1. Chapter 13 Structure Determination: Nuclear Magnetic Resonance Spectroscopy

2. Learning Objectives (13.1) Nuclear magnetic resonance spectroscopy
(13.2)
The nature of NMR absorptions
(13.3)
The chemical shift
(13.4)
Chemical shifts in 1H NMR spectroscopy

3. Learning Objectives (13.5)
Integration of 1H NMR absorptions: Proton counting
(13.6)
Spin–spin splitting in 1H NMR spectra
(13.7)
1H NMR spectroscopy and proton equivalence
(13.8)
More complex spin–spin splitting patterns

4. Learning Objectives (13.9) Uses of 1H NMR spectroscopy (13.10)
13C NMR spectroscopy: Signal averaging and FT–NMR
(13.11)
Characteristics of 13C NMR spectroscopy
(13.12)
DEPT 13C NMR spectroscopy

5. Learning Objectives
(13.13)
Uses of 13C NMR spectroscopy

6. Nuclear Magnetic Resonance Spectroscopy
Nuclei are positively charged and interact with an external magnetic field denoted by B0
Magnetic rotation of nuclei is random in the absence of a magnetic field
In the presence of a strong magnet, nuclei adopt specific orientations
Nuclear magnetic resonance spectroscopy

7. Nuclear Magnetic Resonance Spectroscopy
When exposed to a certain frequency of electromagnetic radiation, oriented nuclei absorb energy and causes a spinflip from a state of lower energy to higher energy
Nuclear magnetic resonance - Nuclei are in resonance with applied radiation
Frequency that causes resonance depends on:
Strength of external magnetic field
Identity of the nucleus
Electronic environment of the nucleus
Nuclear magnetic resonance spectroscopy

8. Nuclear Magnetic Resonance Spectroscopy
Larmor equation
Relation between
Resonance frequency of a nucleus
Magnetic field and the magnetogyric ratio of the nucleus
Nuclear magnetic resonance spectroscopy

9. Worked Example
Calculate the amount of energy required to spin-flip a proton in a spectrometer operating at 300 MHz
Analyze if the increase of spectrometer frequency from 200 MHz to 300 MHz increases or decreases the amount of energy necessary for resonance
Nuclear magnetic resonance spectroscopy

10. Worked Example Solution:
Increasing the spectrometer frequency from 200 MHz to 300 MHz increases the amount of energy needed for resonance
Nuclear magnetic resonance spectroscopy

11. The Nature of NMR Absorptions
Absorption frequencies differ across 1H and 13C molecules
Shielding: Opposing magnetic field produced by electrons surrounding nuclei to counteract the effects of an external magnetic field
Effect on the nucleus is lesser than the applied magnetic field
Beffective = Bapplied – Blocal
Individual variances in the electronic environment of nuclei leads to different shielding intensities
The nature of NMR absorptions

12. Figure 13.3 - NMR Spectrum of 1H and 13C
The nature of NMR absorptions

13. Working of an NMR Spectrometer
Organic sample dissolved in a suitable solvent is placed in a thin glass tube between the poles of a magnet
1H and 13C nuclei respond to the magnetic field by aligning themselves to one of the two possible orientations followed by rf irradiation
Constant and varied strength of the applied field causes each nucleus to resonate at a slightly varied field strength
Absorption of rf energy is monitored by a sensitive detector that displays signals as a peak
The nature of NMR absorptions

14. Figure 13.4 - Operation of a Basic NMR Spectrometer
The nature of NMR absorptions

15. NMR Spectrometer Time taken by IR spectroscopy is about 10–13 s
Time taken by NMR spectroscopy is about 10–3 s
Provides a blurring effect that is used in the measurement of rates and activation energies of vary fast processes
The nature of NMR absorptions

16. Worked Example
Explain why 2-chloropropene shows signals for three kinds of protons in its 1H NMR spectrum
Solution:
2-Chloropropene has three kinds of protons
Protons b and c differ because one is cis to the chlorine and the other is trans
The nature of NMR absorptions

17. The Chemical Shift The left segment of the chart is the downfield
Nuclei absorbing on the downfield have less shielding as they require a lower field for resistance
The right segment is the upfield
Nuclei absorbing on the upfield have more shielding as they require a higher field strength for resistance
The chemical shift

18. Figure The NMR Chart
The chemical shift

19. The Chemical Shift
Chemical shift is the position on the chart at which a nucleus absorbs
The delta (δ) scale is used in calibration of the NMR chart
1 δ = 1 part-per-million of the spectrometer operating frequency
The delta scale is used as the units of measurement can be used to compare values across other instruments
The chemical shift

20. Worked Example
The 1H NMR peak of CHCl3 was recorded on a spectrometer operating at 200 MHz providing the value of 1454 Hz
Convert 1454 Hz into δ units
Solution:
The chemical shift

21. Chemical Shifts in 1H NMR Spectroscopy
Chemical shifts are due to the varied electromagnetic fields produced by electrons surrounding nuclei
Protons bonded to saturated, sp3-hybridized carbons absorb at higher fields
Protons bonded to sp2-hybridized carbons absorb at lower fields
Protons bonded to electronegative atoms absorb at lower fields
Chemical shifts in 1H NMR spectroscopy

22. Table 13.2 - Regions of the 1H NMR Spectrum
Chemical shifts in 1H NMR spectroscopy

23. Worked Example CH2Cl2 has a single 1H NMR peak Solution:
Determine the location of absorption
Solution:
For CH2Cl2 , δ = 5.30
The location of absorption are the protons adjacent to the two halogens
Chemical shifts in 1H NMR spectroscopy

24. Integration of 1H NMR Absorptions: Proton Counting
In the figure, the peak caused by (CH3)3C–protons is larger than the peak caused by –OCH protons
Integration of the area under the peak can be used to quantify the different kinds of protons in a molecule
Integration of 1H NMR absorptions: Proton counting

25. Worked Example
Mention the number of peaks in the 1H NMR spectrum of 1,4-dimethyl-benzene (para-xylene or p-xylene)
Mention the ratio of peak areas possible on integration of the spectrum
Integration of 1H NMR absorptions: Proton counting

26. Worked Example Solution:
There are two absorptions in the 1H NMR spectrum of p-xylene
The four ring protons absorb at 7.05 δ and the six methyl-groups absorb at 2.23 δ
The peak ratio of methyl protons:ring protons is 3:2
Characteristics of 13C NMR spectroscopy

27. Worked Example
Characteristics of 13C NMR spectroscopy

28. Spin-Spin Splitting in 1H NMR Spectra
Multiplet: Absorption of a proton that splits into multiple peaks
The phenomenon is called spin-spin splitting
Caused by coupling of neighboring spins
Spin-spin splitting in 1H NMR spectra

29. Spin-Spin Splitting in 1H NMR Spectra
Alignment of –CH2Br proton spins with the applied field can result in:
Slightly larger total effective field and slight reduction in the applied field to achieve resonance
There is no effect if one of the –CH2Br proton spins aligns with the applied field and the other aligns against it
Alignment of –CH2Br proton spins against the applied field results in:
Smaller effective field and an increased applied field to achieve resonance
Spin-spin splitting in 1H NMR spectra

30. Figure 13.8 - The Origin of Spin-Spin Splitting in Bromoethane
Spin-spin splitting in 1H NMR spectra

31. Spin-Spin Splitting in 1H NMR Spectra
n + 1 rule: Protons that exhibit n + 1 peaks in the NMR spectrum possess
n = number of equivalent neighboring protons
Coupling constant is the distance between peaks in a multiplet
Spin-spin splitting in 1H NMR spectra

32. Spin-Spin Splitting in 1H NMR Spectra
It is possible to identify multiplets in a complex NMR that are related
Multiplets that have the same coupling constant can be related
Multiplet-causing protons are situated adjacent to each other in the molecule
Spin-spin splitting in 1H NMR spectra

33. Rules of Spin-Spin Splitting
Chemically equivalent protons do not show spin-spin splitting
The signal of a proton with n equivalent neighboring protons is split into a multiplet of n + 1 peaks with a coupling constant
Two groups of photons coupled together have the same coupling constant, J
Spin-spin splitting in 1H NMR spectra

34. Worked Example
The integrated 1H NMR spectrum of a compound of formula C4H10O is shown below
Propose a structure
Spin-spin splitting in 1H NMR spectra

35. Worked Example Solution:
The molecular formula (C4H10O) indicates that the compound has no multiple bonds or rings
The 1H NMR spectrum shows two signals, corresponding to two types of hydrogens in the ratio 1.50:1.00, or 3:2
Since the unknown contains 10 hydrogens, four protons are of one type and six are of the other type
The upfield signal at 1.22 δ is due to saturated primary protons
Spin-spin splitting in 1H NMR spectra

36. Worked Example
The downfield signal at 3.49 δ is due to protons on carbon adjacent to an electronegative atom - in this case, oxygen
The signal at 1.23 δ is a triplet, indicating two neighboring protons
The signal at 3.49 δ is a quartet, indicating three neighboring protons
This splitting pattern is characteristic of an ethyl group
The compound is diethyl ether, CH3CH2OCH2CH3
Spin-spin splitting in 1H NMR spectra

37. 1H NMR Spectroscopy and Proton Equivalence
Proton NMR is much more sensitive than 13C and the active nucleus (1H) is nearly 100 % of the natural abundance
Shows how many kinds of nonequivalent hydrogens are in a compound
Theoretical equivalence can be predicted by comparing structures formed by replacing each H with X gives the same or different outcome
Equivalent H’s have the same signal while nonequivalent are different
There are degrees of nonequivalence
1H NMR spectroscopy and proton equivalence

38. 1H NMR Spectroscopy and Proton Equivalence
One use of 1H NMR is to ascertain the number of electronically non-equivalent hydrogens present in a molecule
In relatively small molecules, a brief look at the structure can help determine the kinds of protons present and the number of possible NMR absorptions
Equivalence or nonequivalence of two protons can be determined by comparison of structures formed if each hydrogen were replaced by an X group
1H NMR spectroscopy and proton equivalence

39. 1H NMR Spectroscopy and Proton Equivalence
Possibilities
If the protons are chemically unrelated and non-equivalent, the products formed by substitution would be different constitutional isomers
1H NMR spectroscopy and proton equivalence

40. 1H NMR Spectroscopy and Proton Equivalence
If the protons are chemically identical, the same product would be formed despite the substitution
1H NMR spectroscopy and proton equivalence

41. 1H NMR Spectroscopy and Proton Equivalence
If the hydrogens are homotopic but not identical, substitution will form a new chirality center
Hydrogens that lead to formation of enantiomers upon substitution with X are called enantiotopic
1H NMR spectroscopy and proton equivalence

42. 1H NMR Spectroscopy and Proton Equivalence
If the hydrogens are neither homotopic nor enantiotopic, substitution of a hydrogen at C3 would form a second chirality center
1H NMR spectroscopy and proton equivalence

43. Worked Example
How many absorptions will (S)-malate, an intermediate in carbohydrate metabolism have in its 1H NMR spectrum? Explain
1H NMR spectroscopy and proton equivalence

44. Worked Example Solution:
Because (S)-malate already has a chirality center(starred), the two protons next to it are diastereotopic and absorb at different values
The 1H NMR spectrum of (S)-malate has four absorptions
1H NMR spectroscopy and proton equivalence

45. More Complex Spin-Spin Splitting Patterns
Some hydrogens in a molecule possess accidentally overlapping signals
In the spectrum of toluene (methylbenzene), the five aromatic ring protons produce a complex, overlapping pattern though they are not equivalent
More complex spin–spin splitting patterns

46. More Complex Spin-Spin Splitting Patterns
Splitting of a signal by two or more nonequivalent kinds of protons causes a complication in 1H NMR spectroscopy
More complex spin–spin splitting patterns

47. Figure 13.14 - Tree Diagram for the C2 proton of trans-cinnamaldehyde
More complex spin–spin splitting patterns

48. Worked Example
3-Bromo-1-phenyl-1-propene shows a complex NMR spectrum in which the vinylic proton at C2 is couples with both the C1 vinylic proton (J = 16 Hz) and the C3 methylene protons (J = 8 Hz)
Draw a tree diageam for the C2 proton signal and account for the fact that a live-line multiplet is observed
More complex spin–spin splitting patterns

49. Worked Example Solution:
C2 proton couples with vinylic proton (J = 16) Hz
C2 proton’s signal is split into a doublet
C2 proton also couples with the two C3 protons (J = 8 Hz)
Each leg of the C2 proton doublet is split into a triplet to produce a total of six lines
More complex spin–spin splitting patterns

50. Worked Example
More complex spin–spin splitting patterns

51. Uses of 1H NMR Spectroscopy
The technique is used to identify likely products in the laboratory quickly and easily
NMR can help prove that hydroboration-oxidation of alkenes occurs with non-Markovnikov regiochemistry to yield the less highly substituted alcohol
Uses of 1H NMR spectroscopy

52. Figure 13.15 - 1H NMR Spectra of Cyclohexylmethanol
Uses of 1H NMR spectroscopy

53. Worked Example
Mention how 1H NMR is used to determine the regiochemistry of electrophilic addition to alkenes
Determine whether addition of HCl to 1-methylcyclohexene yields 1-chloro-1-nethylcyclohexane or 1-chloro-2-methylcyclohexane
Uses of 1H NMR spectroscopy

54. Worked Example Solution: Referring to 1H NMR methyl group absorption
The unslpit methyl group in the left appears as a doublet in the product on the right
Bonding of a proton to a carbon that is also bonded to an electronegative atom causes a downfield absorption in the 2.5–4.0 region
1H NMR spectrum of the product would confirm the product to be 1-chloro-1-methylcyclohexane
Uses of 1H NMR spectroscopy

55. 13C NMR Spectroscopy: Signal Averaging and FT–NMR
Carbon-13 is the only naturally occurring carbon isotope that possesses a nuclear spin, but its natural abundance is 1.1%
Signal averaging and Fourier-transform NMR (FT–NMR) help in detecting carbon 13
Due to the excess random electronic background noise present in 13C NMR, an average is taken from hundreds or thousands of individual NMR spectra
13C NMR spectroscopy: Signal averaging and FT–NMR

56. Figure 13.16 - Carbon-13 NMR Spectra of 1-Pentanol
13C NMR spectroscopy: Signal averaging and FT–NMR

57. 13C NMR Spectroscopy: Signal Averaging and FT–NMR
Spin-spin splitting is observed only in 1H NMR
The low natural abundance of 13C nucleus is the reason that coupling with adjacent carbons is highly unlikely
Due to the broadband decoupling method used to record 13C spectra, hydrogen coupling is not seen
13C NMR spectroscopy: Signal averaging and FT–NMR

58. Characteristics of 13C NMR Spectroscopy
13C NMR provides a count of the different carbon atoms in a molecule
13C resonances are 0 to 220 ppm downfield from TMS
Characteristics of 13C NMR spectroscopy

59. Characteristics of 13C NMR Spectroscopy
General factors that determine chemical shifts
The electronegativity of nearby atoms
The diamagnetic anisotropy of pi systems
The absorption of sp3-hybridized carbons and sp2 carbons
Characteristics of 13C NMR spectroscopy

60. Figure 13.18 - Carbon-13 Spectra of 2-butanone and para-bromoacetophenone
Characteristics of 13C NMR spectroscopy

61. Worked Example
Classify the resonances in the 13C spectrum of methyl propanoate, CH3CH2CO2CH3
Characteristics of 13C NMR spectroscopy

62. Worked Example Solution:
Methyl propanoate has four unique carbons that individually absorb in specific regions of the 13C spectrum
Integration of 1H NMR absorptions: Proton counting

63. DEPT 13C NMR Spectroscopy
DEPT-NMR (distortionless enhancement by polarization transfer)
Stages of a DEPT experiment
Run a broadband-decoupled spectrum
Run a DEPT-90
Run a DEPT-135
The DEPT experiment manipulates the nuclear spins of carbon nuclei
DEPT 13C NMR spectroscopy

64. Figure 13.20 – DEPT-NMR Spectra for 6-methyl-5-hepten-2-ol
DEPT 13C NMR spectroscopy

65. Uses of 13C NMR Spectroscopy
Helps in determining molecular structures
Provides a count of non-equivalent carbons
Provides information on the electronic environment of each carbon and the number of attached protons
Provides answers on molecule structure that IR spectrometry or mass spectrometry cannot provide
Uses of 13C NMR spectroscopy

66. Figure 13.21 - 13C NMR Spectrum of 1-methylcyclohexane
Uses of 13C NMR spectroscopy

67. Worked Example
Propose a structure for an aromatic hydrocarbon, C11H16, that has the following 13C NMR spectral data:
Broadband decoupled: 29.5, 31.8, 50.2, 125.5, 127.5, 130.3, δ
DEPT-90: 125.5, 127.5, δ
DEPT-135: positive peaks at 29.5, 125.5, 127.5, δ; negative peak at 50.2 δ
Uses of 13C NMR spectroscopy

68. Worked Example Solution:
Calculate the degree of unsaturation of the unknown compound
C11H16 has 4 degrees of unsaturation
Look for elements of symmetry
7 peaks appearing in the 13C NMR spectrum indicate a plane of symmetry
According to the DEPT-90 spectrum, 3 of the kinds of carbons in the aromatic ring are CH carbons
Spin–spin splitting in 1H NMR spectra

69. Worked Example
The unknown structure is a monosubstituted benzene ring with a substituent containing CH2 and CH3 carbons
Spin–spin splitting in 1H NMR spectra

70. Summary
Nuclear magnetic resonance spectroscopy or NMR is the most important spectroscopic technique used in the determination of molecular structure
Magnetic nuclei such as 1H and 13C spin-flip from a lower energy state to a higher energy state when they absorb radiofrequency waves
Each 1H or 13C nucleus possesses a unique electromagnetic field that causes it to resonate at different values of the applied field causing peaks whose exact position is termed a chemical shift

71. Summary Delta (δ) is the unit of calibration in NMR charts
Tetramethylsilane (TMS) is a reference point on the NMR chart
TMS absorption that occurs at the right-hand (upfield) side of the chart is assigned a value of 0 δ
Fourier-transform NMR (FT–NMR) spectrometers are used to obtain 13C spectra using broadband decoupling of proton spins

72. Summary
Electronic integration of the area under each absorption peak in 1H NMR spectra is used to determine the number of hydrogens that cause each peak
Neighboring nuclear spins can couple to cause the spin-spin splitting of NMR peaks into multiplets
The NMR signal of a hydrogen neighbored by n equivalent adjacent hydrogens splits into n + 1 peaks (the n + 1 rule) with coupling constant J