1. Chapter 13 NMR Spectroscopy
NMR - Nuclear Magnetic Resonance
NMR is a form of spectroscopy that uses an instrument with a powerful magnet to analyze organic compounds.
Invented by physicists (1950’s), then used by chemists (1960’s).
MRI – Magnetic Resonance Imaging (1980’s) A special form of NMR used in medicine.

2. What is NMR?
NMR – a tool to determine the structure of an organic compound.
NMR Spectrometer
magnet
This instrument gives you information about an organic compound’s structure.
1H NMR Spectrum
computer

3. What is NMR? NMR Instruments
Small, 60 mHz instrument for undergraduate student use.
computer
magnet
student

4. What is NMR? NMR Instruments
Research grade instrument, 300 mHz magnet, that we use at Western.
magnet

5. What is NMR? NMR Instruments
Research grade instrument, 300 mHz magnet, that we use at Western.
computer

6. What is NMR? NMR Instruments
researcher
State-of-the-art instrument, 950 mHz magnet.
Rather large and expensive!
magnet

7. generates magnetic field
Why is it called NMR?
Nuclear Magnetic Resonance
Nuclear – because it looks at the nucleus of an atom, most commonly a hydrogen atom.
A hydrogen atom nucleus consists of one proton with a +1 charge and “spin” of ½. It acts like a tiny bar magnet.
spinning proton
proton
bar magnet
generates magnetic field

8. NMR – Effect of Magnetic Field
No External Magnetic Field Nuclear spins are pointed in random directions
Sample in Magnetic Field Spins align with or against the external magnetic field

9. NMR – Effect of Magnetic Field
hydrogen nuclei
aligned against field (higher energy)
aligned with field (lower energy)
Sample placed in an external magnetic field H0
No external magnetic field applied to sample
Random orientation of nuclear spins
Spins align with or against field (most align with field)

10. NMR: Absorption of Energy
radio waves
nucleus absorbs energy
Scan with RF field – nucleus absorbs energy, giving a signal in the NMR spectrum
Initial State – nucleus at low energy level

11. NMR: Information Obtained from a Spectrum
An NMR Spectrum will generally provide three types of information:
Chemical Shift – indicates the electronic environment of the nucleus (shielded or deshielded)
Integration – gives the relative number of nuclei producing a given signal
Spin-Spin Coupling – describes the connectivity

12. signal from protons in H20
1H NMR Spectrum – H2O
signal from protons in H20
scanning
A sample of water is placed in an NMR instrument, and a proton spectrum is recorded (scanned from left to right).
An NMR signal appears. This proves that water contains hydrogen atoms!

13. NMR – Effect of Magnetic Field
aligned with field (lower energy)
Magnetic Fields:
1. from magnet
2. from protons
aligned against field (higher energy)
Sample placed in an external magnetic field
Spins align with or against field (most align with field)
H0 – strong external magnetic field from NMR instrument
No external magnetic field applied to sample
Random orientation of nuclear spins

14. When does nucleus absorb energy?
Not all
protons are
the same!
Magnetic Fields:
1. from spinning proton
2. from magnet
3. from electrons 3.
2, External Field (Ho) from magnet
Absorption depends on shielding by electron cloud around the nucleus. More electron density = more shielding = signal shifted to the right.

15. NMR: Scanning for All Nuclei
13C area is wider
1H area is small
To see both proton and C-13 nuclei, a very wide region would have to be scanned.
An instrument can only examine one area at a time.

16. NMR: Simple 1H NMR Spectrum Showing Chemical Shift
location of the signal on the spectrum.
Right Side: high electron density
Left Side: low electron density
Two types of protons (a CH2 and a CH3) give two separate signals at two different chemical shifts.

17. NMR: Chemical Shift Practice
-OCH3
Group EN
Cl3C-H
-CCH3
3 electronegative atoms
-O-CH3
-Si-CH3
-C-CH3
Cl3C-H
3.5
1.8
2.5
3.0
Left Side: low electron density (high EN)
-SiCH3
Assign the four groups shown to the four NMR singals, based on each element’s electronegativity.

18. NMR: Chemical Shift Reference
Chemical shift zero is set to TMS (tetramethylsilane).
TMS =
(silicon – low electroneg.)
Chemical shift measured in ppm. For 1H: roughly 0 to 10 ppm.

19. NMR: Chemical Shift Regions
-CH2-CH3
Alkane region (high electron density) is from about .8 – 2.5 ppm.

20. NMR: Chemical Shift Regions
-O-CH3
Heteroatom region (low electron density) is from about 2.5 to 5.

21. NMR: Chemical Shift Regions
C=C H
Double bond region is on the left, from about 5 – 10 ppm.

22. NMR: Chemical Equivalence and Number of Signals
How many signals will the following compounds show in their 1H NMR Spectrum? (Hint: check for symmetry)

23. NMR: Chemical Equivalence and Number of Signals
How many signals should appear in the proton NMR spectrum for these compounds? 2 4 1 3
In theory:
Signals actually resolved:

24. NMR: Overlapping Proton Signals
octane
The -CH2- groups all appear in the same spot
(not resolved)
Protons b, c, and d are in roughly the same environment, and their chemical shifts are also about the same.

25. Review: How Many NMR Signals?
How many signals will the following compounds show in their 1H NMR Spectrum? (Hint: check for symmetry)
These H’s are different
Fast chair
flips at RT
Fast rotation about
C-C single bond
No rotation about
double bonds

26. NMR: Chloroethane
Fast rotation around single bonds gives an “averaged” spectrum for the three methyl hydrogens.
An NMR spectrometer is like a camera with a slow shutter speed.

27. NMR: Chair Cyclohexane
Rapid chair flipping makes all H’s equivalent.
Cylcohexane gives one peak in the 1H NMR spectrum.
An NMR spectrometer is like a camera with a slow shutter speed.

28. NMR: A Second Proton Spectrum
bigger (9 H’s)
smaller (2 H’s)
Note: the signal for the nine methyl H’s (red) is larger than the signal for the CH2 group (blue)

29. NMR: Information Obtained from a Spectrum
An NMR Spectrum will generally provide three types of information:
Chemical Shift – indicates the electronic environment of the nucleus (shielded or deshielded)
Integration – gives the relative number of nuclei that produces a given signal. The integral (area under the curve) is drawn on the spectrum by the instrument.
Spin-Spin Coupling – describes the connectivity

30. NMR: Integration Indicates Relative Number of Nuclei
Integral has relative height 9
Relative height 2
The height of the integration line (“integral”) gives you the relative number of nuclei producing each signal.

31. NMR: Information Obtained from a Spectrum
An NMR Spectrum will generally provide three types of information:
Chemical Shift – indicates the electronic environment of the nucleus (shielded or deshielded)
Integration – gives the relative number of nuclei producing a given signal
Spin-Spin Coupling: - describes the carbon connectivity follows the “n+1”rule”

32. NMR: Splitting into a Doublet
Note that the red signal at 1.6 ppm for the methyl group is split into two peaks.
Remember that this is one signal, composed of two separate peaks.

33. NMR: Signal Splitting, n+1 Rule
A signal is often split into multiple peaks due to interactions with protons on carbons next door. Called spin-spin splitting
The splitting is into one more peak than the number of H’s on adjacent carbons (“n+1 rule”)
Splitting of a signal can give doublets (two peaks), triplets (three peaks), quartets (4 peaks), ect.
The relative intensities given by Pascal’s Triangle: doublet 1 : 1 triplet : 2 : 1 quartet : 3 : 3 : 1 pentet: : 4 : 6 : 4 : 1

34. NMR: Signal Splitting, n+1 Rule
n+1 Rule: A signal in the proton NMR spectrum will be split into n+1 peaks, where n is the number of protons on adjacent carbons.
Example: CH3-CH2-Br
For the Methyl Group: There are two protons ‘next door’ (n=2), so the methyl signal will be split into three peaks (2+1), which is called a triplet. Chemical shift will be about 1.5 (alkane region), integration = 3.
For the -CH2- Group: Three protons next door means the CH2 signal will be split into 4 (3+1) peaks, called a quartet. Chemical shift = 3.3 (heteroatom region), integration = 2.

35. 1H NMR Spectrum for Bromoethane
Four peaks, a quartet (1:3:3:1)
Three peaks, a triplet (1:2:1)
integration:
2 H H
Note the expansions printed above the spectrum

36. NMR: Signal Splitting, n+1 Rule
Peak Heights -
Pascal’s Triangle
singlet doublet : 1 triplet : 2 : 1 quartet : 3 : 3 : 1 pentet 1 : 4 : 6 : 4 : 1

37. NMR: Signal Splitting, n+1 Rule
many lines = “mulitplet”

38. NMR: Signal Splitting, n+1 RuleH
seven peaks
How many neighbors?
n + 1 = 7
n = 6

39. NMR: Origin of Spin-Spin Splitting

40. NMR: Origin of Spin-Spin Splitting

41. NMR: Doublets and Triplets
Doublet: the one proton next door can be either up or down (α or β)
Triplet: for the two protons next door, there are four combinations possible: α α α β β β β α

42. NMR: Signal Splitting, n+1 Rule

43. NMR: Using the n+1 Rule
Using the n+1 rule, predict the 1H NMR spectrum of 2-iodopropane. Give splitting pattern, integration, and approximate chemical shift.
six neighbors
one neighbor
Note that the methyl groups are equivalent, so they will give one signal in the NMR spectrum.

44. NMR: Spectrum of 2-iodopropane
Seven line pattern
doublet

45. NMR: Rules for Spin-Spin Splitting
The signal of a proton with n equivalent neighboring H’s is split into n + 1 peaks
Protons that are farther than two carbon atoms apart do not split each other
Equivalent protons do not split each other

46. Common 1H NMR Patterns 1. triplet (3H) + quartet (2H) -CH2CH3
2. doublet (1H) + doublet (1H) CH-CH-
3. large singlet (9H) t-butyl group
4. singlet 3.5 ppm (3H) OCH3 group
5. large double (6H) + muliplet (1H) isopropyl
6. singlet 2.1 ppm (3H) methyl ketone

47. Common 1H NMR Patterns
7. multiplet ~7.2 ppm (5H) aromatic ring, monosubstituted
8. multiplet ~7.2 ppm (4H) aromatic ring, disubstituted
9. broad singlet, variable OH or –NH chemical shift (H on heteratom)

48. Solving NMR Problems
1. Check the molecular formula and degree of unsaturation. How many rings/double bonds?
2. Make sure that the integration adds up to the total number of H’s in the formula.
3. Are there signals in the double bond region?
4. Check each signal and write down a possible sub-structure for each one.
5. Try to put the sub-structures together to find the structure of the compound.

49. Proton NMR Spectrum: C9H12
aromatic,
disubst.
Degree of Unsat = 4

50. 1H NMR Spectrum: C4H7O2Br s t t 3H 2H 2H 5.0 4.0 3.0 2.0 1.0 0
Degree of Unsat = 1 s 3H t 2H t 2H

51. Electronegative Substituents: Shift Left
Propane:
heteroatom region
small effect
~no effect
d 0.9
d 1.3
d 0.9
d 4.3
d 2.0
d 1.0
H3C—CH2—CH3
O2N—CH2—CH2—CH3
Effect is cumulative
CH3Cl (one Cl)
CH2Cl (two Cl’s)
CHCl (three Cl’s)

52. Hydrogens on Heteroatoms
Chemical shifts for protons on heteroatoms are variable, and signals are often broad (not generally useful).
Chemical shift (ppm)
Type of proton
1-3 H NR
0.5-5 H OR
6-8 H
OAr C O HO
far left
10-13
may be useful

53. 13C NMR Spectroscopy
Carbon-13: only carbon isotope with a nuclear spin natural abundance of 13C is only 1.1% (99% of carbon atoms are 12C, with no NMR signal)
All signals are obtained simultaneously using a broad pulse of energy. The resulting “mass signal” changed into an NMR spectrum mathematically using the operation of Fourier transform (FT-NMR)
Frequent repeated pulses give many data sets that are averaged to eliminate noise

54. 13C NMR Spectroscopy No signal overlap!
13C signals go from 0 to 240 ppm C signals: always sharp singlets.
(wider range than in 1H NMR) (1H signals: broad multiplets)
These two facts mean that in carbon-13 NMR, each separate signal is usually visible, and you can accurately count the number of different carbons in the molecule.
Chemical shift affected by electronegativity of nearby atoms: alkane-like range: – 40 ppm (R-CH2-R) heteroatom range: 50 – 100 ppm (O-CH2-R) double bond range: 100 – 220 ppm (sp2 carbons)
No signal overlap!

55. NMR: Scanning for All Nuclei
13C area is much wider
1H area is small
To see both proton and C-13 nuclei, a very wide region would have to be scanned.
An instrument can only examine one area at a time.

56. Why does 13C NMR give singlets?
13C is only 1.1% natural abundant, so most carbons are 12C, and give no NMR signal.
No splitting seen with carbon, because carbons next to the 13C are likely to be carbon-12:
Sample of 1-Propanol:
12CH3-12CH2-12CH2-OH CH3-12CH2-12CH2-OH
12CH3-13CH2-12CH2-OH CH3-12CH2-12CH2-OH
12CH3-12CH2-12CH2-OH CH3-12CH2-12CH2-OH
12CH3-13CH2-13CH2-OH CH3-12CH2-12CH2-OH

57. NMR: Number of Signals for 13C NMR
How many signals should appear in the carbon-13 NMR spectrum for these compounds?
In theory:
Signals actually resolved:

58. 13C NMR Example
Note the wide spectral width and the sharp singlets in the spectrum below.
Also note that there is no integration with 13C NMR.

59. 13C NMR: smaller signal to noise ratio

60. 13C NMR: smaller signal to noise ratio
more
scans
(noise smaller)

61. 13C NMR Spectrum: C5H11Cl
D. of Unsat = 0
five 13C signals

62. 13C NMR Spectrum: C4H7O2Br D. of Unsat = 1 double bond region CDCl3
double bond region