1. IB Chemistry - Option A : Modern Analytical Chemistry
NUCLEAR MAGNETIC RESONANCE

2. Different Types of NMR Electron Spin Resonance (ESR)
1-10 GHz (frequency) used in analyzing free radicals (unpaired electrons)
Magnetic Resonance Imaging (MRI)
MHz (frequency) for diagnostic imaging of soft tissues (water detection)
NMR Spectroscopy (MRS)
MHz (frequency) primarily used for compound ID and characterization

3. NMR in Everyday Life
Magnetic Resonance Imaging

4. NMR Spectroscopy

5. Explaining NMR
UV/Vis spectroscopy
Sample

6. Explaining NMR

7. Principles of NMR
Measures nuclear magnetism or changes in nuclear magnetism in a molecule
NMR spectroscopy measures the absorption of light (radio waves) due to changes in nuclear spin orientation
NMR only occurs when a sample is in a strong magnetic field
Different nuclei absorb at different energies (frequencies)

8. Bigger Magnets are Better
Increasing magnetic field strength
low frequency high frequency

9. Different Isotopes Absorb at Different Frequencies2H
15N
13C
19F 1H
30 MHz MHz MHz MHz MHz
low frequency high frequency

10. Which Elements or Molecules are NMR Active?
Any atom or element with an odd number of neutrons and/or an odd number of protons
Any molecule with NMR active atoms
1H - 1 proton, no neutrons, AW = 1
13C - 6 protons, 7 neutrons, AW =13
15N - 7 protons, 8 neutrons, AW = 15
19F = 9 protons, 10 neutrons, AW = 19

11. 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 …..

12. Spin Quantum Numbers of Some Common Nuclei
The most abundant isotopes of C and O do not have spin.
Element 1H 2H 12C 13C 14N 16O 17O 19F
Nuclear Spin
Quantum No 1/ / /2 1/2
( 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.

13. 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.

14. 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

15. THE “RESONANCE” PHENOMENON
absorption of energy by the
spinning nucleus

16. w N Nuclei precess at frequency w when placed in a strong
magnetic field.
RADIOFREQUENCY
MHz hn
NUCLEAR
MAGNETIC
RESONANCE
If n = w then
energy will be
absorbed and
the spin will
invert.
NMR S

17. Typical 1H NMR Spectrum
Absorbance

18. CLASSICAL INSTRUMENTATION

19. NMR Magnet

20. NMR Magnet Cross-Section
Sample Bore
Cryogens
Magnet Coil
Magnet Legs
Probe

21. IN THE CLASSICAL NMR EXPERIMENT THE INSTRUMENT
SCANS FROM “LOW FIELD” TO “HIGH FIELD”
LOW
FIELD
HIGH
FIELD
NMR CHART
increasing Bo
DOWNFIELD
UPFIELD
scan

22. NMR Spectrum of Phenylacetone
NOTICE THAT EACH DIFFERENT TYPE OF PROTON COMES
AT A DIFFERENT PLACE - YOU CAN TELL HOW MANY
DIFFERENT TYPES OF HYDROGEN THERE ARE

23. The Composite FID is Transformed into a classical NMR Spectrum :

24. INTEGRATION

25. NMR Spectrum of Phenylacetone
Each different type of proton comes at a different place .
You can tell how many different types of hydrogen
there are in the molecule.

26. INTEGRATION OF A PEAK Integration = determination of the area
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.

27. Benzyl Acetate 55 : 22 : 33 = 5 : 2 : 3 METHOD 1 integral line
The integral line rises an amount proportional to the number of H in each peak
METHOD 1
integral line
integral
line
55 : 22 : = : 2 : 3
simplest ratio
of the heights

28. Benzyl Acetate (FT-NMR)
Actually :
/ 11.3
= 5.14
/ 11.3
= 1.90
/ 11.3
= 3.00
METHOD 2
assume CH3
/ 3 = 11.3
digital
integration
Integrals are
good to about
10% accuracy.
Modern instruments report the integral as a number.

29. CHEMICAL SHIFT

30. 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”
Highly shielded
protons appear
way upfield.
TMS
Chemists originally
thought no other
compound would
come at a higher
field than TMS.
shift in Hz
downfield n

31. 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

32. 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 (60 MHz, 100 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).

33. HERZ EQUIVALENCE OF 1 PPM
What does a ppm represent?
1 part per million
of n MHz is n Hz
1H Operating
Frequency
Hz Equivalent
of 1 ppm 1
n MHz = n Hz ( )
60 Mhz Hz
106
100 MHz Hz
300 MHz Hz 7 6 5 4 3 2 1
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).

34. NMR Correlation Chart d (ppm)
-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.
This chart is general, the next slide is more definite.

35. R-CH3 0.7 - 1.3 R-N-C-H 2.2 - 2.9 R-C=C-H R-CH2-R 1.2 - 1.4 4.5 - 6.5
APPROXIMATE CHEMICAL SHIFT RANGES (ppm) FOR SELECTED TYPES OF PROTONS
R-CH
R-N-C-H
R-C=C-H
R-CH2-R
R-S-C-H
R3CH
I-C-H H
R-C=C-C-H
Br-C-H O
Cl-C-H
R-C-C-H O O
RO-C-H
R-C-N-H
RO-C-C-H
HO-C-H O O O
R-C-H
HO-C-C-H
R-C-O-C-H O
N C-C-H
O2N-C-H
R-C-O-H
R-C C-C-H
F-C-H
C-H
R-N-H Ar-N-H R-S-H
R-O-H Ar-O-H
R-C C-H

36. Characteristic Chemical Shifts

37. 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 attached to an
electronega-tive atom
CH on C
next to
pi bonds
acid
COOH
aldehyde
CHO
benzene CH
alkene
=C-H
aliphatic
C-H
X=C-C-H
X-C-H 12 10 9 7 6 4 3 2
MOST SPECTRA CAN BE INTERPRETED WITH
A KNOWLEDGE OF WHAT IS SHOWN HERE

38. Chemical Shifts Key to the utility of NMR in chemistry
Different 1H in different molecules exhibit different absorption frequencies
Arise from the electron cloud effects of nearby atoms or bonds, which act as little magnets to shift absorption n up or down
Mostly affected by electronegativity of neighbouring atoms or groups

39. Spin-Spin Coupling
Many 1H NMR spectra exhibit peak splitting (doublets, triplets, quartets)
This splitting arises from adjacent hydrogens (protons) which cause the absorption frequencies of the observed 1H to jump to different levels
These energy jumps are quantized and the number of levels or splittings = n + 1 where “n” is the number of nearby 1H’s

40. 1H NMR Spectra Exhibit...
Chemical Shifts (peaks at different frequencies or ppm values)
Splitting Patterns (from spin coupling)
Different Peak Intensities (# 1H)

41. Spin-Spin Coupling H | H | H | H | C - Y C - CH C - CH2 C - CH3 X Z XJ
singlet doublet triplet quartet

42. Spin Coupling Intensities1
1 1
1 2 1
3 3 2
1 1
Pascal’s Triangle

43. NMR Peak Intensities Y | Y | Y | C - CH C - CH2 C - CH3 X Z X Z X Z
AUC = 1 AUC = 2 AUC = 3

44. ELECTRONEGATIVE ELEMENTS
DESHIELDING BY
ELECTRONEGATIVE ELEMENTS

45. Substitution Effects on Chemical Shift
most
deshielded
The effect
increases with
greater numbers
of electronegative
atoms.
CHCl3 CH2Cl2 CH3Cl
ppm
most
deshielded
-CH2-Br CH2-CH2Br -CH2-CH2CH2Br
ppm
The effect decreases
with incresing distance.

46. 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.

47. Applications
Determination of exact structure of drugs and drug metabolites - MOST POWERFUL METHOD KNOWN
Detection/quantitation of impurities
Detection of enantiomers (shift reagents)
High throughput drug screening
Analysis/deconvolution of liquid mixtures
Water content measurement

48. NMR vs. IR NMR has narrower peaks relative to IR
NMR yields far more information than IR
NMR allows you to collect data on solids & liquids but NOT gases
NMR is more quantitative than IR or UV
NMR samples are easier to prepare
NMR is much less sensitive than IR or UV
NMR spectrometers are very expensive

49. IR vs. NMR
Absorbance