NMR: Nuclear Magnetic Resonance

NMR spectroscopy works by allowing somebody to “see”

the nuclei in a molecule as well as the chemical
neighborhood of those nuclei which helps to establish the
structure of the molecule

Some nuclei, however, are NMR active, and some are NMR
inactive. Fortunately, both carbon and hydrogen nuclei are
NMR active

NMR is concerned with change in the direction of spin

orientation of nucleus as the result of the absorption of
radiofrequency radiation
About Spin States

• When a charged particle spins on its axis, it creates a

magnetic field. The resulting spin-magnet has a magnetic
moment (μ) proportional to the spin
• The same effect holds for certain atomic nuclei.
– Any atomic nucleus that has an odd mass number, an
odd atomic number, or both, also has a spin and a
resulting nuclear magnetic moment.
– The allowed nuclear spin states are determined by the
spin quantum number, I, of the nucleus given by the
formula 2I+1
 Nuclear Spin

NMR Active Nuclei: nuclear spin quantum number (I) ≠ 0

Even mass nuclei that have even number of neutron have I = 0 (NMR
inactive)

Even mass nuclei that have odd number of neutrons have an integer
spin quantum number (I = 1, 2, 3, etc)
Odd mass nuclei have half-integer spin quantum number
(I = 1/2, 3/2, 5/2, etc)

I= 1/2: 1H,

This spinning involves the movement of a positive charge, and, according to

the laws of physics, the movement of charged particles creates a magnetic
field with a magnetic moment. The magnetic moments that come from the
nuclear spins have direction.
+
Nuclear Spin
The distribution of
nuclear spins is random
in the absence of an +
external magnetic field.

+
+
Nuclear Spin
• An external magnetic field causes
nuclear magnetic moments to align
parallel and anti-parallel to applied
field
• There is a slight excess of nuclear
magnetic moments aligned parallel to
the applied field
Nuclear Spin state in Ext. Magnetic Field(B0)

For 1H ; I =1/2, States = 2I+1 = 2.1/2 +1 = 2

Nuclear Spin state in Ext. Magnetic Field(B0)

As the strength of the external magnetic field (Bo) increases,

the difference in energy (ΔE) between the spins aligning
with the magnetic field (α) and those going against the
magnetic field (β) also increases . This energy gap between
the two kinds of spins — α and β — is what an NMR
experiment measures.
E and Magnet Strength
• Energy difference is proportional to the magnetic field
strength
• E = h =  h B0 The Larmor Equation
2
• Gyromagnetic ratio, , is a constant for each nucleus
(26,753 s-1gauss-1 for H)
How to Get NMR Signal?
-state

a process called spin flipping

The nucleus is said to be in resonance
E = h

- State Signal

How the energy gap is measured by an NMR

spectrometer? Like most types of spectroscopy, NMR
spectroscopy uses Radio wave to effect a transition
between energy levels.
 Nuclear Magnetic Resonance
(a) Precession and (b) after absorption of electromagnetic
radiation.
 A Simplified 60 MHz NMR Spectrometer

RF (60 MHz) h
Oscillator absorption RF
Recorder
signal Detector
Transmitter
Receiver

MAGNET MAGNET

N S

Probe
The sample is placed inside a huge magnet (called the external magnetic field, or B
The direction of the magnetic moments of the nuclei line up either with the external magnetic field (an α spin) or
against it (a β spin).
The energy difference between an α spin and a β spin is the ΔE.o). Upon absorption of light that has energy equal to
the energy gap (ΔE), the nuclei come into resonance, and α spins are flipped into β spins.
A detector measures the frequency of the absorbed light (which is proportional to the energy gap between the α and
β spins) and then plots the frequency of the light absorbed on the NMR spectrum versus the intensity of light absorption.
Secondary Magnetic Field: Important for NMR
So, that’s how an NMR spectrometer determines the energy gap.
But if all the hydrogen nuclei would have the same energy gap
between α and β spins, the NMR spectrum would show only a single
peak (or single light absorption), representing all the hydrogens in
the molecule. And that wouldn’t be particularly helpful. But
discussion so far has omitted one key ingredient — electrons! So
far, this discussion has been limited to bare nuclei that have no
electrons surrounding them.

Secondary Magnetic Field

Secondary Magnetic Field: Shielding
• A moving charge (electron) creates a secondary magnetic field
which opposes the applied magnetic field Bo
• 1H nuclei are shielded by the magnetic field produced by
the surrounding electrons. The higher the electron density
around the nucleus, the higher the magnetic field required
to cause resonance
This represents the electron density of a C-H bond. How much electron
Z density is on the proton depends on what else is attached to the carbon. If Z
C H is an elelctronegative atom, the carbon becomes electron deficient and pulls
some of the electron density away from the H. if Z is an electron donating
group, more electron density ends up on the H.
B
o
Effective Magnetic Field: Shielding and Deshielding
The effective/resultant magnetic field, therefore, what the hydrogen nuclei
actually “sense” through the surrounding electronic environment is always
less than the actual applied magnetic field B0.

Beffective = Bapplied  Blocal

In the classical NMR experiment, magnetic field strength must be increased for
a shielded proton to flip at the same frequency.
Shielding of Nuclei : Concept of Chemical Shift

Ha Hb

Nmr spectrum
Chemical Shift: Internal Standard
Chemical Shift: Internal Standard

A reference compound: Internal Standard

 Internal Standard: TMS

Tetra Methyl Silane: TMS

TMS has following advantages as the reference compound:

• 1. It is chemically inert and non-toxic.

• 2. It is volatile (b.pt 270C) and soluble in most organic
solvents.
• 3. It gives a single sharp peak as it has 12 equivalent
hydrogens.
. 4. Since silicon is less electronegative than carbon, TMS
protons are highly shielded. Signal defined as zero.
• 5. Organic protons absorb downfield (to the left) of the TMS
signal.
Internal Standard: TMS
 Chemical Shift
The shifts from TMS in Hz are bigger in higher field instruments
(300 MHz, 500 MHz) than they are in the lower field instruments (100
MHz, 60 MHz).

We can adjust the shift to a field-independent value,

the “chemical shift” in the following way:

parts per
million

shift in Hz
chemical
shift
= d = = ppm
spectrometer frequency in MHz

This division gives a number independent

of the instrument used.

A particular proton in a given molecule will always come

at the same chemical shift (constant value).
Scale of 1H NMR
 Factors affecting e-Density: Deshielding
Four major factors account for the resonance
positions (on the ppm scale) of most protons

• Deshielding by electronegative elements

Inductive effect by electronegative groups

• s-character (hybridization effect)

• Magnetic Anisotropic effect (magnetic fields usually

due to -bonded electrons in the molecule(

• Hydrogen bonding
 Deshielding by Electronegative Elements
Dependence of the Chemical Shift of CH3X on the Element X

Compound CH3X CH3F CH3OH CH3Cl CH3Br CH3I CH4 (CH3)4Si

Element X F O Cl Br I H Si
Electronegativity of X 4.0 3.5 3.1 2.8 2.5 2.1 1.8
Chemical shift d 4.26 3.40 3.05 2.68 2.16 0.23 0

most deshielding increases with the

electronegativity of atom X TMS
deshielded

Cumulative Effect
The effect
increases with
CHCl3 CH2Cl2 CH3Cl greater numbers
7.27 5.30 3.05 ppm of electronegative
atoms.
 S-Character: Hybridization Effect
 As s-character of carbon atom increases, the electronic cloud is held
more closer to the carbon and provides less electron density for
shielding of protons, and thus the chemical shift, δ, increases (shifted
downfield).
 According to the above reasoning, the following trend for the chemical
shift is expected:

expected to be observed at d
>7
(down field - higher d)
 But in fact, we have the following order: actually observed at
d = 2-3

 This suggested that other factors than the sp character of carbon

might affect the chemical shift in this case. The above discrepancy
can be explained by what is called Magnetic Anisotropic Effect. 25
 Magnetic Anisotropic Effect
Whereas the local circulation of electrons around a proton a shielding effect (i.e., to
the right in the NMR spectrum, -δ(, there can be both shielding and deshielding effects
from electron motion in other parts of the molecule. We refer to such interactions
as magnetic anisotropy effects, since they are caused by anisotropic electron
circulation (i.e., the electron circulation is stronger in some orientations of the molecule
in the magnetic field than in others).
The most dramatic examples of anisotropy effects are seen with benzene and other
aromatic rings, which cause very large shielding (-δ( effects for protons placed above
the ring, and smaller deshielding (+δ( effects for protons to the side of it. These chemical
shift effects occur because electron circulation is stronger when the plane of the
benzene ring is perpendicular to the magnetic field than when it is parallel to it
 Magnetic Anisotropic Effect
The presence of a nearby pi bond or pi system greatly
affects the chemical shift.

Aromatic protons
d = 7-8 ppm
 Magnetic Anisotropic Effect

Vinyl (Olefinic) protons, Acetylene protons

d = 5-6 ppm d̃ ≈ 2.5 ppm

Aldehyde proton, d= 9-10 ppm

Hydrogen Bonding: O-H and N-H Signals

HYDROGEN BONDING DESHIELDS PROTONS

The chemical shift depends

R on how much hydrogen bonding
is taking place (observed in high
concentrated solutions).
O H H
Hydrogen bonding lengthens the
O H O R O-H bond and reduces the valence
electron density around the proton
R
 it is deshielded and shifted
downfield in the NMR spectrum.

Alcohols vary in chemical shift D2O-exchangeable (peak for OH proton

from 0.5 ppm (free OH) to about in alcohol and NH in amines disappears
5.0 ppm (lots of H bonding). upon shaking with D2O) 29
 Some More Extreme Examples
δ- δ+ δ-
-I
Carboxylic acids have strong
hydrogen bonding - they
form dimers.

δ- δ+ δ-
 Resonance, electronegativity of oxygen and the formation of hydrogen
bonding withdraw electron cloud from the acid protons.
 Thus, protons attached to carboxylic acids are the least shielded protons
and have a chemical shift of 10-12 ppm.

H3C O
O In methyl salicylate, which has strong
H internal hydrogen bonding, the NMR
absorption for O-H is at about 14 ppm,
O (highly downfield(

Notice that a stable 6-membered ring is formed

 NMR Correlation Chart
Chemical shift gives the electronic environment of protons

(Shielding and Deshielding)

PROTON IN PROTON IN
ELECTRON-POOR disappears upon shaking ELECTRON-RICH
ENVIRONMENTS with D2O ENVIRONMENTS
aromatic -OH -NH
DESHIELDED SHIELDED
DOWNFIELD UPFIELD
HIGH FREQUENCY CHCl3 , H 0-5 LOW FREQUENCY
LARGE d 3-5 SMALL d

10-12 7-8 1.5 - 3

9-10 4.5 - 7 0–2 TMS

12 11 10 9 8 7 6 5 4 3 2 1 0 d (ppm)
H
CH2F CH2Ar C-CH-C
RCOOH RCHO C=C CH2Cl CH2NR2
CH2S C
acid aldehyde olefinic CH2Br
CH2I C C-H C-CH2-C
sp2
CH2O C=C-CH2 C-CH3
CH2NO2 CH2-C- sp3
sp3 sp sp3 O
 Till Now: We Deal With
 Splitting of the spin states of the nucleus of a proton in a molecule under
an external magnetic field
 We are able to find the electronic environment of a proton i.e. we can
distinguish between shielded/ deshielded proton.
 Accordingly we can get a peak/signal with respect to TMS signal in our
NMR frame.

But ??????????

• Do the signals
exhibit same pattern?
• How does the
signal indicate about
the numbers of
protons
Nature and Intensity of Signals
Coupling with
neighbor proton

Some of the individual absorptions split

further into smaller peaks. This is
called coupling. Coupling is a
phenomenon that’s useful in determining
how each piece of the molecule is
connected to the others, coupling tells
you how many hydrogens live next door
to that hydrogen. Coupling comes from
the interaction of the magnetic moments
Actual spectrum of the hydrogens with the magnetic
moments of the neighboring hydrogens.
In most cases, hydrogens only couple the
hydrogens that are on adjacent carbons.
Chemically equivalent hydrogens don’t
couple, which is why hydrogens on the
same carbon don’t couple most of the
time and why the six hydrogens in
benzene don’t couple.
 Nature of Signals
The “n + 1 rule” and the coupling constant
Coupling follows what is called the n + 1 rule. This rule says that a peak will be split n + 1
times, where n is the number of equivalent neighboring hydrogens.
A peak that does not couple and just shows a single line is called a singlet. The alcohol
hydrogen in ethanol does not couple so it gives a singlet. A peak that’s split into two is
called a doublet, three a triplet, four a quartet, and so on.

The coupling constant, or J value, is proportional to the distance between the lines (or the
tops of the peaks) in a signal. This value is given in frequency units (hertz, or Hz), rather
than in ppm, to make the coupling constant independent of the size of the external
magnetic field.
Coupling Constant (J and J value)
1,2 1,3
 Intensity of Signals
The peak intensity — or the area underneath a peak on a spectrum — is related to the
number of hydrogens that the peak represents. A computer uses the mathematical
process of integration to find the areas underneath each peak. Traditionally, integration
is shown on the spectrum by the addition of an integration curve (see below fig.),
although modern computing has made digital integration common that doesn’t require
you to do any measuring. The height of this integration curve is proportional to the area
underneath a peak, so this height is proportional to the number of hydrogens the peak
represents.
Pascal’s Triangle
Pascal’s Triangle
 Important Points in NMR Spectrum
· Chemical shift: Refers to where a peak appears on a spectrum, relative
to the reference molecule TMS (also called the δ value). The chemical shift is
given in units of parts per million (ppm). It gives you an idea of what kinds of
functional groups a hydrogen or carbon is surrounded by.
· Integration: Tells you the area underneath a peak, which in turn gives you
information about how many hydrogens a peak represents, relative to the other
peaks in the spectrum. Carbon NMR usually does not have integration on the
peaks.
· Coupling: Tells you how many hydrogen neighbors a hydrogen sees,
following the n + 1 rule. The n + 1 rule can be applied all at once if a hydrogen is
surrounded only by chemically equivalent hydrogens. It must be done individually
when it’s surrounded by two or more chemically nonequivalent hydrogens. NMR
tree-splitting diagrams are used to predict how many peaks will be found in the
spectrum of a given hydrogen that’s surrounded by two or more nonequivalent
hydrogens. Hydrogens on either nitrogen or oxygen generally don’t couple
because of fast exchange processes — these hydrogens generally show up as fat
singlets (which go away when the sample is shaken with D2O).
· Coupling constant: Is proportional to the distance between the tops of
the peaks in a multiplet. The coupling constant is referred to as the J value (given
in units of Hz). This value can tell you which hydrogens are coupled to each other
because coupled hydrogens have the same coupling constant.
 Application of NMR
• Structure Determination of Organic Compounds: By using this
technique, one can able to determine the C-C, C-H bond connectivity in
a molecule.

• Reaction monitoring: One can able to monitor the progress of a

reaction.

Aldehyde Ketone
Structure Determination of Organic Compounds

H3C H
C C
H3C CH3
Structure Determination of Organic Compounds

H O H H d= 2.0 d= 1.2
3H 3H
H C C O C C H
H H H
d= 4.1
2H
Structure Determination of Organic Compounds
H H
d= 1.2, t
H H J= 7.0, 3H
H C C H
d= 7.4-7.1,
H H m, 5H d= 2.6, q,
H H J= 7.0, 2H