Nuclear Magnetic Resonance Spectroscopy: Tools for Structure Determination

Transcription

1 Nuclear Magnetic Resonance Spectroscopy: Tools for Structure Determination Chung-Ming Sun Department of Applied Chemistry National Chiao Tung University Hualien 300, Taiwan

2 Introduction NMR (Nuclear Magnetic Resonance) is the most powerful tool available for organic structure determination. It is used to study a wide variety of nuclei: 1 H 13 C 15 N 19 F 31 P => Chapter 13 2

3 Nuclear Spin A nucleus with an odd atomic number or an odd mass number has a nuclear spin. 1 H has a spin quantum number I = 1/2 and has allowed spin states of +1/2 or -1/2 Other nuclei with I = 1/2 are 13 C, 19 F and 31 P and these also respond to an external magnetic field Nuclei with I = 0 do not have spin ( 12 C and 16 O) and do not respond to an external magnetic field Chapter 13 3

4 The spinning charged nucleus generates a magnetic field. Chapter 13 4

5 External Magnetic Field When placed in an external field, spinning protons act like bar magnets. The nuclei of NMR-active nuclei behave like tiny bar magnets Chapter 13 5 =>

6 alpha-spin state and beta-spin state Chapter 13 6

7 Nuclear Spin: The Origin of the Signal Chapter 13 7

8 In the absence of an external magnetic field, proton magnetic oments have random orientations. Chapter 13 8

9 The magnetic fields of the spinning nuclei will align either with the external field, or against the field. A photon with the right amount of energy can be absorbed and cause the spinning proton to flip. NMR absortion Chapter 13 9

10 E and Magnet Strength Energy difference is proportional to the magnetic field strength. E = h = h B 0 2 Gyromagnetic ratio,, is a constant for each nucleus (26,753 s -1 gauss -1 for H). In a 14,092 gauss field, a photon of 60 MHz is required to flip a proton. Low energy, radio frequency. => Chapter 13 10

11 NMR involves absorption of energy in the radiofrequency rang p.510 Chapter 13 11

12 The stronger the external magnetic field, the higher the radio frequency energy required to flip the nuclear spin Chapter 13 12

13 Magnetic Shielding If all protons absorbed the same amount of energy in a given magnetic field, not much information could be obtained. But protons are surrounded by electrons that shield them from the external field. Circulating electrons create an induced magnetic field that opposes the external magnetic field. => Chapter 13 13

14 Shielded Protons Magnetic field strength must be increased for a shielded proton to flip at the same frequency. Chapter 13 14

15 Protons in a Molecule Depending on their chemical environment, protons in a molecule are shielded by different amounts. Chapter =>

16 NMR Signals The number of signals shows how many different kinds of protons are present. The location of the signals shows how shielded or deshielded the proton is. The intensity of the signal shows the number of protons of that type. Signal splitting shows the number of protons on adjacent atoms. => Chapter 13 16

17 The NMR Spectrometer Chapter =>

18 Chapter 13 18

19 The NMR Graph The absorptions of more shielded protons appear upfield, toward the right of the spectrum Chapter =>

20 H 3 C CH 3 Si CH 3 CH 3 Tetramethylsilane TMS is added to the sample. Since silicon is less electronegative than carbon, TMS protons are highly shielded. Signal defined as zero. Organic protons absorb downfield (to the left) of the TMS signal. Chapter 13 20

21 Chemical Shift Measured in parts per million (ppm). Ratio of shift downfield from TMS (Hz) to total spectrometer frequency (Hz). Same value for 60, 100, or 300 MHz NMR machine. Called the delta (d) scale. Each d unit is 1 ppm difference from TMS: 60 Hz at 60 MHz and 300 Hz at 300 MHz Chapter 13 21

22 Table 13-1 The chemical shift of the methyl protons depends on the electronegativity of the substituent. With more electronegative substituents deshielding more and giving larger chemical shifts. The effect of an electron-withdrawing substituent decreases with increasing distance. Chapter 13 22

23 Delta Scale Chapter =>

24 Location of Signals More electronegative atoms deshield more and give larger shift values. Effect decreases with distance (< four bonds). Additional electronegative atoms cause increase in chemical shift about 2-3 ppm each time. Chapter 13 24

25 Typical Values Chapter =>

26 Aromatic Protons, d7-8 ppm => Chapter 13 26

27 Chapter 13 27

28 Vinyl Protons, d5-6 ppm Chapter =>

29 Acetylenic Protons, d2.5 Chapter =>

30 Aldehyde Proton, d9-d10 Electronegative oxygen atom Chapter =>

31 O-H and N-H Signals Chemical shift depends on concentration. Hydrogen bonding in concentrated solutions deshield the protons, so signal is around d 3.5 for N-H and d 4.5 for O-H. Proton exchanges between the molecules broaden the peak. Chapter 13 31

32 Carboxylic Acid Proton, d10+ Chapter =>

33 Number of Signals Equivalent hydrogens have the same chemical shift. Chapter =>

34 Intensity of Signals The area under each peak is proportional to the number of protons. Shown by integral trace. Chapter =>

35 How Many Hydrogens? When the molecular formula is known, each integral rise can be assigned to a particular number of hydrogens (p.575). Chapter 13 35

36 Spin-Spin Splitting Nonequivalent protons on adjacent carbons have magnetic fields that may align with or oppose the external field. This magnetic coupling causes the proton to absorb slightly downfield when the external field is reinforced and slightly upfield when the external field is opposed. All possibilities exist, so signal is split. Chapter 13 36

37 1,1,2-Tribromoethane Nonequivalent protons on adjacent carbons. Chapter =>

38 Doublet: 1 Adjacent Proton => Chapter 13 38

39 Triplet: 2 Adjacent Protons => Chapter 13 39

40 The N + 1 Rule If a signal is split by N equivalent protons, it is split into N + 1 peaks. Chapter =>

41 Range of Magnetic Coupling (p.579) Equivalent protons do not split each other. Protons bonded to the same carbon will split each other only if they are not equivalent- 2 J(geminal coupling) Protons on adjacent carbons normally will couple- 3 J(vicinal coupling) Protons separated by four or more bonds will not couple( 距離太遠 )- 4 J~0 => Chapter 13 41

42 Chapter 13 42

43 Splitting for Ethyl Groups p.579 => Chapter 13 43

44 Roof effect A multiplet often lean upward toward the protons that are causing the splitting Chapter 13 44

45 Splitting for Isopropyl Groups (p.581) => Chapter 13 45

46 Coupling Constants (J) Distance between the peaks of multiplet Measured in Hz Not dependent on strength of the external field Multiplets with the same coupling constants may come from adjacent groups of protons that split each other (p.581). Chapter 13 46

47 Values for Coupling Constants => Chapter 13 47

48 Para, ortho and meta isomers of nitrotoluene Chapter 13 48

49 Cis coupling constant of two vinyl protons is J = 9 Hz. Chapter 13 49

50 trans coupling constant of two vinyl protons is J = 15 Hz. (p.584) Chapter 13 50

51 H a C C c H Hb Complex Splitting Signals may be split by adjacent protons, different from each other, with different coupling constants. Example: H a of styrene which is split by an adjacent H trans to it (J = 17 Hz) and an adjacent H cis to it (J = 11 Hz). => Chapter 13 51

52 H a C C c H Hb Splitting Tree => Chapter 13 52

53 Spectrum for Styrene => Chapter 13 53

54 Stereochemical Nonequivalence Usually, two protons on the same C are equivalent and do not split each other. If the replacement of each of the protons of a -CH 2 group with an imaginary Z gives stereoisomers, then the protons are nonequivalent and will split each other. => Chapter 13 54

55 Some Nonequivalent Protons H a C C c H Hb d H c H a OH H b CH 3 H Cl ah Hb => Cl Chapter 13 55

56 Chapter 13 56

57 Chapter 13 57

58 Chapter 13 58

59 H c (H e ) are diastereotopic to H d (H f ) and two sets of protons absorb at different magnetic field and are capable of splitting each other Chapter 13 59

60 The two protons on the CH 2 Cl group are diastereotopic Chapter 13 60

61 Diastereotopic protons in 1,2- dichloropropane Chapter 13 61

62 Time Dependence Molecules are tumbling relative to the magnetic field, so NMR is an averaged spectrum of all the orientations. Axial and equatorial protons on cyclohexane interconvert so rapidly that they give a single signal.(p.591) Proton transfers for OH and NH may occur so quickly that the proton is not split by adjacent protons in the molecule. => Chapter 13 62

63 Chapter 13 63

64 Hydroxyl Proton Ultrapure samples of ethanol show splitting. Ethanol with a small amount of acidic or basic impurities will not show splitting. Chapter =>

65 N-H Proton Moderate rate of exchange. Peak may be broad. => Chapter 13 65

66 Identifying the O-H or N-H Peak Chemical shift will depend on concentration and solvent. To verify that a particular peak is due to O-H or N-H, shake the sample with D 2 O Deuterium will exchange with the O-H or N-H protons. On a second NMR spectrum the peak will be absent, or much less intense. Chapter 13 66

67 Common chemical shifts in the 1 H NMR spectrum(p-594) Chapter 13 67

68 Carbon C has no magnetic spin. 13 C has a magnetic spin, but is only 1% of the carbon in a sample. The gyromagnetic ratio of 13 C is onefourth of that of 1 H. Signals are weak, getting lost in noise. Hundreds of spectra are taken, averaged. => Chapter 13 68

69 Fourier Transform NMR Nuclei in a magnetic field are given a radio-frequency pulse close to their resonance frequency. The nuclei absorb energy and precess (spin) like little tops. A complex signal is produced, then decays as the nuclei lose energy. Free induction decay is converted to spectrum. => Chapter 13 69

70 Hydrogen and Carbon Chemical Shifts Chapter =>

71 Combined 13 C and 1 H Spectra Chapter =>

72 Differences in 13 C Technique Resonance frequency is ~ one-fourth, 15.1 MHz instead of 60 MHz. Peak areas are not proportional to number of carbons. Carbon atoms with more hydrogens absorb more strongly. => Chapter 13 72

73 Spin-Spin Splitting It is unlikely that a 13 C would be adjacent to another 13 C, so splitting by carbon is negligible. 13 C will magnetically couple with attached protons and adjacent protons. These complex splitting patterns are difficult to interpret. => Chapter 13 73

74 Proton Spin Decoupling To simplify the spectrum, protons are continuously irradiated with noise, so they are rapidly flipping. The carbon nuclei see an average of all the possible proton spin states. Thus, each different kind of carbon gives a single, unsplit peak. => Chapter 13 74

75 Off-Resonance Decoupling 13 C nuclei are split only by the protons attached directly to them. The N + 1 rule applies: a carbon with N number of protons gives a signal with N + 1 peaks. => Chapter 13 75

76 Interpreting 13 C NMR The number of different signals indicates the number of different kinds of carbon. The location (chemical shift) indicates the type of functional group. The peak area indicates the numbers of carbons (if integrated). The splitting pattern of off-resonance decoupled spectrum indicates the number of protons attached to the carbon. => Chapter 13 76

77 Two 13 C NMR Spectra Chapter =>

78 Chapter 13 78

79 MRI Magnetic resonance imaging, noninvasive Nuclear is omitted because of public s fear that it would be radioactive. Only protons in one plane can be in resonance at one time. Computer puts together slices to get 3D. Tumors readily detected. => Chapter 13 79