1. 1 Chapter 13 Nuclear Magnetic Resonance Spectroscopy Leroy Wade

2. 2 Mass No. At. No. Nuclear Spin, I Nuclei Odd Odd or even 1/2, 3/2, 5/2 1 H, 13 C, 19 F Even 0 12 C, 16 O evenodd1, 2, 3 2 H, 14 N

3. 3 Origin of NMR Signals

4. 4 1-Chlorobutane CH 3 CH 2 CH 2 CH 2 Cl Information contained in an NMR spectrum includes: 1.Position (chemical shift) of the peaks – amount of shielding. 2.Intensities of signals – number of protons producing each signal.

5. 5 3.Splitting pattern – number of neighboring protons. 4.Number of signals – different types of proton present in the molecule. - protons that have different chemical shifts are chemically nonequivalent – exist in different molecular environment.

6. 6 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) CCH 2 OCH 3 N OCH 3 NCCH 2 O

7. 7 are in identical environments - have same chemical shift Replacement test: replacement by some arbitrary "test group" generates same compound H 3 CCH 2 CH 3 chemically equivalent Chemically equivalent protons

8. 8 Replacing protons at C-1 and C-3 gives same compound (1-chloropropane) C-1 and C-3 protons are chemically equivalent and have the same chemical shift H 3 CCH 2 CH 3 chemically equivalent CH 3 CH 2 CH 2 Cl ClCH 2 CH 2 CH 3

9. 9 2. CHEMICAL SHIFTS All protons present in a molecule don’t produce a single NMR signal. Protons in different chemical environments produce signal at different positions on the spectrum. For example, CH 3 CH 2 CH 2 CH 2 Cl produce a set of four signals, one for methyl and three for methylene protons. The position of signal’s appearance on NMR spectrum is known as Chemical Shift.

10. 10 Measurement of Chemical Shift Position of resonance signals are measured relative to (CH 3 ) 4 Si, tetramethylsilane (TMS), used as a NMR reference substance or standard. All 12 protons of TMS produce a single sharp line on NMR spectrum.

11. 11 Resonance frequency of nuclei depends on the applied magnetic resonance frequency. In order to make the chemical shift values independent of the magnet strength, a ppm scale is introduced. This dimensionless chemical shift is represented by  is defined as follows.

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13. 13

14. 14 Characteristic Values of Chemical Shifts

15. 15 Vinyl and Aromatic Protons

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18. 18 Areas of the Peaks

19. 19

20. 20 Not all NMR peaks are singlets. When two different types of protons are close enough their magnetic fields interact with each other and signals are splitted. Spin-Spin Splitting

21. 21 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) Cl 2 CHCH 3 4 lines; quartet 2 lines; doublet CH3CH3CH3CH3 CHCHCHCH

22. 22 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) Cl 2 CHCH 3 4 lines; quartet 2 lines; doublet CH3CH3CH3CH3 CHCHCHCH coupled protons are vicinal (three-bond coupling) CH splits CH 3 into a doublet CH 3 splits CH into a quartet

23. 23 Why do the methyl protons of 1,1-dichloroethane appear as a doublet? C C HH Cl Cl HH signal for methyl protons is split into a doublet To explain the splitting of the protons at C-2, we first focus on the two possible spin orientations of the proton at C-1

24. 24 Why do the methyl protons of 1,1-dichloroethane appear as a doublet? C C HH Cl Cl HH signal for methyl protons is split into a doublet There are two orientations of the nuclear spin for the proton at C-1. One orientation shields the protons at C-2; the other deshields the C-2 protons.

25. 25 Why do the methyl protons of 1,1-dichloroethane appear as a doublet? C C HH Cl Cl HH signal for methyl protons is split into a doublet The protons at C-2 "feel" the effect of both the applied magnetic field and the local field resulting from the spin of the C-1 proton.

26. 26 C C HH Cl Cl HH "true" chemical shift of methyl protons (no coupling) this line corresponds to molecules in which the nuclear spin of the proton at C-1 reinforces the applied field this line corresponds to molecules in which the nuclear spin of the proton at C-1 opposes the applied field

27. 27 Why does the methine proton of 1,1-dichloroethane appear as a quartet? C C HH Cl Cl HH signal for methine proton is split into a quartet The proton at C-1 "feels" the effect of the applied magnetic field and the local fields resulting from the spin states of the three methyl protons. The possible combinations are shown on the next slide.

28. 28 C C HH Cl Cl HH There are eight combinations of nuclear spins for the three methyl protons. These 8 combinations split the signal into a 1:3:3:1 quartet. Why does the methine proton of 1,1-dichloroethane appear as a quartet?

29. 29 For simple cases, the multiplicity of a signal for a particular proton is equal to the number of equivalent vicinal protons + 1. The N+1 rule

30. 30 The range of Magnetic coupling

31. 31

32. 32 Splitting Patterns of Common Multiplets Number of equivalentAppearanceIntensities of lines protons to which H of multipletin multiplet is coupled 1Doublet1:1 2Triplet1:2:1 3Quartet1:3:3:1 4Pentet1:4:6:4:1 5Sextet1:5:10:10:5:1 6Septet1:6:15:20:15:6:1

33. 33 Splitting Patterns: The Ethyl Group CH 3 CH 2 X is characterized by a triplet- quartet pattern (quartet at lower field than the triplet)

34. 34 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) BrCH 2 CH 3 4 lines; quartet 3 lines; triplet CH3CH3CH3CH3 CH2CH2CH2CH2

35. 35 Splitting Patterns: The Isopropyl Group (CH 3 ) 2 CHX is characterized by a doublet- septet pattern (septet at lower field than the doublet)

36. 36 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) 7 lines; septet 2 lines; doublet CH3CH3CH3CH3 CHCHCHCH

37. 37 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) OCH 3 skewed doublets HHHH Cl OCH 3

38. 38 Couplinmg Constants The distance between the peaks of a multiplet (in Hz) is called the Coupling Constant. Coupling constants are represented by J, and the coupling constant between Ha and Hb is represented by J ab.

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40. 40

41. 41 Exercise: Fig 13-30

42. 42 Complex Splitting

43. 43 m-Nitrostyrene Consider the proton shown in red. It is unequally coupled to the protons shown in blue and yellow. J cis = 12 Hz; J trans = 16 HzHH O2NO2NO2NO2N H

44. 44 m-Nitrostyrene 16 Hz 12 Hz The signal for the proton shown in red appears as a doublet of doublets.HH O2NO2NO2NO2N H

45. 45HH O2NO2NO2NO2N H doublet of doublets doublet doublet

46. 46 Time Dependence of NMR Spectroscopy Most conformational changes occur faster than NMR can detect them. An NMR spectrum is the weighted average of the conformations. For example: Cyclohexane gives a single peak for its H atoms in NMR. Half of the time a single proton is axial and half of the time it is equatorial. The observed chemical shift is half way between the axial chemical shift and the equatorial chemical shift.

47. 47 1 H NMR Spectra of O-H, N-H proton containing molecules The chemical shift for O—H and N-H is variable (  0.5-5 ppm) and depends on temperature and concentration. Splitting of the O—H proton is sometimes observed, but often is not. It usually appears as a broad peak. Adding D 2 O converts O—H to O—D. The O—H peak disappears.

48. 48 13.12 13 C NMR Spectroscopy

49. 49 1 H and 13 C NMR compared: both give us information about the number of chemically nonequivalent nuclei (nonequivalent hydrogens or nonequivalent carbons) both give us information about the environment of the nuclei (hybridization state, attached atoms, etc.) it is convenient to use FT-NMR techniques for 1 H; it is standard practice for 13 C NMR

50. 50 1 H and 13 C NMR compared: 13 C requires FT-NMR because the signal for a carbon atom is 10 -4 times weaker than the signal for a hydrogen atom a signal for a 13 C nucleus is only about 1% as intense as that for 1 H because of the magnetic properties of the nuclei, and at the "natural abundance" level only 1.1% of all the C atoms in a sample are 13 C (most are 12 C)

51. 51 1 H and 13 C NMR compared: 13 C signals are spread over a much wider range than 1 H signals making it easier to identify and count individual nuclei Figure 1 shows the 1 H NMR spectrum of 1- chloropentane; Figure 2 shows the 13 C spectrum. It is much easier to identify the compound as 1-chloropentane by its 13 C spectrum than by its 1 H spectrum.

52. 52 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) ClCH 2 Figure 1 CH3CH3CH3CH3 ClCH 2 CH 2 CH 2 CH 2 CH 3 1H1H1H1H

53. 53 Chemical shift ( , ppm) Figure 2 ClCH 2 CH 2 CH 2 CH 2 CH 3 020406080100120140160180200 13 C CDCl 3 a separate, distinct peak appears for each of the 5 carbons

54. 54 13 C Chemical Shifts are measured in ppm (  ) from the carbons of TMS

55. 55 13 C Chemical shifts are most affected by: electronegativity of groups attached to carbonelectronegativity of groups attached to carbon hybridization state of carbonhybridization state of carbon

56. 56 Electronegativity Effects Electronegativity has an even greater effect on 13 C chemical shifts than it does on 1 H chemical shifts.

57. 57 Types of Carbons (CH 3 ) 3 CH CH4CH4CH4CH4 CH3CH3CH3CH3CH3CH3CH3CH3 CH 3 CH 2 CH 3 (CH 3 ) 4 C primarysecondary tertiary quaternary Classification Chemical shift,  1H1H1H1H 13 C 0.2 0.9 1.3 1.7-28 16 25 28 Replacing H by C (more electronegative) deshields C to which it is attached.

58. 58 Electronegativity effects on CH 3 CH3FCH3FCH3FCH3F CH4CH4CH4CH4 CH 3 NH 2 CH 3 OH Chemical shift,  1H1H1H1H0.2 2.5 3.4 4.3 13 C -2 27 50 75

59. 59 Electronegativity effects and chain length Chemical shift,  Cl CH 2 CH 3 4533292214 Deshielding effect of Cl decreases as number of bonds between Cl and C increases.

60. 60 13 C Chemical shifts are most affected by: electronegativity of groups attached to carbonelectronegativity of groups attached to carbon hybridization state of carbonhybridization state of carbon

61. 61 Hybridization effects sp 3 hybridized carbon is more shielded than sp 2 114 138 36 36126-142 sp hybridized carbon is more shielded than sp 2, but less shielded than sp 3 CH 3 HCC CH 2 6884222013

62. 62 Carbonyl carbons are especially deshielded O CH 2 C O CH 3 127-134 411461171

63. 63 Table: 13 C Chemical Shift Type of carbon Chemical shift (  ), ppm Type of carbon Chemical shift (  ), ppm RCH3RCH3RCH3RCH30-35 CR2CR2CR2CR2 R2CR2CR2CR2C65-90 CRCRCRCR RCRCRCRC R2CH2R2CH2R2CH2R2CH215-40 R3CHR3CHR3CHR3CH25-50 R4CR4CR4CR4C30-40 100-150 110-175

64. 64 Type of carbon Chemical shift (  ), ppm Type of carbon Chemical shift (  ), ppm RCH 2 Br 20-40 RCH 2 Cl 25-50 35-50 RCH 2 NH 2 50-65 RCH 2 OH RCH 2 OR 50-65 RCOR O160-185 RCRRCRRCRRCRO190-220 RCRCRCRCN 110-125

65. 65 13 C NMR and Peak Intensities Pulse-FT NMR distorts intensities of signals. Therefore, peak heights and areas can be deceptive.

66. 66 CH 3 OH Figure 3 Chemical shift ( , ppm) 020406080100120140160180200 7 carbons give 7 signals, but intensities are not equal