NUCLEOPHILIC SUBSTITUTION:

In a substitution reaction, an alkyl halide reacts with a nucleophile to give a product in

which the nucleophile replaces the halogen, which is expelled as a leaving group. There
are two competing mechanisms for nucleophilic substitution:

1. SN1
2. SN2

1. SN1

The SN1 reaction is a substitution reaction in organic chemistry. "SN1" stands

for unimolecular nucleophilic substitution

SALIENT FEATURES OF SN1 MECHANISM

The "1" represents the fact that the rate-determining stepis unimolecular. Thus, the rate
equation is often shown as having first-order dependence on electrophile and zero-
order dependence on nucleophile. This relationship holds for situations where the
amount of nucleophile is much greater than that of the carbocation intermediate.
Instead, the rate equation may be more accurately described using steady-state
kinetics. The reaction involves a carbocation intermediate and is commonly seen in
reactions of secondary or tertiary alkyl halides under strongly basic conditions or, under
strongly acidic conditions, with secondary or tertiary alcohols.

MECHANISM
An example of a reaction taking place with an SN1 reaction mechanism is
the hydrolysis of tert-butyl bromide with water forming tert-butanol:

This SN1 reaction takes place in three steps:

 Formation of a tert-butyl carbocation by separation of a leaving

group (a bromide anion) from the carbon atom: this step is slow and reversible.[4]
  Nucleophilic attack: the carbocation reacts with the nucleophile. If
the nucleophile is a neutral molecule (i.e. a solvent) a third step is
required to complete the reaction. When the solvent is water, the
intermediate is an oxonium ion. This reaction step is fast.

 Deprotonation: Removal of a proton on the protonated nucleophile by

water acting as a base forming the alcohol and a hydronium ion. This
reaction step is fast.

FACTORS AFFECTING THE RATE OF SN1 REACTION

SN1 reactions are affected by the nature of the substrate, the nature of the nucleophile,
and the nature of the solvent.
i. Nature of Substrate
A tertiary substrate is most likely to undergo an SN1 reaction because of steric
hindrance.

SN1 reaction of molecules from www.meritnation.com.

An approaching nucleophile is unable to attack the back side of the carbon bearing the
leaving group.
ii. Nature of the Nucleophile
The weaker the nucleophile, the less likely it is able to attack the carbon atom.
So it is more likely that the leaving group will leave first in an SN1 reaction.
iii. Nature of the Solvent
Polar protic solvents favour SN1reactions.
They form a solvent shell around the nucleophile, and this hinders nucleophilic attack on
the substrate.
This again makes it more likely that the leaving group will leave in an SN1mechanism.

EXAMPLES
An example ofthe Sn1 Mechanism

2.SN2

In the SN2 reaction, the addition of the nucleophile and the departure of the leaving
group occur in a concerted(taking place in a single step) manner, hence the name SN2:
substitution, nucleophilic, bimolecular. In the SN2 reaction, the nucleophile approaches
the carbon atom to which the leaving group is attached. As the nucleophile forms a
bond with this carbon atom, the bond between the carbon atom and the leaving group
breaks. The bond making and bond breaking actions occur simultaneously. Eventually,
the nucleophile has formed a complete bond to the carbon atom and the bond between
the carbon atom and the leaving group is completely broken.

SALIENT FEATURES OF SN2

1. The rate of the reaction depends on the concentration of both the nucleophile
and the molecule undergoing attack. The reaction requires a collision between
 the nucleophile and the molecule, so increasing the concentration of either will
increase the rate of the reaction.
2. Since the unique geometry of back side attack is required, the most important
factor in determining whether an SN2 reaction will occur is steric effects. Steric
effects refer to the unfavorable interaction created when atoms are brought too
close together. In effect, if the nucleophile or the molecule undergoing attack
have too many substituents or substituents which are too bulky, the reaction
cannot occur since the nucleophile will be unable to get close enough to the
molecule to do a backside attack.
3. With primary and secondary alkyl halides, the SN2 reaction occurs
MECHANISM

In the example of the SN2 reaction, the attack of Br− (the nucleophile) on an ethyl
chloride (the electrophile) results in ethyl bromide, with chloride ejected as the leaving
group.:

SN2 reaction of chloroethane with bromide ion

SN2 attack occurs if the backside route of attack is not sterically
hindered by substituents on the substrate. Therefore, this mechanism usually occurs at
unhindered primary and secondary carbon centres. If there is steric crowding on the
substrate near the leaving group, such as at a tertiary carbon centre, the substitution will
involve an SN1 rather than an SN2 mechanism, (an SN1 would also be more likely in this
case because a sufficiently stable carbocation intermediary could be formed).

FACTORS AFFECTING THE RATE OF THE REACTION

Four factors affect the rate of the reaction:[2]
i. Substrate
The substrate plays the most important part in determining the rate of the reaction. This
is because the nucleophile attacks from the back of the substrate, thus breaking the
carbon-leaving group bond and forming the carbon-nucleophile bond. Therefore, to
maximise the rate of the SN2 reaction, the back of the substrate must be as unhindered
as possible. Overall, this means that methyl and primary substrates react the fastest,
followed by secondary substrates. Tertiary substrates do not participate in S N2
reactions, because of steric hindrance. Structures that can form highly stable cations by
simple loss of the leaving group, for example, as a resonance-stabilized carbocation,
are especially likely to react via an SN1 pathway in competition with SN2.
ii. Nucleophile
Like the substrate, steric hindrance affects the nucleophile's strength.
The methoxide anion, for example, is both a strong base and nucleophile because it is a
methyl nucleophile, and is thus very much unhindered. tert-Butoxide, on the other hand,
is a strong base, but a poor nucleophile, because of its three methyl groups hindering its
approach to the carbon. Nucleophile strength is also affected by charge
and electronegativity: nucleophilicity increases with increasing negative charge and
decreasing electronegativity. For example, OH− is a better nucleophile than water, and
I− is a better nucleophile than Br− (in polar protic solvents). In a polar aprotic solvent,
nucleophilicity increases up a column of the periodic table as there is no hydrogen
bonding between the solvent and nucleophile; in this case nucleophilicity mirrors
basicity. I− would therefore be a weaker nucleophile than Br− because it is a weaker
base. Verdict - A strong/anionic nucleophile always favours SN2 manner of nucleophillic
substitution.
iii. Solvent
The solvent affects the rate of reaction because solvents may or may not surround a
nucleophile, thus hindering or not hindering its approach to the carbon atom. Polar
aprotic solvents, like tetrahydrofuran, are better solvents for this reaction than
polar protic solvents because polar protic solvents will hydrogen bond to the
nucleophile, hindering it from attacking the carbon with the leaving group. A polar
aprotic solvent with low dielectric constant or a hindered dipole end will favour S N2
manner of nucleophilic substitution reaction. Examples: DMSO, DMF, acetone etc. In
polar aprotic solvent, nucleophilicity parallels basicity.
iv. Leaving group
The stability of the leaving group as an anion and the strength of its bind to the carbon
atom both affect the rate of reaction. The more stable the conjugate base of the leaving
group is, the more likely that it will take the two electrons of its bond to carbon during
the reaction. Therefore, the weaker the leaving group is as a conjugate base, and thus
the stronger its corresponding acid, the better the leaving group. Examples of good
leaving groups are therefore the halides (except fluoride, due to its strong bond to the
carbon atom) and tosylate, whereas HO− and H2N− are not.
EXAMPLES
The mechanism for an SN2 reaction is a backside-attack of the electrophilic
carbon, inverting the stereochemistry at that carbon.

. In the following example, the hydroxide ion is acting as the nucleophile and bromine is
the leaving group:
Because of the backside attack of the nucleophile, inversion of configuration occurs.

ELIMINATION REACTIONS
there are two mechanisms of substitution (SN2 and SN1), there are two mechanisms of
elimination (E2 and E1).

1) E2 mechanism — bimolecular elimination

2) E1 mechanism — unimolecular elimination

The E2 and E1 mechanisms differ in the timing of bond cleavage and bond formation,
analogous to the SN2 and SN1 mechanisms. E2 and SN2 reactions have some
features in common, as do E1 and SN1 reactions

1) E1 MECHANISM
E1 is a model to explain a particular type of chemical elimination reaction. E1 stands
for unimolecular elimination and has the following specificities.
SALIENT FEATURES OF E1

 It is a two-step process of elimination: ionization and deprotonation.

 Ionization: the carbon-halogen bond breaks to give a carbocation intermediate.
 Deprotonation of the carbocation.
 E1 typically takes place with tertiary alkyl halides, but is possible with some
secondary alkyl halides.
 The reaction rate is influenced only by the concentration of the alkyl halide because
carbocation formation is the slowest step, aka the rate-determining step.
Therefore, first-order kinetics apply (unimolecular).
 The reaction usually occurs in the complete absence of a base or the presence of
only a weak base (acidic conditions and high temperature).
 E1 reactions are in competition with SN1 reactions because they share a common
carbocationic intermediate.

 MECHANISM
 An example is the pyrolysis of a certain sulfonate ester of menthol:

Only reaction product A results from antiperiplanar elimination. The presence of

product B is an indication that an E1 mechanism is occurring.[3]

 It is accompanied by carbocationic rearrangement reactions

FACTORS AFFECTING THE RATE OF AN E1 REACTION

a) Identity of R group –

More substituted halides react faster Rate: R 3CX > R 2CHX > RCH 2 X

b) Strength of the base

– Favored by weaker bases such as H 2O and ROH

c) Leaving group

– Better leaving group leads to faster reaction rates. Just as in S N 1 reactions

reactions, the rate determining determining step involves the C—X bond cleavage

d) Type of solvent –

Favored by polar protic solvents, which can stabilize the ionic intermediates

EXAMPLES
:

E2 MECHANISM
During the 1920s, Sir Christopher Ingold proposed a model to explain a peculiar type of
chemical reaction: the E2 mechanism. E2 stands for bimolecular elimination. The
reaction involves a one-step mechanism in which carbon-hydrogen and carbon-
halogen bonds break to form a double bond (C=C Pi bond).

 SALIENT FEATURES OF E2
 E2 is a single step elimination, with a single transition state.
 It is typically undergone by primary substituted alkyl halides, but is possible with
some secondary alkyl halides and other compounds.
 The reaction rate is second order, because it's influenced by both the alkyl halide
and the base (bimolecular).
 Because the E2 mechanism results in the formation of a pi bond, the two leaving
groups (often a hydrogen and a halogen) need to be antiperiplanar.
An antiperiplanar transition state has staggered conformation with lower energy than
a synperiplanar transition state which is in eclipsed conformation with higher energy.
The reaction mechanism involving staggered conformation is more favorable for E2
reactions (unlike E1 reactions).

 MECHANISM
 E2 typically uses a strong base. It must be strong enough to remove a weakly acidic
hydrogen.
 In order for the pi bond to be created, the hybridization of carbons needs to be
lowered from sp3 to sp2.
 The C-H bond is weakened in the rate determining step and therefore a
primary deuterium isotope effect much larger than 1 (commonly 2-6) is observed.
 E2 competes with the SN2 reaction mechanism if the base can also act as a
nucleophile (true for many common bases).

 For instance, the base-induced elimination of "HX" (dehydrohalogenation) of an alkyl
halide gives rise to an alkene (illustrated below for the conversion of tert- butyl
bromide to isobutylene).


 E2 eliminations, in contrast to E1 reactions are promoted by strong base. The
base vital to the reaction; it is directly involved in the rate-determining step. The
reaction is bimolecular--that is, it involves "second-order kinetics--because two
molecules must come together for the reacti on to occur. The mechanism of an E2
elimination reaction is shown below:


 Notice that the hydrogen that is removed is on the carbon atom that is adjacent to
the one bearing the halogen. For some reason, beginning students are often
confused on this point, although it is mysterious as to why they should be. Carbon-
carbon double bonds, by definition,exist between two adjacent carbon atoms.
Likewise, the "H" and the "X" atoms that are eliminated during the
dehydrohalogenation of an alkyl halide must be on the carbon atoms.

FACTORS AFFECTING THE RATE OF AN E2 REACTION

There are close parallels between E2 and SN2 mechanisms in how the identity of the
base, the leaving group and the solvent affect the rate.
 a. Strenght of bases

The base appears in the rate equation, so the rate of the E2 reaction increases as the
strength of the base increases. E2 reactions are generally run with strong negatively
charged bases like OH E2 − reactions are generally run with strong, negatively charged
bases like OH and OR−

b. solvents

Polar aprotic solvents increase the rate of E2 reactions

c. Leaving group

There is a partial breaking of the bond to the leaving group in the transition state. So,
the better the leaving group the faster the E2 reaction.

d. Rate of reaction Rate of reaction follows the order Rate of reaction follows the
order, R−I > R−Br > R−Cl > R−F

EXAMPLES

the mechanism of E2 elimination from an alkyl halide, RX.

https://study.com/cimages/multimages/16/devino_rx_
e2.jpg

Bimolecular elimination occurs in a

single, concerted step.

An example of this type of reaction in is the reaction

of isobutylbromide with potassium ethoxide in ethanol. The reaction products
are isobutylene, ethanol and potassium bromide.