Used to determine relative location of atoms within a molecule Most helpful spectroscopic technique in organic chemistry Related to MRI in medicine

Transcription

1 Structure Determination: Nuclear Magnetic Resonance CHEM 241 UNIT 5C 1

2 The Use of NMR Spectroscopy Used to determine relative location of atoms within a molecule Most helpful spectroscopic technique in organic chemistry Related to MRI in medicine (Magnetic Resonance Imaging) Maps carbon-hydrogen framework of molecules Depends on very strong magnetic fields 2

3 Nuclear Magnetic Resonance Spectroscopy 1 H or 13 C nucleus spins and the internal magnetic field aligns parallel to or against an aligned external magnetic field (See Figure 13.1) Parallel orientation is lower in energy making this spin state more populated Radio energy of exactly correct frequency (resonance) causes nuclei to flip into anti-parallel state Energy needed is related to molecular environment (proportional to field strength, B) see Figure

4 NMR Spectroscopy When a sample containing these nuclei is placed between the poles of a strong magnet, the nuclei orient themselves with the magnetic field like the needle of a compass. These two orientations do not have the same energy and therefore are not equally likely to occur. 4

5 Resonance 5

6 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) 6

7 Resonance The nucleus begins to precess and traces out a cone-shaped surface, in much the same way a spinning top or gyroscope traces out cone-shaped surface as it precesses in the earth s gravitational field We express the rate of precession as a frequency in hertz 7

8 The Nature of NMR Absorptions Electrons in bonds shield nuclei from magnetic field Different signals appear for nuclei in different environments 1 H 13 C 8

9 The NMR Measurement The sample is dissolved in a solvent that does not have a signal itself and placed in a long thin tube The tube is placed within the gap of a magnet and spun Radiofrequency energy is transmitted and absorption is detected Species that interconvert give an averaged signal that can be analyzed to find the rate of conversion 9

10 The NMR Measurement 10

11 Chemical Shifts The relative energy of resonance of a particular nucleus resulting from its local environment is called chemical shift NMR spectra show applied field strength increasing from left to right Left part is downfield; right part is upfield Nuclei that absorb on upfield side are strongly shielded. Chart calibrated versus a reference point, set as 0, tetramethylsilane [TMS] 11

12 Measuring Chemical Shift Numeric value of chemical shift: difference between strength of magnetic field at which the observed nucleus resonates and field strength for resonance of a reference Difference is very small but can be accurately measured Taken as a ratio to the total field and multiplied by 10 6 so the shift is in parts per million (ppm) Absorptions normally occur downfield of TMS, to the left on the chart Calibrated on relative scale in delta (δ) scale δ is the number of parts per million (ppm) of the magnetic field expressed as the spectrometer s operating frequency (used ahead of value as it is a ratio and not a unit) Independent of instrument s field strength 12

13 13

14 Nuclear Spin States Elements with either odd mass or odd atomic number have the property of nuclear spin. The number of spin states is 2I + 1, where I is the spin quantum number (allowed values I, I..) 14

15 Nuclear Magnetic 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

16 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

17 Nuclear Magnetic Resonance 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

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) CH 3 H 3 C Si CH 3 CH 3 Tetramethylsilane (TMS) 18

19 NMR Spectra 19

20 Nuclear Magnetic Resonance For a 1 H-NMR spectrum, signals are reported by their shift from the H signal in TMS For a 13 C-NMR spectrum, signals are reported by their shift from the C signal in TMS Chemical shift (δ): the shift in ppm of an NMR signal from the signal of TMS Observed chemical shift (number of Hz away from TMS) δ = Spectrometer frequency in MHz this division gives a number independent of the instrument used 20

21 Nature of NMR Absorptions Local magnetic fields act in opposition to the applied magnetic field. The effective magnetic filed felt by the nucleus is smaller then the applied field. H effective = H applied - H local 21

22 Shielding Nuclei are shielded from the full effect of the applied field by the circulating electrons that surround them. Each nucleus in a molecule is in a slightly different electronic environment. 22

23 The Shielding Effect Electrons under the influence of a magnetic field generate their own magnetic field opposing the applied field-the shielding effect. Shielding exists within the cones of concentrated electrons and deshielding occurs outside these cones. 23

24 Shielding Effects The position of an NMR peak is controlled by the shielding or deshielding of the nucleus (by electrons). The free proton is a nucleus free of any influence by exterior, electronic. However organic molecules contain covalently bonded nuclei, not free protons. 24

25 Shielding Effects Protons in organic molecules are surrounded by electrons. The electron density about the protons varies according to several factors: bond polarity the hybridization state of the atom to which a given hydrogen is bonded the presence of electron attracting or donating groups 25

26 Shielding Effects When a nucleus is placed in a magnetic field, the electrons surrounding it are in motion about the nucleus and create a small, localized magnetic field which opposes the applied field + H 0 circulating electron cloud induced local field that opposes the applied field, H 0 The electrons generate a small magnetic field that shields the proton from the external field. 26 E.V. Blackburn, 2001

27 NMR Instrument Organic sample is dissolved in a solvent, most commonly CDCl 3 or D 2 O, and put in a thin glass tube. The tube spins between the poles of a magnet. Magnetic field causes the proton and carbon nuclei to align themselves according to their nuclear spin. 27

28 1 H NMR Spectroscopy and Proton Equivalence Proton NMR is much more sensitive than 13 C and the active nucleus ( 1 H) is nearly 100 % of the natural abundance Shows how many kinds of nonequivalent hydrogens are in a compound Theoretical equivalence can be predicted by seeing if replacing each H with X gives the same or different outcome Equivalent H s have the same signal while nonequivalent are different There are degrees of nonequivalence 28

29 frequency domain spectrum 29

30 Nonequivalent H s Replacement of each H with X gives a different constitutional isomer Then the H s are in constitutionally heterotopic environments and will have different chemical shifts they are nonequivalent under all circumstances 30

31 Equivalent H s Two H s that are in identical environments (homotopic) have the same NMR signal Test by replacing each with X if they give the identical result, they are equivalent 31

32 Equivalent Hydrogens Equivalent hydrogens: have the same chemical environment Molecules with 1 set of equivalent hydrogens give 1 NMR signal 2 or more sets of equivalent hydrogens give a different NMR signal for each set Cl Cl CH 3 CH 3 CHCl O C C 1,1-Dichloroethane (2 signals) Cyclopentanone (2 signals) H H (Z)-1-Chloropropene (3 signals) Cyclohexene (3 signals) 32

33 Enantiotopic Distinctions If H s are in environments that are mirror images of each other, they are enantiotopic Replacement of each H with X produces a set of enantiomers The H s have the same NMR signal (in the absence of chiral materials) 33

34 Diastereotopic Distinctions In a chiral molecule, paired hydrogens can have different environments and different shifts Replacement of a pro-r hydrogen with X gives a different diastereomer than replacement of the pro-s hydrogen Diastereotopic hydrogens are distinct chemically and spectrocopically 34

35 1 H NMR Spectroscopy General Features Number of NMR absorptions Chemical shifts Integration of NMR absorptions Spin spin splitting 35

36 Chemical Shifts in 1 H NMR Spectroscopy Proton signals range from δ 0 to δ 10 Lower field signals are H s attached to sp 2 C Higher field signals are H s attached to sp 3 C Electronegative atoms attached to adjacent C cause downfield shift See Tables 13-2 and 13-3 for a complete list 36

37 NMR Correlation Chart 37

38 Nuclei that are shielded absorb upfield. Nuclei that are not shielded resonate downfield. Chemical Shifts 38

39 1 H Chemical Shift Correlation 39

40 Integration of 1 H NMR Absorptions: Proton Counting The relative intensity of a signal (integrated area) is proportional to the number of protons causing the signal This information is used to deduce the structure For example in ethanol (CH 3 CH 2 OH), the signals have the integrated ratio 3:2:1 For narrow peaks, the heights are the same as the areas and can be measured with a ruler integrated ratio 1:3 40

41 Spin-Spin Splitting in 1 H NMR Spectra Peaks are often split into multiple peaks due to interactions between nonequivalent protons on adjacent carbons, called spin-spin splitting The splitting is into one more peak than the number of H s on the adjacent carbon ( n+1 rule ) The relative intensities are in proportion of a binomial distribution and are due to interactions between nuclear spins that can have two possible alignments with respect to the magnetic field The set of peaks is a multiplet (2 = doublet, 3 = triplet, 4 = quartet) 41

42 Simple Spin-Spin Splitting An adjacent CH 3 group can have four different spin alignments as 1:3:3:1 This gives peaks in ratio of the adjacent H signal An adjacent CH 2 gives a ratio of 1:2:1 The separation of peaks in a multiplet is measured is a constant, in Hz J (coupling constant) 42

43 Rules for Spin-Spin Splitting Equivalent protons do not split each other The signal of a proton with n equivalent neighboring H s is split into n + 1 peaks Protons that are farther than two carbon atoms apart do not split each other 43

44 Signal Splitting (n + 1) n = 1. Their signal is split into (1 + 1) or 2 peaks ; a doublet Cl CH 3 -CH-Cl n = 3. Its signal is split into (3 + 1) or 4 peaks; a quartet Problem: predict the number of 1 H- NMR signals and the splitting pattern of each O O H CH 3 CH 2 C CH 2 CH 3 CH 3 C C CH 3 CH 3 44

45 Signal Splitting (n + 1) O CH 3 CH 2 C CH 2 CH 3 45

46 Signal Splitting (n + 1) CH 3 O C H C CH 3 CH 3 46

47 1,1,2-Trichloroethane integral = 2 integral = 1 H Cl H C C Cl Cl H 47

48 Multiplets H C H C H two neighbors n+1 = 3 triplet H C H C H one neighbors n+1 = 2 doublet singlet doublet triplet quartet quintet sextet septet 48

49 SOME COMMON SPLITTING PATTERNS X CH CH Y CH 3 CH ( x = y ) CH 2 CH CH 3 CH 2 X CH 2 CH 2 Y CH 3 CH ( x = y ) CH 3 49

50 NMR Spectrum of Bromoethane Br CH 2 CH 3 50

51 NMR Spectrum of 2- H Nitropropane CH 3 C CH 3 O N + O - 51

52 NMR Spectrum of Acetaldehyde O CH 3 C H offset = 2.0 ppm 52

53 Spin-Spin Splitting 53

54 The Coupling Constant The coupling constant is the distance J (measured in Hz) between the peaks in a multiplet. J is a measure of the amount of interaction between the two sets of hydrogens creating the multiplet. 54

55 Types of Information from the NMR Spectrum 1. Each different type of hydrogen gives a peak or group of peaks (multiplet). 2. The chemical shift (δ, in ppm) gives a clue as to the type of hydrogen generating the peak (alkane, alkene, benzene, aldehyde, etc.) 3. The integral gives the relative numbers of each type of hydrogen. 4. Spin-spin splitting gives the number of hydrogens on adjacent carbons. 5. The coupling constant, J, also gives information about the arrangement of the atoms involved. 55

56 Uses of 1 H NMR Spectroscopy The technique is used to identify likely products in the laboratory quickly and easily Example: regiochemistry of hydroboration/oxidation of methylenecyclohexane Only that for cyclohexylmethanol is observed 56

57 O CH 3 C CH 2 CH 3 57

58 O CH 3 C O CH 2 CH 3 58

59 CH 3 O CH C Cl OH 59

60 O CH 3 CH 3 C C CH 3 CH 3 60

61 + O CH 3 CH 2 CH 2 N O - 61

62 Cl CH 2 CH 2 CH 2 Cl 62

63 O CH 3 CH 2 CH C OH Br 63

64 O CH 2 CH 2 O C CH 3 64

65 O O CH 3 CH 2 O C CH 2 CH 2 C O CH 2 CH 3 65

66 O O CH 3 CH 2 O C C C C O CH 2 CH 3 H H 66

67 CH 3 CH 2 OH 67

68 CH 2 OH 68