Reactions of Aromatic Compounds Based on Solomons , Fryhle Organic Chemistry 10 th . Edition

1. . Reactions of Aromatic Compounds Based on Solomons , Fryhle Organic Chemistry 10th. Edition

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. Electrophilic AromaticSubstitution Reactions • Overall reaction

5. A General Mechanism for Electro-philic Aromatic Substitution • Different chemistry with alkene

6. Benzene does not undergo electrophilicaddition, but it undergoes electrophilic aromatic substitution

7. Mechanism • Step 1

8. Mechanism • Step 2

10. Halogenation of Benzene • Benzene does not react with Br2 or Cl2 unless a Lewis acid is present (catalytic amount is usually enough)

11. Examples • Reactivity: F2 > Cl2 > Br2 > I2

12. Mechanism

13. Mechanism (Cont’d)

14. Mechanism (Cont’d)

15. F2: too reactive, give mixture of mono-, di- and highly substituted products

16. I2: very unreactive even in the presence of Lewis acid, usually need to add an oxidizing agent (e.g. HNO3, Cu2+, H2O2)

17. Nitration of Benzene • Electrophile in this case is NO2 (nitronium ion)

18. Mechanism

19. Mechanism (Cont’d)

20. Mechanism (Cont’d)

21. Sulfonation of Benzene • Mechanism • Step 1 • Step 2

22. Step 3 • Step 4

23. Sulfonation & Desulfonation

24. Friedel–Crafts Alkylation • Electrophile in this case is R • R = 2o or 3o • Or (R = 1o)

25. Mechanism

26. Mechanism (Cont’d)

27. Mechanism (Cont’d)

28. Note: Not necessary to start with alkyl halide, other possible functional groups can be used to generate a reactive carbocation

30. Friedel–Crafts Acylation • Acyl group: • Electrophile in this case is R–C≡O (acylium ion)

31. Mechanism

32. Mechanism (Cont’d)

33. Mechanism (Cont’d)

34. Acid chlorides (or acyl chlorides) • Can be prepared by

35. Limitations of Friedel–CraftsReactions • When the carbocation formed from an alkyl halide, alkene, or alcohol can rearrange to one or more carbocations that are more stable, it usually does so, and the major products obtained from the reaction are usually those from the more stable carbocations

36. (not formed) (How is this Formed?) • For example

37. Reason 1o cation (not stable) 3o cation (more stable)

38. Friedel–Crafts reactions usually give poor yields when powerful electron-withdrawing groups are present on the aromatic ring or when the ring bears an –NH2, –NHR, or –NR2 group. This applies to both alkylations and acylations These usually give poor yields in Friedel-Crafts reactions

39. The amino groups, –NH2, –NHR, and –NR2, are changed into powerful electron-withdrawing groups by the Lewis acids used to catalyze Friedel-Crafts reactions Does not undergo a Friedel-Crafts reaction

40. Aryl and vinylic halides cannot be used as the halide component because they do not form carbocations readily sp2 sp2

41. Polyalkylations often occur

42. Synthetic Applications ofFriedel-Crafts Acylations: The Clemmensen Reduction • Clemmensen ketone reduction

43. Clemmensen ketone reduction • A very useful reaction for making alkyl benzene that cannot be made via Friedel-Crafts alkylations

44. Clemmensen ketone reduction • Cannot use Friedel-Crafts alkylation

45. Rearrangements of carbon chain do not occur in Friedel-Crafts acylations (no rearrangement of the R group)

47. Substituents Can Affect Boththe Reactivity of the Ring and the Orientation of the Incoming Group • Two questions we would like to address here • Reactivity • Regiochemistry

48. Reactivity faster or slower than Y = EDG (electron-donating group) or EWG (electron-withdrawing group)

49. Regiochemistry Statistical mixture of o-, m-, p- products or any preference?

50. d+ d- Electrophilic reagent Arenium ion A substituted benzene