Nuclear Magnetic Resonance Spectroscopy (NMR)
References:
Vollhardt and Schore; Organic Chemistry (2nd Edition), Chapter 10
Williams and Fleming ; Spectroscopic Methods in Organic Chemistry
(4th Edition, revised)
Internet: http://www.cis.rit.edu/htbooks/nmr
Synthesis of compounds and study of reaction mechanisms
requires the ability to determine the structure of the compound(s)
present
There are a range of techniques used by organic chemists to do
this: e.g. Mass Spectrometry (MS), Ultra-violet spectroscopy (UV),
Infrared spectroscopy (IR) and Nuclear Magnetic Resonance
Spectroscopy (NMR)
Each of these provides different structural information and these
four major techniques tend to be used in combination to provide a
more complete picture.
NMR is the most recent of these techniques to be developed
(1960s)
Spectroscopy: The study of the absorption of radiation, by a sample of
compound (or compound mixtures), Which occurs via a transition from
ground-state to an excited state.
The energy required to achieve this transition (∆E) is dependent on the
type of transition; e.g. UV light is used to measure electronic transitions
and IR for vibrational/ rotational transitions.
NMR spectroscopy: The study of the absorption of radio waves by a
sample in a magnetic field. This measures transitions in nuclear spin.
Samples (1-30mg) are dissolved in a solvent not containing the type of
nucleus of interest, and placed in a special glass tube,for use in the NMR
machine.
Principles of NMR
1) All atomic nuclei containing an odd number of either protons or
neutrons (e.g. 1H, 13C, 31P) have a property called nuclear spin.
2) This spin causes a magnetic field local to the nucleus to arise, thus
leading to the nucleus behaving like a small magnet.
3) When an external magnetic field is applied, the nucleus may align
with or against the magnetic field. Alignment against the field is a
higher energy state than alignment with the field.
Hydrogen nuclei (Protons) are the simplest example of this, and are the
most commonly observed nucleus.
External
Magnetic
Field
(H 0)
Schematic of spin states in a magnetic field
Against (ß spin)
Energy
E = h 
With (spin)
Energy level diagram for spin states
Irradiation with the correct frequency radio waves results in the
nucleus making a transition from ground-state (aligned with the
field, called ) to the higher energy  spin state (against the
applied field).
This absorbs energy (E) and is called spin-flipping. When spinflipping occurs the nucleus is said to be in resonance.
The energy is then released in a a variety of complex processes,
and the nucleus can relax back to the ground state.
The frequency () of the radio wave giving resonance for any particular
nucleus is proportional to the energy absorbed by the nucleus during
spin-flipping (E).

E is proportional to the strength of the applied field (H0)
E for any given nucleus is also dependent on its atomic identity and
local chemical environment.
H0 ranges from 14,100 to 176,250Gauss for modern spectrometers, thus
giving operating frequencies () of 60 to 750MHz (designated based on
the resonance of protons in (CH3)4Si)
Older, lower-field strength (60-90MHz) spectrometers are based on
permanent electromagnets and a single sweep plotted straight to chart
paper. Modern high-field machines use a superconducting magnet and
complex hardware and computer software to collate and process the
data.
Increasing field strength gives increased resolution - and thus better
spectra. The use of fast and powerful computers allows more complex
data analysis - new techniques are continually under development.
Structural Information from NMR spectra
A) Chemical Shift
Because all nuclei are surrounded by electrons, which produce their
own magnetic field, they are shielded from the applied field. This
shielding varies according to the local chemical environment, which
gives rise to variation in electron density and distribution.
for any particular
nucleus is proportional to
field strength felt by that nucleus = applied field - local electronic field
Increased electron density gives increased shielding of the nucleus.
Thus  of chemically different nuclei are different, and by measuring a
range covering the resonating frequencies of the type of nuclei to be
observed (e.g. the protons in a molecule) a spectrum can be recorded.
The differences in between chemically different protons is large
enough to be measured accurately - but is small compared to the
difference between other nuclei and protons. This allows the
measurement by NMR spectroscopy of one type of atomic nuclei at a
time.
 is measured in Hz and as it varies with spectrometer frequency can be
confusing. The position of a signal from a particular proton is therefore
measured relative to tetramethylsilane (most protons resonate at a
higher frequency than these). is known as chemical shift () and is
quoted in parts per million (ppm).


 = Distance from TMS signal (Hz)
Spectrometer frequency (MHz)
in ppm
1H NMR spectra are normally of the range 0-10ppm (gives a 900 Hz
range on a 90MHz machine).
Chemical Shift is dependent on the local chemical environment,
particularly:
1) Electronegative Atoms: e.g. O, F
Neighbouring electronegative atoms reduce electron density
(deshielding) surrounding the observed nucleus, thus increasing the
effective field felt, and thus the frequency  required for resonance.
This causes a downfield shift in the signal observed (leftwards in the
spectrum).
i.e 1H for RCH3< RCH2Br< RCH2OH
Because hydrogen is more electropositive than carbon, increasing
substitution also gives a downfield shift.
i.e 1H  for RCH3 < RR’CH2 < RR’R”CH
These effects decrease rapidly with distance.
2) Unsaturated systems: i.e. Alkenes, alkynes
π -bonds are regions of high electron density, and can set up
magnetic fields which are stronger in one direction than another. This is
called anisotropy, and leads to a downfield shift in alkenic and alkyne
protons (and carbons).
Aldehyde (RCHO) protons are observed the furthest downfield as they
combine an electronegative atom and a double bond.
3) Amines and Alcohols:
Protons attached directly to nitrogen or oxygen give broad,
variable position signals, because they become involved in
hydrogen-bonding which affects their electron density.
Chemical Equivalence : Nuclei in identical environments have the same
chemical shifts and therefore give only one signal.
Atoms are said to be chemically equivalent if mentally substituting one
of them would give identical results as substituting another.
e.g. RCH2Br : These protons are chemically equivalent.
Equivalence can be identified using symmetry:
(i) Plane of symmetry: Atoms that are reflections of each other through a
plane of symmetry are equivalent.
(ii) Rotational symmetry: Atoms that can be interchanged by rotation
about a chemical bond are equivalent (e.g. methyl protons) provided
that bond is able to rotate freely.
(B) Integration:
The greater the number of equivalent nuclei giving rise to a
particular signal, the larger that signal.
By integrating the area under a particular signal we can discern
relative numbers of atoms with that particular chemical shift. Modern
spectrometers provide this facility as part of the processing package.
Thus an ethyl group CH3CH2R will give two proton signals for the
two groups of protons with an integration ratio of 3:2.
(C) Spin-spin splitting:
Nuclei that are not equivalent, but are in close proximity to each other
affect each other’s local magnetic fields. This leads to splitting of signals
due to each nucleus.
Rule of thumb: Signals from nuclei with n non-equivalent neighbours
are split into n+1 signals.
e.g The signal for a proton with one non equivalent nearby proton will
be split into two. The neighbour may be in one of two states: or .
This affects the effective field felt by the proton, leading to two possible
values for . In a normal situation, approximately half the molecules in
a sample will have the neighbour in state and half in state giving
two equal height signals (a doublet).
Equally, for a proton with two neighbours; they may be in states
or . As and produce the same effect the signal will
comprise a triplet in the ratio 1:2:1.
The neighbours’ signal will also be split by the original proton, by the
same amount. These coupling constants (J) are measured in Hz - and
are not dependent on the external field.
Saturated compounds (alkanes): For coupling to occur the protons must
be within three bonds or less distance from each other.
Unsaturated compounds (alkenes, alkynes): They must be within four
bonds or less distance.
The coupling constants arising from these interactions are of distinctive
size for the type of interaction occurring:
Saturated: e.g. CH3CH2: J~7Hz : Two signals, one triplet, one quartet.
Unsaturated: Depends on position: =CH2 geminal J~2Hz
CH=CH2 cis protons J~7-11Hz
CH=CH2 trans protons J~12-18Hz
CH2-CH=CH2 allylic J~2Hz
Aromatic; Jortho ~ 6-9Hz, Jmeta~1-3Hz, Jpara~0-1Hz
Exceptions to n+1 rule:
(i) More than one set of neighbours must be treated sequentially: leading
to complex splitting patterns: e.g. CHBCl2-C(HA)2-C(HC)2-CH3
The protons shown in bold are equivalent, and couple to both the
proton to the left, and the two to the right of them. As these two sets are
not equivalent the expected signal produced would be a doublet of
triplets:
JAB
JAC
(ii) For protons which may be exchanging rapidly in solution e.g. amine
or alcohol protons, coupling may not be observed.
All processes which occur faster than about once every half second are
“seen” by NMR spectroscopy as averaged. e.g. conformation flipping,
rotation of methyl groups etc.
Carbon NMR spectroscopy
Principles as for proton NMR spectroscopy, but difference in E
involved. (4 times less than that for protons)
12C (~99.5% natural abundance) does not have a nuclear spin, and so
cannot be studied by NMR spectroscopy. 13C has spin=1/2 (same as
1H) but is only of 1.11% abundance. It requires much longer time to
acquire a 13C spectrum (or much greater sample strength), and because
the chances of two 13C atoms occurring adjacent to one another in the
same molecule are low, 13C-13C spin coupling is not observed.
13C-1H coupling can be observed, but more commonly a technique
called decoupling is used to simplify the resultant spectrum by
removing splitting.

 for 13C NMR spectra are affected by the same constraints as for
1H NMR spectroscopy, although the range is of the order 1-200ppm (as
opposed to 1-10ppm).
Advanced Techniques
With the advent of Fourier-Transform NMR spectroscopy in the 1970’s,
and the later development of fast and powerful, affordable computer
technology a whole range of more complex techniques has become
available. The uses of a few of the more commonly used methods are
outlined below:
Spin decoupling: Simplifies the spectrum by removing splitting of
signals
Difference decoupling: Subtracts spectrum with one or more signals
decoupled from a “normal” spectrum to allow study of overlapping
signals
Correlation spectroscopy (COSY): uses a complex pulse pattern to
produce a 3-D spectrum mapping coupling interactions.
Nuclear Overhauser Effect: Used to map through space (rather than
along bonding) interactions. Can provide information about spatial
arrangement of a molecule.