1. Chapter 13 Spectroscopy Infrared spectroscopy Ultraviolet-visible spectroscopy Nuclear magnetic resonance spectroscopy Mass spectrometry Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

2. 13.1 Principles of Molecular Spectroscopy: Electromagnetic Radiation

3. Cosmic rays  Rays X-rays Ultraviolet light Visible light Infrared radiation Microwaves Radio waves Figure 13.1: The Electromagnetic Spectrum Energy Hi, Short Lo, Long

4. Is propagated at the speed of light, has properties of particles and waves, and the energy of a photon is proportional to its frequency. Electromagnetic Radiation  E = h

5. Figure 13.1: The Electromagnetic Spectrum 400 nm750 nm Visible Light Longer Wavelength ( )Shorter Wavelength ( ) Higher Frequency ( )Lower Frequency ( ) Higher Energy (E)Lower Energy (E) UltravioletInfrared The UV, VIS, IR region.

6. 13.2 Principles of Molecular Spectroscopy: Quantized Energy States

7. Electromagnetic radiation is absorbed when the energy of photon corresponds to difference in energy between two states.  E = h

8. Effect Electron excitation Vibration of bonds Rotation of molecules Nuclear spin states Energy UV-Vis infrared microwave radiofrequency Energy and its Effect

9. 13.3 Introduction to 1 H NMR Spectroscopy (Proton NMR)

10. 1 H and 13 C Both have nuclear spin = ±1/2. 1 H is 99% at natural abundance. 13 C is 1.1% at natural abundance. 12 C is 98.9% at natural abundance ) but is not NMR active. The Nuclei that are Most Useful to Organic Chemists are:

11. 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. + +

12. + + + + + The distribution of nuclear spins is random in the absence of an external magnetic field B 0.

13. + + + + + B 0 = field strength An external magnetic field (B 0 ) causes nuclear magnetic moments to align parallel or antiparallel to applied field.

14. + + + + + B0B0 There is a slight excess of nuclear magnetic moments aligned parallel to the applied field.

15. There is no difference in energy in the two spin states absence of a magnetic field. ΔE (the energy required to flip states) is proportional to strength of external magnetic field. Energy Differences Between Nuclear Spin States + + EE  E ' increasing field strength

16. Energy Required to Flip Spin States H o = B 0 (Terms for the applied field, in gauss below).

17. 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. Units Hz kJ/mol (kcal/mol) tesla (T)

18. 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 )

19. Some Important Relationships in NMR The frequency of the electromagnetic radiation absorbed to flip spin states for a particular nucleus (such as 1 H) depends on its molecular environment. So, hydrogens in different environments in the same compound will absorb energy of different frequencies. This makes NMR a very useful tool for structure determination.

20. 13.4 Nuclear Shielding and 1 H Chemical Shifts What do we mean by "shielding"? What do we mean by "chemical shift"?

21. Shielding 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, B i, is opposite to that of the applied field. C H B0B0 BiBi

22. Shielding The induced field shields the nuclei (in this case, C and H) from the applied field. So, a stronger external field is needed in order for the energy difference between spin states to match energy of radiofrequency (rf) radiation. C H B0B0 BiBi

23. 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 which results in different chemical shifts. C H B0B0 BiBi

24. Chemical Shift Chemical shifts (  ) are measured relative to the protons in tetramethylsilane (TMS) as a standard. TMS has highly shielded hydrogens and the peak for these Hs in a scan is set at 0 . Si CH 3 H3CH3C  = position of signal - position of TMS peak spectrometer frequency x 10 6

25. 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)

26. 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

27. Chemical shift ( , ppm)  7.28 ppm H C Cl 01.02.03.04.05.06.07.08.09.010.0 The more electron electron density that is withdrawn from a hydrogen results in a smaller field induced from the remaining electrons.

28. 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.

29. 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 A more electronegative atom will remove more electron density from hydrdogen.

30. 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 CHCl 3  7.3 CH 2 Cl 2  5.3 CH 3 Cl  3.1

31. Methyl, Methylene, and Methine CH 3 more shielded than CH 2 ; CH 2 more shielded than CH H3CH3C C CH3CH3 CH 3 H  0.9  1.6  0.8 H3CH3C C CH3CH3 CH 3 CH2CH2  0.9 CH 3  1.2

32. Protons Attached to sp 2 Hybridized Carbon are Less Shielded than those Attached to sp 3 Hybridized Carbon HH HH H H C C HH HH CH 3  7.3  5.3  0.9

33. But Protons Attached to sp Hybridized Carbon are More Shielded than those Attached to sp 2 Hybridized Carbon  2.4 CH 2 OCH 3 C C H C C HH HH  5.3

34. Protons Attached to Benzylic and Allylic Carbons are Somewhat Less Shielded than Usual  1.5  0.8 H3CH3CCH 3  1.2 H3CH3CCH 2  2.6 H 3 C—CH 2 —CH 3  0.9  1.3 Allylic Benzylic Alkyl

35. Proton Attached to C=O of Aldehyde is Most Deshielded C—H  2.4  9.7  1.1 CC O H H CH 3 H3CH3C

36. Table 13.1 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 C O 2.1-2.3 C H NC C HAr 2.3-2.8

37. Table 13.1 Type of proton Chemical shift (  ), ppm Type of proton Chemical shift (  ), ppm C HBr 2.7-4.1 9-10 C O H 2.2-2.9 C HNR 3.1-4.1 C HCl 6.5-8.5HAr C C H 4.5-6.5 3.3-3.7 C H O

38. Table 13.1 Type of proton Chemical shift (  ), ppm 1-3HNR 0.5-5HOR 6-8HOAr 10-13 C O HOHO

39. 13.6 Interpreting 1 H NMR Spectra

40. 1.Number of signals. 2.Position of signals. 3. Signal intensity (measured by area under peak). 4. Splitting pattern (multiplicity). Information Contained in an NMR Spectrum Includes:

41. Number of Signals Protons that have different chemical shifts are chemically nonequivalent. They exist in different molecular environments. Protons that have the same chemical shift are chemically equivalent.

42. Chemical shift ( , ppm) CCH 2 OCH 3 N OCH 3 NCCH 2 O Figure 13.12 chemically nonequivalent

43. 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

44. H 3 CCH 2 CH 3 chemically equivalent CH 3 CH 2 CH 2 ClClCH 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.

45. Diastereotopic protons are those whoswe replacement by some arbitrary test group generates diastereomers. Diastereotopic protons can have different chemical shifts. Diastereotopic Protons C C Br H3CH3C H H  5.3 ppm  5.5 ppm

46. Enantiotopic protons are those whose replacement by some arbitrary test group generates enantiomers. They are in mirror-image environments. Enantiotopic protons have the same chemical shift. Enantiotopic Protons

47. C CH 2 OH H3CH3C H H Enantiotopic Protons C CH 2 OH H3CH3C Cl H C CH 2 OH H3CH3C H Cl R S

48. 13.7 Spin-Spin Splitting in 1 H NMR Spectroscopy Not all peaks are singlets. Signals can be split by coupling of nuclear spins.

49. Chemical shift ( , ppm) Cl 2 CHCH 3 Figure 13.13 4 lines; quartet 2 lines; doublet CH 3 CH

50. 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)

51. 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

52. 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) Cl 2 CHCH 3 Figure 13.13 4 lines; quartet 2 lines; doublet CH 3 CH coupled protons are vicinal (three-bond coupling) CH splits CH 3 into a doublet CH 3 splits CH into a quartet

53. Why Do the Methyl Protons of 1,1-Dichloroethane Appear as a Doublet? C C HH Cl H H 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.

54. Why Do the Methyl Protons of 1,1-Dichloroethane Appear as a Doublet? A result of spin- spin spliting. 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. 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. C C HH Cl H H

55. Why Do the Methyl Protons of 1,1-Dichloroethane Appear as a Doublet? "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. C C HH Cl H H

56. Why Does the Methine Proton of 1,1-Dichloroethane Appear as a Quartet? 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. C C HH Cl H H

57. 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? C C HH Cl H H

58. For simple cases, the multiplicity of a signal for a particular proton is equal to the number of equivalent vicinal protons + 1. Called the N + 1 Rule. The Splitting Rule for 1 H NMR

59. 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).

60. Chemical shift ( , ppm) BrCH 2 CH 3 Figure 13.16 4 lines; quartet 3 lines; triplet CH 3 CH 2

61. 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

62. 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).

63. Chemical shift ( , ppm) ClCH(CH 3 ) 2 Figure 13.18 7 lines; septet 2 lines; doublet CH 3 CH

64. 13.10 Splitting Patterns: Pairs of Doublets Splitting patterns are not always symmetrical, but lean in one direction or the other.

65. Pairs of Doublets Consider coupling between two vicinal protons. If the protons have different chemical shifts, each will split the signal of the other into a doublet. C C HH

66. Pairs of Doublets Let  be the difference in chemical shift in Hz between the two hydrogens. Let J be the coupling constant between them in Hz. C C HH

67. AX When  is much larger than J the signal for each proton is a doublet, the doublet is symmetrical, and the spin system is called AX. JJ  C C HH

68. AM As  /J decreases, the signal for each proton remains a doublet, but becomes skewed. The outer lines decrease while the inner lines increase, causing the doublets to "lean" toward each other. JJ  C C HH

69. AB When  and J are similar, the spin system is called AB. Skewing is quite pronounced. It is easy to mistake an AB system of two doublets for a quartet. J J  C C HH

70. A2A2 When  = 0, the two protons have the same chemical shift and don't split each other. A single line is observed. The two doublets have collapsed to a singlet. C C HH

71. Chemical shift ( , ppm) Figure 13.20 OCH 3 skewed doublets HH HH Cl OCH 3

72. 13.11 Complex Splitting Patterns: Multiplets of multiplets

73. m-Nitrostyrene Consider the proton shown in red. It is unequally coupled to the protons shown in blue and white. J cis = 12 Hz; J trans = 16 Hz H H O2NO2N H

74. m-Nitrostyrene 16 Hz 12 Hz The signal for the proton shown in red appears as a doublet of doublets. H H O2NO2N H

75. Figure 13.21 H H O2NO2N H doublet of doublets doublet

76. 13.12 1 H NMR Spectra of Aldohols What about H bonded to O ?

77. O—H The chemical shift for O—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. C O HH

78. 13.13 NMR and Conformations

79. NMR is “Slow” Most conformational changes occur faster than NMR can detect them. An NMR spectrum shows 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 halfway between the axial chemical shift and the equatorial chemical shift.

80. 13.14 13 C NMR Spectroscopy

81. 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.

82. 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).

83. 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 13.26 (a) shows the 1 H NMR spectrum of 1-chloropentane; Figure 13.26 (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.

84. Chemical shift ( , ppm) ClCH 2 Figure 13.26(a) CH3CH3 ClCH 2 CH 2 CH 2 CH 2 CH 3 1H1H

85. Chemical shift ( , ppm) Figure 13.26(b) 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.

86. 13.15 13 C Chemical Shifts Are measured in ppm (  ) from the carbons of TMS

87. 13 C Chemical Shifts are Most Affected By: Electronegativity of groups attached to carbon Hybridization state of carbon Electronegativity has an even greater effect on 13 C chemical shifts than it does on 1 H chemical shifts.

88. Types of Carbons (CH 3 ) 3 CH CH4CH4 CH 3 CH 3 CH 2 CH 3 (CH 3 ) 4 C primary secondary tertiary quaternary Classification Chemical shift,  1H1H 13 C 0.2 0.9 1.3 1.7 -2 8 16 25 28 Replacing H with C (more electronegative) deshields C to which it is attached.

89. Electronegativity Effects on CH 3 CH 3 F CH 4 CH 3 NH 2 CH 3 OH Chemical shift,  1H1H 0.2 2.5 3.4 4.3 13 C -2 27 50 75

90. Electronegativity Effects and Chain Length Chemical shift,  ClCH 2 CH 3 4533292214 Deshielding effect of Cl decreases as number of bonds between Cl and C increases.

91. Hybridization Effects sp 3 hybridized carbon is more shielded than sp 2. 114 138 36 126-142 sp hybridized carbon is more shielded than sp 2, but less shielded than sp 3. CH 3 HCCCH 2 6884222013

92. Carbonyl Carbons are Especially Deshielded O CH 2 C O CH 3 127-134 411461171

93. Table 13.3 Type of carbon Chemical shift (  ), ppm Type of carbon Chemical shift (  ), ppm RCH3RCH3 0-35 CR2CR2 R2CR2C 65-90 CRCRRCRC R2CH2R2CH2 15-40 R3CHR3CH25-50 R4CR4C30-40 100-150 110-175

94. Table 13.3 Type of carbon Chemical shift (  ), ppm Type of carbon Chemical shift (  ), ppm RCH 2 Br20-40 RCH 2 Cl25-50 35-50 RCH 2 NH 2 50-65 RCH 2 OH RCH 2 OR50-65 RCOR O 160-185 RCRRCR O 190-220 RCRC N 110-125

95. 13.16 13 C NMR and Peak Intensities Pulse-FT NMR distorts intensities of signals. Therefore, peak heights and areas can be deceptive.

96. CH 3 OH Figure 13.27 Chemical shift ( , ppm) 7 carbons give 7 signals, but intensities are not equal.

97. 13.17 13 C-H Coupling

98. 13 C— 13 C splitting is not seen because the probability of two 13 C nuclei being in the same molecule is very small. 13 C— 1 H splitting is not seen because spectrum is measured under conditions that suppress this splitting (broadband decoupling). Peaks in a 13 C NMR Spectrum are Typically Singlets

99. 13.18 Using DEPT to Count the Hydrogens Attached to 13 C Distortionless Enhancement of Polarization Transfer

100. 1. Equilibration of the nuclei between the lower and higher spin states under the influence of a magnetic field 2. Application of a radiofrequency pulse to give an excess of nuclei in the higher spin state 3. Acquisition of free-induction decay data during the time interval in which the equilibrium distribution of nuclear spins is restored 4. Mathematical manipulation (Fourier transform) of the data to plot a spectrum Measuring a 13 C NMR Spectrum Involves

101. In DEPT, a second transmitter irradiates 1 H during the sequence, which affects the appearance of the 13 C spectrum. Some 13 C signals stay the same. Some 13 C signals disappear. Some 13 C signals are inverted. Measuring a 13 C NMR Spectrum Involves

102. Chemical shift ( , ppm) Figure 13.29 (a) O C C CH CH 2 CH 3 CCH 2 CH 2 CH 2 CH 3 O 020406080100120140160180200 DEPT 45

103. Chemical shift ( , ppm) Figure 13.29 (b) CH CH 2 CH 3 CCH 2 CH 2 CH 2 CH 3 O CH and CH 3 unaffected C and C=O nulled CH 2 inverted DEPT 135