tot^1
of four structural isomers.
The correct answer is choice C.
&.{
C1
HYDROCARI]ONS EXPLANATIONS
4.
Choice B is correct. Bromination is highly selective for tertiary carbons over secondary and primary carbons, so
the exact quantity of each type of hydrogen need not be accounted for. The most abundant product from
bromination results from the bromination of a tertiary carbon. Carbon number two is tertiary, so the most
abundant product is 2-bromo-2-methylbutane. Pick B, and be a chemistry master.
5.
Choice B is correct. 1-chloropentane and 2-chloropentane are formed from chlorination of a primary and
secondary carbon, respectively. There is a difference in reactivity between primary and secondary carbons in
free radical chlorination reactions. Secondary carbons are 2.5 times as reactive as primary carbons. This means
that the ratio of hydrogens (abundance) and the relative reactivity must both be accounted for when
estimating the final ratio. Drawn below is the application of quantity and reactivity. Hydrogens symbolized
by Hu lead to 1-chloropentane and hydrogens symbolized by HU lead to 2-chloropentane. They are multiplied
by their respective reactivity factor.
"\
/to
"\ l'
4-.^-c-.^-C\^,,
L
Hu-l
Ha
H,
\-
Ha
H,
6Hux7=6:4H6x2.5=10
@'ffi
n*'"irr{--
i----
2-chloropentane
The ratio is 10: 6, which reduces to 5 : 3. This makes choice B the best answer.
6.
Choice B is correct. Four secondary hydrogens lead to 2-chlorohexane and four secondary hydrogens lead to 3chlorohexane, sotheproductratio shouldbe 1:1. Becausethe ratio is7.07: l andnot 1: l,choiceAis
eliminated. There is no resonance in the molecules (because there are no lone pairs and no n-bonds), so choice C
is eliminated. The inductive effect wouid favor the formation of 3-chloropentane, so choice D is eliminated.
Steric hindrance is the best explanation why the carbon-2 is selected over carbon-3, so choice B is best.
7.
Choice B is correct. The question addresses ring strain destabilizing not only the alkane, but the free radical
intermediate. Based on that, choices A and C are eliminated, because they are not ring structures. A threemembered ring has more ring strain than a four membered ring, so the best answer is choice B.
8.
Choice C is correct. The stability of the carbon free radical is attributed to the donation of electron density
from the alkyl substituents through hyperconjugation. Because hydrogens cannot donate electron density
through hyperconjugation, the stability of a free radical depends on the number of alkyl substituents attached.
As a result, the stability of free radicals is tertiary > secondary > primary (3' > 2" > 1"). Quaternary free
radicals cannot exist, because the presence of four bonds and a free electron on carbon would exceed the octet rule
for carbon. The best answer is therefore choice C.
9.
Choice D is correct. According to Table 1, the enthalpy change is positive for the reaction of iodine with an
alkene, so it is an endothermic reaction. This means that the products are in a higher energy state than the
reactants, which eliminates choices A and B. In the next to the last sentence of the first paragraph, it is stated
that the second transition state is of higher energy than the first transition state, so the best answer is choice
D. If you find yourself asking "do they really expect me to know this?", it's probably in the passage... find it!
10.
Choice B is correct. Initiation forms the halogen free radical (X.), so the first propagation step involves the
halogen free radical as a reactant. This eliminates choices A and C. In propagation step 1, the free radical
abstracts a hydrogen from an alkane, which is choice B. Eliminate choice D, because it is a termination step.
1.L"
Choice B is correct. According to the data in Table 1, the strongest halogen-halogen bond is formed between two
chlorine atoms. Chlorine is the second halogen from the top in the column VII of the periodic table. Atomic
radius increases as you descend a column of the periodic table, so chlorine is the second smallest halogen.
Therefore, the strongest halogen-halogen bond is formed between the second smallest halogen. The fluorinefluorine bond is an exception to the shorter bond equals stronger bond rule, because of inter-nuclear repulsion and
the odd fact that the single bond is actually a pi-bond, rather than a sigma-bond. The best answer is choice B.
HYDROCARBONS EXPLANATIONS
12.
Choice A is correct. Hydrogen free radical is unstable, and thus it cannot be formed
in the reaction mechanism.
Choice A produces a hydrogen free radical, therefore the best answer is choice
A.
13.
Cl'roice C is correct. If the halogen were to stabilize the free radical when attached,
it would lower the
transition state and make the reaction pathway for adding a second halogen more favorable.
The halogen will
not stabilize the free radical, because halogens are election withdrawiig by the inductive
effect. Hilogens
therefore do not heip stabilize the free radical intermediate so statement I is true. Because
a second halide
does not add to an alkyl halide, but a halide does add to an alkane, we assume
that the alkane is more
reactive' The difference is either in the bond broken or the bond formed. It is safe to assume
that the
wili choose a pathway of lowest energy so by breaking the C-H bond of the alkane preferentially over reaction
the C-H
of the alkyl halide, it can be concluded that the bond broken is of lower energy. rhi, makes
statement II true.
If statement II is true, then statement III cannot be true. The best answer is therefore choice C. As
a note, an RH bond is stronger than an R-X bond, so if a halogen free radical (X.) were to react with an alkyl haiide,
it
would abstract the halide, not a hydrogen. This is the more logical explanation for the absence of multiple
substitution products with free radical halogenation.
14.
15
Choice D is correct'-. Wl"l comparing Trial I with Trial II, both the electrophile
concentration and reaction
rate have doubled. This behavior is expected no matter what mechanism
is employed. When comparing
Trial
I with Trial III, the base concentration has doubled, the electrophiie concent.ation
t6.
Choice C is correct. The most stable conformation has the largest substituents
with anti orientation to one
another' The bulkiest group on carbon two is the methyl group comprised of carbon
1 and the bulkiest group on
carbon three is the ethyl group comprised of carbons + anJ s, so choiie C is
correct. The Newman projections for
the three staggered conformations are drawn below:
Br.
"-;,-4i'"'
HsC
cH2cH3
Conformer from
the example
CHs
.CH"
\->cir.cH"
H\Y
HsC
HsC-r
cH2cH3
cHs
CH2CH3
'l'7'
Br.
.*CH"CH3
"t,><
HsC
CHs
Conformer with
C1 and Cn anti
H3CH2C
CHs
CH:
CHs
18'
Choice D is correct. From the perspective of the eye as shown, the bromine atom is bonded
to the rear (eclipsed)
carbon, therefore choices A and C are eliminated. From the perspective of the eye, the methyl
would stick out
to the left and the hydrogen would stick out to the right. The-besi choice is thus answer choice
D.
312
HYDROCARBONS EXPLANATIONS
't9.
Choice C is correct. The enantiomer of the reactant is its mirror image, therefore both chiral
centers must be
opposite that of the reactant's chiral centers. The determination oiboth of the reactant's
chiral centers is
shown below. The chirai centers of the enantiomer are 23 and 3R. The best answer is choice
C.
1
Br
cHg
cH2cH3
Carbon 2 = R
20.
H$)
HsC
Carbon 3 =
Choice A is correct. The role of a strong acid in an elimination reaction is to protonate the leaving group and
increase its tendency to leave. Protonation occurs in the E1 reaction rather thin the E2 reaction.
T;hI acii will
not dehydrate the solvent, so choice B is eliminated. The sulfate ion is not a strong enough base to remove a
proton, so choice C is both wrong and impossible. Choice D should be eliminatia i*J"aiutely,
because
carbocation cannot be protonated. The best answer is choice A.
21..
Choice C is correct. Chlorocyclohexane when treated with a strong base und.ergoes an elimination
reaction by
way of an E2 mechani-sm to yield cyclohexene. There are two units of unsaturatiion in cyclohexene,
one unit of
unsaturation for the n-bond and one unit of nnsaturation for the ring. The correct answer is
choice
C.
))
Choice D is correct. This question is another way of asking, "Which reaction proceeds via a carbocation
intermediate in its mechanism?" The first two reactions proceed by an E2-mechanism, which is a one-step
process having no intermediate. The E2-mechanism is predictable, becaur" of th" presence of
the strong, bulky
base. The base must be strong enough to remove a proton from carbon and it must te bulky enough
to #inimize
competition with an Sp2-reaction. Reaction III proceeds by an E1-mechanism, because of the preJence of
strong
acid, which protonates the hydroxyl group. This makes a better leaving group, and ultimaiely
facilitates the
formation of a carbocation. In fact, the location of the doubie bond in theiiial product can only be explained
by
a hydride shift. The hydride shift results in the conversion from a ,".orliury carbocation into a tertiary
carbocation. Only Reaction iii exhibits rearrangement, so the best answer is choice D.
23.
Choice B is correct. This question involves counting the chiral centers in each product in Figure 1
to see which
molecules are chiral, and then analyzing to see if chirality is involved in the reaction. The m-ajor
products from
Reaction I and Reaction II both have chiral centers present. In Reaction I, two of the original three
chiral
centers are lost , but that still leaves one remaining chiral center, so the mixture is optically uJtirr".
In Reaction
II, one of the original three chiral centers is lost , which leaves two remaining chiral centers, so the mixture is
optically active' In Reaction III, all three chiral centers are lost, so the fiial product mixture exhibits no
optical activity. The best answer is choice B.
,t
Choice C is correct. The reaction involves the use of concentrated strong acid at high temperature, so the
reaction is apt to proceed via an E1-mechanism, An E1-mechanism entails the hydroxyl
[roup being protonated
and then leaving, producing a secondary carbocation. A hydride shift resuits in ihe conversion fropf secondary
carbocation into a tertiary carbocation, which is the intermediate from which deprotonation to form the
alkene product occurs. A11 three chiral centers are lost, which is also seen in Reaction III. This is best
explained in choice C. On the MCAT, test-takers are expected to be able to see the analogy between the
reaction in a question and a reaction in the passage.
25.
JIJ
HYDROCARBONS EXPLANATIONS
26.
Choice C is correct' First and foremost, with,a strong, bulky base, the reaction
proceeds by an E2-mechanism.
This eliminates choices A and B' The E2-mechanism-requires that the hydrogeir
being lost be oriented anti to
the- leavrng group, in this case chlorine. In Reaction I, there
are two anti irydrigens, and the one that is chosen,
is the one that leads to the more substituted alkene product. In Reaction
Ii, the"re is only one anti hydrogen, so
only one-product may be. formed. The hydrog"n o., ii-," more substituted alpha
carbon has gauche orientation, so
'
Choice C is correct. The two carbons common to both rings finish as doubie
bond carbons in Reaction III, so they
both finish with sp2-hybridization. Only choice C finish"es witn spi 1-rrAr1ii")ution,
so it is the best answer.
28.
27
29. Choice A is correct' The Silkworm Moth sex phermone has two double
bonds, one that is cis substituted and the
other that is trans substituted. This eliminates choice B. All of the carbons
are part of a straight chain with no
branching, so it has two terminal carbons that are primary and all the internal
.uiborr, are secondary. There are
C.is eliminar:d
sinsle bond separates the two doubie bonds, so they are in
l"^:"1:::I_:11,,""?,::
91y:ne
fact coni
eliminates choice D. Ali
of the carbons have at least two identical substituents br they
l1::^t"T1q111,_lllt
nave sp'-hybridization, so there are no stereogenic centers. This makes choice A
the best answer.
t:tu:
30'
Choice D is correct. The Oriental Fruit Moth sex phermone differs from the structure
in the question at the
position of the double bond. The structure in the question ha9 cis geometry,
while the phermone in Figure t has
trans geometry. This can be misleadingand tempt you to pick choice g. gut,
the conneitivity is not the same, so
the structures are structural isomers. The n-boncl is between carbons B ancl
9 in the Oriental Fruit Moth sex
phermone, but it is between carbons 9 and 10 in the compound that is shown.
This makes choice D the best
answer' The two structures are not interchangeable by a rotation about a bond, so
they are not conformational
isomers' This eliminates choice A. There is no itereogenic carbon, so the two structures
cannot be optical isomers.
This eliminates choice C. The two structures are structural isomers, making choice
D the best answer.
31'
32' Choice D is correct. Muscalure is a cis alkene made of 23 carbons and 46 hydrogens. It is a long chain
hydrocarbon, so it has low water miscibitity. Choice A is a valid statement, and ttereby
eliminated. It is
excreted, so it must be a liquid under ambient conditions. This makes choice
B a valid statement, which
eliminates it. Because it is a long chain-hydrocarbon, lipids can dissolve into it.
It has high lipid solubility,
making choice C a valid statement, thereby eliminating it. There are no stereogenic
centers on muscalure, so it
will not rotate plane-poiarized light. This makes
33'
Choice A is correct. All of the compounds in Figure t have straight chains (no rings),
so each has at least two
primary carbons' only 2-methylheptadecane his branching, ro lt hu, an extra primary carbon.
No other
str.ucture in Figure t has any branching, so 2-methylheptadeiane, the Tiger Moth
sex phermone, has the rnost
314
HYDROCARBONS EXPLANATIONS
34.
Choice D is correct. The Green Peach Aphid defense phermone has 15 carbons connected in such a
way that it can
be partitioned into three isoprene subunits. Choice A is a valid statement, so it is eliminated.
The Green peach
Aphid defense phermone has four double boncls, so it has eight sp2-hybridized carbons. With fifteen
carbons
total, more than half of the carbons are sp2-hybridized. Choiie B is a valid statement, so it is eliminated.
The
Green Peach Aphid defense phermone has a conjugated diene, so it can undergo 1,4-addition
of an electrophile.
Choice C is a valid statement, which eliminates it. Because of all of the n-donds in the Green peach
Aphid
defense phermone, it is not very flexible. Choice D is an invalid statement, which makes it the best
answer.
35.
Choice D is correct. The Oriental Fruit Moth sex phermone has an ester group. A carbonyl has an IR absorbance
above 1700 crn-l , so an ester accounts for the IR absorbance at1741 .i',-r.'Ch"i;; A is a valid correlation of
structure to spectroscopic observation, so it is eliminated. Bombykol has two n-bonds in a conjugated network.
The presence of n-bonds in a structure results in an absorbance in the ultraviolet-visible tuig" of the EM
spectrum, so an absorbance of 227 nm seems viable for a conjugated diene. Choice B is a valid iorrelation of
structure to spectroscopic observation, so it is eliminated. Muscalure has two carbons involved in double bonds,
each of which has a hydrogen attached. This means that the hydrogens on those carbons will be found
downfield, resuiting in two signals with values around 5.00 ppm in-lUx"traR. Choice C is a valid correlation of
structure to spectroscopic observation, so it is eliminated. The Tiger Moth sex phermone has eighteen carbons
oj.srynmetry. There are two equivalent methyl gtorrp!, so there arJseventeen uniqui carbons. The
?*.i:-{""e
TTCNMR would show 17 signals
if it were of high enough iesolution. The reality is that ,.uny of the signals
would overlap, so it would likely show less. It will not show fourteen signals in its 13CNMR spectrum,
so choice
D is an invalid correlation of structure to spectroscopic observation, makLg it the best answer.
36.
Choice A is correct. Reaction I is a Diels-Alder reaction. Diels-Alder reactions involve the reaction of a
conjugated diene and a dienophile. Normally we think of the dienophile as an alkene, but the only
requirement is that it has a r-bond. The alkyne meets this requirement, so it is a dienophile. The best answer
is choice A. There is no nucleophilic substitution gorng on, so choices B and C are eliminated. There is
no change
in oxidation state, so the compound is not an oxidant or reductant, eliminating choice D.
J/.
Choice A is correct. Each of the answer choices is lacking two hydrogens from the formula of the final product,
CaHgO. This means that hydrogenation converts the intermediate to tne final product. The final product is an
aldehyde and hydrogenation cannot convert a cyclic ether into a carbonyl, so choices C and D can be eliminated.
Hydrogenation adds two hydrogen atoms to neighboring carbons. Because an aldehyde is generated, we know
that one of the hydrogen atoms is added to the carbonyl carbon. The ring is cleaved, so iydrogenation must
break the strained ring by adding a hydrogen to the carbonyl carbon and a h"ydrogen to the neighbJring atom.
In
choice A, the hydrogen atoms are correctly displaced on the intermediate-(CH2-CH-CH3) to lorm both
aidehyde products (CH2-CH2-CH3 and CH3-CU-CH3) when a single hydrogen is added to tne akyl chain.
This is not the case in choice B (CH2-CHZ-CHZ), so it is eliminated.
38.
Choice A is correct. On the product of Reaction I, ail of the functional groups are bonded to sp2-hybridized
carbons, so there are no stereocenters. This eliminates choices B and C. Bised bn the remaini.,g ur,r*", choices,
Reaction III must have formed a new stereocenter. The new stereocenter is located on the rin{ carbon with the
methyl substituent. Hydrogenation can occur from above or below the ring, so the methyl is albove the plane in
fifty percent of the product mixture and below the plane in fifty percent of tnu mixture. Reaction III forms
racemic mixture. In Reaction II, the products have no chiral centers, so no new stereocenters were formed during
the reaction. This eliminates choice D and makes choice A the best answer.
39'
Choice B is correct. The basic tenet of green chemistry is to minimize waste and side products and maximize
atom-economy. Atom-economy aims to get every atom added to the reaction containe. et-rait-rg up in the product.
Using a supercritical fluid as a solvent makes for easy recovery and reuse of the solventl Iieaction III uses
supercritical CO2, so choice A is valid and thus eliminated. Using protecting groups adds extra atoms to the
solution that are not destined to be part of the product, so it violatei ine princfof, of atom-ecor-romy. protecting
groups are difficult to recycle without spending a great deal of solvent, so they do not fit the green chemistr!
philosophy. Choice B is an exception. If catalysts are part of the lab equipment, such as cataljrtic beads, then
they are easily recovered and reused. This makes choice C in philosopnicat agreement with ti-re principles of
green chemistry. This eliminates choice C. It is stated in the passage that direcl oxidation using oxygen fits in
the philosophy of green chemistry, so choice D is eliminated. Choose B and be on top of your gui".
315
HYDROCARBONS EXPLANATIONS
40.
Choice D is correct. Reaction III is described in the passage as hydrogenation, the term applied
to a reaction
that adds hydrogen atoms. This eliminates choice g. rne gain of Uoias to hydrogen, u i"r,
electronegative
atom than carbon, is defined as reduction, so choice A is eliminated. Although it is not specified
in the
passage, when hydrogenating with a metal catalyst, the process adds the hydrJgen atoms in
a syn fashion,
which means that the reaction is stereoselective. This eiiminates choice C.- Both carbons gain a hydrogen
atom, so there is no regioselectivity. This makes choice D the best answer. Choose D for the
safe of correctness.
41..
Choice C is correct. The reaction is a Diels-Alder reaction, similar to Reaction I, except an alkene
is serving as
the dienophile, rather than an alkyne. A Diels-Alder reaction results in the formation of a new six-membered
ring, which is observed in all of the choices. When the reaction involves a conjugated cliene and an alkene,
the
product is a cyclohexene ring, so choices B and D are eliminated. To form choice"B, the dienophile would have
needed to be an alkyne, like Reaction I. The n-bond in the product is located between the two internal
carbons
of the-original conjugated diene, so they should be found otr the left side of the central ring. This makes choice
C the best arswer. Choose C for a brighter smile when scoring iike you did.
eK-r+
42.
_^*
e[("
{).
Choice A is correct. Compound III and Compound IV are structural isomers of one another. They
each have a
hydroxyl
.group and an aikene functionality, so infrared spectroscopy yields the same key absorbances. This
makes infrared spectroscopy ineffective at distinguishing the two iilyiic alcoho1s, so choice B is eliminated.
Ultraviolet spectroscopy is great for determining the amount of conjugation in a system. However, both
compounds have the same number of rc-bonds, one, so ultraviolet spectroscopy yields essentially the same
spectrum for both compounds. Choice C is eliminated. Neither structure absorbs light in the visible range,
given that neither structure has extensive conjugation. This can be inferred from the passage when thly
mention that the peak at 779 nm disappears. That peak is associated with Compound I, which tappens to be
one of the two enantiomers represented by Compound III. Choice D is eliminatei, because 1,79 nmis not in the
visible range of the EM spectrum. The best method is 1HNMR, which can distinguish structurai isomers by
their equivalent hydrogens. Choice A is the best answer.
44.
Choice D is correct' The tertiary carbon with the hydroxyl group has four unique substituents, so it is chiral.
This eliminates choice A. There is only one chiral center, so diastereomers are not possible (there must be at
least two chiral centers for diastereomers to be possible). This eliminates choice b. Because the hydroxyl
group can be above the plane or below the plane, there is more than one structure possible for Compound IV.
This eliminates choice B and makes choice D the best answer.
OH
Compound IV
Copyright O by The Berkeley Review@
m
OH
Enantiomers
HYDROCARBONS EXPLANATIONS
45.
Choice A is correct. The first paragraph of the passage implies that Compound I is an allylic alcohol. If you
recall your general nomenclature, then you should know that when a functional group, in this case the hydroxyl
group, is on the carbon bonded to the alkene carbon, it is said to be allylic. Choice A fits this description.
Choice D should have been eliminated early, because it does not contains a n-bond. Choice B is eliminated,
because it is a vinylic alcohol (hydroxyl group directly bonded to the alkene carbon). Choice C has the double
bond too far from the alcohol group to be allylic, so it is eliminated as well.
46.
Choice C is correct. The option for either 1,2-addition or 1,4-addition occurs when the reactant has conjugated
n-bonds. Choices A and D should be eliminated immediately, because when the two numbers describing the nbonds differ by 2, then the n-bonds are conjugated. Cyclopentadiene has only five carbons, so one n-bond must be
between carbons one and two. The second ru-bond must be between carbons three and four, because in a five-carbon
ring, no matter how you place two double bonds, for the ring to not be so strained it can't exist, they must be
conjugated. Only in choice C are the n-bonds not conjugated, so choice C is the best answer.
Choice A
.A/
47.
f'*
Choice B
Choice C
Choice D
Choice B is correct. The hydration of Compound II starts with the addition of a proton to the conjugated nnetwork. The easiest carbon to protonate, because of steric hindrance and resonance stability, is the secondary,
terminal carbon of the system. This generates the structure in choice C, so choice C is eliminated. That
structure can undergo resonance to generate the structure shown in choice D. This eliminates choice D. If water
were to attack the structure shown in choice C, the structure in choice A, a new intermediate, forms. This
eliminates choice A. By default, the best answer is choice B. Choice B is not possible, because the structure
would have to gain a proton at the more sterically hindered terminal carbon of the n-system.
,
Ha
)
.:--\
H,o.
\
-'
lra
eI).\eD
Choice C
m
48.
Choice A is correct. At 35"C, the hydration of Compound II using sulfuric acid and water yields abottt 40"h
secondary alcohol and 60"h tertiary alcohol. It is stated in the passage that "the percentage of the secondary
alcohol formed increases as the temperature of the hydration reaction increases. This is attributed to a shift
from kinetic control to thermodynamic control." This means that at 75'C,it is reasonable to suspect that the
secondary, allylic alcohol is the major product. This eliminates choice C. The product is not a vinylic alcohol,
so choices B and D are eliminated. In choice A, a secondary allylic alcohol is formed, so it is the best answer.
Taking the information in the third paragraph of the passage and Figure 1, and erasing the cyclopentane ring
could aiso solve this question.
49.
Choice D is correct. It is easiest to start by evaluating which pair represents enantiomers. Enantiomers, you
recall, are non-superimposable mirror images. In this case, it is easier to compare the chiral centers rather
than reorient the structures to see if they are mirror images. If all of the chiral centers differ, then the two
structures are enantiomers. In choices A and C, only one of the three chiral centers differs between the pair, so
they are diastereomers, not enantiomers. The next factor to consider is the alignment of the carbonyl
substituents. They are cis to begin with (on the alkene reactant), so they should finish cis. In choice B, the two
carbonyl substituents are trans, so choice B is eliminated. In choice D, the groups are cis, so it is the best answer.
Copyright @ by The Berkeley Revierv@
31'/
HYDROCARBONS EXPLANATIONS
50.
51.
Choice A is correct' According to the passage, the addition of a Lewis acid to the
system increases the rate of
the Diels-Alder reaction. Choice A, AlC13, is a Lewis acid, because the aluminum lacks
a complete octet.
Choice B, CCl4, is a common organic solvent where each atom has a satisfied octet. Because
CCI4 acts like a
solvent and not a Lewis acid, choice B is eliminated. Choice C, KH, is a strong base that
reaaity donates
electrons. Because KH acts like a base and not a Lewis acid, choice C is eliminaied. Choice
D, LiAiH4, is a
strong reducing agent where each atom has a satisfied octet. Because LiAIH4 acts like a reducing
agent and not
a Lewis acid, choice D is eiiminated. The best answer is choice A.
52.
electrophiie is
a ttack.
o?
cHe
The second intermediate drawn matches choice D, so choice D is the best answer.
Choices B and C could have
been elimi'ated by the incorrect location of the positive charge.
53'
Choice A is correct. The dienophile is the same in Trial 2 and Trial 4, so the difference in
reactivity must be
attributed to the conjugated diene' This eiiminates choice D. Methyl groups, when bonded
to a structure, do not
act as Lewis acids, because their octets are complete. This eliminates choice C. The
methyl groups are mildiy
electron-donating, not eiectron-withdrawing, to .hoi." B is incorrect. The most significant
iacior in the reaction
rate is that the extra methyl group on the diene in Trial 4 causes steric hindrance in the
transition state. No
matter how the diene contorts, one of the two methyl groLlps interferes with the incoming dienophiie.
The best
answer is choice A.
,f.
U
r.3
&ilf*'--->U;
__>
Choice D is correct. It is stated in the passage that a dienophile is enhanced when it has
an electronwithdrawing group conjugated to the alkene. Choice A is enhanied by the carbonyl groups conjugated
to the
alkene, so choice A is eliminated. Choice B, albeit an alkyne and not an alkene, has el-ectronlwlthdrawing
ester groups conjugated with the n-bond, so it is enhanced as a dienophile. Choice B is
eliminated. Choice C is
enhanced by the carhonyl groups conjugated to the aikene, so choice C is eliminated.
In choice D, the amine
group is an electron-donating group that lessens the reactivity of the dienophile. Choice D is the best
answer.
Copyright @ by The Berkeley Review@
3r8
HYDROCARBONS EXPLANATIONS
55.
Choice D is correct. If the Y-group is a carbonyl group, then it is the exact same substituent as the other
carbonyl group (on the adjacent carbon), making the compound symmetric and thus indistinguishabie. Both
Product A and Product B are the same compound, if the reactant is symmetric, so choice D is the best answer.
5b.
Choice A is correct. In the second paragraph of the passage it is stated that when X is an electron-donating
group/ product A is the major product. Because the OCH3 reactant yields more Product A than the CH3 reactant
in comparable reactions, it can be concluded that an OCH3 group is more electron donating than a CH3 group.
The best answer is choice A. Choices B and D should have been eliminated, because tie major prlJuct is
product A, not product B.
57.
Choice A is correct. By analogy, OCH2CH3 (ethoxy) is an electron donating group like OCH3 (methoxy). The
presence of the eiectron-donating group makes Product A the more favorable product. Product A fiom the
generic reaction of the passage is choice A. Be careful not to choose B without paying attention to the location
of the double bond. The double bond in choice B is on the side opposite from where it should be.
58.
Choice A is correct. Two five-carbon species are combined, so the final product can have only ten carbons
altogether. Choice D is eliminated for having twelve carbons total. One o] the double bonds is in the wrong
location in both choice B and choice C. The best answer is therefore choice A. The stereochemistry with the
new cyclopentyl ring trans to the bridging carbon is what is referred to as the "endo product." The arrowpushing schematic from the reactant to the product is drawn below:
ryO->OrO
..rrrl\\
.,,tttlll
59.
Choice D is correct. Structural isomers have different bonds (connectivity of atoms). Product A and Product B in
the sample reaction in Figure 1 are structural isomers. Structural isomers result when both reactants are
asymmetric. The best answer is choice D.
50.
Choice C is correct. For the reaction as drawn in the question, with two asymmetric reactants, there are two
possible structural isomers (corresponding to product A and product B in the generic reaction) that can form. In
both structural isomers, there are two new chiral centers formed. For a compound with two chiral centers, there
are four (22) possible stereoisomers, meaning that there are four possible stereoisomers for each structural
isomer. The result is that there are eight possible isomers total, so the best answer is choice C. In reality, not
all eight isomers are observed to any measurable level in a Diels-Alder reaction. The major product results
from the transition state of least steric hindrance. In a typical Diels-Alder reaction suclt as thir, th" major
products are an enantiomeric pair of one of the two possible structural isomers. The less favorable structural
isomer may also be formed, resulting in an enantiomeric pair, but it is generally in much lower concentration
than the more favorable structural isomer.
6't.
Choice D is correct. A concerted reaction occurs in one step. Given that a sigmatropic rearrangement involves
just one molecule, if it occurs in just one step, then only one product can be formed. This eliminates choice C,
because there are not multiple products, let alone cross products. The stereochemistry can be lost at centers that
go from sp3-hybridizationl, sp2-hybridization and it can be gained at centers that go from sp2-hybridization
to spr-hybridization. Carbons that do not change hybridization cannot experience a change in stereochemistry.
This means that there is no set rule about the complete retention or the complete inversion of all stereocenters.
This eliminates choices A and B. The only possible answer is the one that supports no cross products being
formed, because the molecule only reacts one way. Choice D is the best answer.
62.
Choice D is correct. Step III converts a cyclic ketone into a phenol, so the product has aromaticity that the
reactant does not. The gain of aromaticity drives the reaction, so choices A and C are eliminated. The
conversion from a ketone to phenol shifts the n-bond from the carbonyl to the benzene ring, so it is the result of
tautomerization, not reduction. The best answer is choice D.
319
HYDROCARBONS EXPLANATIONS
63.
Choice A is correct. The role of heat in any pericyclic reaction is to provide energy for the
reactant to realign
its orbitals to achieve the transition state. The best answer is choice A. c-hoice B should have been
eliminated, because exothermic reactions generate heat, so no heat must be added to drive
them. Heat is
released when bonds are formed, sigma or pi, so choices C and D are elimilated.
64.
Choice B is correct. The Cope rearrangement involves a 1,S-diene, so there are six carbons within
the molecular
orbital of the transition state. Choice A is elimrnated because it has only four carbons. Choice C is eliminated
because the orbitals show no fi-overiap between adjacent carbons. Choice D is eliminated because
there is no
overlap across the complete cycle. The best overlap is choice B, where the sigma-bond is present o1 the
left and
the terminal orbitals are aligned correctly to form i pi-bond.
65.
Choice B is correct. The oxygen is directly bonded to the benzene ring in the reactant, so it is phenylic a'd not
benzylic. This eliminates choices A and C. The oxygen is also bonded to the carbon alpha to ihe aikene. This
makes the carbon allylic, so choice B is the best answer.
66.
Choice A is correct. The Claisen rearrangement converts an ether into a carbonyl, so the spectroscopic evidence
must depict either the loss of an ether or gain of a carbonyl group. Aldehyde protons shor,n, a signai
around 9.5
ppm in the 1HNMR, so the formation of in aldehyde wouliin fact correspond with the appearince of a
signal
around 9.5 ppm. Choice A is the best answer. Infrared absorbances uro.r,-rd 1700 cm-l inaicate the presence
of a
carbonyl grouP and broad infrared absorbances around 3400 cm-1 indicate the presence of an alcohol
group. No
hydroxyl group appears in either the reactant or product, so choice B is eliminated. The reaction would
be
supported by the appearance of an absorbance around 1700 cm-1 in infrared spectroscopy, not a disappearance,
so
choice C is eliminated' Signals between 5 and 6 ppm in the 1HNMR co.respond to vinylic hydroge-ns
bonded to
aikene carbons, which are present before and afier the reaction, so choice D is eliminated.
67.
Choice C is correct- The first reaction in the synthesis in Figure 2, Step I, invoives the oxygen. The Claisen
rearrangement involves oxygen as the ether is converted into a ketone. This eliminates ihoices B and D.
According to the remaining choices, Step II is a Cope rearrangement. To determine the best answer, we must
decide if the units of unsaturation decrease by one cluring the Claisen rearrangement or r,r.hether they remail
constant at five. In all compounds in Figure 2, there are four n-bonds and one .lig, ,o there are aiways iive
units
of unsaturation. This makes choice C the best answer. You could also conclud"J thut the units of unsaturation
do not change by looking at the Claisen rearrangement in Figure 1, where there are two n-bonds in both the
redctant and product.
68.
Choice D is correct. Terpenes are composed of isoprene subunits which are made of five carbons. To be a terpene,
five. Stearol has eighteen carbons, so it cannot be
69.
Choice C is correct- If the sesquiterpene were derived from a natural source (such as extraction or distillation
from a plant), then any impurities would be naturally occurring impurities. If there were two enantiomers
present, that would be explained by attack at a planar site from two sides. This can occur in nature although
enzymes strongly favor synthesis of one enantiomer over another. Choices A and B are eliminated, because
chiral impurities can occur in nature. The dead give-away would be an impurity with sixteen carbons. Terpenes
have muitiples of five for their carbon values. Because sixteen carbons is not possible, choice C is the best
choice. A twenty-carbon impurity is a terpene, thurs it is naturally occurring.
v0.
Choice D is correct. The carbon that is most susceptible to nucleophilic attack is the carbon with a leaving
group attached" Carbon four, with the pyropl-rosphate leaving group; is the most electrophilic. Alkene carboni
do,act as electrophiles oir occasion, but in this iornpound, carbon four is more electrophilic than an alkene
carbon" The best answer is choice D.
71"
Choice A is correct. Combining three acetyl coenzyme A molecules result in six carbons total. Isoprene units
have only five carbons, so one carbon must be in a side product. Carbon dioxide contains only one carbon, so
choice A is the best choice. Ethanol and acetic acid each contain two carbons ancl isopropanol contains three
carbons. Choices B, C, and D are all eliminated.
HYDROCARBONS EXPLANATIONS
nt
Choice C is correct. A Diels-Alder reaction forms cyclohexene, so caryophyllene and citronellol cannot have
been formed from a Diels-Alder reaction. This eliminates choices A and B. Both c,-pinene and Vitamin 41
have a cyclohexene moiety, so we must look closer. Diels-Alder reactions involve a di"ne and dienophile, so
we can look at the compounds in a retrosynthetic fashion. In Vitamin ,A.1, the retro Diels-Alder reaction does
not generate terpene fragments, so choice D is eliminated. Choice C is the best answer by default.
J.
Choice B is correct. Bond a can be eliminated immediately, because the fragments formed from the break are
three carbons and seven carbons. Bond c can be also eliminated immediately, because the fragments formed from
the break are nine carbons and one carbon. These are not multiples of five, therefore the two fragments cannot
be involved in the synthesis. This eliminates choices A and C. Bond b and Bond d when broken can leave a ten
carbon molecule, so neither can be eliminated. The trouble with bond d is that the fragment to the right of the
break cannot form a 2-methylbutene, because it loses the tertiary carbon. Choice D is eliminated. Isoprene
,/
units must be isopentenyl, not straight chain pentenyl, thus the break is not allowed. The two possible retro
synthesis pathways are shown below, and only Bond b is involved. Choice B is the best answer.
Bond d
Bond d
CFI?
CIT
74.
Choice A is correct. Carvone differs from limin by a carbonyl group. To go from iimin to carvone, a carbon must
lose two bonds to hydrogen and gain a double bond to oxygen. This is oxid.ation, so choice A is the best answer.
75.
Choice A is correct. Ozonolysis is the oxidative cleavage of a double bond between two carbons. The resulting
products are carbonyl compounds that vary from aldehydes to ketones to carboxylic acids, depending on the
work up step. To undergo ozonolysis, the reactant must contain an alkene functional group. All of the compounds
have an alkene functionality except for camphor. This makes choice A, camphor, the best answer.
76.
Choice B is correct. Singlets in the proton NMR are caused by unique hydrogen atoms in an environment where
the adjacent atoms have no bonds to hydrogen, and thus there are no neighboring hydrogens with which
coupiing can take place. In camphor, ali of the methyl groups are bonded to quaternary carbons, so they all fit
this description. Because the cyciic structure is incapable of rotation, like an alkene, the two methyl groups
bonded to the bridge carbon are not equivalent, causing them to express different NMR signals. The result is
that each of the methyl groups are represented by a singlet in the proton NMR. All of the remaining hydrogens
on camphor are on carbons adjacent to neighboring carbons with hydrogens, so there are no other singlets than
the ones from the methyl groups. This generates three proton NMR singlets, so the best answer is choice B.
No Hs on neighbor, cannot be
rotated to be equivalentwith
No Hs on neighbor, cannot be
rotated to be equivalent with
g H3cs
77.
)g--
No Hs on neighbor, isolated
methyl grorrpl (3H singlet)
Choice C is correct. Myrcene contains ten carbon atoms, so the addition of another isoprene unit would result in a
product with fifteen carbons total. According to the first paragraph of the passage, terpenes having fifteen
carbons are referred to as sesquiterpene, making choice C the best answer.
321
HYDROCARBONS EXPLANATIONS
Choice B is correct. Can-rphor has a carbonyl group (water soluble) and a iarge alkyl ring system (not water
soluble). It is hard to decide based on the structure. It happens that the compound is watei soluble, which you
may know first hand from using camphor-containing cleaning agents for skin. The question is whether or not it
is highly water soluble. Because there is some ambiguity, let's say for now thai it 1ikely not highly water
soluble, and consider statement I to be invalid. Camphor is a liquid at room temperature, as you ti-tignt n^rr"
seen if you synthesized it in a lab experiment. Being a liquid at standard temperature, its boiling point"is above
298 K. Statement II is valid. Camphor has two chiral carbons, so it rotates plane-polarized lighi. This makes
statement iII invalid. Choice B is the best answer, but not with one hundred percent certainty.
79.
Choice D is correct. It is stated in the passage that carvone has a strong UV absorbance (e > 10,000). Carvone
has conjugation, which causes its intense UV absorbance. On the other hand, limin has no conjugation, so its UV
absorbance is not as intense as that of carvone. This means that the UV absorbance for limin his an e less than
10,000 (therefore, log e < 1og 104 = 4). The best answer is choice D. This question required some background
information on UV spectroscopy. The minimum you should know is that n-bonds ire UV active, and with
conjugation, the intensity of the absorbance increases and the energy of the absorbance decreases.
80.
Choice C is correct. A Diels-Alder reaction is a cyclization reaction that involves the addition of a diene to a
dienophile (alkene) to form a cyclohexene product. Both limin and carvone are cyclohexene compounds,
eliminating choices A and D, but carvone has a carbonyl group and isoprene contains only Cs and Hs. The best
answer is limin, choice C.
81.
Choice B is correct. It is stated in the passage that corn oil is 63'/, iinoleic acid. Looking at table 1 shows that
linoleic acid is made up of eighteen carbons and has two n-bonds. Choices C and D are eliminated, because they
only have sixteen carbons. Choice A is eliminated, because it l-ras three n-bonds. The best answer is choice B.
You can try to match the exact location of each n-bond from the formula in Table 1 to the drawing in the answer
choices, but doing so is not time efficient.
82.
Choice D is correct. Linoleic acid contains two n-bonds, both with cis geometry. When linoleic acid is treated
with FADH2, the result is hydrogenation of the diene and the formation of the aliphatic carboxylic acid (of
eighteen carbons) stearic acid. The gain of four hydrogen atoms increases the moleCular mass of tne acid (by
four), and the loss of unsaturation results in more molecular flexibility, which results in a higher melting poini.
Unsaturated fats, with less flexibility and therefore less ability to engage in intermoleculaiinteractioni, have
lower melting points than saturated fats of comparable mass. This is Co**orl organic chemistry knowledge
that you should have addressed when comparing vegetable and animal fats. The coirect answer is choice D.
83.
Choice C is correct. Oleic acid is an eighteen-carbon acid with one n-bond between the eighth and ninth
carbons. The a-bond in oleic acid has cis orientation. Treating oleic acid with deuterium (D2) and a catalytic
metal like pailadium adds two deuterium atoms across the n-bond of the alkene molecule. The two deuterium
atoms add syn to one another at carbons eight and nine. The result is the formation of two new chiral centers.
There are no chiral centers to begin with, so the product has tr.tro chiral centers. The best answer is choice C.
84.
Choice D is correct. Potassium permanganate reacts with alkenes to form diols by adding two hydroxyl groups
is a syn addition fashion to the carbons of the n-bond. Linolenic acid has three n-bonds, located between
carbons 9 and 10, carbons 12 and L3, and carbons 15 and 1,6 when the carboxylic acid carbon is considered to be
carbon one (IUPAC convention). Hydroxyl groups form at all sp2-hybridized carbon sites. This results in a
product with hydroxyl groups at carbons 9,70, 12,13, 15, and 16, as listed in choice D.
85^
Choice B is correct. The most bromine per moiecule is consumed by the fatty acid with the greatest number of nbonds present. For every n-bond present, one molecule of bromine tiquid will be consumed. Arachidonic acid has
four n-bonds. Arachidic acid has no n-bonds present in its structure, linoleic acid has two n-bonds present in its
structure, and linolenic acid has three n-bonds present in its structure. Arachidonic acid is the mosiunsaturated
of the choices. The correct answer is thus choice B.
86.
Choice B is correct. Paimitoleic acid has sixteen carbons and one n-bond. When palmitoleic acid is fuliy
hydrogenated, it forms the aliphatic acid of sixteen carbons (listed in Table t as pilmltic acid). The best
answer choice is B.
322
HYDROCAR.BONS EXPLANATIONS
87.
,;a_i;;fi;ii;"
""inl.i#J:T:.ffi:ffil":J""f:tJ:ii::
88.
89.
90.
150'C
____*>
Cyclohexene
Lactone (not lactam)
Carbonyl is NOT conjugated to alkene
o-
C02Me
Compound
CO2Me
CO2Me
1
1)
92.
93'
.11i
HYDROCARBONS EXPLANATIONS
94.
Choice D is correct.
in the presence of light, adds to the most substituted carbon of an alkane by way
,Bromine,
of a free radical mechanism. The most substituted carbon is tertiary, so the choice with bromine added to the
tertiary carbon (most substituted) is the best answer. This makes choice D the correct choice. T'he product
shown, as well as its enantiomer, are both formed.
95.
Choice D is correct., Free radical propagation reactions keep the free radical reaction going, so to be a
propagation reaction, there must be the same number of free radicals on each side of the equation. In choice A,
there is one free radical on the reactant side and three free radicals on the product side, so it is not a
propagation step. Choice A is eliminated. In choice B, there are two free radicals on the reactant side and no
free radicals on the product side, so it is a termination step and not a propagation step. Choice B is eliminated.
In choice C, there is one free radical on the reactant side and two free radicals on the product side, so it is not a
propagation step. Choice C is eliminated. In choice D, there is one free radical on the reactant side and one
free radical on the product side, so it is a propagation step. Choice D is the best answer. You may not recognize
the reaction from the overall mechanism, but it converts a less stable free radical into a more stable free
radical, which ultimately impacts the product distribution.
Choice A is correct. Bergamontene contains fifteen carbons, so it is likely made from three S-carbon isoprene
units. We can't be sure without analyzing the structtire to find the isoprene fragments, but that is not time
efficient. Choice A is the best answer so far, and shall remain our choice until a better one comes.
Bergamontene is a hydrocarbon with no heteroatoms, so it is a terpene and not a terpenoid. This eliminates
choice B. Bergamontene has two n-bonds and a cyclohexane ring, so at first look choice C is tempting. But the
molecule is bicyclic, meaning it has a second ring, the four-membered ring connected to the cycioheiane ring.
Bergamontene has four units of unsaturation, not three. This eliminates choice C. To verify this, bergamontene
has 24 hydrogens and therefore a formula of C15H24. The units of unsaturation are
1z1iS; + Z -24\/2 = 4, so
choice C is eliminated. There are three chiral centers on bergamontene, so 8 (23) is the maximum number of
stereoisomers, not 16. This elimir-rates choice D and secures choice A as the best answer.
97
Choice D is correct. Both the Claisen rearrangement and the Cope rearrangement require dienes, but they need
not be conjugated. The two n-bonds must be separated by three sigma bonds, so choices A and C are eliminated.
Clemmensen reduction converts a carbonyl into an alkane, so no diene of any kind is required. Choice B is
eliminated. A Diels-Alder reaction involves the cyclization of a conjugated diene and a dienophile, so it must
l-rave a conjugated diene. This makes choice D the best answer.
Choice C is correct. For an E2 reaction, the base must be strong enough to remove a proton from carbon and bulky
enough to not undergo substitution. This makes choice A a valid statement and thereby eliminates it. For an E2
reaction, the leaving group and proton being lost from carbon must be positior-red anti to one another, so the
geometry of the product is dependent upon the alignment of the reactant. Cis versus trans results from the
orientation and stereochemistry, so choice B is a valid statement and thereby eliminated. For an E1 reaction, a
leavilg group first leaves, resulting in a carbocation. With carbocations, rearrangement can be observed, so it is
with E1 reactions that we see rearrangement, not E2 reactions. Because E2 reactions are concerted, there is no
rearrangement, so choice C is an invalid statement and thereby the correct answer. Heat is required to drive
both El and E2 reactions, so choice D is a valid statement. It is eliminated, leaving choice C as our choice.
99.
Choice D is correct. Terpenes are hydrocarbons of 70,15,20, etc... carbons, so they are somewhat massive lipids.
Because they are hydrocarbons, they are lipid soluble, so choice A is a valid statement. Choice A is
consequently eliminated. Terpenes have molecular masses of about 140 g/mole, about 210 g/mole, about 280
g/moie, etc..., so they have somewhat high boiling points. High is a relative term, so we ian't be certain in
eliminating choice B. However, choices B and C are the same concept, so they mutually exclude one another
from consideration. It is important that you use all of your test taking stcllls. The specific rotation of a
compor-rnd is dictatecl by its chiral centers, which a terpene may or may not have. Given that there is no
general rule about the chirality of terpenes, we cannot conclude that they have high specific rotations" Choice
D is the best answer.
100.
Choice C is correct. To have a dipoie nol eqr-ral to zero is to have a dipole. To have a dipole is to be polar. Cis
compouuds are always polar so Compound III is polar. Ethvlene is perfectly symmetric, io choice Compound II
is nonpolar. The question comes down to: "Is Compound I polar?" Compound I is not polar, because thl methyl
groups on t1-ie alkene cancel one another and sum to a resultant vector of 0. Choose C for best results.
)1+
HYDROCARI}ONS EXPLANATIONS