2. Introduction Spectroscopy is an analytical technique which helps determine structure. It destroys little or no sample. The amount of light absorbed by the sample is measured as wavelength is varied. =>

3. Dorothy Crowfoot Hodgkin 1910-1994

4. Accomplishments

5. Vit B-12

6. Insulin

7. Cholesterol Story Isolated in 1832 Structure First reported in 1927 Structure Determined in 1942 by Dorothy Crowfoot Hodgson Synthesized in 1971

8. Proposed Structures for Cholesterol

9. Percy Julian

10. Synthesized Cortisone

11. Synthesized physotigmine

12. Photos

13. Chapter 13 Spectroscopy Infrared spectroscopy Ultraviolet-Visible spectroscopy Nuclear magnetic resonance spectroscopy Mass Spectrometry

14. 13.1 Principles of Molecular Spectroscopy: Electromagnetic Radiation

15. is propagated at the speed of light has properties of particles and waves the energy of a photon is proportional to its frequency Electromagnetic Radiation

16. Figure 13.1: The Electromagnetic Spectrum 400 nm 750 nm Visible Light Longer Wavelength ( ) Shorter Wavelength ( ) Higher Frequency ( ) Lower Frequency ( ) Higher Energy (E) Lower Energy (E)

17. Figure 13.1: The Electromagnetic Spectrum UltravioletInfrared Longer Wavelength ( ) Shorter Wavelength ( ) Higher Frequency ( ) Lower Frequency ( ) Higher Energy (E) Lower Energy (E)

18. Cosmic rays  Rays X-rays Ultraviolet light Visible light Infrared radiation Microwaves Radio waves Cosmic rays  Rays X-rays Ultraviolet light Visible light Infrared radiation Microwaves Radio waves Figure 13.1: The Electromagnetic Spectrum Energy

19. 13.2 Principles of Molecular Spectroscopy: Quantized Energy States

20. Electromagnetic radiation is absorbed when the energy of photon corresponds to difference in energy between two states.  E = h  E = h

21. electronicvibrationalrotational nuclear spin UV-Visinfraredmicrowaveradiofrequency What Kind of States?

22. 13.3 Introduction to 1 H NMR Spectroscopy

23. 1 H and 13 C both have spin = ±1/2 1 H is 99% at natural abundance 13 C is 1.1% at natural abundance The nuclei that are most useful to organic chemists are:

24. Nuclear Spin A spinning charge, such as the nucleus of 1 H or 13 C, generates a magnetic field. The magnetic field generated by a nucleus of spin +1/2 is opposite in direction from that generated by a nucleus of spin –1/2. + +

25. + + + + + The distribution of nuclear spins is random in the absence of an external magnetic field.

26. NMR Spectroscopy Brief Intro Certain nuclei behave as bar magnets - consider proton  E =  h  Ho Using magnet Ho = 25,000 Gauss  E = 0.019 cals/mol!!! Radio region 499,990 500,010only 20 nuclei excess!!! Ho

27. + + + + + An external magnetic field causes nuclear magnetic moments to align parallel and antiparallel to applied field. H0H0H0H0

28. + + + + + There is a slight excess of nuclear magnetic moments aligned parallel to the applied field. H0H0H0H0

29. Energy Differences Between Nuclear Spin States + + EEEE  E ' increasing field strength

30. Requirement for nuclei to behave as a bar magnet 1) odd mass number 1H1H 13 C 19 F 35 P 2) odd atomic number 14 N 7 NOTE: nuclei with even mass no and atomic number do not behave as a bar magnet! 12 C and 16 O WONDERFUL : can obtain proton resonances NMR without interference by these ubiquitous isotopes. Questions: Since many atoms are NMR active, will we not get overlapping signals in 1H-NMR spectra? NO!! We are saved by the fact that each NMR active nuclei has a different gyromagneto ratio - different region of radio radiation

31. Some important relationships in NMR The frequency of absorbed electromagnetic radiation is proportional to the energy difference between two nuclear spin states which is proportional to the applied magnetic field UnitsHz kJ/mol (kcal/mol) tesla (T)

32. 150th Birthday http://www.teslasociety.com/happybirthday.ht mhttp://www.teslasociety.com/happybirthday.ht m Most of us, think of Guglielmo Marconi as the father of radio, and Tesla is unknown for his work in radio. Marconi claimed all the first patents for radio, something originally developed by Tesla. Nikola Tesla tried to prove that he was the creator of radio but it wasn't until 1943, where Marconi's patents were deemed invalid; however, people still have no idea about Tesla's work with radio.

33. Some important relationships in NMR The frequency of absorbed electromagnetic radiation is different for different elements, and for different isotopes of the same element. For a field strength of 4.7 T: 1 H absorbs radiation having a frequency of 200 MHz (200 x 10 6 s -1 ) 13 C absorbs radiation having a frequency of 50.4 MHz (50.4 x 10 6 s -1 )

34. Some important relationships in NMR The frequency of absorbed electromagnetic radiation for a particular nucleus (such as 1 H) depends on its molecular environment. This is why NMR is such a useful tool for structure determination.

35. 13.4 Nuclear Shielding and 1 H Chemical Shifts What do we mean by "shielding?" What do we mean by "chemical shift?"

36. Shielding An external magnetic field affects the motion of the electrons in a molecule, inducing a magnetic field within the molecule. The direction of the induced magnetic field is opposite to that of the applied field. C H H 0H 0H 0H 0

37. Shielding The induced field shields the nuclei (in this case, C and H) from the applied field. A stronger external field is needed in order for energy difference between spin states to match energy of rf radiation. C H H 0H 0H 0H 0

38. Chemical Shift Chemical shift is a measure of the degree to which a nucleus in a molecule is shielded. Protons in different environments are shielded to greater or lesser degrees; they have different chemical shifts. C H H 0H 0H 0H 0

39. Chemical Shift Chemical shifts (  ) are measured relative to the protons in tetramethylsilane (TMS) as a standard. Si CH 3 H3CH3CH3CH3C  = position of signal - position of TMS peak spectrometer frequency x 10 6

40. 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm) measured relative to TMS Upfield Increased shielding Downfield Decreased shielding (CH 3 ) 4 Si (TMS)

41. Chemical Shift Example: The signal for the proton in chloroform (HCCl 3 ) appears 1456 Hz downfield from TMS at a spectrometer frequency of 200 MHz.  = position of signal - position of TMS peak spectrometer frequency x 10 6  = 1456 Hz - 0 Hz 200 x 10 6 Hx x 10 6  = 7.28

42. 01.02.03.04.05.06.07.08.09.010.0 Chemical shift ( , ppm)  7.28 ppm H C Cl ClCl

43. 13.5 Effects of Molecular Structure on 1 H Chemical Shifts protons in different environments experience different degrees of shielding and have different chemical shifts

44. Electronegative substituents decrease the shielding of methyl groups least shielded H most shielded H CH 3 F CH 3 OCH 3 (CH 3 ) 3 N CH 3 CH 3 (CH 3 ) 4 Si  4.3  3.2  2.2  0.9  0.0

45. Electronegative substituents decrease shielding H 3 C—CH 2 —CH 3 O 2 N—CH 2 —CH 2 —CH 3  0.9  1.3  1.0  4.3  2.0

46. Effect is cumulative CHCl 3  7.3 CH 2 Cl 2  5.3 CH 3 Cl  3.1

47. Methyl, Methylene, and Methine CH 3 more shielded than CH 2 ; CH 2 more shielded than CH H3CH3CH3CH3C C CH3CH3CH3CH3 CH 3 H  0.9  1.6  0.8 H3CH3CH3CH3C C CH3CH3CH3CH3 CH 3 CH2CH2CH2CH2  0.9 CH 3  1.2

48. Protons attached to sp 2 hybridized carbon are less shielded than those attached to sp 3 hybridized carbon HH HH HH C CHHHH CH 3 CH 3  7.3  5.3  0.9

49. But protons attached to sp hybridized carbon are more shielded than those attached to sp 2 hybridized carbon C C HH HH  5.3  2.4 CH 2 OCH 3 C C H

50. Protons attached to benzylic and allylic carbons are somewhat less shielded than usual  1.5  0.8 H3CH3CH3CH3C CH 3  1.2 H3CH3CH3CH3C CH 2  2.6 H 3 C—CH 2 —CH 3  0.9  1.3

51. Proton attached to C=O of aldehyde is most deshielded C—H  2.4  9.7  1.1 CC O H H CH 3 H3CH3CH3CH3C

52. Table 13.1 (p 554) Type of proton Chemical shift (  ), ppm Type of proton Chemical shift (  ), ppm C HR 0.9-1.8 1.5-2.6 C H CC 2.0-2.5 C H CO2.1-2.3 C H NC C HAr 2.3-2.8 2.5 C H CC

53. Table 13.1 (p 554) Type of proton Chemical shift (  ), ppm Type of proton Chemical shift (  ), ppm C HBr 2.7-4.1 9-10 COH 2.2-2.9 C HNR 3.1-4.1 C HCl 6.5-8.5HAr C CH4.5-6.5 3.3-3.7 C H O

54. Table 13.1 (p 554) Type of proton Chemical shift (  ), ppm 1-3HNR0.5-5HOR6-8HOAr10-13 CO HOHOHOHO