1. Che 440/540 Proton Nuclear Magnetic Resonance (NMR) Spectroscopy

2. Fundamental NMR Equations Number of energy levels = 2I + 1 I = the spin quantum number (1/2 for 1 H and 13 C) Therefore, there are two possible spin states for these nuclei. E = h ; h = Planck’s constant, = resonant frequency, Hz =  B o /2  B o = applied magnetic field  = gyromagnetic ratio (unique for each NMR active nucleus)  E = h  B o /2 

3. Isotope Natural % Abundance Spin (I) Magnetic Moment (μ)* Magnetogyric Ratio (γ) † 1H1H99.98441/22.792726,753 2H2H0.015610.85744,107 11 B81.173/22.6880-- 13 C1.1081/20.70226,728 17 O0.0375/2-1.8930-3,628 19 F100.01/22.627325,179 29 Si4.7001/2-0.5555-5,319 31 P100.01/21.130510,840 * μ in units of nuclear magnetons = 5.0507810 -27 JT -1 † γ in units of 10 7 rad T -1 sec -1 Characteristics of Some NMR Active Nuclei

4. no magnetic field present B o magnetic field present Nuclear Spins in the Absence and Presence of a Magnetic Field Slide by Joanna LeFevre

5.  spin state  spin state (slight excess) N  /N  = e -  E/kT For a 300 MHz instrument, N  /N  = 1,000,000/1,000,048. Therefore, for every two million nuclei, there are only 48 excess nuclei in the  spin state!! Therefore NMR is an inherently insensitive technique. http://teaching.shu.ac.uk/hwb/chemistry/tutorials/molspec/nmr1.htm

6. magnetic moment, μ http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b A spinning gyroscope in a gravitational field A spinning charge in a magnetic field I = +1/2 I = -1/2

7. http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b Net Macroscopic Magnetization of a Sample in an External Magnetic Field B o

8. Excitation by RF Energy and Subsequent Relaxation T 1 = spin-lattice relaxation time; establishes the z axis equilibrium. T 1 ’s are usually short ( 1 min) in 13 C NMR. T 2 = spin-spin relaxation time; causes a decrease in magnetization in the x-y plane. For a good magnet, T 2 = 1-2 sec. http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b

9. http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#pulse Four different frequencies Complex summation wave (FID) Fourier transformation Generation and Fourier Transformation (FT) of a Free Induction Decay (FID) Pattern

10. http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#pulse seconds 0 1 2 3 4 5 Free Induction Decay (FID) Signal: A Decaying Cosine Curve 5 Hz signal Assume T 2 = 2 sec I t = I o e -t/T2 ~35% of signal remains after 2 sec.

11. Time (sec) 0.02 0.04 0.06 0.08 0.1 Portion of the FID of Betulin

12. 1 H Spectrum of Betulin after Fourier Transformation

13. Presentation of NMR Data  = chemical shift (Hz) – shift of tetramethyl silane (TMS; 0 Hz) = ppm spectrometer frequency (MHz) For example, in CH 2 Cl 2 a sharp singlet occurs at 1,590 Hz using a 300 MHz spectrometer frequency. The chemical shift is: (1,590 – 0) Hz = 5.3 ppm 300 MHz

14. Shielding vs Deshielding Increasing deshielding Increasing shielding, B o Downfield Upfield

15. Compound, CH 3 X CH 3 F CH 3 OH CH 3 ClCH 3 BrCH 3 I CH 4 (CH 3 ) 4 Si X FOClBrIHSi Electronegativity of X 4.03.53.12.82.52.11.8 Chemical shift,  / ppm 4.263.43.052.682.16 0.23 0 Electronegative groups attached to the C-H system decrease the electron density around the protons, and there is less shielding (i.e. deshielding) so the chemical shift increases. These effects are cumulative, so the presence of more electronegative groups produce more deshielding and therefore, larger chemical shifts. CompoundCH 4 CH 3 ClCH 2 Cl 2 CHCl 3  / ppm 0.233.055.307.27

16. http://www.chem.ucalgary.ca/courses/351/Carey/Useful/nmr1.gif&imgrefurl Anisotropic Shielding and Deshielding

17. 1 H NMR Spectrum of 4-Methylbezaldehyde deshielded protons

18. http://orgchem.colorado.edu/hndbksupport/nmrtheory/NMRtutorial.html Chemical Shifts of Various Protons

19. Integrations: Relative Numbers of Protons

20. 1 H NMR Spectrum of Isopentyl Acetate

21. Spin-Spin Splitting: The n+1 rule in Vicinal Coupling (H A -C-C-H B ) Equivalent nuclei do not couple each other. The number of lines in a multiplet is determined by the number of equivalent protons on neighboring atoms plus one, i.e. the n + 1 rule The distance between the peaks is called the coupling constant ( 3 J). The coupling constant is not dependent on the applied field strength. A B B B J AB = 7 Hz

22. http://teaching.shu.ac.uk/hwb/chemistry/tutorials/molspec/nmr1.htm The Origin of Spin-Spin Splitting

23. Some Common Splitting Patterns

24. Condition for Applying the n+1 Rule If J HA-HB = J HA’-HB then the n+1 rule applies and H B appears as a 1:2:1 triplet.

25. However, if the relevant J values are not the same, the splitting is more complex.

26. Example: Cis and Trans Coupling in a Carbon-Carbon Double Bond

27. The Karplus Relationship The vicinal coupling constant ( 3 J) is dependent upon the dihedral angle, . http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b

28. Menthol H1H1

29. Some Alkene Splitting Patterns http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b

30. Typical 1 H- 1 H Coupling Constants http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr1.htm

31. First-Order Coupling The splitting pattern shown below displays the ideal or "First-Order" arrangement of lines. This is usually observed if the spin-coupled nuclei have very different chemical shifts. The condition that must be met is  /J > 6. Consider ethyl acetate. H A = 1.26 ppm x 90 Hz/ppm = 113.4 Hz H C = 4.11 ppm x 90 Hz/ppm = 369.9 Hz  /J = (369.9 – 113.4)Hz/7.2 Hz = 35.6 http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b

32. However, if the ratio of Δν to J decreases to less than 10 a significant distortion of the expected pattern will take place. Second-Order Coupling First-order http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b

33. Example of a Second-Order Coupling Pattern http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b

34. Magnetic Non-equivalence H(A) and H(B) are magnetically non-equivalent. H(A) and H(A)* couple differently to H(B) [and to H(B*)]. * *

35. Para and Meta-Disubstituted Benzene Rings

36. Increasing the field strength leads to greater dispersion of signals. Mono-Substituted Benzene Ring http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b

37. Chemical Shift Equivalence H’s are homotopic: Related by a 180 o rotational axis, Cn. They have the same chemical shift.

38. Chemical Shift Equivalence H’s are enantiotopic: Related by a mirror plane, . They have the same chemical shift.

39. Chemical Shift Equivalence H A and H B are diastereotopic: They are not related by a rotational axis or a mirror plane. They have different chemical shifts, and they split each other.

40. Homotopic Methyl Groups These methyls are homotopic: they are related by a 180 o rotational axis, Cn. They have the same chemical shift.

41. Enantiotopic Methyl Groups These methyls are enantiotopic: They are related by a mirror plane, . They have the same chemical shift.

42. Diastereotopic Methyl Groups These methyls are diastereotopic: They are not related by a rotational axis or a mirror plane. They have different chemical shifts. Notice that a chiral center* is present. Compare with isopentyl acetate (enantiotopic methyls)

43. For the following molecules label any groups that are homotopic, enantiotopic, or diastereotopic.

44. http://www.cis.rit.edu/class/schp740/docu/avance/noediff.pdf NOE Difference Spectra of Pamoic Acid Ha Hd

45. NOE Difference Spectrum of Betulin

46. Pople Notation: Describes sets of spins If  /J > 8, the pattern is called AX (i.e. ethyl acetate). A3A3 X2X2 CH 3 CO 2 CH 2 CH 3 : A 3 X 2

47. If  /J < 8, the pattern is called AB (i.e. 2-chloroacrylonitrile) A B

48. Three weakly coupled sets are designated AMX; (i.e. styrene) A M X

49. AA’XX’ pattern

50. AA’BB’ pattern * *

51. A compound whose 1 H NMR spectrum appears below has a molecular formula of C 7 H 14 O 2. The IR spectrum shows a strong absorbance at 1739 cm -1. Suggest a structure for this compound. 15 mm 23 mm