NUCLEAR MAGNETIC RESONANCE
WHAT IS SPECTROSCOPY ?
The study of molecular structure and
dynamics
through
the
absorption,
emission, and scattering of light.
THE ELECTROMAGNETIC SPECTRUM
high
Frequency (n)
low
high
Energy
low
X-RAY
INFRARED MICROWAVE
ULTRAVIOLET
Vibrational
infrared
Visible
Ultraviolet
2.5 mm
200 nm
400 nm
BLUE
short
15 mm
RADIO
Nuclear
magnetic
resonance
1m
800 nm
RED
Wavelength (l)
FREQUENCY
long
5m
SPECTROSCOPIC TECHNIQUES AND THEIR USES IN
ORGANIC CHEMISTRY
Radiation
Absorbed
Ultravioletvisible
l, 190-400 nm
and 400-800
Effect on the Molecule
Infra-red (mid
infra-red)
l, 2.5-25 mm n,
400-4000 cm-1
Changes in the vibrational and
rotational movements of the
molecule
Detection of functional
groups, which have
specific vibration
frequenciesfor
example, C=O, NH2, OH,
etc.
Microwave
Electron spin resonance or
electron paramagnetic resonance;
induces changes in the magnetic
properties of unpaired electrons
Detection of free radicals
and the interaction of the
electron with, for
example, nearby protons
Information Deduced
Changes in electronic energy levels Extent of -electron
within the molecule
systems. Presence of
conjugated unsaturation,
and conjugation with
nonbonding electrons
SPECTROSCOPIC TECHNIQUES IN ORGANIC
CHEMISTRY AND THEIR USES
Radiation
Absorbed
Effect on the Molecule
Information Deduced
NMR Radio
frequency
l, 1-5m
Nuclei placed under the static
magnetic field change their spins
after absorption of
radiofrequency radiations
The electronic
environment of nuclei,
their numbers and
number of neighboring
atoms.
Radio waves
 Longest
wavelength EM waves
 Uses:





TV broadcasting
AM and FM broadcast radio
Heart rate monitors
Cell phone communication
MRI (MAGNETIC RESONACE IMAGING)

Uses Short wave radio waves with a magnet to create an image
ALL SPECTROMETERS HAVE SOME COMMON
ESSENTIAL FEATURES
Electromagnetic
Radiation
Source
SAMPLE
HOLDER
ANALYZER
DETECTOR
RECORDER
(or Computer)
 A source of electromagnetic radiations of the appropriate frequency range.
 A sample holder to permit efficient irradiation of the sample.
 A frequency analyzer which separates out all of the individual frequencies
generated by the source.
 A detector for measuring the intensity of radiations at each frequency,
allowing the measurement of how much energy has been absorbed at each of
these frequencies by the sample; and
 A recorder – either a pen recorder or computerized data station, with a VDU
for initial viewing of the spectrum, with the possibility of manipulation.
 NUCLEAR-
Study of nuclear spins
 MAGNETIC-
Under the influence of applied
magnetic field
 RESONANCE-
Record the resulting resonance in
nuclear spin through the absorption
of RF
COMPARISON BETWEEN THE PRINCIPAL
SPECTROSCOPIC METHODS: GOOD FEATURES
Method
13C-
1H-
NMR
NMR
Identification of functional
groups
**
Measurement of molecular
complexity
IR
MS
UV/VIS
**
***
**
*
**
**
*
***
*
Sensitivity
(sample size needed)
*
**
***
***
***
Quantitative information
*
**
**
*
***
Interpretability of the data
***
***
**
*
*
Theory needed to interpret
spectra
*
*
***
**
**
Ease of instrument operation
*** = Good
** = Average
Instrument cost, running cost
**
**
* = Poor
**
***
*
***
***
*
***
Feature
**
CHARACTERISTICS OF PRINCIPAL
SPECTROMETRIC METHODS
1H-NMR
13C-NMR
MS
IR
Scale
0-15 ppm
1-220 ppm
50-4000
amu
400-4000
cm-1
Sample
1 mg
5-10 mg
< 1 mg
< 1 mg
Molecular
formula
Partial
Partial
Yes
No
Functional group ~ yes
~ yes
Limited
Yes
Substructure
yes
yes
yes
Very
limited
C-Connection
yes
yes
No
Very
limited
Stereochem. &
regiostereochemistry
yes
yes
No
Very
limited
 NUCLEAR-
Study of nuclear spins
 MAGNETIC-
Under the influence of applied
magnetic field
 RESONANCE-
Record the resulting resonance in
nuclear spin through the absorption
of RF
NUCLEAR SPIN
The nuclei of some atoms have a property called “SPIN”.
These nuclei behave as if
they were spinning.
….. we don’t know if they actually do spin!
This is like the spin property
of an electron, which can have
two spins: +1/2 and -1/2 .
Each spin-active nucleus has a number of spins defined by
its spin quantum number, I.
The spin quantum numbers of some common nuclei follow …..
Spin Quantum Numbers of Some Common Nuclei
The most abundant isotopes of C and O do not have spin.
Element
Nuclear Spin
Quantum No
1H
2H
12C
13C
14N
16O
17O
19F
1/2
1
0
1/2
1
0
5/2
1/2
2
3
0
2
3
0
6
2
(I)
No. of Spin
States
Elements with either odd mass or odd atomic number
have the property of nuclear “spin”.
The number of spin states is 2I + 1,
where I is the spin quantum number.
THE PROTON
Although interest is increasing in other nuclei,
particulary C-13, the hydrogen nucleus (proton)
is studied most frequently, and we will devote
our attention to it first.
NUCLEAR SPIN STATES - HYDROGEN NUCLEUS
The spin of the positively
charged nucleus generates
m
a magnetic moment vector, m.
+
+
m
+ 1/2
- 1/2
TWO SPIN STATES
The two states
are equivalent
in energy in the
absence of a
magnetic or an
electric field.
Precession of Spinning Top
A rapidly spinning top will precess in a direction determined by
the torque exerted by its weight. The precession angular velocity
is inversely proportional to the spin angular velocity, so that the
precession is faster and more pronounced as the top slows
down.
The direction of the precession torque can be visualized with the
help of the right-hand rule.
Spin a top on a flat surface, and you will see it's top end slowly
revolve about the vertical direction, a process called precession.
As the spin of the top slows, you will see this precession get
faster and faster. It then begins to bob up and down as it
precesses, and finally falls over. Showing that the precession
speed gets faster as the spin speed gets slower is a classic
problem in mechanics.
Gyromagnetic ratio
In physics, the gyromagnetic ratio or magnetogyric
ratio of a particle or system is the ratio of its magnetic
dipole moment to its angular momentum, and it is
often denoted by the symbol γ, gamma. Its SI units
are radian per second per tesla (rad s−1·T -1) or,
equivalently, coulomb per kilogram (C·kg−1).
Gyromagnetic ratio for a classical rotating body
Consider a charged body rotating about an axis of
symmetry. According to the laws of classical physics, it
has both a magnetic dipole moment and an angular
momentum due to its rotation. It can be shown that as
long as its charge and mass are distributed identically
(e.g., both distributed uniformly), its gyromagnetic
ratio is
γ q  2m
\where q is its charge and m is its mass.
Gyromagnetic ratio and Larmor precession
Any free system with a constant gyromagnetic ratio,
such as a rigid system of charges, a nucleus, or an
electron, when placed in an external magnetic field B
(measured in teslas) that is not aligned with its
magnetic moment, will precess at a frequency n
(measured in hertz), that is proportional to the
external field:
n =γ
THE “RESONANCE” PHENOMENON
absorption of energy by the
spinning nucleus
Nuclear Spin Energy Levels
N
-1/2
unaligned
In a strong magnetic
field (Bo) the two
spin states differ in
energy.
+1/2
Bo
S
aligned
Absorption of Energy
quantized
Opposed
-1/2
-1/2
DE
DE = hn
Radiofrequency
+1/2
Applied
Field
Bo
Aligned
+1/2
THE ENERGY SEPARATION DEPENDS ON Bo
- 1/2
DE
= kBo = hn
degenerate
at Bo = 0
+ 1/2
Bo
increasing magnetic field strength
The Larmor Equation!!!
DE = kBo = hn
can be transformed into
gyromagnetic
frequency of
the incoming
radiation that
will cause a
transition
nn 
gBg0


ratio g
Bo
strength of the
magnetic field
g is a constant which is different for
each atomic nucleus (H, C, N, etc)
A SECOND EFFECT OF A STRONG MAGNETIC FIELD
WHEN A SPIN-ACTIVE HYDROGEN ATOM IS
PLACED IN A STRONG MAGNETIC FIELD
….. IT BEGINS TO PRECESS
OPERATION OF AN NMR SPECTROMETER DEPENDS
ON THIS RESULT
N
w
Nuclei precess at
frequency w when
placed in a strong
magnetic field.
RADIOFREQUENCY
40 - 600 MHz
hn
If n = w then
energy will be
absorbed and
the spin will
invert.
NUCLEAR
MAGNETIC
RESONANCE
NMR
S
Effect of Static Magnetic Bo
Field on Magnetic Moment
Resonance Frequencies of Selected Nuclei
Isotope Abundance Bo (Tesla)
Frequency
(MHz)
g10-6(radians/Tesla/sec)
1H
99.98%
1.00
1.41
2.35
7.05
42.6
60.0
100.0
300.0
2H
0.0156%
1.00
7.05
6.5
45.8
41.1
13C
1.108%
1.00
2.35
7.05
10.7
25.0
75.0
67.28
100.0%
1.00
40.0
19F
267.53
251.7
4:1
POPULATION AND SIGNAL STRENGTH
The strength of the NMR signal depends on the
Population Difference of the two spin states
Radiation
induces both
upward and
downward
transitions.
resonance
induced
emission
For a net positive signal
there must be an excess
of spins in the lower state.
Saturation = equal populations = no signal
excess
population
Fortunately, different types of protons precess at
different rates in the same magnetic field.
Bo = 1.41 Tesla
N
EXAMPLE:
59.999995 MHz
59.999700 MHz
O
CH2 C CH3
hn
60 MHz
59.999820 MHz
S
Differences are very small,
in the parts per million range.
To cause absorption
of the incoming 60 MHz
the magnetic field strength,
Bo , must be increased to
a different value for each
type of proton.
NMR Spectrum of Phenylacetone
O
CH2 C CH3
NOTICE THAT EACH DIFFERENT TYPE OF PROTON COMES
AT A DIFFERENT PLACE - YOU CAN TELL HOW MANY
DIFFERENT TYPES OF HYDROGEN THERE ARE
DIAMAGNETIC ANISOTROPY
SHIELDING BY VALENCE ELECTRONS
Diamagnetic Anisotropy
The applied field
induces circulation
of the valence
electrons - this
generates a
magnetic field
that opposes the
applied field.
valence electrons
shield the nucleus
from the full effect
of the applied field
magnetic field
lines
Bo applied
B induced
(opposes Bo)
fields subtract at nucleus
PROTONS DIFFER IN THEIR SHIELDING
All different types of protons in a molecule
have a different amounts of shielding.
They all respond differently to the applied magnetic
field and appear at different places in the spectrum.
This is why an NMR spectrum contains useful information
(different types of protons appear in predictable places).
DOWNFIELD
Less shielded protons
appear here.
SPECTRUM
UPFIELD
Highly shielded
protons appear here.
It takes a higher field
to cause resonance.
CHEMICAL SHIFT
PEAKS ARE MEASURED RELATIVE TO TMS
Rather than measure the exact resonance position of a
peak, we measure how far downfield it is shifted from TMS.
reference compound
tetramethylsilane
“TMS”
CH3
CH3 Si CH3
CH3
Highly shielded
protons appear
way upfield.
TMS
shift in Hz
downfield
n
0
Chemists originally
thought no other
compound would
come at a higher
field than TMS.
REMEMBER FROM OUR EARLIER DISCUSSION
field
strength
frequency
hν =
γ B
o
2π
constants
ν = ( K) Bo
Stronger magnetic fields (Bo) cause
the instrument to operate at higher
frequencies (ν).
NMR Field
Strength
1.41 T
2.35 T
7.05 T
1H
Operating
Frequency
60 Mhz
100 MHz
300 MHz
HIGHER FREQUENCIES GIVE LARGER SHIFTS
The shift observed for a given proton
in Hz also depends on the frequency
of the instrument used.
Higher frequencies
= larger shifts in Hz.
TMS
shift in Hz
downfield
n
0
THE 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
chemical
=
shift
δ
shift in Hz
=
spectrometer frequency in MHz
= ppm
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).
HERZ EQUIVALENCE OF 1 PPM
What does a ppm represent?
1H
Operating
Frequency
60 Mhz
100 MHz
300 MHz
7
6
1 part per million
of n MHz is n Hz
Hz Equivalent
of 1 ppm
n MHz (
60 Hz
100 Hz
300 Hz
5
4
3
2
1
1
= n Hz
)
6
10
0
ppm
Each ppm unit represents either a 1 ppm change in
Bo (magnetic field strength, Tesla) or a 1 ppm change
in the precessional frequency (MHz).
NMR Correlation Chart
-OH -NH
DOWNFIELD
DESHIELDED
UPFIELD
SHIELDED
CHCl3 , H
TMS
12
11
10
9
8
7
6
H
RCOOH
RCHO
C=C
5
4
CH2F
CH2Cl
CH2Br
CH2I
CH2O
CH2NO2
3
2
1
0
d (ppm)
CH2Ar
C-CH-C
CH2NR2
C
CH2S
C-CH2-C
C C-H
C=C-CH2 C-CH3
CH2-CO
Ranges can be defined for different general types of protons.
This chart is general, the next slide is more definite.
APPROXIMATE CHEMICAL SHIFT RANGES (ppm) FOR SELECTED TYPES OF PROTONS
R-CH3
R-CH2-R
R3CH
0.7 - 1.3
1.2 - 1.4
1.4 - 1.7
R-C=C-C-H
O
1.6 - 2.6
R-C-C-H
O
2.1 - 2.4
RO-C-C-H
O
2.1 - 2.5
HO-C-C-H
2.1 - 2.5
N C-C-H
2.1 - 3.0
R-C C-C-H
2.1 - 3.0
C-H
R-C C-H
2.3 - 2.7
1.7 - 2.7
R-N-C-H
2.2 - 2.9
R-S-C-H
2.0 - 3.0
I-C-H
2.0 - 4.0
Br-C-H
2.7 - 4.1
Cl-C-H
3.1 - 4.1
RO-C-H
3.2 - 3.8
HO-C-H
O
3.2 - 3.8
R-C-O-C-H
3.5 - 4.8
O2N-C-H
4.1 - 4.3
F-C-H
4.2 - 4.8
R-C=C-H
4.5 - 6.5
H
6.5 - 8.0
O
R-C-N-H
5.0 - 9.0
O
R-C-H
9.0 - 10.0
O
R-C-O-H
11.0 - 12.0
R-N-H 0.5 - 4.0 Ar-N-H 3.0 - 5.0 R-S-H
R-O-H 0.5 - 5.0 Ar-O-H 4.0 - 7.0 1.0 - 4.0
YOU DO NOT NEED TO MEMORIZE THE
PREVIOUS CHART
IT IS USUALLY SUFFICIENT TO KNOW WHAT TYPES
OF HYDROGENS COME IN SELECTED AREAS OF
THE NMR CHART
C-H where C is
CH on C
attached
to
an
aliphatic
acid
aldehyde benzene alkene
next to
C-H
COOH
CHO
CH
=C-H electronega- pi bonds
tive atom
X=C-C-H
X-C-H
12
10
9
7
6
4
3
2
0
MOST SPECTRA CAN BE INTERPRETED WITH
A KNOWLEDGE OF WHAT IS SHOWN HERE
DESHIELDING AND ANISOTROPY
Three major factors account for the resonance
positions (on the ppm scale) of most protons.
1. Deshielding by electronegative elements.
2. Anisotropic fields usually due to pi-bonded
electrons in the molecule.
3. Deshielding due to hydrogen bonding.
We will discuss these factors in the sections that
follow.
DESHIELDING BY
ELECTRONEGATIVE ELEMENTS
DESHIELDING BY AN ELECTRONEGATIVE ELEMENT
d-
Cl
d+
C
d-
electronegative
element
H
d+
Chlorine “deshields” the proton,
that is, it takes valence electron
density away from carbon, which
in turn takes more density from
hydrogen deshielding the proton.
NMR CHART
“deshielded“
protons appear
at low field
highly shielded
protons appear
at high field
deshielding moves proton
resonance to lower field
Electronegativity Dependence
of Chemical Shift
Dependence of the Chemical Shift of CH3X on the Element X
Compound CH3X
Element X
Electronegativity of X
Chemical shift
d
most
deshielded
CH3F
CH3OH
CH3Cl
CH3Br
CH3I
CH4
(CH3)4Si
F
O
Cl
Br
I
H
Si
4.0
3.5
3.1
2.8
2.5
2.1
1.8
4.26
3.40
3.05
2.68
2.16
0.23
0
TMS
deshielding increases with the
electronegativity of atom X
Substitution Effects on
Chemical Shift
most
deshielded
most
deshielded
CHCl3 CH2Cl2 CH3Cl
7.27 5.30
3.05 ppm
-CH2-Br
3.30
-CH2-CH2Br
1.69
The effect
increases with
greater numbers
of electronegative
atoms.
-CH2-CH2CH2Br
1.25
ppm
The effect decreases
with incresing distance.
ANISOTROPIC FIELDS
DUE TO THE PRESENCE OF PI BONDS
The presence of a nearby pi bond or pi system
greatly affects the chemical shift.
Benzene rings have the greatest effect.
Ring Current in Benzene
Circulating  electrons
H
Bo
H
Deshielded
fields add together
Secondary magnetic field
generated by circulating 
electrons deshields aromatic
protons
ANISOTROPIC FIELD IN AN ALKENE
protons are
deshielded
Deshielded
fields add
H
shifted
downfield
C=C
H
Bo
H
H
secondary
magnetic
(anisotropic)
field lines
ANISOTROPIC FIELD FOR AN ALKYNE
H
C
C
H
Bo
Shielded
fields subtract
hydrogens
are shielded
secondary
magnetic
(anisotropic)
field
HYDROGEN BONDING
HYDROGEN BONDING DESHIELDS PROTONS
R
O
H
H
O
H
O R
The chemical shift depends
on how much hydrogen bonding
is taking place.
Alcohols vary in chemical shift
from 0.5 ppm (free OH) to about
5.0 ppm (lots of H bonding).
R
Hydrogen bonding lengthens the
O-H bond and reduces the valence
electron density around the proton
- it is deshielded and shifted
downfield in the NMR spectrum.
SOME MORE EXTREME EXAMPLES
O
H
O
C R
R C
O
H
O
Carboxylic acids have strong
hydrogen bonding - they
form dimers.
With carboxylic acids the O-H
absorptions are found between
10 and 12 ppm very far downfield.
H3C O
O
H
O
In methyl salicylate, which has strong
internal hydrogen bonding, the NMR
absortion for O-H is at about 14 ppm,
way, way downfield.
Notice that a 6-membered ring is formed.
INTEGRATION
NMR Spectrum of Phenylacetone
O
CH2 C CH3
RECALL
from last
time
Each different type of proton comes at a different place .
You can tell how many different types of hydrogen
there are in the molecule.
INTEGRATION OF A PEAK
Not only does each different type of hydrogen give a
distinct peak in the NMR spectrum, but we can also tell
the relative numbers of each type of hydrogen by a
process called integration.
Integration = determination of the area
under a peak
The area under a peak is proportional
to the number of hydrogens that
generate the peak.
Benzyl Acetate
The integral line rises an amount proportional to the number of H in each peak
METHOD 1
integral line
integral
line
55 : 22 : 33
=
5:2:3
simplest ratio
of the heights
Benzyl Acetate (FT-NMR)
Actually :
5
58.117 / 11.3
= 5.14
2
21.215 / 11.3
= 1.90
3
33.929 / 11.3
= 3.00
O
CH2 O C CH3
METHOD 2
digital
integration
assume CH3
33.929 / 3 = 11.3
Integrals are
good to about
10% accuracy.
Modern instruments report the integral as a number.
CLASSICAL INSTRUMENTATION
typical before 1960
field is scanned
A Simplified 60 MHz
NMR Spectrometer
RF (60 MHz)
Oscillator
hn
Transmitter
absorption
signal
RF
Detector
Recorder
Receiver
MAGNET
MAGNET
N
S
Probe
~ 1.41 Tesla
(+/-) a few ppm
IN THE CLASSICAL NMR EXPERIMENT THE INSTRUMENT
SCANS FROM “LOW FIELD” TO “HIGH FIELD”
LOW
FIELD
HIGH
FIELD
NMR CHART
DOWNFIELD
UPFIELD
scan
MODERN INSTRUMENTATION
PULSED FOURIER TRANSFORM
TECHNOLOGY
FT-NMR
requires a computer
PULSED EXCITATION
N
n1
BROADBAND
RF PULSE
contains a range
of frequencies
(n1 ..... nn)
n2
O
CH2 C CH3
n3
S
All types of hydrogen are excited
simultaneously with the single RF pulse.
FREE INDUCTION DECAY
( relaxation )
n1
O
n2
CH2 C CH3
n3
n1, n2, n3 have different half lifes
COMPOSITE FID
“time domain“ spectrum
n1 + n2 + n3 + ......
time
FOURIER TRANSFORM
A mathematical technique that resolves a complex
FID signal into the individual frequencies that add
together to make it. ( Details not given here. )
TIME DOMAIN
converted to
FID
COMPLEX
SIGNAL
FREQUENCY DOMAIN
NMR SPECTRUM
FT-NMR
computer
Fourier
Transform
a mixture of frequencies
decaying (with time)
DOMAINS ARE
MATHEMATICAL
TERMS
n1 + n2 + n3 + ......
individual
frequencies
converted to a spectrum
The Composite FID is Transformed into
a classical NMR Spectrum :
O
CH2 C CH3
“frequency domain” spectrum
COMPARISON OF
CW AND FT TECHNIQUES
CONTINUOUS WAVE (CW) METHOD
THE OLDER, CLASSICAL METHOD
The magnetic field is “scanned” from a low field
strength to a higher field strength while a constant
beam of radiofrequency (continuous wave) is
supplied at a fixed frequency (say 100 MHz).
Using this method, it requires several minutes to plot
an NMR spectrum.
SLOW, HIGH NOISE LEVEL
PULSED FOURIER TRANSFORM
(FT) METHOD
FAST
THE NEWER COMPUTER-BASED METHOD
LOW NOISE
Most protons relax (decay) from their excited states
very quickly (within a second).
The excitation pulse, the data collection (FID), and
the computer-driven Fourier Transform (FT) take
only a few seconds.
The pulse and data collection cycles may be repeated
every few seconds.
Many repetitions can be performed in a
very short time, leading to improved signal …..
IMPROVED SIGNAL-TO-NOISE RATIO
By adding the signals from many pulses together, the
signal strength may be increased above the noise level.
noise
signal
enhanced
signal
1st pulse
2nd pulse
nth pulse
add many
pulses
etc.
noise is random
and cancels out