Organic Chemistry

1. Organic Chemistry William H. Brown Christopher S. Foote Brent L. Iverson

2. Nuclear Magnetic Resonance Chapter 13

3. Molecular 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 1H-NMR spectroscopy carbon atoms using 13C-NMR spectroscopy phosphorus atoms using 31P-NMR spectroscopy

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 The same effect holds for certain atomic nuclei any atomic nucleus that has an odd mass number, 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

5. Nuclear Spin States a nucleus with spin quantum number I has 2I + 1 spin states; if I = 1/2, there are two allowed spin states Table 13.1 gives the spin quantum numbers and allowed nuclear spin states for selected isotopes of elements common to organic compounds

6. Nuclear Spins in B0 within a collection of 1H and 13C atoms, nuclear spins are completely random in orientation when placed in a strong external magnetic field of strength B0, 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

7. Nuclear Spins in B0 for 1H and 13C, only two orientations are allowed

8. Nuclear Spins in B0 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 1H is approximately 0.120 J (0.0286 cal)/mol, which corresponds to electromagnetic radiation of 300 MHz (300,000,000 Hz) 13C is approximately 0.030 J (0.00715 cal)/mol, which corresponds to electromagnetic radiation of 75MHz (75,000,000 Hz)

9. Nuclear Spin in B0 the energy difference between allowed spin states increases linearly with applied field strength values shown here are for 1H nuclei

10. 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

11. 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)

12. Nuclear Magnetic Resonance Figure 13.3 the origin of nuclear magnetic �resonance

13. Nuclear Magnetic Resonance Resonance: in NMR spectroscopy, resonance is the absorption of electromagnetic radiation by a precessing nucleus and the resulting �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 signal: a recording in an NMR spectrum of a nuclear magnetic resonance

14. Nuclear Magnetic Resonance if we were dealing with 1H nuclei isolated from all other atoms and electrons, any combination of applied field and radiation that produces a signal for one 1H would produce a signal for all 1H. The same is true of 13C 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 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

15. Nuclear Magnetic Resonance the difference in resonance frequencies among the various hydrogen nuclei within a molecule due to shielding/deshielding is generally very small the difference in resonance frequencies for hydrogens in CH3Cl compared to CH3F under an applied field of 7.05T is only 360 Hz, which is 1.2 parts per million (ppm) compared with the irradiating frequency

16. Nuclear Magnetic Resonance signals are measured relative to the signal of the reference compound tetramethylsilane (TMS) for a 1H-NMR spectrum, signals are reported by their shift from the 12 H signal in TMS for a 13C-NMR spectrum, signals are reported by their shift from the 4 C signal in TMS Chemical shift (?): the shift in ppm of an NMR signal from the signal of TMS

17. NMR Spectrometer

18. 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 CDCl3 or D2O, 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

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

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

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

22. 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

24. Chemical Shift - 1H-NMR

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

26. Chemical Shift Hybridization of adjacent atoms

27. Chemical Shift Diamagnetic effects of pi bonds 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

28. Chemical Shift magnetic induction in the pi bonds of a carbon-carbon triple bond (Fig 13.9)

29. Chemical Shift magnetic induction in the pi bond of a carbon-carbon double bond (Fig 13.10)

30. Chemical Shift magnetic induction of the pi electrons in an aromatic ring (Fig. 13.11)

31. Signal Splitting; the (n + 1) Rule Peak: the units into which an NMR signal is split; doublet, triplet, quartet, etc. Signal splitting: splitting of an NMR signal into a set of peaks by the influence of neighboring nonequivalent hydrogens (n + 1) rule: if a hydrogen has n hydrogens nonequivalent to it but equivalent among themselves on the same or adjacent atom(s), its 1H-NMR signal is split into (n + 1) peaks

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

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

34. Origins of Signal Splitting Signal coupling: an interaction in which the nuclear spins of adjacent atoms influence each other and lead to the splitting of NMR signals Coupling constant (J): the separation on an NMR spectrum (in hertz) between adjacent peaks in a multiplet; a quantitative measure of the influence of the spin-spin coupling with adjacent nuclei

35. Origins of Signal Splitting

36. Origins of Signal Splitting because splitting patterns from spectra taken at 300 MHz and higher are often difficult to see, it is common to retrace certain signals in expanded form 1H-NMR spectrum of 3-pentanone; scale expansion shows the triplet quartet pattern more clearly

37. Coupling Constants 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

38. Origins of Signal Splitting

39. 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

40. Physical Basis for (n + 1) Rule Coupling of nuclear spins is mediated through intervening bonds H atoms with more than three bonds between them generally do not exhibit noticeable coupling for H atoms three bonds apart, the coupling is referred to as vicinal coupling

41. Coupling Constants an important factor in vicinal coupling is the angle a between the C-H sigma bonds and whether or not it is fixed coupling is a maximum when a is 0� and 180�; it is a minimum when a is 90�

42. More Complex Splitting Patterns thus far, we have concentrated on spin-spin coupling with only one other nonequivalent set of H atoms more complex splittings arise when a set of H atoms couples to more than one set H atoms a tree diagram shows that when Hb is adjacent to nonequivalent Ha on one side and Hc on the other, the resulting coupling gives rise to a doublet of doublets

43. More Complex Splitting Patterns if Hc is a set of two equivalent H, then the observed splitting is a doublet of triplets

44. More Complex Splitting Patterns because the angle between C-H bond determines the extent of coupling, bond rotation is a key parameter in molecules with relatively free rotation about C-C sigma bonds, H atoms bonded to the same carbon in CH3 and CH2 groups generally are equivalent if there is restricted rotation, as in alkenes and cyclic structures, H atoms bonded to the same carbon may not be equivalent nonequivalent H on the same carbon will couple and cause signal splitting this type of coupling is called geminal coupling

45. More Complex Splitting Patterns in ethyl propenoate, an unsymmetrical terminal alkene, the three vinylic hydrogens are nonequivalent

46. More Complex Splitting Patterns a tree diagram for the complex coupling of the three vinylic hydrogens in ethyl propenoate

47. More Complex Splitting Patterns cyclic structures often have restricted rotation about their C-C bonds and have constrained conformations as a result, two H atoms on a CH2 group can be nonequivalent, leading to complex splitting

48. More Complex Splitting Patterns a tree diagram for the complex coupling in 2-methyl-2-vinyloxirane

49. More Complex Splitting Patterns Complex coupling in flexible molecules coupling in molecules with unrestricted bond rotation often gives only m + n + I peaks that is, the number of peaks for a signal is the number of adjacent hydrogens + 1, no matter how many different sets of equivalent H atoms that represents the explanation is that bond rotation averages the coupling constants throughout molecules with freely rotation bonds and tends to make them similar; for example in the 6- to 8-Hz range for H atoms on freely rotating sp3 hybridized C atoms

50. More Complex Splitting Patterns simplification of signal splitting occurs when coupling constants are the same

51. More Complex Splitting Patterns an example of peak overlap occurs in the spectrum of 1-chloro-3-iodopropane the central CH2 has the possibility for 9 peaks (a triplet of triplets) but because Jab and Jbc are so similar, only 4 + 1 = 5 peaks are distinguishable

52. Stereochemistry & 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

53. Stereochemistry & Topicity Homotopic atoms or groups homotopic atoms or groups have identical chemical shifts under all conditions

54. Stereochemistry & Topicity Enantiotopic groups enantiotopic atoms or groups have identical chemical shifts in achiral environments they have different chemical shifts in chiral environments

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

56. Stereochemistry & 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 chiral center is created because there is already one chiral center, diastereomers are now possible protons of the methyl groups on carbon 3 have different chemical shifts

57. Stereochemistry and Topicity 1H-NMR spectrum of 3-methyl-2-butanol the methyl groups on carbon 3 are diastereotopic and appear as two doublets

58. 13C-NMR Spectroscopy Each nonequivalent 13C gives a different signal a 13C signal is split by the 1H 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 13C-NMR spectrometer is a hydrogen-decoupled mode

59. 13C-NMR Spectroscopy In a hydrogen-decoupled mode, a sample is irradiated with two different radio frequencies one to excite all 13C 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 13C-NMR spectrum, each hydrogen is in an average or effectively constant nuclear spin state, with the result that 1H-13C spin-spin interactions are not observed; they are decoupled

60. 13C-NMR Spectroscopy hydrogen-decoupled 13C-NMR spectrum of 1-bromobutane

61. Chemical Shift - 13C-NMR

62. Chemical Shift - 13C-NMR

63. The DEPT Method In the hydrogen-decoupled mode, information on spin-spin coupling between 13C and hydrogens bonded to it is lost The DEPT method is an instrumental mode that provides a way to acquire this information Distortionless Enhancement by Polarization Transfer (DEPT): an NMR technique for distinguishing among 13C signals for CH3, CH2, CH, and quaternary carbons

64. The DEPT Method The DEPT methods uses a complex series of pulses in both the 1H and 13C ranges, with the result that CH3, CH2, and CH signals exhibit different phases; signals for CH3 and CH carbons are recorded as positive signals signals for CH2 carbons are recorded as negative signals quaternary carbons give no signal in the DEPT method

65. Isopentyl acetate 13C-NMR: (a) proton decoupled and (b) DEPT

66. Interpreting NMR Spectra Alkanes 1H-NMR signals appear in the range of ? 0.8-1.7 13C-NMR signals appear in the considerably wider range of ? 10-60 Alkenes 1H-NMR signals appear in the range ? 4.6-5.7 1H-NMR coupling constants are generally larger for trans vinylic hydrogens (J= 11-18 Hz) compared with cis vinylic hydrogens (J= 5-10 Hz) 13C-NMR signals for sp2 hybridized carbons appear in the range ? 100-160, which is downfield from the signals of sp3 hybridized carbons

67. Interpreting NMR Spectra 1H-NMR spectrum of vinyl acetate (Fig 13.33)

68. Interpreting NMR Spectra Alcohols 1H-NMR O-H chemical shifts often appears in the range ? 3.0-4.0, but may be as low as ? 0.5. 1H-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 1H-MNR spectra of ethers is the chemical shift, ? 3.3-4.0, of hydrogens on carbon attached to the ether oxygen

69. Interpreting NMR Spectra 1H-NMR spectrum of 1-propanol (Fig. 13.34)

70. Interpreting NMR Spectra Aldehydes and ketones 1H-NMR: aldehyde hydrogens appear at ? 9.5-10.1 1H-NMR: a-hydrogens of aldehydes and ketones appear at ? 2.2-2.6 13C-NMR: carbonyl carbons appear at ? 180-215 Amines 1H-NMR: amine hydrogens appear at ? 0.5-5.0 depending on conditions

71. Interpreting NMR Spectra Carboxylic acids 1H-NMR: carboxyl hydrogens appear at ? 10-13, lower than most any other hydrogens 13C-NMR: carboxyl carbons in acids and esters appear at ? 160-180

72. Interpreting NMR Spectra Spectral Problem 1; molecular formula C5H10O

73. Interpreting NMR Spectra Spectral Problem 2; molecular formula C7H14O

74. Nuclear Magnetic Resonance End Chapter 13