1. 13 13-1 Organic Chemistry William H. Brown & Christopher S. Foote

2. 13 13-2 Nuclear Magnetic Resonance Chapter 13

3. 13 13-3 Molecular Spectroscopy  Nuclear magnetic resonance (NMR) spectroscopy:  Nuclear magnetic resonance (NMR) spectroscopy: a spectroscopic technique that gives us information about the number and types of atoms in a molecule, for example, about the number and types of hydrogen atoms using 1 H-NMR spectroscopy carbon atoms using 13 C-NMR spectroscopy phosphorus atoms using 31 P-NMR spectroscopy

4. 13 13-4 Nuclear Spin States  An electron has a spin quantum number of 1/2 with allowed values of +1/2 and -1/2 this spinning charge creates an associated magnetic field in effect, an electron behaves as if it is a tiny bar magnet and has what is called a magnetic moment  Pauli exclusion principle:  Pauli exclusion principle: two electrons can occupy the same atomic or molecular orbital only if they have paired (opposite) spins

5. 13 13-5 Nuclear Spin States  Any atomic nucleus that has an odd mass, an odd atomic number, or both also has a spin and a resulting nuclear magnetic moment  The allowed nuclear spin states are determined by the spin quantum number, I, of the nucleus I2I + 1  A nucleus with spin quantum number I has 2I + 1 spin states. If I = 1/2, there are two allowed spin states

6. 13 13-6 Nuclear Spin States  Spin quantum numbers and allowed nuclear spin states for selected isotopes of elements common to organic compounds

7. 13 13-7 Nuclear Spins in B 0  Within a collection of 1 H and 13 C atoms, nuclear spins are completely random in orientation  When placed in a strong external magnetic field of strength B 0, however, interaction between nuclear spins and the applied magnetic field is quantized, with the result that only certain orientations of nuclear magnetic moments are allowed

8. 13 13-8 Nuclear Spins in B 0  For 1 H and 13 C, only two orientations are allowed.

9. 13 13-9 Nuclear Spins in B 0  In an applied field strength of 7.05T, which is readily available with present-day superconducting electromagnets, the difference in energy between nuclear spin states for 1 H is approximately 0.120 J (0.0286 cal)/mol, which corresponds to electromagnetic radiation of 300 MHz (300,000,000 Hz) 13 C is approximately 0.030 J (0.00715 cal)/mol, which corresponds to electromagnetic radiation of 75MHz (75,000,000 Hz)

10. 13 13-10 Nuclear Spin in B 0  The energy difference between allowed spin states increases linearly with applied field strength. values shown here are for 1 H nuclei.

11. 13 13-11 Nuclear Magnetic Resonance  When nuclei with a spin quantum number of 1/2 are placed in an applied field, a small majority of nuclear spins are aligned with the applied field in the lower energy state  The nucleus begins to precess and traces out a cone-shaped surface, in much the same way a spinning top or gyroscope traces out a cone- shaped surface as it precesses in the earth’s gravitational field  We express the rate of precession as a frequency in hertz

12. 13 13-12 Nuclear Magnetic Resonance  If the precessing nucleus is irradiated with electromagnetic radiation of the same frequency as the rate of precession, the two frequencies couple, energy is absorbed, and the nuclear spin is flipped from spin state +1/2 (with the applied field) to -1/2 (against the applied field)

13. 13 13-13 Nuclear Magnetic Resonance  Coupling of precession frequency and the frequency of electromagnetic radiation

14. 13 13-14 Nuclear Magnetic Resonance  Resonance:  Resonance: the absorption of electromagnetic radiation by a precessing nucleus and the flip of its nuclear spin from a lower energy state to a higher energy state  The instrument used to detect this coupling of precession frequency and electromagnetic radiation records it as a signal

15. 13 13-15 Nuclear Magnetic Resonance  If we were dealing with 1 H nuclei isolated from all other atoms and electrons, any combination of applied field and radiation that produces a signal for one 1 H would produce a signal for all 1 H. The same is true of 13 C nuclei  But hydrogens in organic molecules are not isolated from all other atoms; they are surrounded by electrons, which are caused to circulate by the presence of the applied field

16. 13 13-16 Nuclear Magnetic Resonance diamagnetic current diamagnetic shielding  The circulation of electrons around a nucleus in an applied field is called diamagnetic current and the nuclear shielding resulting from it is called diamagnetic shielding  The difference in resonance frequencies among the various hydrogen nuclei within a molecule due to shielding/deshielding is generally very small

17. 13 13-17 Nuclear Magnetic Resonance  The difference in resonance frequencies for hydrogens in CH 3 Cl compared to CH 3 F under an applied field of 7.05T is only 360 Hz, which is 1.2 parts per million (ppm) compared with the irradiating frequency

18. 13 13-18 Nuclear Magnetic Resonance  It is customary to measure the resonance frequency (signal) of individual nuclei relative to the resonance frequency (signal) of a reference compound  The reference compound now universally accepted is tetramethylsilane (TMS)

19. 13 13-19 Nuclear Magnetic Resonance  For a 1 H-NMR spectrum, signals are reported by their shift from the 12 H signal in TMS  For a 13 C-NMR spectrum, signals are reported by their shift from the 4 C signal in TMS  Chemical shift (  ):  Chemical shift (  ): the shift in ppm of an NMR signal from the signal of TMS

20. 13 13-20 NMR spectrometer

21. 13 13-21 NMR Spectrometer  Essentials of an NMR spectrometer are a powerful magnet, a radio-frequency generator, and a radio-frequency detector  The sample is dissolved in a solvent, most commonly CDCl 3 or D 2 O, and placed in a sample tube which is then suspended in the magnetic field and set spinning  Using a Fourier transform NMR (FT-NMR) spectrometer, a spectrum can be recorded in about 2 seconds

22. 13 13-22 NMR Spectrum  1 H-NMR spectrum of methyl acetate Downfield:Downfield: the shift of an NMR signal to the left on the chart paper Upfield:Upfield: the shift of an NMR signal to the right on the chart paper

23. 13 13-23 Equivalent Hydrogens  Equivalent hydrogens:  Equivalent hydrogens: have the same chemical environment a molecule with 1 set of equivalent hydrogens gives 1 NMR signal

24. 13 13-24 Equivalent Hydrogens a molecule with 2 or more sets of equivalent hydrogens gives a different NMR signal for each set

25. 13 13-25 Signal Areas  Relative areas of signals are proportional to the number of H giving rise to each signal  Modern NMR spectrometers electronically integrate and record the relative area of each signal

26. 13 13-26 Chemical Shift - 1 H-NMR

27. 13 13-27 Chemical Shift - 1 H-NMR

28. 13 13-28 Chemical Shift  Depends on (1) electronegativity of nearby atoms, (2) the hybridization of adjacent atoms, and (3) diamagnetic effects from adjacent pi bonds electronegativity

29. 13 13-29 Chemical Shift hybridization of adjacent atoms

30. 13 13-30 Chemical Shift  Magnetic induction in pi bonds of a a carbon-carbon triple bond shields an acetylenic hydrogen and shifts its signal upfield (to the right) to a smaller  value a carbon-carbon double bond deshields vinylic hydrogens and shifts their signal downfield (to the left) to a larger  value

31. 13 13-31 Chemical Shift magnetic induction in the pi bonds of carbon- carbon triple bond (Fig 13.7)

32. 13 13-32 Chemical Shift magnetic induction in the pi bond of a carbon- carbon double bond (Fig 13.8)

33. 13 13-33 Chemical Shift magnetic induction of the pi electrons in an aromatic ring (Fig. 13.9)

34. 13 13-34 Signal Splitting (n + 1)  Peak:  Peak: the units into which an NMR signal is split; doublet, triplet, quartet, etc.  Signal splitting:  Signal splitting: splitting of an NMR signal into a set of peaks by the influence of neighboring nonequivalent hydrogens  (n + 1) rule:  (n + 1) rule: the 1 H-NMR signal of a hydrogen or set of equivalent hydrogens is split into (n + 1) peaks by a nonequivalent set of n equivalent neighboring hydrogens

35. 13 13-35 Signal Splitting (n + 1) 1 H-NMR spectrum of 1,1-dichloroethane

36. 13 13-36 Signal Splitting (n + 1) Problem Problem: predict the number of 1 H-NMR signals and the splitting pattern of each

37. 13 13-37 Origin of Signal Splitting  When the chemical shift of one nucleus is influenced by the spin of another, the two are said to be coupled  Consider nonequivalent hydrogens H a and H b on adjacent carbons the chemical shift of H a is influenced by whether the spin of H b is aligned with or against the applied field

38. 13 13-38 Origin of Signal Splitting

39. 13 13-39 Origin of Signal Splitting  The signal of H a is split into two peaks of equal area (a doublet) by its nonequivalent neighbor H b.

40. 13 13-40 Signal Splitting  Pascal’s Triangle. As illustrated by the highlighted entries, each entry is the sum of the values immediately above it to the left and the right.

41. 13 13-41

42. 13 13-42 Coupling Constants  Coupling constant (J):  Coupling constant (J): the distance between peaks in a split signal, expressed in hertz the value is a quantitative measure of the magnetic interaction of nuclei whose spins are coupled

43. 13 13-43 Coupling Constants  J ab for a doublet and a triplet from splitting of H a by nonequivalent hydrogen(s) H b.

44. 13 13-44 Coupling Constants 1 H-NMR spectrum of 3-pentanone; scale expansion shows the triplet quartet pattern more clearly

45. 13 13-45 Stereochem & Topicity  Depending on the symmetry of a molecule, otherwise equivalent hydrogens may be homotopic enantiotopic diastereotopic  The simplest way to visualize topicity is to substitute an atom or group by an isotope. Is the resulting compound the same as its mirror image different from its mirror image are diastereomers possible

46. 13 13-46 Stereochem & Topicity  Homotopic atoms or groups homotopic atoms or groups have identical chemical shifts under all conditions

47. 13 13-47 Stereochem & Topicity  Enantiotopic groups enantiotopic atoms or groups have identical chemical shifts in achiral environments they have different chemical shifts in achiral environments

48. 13 13-48 Stereochem & Topicity  Diastereotopic groups H atoms on C-3 of 2-butanol are diastereotopic substitution by deuterium creates a stereocenter because there is already a stereocenter in the molecule, diastereomers are now possible diastereotopic hydrogens have different chemical shifts under all conditions

49. 13 13-49 Stereochem & Topicity  The methyl groups on carbon 3 of 3-methyl-2- butanol are diastereotopic if a methyl hydrogen of carbon 4 is substituted by deuterium, a new stereocenter is created because there is already one stereocenter, diastereomers are now possible protons of the methyl groups on carbon 3 have different chemical shifts

50. 13 13-50 Stereochem and Topicity  1 H-NMR spectrum of 3-methyl-2-butanol the methyl groups on carbon 3 are diastereotopic and appear as two doublets

51. 13 13-51 13 C-NMR Spectroscopy  Each nonequivalent 13 C gives a different signal a 13 C signal is split by the 1 H bonded to it according to the (n + 1) rule coupling constants of 100-250 Hz are common, which means that there is often significant overlap between signals, and splitting patterns can be very difficult to determine  The most common mode of operation of a 13 C- NMR spectrometer is a hydrogen-decoupled mode

52. 13 13-52 13 C-NMR Spectroscopy  In a hydrogen-decoupled mode, a sample is irradiated with two different radio frequencies one to excite all 13 C nuclei a second broad spectrum of frequencies to cause all hydrogens in the molecule to undergo rapid transitions between their nuclear spin states  On the time scale of a 13 C-NMR spectrum, each hydrogen is in an average or effectively constant nuclear spin state, with the result that 1 H- 13 C spin-spin interactions are not observed; they are decoupled

53. 13 13-53 13 C-NMR Spectroscopy hydrogen decoupled 13 C-NMR spectrum

54. 13 13-54 Chemical Shift - 13 C-NMR

55. 13 13-55 The DEPT Method  In the hydrogen-decoupled mode, information on spin-spin coupling between 13 C and attached hydrogens is lost  The DEPT method is an instrumental mode that provides a way to acquire this information Distortionless Enhancement by Polarization TransferDEPTDistortionless Enhancement by Polarization Transfer (DEPT) is an NMR technique for distinguishing among 13 C signals for CH 3, CH 2, CH, and quaternary carbons

56. 13 13-56 The DEPT Method  The DEPT methods uses a complex series of pulses in both the 1 H and 13 C ranges, with the result that CH 3, CH 2, and CH signals exhibit different phases; signals for CH 3 and CH carbons are recorded as positive signals signals for CH 2 carbons are recorded as negative signals quaternary carbons give no signal in the DEPT method

57. 13 13-57 Isopentyl acetate (a) proton decoupled and (b) DEPT

58. 13 13-58 Interpreting NMR Spectra  Alkanes 1 H-NMR signals appear in the range of  0.8-1.7 13 C-NMR signals appear in the considerably wider range of  10-60  Alkenes 1 H-NMR signals appear in the range  4.6-5.7 1 H-NMR coupling constants are generally larger for trans vinylic hydrogens (J= 11-18 Hz) compared with cis vinylic hydrogens (J= 5-10 Hz) 13 C-NMR signals for sp 2 hybridized carbons appear in the range  100-160, which is downfield from the signals of sp 3 hybridized carbons

59. 13 13-59 Interpreting NMR Spectra 1 H-NMR spectrum of vinyl acetate (Fig 13.18)

60. 13 13-60 Interpreting NMR Spectra graphical analysis of signal splitting of the three vinylic hydrogens in vinyl acetate (Fig 13.19)

61. 13 13-61 Interpreting NMR Spectra  Alcohols  1 H-NMR O-H chemical shifts often appears in the range  3.0-4.0, but may be as low as  0.5. 1 H-NMR chemical shifts of hydrogens on the carbon bearing the -OH group are deshielded by the electron-withdrawing inductive effect of the oxygen and appear in the range  3.0-4.0  Ethers a distinctive feature in the 1 H-MNR spectra of ethers is the chemical shift,  3.3-4.0, of hydrogens on carbon attached to the ether oxygen

62. 13 13-62 Interpreting NMR Spectra 1 H-NMR spectrum of 1-propanol (Fig. 13.20)

63. 13 13-63 Interpreting NMR Spectra  Aldehydes and ketones 1 H-NMR: aldehyde hydrogens appear at  9.5-10.1 1 H-NMR:  -hydrogens of aldehydes and ketones appear at  2.2-2.6 13 C-NMR: carbonyl carbons appear at  180-215  Carboxylic acids 1 H-NMR: carboxyl hydrogens appear at  10-13, lower than most any other hydrogens 13 C-NMR: carboxyl carbons appear at  160-180  Amines 1 H-NMR: amine hydrogens appear at  0.5-5.0 depending on conditions

64. 13 13-64 Index of H Deficiency  Index of hydrogen deficiency (IHD):  Index of hydrogen deficiency (IHD): the sum of the number of rings and pi bonds in a molecule  To determine IHD, compare the number of hydrogens in an unknown compound with the number in a reference hydrocarbon of the same number of carbons and with no rings or pi bonds the molecular formula of the reference hydrocarbon is C n H 2n+2

65. 13 13-65 Index of H Deficiency for each atom of a Group 7 element (F, Cl, Br, I), add one H no correction is necessary for the addition of atoms of Group 6 elements (O,S) to the reference hydrocarbon for each atom of a Group 5 element (N, P), subtract one hydrogen

66. 13 13-66 Index of H Deficiency Problem: Problem: isopentyl acetate has a molecular formula of C 7 H 14 O 2. Calculate its IHD reference hydrocarbon C 7 H 16 IHD = (16-14)/2 = 1 Problem: Problem: calculate the IHD for niacin, molecular formula C 6 H 6 N 2 O reference hydrocarbon C 6 H 16 IHD = (16 - 6)/2 = 5

67. 13 13-67 Prob 13.13 Calculate the index of hydrogen deficiency of each compound.

68. 13 13-68 Prob 13.16 Assign each constitutional isomers its spectrum.

69. 13 13-69 Prob 13.17 Assign each compound its 13 C spectrum.

70. 13 13-70 Prob 13.23 Compound K, molecular formula C 6 H 14 O, readily undergoes acid-catalyzed dehydration when warmed with phosphoric acid to give compound L, molecular formula C 6 H 12, as the major organic product. The 1 H-NMR spectrum of compound K shows signals at  0.90 (t, 6H), 1.12 (s, 3H), 1.38 (s, 1H), and 1.48 (q, 4H). The 13 C-NMR spectrum of compound K shows signals at  72.98, 33.72, 25.85, and 8.16. Deduce the structural formulas of compounds K and L.

71. 13 13-71 Prob 13.28 Assign each carbon in each compound its correct 13 C chemical shift.

72. 13 13-72 Prob 13.28 (cont’d) Assign each carbon in each compound its correct 13 C chemical shift.

73. 13 13-73 Prob 13.28 (cont’d) Assign each carbon in each compound its correct 13 C chemical shift.

74. 13 13-74 Prob 13.28 (cont’d) Assign each carbon in each compound its correct 13 C chemical shift.

75. 13 13-75 Nuclear Magnetic Resonance End Chapter 13