1. Nuclear Magnetic Resonance Spectroscopy
Introduction

2. Over the past fifty years nuclear magnetic resonance spectroscopy, commonly referred to as NMR, has become the preeminent technique for determining the structure of organic compounds.
Nuclear magnetic resonance (NMR) spectroscopy:
A spectroscopic technique that gives us information about the number and types of nuclei in a molecule.
For example, about the number and types of
Hydrogen nuclei using 1H-NMR spectroscopy.
Carbon nuclei using 13C-NMR spectroscopy.
Phosphorus nuclei using 31P-NMR spectroscopy.

3. Nuclear Magnetic Resonance spectroscopy involves the transition of a nucleus from one spin state to another with the resultant absorption of electromagnetic radiation by spin active nuclei when they are placed in a magnetic field.
The following features lead to the NMR phenomenon:
1. A spinning charge generates a magnetic field, as shown by the animation on the right.
The resulting spin-magnet has a magnetic moment (μ) proportional to the spin.

4. The nuclei of many elemental isotopes have a characteristic spin (I).
Some nuclei have integral spins (e.g. I = 1, 2, ),
some have fractional spins (e.g. I = 1/2, 3/2, 5/2 ....), and
a few have no spin, I = 0 (e.g. 12C, 16O, 32S, ....).
Isotopes of particular interest and use to organic chemists are 1H, 13C, 19F and 31P, all of which have I = 1/2. Since the analysis of this spin state is fairly straightforward, our discussion of NMR will be limited to these and other I = 1/2 nuclei.

6. NUCLEAR SPIN STATES - HYDROGEN NUCLEUS
The spin of the positively
charged nucleus generates
a magnetic moment vector, m. m + +
The two states
are equivalent
in energy in the
absence of a
magnetic or an
electric field. m
+ 1/2
- 1/2
TWO SPIN STATES

7. In the presence of an external magnetic field (B0), two spin states exist, +1/2 and -1/2.
The magnetic moment of the lower energy +1/2 state is alligned with the external field, but that of the higher energy -1/2 spin state is opposed to the external field. Note that the arrow representing the external field points North.

8. Nuclear Spins in Strong External Magnetic Fields
-1/2
In a strong magnetic
field (Bo) the two
spin states differ in
energy.
+1/2 Bo S

10. THE ENERGY SEPARATION DEPENDS ON Bo
- 1/2
= kBo = hn DE
degenerate
at Bo = 0
+ 1/2 Bo
increasing magnetic field strength

11. The Larmor Equation!!! n = Bo 2p
DE = kBo = hn can be transformed into
gyromagnetic
ratio g g
n = 2p
frequency of
the incoming
radiation that
will cause a
transition Bo
strength of the
magnetic field
g is a constant which is different for
each atomic nucleus (H, C, N, etc)

12. More nucleons will be in the lower energy state aligned with the magnetic field.
A nucleon can absorb a quantum of energy in the radio frequency range and align against the magnetic field.
It emits a radio frequency when it drops back to its original position.

13. Absorption of Energy Bo quantized -1/2 -1/2 DE DE = hn +1/2 +1/2
Opposed
-1/2
-1/2 DE
DE = hn
Radiofrequency
+1/2
+1/2
Applied
Field Bo
Aligned

14. 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

16. If rf energy having a frequency matching the Larmor frequency is introduced at a right angle to the external field (e.g. along the x-axis), the precessing nucleus will absorb energy and the magnetic moment will flip to its I = -1/2 state. This excitation is shown in the following diagram.

17. Nuclear Magnetic Resonance
Resonance: In NMR spectroscopy, resonance is due to the absorption of energy by a precessing nucleus and the results in “flip” of its nuclear spin from a lower energy state to a higher energy state.
The precessing spins induce an oscillating magnetic field that is recorded as a signal by the instrument.
Signal: A recording in an NMR spectrum of a nuclear magnetic resonance.

18. Strong magnetic fields are necessary for NMR spectroscopy.
The earth's magnetic field is not constant, but is approximately 10-4 T at ground level. Modern NMR spectrometers use powerful magnets having fields of 1 to 20 T.
Even with these high fields, the energy difference between the two spin states is less than 0.1 cal/mole.

19. Resonance Frequencies of Selected Nuclei
Isotope Abundance Bo (Tesla) Frequency(MHz) g(radians/Tesla)
1H %
2H %
13C %
19F 100.0%
4:1

20. For NMR purposes, this small energy difference (ΔE) is usually given as a frequency in units of MHz (106 Hz), ranging from 20 to 900 Mz, depending on the magnetic field strength and the specific nucleus being studied.
Irradiation of a sample with radio frequency (rf) energy corresponding exactly to the spin state separation of a specific set of nuclei will cause excitation of those nuclei in the +1/2 state to the higher -1/2 spin state.
The nucleus of a hydrogen atom (the proton) has a magnetic moment μ = , and has been studied more than any other nucleus

21. NMR SPECTROMETER - INSTRUMENTATION

22. DIAMAGNETIC ANISOTROPY
SHIELDING BY VALENCE ELECTRONS

23. Anisotropy valence electrons shield the nucleus from the full effect
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

24. 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).
UPFIELD
DOWNFIELD
Highly shielded
protons appear here.
Less shielded protons
appear here.
SPECTRUM
It takes a higher field
to cause resonance.

25. CHEMICAL SHIFT

26. To standardise measurements on different NMR instruments, a standard reference sample is used in each experiment. This is tetramethylsilane (TMS).
This is a symmetrical and inert molecule. All H atoms have the same chemical environment and a single peak is produced from this molecule.

27. The chemical shift of TMS is defined as zero
The difference in energy needed to change the spin state in the sample is compared to TMS and is called the CHEMICAL SHIFT.
The chemical shift of TMS is defined as zero
The symbol d represents chemical shift and is measured in ppm. The chemical shift scale is measured from right to left on the spectrum.
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).

28. Ranges can be defined for different general types of protons.
NMR Correlation Chart
-OH
-NH
DOWNFIELD
UPFIELD
DESHIELDED
SHIELDED
CHCl3 ,
TMS
d (ppm) 12 11 10 9 8 7 6 5 4 3 2 1 H
CH2F
CH2Cl
CH2Br
CH2I
CH2O
CH2NO2
CH2Ar
CH2NR2
CH2S
C C-H
C=C-CH2
CH2-C-
C-CH-C
RCOOH
RCHO
C=C C
C-CH2-C
C-CH3 O
Ranges can be defined for different general types of protons.

29. IT IS USUALLY SUFFICIENT TO KNOW WHAT TYPES
OF HYDROGENS COME IN SELECTED AREAS OF
THE NMR CHART
C-H where C is attached to an
electronegative atom
CH on C
next to
pi bonds
acid
COOH
aldehyde
CHO
benzene CH
alkene
=C-H
aliphatic
C-H 12 10 9 7 6 3 2 4
X-C-H
X=C-C-H
MOST SPECTRA CAN BE INTERPRETED WITH
A KNOWLEDGE OF WHAT IS SHOWN HERE

30. Factors influencing the Chemical Shift
Inductive effect by Electronegative groups
Magnetic Anisotropy
Hydrogen Bonding

31. Cl C H d- d+ DESHIELDING BY AN ELECTRONEGATIVE ELEMENT d- 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. Cl C H d- d+
electronegative
element
NMR CHART
“deshielded“
protons appear
at low field
highly shielded
protons appear
at high field
deshielding moves proton
resonance to lower field

32. Electronegativity Dependence of Chemical Shift
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
Chemical shift d
most
deshielded
TMS
deshielding increases with the
electronegativity of atom X

33. 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.

34. fields add together

35. H H C=C H H ANISOTROPIC FIELD IN AN ALKENE Bo protons are deshielded
shifted
downfield
fields add
C=C H H
secondary
magnetic
(anisotropic)
field lines Bo

36. H C C H ANISOTROPIC FIELD FOR AN ALKYNE Bo secondary magnetic
Shielded Bo
hydrogens
are shielded
fields subtract

37. HYDROGEN BONDING DESHIELDS PROTONS
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).
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.

38. NMR Spectrum of Acetaldehyde
offset = 2.0 ppm

39. SPIN-SPIN SPLITTING
Often a group of hydrogens will appear as a multiplet
rather than as a single peak.
Multiplets are named as follows:
Singlet Quintet
Doublet Septet
Triplet Octet
Quartet Nonet
This happens because of interaction with neighboring
hydrogens and is called
SPIN-SPIN SPLITTING.

40. 1,1,2-Trichloroethane
The two kinds of hydrogens do not appear as single peaks,
rather there is a “triplet” and a “doublet”.
integral = 2
integral = 1
The subpeaks are due to
spin-spin splitting and are
predicted by the n+1 rule.
triplet
doublet

41. singlet doublet triplet quartet quintet sextet septet MULTIPLETS
this hydrogen’s peak
is split by its two neighbors
these hydrogens are
split by their single
neighbor
MULTIPLETS
singlet
doublet
triplet
quartet
quintet
sextet
septet
two neighbors
n+1 = 3
triplet
one neighbor
n+1 = 2
doublet

42. SOME COMMON SPLITTING PATTERNS
( x = y )
( x = y )

43. INTENSITIES OF
MULTIPLET PEAKS
PASCAL’S TRIANGLE

44. PASCAL’S TRIANGLE
Intensities of
multiplet peaks 1
singlet
1 1
The interior
entries are
the sums of
the two
numbers
immediately
above.
doublet
triplet
quartet
quintet
sextet
septet
octet

45. THE CHEMICAL SHIFT OF PROTON HA IS
AFFECTED BY THE SPIN OF ITS NEIGHBORS
aligned with Bo
opposed to Bo
+1/2
-1/2
50 % of
molecules
50 % of
molecules H H H H A A C C C C Bo
downfield
upfield
neighbor aligned
neighbor opposed
At any given time about half of the molecules in solution will
have spin +1/2 and the other half will have spin -1/2.

46. SPIN ARRANGEMENTS H H H H C C C C one neighbor one neighbor n+1 = 2
doublet
one neighbor
n+1 = 2
doublet H H H H C C C C
yellow spins
blue spins
The resonance positions (splitting) of a given hydrogen is
affected by the possible spins of its neighbor.

47. SPIN ARRANGEMENTS two neighbors n+1 = 3 triplet one neighbor n+1 = 2
doublet
methine spins
methylene spins

48. SPIN ARRANGEMENTS C H C H three neighbors n+1 = 4 quartet
two neighbors
n+1 = 3
triplet C H C H
methylene spins
methyl spins

49. THE COUPLING CONSTANT J J J J J
The coupling constant is the distance J (measured in Hz)
between the peaks in a multiplet.
J is a measure of the amount of interaction between the
two sets of hydrogens creating the multiplet.

50. APPLICATIONS
GEOPHYSICAL: Used to determine the water content in the geophysical samples.
Engineering Applications: It is used to study the Process engineering aspects like the kinetic and equilibrium studies of Formaldehyde – water – methanol systems.
Non- destructive testing of DNA, proteins etc.
This is very much useful in Data acquisition in Petroleum Industry. Here NMR probes are developed and Used.

51. MRI Magnetic resonance imaging, noninvasive
“Nuclear” is omitted because of public’s fear that it would be radioactive.
Only protons in one plane can be in resonance at one time.
Computer puts together “slices” to get 3D.
Tumors readily detected.