1. BenZene Ractions Dr Md Ashraful Alam Assistant Professor Department of Pharmaceutical Sciences

2. Benzene does not undergo electrophilic addition It undergoes electrophilic aromatic substitution maintaining the aromatic core Electrophilic aromatic substitution replaces a proton on benzene with a.nother electrophile 2

3. 3 electrophilic aromatic substitution

4. Electrophilic Aromatic Substitution

5. Ortho-Para and Meta Directing Substituents When substituted benzenes undergo further substituents, the substituent group present in the benzene derivative will influence electrophilic substitution in 2 ways which are: i) Reactivity ii)Orientation

6. EFFECTS OF SUBSTITUENTS ON THE REACTIVITY OF ELECTROPHILIC AROMATIC SUBSTITUTION Substituent group present in the benzene ring can influence the rate of reaction of further substitutions. Electron-donating groups make the ring more reactive (called activating groups) thus influence the reaction become faster. Electron-withdrawing groups make the ring less reactive (called deactivating groups) thus influence the reaction become slower.

7. A substituents group already in the ring influences the position of further electrophilic substitution whether at ortho, meta or para position. Ortho-para directors: the groups that tend to direct electrophilic substitution to the C2 and C4 positions. Meta directors: the groups that tend to direct electrophilic substitution to the C3 position. EFFECTS OF SUBSTITUENTS ON THE ORIENTATION OF ELECTROPHILIC AROMATIC SUBSTITUTION

8. Effetcs of substituent groups on the benzene ring Activating groups (electron donating) Deactivating groups (electron-withdrawing) -NH 2 -R -OH -OR -NHCOCH 3 -F -Cl -Br -I ortho-para directors meta directors

9. Disubstituted Benzenes : Orientation Orientation Effects of Substituents in Electrophilic Aromatic Substitution : Meta directorsOrtho, para directors -NO2 -SO3H -COOH, -COOR -CHO, -COR -CN -OH, -OR -NH2, -NHR, -NR2 -C6H5 -CH3, -R (alkyl) -F, -Cl, -Br, -I

10. 10 Substituent Effects in Aromatic Rings Substituents can cause a compound to be (much) more or (much) less reactive than benzene Substituents affect the orientation of the reaction – the positional relationship is controlled –ortho- and para-directing activators, ortho- and para- directing deactivators, and meta-directing deactivators

11. 11 Activators/ Deactivators

12. Specific Electrophilic Aromatic : Substitution Reactions

13. EAS Reactions of Benzene

14. Benzene’s  electrons participate as a Lewis base in reactions with Lewis acids –Lewis acid: electron pair acceptor –Lewis base: electron pair donor The product is formed by loss of a proton, which is replaced by a halogen 14 Bromination / Chlorination

16. Bromination Mechanism

17. Nitration

18. Nitration Mechanism

19. Nitration of Toluene

20. Sulfonation is Reversible

21. Desulfonation

22. Friedel-Crafts Acylation

24. 1 st, Formaton of Electrophile

25. Acylation Mechanism

26. Intermediate is Resonance-Stabilized

27. An Acylation

28. Friedel-Crafts Alkylation many more limitations

30. Mechanism

31. Carbocation Generated From Alkene

32. Unexpected Product?

33. Carbocations Rearrange…

34. 1 o RX Typically Undergoes Shift

35. Side Chain Reactions 1) Reduction of Aromatic Ketones

36. Straight-chain Alkylation can be Accomplished in 2 steps: Acylation, then Reduction

37. 2) Oxidation of Alkyl Substituents

38. 3) Benzylic Bromination with NBS N-Bromosuccinimide

39. 4) Alkali Fusion of Sulfonic Acids

40. 5) Reduction of Nitro Groups

41. Directing Effects

42. ortho/para-Directing Activating Groups

43. Nitration of Anisole

44. Nitration Affords ortho and para Products

45. Activating ortho/para directors

46. meta-Directing Deactivating Groups

47. Electron-Withdrawing Nitro Group Directs meta

49. meta Directors

50. Comparison

51. More Limitations with Friedel Crafts Reactions

52. Substituent Summary

53. Halogens are the Anomoly Deactivators and o,p-Directors

54. Reactions of Rings With Two or More Substituents

55. The (More) Activated Ring Reacts

56. Mixtures with Conflicting Directing Effects

57. Provide the Reagents

58. Must Acylate First

59. Sulfonic Acid Blocks para Position

60. Give the Reagents

61. Provide the Reagents

65. 65 Reactions of Benzene