NMR Spectroscopy
Introduction
 Over the past fifty years nuclear magnetic resonance
spectroscopy, commonly referred to as nmr, has become the
most important technique for determining the structure of
organic compounds.
 Although larger amounts of sample are needed than for mass
spectroscopy, nmr is non-destructive, and with modern
instruments good data may be obtained from samples weighing
less than a milligram.
1
Principles of NMR Spectroscopy
NMR spectroscopy is basically another form of absorption
spectroscopy, similar to IR or UV spectroscopy.
Under appropriate conditions, a sample can absorb electromagnetic
radiation in the radio-frequency region at frequencies governed by the
characteristic of the sample.
2
Principles of NMR Spectroscopy
In NMR, absorption is a function of certain nuclei in
the molecule.
A plot of the frequencies of the absorption peaks
versus peak intensities constitutes an NMR
spectrum.
3
Principles of NMR Spectroscopy
All nuclei carry a charge.
In some nuclei this charge “spins” on the nuclear axis, and this
circulation of nuclear charge generates a magnetic dipole along
the axis.
The most important nuclei for organic structure determination
are 1H (ordinary hydrogen) and 13C, a stable nonradioactive
isotope of ordinary carbon.
Although 12C and 16O are present in most organic compounds,
they do not possess a spin and do not give NMR spectra.
4
Principles of NMR Spectroscopy
When nuclei with spin are placed between the poles of powerful
magnet, they align their magnetic fields with or against the field
of the magnet.
Nuclei aligned with the applied field have a slightly lower energy
than those aligned against the field.
By applying energy in the radio frequency range, it is possible to
excite nuclei in the lower energy spin state to the higher energy
spin state.
5
Principles of NMR Spectroscopy
The energy gap between the two spin states depends on the strength
of the applied magnetic field; the stronger the field, the larger the
energy gap.
Instruments currently in use have magnetic fields that range from about
1.4 to 14 tesla (T) (by comparison, the earth's magnetic field is only
about 0.0001 T).
At these field strengths, the energy gap corresponds to a radio
frequency of 60 to 600 MHz (megahertz; 1 MHz = 106 Hz or 106 cycles
per second).
This energy corresponds to 6-60 x 10-6 kcal/mole.
6
Measuring an NMR Spectrum
A 1H-NMR spectrum is usually obtained by dissolving the
sample in some inert solvent that does not contain 1H nuclei.
Examples of such solvents are CCl4, or solvents with the
hydrogens replaced by deuterium, such as CDCl3, and
CD3COCD3.
A small amount of a reference compound is also added.
The solution, in a thin glass tube, is placed in the center of a
radio frequency (rf) coil, between the pole faces of a powerful
magnet.
7
Measuring an NMR Spectrum
The nuclei align themselves with or against the field.
Continuously increasing amounts of energy is then applied to the
nuclei by the rf coil.
When this energy corresponds exactly to the energy gap between the
lower and higher energy spin states, it is absorbed by the nuclei.
At this point, the nuclei are said to be in resonance with the applied
frequency – hence the term nuclear magnetic resonance.
A plot of the energy absorbed by the sample against the applied
frequency of the rf coil gives an NMR spectrum.
8
The Mechanism of Absorption
 (a) A top precessing in the earth’s gravitational field; (b) the
precession of a spinning nucleus resulting from the influence of
an applied magnetic field.
9
The Mechanism of Absorption
 The nuclear magnetic resonance process: absorption occurs
when ν = ω.
 Where ν is applied radio frequency and ω is the angular
frequency of precession.
10
Population densities of nuclear spin
states
 For a proton, if the applied magnetic field
strength is 1.41 Tesla, resonance occurs at
about 60 MHz.
 The energy different between the two spin
states is about 6 x 10-6 kcal/mole.
 At room temperature both the states are
almost equally populated.
 There is slight excess of nucleii in the lower
energy state.
11
Population densities of nuclear spin
states
12
Measuring an NMR Spectrum
In practice, there are two ways by which the resonance
frequencies of 1H nuclei can be determined.
Because the magnetic field strength and the size of the energy
gap between nuclear spin states are directly related, either the
magnetic field strength or the rf can be varied.
In earlier NMR spectrometers a constant radio frequency was
applied, the strength of the applied magnetic field was varied,
and different nuclei resonated at different magnetic field
strengths.
13
Measuring an NMR Spectrum
In modern Fourier transform (FT-NMR) spectrometer, the
applied magnetic field is held constant, and the radio frequency
is varied.
The instrument computer uses a mathematical process called
Fourier transformation to sort the signal that is produced into the
resonance rfs of the different 1H nuclei.
Whether it is the magnetic field field strength or the rf that is
varied, this variable increases from left to right in the recorded
spectra.
14
The NMR instrument
15
Chemical Shifts and Peak Areas
Not all 1H nuclei flip their spins at precisely the same radio
frequency because they may differ in chemical (and, more
particularly, electronic) environment.
The NMR spectrum of
p-xylene:
The spectrum is very
simple and consists
of two peaks.
The positions of the
peaks are measured
in  (delta) units from the peak of a reference compound, which is
tetramethylsilane (TMS), (CH3)4Si.
16
The reasons for selecting TMS as a
reference compound
All 12 nuclei of its hydrogens are equivalent, so it
shows only one sharp NMR signal, which serves as a
reference point.
Its hydrogen signals appear at higher field than do
most 1H signals in other organic compounds, thus
making it easy to identify the TMS peak.
TMS is inert, so it does not react with most organic
compounds, and it is low boiling and can be removed
easily at the end of a measurement.
17
Chemical Shifts and Peak Areas
Most organic compounds have peaks downfield (at low field) from
TMS and are given positive  values.
low field
high field
18
Chemical Shifts and Peak Areas
A  value of 1.00 means that a peak appears 1 part per million
(ppm) downfield from the TMS peak.
low field
high field
19
Chemical Shifts and Peak Areas
If the spectrum is measured at 60 MHz (60 x 106 Hz), then 1 ppm is 60
Hz (one-millionth of 60 MHz) downfield from TMS.
If the spectrum is run at 100 MHz, a  value of 1 ppm is 100 Hz downfield
from TMS, and so on.
low field
high field
20
Chemical Shifts and Peak Areas
The chemical shift of a particular kind of 1H signal is its  value
with respect to TMS.
It is called a chemical shift because it depends on the chemical
environment of the hydrogens.
The chemical shift is independent of the instrument on which it is
measured.
Chemical shift =  =
distance of peak from TMS, in Hz
-------------------------------------------spectrometer frequency in MHz
ppm
21
Chemical Shifts and Peak Areas
In the spectrum of p-xylene, we see a peak at  2.30 and another at  7.10.
It seems reasonable that these peaks are caused by two different “kinds” of 1H nuclei
in the molecule: the methyl hydrogens and the aromatic ring hydrogens.
How can we tell which is which?
low field
high field
22
Chemical Shifts and Peak Areas
One way to identify the hydrogens is to integrate the area under each peak.
The peak area is directly proportional to the number of 1H nuclei responsible for the
particular peak.
All the commercial NMR spectrometers are equipped with electronic integrators
that can print an integration line over the peaks.
low field
high field
23
Chemical Shifts and Peak Areas
The ratio of heights of the vertical parts of this line is the ratio of peak
areas..
The areas of the peaks at 2.30 and 7.10 in p-xylene spectrum give a ratio
of 3 : 2 (or 6 : 4).
These areas allow us to assign the peak at  2.30 to the methyl
hydrogens and the peak at  7.10 to the four aromatic ring hydrogens.
low field
high field
24
Chemical Shifts and Peak Areas
A more general way to assign peaks is to compare chemical shifts
with those of similar protons in a known reference compound.
For example, benzene has six equivalent hydrogens and shows a
single peak in its 1H NMR spectrum at  7.24.
Other aromatic compounds also show a peak in this region. We
can conclude that most aromatic ring hydrogens will have
chemical shifts at about  7.
Similarly, most CH3 — Ar hydrogens appear at  2.2 – 2.5.
25
Chemical Shift
6 regions of NMR spectrum
The chemical shifts of 1H nuclei in various chemical environments
have been determined by 1H NMR spectra of a large number of
compounds with known, relatively simple structures.
The chart above gives the chemical shifts for several common
types of 1H nuclei.
26
Table of chemical shifts
27
Factors that influence chemical shifts
The electronegativity of groups in the immediate environment of
the 1H nuclei.
Electron withdrawing groups generally cause a downfield chemical
shift.
Compare, for example, the following chemical shifts:
 CH3
~ 0.9
 CH2Cl
~ 3.7
CHCl2
~ 5.8
Electrons in motion near a 1H nucleus create a small magnetic
field in its microenvironment that tends to shield the nucleus from
the externally applied magnetic field.
28
Factors that influence chemical shifts
Electrons in motion near a 1H nucleus create a small magnetic
field in its microenvironment that tends to shield the nucleus from
the externally applied magnetic field.
29
Factors that influence chemical shifts
 CH3
~ 0.9
 CH2Cl
~ 3.7
CHCl2
~ 5.8
Chlorine is an electron-withdrawing group.
Withdrawal of electron density by the chlorine therefore
“deshields” the nucleus, allowing it to flip its spin at a lower applied
external field or lower frequency.
The more chlorines, the larger the effect.
30
Factors that influence chemical shifts
The presence of  electrons
Hydrogens attached to a carbon that is part of a multiple bond or aromatic
ring usually appears downfield from hydrogens attached to saturated
carbons.
The pi-electrons associated with
a benzene ring provide a striking
example of this phenomenon.
The electron cloud above and below the plane of the ring circulates in
reaction to the external field so as to generate an opposing field at the
center of the ring and a supporting field at the edge of the ring.
31
Factors that influence chemical shifts
This kind of spatial variation is called anisotropy, and it is
common to nonspherical distributions of electrons.
Regions in which the induced
field supports or adds to the
external field are said to be
deshielded, because a slightly
weaker external field will bring
about resonance for nuclei in
such areas.
However, regions in which the induced field opposes the external
field are termed shielded because an increase in the applied field
is needed for resonance.
32
Examples of Anisotropy Influences on
Chemical Shift
The structural constraints of the bridging chain require the middle
two methylene groups to lie over the face of the benzene ring,
which is a nmr shielding region.
33
Spin – Spin Splitting
Many compounds give spectra that show more complex peaks than just single peaks
(singlets) for each type of hydrogen.
Based on chemical shifts, the 1H NMR spectrum of diethyl ether is expected to have
two lines:
one in the region of  0.9 for the six equivalent CH3 Hydrogens and one at about 3.5
for the four equivalentCH2 hydrogens adjacent to the oxygen atom, with relative areas
6 : 4.
In the spectrum, we see absorptions in each of these regions, with the expected total
34
area ratio.
Spin – Spin Splitting
But, we do not see singlets!
Instead, the methyl signal is split into three peaks, a triplet, with relative
areas 1:2:1; and the methylene signal is split into four peaks, a quartet,
with relative areas 1:3:3:1.
35
Spin – Spin Splitting
Spin-spin splittings, tell us quite a bit about molecular structure.
Each 1H nucleus in the molecule acts as a tiny magnet, and each
hydrogen “feels” not only the very large applied magnetic field but also
a tiny field due to its neighboring hydrogens.
When 1H nuclei on one carbon is excited, the 1H nuclei on neighboring
carbons can be in either the lower or the higher spin state, with nearly
equal probabilities.
Due to this, the magnetic field of the nuclei whose peak is observed is
perturbed slightly by the tiny fields of its neighboring 1H nuclei.
36
Spin – Spin Splitting
The splitting pattern can be predicted by the n + 1 rule: if a 1H nucleus
or a set of equivalent 1H nuclei has n 1H neighbors with a substantially
different chemical shift, its NMR signal will be split into n + 1 peaks.
In diethyl ether, each CH3 hydrogen has two 1H neighbors (on the CH2
group).
Therefore, the CH3 signal is split into 2 + 1 = 3 peaks.
At the same time, each CH2 hydrogen has three 1H neighbors (on the
CH3 group). The CH2 signal is therefore split into 3 + 1 = 4 peaks.
37
n + 1 rule for signal splitting
38
n + 1 rule for signal splitting
39
n + 1 rule for signal splitting
40
n + 1 rule for signal splitting
In the spectrum of 1,1-dichloroethane shown below, it is clear that
the three methyl hydrogens (red) are coupled with the single
methyne hydrogen (orange) in a manner that causes the former to
appear as a doublet and the latter as a quartet.
41
n + 1 rule for signal splitting
The statistical distribution of spins within each set explains both the n+1
rule and the relative intensities of the lines within a splitting pattern.
The action of a single neighbouring proton is easily deduced from the fact
that it must have one of two possible spins. Interaction of these two spin
states with the nuclei under observation leads to a doublet located at the
expected chemical shift.
42
n + 1 rule for signal splitting
The corresponding action of the three protons of the methyl group requires a
more detailed analysis.
In the display of this interaction four possible arrays of their spins are shown.
The mixed spin states are three times as possible as the all +1/2 or all _1/2
collection.
Consequently, we expect four signals, two above the chemical shift and two
below it. This spin analysis also suggests that the intensity ratio of these
signals will be 1:3:3:1.
43
n + 1 rule for signal splitting
Pascal’s Triangle
A simple way of estimating the relative intensities of the lines in a first-order
coupling pattern is shown below.
This array of numbers is known as Pascal's triangle, and is easily extended
to predict higher multiplicities.
44
Spin – Spin Splitting
Coupling Constant
1H nuclei that split one another’s signals are said to be coupled.
The extent of the coupling, or the number of hertz by which the signals split, is
called the coupling constant (abbreviated J).
45
Spin – Spin Splitting
46
Spin – Spin Splitting
Coupling Constant
Spin – spin splitting falls off with distance.
Whereas hydrogens on adjacent carbons may show appreciable
splitting ( J = 6 – 8 Hz), hydrogens farther apart hardly “feel” each
other’s presence ( J = 0 – 1 Hz).
Coupling constants can even be used at times to distinguish between
cis – trans isomers or between positions of substituents on a benzene
ring.
Chemically equal 1H nuclei do not split each other. For example,
BrCH2CH2Br shows only a sharp singlet in its 1H NMR spectrum for
all four hydrogens.
47
Measuring Coupling Constant
 Each ppm of chemical shift represents 60Hz.
 There are 12 grid lines per ppm, each grid line represents 60Hz/12 = 5
Hz.
48
Measuring coupling constant
 The spacing between the component peaks is approximately 1.5
chart divisions.
 Therefore, J = 1.5 div x 5 Hz/1 div = 7.5 Hz
49
Measuring coupling constant
 Most aliphatic protons in acylic systems, the magnitutes of
coupling constants are always near 7.5 Hz.
 The coupling constants of the groups of protons that split one
another are identical within experimental error.
 This information is useful in interpreting a spectrum that may
have several multiplets, each with a different coupling constant.
50
Measuring coupling constants on
modern FT-NMR spectrometers
 Coupling constants are determined by printing Hertz
values directly on the peaks.
 The values are subtracted to determine the coupling
constants.
51
Measuring coupling constants on
modern FT-NMR spectrometers
52
Measuring coupling constants on
modern FT-NMR spectrometers
53
Multiplet Skewing (leaning)
 Multiplet skewing can sometimes be used to link interacting
multiplets.
 There is a tendency for the outermost lines of a multiplet to have
nonequivalent heights.
 If arrows are drawn on both multiplets in the directions of their
respective skewing, these arrows will point at each other.
54
NMR spectra of alcohols
55
NMR spectra of alcohols
 The chemical shift of –OH hydrogen is variable.
 Its position depending on concentration, solvent,
temperature, and presence of water, or acidic or
basic impurities.
 This peak can be found anywhere in the range of 0.5-
5.0 ppm.
56
NMR spectra of alcohols
 The variability of this absorption is dependent on the
rates of –OH proton exchange and the amount of
hydrogen bonding in the solution.
 The –OH hydrogen is usually not split by hydrogens
on the adjacent carbon (-CH-OH) because rapid
exchange decouples this interaction.
57
Deuterium exchange for identifying
the –OH absorption
 A drop of D2O is added to the NMR tube containing
the alcohol solution.
 After shaking the sample and sitting for few minutes,
the NMR spectrum is recorded.
 The disappearance of the –OH signal in the spectrum
is used to confirm the presence of –OH group in the
sample.
58
Deuterium exchange for identifying
amines and carboxylic acids
 Amino hydrogens exhibit deuterium
exchange.
 Carboxylic hydrogen exhibit deuterium
exchange.
59
Interpreting NMR spectra
60