1. Dr. Wolf's CHM 201 & 202 13- 1 13.3 Introduction to 1 H NMR Spectroscopy

2. Dr. Wolf's CHM 201 & 202 13- 2 1 H and 13 C both have spin = ±1/2 1 H is 99% at natural abundance 13 C is 1.1% at natural abundance The nuclei that are most useful to organic chemists are:

3. Dr. Wolf's CHM 201 & 202 13- 3 Nuclear Spin A spinning charge, such as the nucleus of 1 H or 13 C, generates a magnetic field. The magnetic field generated by a nucleus of spin +1/2 is opposite in direction from that generated by a nucleus of spin –1/2. + +

4. Dr. Wolf's CHM 201 & 202 13- 4 + + + + + The distribution of nuclear spins is random in the absence of an external magnetic field.

5. Dr. Wolf's CHM 201 & 202 13- 5 + + + + + An external magnetic field causes nuclear magnetic moments to align parallel and antiparallel to applied field. H0H0H0H0

6. Dr. Wolf's CHM 201 & 202 13- 6 + + + + + There is a slight excess of nuclear magnetic moments aligned parallel to the applied field. H0H0H0H0

7. Dr. Wolf's CHM 201 & 202 13- 7 no difference in absence of magnetic field proportional to strength of external magnetic field Energy Differences Between Nuclear Spin States + + EEEE  E ' increasing field strength

8. Dr. Wolf's CHM 201 & 202 13- 8 Some important relationships in NMR The frequency of absorbed electromagnetic radiation is proportional to the energy difference between two nuclear spin states which is proportional to the applied magnetic field UnitsHz kJ/mol (kcal/mol) tesla (T)

9. Dr. Wolf's CHM 201 & 202 13- 9 Some important relationships in NMR The frequency of absorbed electromagnetic radiation is different for different elements, and for different isotopes of the same element. For a field strength of 4.7 T: 1 H absorbs radiation having a frequency of 200 MHz (200 x 10 6 s -1 ) 13 C absorbs radiation having a frequency of 50.4 MHz (50.4 x 10 6 s -1 )

10. Dr. Wolf's CHM 201 & 202 13- 10 Some important relationships in NMR The frequency of absorbed electromagnetic radiation for a particular nucleus (such as 1 H) depends on its molecular environment. This is why NMR is such a useful tool for structure determination.

11. Dr. Wolf's CHM 201 & 202 13- 11 13.4 Nuclear Shielding and 1 H Chemical Shifts What do we mean by "shielding?" What do we mean by "chemical shift?"

12. Dr. Wolf's CHM 201 & 202 13- 12 ShieldingShielding An external magnetic field affects the motion of the electrons in a molecule, inducing a magnetic field within the molecule. The direction of the induced magnetic field is opposite to that of the applied field. C H H 0H 0H 0H 0

13. Dr. Wolf's CHM 201 & 202 13- 13 ShieldingShielding The induced field shields the nuclei (in this case, C and H) from the applied field. A stronger external field is needed in order for energy difference between spin states to match energy of rf radiation. C H H 0H 0H 0H 0

14. Dr. Wolf's CHM 201 & 202 13- 14 Chemical Shift Chemical shift is a measure of the degree to which a nucleus in a molecule is shielded. Protons in different environments are shielded to greater or lesser degrees; they have different chemical shifts. C H H 0H 0H 0H 0

15. Dr. Wolf's CHM 201 & 202 13- 15 Chemical Shift Chemical shifts (  ) are measured relative to the protons in tetramethylsilane (TMS) as a standard. Si CH 3 H3CH3CH3CH3C  = position of signal - position of TMS peak spectrometer frequency x 10 6

16. Dr. Wolf's CHM 201 & 202 13- 16 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) measured relative to TMS Upfield Increased shielding Downfield Decreased shielding (CH 3 ) 4 Si (TMS)

17. Dr. Wolf's CHM 201 & 202 13- 17 Chemical Shift Example: The signal for the proton in chloroform (HCCl 3 ) appears 1456 Hz downfield from TMS at a spectrometer frequency of 200 MHz.  = position of signal - position of TMS peak spectrometer frequency x 10 6  = 1456 Hz - 0 Hz 200 x 10 6 Hx x 10 6  = 7.28

18. Dr. Wolf's CHM 201 & 202 13- 18 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm)  7.28 ppm H C Cl ClCl

19. Dr. Wolf's CHM 201 & 202 13- 19 13.5 Effects of Molecular Structure on 1 H Chemical Shifts protons in different environments experience different degrees of shielding and have different chemical shifts

20. Dr. Wolf's CHM 201 & 202 13- 20 Electronegative substituents decrease the shielding of methyl groups least shielded Hmost shielded H CH 3 FCH 3 OCH 3 (CH 3 ) 3 NCH 3 (CH 3 ) 4 Si  4.3  3.2  2.2  0.9  0.0

21. Dr. Wolf's CHM 201 & 202 13- 21 Electronegative substituents decrease shielding H 3 C—CH 2 —CH 3 O 2 N—CH 2 —CH 2 —CH 3  0.9  1.3  1.0  4.3  2.0

22. Dr. Wolf's CHM 201 & 202 13- 22 Effect is cumulative CHCl 3  7.3 CH 2 Cl 2  5.3 CH 3 Cl  3.1

23. Dr. Wolf's CHM 201 & 202 13- 23 Methyl, Methylene, and Methine CH 3 more shielded than CH 2 ; CH 2 more shielded than CH H3CH3CH3CH3C C CH3CH3CH3CH3 CH 3 H  0.9  1.6  0.8 H3CH3CH3CH3C C CH3CH3CH3CH3 CH 3 CH2CH2CH2CH2  0.9 CH 3  1.2

24. Dr. Wolf's CHM 201 & 202 13- 24 Protons attached to sp 2 hybridized carbon are less shielded than those attached to sp 3 hybridized carbon HH HH HH C CHHHH CH 3 CH 3  7.3  5.3  0.9

25. Dr. Wolf's CHM 201 & 202 13- 25 But protons attached to sp hybridized carbon are more shielded than those attached to sp 2 hybridized carbon C C HH HH  5.3  2.4 CH 2 OCH 3 C C H

26. Dr. Wolf's CHM 201 & 202 13- 26 Protons attached to benzylic and allylic carbons are somewhat less shielded than usual  1.5  0.8 H3CH3CH3CH3C CH 3  1.2 H3CH3CH3CH3C CH 2  2.6 H 3 C—CH 2 —CH 3  0.9  1.3

27. Dr. Wolf's CHM 201 & 202 13- 27 Proton attached to C=O of aldehyde is most deshielded C—H  2.4  9.7  1.1 CC O H H CH 3 H3CH3CH3CH3C

28. Dr. Wolf's CHM 201 & 202 13- 28 Type of proton Chemical shift (  ), ppm Type of proton Chemical shift (  ), ppm C HR 0.9-1.8 1.5-2.6 C H CC 2.0-2.5 C H CO2.1-2.3 C H NC C HAr 2.3-2.8 2.5 C H CC

29. Dr. Wolf's CHM 201 & 202 13- 29 Type of proton Chemical shift (  ), ppm Type of proton Chemical shift (  ), ppm C HBr 2.7-4.1 9-10 COH 2.2-2.9 C HNR 3.1-4.1 C HCl 6.5-8.5HAr C CH4.5-6.5 3.3-3.7 C H O

30. Dr. Wolf's CHM 201 & 202 13- 30 Type of proton Chemical shift (  ), ppm 1-3HNR0.5-5HOR6-8HOAr10-13 CO HOHOHOHO

31. Dr. Wolf's CHM 201 & 202 13- 31 13.6 Interpreting Proton NMR Spectra

32. Dr. Wolf's CHM 201 & 202 13- 32 1. number of signals 2. their intensity (as measured by area under peak) 3. splitting pattern (multiplicity) Information contained in an NMR spectrum includes:

33. Dr. Wolf's CHM 201 & 202 13- 33 Number of Signals protons that have different chemical shifts are chemically nonequivalent exist in different molecular environment

34. Dr. Wolf's CHM 201 & 202 13- 34 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) CCH 2 OCH 3 N OCH 3 NCCH 2 O

35. Dr. Wolf's CHM 201 & 202 13- 35 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

36. Dr. Wolf's CHM 201 & 202 13- 36 H 3 CCH 2 CH 3 chemically equivalent CH 3 CH 2 CH 2 Cl ClCH 2 CH 2 CH 3 Chemically equivalent protons 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

37. Dr. Wolf's CHM 201 & 202 13- 37 replacement by some arbitrary test group generates diastereomers diastereotopic protons can have different chemical shifts Diastereotopic protons C CBr H3CH3CH3CH3C H H  5.3 ppm  5.5 ppm

38. Dr. Wolf's CHM 201 & 202 13- 38 not all peaks are singlets signals can be split by coupling of nuclear spins 13.7 Spin-Spin Splitting in NMR Spectroscopy

39. Dr. Wolf's CHM 201 & 202 13- 39 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) Cl 2 CHCH 3 Figure 13.12 (page 536) 4 lines; quartet 2 lines; doublet CH3CH3CH3CH3 CHCHCHCH

40. Dr. Wolf's CHM 201 & 202 13- 40 Two-bond and three-bond coupling C C H H C C HH protons separated by two bonds (geminal relationship) protons separated by three bonds (vicinal relationship)

41. Dr. Wolf's CHM 201 & 202 13- 41 in order to observe splitting, protons cannot have same chemical shift coupling constant ( 2 J or 3 J) is independent of field strength Two-bond and three-bond coupling C C H H C C HH

42. 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) Cl 2 CHCH 3 Figure 13.12 (page 536) 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

43. Dr. Wolf's CHM 201 & 202 13- 43 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

44. Dr. Wolf's CHM 201 & 202 13- 44 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.

45. Dr. Wolf's CHM 201 & 202 13- 45 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.

46. Dr. Wolf's CHM 201 & 202 13- 46 Why do the methyl protons of 1,1-dichloroethane appear as a doublet? 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

47. Dr. Wolf's CHM 201 & 202 13- 47 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.

48. Dr. Wolf's CHM 201 & 202 13- 48 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?

49. Dr. Wolf's CHM 201 & 202 13- 49 For simple cases, the multiplicity of a signal for a particular proton is equal to the number of equivalent vicinal protons + 1. The splitting rule for 1 H NMR

50. Dr. Wolf's CHM 201 & 202 13- 50 13.8 Splitting Patterns: The Ethyl Group CH 3 CH 2 X is characterized by a triplet-quartet pattern (quartet at lower field than the triplet)

51. Dr. Wolf's CHM 201 & 202 13- 51 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

52. Dr. Wolf's CHM 201 & 202 13- 52 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 Table 13.2 (page 540)

53. Dr. Wolf's CHM 201 & 202 13- 53 13.9 Splitting Patterns: The Isopropyl Group (CH 3 ) 2 CHX is characterized by a doublet- septet pattern (septet at lower field than the doublet)

54. Dr. Wolf's CHM 201 & 202 13- 54 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) BrCH(CH 3 ) 2 7 lines; septet 2 lines; doublet CH3CH3CH3CH3 CHCHCHCH

55. Dr. Wolf's CHM 201 & 202 13- 55 13.14 13 C NMR Spectroscopy

56. Dr. Wolf's CHM 201 & 202 13- 56 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

57. Dr. Wolf's CHM 201 & 202 13- 57 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)

58. Dr. Wolf's CHM 201 & 202 13- 58 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 13.23 (a) shows the 1 H NMR spectrum of 1-chloropentane; Figure 13.23 (b) 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.

59. Dr. Wolf's CHM 201 & 202 13- 59 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) ClCH 2 CH3CH3CH3CH3 ClCH 2 CH 2 CH 2 CH 2 CH 3 1H1H1H1H

60. Dr. Wolf's CHM 201 & 202 13- 60 Chemical shift ( , ppm) 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

61. Dr. Wolf's CHM 201 & 202 13- 61 13.15 13 C Chemical Shifts are measured in ppm (  ) from the carbons of TMS

62. Dr. Wolf's CHM 201 & 202 13- 62 13 C Chemical shifts are most affected by: electronegativity of groups attached to carbon hybridization state of carbon

63. Dr. Wolf's CHM 201 & 202 13- 63 Electronegativity Effects Electronegativity has an even greater effect on 13 C chemical shifts than it does on 1 H chemical shifts.

64. Dr. Wolf's CHM 201 & 202 13- 64 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.

65. Dr. Wolf's CHM 201 & 202 13- 65 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

66. Dr. Wolf's CHM 201 & 202 13- 66 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.

67. Dr. Wolf's CHM 201 & 202 13- 67 13 C Chemical shifts are most affected by: electronegativity of groups attached to carbon hybridization state of carbon

68. Dr. Wolf's CHM 201 & 202 13- 68 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

69. Dr. Wolf's CHM 201 & 202 13- 69 Carbonyl carbons are especially deshielded O CH 2 C O CH 3 127-134 411461171

70. Dr. Wolf's CHM 201 & 202 13- 70 Table 13.3 (p 549) 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

71. Dr. Wolf's CHM 201 & 202 13- 71 Table 13.3 (p 549) 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

72. Dr. Wolf's CHM 201 & 202 13- 72 13.16 13 C NMR and Peak Intensities Pulse-FT NMR distorts intensities of signals. Therefore, peak heights and areas can be deceptive.

73. Dr. Wolf's CHM 201 & 202 13- 73 CH 3 OH Figure 13.24 (page 551) Chemical shift ( , ppm) 020406080100120140160180200 7 carbons give 7 signals, but intensities are not equal

74. Dr. Wolf's CHM 201 & 202 13- 74 End of Chapter 13