STRUCTURE DETERMINATION BY SPECTROSCOPIC METHODS This information is designed to be of help when you are using spectroscopic methods, namely

Nuclear Magnetic Resonance (NMR), Infrared (IR) and mass spectrometry (MS), to determine molecular structure. The information comes in two forms, first there is advice on how to approach structure determination, and second there is a whole host of tabulated values to enable you to link the spectroscopic information to the structure. Principally the information will be used during the second year, first semester seminars, however, you will also find it useful during various laboratory classes, for the third year advanced structure determination course, and during project work and beyond. The object is to give practice in the identification of organic compounds, utilising spectroscopic information which can readily be obtained in all modern laboratories. Generally, the information available from modern spectroscopic methods means that chemical methods of structure determination are no longer necessary, and so such methods do not feature in this course. Spectroscopic Analysis There are no set rules on how to tackle the determination of structure from available spectra, nor is there any prescribed way of writing up your attempts. However, it is often useful to begin with the infrared (IR) spectrum because this will give an overview of the functional groups present in the unknown structure, e.g., carboxylic acid or alcohol or nitrile etc. Such knowledge then becomes useful when you are using the nuclear magnetic resonance (1H and 13 C) spectra to determine the chemical environment of protons and carbons in the structure. The mass spectrum (MS) is extremely useful because it gives the molecular mass, and an accurate mass spectrum can give the molecular formula, so an initial look at the mass spectrum would also be very helpful. Usually no one technique will determine the structure, you will need to use all of the information provided to some extent, and you will need to be constantly referring to all of the spectra provided. This approach will enable you to produce several sub-structures, which can eventually be connected together in a way that fits the spectroscopic data, and hence eventually lead to the correct structure. Remember to keep an open mind, the information may actually lead you to the wrong conclusion, and in some cases it may be possible, given that you are in the early stages of learning, to fully determine the actual structure and you may need to list two or three possibilities which you feel fit the data. Overall, the information provided should allow you to determine the functional groups likely to be present in the molecule, the nature, relative number, and environment of the hydrogen atoms (protons), and the number and nature of the different carbon atoms in the skeleton, and the molecular mass and sometimes the molecular formula. For the purposes of the learning exercise you should always show clearly the reasoning behind your assignments and relate them to your proposed structure (you may in fact have more than one possible structure).

Notes on the Infrared (IR) Spectra of Organic Compounds (i) An IR spectrum is usually very complex, it is impossible to assign every peak, and in any case may lead to confusion. For some exercises, in order to facilitate interpretation, the significant bands have been marked with an arrow (). In cases where arrows are not provided, only those bands which reveal a significant functional groups need be interpreted. In each case their positions should be recorded in cm1 and an assignment made with the aid of the Tables in Appendix 1. There are no rigid rules for the interpretation of an IR spectrum, but it is convenient to divide the spectrum into various regions and examine each in turn. The lists in paragraph (iii) show the functional groups which absorb within a given region. Examination of these will give a possible assignment of a particular band. Reference to the Tables (Appendix 1) will give detailed IR information about the suspected functional group and indicate the appropriate confirmatory bands.

(ii)

(iii) Region 1, 1640-1859 cm1 (The "Carbonyl" Region) All carbonyl compounds (aldehydes, ketones, esters, lactones, acid chlorides, anhydrides, carboxylic acids, amides). Bands are due to C=O stretching. Region 2, 2500-3700 cm1 Alcohols, phenols, carboxylic acids (O-H stretching) Primary and secondary amines and amides (N-H stretching) Aldehydes (C-H stretching) NOTE: Other C-H stretching bands occur within this region. They are of limited use, since most organic compounds contain C-H bonds. Region 3, 1850-2500 cm1 Nitriles (CN stretching) HIGHLY CHARACTERISTIC Region 4, 1350-1640 cm1 Alkanes (C-H deformation). Of limited value. Alkenes, aromatic compounds (C=C stretching) Amides Nitro-compounds (NO2 stretching) Tertiary aromatic amines (C-N stretching) Region 5, 650-900 cm1 Aromatic compounds (C-H out-of-plane deformations). Useful bands; give the orientation of substituents on the ring. Aromatic nitro-compounds Region 6, 990-1350 cm1 Ethers (C-O stretching) Alcohols and Phenols Ketones, esters, and carboxylic acids Amines (some overlap with Region 4) Alkenes NOTE: This region contains many bands which are characteristic only of the compound in question. It is commonly known as the "finger-print" region. (iv) When assigning bands, it is bad practice to try to write down every possibility for each band. It is much better to seek confirmatory evidence as you work through the exercise. For example, if there is a band in the carbonyl region which could be due to a carboxylic acid, a glance at the O-H stretching region will show immediately whether or not a C=O band in the IR spectrum is due to an aldehyde.

(v)

Remember that the absence of bands may give useful information. For example, if there is no band in the carbonyl region, there is no C=O group present in the molecule.

Notes on the Nuclear Magnetic Resonance (NMR) Spectra of Organic Compounds

1

H NMR

(i)

Of the common nuclei (H, C, O, N, halogens) only hydrogen and fluorine give strong NMR signals. NMR spectra are therefore much simpler than infrared spectra, and consist of several bands, all of which must be assigned (except for signals from residual solvent or obvious impurities). The position of each band (known as the 'chemical shift') is dependent upon the environment of the proton concerned. Different types of protons have different chemical shifts. Chemical Shifts The position of a band is usually measured on a scale 0-10 . Tetramethylsilane (SiMe4) is used as a reference standard, the position of its single absorption line being arbitrarily fixed as 0 (this is at a lower precessional frequency than all the common types of protons). A shift towards high precessional frequencies (i.e., towards 10) is commonly referred to as a de-shielding effect or a paramagnetic shift. A shift towards lower precessional frequency (i.e., towards 0 or less) is known conversely as a shielding effect or diamagnetic shift).

(ii)

(iii) An NMR spectrum can be divided roughly into the following regions: > 10 9-11 4.5-8 6.5-8 1-4 acidic protons (-CO2H and intramolecularly H-bonded -OH groups) -CHO (very characteristic) olefinic (alkenic) protons aromatic protons (note possible overlap with olefinic protons) CH3-X, -CH2-X, and -CH-X (the position depends markedly on the nature of X. See paragraph iv).

NOTE: -OH and -NH absorptions occur over a wide range, and the signals are often broad. (iv) In the series CH3-X, -CH2-X , and -CH-X, there is an increasing shift to high precessional frequency as X becomes more electronegative. e.g., CH3-CH3 0.9 C H3 I 2.16 CH3-CH-CH2 1.7 CH3Br 2.68 (CH3)2C=O 2.2 CH3Cl 3.06 CH3-Ph 2.3 CH3-NH2 2.5 CH3-OH 3.5 More precise chemical shifts are listed in Appendix 2.

(v)

Integration The area of a peak is proportional to the number of protons under that peak. Integration of a spectrum enables the relative numbers of protons under different peaks to be established.

(vi) Spin-spin Coupling (splitting) (a) If a CH3, CH2, or CH group is situated adjacent to a carbon atom to which are attached n equivalent protons, the resonance due to that group will be split into n +1 peaks. e.g., in the case of CH3.CH2OH, the CH3 peak is a triplet centred at 1.2 and the CH2 peak is a quartet centred at 3.7.

! 3.7

! 1.2

The distance apart (J) of each of the lines in the triplet and the quartet is equal, and is called the "spin-spin coupling constant". J is usually fairly small, and is therefore measured in Hertz, rather than as a value. The spectra used in the present course were determined on a 60 MHz instrument, so that 1 = 60 Hz or a 270 MHz instrument so that 1 = 270 Hz. (b) Coupling constants are often of value in making structural assignments e.g., in Ph. CH = CH. CO2Et

H!

H"

J
# 7.2

J
5.9

In this case J = 16 Hz, showing that the two olefinic protons are trans-oriented (see below). (c) Spin-spin splitting of aromatic protons often leads to a very complex splitting pattern. In the case of p-disubstituted aromatic compounds, however, the expected pair of doublets often shows up very clearly in the region 4.5 to 8, and is very characteristic.

(d)

The following are some typical spin-spin coupling constants:

sub-structure

J H-H' in Hz
2 to 9 (e.g., 7 Hz for ethanol)

H' H H' 0 to 3.5

cis
H H' H' H H H' H H'

6 to 14

trans

11 to 18

4 to 10

ortho 7 to 10 meta 2 to 3 para 0 to 1

Summary From each signal you should be able to obtain three pieces of information: 1. 2. 3. From the chemical shift, the environment of the proton-containing group; From the integration, the relative number of protons in the proton-containing group; From the splitting, the number of protons on an adjacent carbon atom.

13C NMR

(i)

Sensitivity

Only 1.06% of natural carbon is 13C (12C is nonmagnetic) and the magnetic moment of 13C is about a quarter of that for 1H. These two factors make sensitivity low, however, using 'pulsed Fourier transform' methods the sensitivity can be enhanced by summation of the signals. (ii) Resolution

The positions of the 13C NMR signals (0 to 200 ) are much more spread out than those of 1H NMR and so 13C spectra are much better resolved (x20) and usually more simple.

(iii)

Chemical Shift

The positions of the 13C NMR signals are governed by similar rules to those for 1H NMR, i.e., carbons which are attached to electronegative moieties will give signals at higher frequencies due to a deshielding effect. (iv) Integration

Unlike 1H NMR, 13C NMR is NOT normally quantitative. (v) Spin-spin Coupling (Splitting)

Both 13C and 1H are magnetic and so coupling between 13C-13C and between 13C-1H should be possible. However, the low abundance of 13C means that the probability of two 13C atoms being together is negligible and so 13C-13C coupling does not occur. However, the 13C-1H couplings are observed and make 13C spectra extremely complex. To avoid this, Broad Band Decoupling is applied and this enables each different carbon atom to appear as a single line. This is very useful because it enables the number of different carbon atoms in the unknown structure to be determined. Notes on the Mass Spectra (MS) of Organic Compounds The first process induced by electron bombardment in the mass spectrometer is the removal of a single electron from the molecule to give the molecular ion (i.e., a radical-ion containing one unpaired electron):

The molecular ion is usually sufficiently stable to be recorded; it then appears as the peak of highest mass in the spectrum. The mass of the molecular ion gives directly the molecular weight of the compound. Although no structural information can be gained from the molecular weight alone, it is invaluable when combined with the information provided by NMR and IR. The molecular ion also breaks down into smaller fragment ions, the break down occurs such that the most stable fragments are formed (weakest bonds break). The mass of the fragment ions are also recorded, and by piecing them together some structural information may be provided. The isotopic distribution for some elements provides valuable structural information. For example chlorine is a 3:1 mixture of 35Cl and 37Cl and so a compound with a single chlorine atom would produce two molecular ion peaks in a 3:1 ratio. Similarly, bromine is a 1:1 mixture of 79Br and 81Br, and hence a compound with a single bromine atom would produce two molecular ion peaks in a 1:1 ratio. Accurate mass spectrometry provides the molecular formula of a compound by taking account of the isotopic distributions of all elements present, however, small. For example, the 1.1% of 13C and even the 0.015% of 2H is taken into account to enable a molecular formula to be determined.

APPENDIX 1 TABLES OF IR ABSORPTION FREQUENCIES Introduction (i) Values are given in cm1. (ii) Intensities of bands are indicated as follows (s) (m) (w) (v) strong medium weak variable

(iii) It is not possible to include all types of functional groups, or to include all confirmatory bands. For further information one of the standard texts should be consulted. 1. ALKYL GROUPS N.B. These are more readily detected in the NMR spectrum. C-H Stretching -CH3, -CH2-, -CH-OMe -NMe C-H Deformation C-Me C-Me2 C-Me3 Others -(CH2)n [n 4] 2. ALKENES C=C Stretching C=C (non-conj.) C=C (conj. with C=O or C=C) C=C (conj. with phenyl) CHR=CH2 CHR1=CHR2 (cis) CHR1=CHR2 (trans) CR1R2=CH2 CR1R2=CHR3 1680-1620 (v) 1660-1580 (s) ca. 1625 (s) 1645-1640 (v) 1665-1635 (v) 1675-1665 (v) 1660-1640 (v) 1675-1665 (v) 2975-2860 (m) Of limited value: most organic cpds show C-H absorption 2830-2815 (m) sharp 2820-2760 (m) sharp 1470-1435 1385-1370 1385-1380 1370-1365 1395-1385 1365 750-720 (m) (s) (s) (s) (m) (s) (s) Arom. bands also occur in this region ) Doublet; approx. equal intensity. ) ) Doublet; int. ratio ca. 1:2 )

C-H Out-of-Plane Deformations* CHR1=CH2 CHR1=CHR2 (cis) CHR1=CHR2 (trans) CR1R2=CH2 CR1R2=CHR3

995-985 915-905 1850-1800 1420-1400 730-665 980-960 1310-1290 895-885 1800-1780 1420-1410 850-790

(m) (s) (w) (w) (s) (v) (w) (v) (w) (w) (m)

* NOTE: all show C-H str. bands at ca. 3000. 3. HOMOCYCLIC AROMATIC COMPOUNDS C=C Stretching*
1625-1575

(v) usually close to 1600 1525-1475 (v) usually close to 1500 1590-1575 (v) strong for conj. rings. 1465-1440 (v)

* Also C-H str. at ca. 3050.

All four bands are not always observed.

C-H Out-of-Plane Deformations Indicate the nature of the substitution pattern of the benzene ring. Monosubstitution 1,2-Disubstitution 1,3-Disubstitution 770-730 (s) ) two bands 710-690 (s) ) 770-690 (s) one band

900-860 (m) ) three bands, not 810-750 (s) ) always within 725-680 (m) ) these limits 860-800 (s) one band

1,4-Disubstitution 1,2,4-Trisubstitution 1,3,5-Trisubstitution

860-800 (s) ) two bands 900-860 (m) ) 900-860 (m) ) 865-810 (s) ) three bands 730-675 (s) ) 800-770 (s) ) two bands 720-685 (m) )

1,2,3-Trisubstitution 4. ETHERS C-O Stretching acyclic CH2-O-CH2 aryl or aralkyl

1150-1060 (s) 1270-1230 (s) usually near 1250 1120-1030 (m)

5.

ALCOHOLS AND PHENOLS O-H Stretching free OH (in dil. soln.) H-bonded OH 3670-3580 (v) sharp 3550-3200 (v) often broad

C-O Stretching and O-H in-plane deformations* primary alcohol 1075-1000 (s) 1350-1260 (s) secondary alcohol 1120-1030 (s) 1350-1260 (s) tertiary alcohol 1170-1100 (s) 1410-1310 (s) phenols 1230-1140 (s) 1410-1310 (s) *all of limited value 6. ACYL HALIDES AND ANHYDRIDES C=O Stretching 5-membered cyclic anhydrides acyclic anhydrides acyl halides C-O Stretching cyclic anhydrides acyclic anhydrides 7. KETONES C=O Stretching (all strong) acyclic -unsat. acyclic 5-membered ring 6-membered ring aryl diaryl 1670-1660 -diketones enolised -diketones o-hydroxy-aryl Other vibrations CH3-CH-CH2-CO1725-1700 1695-1660 1750-1740 1720-1700 1700-1680 1730-1710 1640-1535 broad 1655-1610 intramol. H-bonding 1360-1355 (s) 1435-1405 (s) 1870-1830 (s) ) Two bands. Lowered ca 1800-1760 (s) ) 20 cm-1 by conj. 1840-1800 (s) ) Two bands 1780-1740 (s) ) 1800-1770 (s) 1310-1210 (s) 1175-1045 (s)

8.

ALDEHYDES C=O Stretching sat. aliphatic -unsat. aryl o-hydroxy-aryl C-H Stretching all aldehydes 1740-1720 (s) 1705-1685 (s) 1715-1695 (s) 1670-1645 (s) intramol. H-bonding 2880-2650 (w) usually two bands ca. 2820, ca. 2720

9.

CARBOXYLIC ACIDS O-H Vibrations 3300-2500 (O-H str.) v broad, ragged band 955-890 (v) (o.o.p. def.) broad These bands are highly characteristic C=O Stretching (all strong) sat. aliphatic -unsat. aryl o-hydroxy or o-amino aryl -halogeno 1725-1700 1715-1680 1700-1680 1680-1650 1740-1715

10.

ESTERS AND LACTONES C=O Stretching (all strong) sat. aliphatic esters -unsat. and aryl esters phenolic esters -keto-esters enolic -keto-esters o-hydroxy- or o-aminobenzoates -halogeno alkyl esters sat. -lactones sat. -lactones C-O Stretching aromatic esters 1750-1735 1730-1715 1800-1770 1755-1740 1655-1635 intramol. H-bonding 1690-1670 intramol. H-bonding 1770-1755 1780-1760 1750-1735 two bands (s) between 1300 and 1050

11.

AMINES N-H Stretching primary secondary N-H Deformation primary secondary C-N Stretching aliphatic primary arom. secondary arom. tertiary arom. 3500-3300 (v) two bands 3500-3300 (v) one band 1650-1580 (m-s) 1650-1550 (w) 1220-1020 (w-m) 1340-1250 (s) 1350-1280 (s) 1360-1310 (s)

12.

AMIDES N-H Stretching primary secondary primary and secondary ca. 3500 and ca. 3400 (s) ) in dil. soln. only ca. 3450 ) 3350-3100 (m) in solid phase: often several bands

C=O Stretching (Amide I band) (all strong) primary ca. 1690 dil. soln. ca. 1650 solid phase secondary 1700-1665 dil. soln. 1680-1630 solid phase tertiary 1670-1630 Combination bands of NH def. and C-N str. primary 1650-1620 1620-1590 secondary 1570-1515 1550-1510 1305-1200 Other Vibrations primary secondary 13. NITRILES C N Stretching sat. aliphatic -unsat. aryl 14. 2260-2240 2235-2215 2240-2220 (w-m) (s) (m-s) 1420-1400 770-620 630-530 (s) (s) (s) (s) (m) (m) (m) (s) solid phase dil. soln. solid phase dil. soln. Amide III (Amide II) (Amide II) (Amide II) (Amide II)

AROMATIC NITRO COMPOUNDS 1550-1510 1365-1335 860-840 ca. 750 (s) asym. NO2 str. (s) sym. NO2 str. (s) C-N vib. (s)

APPENDIX 2 TABLE OF APPROXIMATE CHEMICAL SHIFTS (a) Protons attached to carbon CH3 C -CH2 C -CH C
! range

0.8-1.2

1.1-1.7

1.5-1.9 1.2-1.9

CH3 C-X (X = O or N) CH3 CH3 -CH2 -CH C=C

1.6-2.3

CO-X (X = C, O, or N)

1.9-2.7

CO-X (X = C, O, or N) CO-X (X = C, O, or N)

2.3-2.9

2.4-3.0

-CH2 -CH

CN CN

2.4-2.9

2.4-2.9

CH3 -CH2 -CH

Ar Ar

2.1-2.6 2.5-3.0

Ar

2.8-3.2

CH3 -CH2 -CH

N N N 2.1-3.2

Table of Approximate Chemical Shifts (cont.) range 3.1-3.7

!

-CH2-halogen CH3-OX -CH2-OX -CH-OX (X = H, R, Ar, COR)

3.2-4.0

3.5-4.5

ArCH2-X (X = halogen, O or N) -CH=C (olefinic)

3.5-5.2

4.3-6.5

-CH=C (aromatic)

6.0-8.6

-CHO

9.4-10.2

(b) Protons attached to oxygen or nitrogen NOTE: Chemical shifts vary with concentration, and the bands are often broad. The following values should be regarded as being very approximate. ! range 1-4 RNH2 ROH 2-5

ArOH

4.5-10.5

ArNH2 and ArNH CONH2 ArNHCO

3-7

5.5-8.0 7-10

Enolic and intramolecularly H-bonded OH

10-16

COOH

9-13

! Values for Carbons in Carbonyl Environments Structural Unit R Ar CHO CHO CHO R CO Ar CO Ar CO CO R' R Ar' Ar O 209-213 214-220 166-181 169-176 164-169 170-178 162-179 CO 163-175 167-172 114-124 ! Range 200-205 190-194 190-194 205-218 196-199 196-199 196-199

C R R Ar COOH

COOR' COOAr' C O CON CO O O

R R

COCl CN

! Values for Carbons in Methyl Groups Structural Unit CH3 CH3 CH3 Ar OAr OR O CH3 C O CH3 C O CH3O CH3 C N O CH3 CH3 N C N O C R 31-39 24 R 51-52 30-45 OR 20-22 R 26-31 ! Range 20-21 56 59

APPENDIX 3 EXAMPLES OF INFORMATION FROM MASS SPECTROMETRY (MS) As mentioned earlier, the peak of highest mass is usually the molecular ion and provides the molecular weight. Other peaks are present that represent fragment ions which are generated according to their stability and from the breakage of the weakest bonds.
43 2-methylpentane

relative abundance 29 57 15

71

86 m/z

10

20

30

40

50

60

70

80

90

2-Methylpentane shows only a small molecular ion peak (at 86) because it is a branched system and readily fragments. The fragmentation occurs to give preferentially the relatively stable secondary cation which shows as the largest peak at 43. It must be remembered that a compound such as CH3Cl is, in fact, a mixture of CH335Cl and CH337Cl (together with minor contributions from 13C and 2H). 35Cl and 37Cl occur naturally in the ratio of 3:1 respectively. Thus, the mass spectrum of CH3Cl will show two main molecular ion peaks (50 and 52) with relative intensities of 3:1. Such a situation is general for any compound containing a single chlorine atom, and provides excellent evidence for such a compound. Bromine contains 79Br and 81Br in the ratio of 1:1. Thus the mass spectrum of CH3Br will show two main molecular ion peaks (94 and 96) of equal intensity. The presence of a chlorine or a bromine in an organic compound cannot be detected by NMR or IR. The presence of an odd number of nitrogens in an organic compound can be detected by MS because the molecular ion peak would be an odd number. Accurate mass spectrometry provides the molecular formula of a compound by taking account of the isotopic distributions of all elements present, however, small. For example, the 1.1% of 13C and even the 0.015% of 2H is taken into account. A molecular weight of 188.2746 represents a molecular formula of C12H16N2, and a molecular weight of 154.2535 represents a molecular formula of C10H18O. The masses of sub-units CO (27.9949), N2 (28.0062) and C2H4 (28.0312) are all 28 by low resolution MS but are clearly distinguished by high resolution MS. In this course, MS data may not be provided initially because such knowledge may impair your ability to interpret NMR and IR spectra. If you have extracted all the information possible from the NMR and IR, and cannot finalise the exact structure then MS data will be provided.