1. Proton Nuclear Magnetic Resonance ( 1 H-NMR) Spectroscopy - Part 1 Lecture Supplement page 133

2. Organic Structure Analysis Crews, Rodriguez, Jaspers 1998 p.5-6

4. 1 H-NMR Spectroscopy Background and Theory Fundamental principle The energy required to cause nuclear spin flip is a function of the magnetic environment of the nucleus. Protons, electrons, neutrons have “spin” ( I ) Motion of charged particle creates magnetic field In absence of external influence, magnetic poles (spin axis) randomly oriented No external magnetic field Spin alignment random With external magnetic field Spins aligned BoBo Add external magnetic field ( B o )  spins align add magnetic field

5. Background and Theory Nuclear Spin Flip I = +1/2 parallel to B o (lower energy); I = -1/2 antiparallel to B o (higher energy) Addition of energy results in nuclear spin flip Excited state Nuclear spin antiparallel to B o Higher energy I = +1/2 I = -1/2 Ground state Nuclear spin parallel to B o Lower energy Increasing energy Absorb energy (excitation) Release energy (relaxation)  E ~ 0.02 cal mol -1 = radio wave photons Contrast this with absorption of infrared light (p. 114 of lecture supplement)

6. Background and Theory Magnetic Field Controls  E  E influenced by magnetic field strength at nucleus Information about magnetic field strength at nucleus Energy required for spin flip (  E)  Information about chemical structure  I = -1/2 I = +1/2 Spin state energy Magnetic field strength at nucleus Large magnetic field  large  E Small magnetic field  small  E EE EE

7. Background and Theory The NMR Spectrum Spectrum = plot of photon energy versus photon quantity Intensity of signal (photon quantity) Spin flip energy (photon energy) NMR signal

8. Background and Theory The NMR Spectrum Nuclear: Manipulation of nuclear spin Magnetic: Magnetic field strength influences  E X Resonance: Tendency of a system to oscillate at maximum amplitude at a certain frequency NMR 1 H nucleus = a proton  1 H-NMR = proton NMR

9. Background and Theory Spectrum  Structure Information from NMR spectrum: Number of signals  number of nonequivalent proton groups in molecule Position of signals (chemical shift)  magnetic environment of protons Relative intensity of signals (integration)  ratio of equivalent proton types Splitting of signals (spin-spin coupling)  proton neighbors How do we deduce structure from NMR spectrum?

10. Number of Signals Proton Equivalency Photon energy controlled by magnetic environment of nucleus Nuclei in same magnetic environment = equivalent Multiple magnetic environments  multiple signals Number of signals = number of equivalent proton sets Protons equivalent One NMR signal Protons not equivalent Two NMR signals NMR signal due to photon absorption

11. Number of Signals Proton Equivalency Equivalent = proton magnetic environments identical in every way Nonequivalent = proton magnetic environments not identical in one or more ways Easier to test for nonequivalency than for equivalency How to test for equivalency? Useful vocabulary CH 3 = methylCH 2 = methyleneCH = methine

12. Number of Signals Proton Equivalency Proton equivalency examples One signalTwo signals ? NMR = camera with slow shutter speed NMR detects only average when rotation is fast Thousands of 360 o bond rotations per second Therefore H a, H b, H c appear equivalent H b, H c equivalent H a, H c not equivalent rapid equilibrium H a, H c equivalent H b, H a not equivalent Single bond rotation in acyclic molecules often allows equivalency

13. Number of Signals Proton Equivalency Proton equivalency examples One signalTwo signals ? H b, H c equivalent H a, H c not equivalent rapid equilibrium H a, H c equivalent H b, H a not equivalent vs.

14. Number of Signals Proton Equivalency More proton equivalency examples Three signalsTwo signalsOne signal Four signals mirror plane One signal

15. Number of Signals Proton Equivalency Verify what we have learned about equivalent protons Which spectrum belongs to this molecule? Sample spectra Three proton sets  three signals

16. Number of Signals Proton Equivalency Which spectrum belongs to this molecule? Two proton sets  two signals

17. Proton Nuclear Magnetic Resonance ( 1 H-NMR) Spectroscopy - Part 2 Lecture Supplement page 139

18. 1 H-NMR Spectroscopy Part 1 Summary Nuclear spin axis can be parallel or antiparallel to external magnetic field ( B o ) Spin parallel to B o ( I = +1/2) lower energy than spin antiparallel to B o ( I = -1/2) Energy difference between spin states (  E) controlled by magnetic field at nucleus Absorption of radio wave photon with energy =  E causes nuclear spin flip NMR spectrum = plot of photon energy (spin flip energy) versus photon quantity Information from NMR spectrum Number of signals reveals number of sets of equivalent protons Equivalency: Protons must be identical in all ways to be equivalent Nonequivalency: Protons can be different in just one way Example: 1 H-NMR spectrum of CH 3 CH 2 OH has three signals Position of signal (chemical shift) Relative intensity of signals (integration) Splitting of signals (spin-spin coupling) Atomic nucleus has spin, and therefore generates a magnetic field Vollhardt, 10-2

19. Position of Signals The Chemical Shift How does spin flip energy relate to molecular structure? Magnetic field strength varies between NMR spectrometers High magnetic field = higher spectral resolution (more spectral detail) Need a spin flip energy scale that is independent of magnetic field strength Chemical shift : Spin flip energy scale normalized to be independent of field strength I = -1/2 I = +1/2 Spin state energy Magnetic field strength at nucleus Large magnetic field  large  E Small magnetic field  small  E Spin flip energy depends on magnetic field strength: EE EE

20. Position of Signals The Chemical Shift How does molecular structure influence chemical shift? Chemical shift controlled by  E which is controlled by magnetic field at nucleus What contributes to magnetic field at nucleus? Electron cloud shields atomic nucleus from external magnetic fields Shielded : Nucleus feels weaker magnetic field Deshielded : Nucleus feels stronger magnetic field Spectrometer’s magnetic field Strong; typically 94 kilogauss Earth’s magnetic field Weak; 0.3-0.6 gauss Other electrons and nuclei in the molecule

21. Position of Signals The Chemical Shift Intensity of signal (photon quantity) Spin flip energy (photon energy) DeshieldedShielded 15 ppm0 ppm Chemical shift scale (ppm) Reference point? 0.00 ppm (CH 3 ) 4 Si Tetramethylsilane (TMS) High Magnetic Field StrengthLow Magnetic Field Strength

22. Position of Signals The Chemical Shift How does molecular structure influence chemical shift? Chemical shifts for H 3 C-X: (CH 3 ) 4 Si 0.00 ppm CH 4 0.23 ppm CH 3 I 2.16 ppm CH 3 Br 2.68 ppm CH 3 Cl 3.05 ppm CH 3 OH 3.42 ppm CH 3 F 4.26 ppm EN of X in CH 3 -X Conclusion:  EN of atoms near H  chemical shift Si 1.8 H 2.1 I 2.5 Br 2.8 Cl 3.0 O 3.5 F 4.0 CH 3 CH 3 0.86 ppm C 2.5

23. Vollhardt, Fig 10-9 Electron cloud shields atomic nucleus from external magnetic fields Shielded : Nucleus feels weaker magnetic field Deshielded : Nucleus feels stronger magnetic field deshielded shielded

24. Position of Signals The Chemical Shift How does electronegativity influence chemical shift? HIHBrHClHF Iodine has low ENFluorine has high EN Electron density at H is highElectron density at H is low H more shieldedH is less shielded H has higher chemical shiftH has lower chemical shift Metaphor: Ozone layer shields Earth Chemical shift related to magnetic field strength at nucleus Electron cloud shields nucleus from effects of B o

25. Position of Signals Do not memorize chemical shifts. Table given on exams.

26. Position of Signals Notes On Characteristic Chemical Shifts Table Characteristic shifts are typical proton averages. Actual shifts may lie outside given range.  Typically 2.0-2.6 ppm  2.01 ppm  2.59 ppm Useful chemical shift trends RCH 3 < RCH 2 R < R 3 CH EN effects decrease with distance: EN of C (in R) > EN of H CH 4 CH 3 OH CH 3 CH 2 OH CH 3 CH 2 CH 2 OH 0.23 ppm3.39 ppm1.18 ppm 0.93 ppm 3.49 ppm 3.59 ppm 1.53 ppm

27. Position of Signals Example: 3.8 ppm not always ROCH 3 2.3 ppm not always ArCH 3 Common exception benzene ring protons 6.5-8.0 ppm usually C=O stretch Avoid this common misconception: “NMR peaks can be assigned based on chemical shift alone”

28. Relative Intensity of Peaks Integration Information from NMR spectrum Number of signals  number of nonequivalent proton groups in molecule Position of signals (chemical shift)  magnetic environment of protons Relative intensity of signals (integration)  ratio of equivalent proton types Splitting of signals (spin-spin coupling)  proton neighbors

29. Relative Intensity of Peaks Integration Beer’s Law: Amount of energy absorbed or released proportional to moles of stuff present ∫ir I∫aac Newton Gottfried Leibniz Inventor∫ of calculu∫ Relative intensities of NMR signals proportional to relative number of equivalent protons Integrals do not always correspond to exact number of protons Example: Integrals of 2:1 might be 2H:1H or 4H:2H or... NMR: Amount of radio wave energy proportional to peak area Measurement of peak areas = integration Peak height Peak area

30. Sample Spectra Verify what we have learned about equivalent protons, chemical shifts, and integration 4.19 ppm: integral = 1.0 3.41 ppm: integral = 3.0 (1 H) (3 H) CH 3 OH has 4 H Assign peaks to corresponding hydrogens:

31. Sample Spectra Assign peaks to corresponding hydrogens: 3.19 ppm: integral = 1.0 1.33 ppm: integral = 1.0 (6 H) C 5 H 12 O 2 has 12 H Two equal integrals Two groups of equivalent H Smallest integral often set = 1 Integration gives proton ratio

32. Sample Spectra Assign peaks to corresponding hydrogens: 3.55 ppm: integral = 1.0 3.39 ppm: integral = 1.5 (4 H) (6 H) Two groups of equivalent H Two unequal integrals C 4 H 10 O 2 has 10 H 10 H / (1.0 + 1.5) = 4 H per unit CH 3 OCH 2 CH 2 OCH 3

33. Lecture Supplement p. 138, 139, 146 CH 3 OCH 2 CH 2 OCH 3 CH 3 CH 2 Br 1 2 3 1 2 2 2 2 2

34. Sample Spectra Assign peaks to corresponding hydrogens: CH 3 CH 2 Br Why the extra peaks? Hint: Think about spin and magnetic fields Four peaks! Three peaks!

35. Proton Nuclear Magnetic Resonance ( 1 H-NMR) Spectroscopy - Part 3 Lecture Supplement page 147 CH 3 CH 2 Br

36. 1 H-NMR Spectroscopy Part 2 Summary 1. Number of signals  how many sets of equivalent protons 2. Position of signals (chemical shift)  magnetic environment of nucleus Deshielding by electronegative atoms  higher chemical shift 3. Relative intensity of signals (integration)  how many hydrogens per signal Integrals give proton ratio ; not always equal to absolute proton count (i.e., 1.5:1) 4. Splitting of signals (spin-spin coupling) Example: 3.55 ppm: integral = 1.0 3.39 ppm: integral = 1.5 4 H 6 H Two groups of equivalent H Two unequal integrals C 4 H 10 O 2 has 10 H 10 H / (1.0 + 1.5) = 4 H per unit CH 3 OCH 2 CH 2 OCH 3 Information from NMR Spectrum

37. Signal Splitting 3.43 ppm: integral = 1.0 1.68 ppm: integral = 1.5 Two unequal integrals 5 H / (1.0 + 1.5) = 2 H per unit 2 H 3 H Four lines A quartet Three lines A triplet Signals are split 1 H-NMR spectrum of CH 3 CH 2 Br has more details... CH 3 CH 2 Br

38. Signal Splitting What is the origin of signal splitting? A nucleus with only one magnetic environment causes a singlet A nucleus with two magnetic environments causes a doublet Each line in signal......has slightly different chemical shift...represents slightly different spin flip energy...represents nucleus with slightly different magnetic environment

39. Signal Splitting How can one nucleus have different magnetic environments? H a feels B o + H b H a feels two different magnetic environments H a has two different spin flip  E H a feels B o - H b BoBo Caused by spin direction of adjacent nuclei Larger  E Smaller  E H a has two different (but very similar) chemical shifts H a signal is split into a doublet NMR signal for H a

40. Signal Splitting Some Useful Terms J Spin-spin coupling : One nuclear spin influences spin of another nucleus Splitting : Effect on NMR signal caused by spin-spin coupling Coupling constant (J ) : Spacing between lines in a splitting pattern

41. Signal Splitting More Than One Neighbor What is splitting when there is more than one neighbor? H a feels B o + H b + H c H a has three different (but very similar) chemical shifts H a signal is split into a triplet BoBo H a feels B o - H b + H c = B o H a feels B o + H b - H c = B o H a feels B o - H b - H c } equal energy 1:2:1 because of energy state population probabilities NMR signal for H a

42. Signal Splitting Rules and Restrictions General rule: The signal for a proton with n neighbors is split into n +1 lines Rules and Restrictions for Proton-Proton Spin-Spin Coupling 1. Only nonequivalent protons couple. H c and H d do not couple because they are equivalent H b couples with H c H b and H a do not couple because they are equivalent X X

43. Signal Splitting Rules and Restrictions 2. Protons separated by more than three single bonds usually do not couple. H a and H b _____ bonds apart Can couple Cannot couple H a and H c _____ bonds apart Can couple Cannot couple H a and H d _____ bonds apart Can couple Cannot couple Pi bonds do not count toward this bond limit, but J may be too small to observe. H a and H b _____ bonds apart Can couple Cannot couple H a and H c _____ bonds apart Can couple Cannot couple H a and H d _____ bonds apart Can couple Cannot couple Free spacer X *But J ad may be very small * * Assuming H a and H b are not equivalent * 2 3 4 2 2 (+1) 3 (+1)

44. Signal Splitting Rules and Restrictions 2. Protons separated by more than three single bonds usually do not couple. Benzene ring = one big free spacer All benzene ring protons may couple with each other but J may be small H a, H b, H c, and H d all couple with each other J ad may be too small to observe Benzene ring is a “gated community”; it blocks some coupling that we expect to observe. X X

45. Signal Splitting Rules and Restrictions 3. Signals for O-H and N-H are usually singlets Splitting of O-H or N-H protons may be observed in rare circumstances singlet triplet

46. Sample Spectra Verify what we have learned about equivalency, chemical shifts, integration, and splitting 3.39 ppm (triplet; integral = 1.0) 1.87 ppm (sextet; integral = 1.0) 1.03 ppm (triplet; integral = 1.5) 7 H / (1.0 + 1.0 + 1.5) = 2 H per unit 2 H 3 H Assign peaks to corresponding hydrogens in structure BrCH 2 CH 2 CH 3

47. Sample Spectra Assign peaks to corresponding hydrogens in structure 3.78 ppm (septet; integral = 1.0) 1.31 ppm (doublet; integral = 6.0) 7 H / (1.0 + 6.0) = 1 H per unit 1 H 6 H

48. Lecture Supplement p. 138, 139, 146 CH 3 OCH 2 CH 2 OCH 3 CH 3 CH 2 Br

49. Sample Spectra For next lecture: 5.66 ppm (multiplet; integral = 1.0) 1.98 ppm (multiplet; integral = 2.0) 1.61 ppm (multiplet; integral = 2.0) Assign peaks to corresponding hydrogens in structure Explain splitting patterns

50. Proton Nuclear Magnetic Resonance ( 1 H-NMR) Spectroscopy - Part 4 Lecture Supplement page 154

51. 1 H-NMR Spectroscopy Part 3 Summary Number of signals  how many sets of equivalent protons Position of signals (chemical shift)  magnetic environment of nucleus Deshielding by electronegative atoms  higher chemical shift Relative intensity of signals (integration)  how many hydrogens per signal Integrals give proton ratio ; not always equal to absolute proton count (i.e., 1.5:1) Splitting of signals (spin-spin coupling) The signal of a proton with n neighbors is split into n +1 lines (first order coupling) Example: CH 3 CH 2 Br CH 3 is a triplet, CH 2 is a quartet More complex patterns (non first-order coupling) are common Information from NMR Spectrum

52. 1 H-NMR Spectroscopy Part 3 Summary Only nonequivalent hydrogens couple with each other Hydrogens can be at most three single bonds distant Pi bonds and benzene rings are “free spacers” Benzene ring “gated community” OH, NH usually do not couple, and usually are not split Splitting rules

53. Sample Spectra Assign peaks to corresponding hydrogens in structure 5.66 ppm (multiplet; integral = 1.0) 1.98 ppm (multiplet; integral = 2.0) 1.61 ppm (multiplet; integral = 2.0) 10 H / (1.0 + 2.0 + 2.0) = 2 H per unit 2 H 4 H Multiplet : A splitting pattern that is too complex to decipher

54. Non-First Order Splitting Why Is Cyclohexene Splitting Not Simple? n+1 rule obeyed; “normal” doublets, triplets, etc. result Non-first order splitting : J values in a splitting pattern are unequal More complex splitting patterns result Example: For Chem 14C we predict J values equal and “normal” coupling results. Exceptions are plentiful. J ab = J ac “normal” triplet J ab ≠ J ac doublet of doublets First order splitting : All J values in a splitting pattern are equal

55. Sample Spectra Effects of Pi Electron Clouds: Magnetic Induction Vinyl protons deshielded by magnetic induction BoBo Deshielded May also cause shielding

56. Sample Spectra Benzene Ring Protons Magnetic induction causes benzene ring proton chemical shifts ~6.5-8.0 ppm 10.00 ppm (singlet) 7.87-7.56 ppm (multiplet) Magnetic induction by C=O causes aldehyde proton chemical shift ~9.5-11 ppm 6.5-8.0 ppm Due to long range coupling, benzene ring proton signals often multiplets 9.5-11 ppm

57. Sample Spectra Benzene Ring Protons Benzene ring proton signals can be deceptively simple... 7.2 ppm = singlet? Benzene ring protons not equivalent When chemical shifts very similar J  0; splitting disappears