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345 NMR Handout PDF
345 NMR Handout PDF
Chem 345
Univ. Wisconsin, Madison
NMR Spectroscopy
Chemical Shifts
Chemical shifts have their origin in the circulation of electrons induced by the magnetic field, which reduces the
actual field at the nucleus. Thus a higher magnetic field has to be applied to achieve resonance. Different types of
protons in a molecule are surrounded by different electron densities, and thus each one sees a slightly different
magnetic field.
Bo
eA
B = Bo - Be
o = B/2
Be
The Larmour precession frequency o depends on the magnetic field strength. Thus at a magnet strength of 1.41
Tesla protons resonate at a frequency of 60 MHz, at 2.35 Tesla at 100 MHz, and so on. Although Hz are the
fundamental energy unit of NMR spectroscopy, the use of Hz has the disadvantage that the position of a peak is
dependent on the magnetic field strength. This point is illustrated by the spectra of 2-methyl-2-butanol shown below at
several different field strengths, plotted at a constant Hz scale.
CH3 b a
HO C CH2 CH3
CH3
d
Me4Si
220 MHz
400
300
200
100
c
a
100 MHz
200
100
100
60 MHz
For this reason, the distance between the reference signal (Me 4Si) and the position of a specific peak in the
spectrum (the chemical shift) is not usually reported in Hz, but rather in dimensionless units of , which is the same on
all spectrometers.
=
H Chemical Shifts
H
H
X=O,Cl,Br
X H
H
O
H
X=N,S
X H
Alkanes
R
H
10
ppm
Downfield
Deshielded
High frequency
Bo decreases
Bo increases
o increases
o decreases
Upfield
Shielded
Low frequency
The ranges above provide an estimate of the chemical shift for simple molecules, but don't help very much when
there are multiple substituents. A simple scheme can be used to estimate chemical shifts of protons on sp 3 carbons.
Use the base shift for methyl groups. CH2 groups, and CH groups, and add to these the increments for each
substituent:
Base Shift
CH3
0.9
CH2
1.2
CH
1.5
Increment
OC(=O)R
OR
Br
Cl
Aryl
C(=O)R
C=C
3.0
2.3
2.2
2.4
1.4
1.0
1.0
1.5
1.4
2.3
Calculated:
Observed:
5.3
4.8
OH
Ph
Cl
1.2
2.4
Calculated:
Observed:
3.6
3.65
-8.8
Me-Te-H
(Me3Si)3Si-Se-H
-5.5
-2
-2.1
-2.2
-2.3
H-Se-CH2Ph
-0.1
-2.4
-2.5
-0.3
-0.4
-2.7
-2.8
-2.9
-0.5
-0.6
-0.7
-3.1
-3
-3.2
-3.3
-3.4
-3.5
-3.6
-3.7
-3.8
-3.9
-4
-1.2
-1.3
-1.4
-1.5
-1.6
-1.7
-1.8
-1.9
-2
(CH3)2Mg
(Me3Si)3Si-S-H
CH3Li
-0.2
-2.6
-0.8
-0.9
-1.1
-1
CH3
NC
CH3
CH3
CH3-CH2-CH3
(CH3)3CCl
CH3-CN
(CH3)3COH
CH3CH2Br
CH3-CO2Me
CH3CH2I
1.9
1.8
HO
1.6
1.5
1.4
1.3
1.2
1.1
0.9
O
H-CC-S-Ph
O
CH3-CO2CH3
(CH3O)2CH2
O
Ph-C-CC-H
CH3O-Ph
Br-CH2CH2-Br
CF3CH2OH
H
O
CH3CH2OH
(CH3)4Sn
(CH3CH2)2CO (CH3)3CH
1.7
(CH3)4C
CH3CH2OH
(CH3)3CBr
(CH3)4Si
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
(Me2N)3P=O
CH3CCl3
(CH3)2N-Ph
Ph-CH2-CH3
(CH3)2O
CH3OH
CH3CH2I CH3Cl
H-CC-Ph
3.4
3.2
2.9
CH3Br
(CH3)3N
(CH3CH2)2CO
(CH3)2S
CH3
H-CC-H
(CH3CH2)3N
Ph-CH3
CH3I
CH3
CH3
3.9
3.8
3.7
3.6
3.5
3.3
3.1
H
H
(CH3O)2CH2
ClCH2CH2Cl
CHCl2CO2Me
5.9
5.8
H Ph
5.7
5.6
5.5
2.6
HC(OEt)3
2.5
2.4
OAc
Ph
H-SnMe3
CH2Cl2
OAc
5.4
5.3
5.2
5.1
H
PhCH2Br
4.9
4.7
HO
CH3F
4.8
4.6
2.1
(CH3)2CHCl
CH2Br2
2.2
H CH3NO2
Me3Si
H2SiPh2
PhCH2Cl
H
2.3
N2
H
2.7
SiMe3
H
O
2.8
4.5
4.4
4.3
4.2
O
Me-C-OCH2CH3
4.1
HCCl3
O
H
Me
H
H
AcO
OMe
H
H
CH3
O
OMe
7.9
7.8
HO2C
7.7
7.6
7.5
7.4
HO
EtO2C
Ph
7.3
7.2
7.1
CO2Et
6.9
6.8
6.7
6.6
6.5
6.4
H
CCl3CCl2H
6.3
6.2
6.1
O
OMe
NO2
O
H
Ph
Me
10
9.9
O2N
NO2
H
9.8
9.7
9.6
9.5
9.4
NMe2
NMe
9.3
9.2
9.1
8.9
8.8
8.7
8.6
8.5
Ph
8.4
8.3
8.2
8.1
10.4
10.3
10.2
10.1
10
N
H
H
H
H
11.1
O
H
H
O
OMe
OMe
O
S
t
Bu
OH
CH3CO2H
H
O
12
11.9
11.8
11.7
11.6
11.5
11.4
11.3
11.2
11.1
11
10.9
10.8
10.7
10.6
10.5
Se
iPr3Si
H
17.3
H
Me
S
O
H
O
H
14.9
14
13.9
13.8
HgH
16.7
13.7
13.6
13.5
13.4
13.3
13.2
13.1
13
12.9
12.8
12.7
12.6
12.5
12.4
12.3
12.2
12.1
12
Reich
Chem 345
NMR is unique among common spectroscopic methods in that signal intensities are directly proportional to the
number of nuclei causing the signal (provided certain conditions are met). In other words, all absorption coefficients
for a given nucleus are identical. This is why proton NMR spectra are routinely integrated, whereas IR and UV spectra
are not. A typical integrated spectrum is shown below, together with an analysis.
30 20 10 0
Hz
26.5 mm
16.2 mm
11.8 mm
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
H
C
If two protons have different chemical shifts and are within 3 bonds of each other (geminal or vicinal) then the
protons will be coupled to each other: the signal will be split into a doublet (two lines separated by the coupling
constant J) due to two magnetic orientations of the other proton. When there are two, three, or more neighbors,
additional splittings can be observed
H
H
C
J1
J2
E
dd
dd
When all of the couplings to a given proton are the same, then regular multiplets are formed, with the intensities
shown below:
# of Vicinal
H atoms
Intensities
Pascal's triangle)
Called:
Examples:
singlet
1 1
doublet
X2CH-CH3 X2CH-CHY2
1 2 1
triplet
X-CH2-CH3 X2CH-CH2-CHX2
1 3 3 1
quartet
X-CH2-CH3 X-CH2-CH-CHX2
1 4 6 4 1
pentet
X-CH2-CH-CH2-X CH3-CH2-CHX2
1 5 10 10 5 1
sextet
CH3-CH2-CH2-X CH3-CHX-CH2-R
1 6 15 20 15 6 1
heptet
X-CH(CH3)2 (X-CH2)3CH
1 7 21 35 35 21 7 1
octet
CH-CH(CH3)2
1 8 29 56 70 56 29 8 1
nonet
XCH2-CH(CH3)2
triplet n = 2
quartet n = 3
pentet n = 4
sextet n = 5
heptet n = 6
However, when some of the coupling constants are different, then more complicated multiplets are seen. The
simplest type is the doublet of doublets (dd) which arises from one proton coupled to two neighboring protons by
different coupling constants.
Coupling Constants
Coupling constants J vary widely in size, but the vicinal couplings in acyclic molecules that we are mostly going to
be interested in are usually 7 Hz. The leading superscript ( 3J) indicates the number of bonds between the coupled
nuclei.
H
J = 2-15 Hz
Typical: -12 Hz
C
H
H
vicinal
geminal
C
J = 2-20 Hz
H
4
Typical: 7 Hz
J = 0-3 Hz
long-range
One situation where the size of J provides important information is in the vicinal coupling across double bonds,
where trans couplings are always substantially larger than cis couplings.
H
H
J = 14 - 18 Hz
J = 8 - 12 Hz
There are also a few situations where coupling across 4 bonds are observed in NMR spectra. This is rarely seen
across single bonds, but small couplings (typically 1-3 Hz) are seen when there are intervening double or triple
bonds.
H
H
H
H
H
H
H
H
Meta
J = 2 to 3 Hz
Allylic
J = 0 to 3 Hz
Propargylic
J = 2 to 4 Hz
Allenic
J = 6 to 7 Hz
Reich
Chem 345
C5H8O4
300 MHz 1H NMR Spectrum
Solv: CDCl3
Source: Aldrich Spectra Viewer/Reich
MeO
OMe
Dimethyl malonate
5.91
2.00
10
C4H8O2
300 MHz 1H NMR Spectrum
Solv: CDCl3
Source: Aldrich Spectral Viewer/Reich
5
ppm
O
OMe
Methoxyacetone
3.16
3.01
2.05
10
5
ppm
8
Reich
Chem 345
Br
Br
1,2-Dibromoethane
10
5
ppm
1-Methoxy-2-bromoethane
3.8
10
3.7
3.6
3.5
3.4
C4H10O2
300 MHz 1H NMR Spectrum
Solv: CDCl3
Source: Aldrich Spectral Viewer/Reich
OMe
MeO
1,2-Dimethoxyethane
6.24
4.00
10
5
ppm
9
Reich
Chem 345
Cl
Cl
Cl
1,1,2-Trichloroethane
2.15
1.00
ppm 5
Cl
Cl
1,1-Dichloroethane
2.86
1.00
10
ppm 5
1.45
1.00
3.5
10
3.4
5
10
1.70 1.65
Reich
Chem 345
Br
1-Bromopropane
1.9
1.8
1.05 1.00
1.49
1.03
1.00
3.40 3.35
10
5
ppm
Br
2-Bromopropane
5.93
4.4
4.3
4.2
1.00
10
5
ppm
11
Practice Problems
Reich
Chem 345
30
20
10
Hz
1.7
1.00
1.6
0.96
0.66
0.64
0.95 0.90
2.35 2.30 2.25
3.70 3.65
10
ppm
Problem R-18C C10H12O
300 MHz 1H NMR spectrum in CDCl3
Source: Aldrich Spectra Viewer/Reich
30
20
10
Hz
2.51
1.00
10
ppm
12
Reich
Chem 345
Cl
30
20
10
Hz
1870.3
1883.9
HO
2244.9
2258.5
J = 13.6 Hz
7.4
12
11
7.2
10
7.0
6.8
6.6
30
HO
20
10
6.2
Hz
1871.4
1879.9
2055.6
2063.7
Cl
6.4
J = 8.1 Hz
7.0
12
11
6.8
10
6.6
6.4
13
6.2
OH and NH Protons
The chemical shifts of OH and NH protons vary over a wide range depending on details of sample concentration and
substrate structure. The shifts are very strongly affected by hydrogen bonding, with strong downfield shifts of H-bonded
groups compared to free OH or NH groups. Thus OH signals tend to move downfield at higher substrate concentration
because of increased hydrogen bonding (see the spectra of ethanol below).
Pure ethanol
OH proton
5% EtOH in CCl4
5.0
4.5
4.0
3.5
3.0
ppm
2.5
2.0
1.5
1.0
0.5
There is a general tendency for the more acidic OH and NH protons to be shifted downfield. This effect is in part a
consequence of the stronger H-bonding propensity of acidic protons, and in part an inherent chemical shift effect. Thus
carboxylic amides and sulfonamides NH protons are shifted well downfield of related amines, and OH groups of phenols
and carboxylic acids are downfield of alcohols.
R=CF3
R-NH3+
R-CO2H
12
R-SH
Ar-NH2
R-NH2
Ar-OH
R-SO3H
13
Ar-SH
O
R-CNH2 R=CH
3
11
10
ppm
14
concentrated
R-OH
dilute
Reich
Chem 345
Br
"leaning"
3.8
10
"leaning"
3.7
3.6
3.5
3.4
In addition there may be more lines than that predicted by the multiplet rules. A nice example is provided by the
compound below. For the BrCH 2CH2O group the two methylenes at 3.48 and 3.81 have a relatively large chemical
shift separation, and they form recognizable triplets (although with a little leaning). For the MeOCH 2CH2O group the
chemical shift between the CH2 groups is small, and the signals are a complicated multiplet with only a vague
resemblance to a triplet.
C5H11BrO2
300 MHz 1H NMR spectrum in CDCl3
Source: Aldrich Spectra Viewer/Reich
3.8
10
3.7
Br
3.6
3.5
3.4
5
ppm
15
HA HB
C C
AB = 40 Hz
AB = 30 Hz
AB = 20 Hz
AB = 10 Hz
AB = 3 Hz
AB
50
40
30
20
10
0
Hz
-10
-20
-30
-40
16
J1
J2
J1 = J2
dd
H3
H4
Br
H6
H3
CH3
30
20
10
Hz
H4
O 2N
8.1
8.0
7.9
ppm
7.8
7.7
Other situations where protons separated by more than 3 bonds show coupling also involve intervening bonds (double or
triple bonds). Such couplings are typically smaller than the 7 Hz often seen for 3-bond couplings. See if you can assign the
signals in the spectrum below, and identify the couplings.
Problem R-27L C5H8O2
250 MHz 1H NMR spectrum in CDCl3
Source: Adam Fiedler/Reich
H
CH3
CH3
3.17
30
20
10
Hz
3.04
7.05
7.00ppm
6.95
6.90
1.01
1.00
5.90 ppm
5.85
5.80
ppm
3.75ppm
3.70
4
17
1.90
ppm 1.85
Diastereotopic Effects
Diastereotopic protons are defined as two protons which have identical connectivity to the rest of the molecule, but have
different chemical shifts because of some stereochemical feature of the molecule. The situation is simple with gem-alkene
protons - it is easy to see how they are different. However, it is more complicated for sp3 carbons.
H
H
Br
Br
These two prrotons are diastereotopic
Cl
It turns out that CH2 groups in any molecule that has a true asymmetic center (a center of chirality) anywhere in the
molecule will be diastereotopic (see the substitution test in the text book). An typical example is 1,2-dibromopropane (NMR
below). Rotation around the 1,2-C-C bond does not actually interchange the environment of the two hydrogens. To convince
yourself of this, make two models of 1,2-dibromopropane, and put both in the same conformation. In one mark one of the
hydrogens at C1, in the other mark the other one. Then see if you put the two marked hydrogens in exactly the same
environment by rotating the bonds (this is the substitution test done with models).
You can see that 1,2-dibromopropane has four sets of signals, with the two protons of the CH2 group separated by about
0.3 ppm. Not only are the shifts of the two C-1 protons different, but the coupling constant to the C-2 proton is also different.
The C-1 H-C-H 2-bond coupling (to the other proton at C-1) is accidentally nearly the same as the H-C-C-H 3-bond coupling
(to the proton at C-2) for one of the protons at C-1. This gives the triplet at 3.55 Some people call these "apparent triplets"
because the two couplings are certainly different, but apparently not by much. For the other proton at C-1 the H-C-C-H
coupling is much smaller, and so a dd is seen at 3.86. The proton at C-2 is pretty complicated - it is actually a doublet of
doublets of quartets (ddq) from coupling to the two different protons at C-1 and the methyl group at C-3.
Br
Br
30
20
10
Hz
1.8
4.3
4.2
4.1
4.0
3.9
3.8
3.7
3.6
3.5
2.90
1.00
0.94
0.89
2
ppm
18
3.13
NH2
2.00
8.5
8.0
7.5
7.0
6.5
6.0
C7H8O
300 MHz 1H NMR spectrum in CDCl3
Source: Aldrich Spectra Viewer/Reich
3.00
2.00
OMe
8.5
8.0
7.5
7.0
6.5
6.0
8.0
7.5
7.0
6.5
6.0
7.0
6.5
6.0
C6H5Cl
300 MHz 1H NMR spectrum in CDCl3
Source: Aldrich Spectra Viewer/Reich
Cl
8.5
C6H5NO2
300 MHz 1H NMR spectrum in CDCl3
Source: Aldrich Spectra Viewer/Reich
3.12
2.00
NO2
8.5
8.0
7.5
ppm
19
Reich
Chem 345
Isomeric Methoxynitrobenzenes
Problem R-19B (C7H7NO3)
300 MHz 1H NMR spectrum in CDCl3
Source: Aldrich Spectra Viewer/Reich
8.2
8.1
10
8.0
7.9
7.8
7.7
7.6
7.5
7.4
7.3
7.2
7.1
7.0
6.9
ppm
8.2
8.1
10
8.0
7.9
7.8
7.7
7.6
7.5
7.4
7.3
7.2
7.1
7.0
6.9
ppm
8.2
10
8.1
8.0
7.9
7.8
7.7
7.6
7.5
5
ppm
20
7.4
7.3
7.2
7.1
7.0
6.9
Reich
Chem 345
20
10
7.6
10
10
7.5
7.4
7.6
10
Hz
7.5
7.3
4
7.4
7.1
7.3
7.5
7.4
7.3
21
7.2
7.0
2
7.2
7.1
7.0
7.2
3
6.9
0
6.9
7.1
2
Reich
Chem 345
200-218
X
Carboxylic esters
acids, amides
C
Me4Si
C=C
C
C
Ketones, aldehydes
C
220
13
200
180
160
140
120
C
R3C-O-
100
Alkyl halide
alkyl amine
80
Alkanes
60
40
20
-20
Me3COH
Me2CHOH
CH3CH2OH
CH2=C=CH2
MeOH
HCCH
Me3N
Me2O +NMe4
HOCH=CH2 CDCl3
88.0
90
100
77.8
69.6
73.9 73.2
70
80
61.2 55.6
64.6
58.2
N
MeCl
Me-Me
Me4Si
CH4
MeSH
MeI
MeBr
MeLi
50.2
47.6
27.8
18.2
25.223.1
39.7
50
60
C O
30
40
20
10.3 5.9
0.0 -2.9
6.5 2.5
-2.1
10
-13.2
-10
-20.0
-20
Me + Me
N
O
CH2=C=CH2
H
C O
H
206.2
199.6
210
190
180
HC(OEt)3
H2C=N-Me
177.0
200
NH2
CH2=CH2
- +
CN-Me
OMe
194.0
211.7
220
H
O
CO3H-
O=C=NMe
160
170
150
22
NC-Me
HOCH=CH2
128.5
123.2 117.7 113.9
127.2 121.7
140
Li
130
120
110
102.6
100
Reich
Chem 345
OH
19.0
25.1
32.0
SiMe4
160
140
120
100
ppm
80
60
200
180
160
140
120
100
ppm
80
60
200
180
160
140
120
100
ppm
80
60
40
40
42.1
211.8
23
20
40
-20
20
-20
20
-20
19.6
180
52.1
200
24.6
130
27.0
25.0
131
CDCl3
130.2
130.0
65.4