Chapter 20

1. Chapter 20 Amines

2. About The Authors These PowerPoint Lecture Slides were created and prepared by Professor William Tam and his wife, Dr. Phillis Chang. Professor William Tam received his B.Sc. at the University of Hong Kong in 1990 and his Ph.D. at the University of Toronto (Canada) in 1995. He was an NSERC postdoctoral fellow at the Imperial College (UK) and at Harvard University (USA). He joined the Department of Chemistry at the University of Guelph (Ontario, Canada) in 1998 and is currently a Full Professor and Associate Chair in the department. Professor Tam has received several awards in research and teaching, and according to Essential Science Indicators, he is currently ranked as the Top 1% most cited Chemists worldwide. He has published four books and over 80 scientific papers in top international journals such as J. Am. Chem. Soc., Angew. Chem., Org. Lett., and J. Org. Chem. Dr. Phillis Chang received her B.Sc. at New York University (USA) in 1994, her M.Sc. and Ph.D. in 1997 and 2001 at the University of Guelph (Canada). She lives in Guelph with her husband, William, and their son, Matthew.

3. Nomenclature • 1o Amines • 2o Amines

4. 3o Amines

5. 1A. Arylamines

6. 1B. Heterocyclic Amines

7. Physical Properties and Structure of Amines 2A. Physical Properties

8. 2B. Structure of Amines • N: sp3 hybridized • Trigonal pyramidal • Bond angles close to 109.5o

9. 3o Amines with three different groups • The two enantiomeric forms interconvert rapidly • Impossible to resolve enantiomers • Pyramidal or nitrogen inversion • Barrier ~ 25 kJ/mol • Enough to occur rapidly at room temperature

10. Ammonium salts with four different groups enantiomers can be resolved

11. Basicity of Amines:Amine Salts

12. The aminium ion of a more basic amine will have a larger pKa than the aminium ion of a less basic amine

13. > > By releasing electrons, R— stabilizes the alkylaminium ion through dispersal of charge >

15. 3A. Basicity of Arylamines

16. Five resonance structures

17. Only two resonance structures

19. 3B. Basicity of Heterocyclic Amines

21. 3C. Amines versus Amides • Amides are far less basic than amines (even less basic than arylamines). The pKa of the conjugate acid of a typical amide is about zero Larger resonance stabilization Smaller resonance stabilization

22. < >

23. 3D. Aminium Salts and QuaternaryAmmonium Salts Cannot act as bases However, R4N⊕⊖OH are strong bases (as strong as NaOH)

24. 3E. Solubility of Amines in AqueousAcids

25. 3F. Amines as Resolving Agents • Enantiomerically pure amines are often used to resolve racemic forms of acidic compounds by the formation of diastereomeric salts

27. Preparation of Amines 4A. Through Nucleophilic Substitution Reactions • Alkylation of ammonia

29. Alkylation of azide ion and reduction

30. The Gabriel synthesis

31. Alkylation of 3o amines

32. 4B. Preparation of Aromatic Amines through Reduction of Nitro Compounds

33. 4C. Preparation of Primary, Secondary, and Tertiary Amines through Reductive Amination

34. Mechanism

35. Examples

36. 4D. Preparation of Primary, Secondary, or Tertiary Amines through Reduction of Nitriles, Oximes, and Amides

37. Examples

38. Examples

39. 4D. Preparation of Primary Amines through the Hofmann and Curtius Rearrangements • Hofmann rearrangement

40. Examples

41. Mechanism

42. Curtius rearrangement

43. Reactions of Amines • Acid-base reactions • Alkylation

44. Acylation

45. Electrophilic aromatic substitution NH2: powerful activating group, ortho-para director

46. 5A. Oxidation of Amines

47. Reactions of Amines withNitrous Acid • Nitrous acid (HONO) is a weak, unstable acid

48. 6A. Reactions of Primary Aliphatic Amines with Nitrous Acid 1o aliphatic amine (aliphatic diazonium salt) (highly unstable)

49. 6B. Reactions of Primary Arylamines with Nitrous Acid (arenediazonium salt) (stable at <5oC)

50. Mechanism