Unit-II Nuclear magnetic resonance spectroscopy-I (13 hrs)

• Introduction, Magnetic properties of nuclei- Resonance condition.

• Nuclear spin, population of nuclear spin levels and NMR isotopes,

Relaxation methods.

• Instrumentation and sample handling, FT-NMR.

• Chemical shift.

• Mechanism of shielding and de-shielding in Alkanes, Alkyl halides,

Alkenes, Aromatic compounds, Carbonyl compounds and Annulenes.

• Pascal’s triangle-low and high resolution, spectrum of ethanol.

Karplus Curve,

• Diamagnetic and paramagnetic effects and magnetic anisotropy.

Equivalence of protons-chemical and magnetic equivalence.

• Spin- systems: First order and second order coupling of AB systems,

Simplifications of complex spectras.

• Spin-spin interactions: AX, AX2, AX3, AMX, AB types.

• Vicinal, geminal and long range coupling-Spin decoupling.

• Chemical shift reagents and deuterium exchange.

• Stereochemistry and hindered rotations. Temperature effects.

1
Introduction
Spectroscopy is the study of the quantised interaction of energy (typically
electromagnetic energy) with matter. In Organic Chemistry, we typically deal
with molecular spectroscopy i.e. the spectroscopy of atoms that are bound
together in molecules.
A schematic absorption spectrum is given in Figure 1. The absorption
spectrum is a plot of absorption of energy (radiation) against its wavelength
(λ) or frequency (γ).

Figure 1. Schematic Absorption Spectrum

An absorption band can be characterised primarily by two parameters:

(a) the wavelength at which maximum absorption occurs

(b) the intensity of absorption at this wavelength compared to base-line (or

background) absorption
A spectroscopic transition takes a molecule from one state to a state of a
higher energy. For any spectroscopic transition between energy states (e.g.
E1 and E2 in figure 2), the change in energy (ΔE) is given by:

ΔE = hγ

Where, h is the Planck's constant and γ is the frequency of the

electromagnetic energy absorbed. Therefore γ ΔE.

Figure 2. Spectroscopic Transition

2
Degree of unsaturation or Index of Hydrogen Deficiency (IHD)

Traditionally, the molecular formula of a compound was derived from

elemental analysis and its molecular weight which was determined
independently. The concept of the degree of unsaturation of an organic
compound derives simply from the tetravalency of carbon. For a non-cyclic
hydrocarbon (i.e. an alkane) the number of hydrogen atoms must be twice
the number of carbon atoms plus two, any “deficiency” in the number of
hydrogens must be due to the presence of unsaturation, i.e. double bonds,
triple bonds or rings in the structure.

The degree of unsaturation can be calculated from the molecular formula for
all compounds containing C, H, N, O, S or the halogens. There are 3 basic
steps in calculating the degree of unsaturation:

Step 1 - take the molecular formula and replace all halogens by hydrogens

Step 2 - omit all of the sulfur or oxygen atoms

Step 3 - for each nitrogen, omit the nitrogen and omit one hydrogen.

After these 3 steps, the molecular formula is reduced to CnHm and the
degree of unsaturation is given by:

𝒎
Degree of Unsaturation = 𝒏 − +𝟏
𝟐

The degree of unsaturation indicates the number of n bonds or rings that

the compound contains.

For example, a compound whose molecular formula is C4H9NO2

Step 1 - take the molecular formula and replace all halogens by hydrogens
(C4H9NO2) Step 2 - omit all of the sulfur or oxygen atoms (C4H9N). Step 3 -
for each nitrogen, omit the nitrogen and omit one hydrogen.(C4H8)
Therefore C4H9NO2 is reduced to C4H8

𝒎
Degree of Unsaturation = 𝒏 − +𝟏
𝟐
𝟖
= 𝟒−𝟐+𝟏

=1

3
which gives a degree of unsaturation of 1 and this indicates that the
molecule must have one π bond or one ring.

Note Any compound that contains an aromatic ring always has a degree of
unsaturation greater than or equal to 4, since the aromatic ring contains a
ring plus three πbonds. Conversely, if a compound has a degree of
unsaturation greater than 4, one should suspect the possibility that the
structure contains an aromatic ring.

Ex 2: C8H8NOBr

Rule 1, replace halogens with hydrogens: C8H9NO

Rule 2, omit oxygens: C8H9N
Rule 3, omit the nitrogen and one hydrogen: C8H8
𝒎
Therefore, Degree of Unsaturation = 𝒏 − +𝟏
𝟐
𝟖
= 𝟖−𝟐+𝟏

=5
This means that the molecule has five rings and/or pi bonds (or any
combination of the two). A degree of unsaturation greater than or equal to 4
suggest the possibility of an aromatic (benzene) ring.

Ex 3: Benzene (C6H6)

𝒎
Degree of Unsaturation = 𝒏 − +𝟏
𝟐
𝟔
= 𝟔−𝟐+𝟏

= 6-3+1 = 4 (3 π bond and 1 ring)

Ex 4: C5H4NCl
Step1 C5H5N, step 2 no O, S, Step 3 C5H4 Reduced to C5H4
𝒎
Degree of Unsaturation = 𝒏 − +𝟏
𝟐
𝟒
= 𝟓−𝟐+𝟏

= 5-2+1 = 4

4
Problem:
1. C9H8O4
2. C21H30O2
3. C17H21NO4
4. C11H15NO2
5. C9H20
6. C7H8
7. C5H7Cl
8. C9H9NO4
9. C8H10N4O2
10. C5H5N
11. C5H5NO2
12. C5H5Br
13. C10H12N2O3X2
Ans:
1 2 3 4 5 6 7 8 9 10 11 12 13
6 7 8 5 0 4 2 6 6 4 4 3 5

Link to cross check your answer

https://scilearn.sydney.edu.au/fychemistry/calculators/degree_of_unsatur
ation.shtml

5
Introduction to NMR
• Nuclear magnetic resonance (NMR) spectroscopy is the single-most
important analytical tool for the organic chemist.
• This technique is based on the fact that nuclei of atoms have magnetic
properties that can be utilized to yield chemical information.
• Hence it is important to introspect and visualize the conditions when
nuclei will feel the magnetic field.
• For that, nuclei should be identified being active or non-active by
determining its spin. It is also crucial to understand the mechanism
and chemistry surrounding those nuclei and to know how shielded
and de-shielded a nucleus is.

Similar to the UV and IR spectroscopy, nuclear magnetic resonance (NMR)

Spectroscopy is also an absorption spectroscopy in which samples absorb
electromagnetic radiation in the radio-frequency region (3 MHz to 30,000
MHz) at frequencies governed by the characteristics of the sample.

NMR spectroscopy deals with nuclear magnetic transitions between

magnetic energy levels of the nuclei in molecules. NMR signals were first
observed in 1945 independently by Prucell at Harvard and Bloch at
Stanford. The first application of NMR to the study of structure was made in
1951 and ethanol was the first studied compound. In 1952, Prucell and
Bloch won the Nobel Prize in Physics for their discovery.

NMR allows characterization of a very small amount of sample (≈ 2 mg), and

does not destroy the sample (non-destructive technique). It can provide vast
information about a molecular structure, and in some cases, the structure
of a compound can be determined using only NMR spectroscopy. In practice,
the structures of complicated molecules are determined through a
combination of techniques that include NMR and IR spectroscopy and mass
spectrometry. Since organic compounds are primarily composed of carbon
(C) and hydrogen (H), NMR identifies the various types of H and C atoms in
organic molecules.
The H-nucleus is the most commonly studied by NMR spectroscopy because
of its high natural abundance of 99.985% and its presence in the majority of
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organic compounds. NMR studying 1H atom is called Hydrogen or proton
NMR spectrum. The proton NMR spectrum gives the information about the
number of different types of protons and also the chemical environment
around it.
Carbon forms the backbone of the organic molecules therefore C NMR is
also important and gives valuable information about the molecule. The 12C

do not absorb radio frequency energy but the other isotope i.e. 13C absorbs
the energy but the 13C has a natural abundance of only about 1%. Therefore
the sensitivity of 13C is less than the 1H NMR and requires longer time to
record. 19F and 31P are also frequently examined to get crucial information
about the structure of the compound containing these elements.

Nuclear Spin Origin:

• The concept of spin is regularly addressed in subatomic particle physics.
• We know that Electrons are subatomic particles which have spin intrinsic
to them. The nucleus is not much different. Spin is just another form of
angular momentum.
• The nucleus consists of protons and neutrons
• Neutrons and protons are comprised of subatomic particles known as
quarks and gluons.
• The neutron has 2 quarks with a -e/3 charge and one quark with a +2e/3
charge resulting in a total charge of 0.
• However, proton has 2 quarks with +2e/3 charge and only one quark with
-e/3 charge giving it a net positive charge. Both protons and neutrons are
spin=1/2

Figure 3

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 Figure 4

NMR active Nuclei

The nuclei are built up of protons and neutrons each possessing an angular
momentum due to its motion about the centre of the nucleus. The total
angular momentum of a particular nucleus is the vector sum of the
individual momentum of the constituent protons and neutrons. The total
angular momentum of a nucleus in its ground state is called as nuclear
spin. This is characterized by a spin quantum number I, which may be
integral, half-integral or 0.
Only those nuclei which have non-zero spin number can absorb/emit
radiofrequency (RF) radiation and hence are NMR active nuclei.

Note: For nuclei to be NMR active: “Nuclear Spin Quantum Number (I) ≠0”
The spin quantum number I is associated with the mass number and atomic
number of the nuclei as follows:

8
The NMR Phenomenon
The Spinning Nucleus: The nucleus of the hydrogen atom (the proton)
behaves as a tiny spinning bar magnet and it does so because it possesses
both electric charge and mechanical spin. Any spinning charged body will
generate a magnetic field, and the nucleus of hydrogen is no exception.

The effect of an external magnetic field: Like all bar magnets, 'the proton
will respond to the influence of an external magnetic field and will tend to
align itself with that field, in the manner of a compass needle in the earth's
magnetic field. Because of quantum restrictions which apply to nuclei but
not to compass needles, the proton can only adopt two orientations with
respect to an external magnetic field-either aligned with the field (the lower
energy state) or opposed to the field (the higher energy state). We can also
describe these orientations as parallel with or antiparallel with the applied
field.

Precessional Motion: Proton is behaving as a spinning magnet, not only

can it align itself with or oppose an external magnetic field, but also it will
move in a characteristic way under the influence of the external magnet.
Consider the behavior of a spinning top: as well as describing its spinning

9
motion, the top will (unless absolutely vertical) also perform a slower waltz-
like motion, in which the spinning axis of the top moves slowly around the
vertical.

G2u0ei.mp4

As the proton is a spinning magnet, it will, like the top, precess around the
axis of an applied external magnetic field, and can do so in two principal
orientations, either aligned with the field (low energy) or opposed to the field
(high energy). This is represented in figure 4

Figure 4

Precessional Frequency: The spinning frequency of the nucleus does not

change, but the speed of precession does. The precessional frequency, ν, is
directly proportional to the strength of the external field, B0: that is,
ν B0
This is one of the most important relationships in NMR spectroscopy.
Nuclear Energy Levels
The magnetic moment of the nucleus forces the nucleus to behave as a tiny
bar magnet. In the absence of an external magnetic field, each magnet is
randomly oriented. During the NMR experiment the sample is placed in an
external magnetic field B0 , which forces the bar magnets to align with (low
energy) or against (high energy) the B0 . During the NMR experiment, a spin
flip of the magnets occurs, requiring an exact quantum of energy. To
understand this rather abstract concept it is useful to consider the NMR
experiment using the nuclear energy levels.

10
 Figure 5
As mentioned above, an exact quantum of energy must be used to induce
the spin flip or transition. For any m, there are 2m+1 energy levels. For a
spin 1/2 nucleus, there are only two energy levels, the low energy level
occupied by the spins which aligned with B0 and the high energy level
occupied by spins aligned against B0. Each energy level is given by
E =−mℏγB0
Where m is the magnetic quantum number, in this case +/- 1/2.
The energy difference between the energy levels is then
ΔE=ℏγB0
where ℏ is Planks constant.
A schematic showing how the energy levels are arranged for a spin=1/2
nucleus is shown below. Note how the strength of the magnetic field plays a
large role in the energy level difference. In the absence of an applied field the
nuclear energy levels are degenerate. The splitting of the degenerate energy
level due to the presence of a magnetic field in known as Zeeman Splitting.

Figure 6

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Energy Transitions (Spin Flip)
In order for the NMR experiment to work, a spin flip between the energy
levels must occur. The energy difference between the two states corresponds
to the energy of the electromagnetic radiation that causes the nuclei to
change their energy levels. For most NMR spectrometers, B0 is on the order
of Tesla (T) while γ is on the order of 107. Consequently, the electromagnetic
radiation required is on the order of 100's of MHz and even GHz. The energy
of a photon is represented by
E=hν
and thus the frequency necessary for absorption to occur is represented as:
ν=γB0/2π
Population of nuclear spin levels
For spin ½ nuclei in an external magnetic field, there are two energy levels
and a slight excess of proton population in the lower energy state (N𝛼 > N𝛽 )
in accordance with the Boltzmann distribution. The states are labeled 𝛼
and 𝛽, or m = ½ and m = −1/2 (m is a quantum number); the energy gap
between them, ΔE, is given by
ΔE = (h𝛾∕2𝜋)B0
where h is Planck’s constant.
The equation simply states that ΔE is proportional to B0, since h, 𝛾, and 𝜋
are constants. B0 represents the magnetic field strength.

Figure 7 Two proton energy levels in a magnetic field of magnitude B0. N is

the population of spins in the upper (N𝛽) and lower (N𝛼) energy states.

12
Using Equation, one can calculate that at 298 K (25°C), for an instrument
operating at 60 MHz there are 1,000,009 nuclei in the lower (favored) spin
state for every 1,000,000 that occupy the upper spin state:

In other words, in approximately 2 million nuclei, there are only 9 more

nuclei in the lower spin state. Let us call this number (9) the excess
population
The excess nuclei are the ones that allow us to observe resonance. When the
60-MHz radiation is applied, it not only induces transitions upward but also
stimulates transitions downward. If the populations of the upper and lower
states become exactly equal, we observe no net signal. This situation is
called saturation.

THEORY

• All nuclei are electrically charged and many have spin.

• Transfer of energy is possible from base energy to higher energy levels

when an external magnetic field is applied.

• The transfer of energy occurs at a wavelength that coincides with the

radio frequency.

• Also, energy is emitted at the same frequency when the spin comes
back to its base level.

• Therefore, by measuring the signal which matches this transfer the

processing of the NMR spectrum for the concerned nucleus is yield.

13
 Figure 8

Relaxation methods.
How do nuclei in the higher energy state return to the lower state? Emission
of radiation is insignificant because the probability of re-emission of photons
varies with the cube of the frequency. At radio frequencies, re-emission is
negligible. In NMR, there are two radiationless processes which enable the
high energy nuclei to lose energy. The radiationless transitions by which a
nucleus in the high energy state returns to the lower energy state are called
relaxation process. This process is very important in NMR as it maintain the
excess of nuclei in the lower energy state, necessary condition for the NMR
phenomenon.
There are two major relaxation processes;
❖ Spin-lattice (longitudinal) relaxation, it is quantified by a time
constant T1
❖ Spin-spin (transverse) relaxation, it is quantified by a time constant
T2
The values of these time constants can vary quite a bit depending on the
nature of the sample and the type of nucleus studied.
Spin-lattice (longitudinal) relaxation: It involves the transfer of energy
from the nucleus in its higher energy state to its environment, i.e. to the
molecular lattice. The sample having all the nuclei is called the lattice.
Nuclei in the lattice are in vibrational and rotational motion, which creates a
complex magnetic field. The magnetic field caused by motion of nuclei within
the lattice is called the lattice field. This lattice field has many components.
Some of these components will be equal in frequency and phase to the
Larmor frequency of the nuclei of interest. These components of the lattice
field can interact with nuclei in the higher energy state, and cause them to
lose energy (returning to the lower state). The energy that a nucleus loses
14
increases the amount of vibration and rotation within the lattice resulting in
a slight increase in the temperature of the sample. The total energy of the
sample remains constant. This process maintains an excess of nuclei in
the lower energy state required for the phenomenon of NMR.
The spin-lattice relaxation process contributes to the width of spectral line.
In solids or viscous liquids, the molecular motions are greatly restricted. As
the mobility increases, the vibrational and rotational frequencies increase,
making it more likely for a component of the lattice field to be able to
interact with excited nuclei. Thus solids and highly viscous liquids exhibit
long spin-lattice relaxation time and hence broadening of the NMR signal.
However, at extremely high mobility, the probability of a component of the
lattice field being able to interact with excited nuclei decreases.
Spin-spin (transverse) relaxation: Spin-spin relaxation describes the
interaction between neighboring nuclei with identical precessional
frequencies but differing magnetic quantum states. In this situation, the
nuclei can exchange quantum states; a nucleus in the lower energy level will
be excited, while the excited nucleus relaxes to the lower energy state. There
is no net change in the populations of the energy states, but this relaxation
process decreases the average lifetime of a nucleus in the excited state.
The spectral line width is inversely proportional to the lifetime of the higher
energy state. The shorter the lifetime of the excited state, greater is the line
width. An efficient relaxation process results the shorter time T2 leading to
the broadening of the NMR peak. Solids and viscous liquids usually have the
properly oriented nuclei in the lower spin state which may exchange the
spins with the nuclei in the higher spin state resulting low value of T2 and
hence peak broadening.
Instrumentation:
Continuous wave and Fourier transform are two general types of
instrumentations in NMR spectrometers. Initially, experiments were
conducted with the help of continuous wave (C.W.) instruments. However, in
1970 the first Fourier transform (F.T.) instruments were build. Since then,
F.T –NMR spectrometers dominates the market.
The schematic diagram of a NMR spectrometer containing the following
components is given in Fig:
(i) A strong magnet with homogeneous field: The strength of its field can be

15
varied continuously and precisely over a relatively narrow range with the
help of the sweep generator.
(ii) A radio-frequency oscillator.
(iii) A radio-frequency receiver and detector.
(iv) A recorder, calibrator and integrator.
(v) A sample holder: It spins the sample to increase the homogeneity of the
magnetic field on the sample, and keeps the sample in the proper position
with respect to the main magnetic field, the radio frequency oscillator and
receiver coils.

Figure 9: Schematic representation NMR spectrometer

The sample under investigation is taken in a glass tube and placed in the
sample holder. Most commonly, NMR spectrometers irradiate the sample
with a beam of constant radio frequency obtained from the radio-frequency
oscillator, while the magnetic field strength is varied with the help of the
sweep generator.
ΔE varies as the Bo varies. At the field strength, when ΔE becomes equal to
the energy of the incident radio frequency, absorption of energy takes place
and transition from a lower spin state to a higher spin state occurs. This
causes a tiny electric current to flow in the coil of the radio frequency
receiver which is amplified and recorded as a signal on the chart paper by
the recorder.
A NMR spectrum is recorded as a plot of a series of peaks (signals)
corresponding to different applied field strengths against their intensities.
Each peak represents a set (a kind) of protons (in case of a PMR spectrum).

16
The areas under the peaks (the intensities of the peaks) are directly
proportional to the number of protons they represent. A typical PMR
spectrum is given in Fig. wave (CW) or field sweep instruments.

Fourier Transform (FT) NMR instruments

To record a complete spectrum using a CW NMR-instrument, it requires a
long time (few minutes) because each transition is induced in succession by
continuous scans from low field to high field. Therefore, each different type
of proton is excited individually and its resonance peak is observed and
recorded independently of all the others. In FT-NMR instrument, an
alternative approach is used where all the protons are excited
simultaneously and the sample is irradiated (at fixed field strength) with a
strong pulse of radio frequency energy containing all the frequencies over
the 1H range. All protons are excited simultaneously and then begin to
return (or decay) to their original spin states and re-emit RF radiation at
their respective resonance frequencies creating an interference pattern in
the resulting RF emission versus time, known as free induction decay (FID).
The frequencies are then extracted from the FID by a mathematical
technique called a Fourier transform.
An FTNMR spectrometer consists of a control console, magnet, and a coil of
wire that serves as the antenna for transmitting and receiving the RF
radiation. (Only one coil is necessary because signal reception does not
begin until after the end of the excitation pulse.) Because the FID results
from the emission due to nuclei in all environments, each pulse contains an

17
interference pattern from which the complete spectrum can be obtained.
Since each FID is acquired in 1–2 seconds, it is possible to acquire
hundreds of FIDs in just a few minutes, and the FIDs can be summed and
averaged to greatly improve the signal to noise ratio of the resulting FID

Figure 10

Sample Handling
To obtain high-quality NMR spectra it is important to prepare sample
correctly. There are some facts which we should be followed while making
sample to record spectra.
NMR Tube selection: For recording NMR, we should use high quality NMR
tube. The diameter of the sample tube should be same to the coil diameter
of the NMR probe in the magnet. We should not use a 5 mm NMR tube in a
10 mm probe unless we have no choice. Bad quality NMR tubes contain
regions where the tube wall thickness varies, and this variation makes our
sample difficult to shim well.
Sample Purity: The sample must be as pure as possible. Peaks due to
impurities can make the spectrum unnecessarily complicated. One should
ensure that the sample is free of magnetic impurities as these can distort
the magnetic field and hence degrade the spectrometer resolution.
Solvent Selection
Samples must be prepared using high-quality deuterated solvents. We must
try to use individual ampules rather taking solvent out of a bottle that
18
originally contained 50 or 100 g of solvent. Deuterated chloroform more
than six months old may be acidic enough to exchange with labile protons
from our sample therefore we must take care if our compound contains
labile hydrogen atoms or H’s particularly susceptible to acid-catalyzed
degradation. If the solvent itself has protons, the spectrum will be saturated
with signals from the solvent, rendering it unreadable. As a result, solvents
without protons must be used. Although there are several solvents that lack
protons, such as CCl4, these solvents do not dissolve all compounds. In
practice, deuterated solvents are generally used.
The nuclei of deuterium also exhibit nuclear spin, and therefore also
resonate, but they absorb RF radiation over a very different range of
frequencies than the protons. In an NMR spectrometer, a very narrow range
of frequencies is used, covering just the frequencies absorbed by protons.
For example, a 300-MHz spectrometer will use a pulse that consists only of
frequencies between 300,000,000 and 300,005,000 Hz. The frequencies
required for deuterium resonance do not fall in this range, so the deuterium
atoms are invisible to the NMR spectrometer. All of the solvents shown
below are routinely used, and many other deuterated solvents are also
available commercially, although quite expensive.

Sample Concentration: Ideally, 1-10 mg of the sample (except polymers) is

generally required to obtain 1H NMR spectrum of an organic compound.
Although, it is possible to obtain spectra from smaller quantities of
compound (dilute concentration) much greater care needs to be taken with
sample preparation
Solubility: Sample should be completely soluble in the chosen solvent. We
must avoid having solids present in the tube. The better is the solubility
better is the sensitivity of the experiment. Solid particles distort the
magnetic field homogeneity which causes broad lines and indistinct spectra
that cannot be corrected. Water must also be removed by drying the sample
prior to dissolution.
19
It is good in practice to filter the NMR solutions before putting it the NMR
tube. Adding small amount of extra solvent to the solution may also help
minimize the line broadening caused by the microscopic nucleation of
colloidal or crystalline particles present in saturated solutions. The solvent
produces NMR signals which will obscure regions of interest in the
spectrum. Example: Benzene (C6D6) and toluene is not suitable if the
compound has several aromatic rings.
Temperature: The melting and boiling points of the solvent should also be
considered especially when the NMR has to be taken above or below room
temperature. Example: DMSO is not appropriate for measurements below
16°C.
Residual Water Peak: Almost all NMR solvents contain traces of water and
most are hygroscopic and hence the longer they are stored the more water
they contain. The presence of a HDO peak will only serve to degrade the
quality of the NMR spectra.
Cost: Cost is also important. In general, prices increase with the number of
deuterated atoms. Example: CDCl3, D2O are relatively cheap, whereas C6D6,
toluene-d8, DMF-d7 are expensive. Hence we must first check the solubility
of our compounds in the cheap solvents.
https://www.youtube.com/watch?v=TJhVotrZt9I

Why should the proton nuclei in different compounds behave

differently in the NMR experiment?
The answer to this question lies with the electron(s) surrounding the proton
in covalent compounds and ions. Since electrons are charged particles, they
move in response to the external magnetic field (Bo) so as to generate a
secondary field that opposes the much stronger applied field. This secondary
field shields the nucleus from the applied field, so Bo must be increased in
order to achieve resonance (absorption of rf energy). As illustrated in the
figure, Bo must be increased to compensate for the induced shielding field.

20
Equivalence:
chemically and magnetically equivalent nuclei resonate at the same energy
and give a single signal or pattern

Chemical equivalence:
All of the protons found in chemically identical environments within a
molecule are chemically equivalent, and they often exhibit the same
chemical shift.

21
When stereochemistry is taken into account, the issue of equivalence vs
nonequivalence in NMR starts to get a little more complicated. It should be
fairly intuitive that hydrogens on different sides of asymmetric ring
structures and double bonds are in different electronic environments, and
thus are non-equivalent and have different resonance frequencies.

22
Note:
• Homotopic: equivalent, Enantiotopic: equivalent; Diastereotopic: non-
equivalent
• Cyclohexane: two different types of protons, axial and equatorial, if
ringflip is inhibited then 2type or 1 peak

June 2019

Shielding, and Deshielding

Under the influence of the applied magnetic field, electrons surrounding a
nucleus start to circulate perpendicular to the applied magnetic field H0,
and so they generate a secondary magnetic field called induced magnetic
field (α H0) which opposes the applied magnetic field in the region of the
nucleus.
The nucleus experiences a weaker magnetic field weaker than the applied
magnetic field H0, and it is said to be shielded. This type of shielding is
termed diamagnetic shielding and its effect is termed as shielding effect, i.e.

where σ is screening or shielding constant

If the induced field reinforces the applied field, then the field experienced by
the proton is greater than the applied field. Such a proton is said to be
deshielded and this effect is termed as deshielding effect.

23
Compared to a naked proton, a shielded proton requires a higher applied
field strength, whereas a deshielded proton requires a lower field strength
for transition. Thus, shielding shifts the absorption position upfield,
whereas deshielding shifts the absorption position downfield and these
effects are termed as shielding and deshielding effects, respectively.

Note that for a spectrometer operating at 200 MHz, 1 ppm corresponds to

200 Hz i.e. for a spectrometer operating at x MHz, 1.00 ppm corresponds to
exactly x Hz.

Chemical Shift

Unlike infrared and uv-visible spectroscopy, where absorption peaks are

uniquely located by a frequency or wavelength, the location of different NMR
resonance signals is dependent on both the external magnetic field strength
and the rf frequency. Since no two magnets will have exactly the same field,
resonance frequencies will vary accordingly and an alternative method for
characterizing and specifying the location of NMR signals is needed. This
problem is illustrated by different compounds shown in the following
diagram. Although resonance signals are distinct and well separated, an
unambiguous numerical locator cannot be directly assigned to each.

The chemical shift in absolute terms is defined by “the frequency of the

resonance expressed with reference to a standard compound which is
defined to be at 0 ppm”. The scale is made more manageable by expressing
it in parts per million (ppm) and is independent of the spectrometer
frequency.

24
Problem 1: In an NMR spectrum, the OH signal at 144 Hz higher frequency
than TMS: how many δ units (ppm) does this correspond to? Given: TMS
frequency is exactly 60 MHz (60 000 000 Hz) on this instrument,

Solution: OH signal is 144 Hz higher in frequency, so the δ value is 144/60

= 2.4. We say 'the OH protons appear at δ 2.4' .

Problem 2:The signal for the CH2 protons in the proton NMR spectrum of
benzyl alcohol appears at δ 4.6. Calculate the difference in frequency,
expressed in hertz , between this and the TMS signal in a 300 MHz NMR
spectrum.

Measurement of Chemical Shift-Internal Standards

The differences in frequency are measured with respect to some reference

group of nuclei. For protons and l3C, the universally accepted reference is
tetramethylsilane, (TMS).

Reason for TMS selection:

• TMS is chosen because it gives an intense sharp signal even at low

concentrations (having 12 protons in magnetically equivalent
positions)
25
 • it is chemically inert and has a low boiling point, so that it is easily
removed from a recoverable sample of a valuable organic compound;
• it is soluble in most organic solvents, and can be added to the sample
solution (0 .01-1.0 per cent) as an internal standard.

Any effect which alters the density or spatial distribution of electrons

around a 1H nucleus will alter the degree of shielding and hence its chemical
shift. 1H chemical shifts are sensitive to both the hybridisation of the atom
to which the 'H nucleus is attached (sp2, sp3 etc.) and to electronic effects
(the presence of neighbouring electronegative/electropositive groups).

Nuclei tend to be deshielded by groups which withdraw electron density.

Deshielded nuclei resonate at higher δ values (away from TMS). Conversely
shielded nuclei resonate at lower 8 values (towards TMS).

Signal integration

The computer in an NMR instrument can be instructed to automatically

integrate the area under a signal or group of signals. This is very useful,
because in 1H-NMR spectroscopy the area under a signal is proportional to
the number of hydrogens to which the peak corresponds.

Figure 12: spectrum of para-xylene (IUPAC name 1,4-dimethylbenzene)

26
Problem

1. Predict how many signals the following molecule would have? Sketch
the spectra and estimate the integration of the peaks.

Factors Influencing Chemical Shift

The chemical shift can be observed based on 2 different parts

• Intramolecular effects
• Intermolecular effects

Intramolecular effects

i) Inductive effects

The degree of shie1ding about any nucleus will be strongly influenced by the
electron density surrounding it, which, in turn, will be affected by the
presence of electronegative and electropositive neighbours. Electron
withdrawing groups will tend to draw electron density away from the
nucleus, so reducing the shielding effect and moving the resonance

27
frequency to higher values (greater chemical shift,); the opposite arguments
apply to electropositive groups.

The effect tends to fall rapidly as the nucleus becomes more distant from the
inductive group. For example, in proton spectroscopy, effects may be readily
observed over two and, to a lesser extent, three bonds, but are often
vanishingly small beyond this. The effects of multiple substituents tend to
be approximately additive.

Note: Mesomeric effect also applicates similarly….

ii) Anisotropic effects

The chemical shift positions (δ) for protons attached to C=C in alkenes is
higher than can be accounted for by electronegativity effects alone. The
same is true of aldehydic protons and aromatic protons, whereas alkyne
protons appear at relatively low δ.

Such anomalies are explained on the basis of anisotropic (direction

dependent) effects produced by circulation of π electrons under the
influence of the applied magnetic field. These effects depend on the
orientation of the molecule with respect to the applied field. Anisotropic
effects are in addition to the induced magnetic field generated by the
circulation of a electrons. Generally, the induced magnetic field generated by
circulating π electrons is stronger than that generated by a electrons.

28
Figure 13: Chemical shift anisotropy caused by some single, double and
triple bonds. (+) indicates deshielding regions (increased chemical shift)
whereas H indicates shielding regions (decreased chemical shift).

Alkenes. When an alkene group is so oriented that the plane of the double
bond is at 90° to the direction of the applied field (as in figure) induced
circulation of the π electrons generates a secondary magnetic field, which is
diamagnetic around the carbon atoms, but paramagnetic in the region of the
alkene protons. Where the direction of the induced magnetic field is parallel
to the applied field, Bo, the net field is greater than Bo. Protons in these
zones come to resonance therefore at higher δ values than expected. Any
group held above or below the plane of the double bond will experience a
shielding effect , since in these areas the induced field opposes Bo.

29
Example : In α-pinene one of the geminal methyl groups is held in just such
a shielded position, and comes to resonance at significantly lower δ
(frequency) than its twin . The third methyl group appears at higher δ
(frequency), since it lies in the plane of the double bond and is thus
deshielded.

In summary, we can divide the space around a double bond into two
categories, as shown in figure 13. Deshielding occurs in the cone shaped
zones, and in these zones δ values will tend to be higher. Shielding is found
outside the cones and protons in these zones are shielded (lower δ values).
Carbonyl compounds: For the carbonyl group a similar situation arises,
although the best representation of shielding and deshielding zones is
slightly different from the alkene pattern; (see figure 13) Two cone shaped
volumes, centered on the oxygen atom, lie parallel to the axis of the C=O
bond; protons within these cones experience deshielding, so that aldehydic
protons, and the formyl protons of formate esters, appear at high δ values.
Protons held above or below these cones will come to resonance at lower &
values.
Alkynes: Whereas alkene and aldehydic protons appear at high δ values,
alkyne protons appear around & 1.5-3.5. Electron circulation around the
triple bond occurs in such a way that the protons experience a diamagnetic
shielding effect. Figure 13 shows how this arises, when the axis of the
alkyne group lies parallel to the direction of Bo. The cylindrical sheath of π
electrons is induced to circulate around the axis, and the resultant annulus-
shaped magnetic field acts in a direction that opposes Bo in the vicinity of
the protons. These protons experience lower values of field; therefore,
acetylenic protons appear at low δ values in the spectrum.
Aromatic compounds: In the molecule of benzene (and aromatic
compounds in general) π electrons are delocalized cyclically over the
aromatic ring. These loops of electrons are induced to circulate in the
30
presence of the applied field, Bo, producing a substantial electric current,
called the ring current. The magnetic field associated with this electric field
has the geometry and direction shown in figure 13.
The induced field is diamagnetic (opposing Bo) in the center of the ring, but
the returning flux outside the ring is paramagnetic (augmenting Bo). Protons
around the periphery of the ring experience an augmented magnetic field ,
and consequently come to resonance at higher δ values than would
otherwise be so. Protons held above or below the plane of the ring resonate
at low δ values. Two examples will illustrate the magnitude of these effects.
In the molecule of toluene the methyl protons resonate at δ 2.34, whereas a
methyl group attached to an acyclic conjugated alkene appears at δ1.95.
This is some measure of the greater deshielding influence of the ring current
in aromatic compounds (cyclically delocalized π electrons) compared with
the deshielding of conjugated alkene groups (having no cyclic delocalization).
Indeed, so important is this observation that NMR has become one of the
principal criteria used in deciding whether an organic compound has
substantial aromatic character (at least in so far as aromatic character
relates to cyclic delocalization of (4n + 2) π electrons). The method has been
applied successfully to heterocyclic systems and to the annulenes; for
example, [18] annulene sustains a ring current, so that the twelve peripheral
protons are deshielded and the six internal proton shielded. The outer
protons appear at 8 8.9, while the inner protons are at a lower frequency
than TMS at 8 - 1.8. (This is true only around 20°C; molecular motion
makes the spectrum change with variable temperature.)
One of the most dramatic observations in NMR work on aromatic systems
involves the dimethyl derivative of pyrene (I), in which the methyl groups
appear at δ -4.2, lower in frequency than TMS. This shows that the cyclic π
electron system around the periphery of the molecule sustains a substantial
ring current, and therefore indicates aromatic character in a non-benzenoid
ring system. The methyl groups are deep in the shielding zone of this ring
current, and it is for this reason that they appear at such an extraordinary δ
value .

31
Alkanes. The equatorial protons in cyclohexane rings come to resonance
about 0.5 ppm higher than axial protons, and this is attributed to
anisotropic deshielding by the σ-electrons in the β-γ bonds, as shown in
figure 14. The effect is small compared with the anisotropic influence of
circulating π electrons, but is readily observed in rigid systems and also in
mobile systems at low temperature.
Simple electronegative (inductive) effects operate only along a chain of
atoms, the effect weakening with distance, but magnetic anisotropy operates
through space irrespective of whether the influenced group is directly joined
to the anisotropic group. For this reason the stereochemistry of molecules
must be carefully studied to predict whether magnetically anisotropic
groups are likely to have an influence on the chemical shift of apparently
distant protons.

32
(iii) Hydrogen Bonding
Hydrogen bonded protons absorb at a lower field than the non-hydrogen
bonded protons. Due to high electronegativity of the atom to which the
proton is hydrogen bonded, the electron density around it is decreased as
compared to that around the non-hydrogen bonded proton. Thus, the
hydrogen bonded protons are highly deshielded and absorb at a lower field
than the non-hydrogen bonded protons. This downfield shift of the
absorption depends on the strength of the hydrogen bonding. The stronger
the hydrogen bonding, the lower will be the field at which the proton
absorbs. Intermolecular and intramolecular hydrogen bonding can easily be
distinguished by PMR spectroscopy because the latter show no shift in
absorption position on changing the concentration of the sample, whereas
the absorption position of the former is concentration-dependent.
For example, the absorption position of the hydroxyl proton of ethanol is
shifted to upfield on diluting the sample with a nonpolar solvent (e.g. carbon
tetrachloride) due to breaking of intermolecular hydrogen bonds. Since
intramolecular hydrogen bonds are not broken on dilution, intramolecularly
hydrogen bonded protons show almost no change in their absorption
position on dilution. Hydrogen bonding explains why and how the chemical
shift of the hydroxylic proton depends on concentration, temperature and
solvent.

(iv) van der Waals Deshielding

In crowded molecules, some protons may occupy sterically bindered position
resulting in van der Waals repulsion. In such a case, electron cloud of a
bulky group (hindering group) will tend to repel the electron cloud
surrounding the proton. Thus, the proton will be deshielded and will absorb
at slightly lower δ field than expected in the absence of this effect. For
example, the proton H in a conformationally rigid cyclohexanone chair
system (I) present in a steroid skeleton will resonate at lower field when R =
CH3 than when R = H.

33
Spin- Spin Coupling (splitting):
Coupling between nuclear spins gives rise to splitting of resonance lines,
providing the chemist with evidence for chemical bonding within a molecule.
This information can be obtained because the fine structure seen within
resonances arises from a through bond effect, and so can be easi1y related to
the common perception of chemical bonding.
The origin of spin-spin coupling
The magnetic field of a nucleus in a chemical bond will directly influence
both the nuclei immediately surrounding it and the electrons in the bond.
As we know, the spin- 1/2nucleus can adopt two possible orientations in
the applied field. Each orientation will have a differing influence on the
electrons in the bond as the electron spins will favour an anti-parallel
orientation relative to the nuclear spin. These electrons relay the effect of the
different nuclear spin states according to the electron spin pairing rules of
the Pauli exclusion principle and of Hund's rules Hence, a nucleus is able to
sense the possible orientations of a neighbouring nucleus when there is a
suitable bonding network between them, and because the effect is operative
only through bonds, it is referred to as coupling

Another way of explanation:

A typical organic molecule contains more than one magnetic nucleus (e.g.
more than one 1H, or 1H and 13C etc.). When one nucleus can sense the
presence of other nuclei through the bonds of the molecule the signals
will exhibit fine structure (splitting or multiplicity). Multiplicity arises because
if an observed nucleus can sense the presence of other nuclei with magnetic
moments, those nuclei could be in either the α or 𝛽 state. The observed
nucleus is either slightly stabilised or slightly destabilised by depending on
which state the remote nuclei are in, and as a consequence, nuclei which
sense coupled partners with an α state have a slightly different energy to
those which sense coupled partners with a β state. The additional fine
structure caused by spin-spin coupling is not only the principal cause of
difficulty in interpreting 1H NMR spectra, but also provides valuable
structural information when correctly interpreted.

34
signal’s multiplicity is the result of the magnetic effects of neighbouring
protons and therefore indicates the number of neighbouring protons.
To illustrate this concept, consider the following example.

If Ha and Hb are not chemically equivalent, they will produce different

signals. The chemical shift of Ha is affected by several electronic effects. All
of these effects modify the magnetic field felt by Ha, thereby affecting the
resonance frequency of Ha. The chemical shift of Ha is also affected by the
presence of Hb, because Hb has a magnetic moment that can either be
aligned with or against the external magnetic field. The chemical shift of Ha
depends on the alignment of nuclear spin of Hb. In some molecules, Hb will
be aligned with the field, while in other molecules Hb will be aligned against
the field. As a result, the chemical shift of Ha in some molecules will be
slightly different than the chemical shift of Ha in other molecules, resulting
in the appearance of two peaks. In other words, the presence of Hb splits the
signal for Ha into a doublet. Ha has the same effect on the signal of Hb,
splitting the signal for Hb into a doublet. This phenomenon is called spin-
spin splitting or coupling

Origin of Doublet
Now consider a scenario in which Ha has two neighbouring protons.

The chemical shift of Ha is impacted by the presence of both Hb protons,

each of which can be aligned either with or against the external field. Once
35
again, each Hb is like a tiny magnet and has an impact on the chemical
shift of Ha. In each molecule, Ha can find itself in one of three possible
electronic environments, resulting in a triplet. If each peak of the triplet is
separately integrated, a ratio of 1:2:1 is observed, consistent with statistical
expectations.

Similarly,

gives quartet

“Splitting of the spectral lines arises because of a coupling interaction

between neighbour protons, and is related to the number of possible spin
orientations that these neighbours can adopt. The phenomenon is called
either spin-spin splitting or spin-spin coupling”.

36
(n + 1) rule. The simple rule is used to find the multiplicity of the signal
from a group of protons, count the number of neighbours (n) and add 1.

The table given below summarizes the splitting patterns and peak intensities
for signals that result from coupling with neighbouring protons. When
analyse this carefully, a uniform pattern emerges. If n is the number of
neighbouring protons, then the multiplicity will be n+1. This observation is
called the n+1 rule.

Lets take an example NMR spectrum of 1,1-dichloroethane and 1,2-

dichloroethane.

• The NMR spectrum of 1,2-dichloroethane displays a single peak from

the four equivalent hydrogens.

37
 • The NMR spectrum of 1,1-dichloroethane shows two signals from the
two different types of hydrogens which are further split into group of
two or more peaks.

Thus signal’s multiplicity is the result of the magnetic effects of

neighbouring protons and therefore indicates the number of neighbouring
protons.

There are two major factors that determine whether or not splitting occurs:

1. Equivalent protons do not split each other.

Consider the two methylene groups in 1,2-dichloroethane. All four protons

are chemically equivalent, and therefore, they do not split each other. In
order for splitting to occur, the neighbouring protons must be different than
the protons producing the signal.

2. Splitting is observed for non-equivalent protons on the same carbon or

adjacent carbons or inother words we can say that splitting is observed
when protons are separated by either two or three σ bonds; that is, when the
protons are either diastereotopic protons on the same carbon atom (geminal)
or when they are connected to adjacent carbon atoms (vicinal).

When two protons are separated by more than three sigma bonds, splitting
is generally not observed. Such long-range splitting is only observed in
olefins, acetylenes, aromatics, heteroaromatics and in strained ring systems
such as bicyclic compounds. This type of long range coupling will be
discussed later.

38
Pascal Triangle
We can easily verify that the intensity ratios of multiplets derived from the n
+ 1 Rule follow the entries in the mathematical mnemonic device called
Pascal’s triangle. Each entry in the triangle is the sum of the two entries
above it and to its immediate left and right.
Below mentioned Figure is an example of this phenomenon.

CSIR- NET

coupling constant:
The separation between two consecutive lines is always constant within a
given multiplet, and is called as coupling constant (J).
The magnitude of J is usually expressed in units of Hz and never in δ (ppm)
values. The value of J remains constant and does not depend on magnetic
field. Therefore the separation between two peaks in a multiplet remains
always constant but if this separation changes that means that they
represent different signals or does not belong to the same peak/multiplet.

39
The separations of peaks (J value) in two coupled multiplets are exactly
equal. In the 1H NMR spectrum of 1,1,2-trichloroethane, two multiplets, one
doublet and one triplet are observed. The J value in the doublet is exactly
the same as in the triplet (6.1 Hz).

In other words, Ha influences Hb to the same extent that Hb influences Ha.

Note: The signal splitting in proton spectra is usually small, ranging from a
small value to 18 Hz. It is designated as J and called as the coupling
constant.

Factors affecting the coupling constant

• Coupling constant is a measure of the effectiveness of spin-spin

coupling. The value of J depends upon the number, type and
geometrical orientation of bonds separating the coupled nuclei.

• One bond coupling is greater than the two bond coupling which in
turn is larger than the three bond coupling and so on.

• The coupling constant unlike the chemical shift expressed in Hz, does
not depends on the applied field strength. This is because the strength
of the magnetic moment of a neighbouring proton, which is the source
of the spin spin coupling phenomenon, does not depend on the
applied field strength.

40
 • In general coupling constant is designated as nJab.
The superscript indicates the number of bonds through which interaction
occurs. For example 1J, 2J, 3J means that the one, two or three bonds are
involved in coupling interaction.
The subscript (ab) tells about the nuclei (Ha and Hb) which are taking part in
the coupling.

Geminal Coupling (2JHH)

• Protons attached to the same carbon are called as germinal protons

and these are separated by two bonds.
• If geminal protons are chemically non-equivalent then only they show
coupling.
• The germinal coupling (2JHH) constant values are usually negative or
near to zero.
• The germinal coupling in general depends on the hybridization of
carbon atom and the bond angle and the substituent such as
electronegative atoms. When s-character is increased, the absolute
value of geminal coupling constant is decreased (move to positive
value) i.e. 2Jsp3> 2Jsp2> 2Jsp. If an electronegative group is attached
nearby the coupled protons, the geminal coupling constant decreases
(move to positive value).

• The bond angle (HCH) also gives rise to change in 2JHH value. In
general, the value of 2J coupling constant increases as the bond angle
between the coupling protons decreases. As the angle decreases, the
41
 two atoms come closer and hence the interaction between the electron
spin become greater.
• Therefore geminal coupling constant can also help in determining the
ring size. As the ring size increases, the absolute value of geminal
coupling constant also increases (as shown below). As the CCC bond
angle in the ring increases (from 3 membered to 6 membered), the
complementary HCH bond angle decreases (from 3 membered to 6
membered) and consequently the germinal coupling constant
increases.

Vicinal coupling (3JHH)2 coupling (3JHH)

Protons attached to the adjacent carbon atoms are called as vicinal protons
and thus are separated by three bonds.
Vicinal coupling constant always has the positive value and depends on the
dihedral angle (angle of rotation, HCCH), the carbon-carbon bond length,
and the effects of electronegative atoms.

Martin Karplus established a relationship between the dihedral (torsion)

angle between vicinal hydrogens and the 3JHH coupling constant using a

42
largely theoretical (valence-bond) approach • This important relationship is
now called the “Karplus relationship”

Karplus Curve
Vicinal proton‐proton coupling constants depend on a variety of
stereochemical parameters such as bond angle, bond length, substituent
electronegativity and orientation, and most importantly on the torsion angle
between the coupling protons. The sensitivity of vicinal proton‐proton
coupling constants 3JHH′, to variations of dihedral angle ϕwas first
rationalized in valence bond terms by Karplus, who showed that the
coupling constants could be approximately fitted to a cos2ϕ function.
Extra
The general form of the Karplus relationship is:

Where, the coefficients (A, B, and C) are parameterized for particular

molecule types, atoms and substituents.

Martin Karplus derived a equation which relates the vicinal coupling

constant with the dihedral angle by a mathematical equation as given below.

43
The dihedral angle dependence of the magnitude of vicinal couplings results
from molecular orbital overlap
• the σ C-C bond and the σ C-H bonds are nearly perpendicular, so there is
little overlap
• overlap of the sp3 hybrid orbitals governs the magnitude of the coupling
• maximum orbital overlap occurs when the dihedral angle is 0° and 180°
(3JHH is large)
• the orbital overlap is minimal when the dihedral angle is 90° (3JHH is
small)

Ex. Ethane derivative

In ethane derivatives (ethyl groups), the dihedral angle for gauche rotamers
1 and 3 is about 60°, whereas for the trans rotamer the dihedral angle is
180°
• Therefore, according to the Karplus curve:
• the coupling constant is about 4 Hz for rotamers 1 and 3 (3J1 = 3J3 ≈ 4Hz)
• the coupling constant is about 13 Hz for rotamer 2 (3J2 ≈ 13 Hz)

44
Why cis alkene has less J value than trans?

Because the magnitudes of the vicinal couplings (3JHH) between cis and
trans is different because of the dihedral angle.

• The parallel C-H bonds in the trans conformer improve orbital overlap (as
opposed to the cis case where the bonds are tilted away from one another)

Long range coupling

The magnitude of J decreases sharply with the distance. It is very less

through more than three covalent bonds but in some cases the coupling is
observable even in case of more than three bonds. Such coupling is most
common in systems such as olefins, acetylenes, aromatics, heteroaromatics,
and strained ring systems (small or bridged rings). This kind of coupling
which occurs beyond three bonds, are called as long range coupling.

Allylic coupling (4JHH)

In addition to the germinal and vicinal coupling, alkenes also show small
coupling between protons substituted on carbons α to the double bond and
those on the opposite end of the double bond. This four bond coupling is
called allylic coupling. Allylic coupling constant are very less about 0-3 Hz.
The π-electrons of the double bond apparently help in coupling the
concerned nuclei and the magnitude of this depends upon the extent of
overlap of the carbon-hydrogen σ-bond with the π-bond. This type of
coupling also occurs in acetylenes.

45
Aromatic coupling

In aromatic systems also, coupling occurs beyond the adjacent carbon

atoms (more than three bonds). The ortho, meta and para protons can all
interact but the ortho coupling is maximum, followed by meta and then
para. In fact, the para coupling is rarely observed.

Hetero-aromatic coupling

The hetero-aromatic systems also show long range coupling analogues to

the aromatic systems.

For example, in furan coupling occurs between all of the ring protons. The
values of the coupling constant are given as follows:

46
CHEMICAL AND MAGNETIC EQUIVALENCE IN NMR

“Two protons are defined as being chemically equivalent if, by virtue of

symmetry within the molecule, their electronic environments are
indistinguishable and, therefore, they possess the same value of chemical
shift”.
“Two protons are defined as being magnetically equivalent if each couples
equally to a third neighbouring proton; otherwise they are magnetically
nonequivalent”.
For Example: p-chloroanisole

Note: 1. chemical equivalence means simply chemical shift equivalence, and

magnetic equivalence means coupling equivalence. 2. All the magnetically
equivalent nuclei are chemically equivalent but the reverse is not always
true.

Spin-spin interactions:
AX, AX2, AX3, AMX, AB types (prescribed syllabus)

Nomenclature of spin system

• Pople developed a convenient method to designate the type of spin-coupled

systems.
• Each chemically different type of protons is assigned a letter of alphabet A,
B, C and so on. Protons which have chemical shifts nearly same are
assigned the letters that are close to one another i.e. A, B and C.
• If the chemical shifts are widely different then the letters which are far apart
from one another are assigned for these protons e.g. A, B, C versus X, Y, Z.
• If groups of nuclei are magnetically equivalent, they are labelled as An, Bn,
AnBn etc.

47
For example CH3 group represents A3 system. The magnetically equivalent protons
have same chemical shift and hence group of one particular magnetically
equivalent protons (An) couple equally with another group of magnetically
equivalent protons (Bn).
• If protons are chemical shift equivalent but not magnetically equivalent, they
are labelled as AA’ system.
• If three types of protons are involved and they have almost same chemical
shifts, the system is assigned as ABC, whereas
• Protons having widely different chemical shift, a letter M (letter from the
middle of the alphabet) is used to designate the system i.e. AMX.
i) Two-Spin Systems (A2, AB, AX)
a. A2 System

A system having two equivalent nuclei is designated as A2 system. This

system always shows a singlet.
Compound 1,1,2,2-tetrachloroethane is an good example of A2 system.

b. AB System
A system containing two protons, say HA and HB which couple with each
other but do not couple with any other proton and their chemical shift
(δA─δB) values difference is comparable to the coupling constant JAB. In
such systems the doublets are distorted i.e. they are not 1:1. The inner lines
become larger and the outer lines smaller.

c. AX System
A system having two protons, say HA and HB with their chemical shift
(δA─δB) values difference much larger to the coupling constant JAB. This
system shows two distinct doublets with all the four lines of equal intensity.
The example of AX system is dichloroacetaldehyde (Cl2CHCHO).

48
Three-spin Systems
d. AX2 System
In this system, two magnetically equivalent protons are coupled to the third
proton which has chemical shift value widely different from the other two
protons. For such system, NMR spectrum shows a proper doublet (1:1) and
a triplet (1:2:1). Examples are Cl2CHCH2Cl, Cl2CHCHClCHCl2.

e. AX3 System
In the case of CH3-COH of an AX3 type. Due to this coupling, the signal of
the methyl group is split into a doublet and that of the OCH proton into a
quartet. The spin system corresponds to an AX3 system.

f. AMX System
In AMX system, three non-equivalent protons are present with large value of
Δν/J. Many vinyl systems (CH2=CHY) display AMX system (Y is strongly
electronegative substituent). There are three coupling constants for such

49
systems. The trans coupling JMX is larger than the cis coupling JAX. JAM is
the geminal coupling with a significant value.
The AMX system exhibits 12 lines of almost equal intensity. The coupling
constants can easily be obtained from the analysis of the spectrum. The
peaks due to the protons HA and HM are split into doublet by coupling with
HX proton. Each line is further split into narrow doublets. The doublet of HA
will split by HM and similarly the doublet of HM will split by HA (Small allylic
coupling JAM). Similarly the hydrogen HX is split into a doublet by coupling
with proton HM and then each line is further split into doublets with proton
HA.

First Order Spectra

If the splitting pattern of a multiplet is given by the (n+1) rule, then the
spectra is called as ideal or “first order” spectra. This is usually observed if
the spin-coupled nuclei have very different chemical shifts (i.e. Δν is large

50
compared to J). The chemical shift value and the coupling constant J can be
measured directly from the spectrum.
The first order spectra can be analysed by the following features
1. The number of component peaks in a multiplet is given by n + 1, where n
is the number of equally coupled protons causing the Splitting. The general
formula which covers all the nuclei is 2nI + 1, where n is the number of the
coupling nuclei with spin I.
2. The relative intensity of the component peaks of a multiplet is given by
the coefficients of the terms in binomial expansion of (x+1)n for nuclei with I
= 1/2.
3. Centre of the multiplet gives the chemical shift of the concerned nucleus.
4. The separations of peaks in two coupled multiplets are exactly equal and
correspond to the coupling constant.
It is well known that the chemical shift measured in Hz depends on the
applied magnetic field and the value of Δν increases as the field strength
increases. The value of coupling constant J remains constant and hence the
value of Δν/J will increase on increasing the field strength. Therefore, at
high field strength, most 1H NMR spectra become first order. It is important
to notice that high field NMR instruments give better resolution and
relatively easily interpretable spectra.
As an example of the analysis of first order NMR spectra, let us analyse the
PMR spectrum of ethyl chloride ( page no 17)
Second Order Spectra
If the coupled nuclei have approximately same chemical shifts and their
chemical shift difference is comparable to the coupling constant between
them, the first order splitting rule (2nI+1) is not applicable. The splitting
pattern in a multiplet is distorted and the bands are no longer symmetrical.
In fact, signal splitting disappears if the chemical shifts of the coupled
nuclei are the same. Such types of spectra are known as second order
spectra. It is difficult to measure the chemical shift and coupling constants
values simply by just analysing the spectra.
As the value of Δν/J decreases, the coupled multiplets approach each other
and the inner lines increase in intensity and the outer peaks decrease. In
some extreme cases the outer lines may become too weak to be observed
and hence the resulting multiplet is wrongly interpreted. Since there is
51
leaning of coupled multiplets towards one another and hence the chemical
shift values cannot be given by the center of the multiplet. In such cases the
chemical shift is given by the center of gravity. The chemical shift values can
be calculated by the following formula:

Simplification of second order or complex Spectra

The complete analysis of a NMR spectrum becomes difficult when signals

overlap and hence useful information is buried due to complexity of the
spectrum. For example, if several closely related methylene groups are
present in a molecule, their signals may overlap and the signals would not
be clearly recognized. There are some important methods to simplify a NMR
spectrum to get the maximum information.
i) High Field Strength
As we know that the chemical shift measured in Hertz is directly
proportional to the applied magnetic field, whereas the coupling constant
(Hz) remains the same. Thus on increasing the field strength, the value of
Δν/J will increases which further gives the more separation between
individual multiplets, overlapped at lower field strength. Thus the NMR
instruments with higher field strength give better resolution and therefore
easily interpretable spectra.
ii) Solvent effect
Chemical shift depends on the solvent used to record NMR spectra. The
interaction between the solvent molecules and the solute molecule may shift
the resonance position of a proton. If the solvent is non-polar such as
hydrocarbons, there will only be weak (van der Walls or London forces)
interactions between solvent and solute molecules and hence the chemical
shift of the protons in a molecule will remain same or very minute changes
will occur.

52
If the solvent is polar in nature such as acetone, chloroform, DMSO etc.,
strong dipole interactions between solvent and solute molecules would be
there especially when the solute molecules also contains polar bonds.
Because of these strong interactions, the observed chemical shift will shift to
a greater extent with respect to that taken in non-polar solvent.
If the solvent has a strong diamagnetic anisotropy (e.g., benzene, pyridine)
the interaction between the compound and the anisotropic field of the
solvent may give rise to a remarkable shifting in the resonance position.
It is observed that the solvents, such as benzene or pyridine cause the
shifting of observed resonance to the lower δ value, whereas other solvents
such as acetonitrile results in shifting to higher δ value. This difference is
believed to be dependent on the nature of the solute-solvent interaction in
the solution.
Thus, we can use these solvent shift effects to resolve the complex spectra to
some extent. By adding a small amount of deuterated benzene or pyridine to
the NMR sample can cause a dramatic difference in the appearance of the
NMR spectrum. The overlapping multiplets can be separated from one
another and hence can be analyzed more accurately.
iii) Spin decoupling or Double Resonance
Spin-spin coupling between neighbouring nuclei splits their signals into
multiplets and the analysis of the splitting patterns is useful for structure
determination of compounds. However, in certain cases, the splitting
patterns and spectra are so complex that for the simplification of spectra,
spin-spin decoupling is desired.
Irradiation of a nucleus or a group of equivalent nuclei at their resonance
using a second strong radio frequency oscillator results in the removal of all
couplings arising from the irradiated nuclei called spin-spin decoupling (spin
decoupling or double irradiation or double resonance) because an additional
radio frequency is used. Such an irradiation imparts extra energy which
causes rapid transitions between the different spin states of the irradiated
group of nuclei. Thus, neighbouring nuclei (e.g. protons) cannot see different
spin states (but they can see only an average view of spin states) of the
irradiated nuclei and consequently spin-spin couplings are effectively
removed. This is very similar to spin-spin decoupling through rapid proton
exchange reaction.

53
Let us take the example of NMR spectrum of ethanol where methyl protons
appear as a triplet due to the spin-spin splitting by the methylene protons. If
the methylene protons are irradiated strongly with an additional radio
frequency at their resonance, then they change their spin states very
rapidly. Thus, the methyl protons can see only an average of the possible
spin orientations of the methylene protons and the coupling will be removed.
Consequently, the triplet resulting from the methyl protons collapses to a
singlet and appears at its usual position and the methylene absorption is
eliminated. The disappearance of the methylene absorption is due to
saturation. Similarly, when the methyl protons are irradiated, the quartet
resulting from the methylene protons collapses to a singlet and the methyl
absorption is eliminated.

iv) Chemical shift reagents

The lanthanide shift reagents were first introduced by Hinckley in 1969.

When such reagents are added to the compounds under investigation, there
is a remarkable shifts in the resonance positions of the protons in the
molecule without increasing the strength of the applied magnetic field i.e., a
second order spectrum is converted to first order spectrum.

The lanthanide shift reagents are β-dicarbonyl complexes of rare earth

metals (lanthanides). The commonly used lanthanides shift reagents are
• Tris-(1,1,1,2,2,3,3-heptafluoro-7,7-dimethyloctane-4,6-dionato)
europium, Eu(fod)3;

54
 • Tris-(dipivaloylmethanato) europium, Eu(dpm)3.

The lanthanide shift reagents are mild Lewis acids, which attach themselves
to the sites which have lone pairs such as amines, hydroxyl, aldehydes,
ketoses, thiols, ethers etc. The amount of shift in resonance position
depends on the lanthanide metal ion, proton under investigation and
concentration of the shift reagent in the solution. More is the availability of
the lone pair, greater is the complexation. The strength of the complex
formation is in the following order, provided the complexation site of the
molecule is not sterically hindered.
NH2 > OH > C=O > ─O─ > ─COOR > CN
The simplification of complex spectra by the addition of shift reagent can be
explained by the example of 1-hexanol. In the absence of shift reagent, the
spectra of 1-hexanol look like as shown in figure given below.
We can clearly see only the signals due to the terminal methyl protons (a
triplet at δ 0.9 ppm) and due to the methylene group next to the hydroxyl
group (triplet at δ 3.8 ppm). The remaining methylene protons come into the
broad and unresolved peak between δ 1.2-1.8. On adding the shift reagent,
the signals due to the methylene protons closer to the hydroxyl group are
shifted downfield resulting in clearly observed signals. The methylene group
which is relatively closer to the OH group is shifted more downfield and as
the distance increase from the OH group, shifting of the peak is less
pronounced. Thus, on addition of shift reagent, spectrum is simplified to
almost to the first order.

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 v) Deuterium exchange.

Deuterium exchange is the most elementary and very useful technique for
assigning the protons of OH, NH2, SH etc groups which are exchangeable
with deuterium.

Due to the above reactions, the peak due to the alcoholic hydrogen will
disappear and a signal due to HOD proton will appear in the spectrum.
For detecting the protons exchangeable with D2O, either the spectrum is
recorded in D2O or a few drops of D2O are added to the sample and the
sample tube is shook properly before recording the NMR spectrum. The
deuterium is not detected in the 1H NMR as it absorbs at different field
strength and hence there will not be any coupling/splitting due to the
proton which has been exchanged with deuterium.

56
Deuterium labelling also simplifies PMR spectra as Illustrated by the
example of ethyl chloride. As methyl hydrogens are replaced by deuterium,
the multiplicity of the methylene signal changes from a quartet (3 + 1) to a
triplet (2 + 1) to a doublet (1 + 1) and finally to a singlet as shown

vi) Stereochemistry and hindered rotations.

Flexibility of chemical bonds is one of the important factors that determine

the properties and reactivity of a molecule. Most chemical bonds, while not
completely rigid, still are not involved in totally free rotation.

(Cis- trans stereochemistry and dihedral angle-based conformations

already discussed)

vii) Temperature effects.

Valuable structural information can be obtained by recording the NMR
spectra of organic compounds at high and low temperatures, when
rotational and intermolecular forces can be grossly changed. The practical
difficulties in introducing a heated or cooled sample into the NMR magnet
are considerable, since magnetic field changes with magnet temperature,
but insulated probes allow variable temperature NMR to be recorded
routinely.
Example: As we already know that the protons in cyclohexane are of two
types; axial and equatorial. Axial protons (shown in red) occupy a different
electronic environment than the equatorial protons shown in blue). That
means axial and equatorial protons are not chemically equivalent hence one
57
can expect two signals in the 1H NMR spectrum; one for the six axial
protons and the other for the six equatorial protons. The NMR spectrum of
cyclohexane, however, shows only a single sharp peak at δ 1.4.

This can be explained by the fact that at room temperature the rate of ring
flipping is high. The NMR spectrometer is too slow to acquire a spectrum of
the individual conformations of cyclohexane and only detect the average
electronic environment of the protons and hence only one signal is observed.
The single peak observed has a chemical shift in between the actual
chemical shifts of the axial and the equatorial protons. The rate of ring
flipping can be slowed down by decreasing the temperature. If the sample is
cool down to −100 °C, ring flipping occurs at a very slow rate, and separate
signals are observed for the axial and equatorial protons.

Nuclear Overhauser effect (NOE)

The nuclear Overhauser effect can be used to demonstrate that two protons
(or groups of protons) are in close proximity within the molecule, and is
therefore of considerable value in the study of molecular geometry.
The basic observation of NOE can be described by reference to the
hypothetical molecule I.

The two protons, Ha and Hb, we must imagine to be close enough to allow
through-space interaction of their fluctuating magnetic vectors; each can
contribute to the other's spin-lattice relaxation process (T1). The number of
intervening bonds between Ha and Hb is too large to allow normal coupling
between them, but this is not a prerequisite for the operation of NOE.

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If we double irradiate at the Hb signal, we shall stimulate absorption and
emission processes for Hb, and this stimulation will be transferred through
space to the relaxation mechanism of Ha. The spin-lattice relaxation of Ha
will be speeded up, leading to a nett increase in the NMR absorption signal
of Ha when, Ha and Hb must be within 3.5 Å of each other.
In summary, provided that Hb makes a significant contribution to the spin-
lattice relaxation process of Ha, then double irradiation of Hb causes an
increase in the intensity of the Ha signal (by 1-50% for protons).
Example: NOE in isovanillin.

If we first record the NMR spectrum for isovanillin normally, and then while
irradiating at the CH3O frequency, the integral for the ortho proton (which
appears as a doublet) is markedly increased.

Extra: Since molecular oxygen is paramagnetic, and can contribute to

nuclear spin-lattice relaxation processes, the NOE experiment should be
carried out on deoxygenated samples, to avoid interference with the NOE
observation.
NOE in various molecules

59
Applications of PMR Spectroscopy

PMR spectroscopy is an important tool in the hands of organic chemists for

getting structural information. lt is also useful in stereochemical studies. An
organic molecule consists of carbon-hydrogen skeleton, and thus NMR
spectroscopy is especially useful in the study of this structural feature of the
molecule. The important applications of PMR spectroscopy, besides
obtaining routine structural information, are summarized as follows.
(i) Identification of Structural Isomers
Structural isomers can easily be distinguished by PMR spectroscopy. For
example
(i) CH3OCH3 and CH3CH2OH
In dimethyl ether, all the six protons are equivalent. Hence, its PMR
spectrum will show only one singlet. In ethanol, there are three kinds of
protons. Thus, its PMR spectrum will exhibit three signals; one triplet due to
the methyl protons, one quartet due to the methylene protons and one
singlet due to the hydroxylic proton.
(ii) 1,1-dichloroethane (CH3CHCl2) and 1,2-dichloroethane (ClCH2CH2Cl)
1,1-dichloroethane has two kinds of protons. Hence, it will exhibit two
signals in its PMR spectrum; one doublet and one quartet due to CH3- and -

groups, respectively. In 1,2-dichloroethane all the four protons are

equivalent. Hence, its PMR spectrum will show only one singlet.
(ii) Detection of Aromaticity
As we know aromatic protons are highly de-shielded due to the circulating π
electrons (ring current) and appear at very low field ( δ 6-8.5). From this, the
aromatic character of a compound under study can be predicted.
(iii) Detection of Hydrogen Bonding
Intermolecular and intramolecular hydrogen bonding can be detected by
PMR spectroscopy because both shift the absorption position of the
hydrogen-bonded proton to downfield. Besides, both types of hydrogen
bonding can also be distinguished, as the intermolecular hydrogen bonding
is concentration-dependent, while the intramolecular hydrogen bonding is
not concentration-dependent.
(iv) Distinction Between cis-trans Isomers and Conformers
PMR spectroscopy can easily distinguish cis and trans isomers because the

60
concerned protons have different values of chemical shifts as well as
coupling constants For example

Similarly, the axial and equatorial positions of protons or groups carrying

protons and various conformations of a molecule can be distinguished on
the basis of different values of their coupling constants, chemical shifts and
peak areas.
(v) Magnetic Resonance Imaging (MRI)
Magnetic Resonance Imaging (MRI) is a non-invasive imaging technology
that produces three dimensional detailed anatomical images. MRI scanners
are particularly well suited to image the non-bony parts or soft tissues of the
body
MRIs employ powerful magnets which produce a strong magnetic field that
forces protons in the body to align with that field. When a radiofrequency
current is then pulsed through the patient, the protons are stimulated, and
spin out of equilibrium, straining against the pull of the magnetic field.
When the radiofrequency field is turned off, the MRI sensors are able to
detect the energy released as the protons realign with the magnetic field.
The time it takes for the protons to realign with the magnetic field, as well as
the amount of energy released, changes depending on the environment and
the chemical nature of the molecules. Physicians are able to tell the
difference between various types of tissues based on these magnetic
properties.

61
Chemical Shift of various Functional groups.

62
63
64
 Questions
1. For which of the following isotopes NMR spectroscopy is possible and
why? 12C, 14N, 2H, 35Cl, 32S, 16O and 31P

2. Discuss the process of absorption of energy during the nuclear

magnetic transitions.
3. Predict the number of signals and their relative intensities in the low
resolution PMR spectra of the following compounds: (a) Toluene (b)
Propanal (d) Propionamide
4. What is chemical shift? Giving examples, discuss the factors which
affect the magnitude of the chemical shift.
5. Explain spin-spin coupling and splitting of signals with examples.
6. Predict the number of signals and their multiplicity in the PMR
spectra of the following compounds:

7. Write notes on: (a) Shielding and deshielding (b) Relaxation processes
(c) Coupling constant
8. (a) Why are the NMR absorption positions expressed relative to a
reference compound? (b) Why is TMS a good reference compound in
NMR spectroscopy?
9. In PMR spectroscopy, what information can be obtained from the
following: (a) Number of signals: (b) Splitting of signals (c) Chemical
shifts (d) Areas under peaks (e) Coupling constants.
10. What is the cause of different chemical shifts for various hydrogens in
NMR spectroscopy?
11. Why are chemical shifts generally expressed in δ or values instead of
in cps?
12. Write explanatory notes on: (a) Shift reagents: (b) Spin-spin
decoupling; (c) Nuclear Overhauser Effect (NOE)

65
13. Using PMR spectroscopy, how will you distinguish the following pairs:
(i) Maleie acid and fumaric acid
(ii) 1-chloropropane and 2-chloropropane
(iii) Intermolecular hydrogen bonding and intramolecular hydrogen
bonding
14. Explain the following:
(a) Acetylenic protons absorb at higher field than olefinic protons.
(b) The hydroxylic proton of ethanol does not split the PMR signal of
its methylene protons in the presence of a trace of acid.
(c) No signal for deuterium is observed in the PMR spectrum of a
compound, e.g. CD3CH2CH3
15. Discuss the characteristic features of the first order PMR spectra. How
can the more complex (second order) PMR spectra be simplified for
obtaining more information?
16. Write notes on: (a) Chemical and magnetic equivalence of protons; (b)
Factors affecting coupling constants.
17. a) Give an account of vicinal and geminal couplings in PMR
spectroscopy. (b) Write a note on chemical exchange and spin-spin
decoupling.
18. (a) How is PMR spectroscopy useful in the detection of aromaticity? (b)
Discuss the use of deuterium exchange and deuterium labelling in
PMR spectroscopy.
19. Cyclohexane gives only one PMR signal (singlet) at the room
temperature, whereas at -l00°C it gives two sharp singlets. Explain
this observation.
20. A pale-yellow organic compound with molecular formula C6H5N03
exhibited an unsymmetrical multiplet in the region 1.8-2.9 (4H) and
a singlet at 0.1τ (IH) in its NMR spectrum. Deduce the structure of the
compound.
21. If the observed chemical shift of a proton is 315 Hz form TMS at a 90
MHz NMR spectrometer, what is the chemical shift in terms of δ?
Express it in value also.

66
 22. Give a structure consistent with each of the following sets of NMR
data:

23. Predict the number of signals and their relative intensities in the PMR
spectra of the following isomers: (a) Acetone and propanal; (b)
Ethylbenzene and p-xylene; (c) 2-pentanone and 3-pentanone.
24. Predict the number of signals and their multiplicity in the PMR
spectra of the following compounds:

25. Acetonitrile (CH3CN) has resonance at 1.97 ppm, whereas methyl

chloride (CH3Cl) has resonance at 3.05 ppm, even though the dipole moment
of acetonitrile is 3.92 D and that of methyl chloride is only 1.85 D. The
larger dipole moment for the cyano group suggests that the electronegativity
of this group is greater than that of the chlorine atom. Explain why the
methyl hydrogens on acetonitrile are actually more shielded than those in

67
methyl chloride, in contrast with the results expected on the basis of
electronegativity.
(Hint: What kind of spatial pattern would you expect for the magnetic
anisotropy of the cyano group, CN?)
26. In benzaldehyde, two of the ring protons have resonance at 7.87 ppm,
and the other three have resonance in the range from 7.5 to 7.6 ppm.
Explain.
27. Predict the appearance of the NMR spectrum of propyl bromide.

68