1. Chapter 17 Reactions of Aromatic Compounds Jo Blackburn Richland College, Dallas, TX Dallas County Community College District  2003,  Prentice Hall Organic Chemistry, 5 th Edition L. G. Wade, Jr.

2. Chapter 172 Electrophilic Aromatic Substitution Electrophile substitutes for a hydrogen on the benzene ring. =>

3. Chapter 173 Mechanism =>

4. Chapter 174 Bromination of Benzene Requires a stronger electrophile than Br 2. Use a strong Lewis acid catalyst, FeBr 3. Animation =>

5. Chapter 175 Energy Diagram for Bromination =>

6. Chapter 176 Chlorination and Iodination Chlorination is similar to bromination. Use AlCl 3 as the Lewis acid catalyst. Iodination requires an acidic oxidizing agent, like nitric acid, which oxidizes the iodine to an iodonium ion. =>

7. Chapter 177 Nitration of Benzene Use sulfuric acid with nitric acid to form the nitronium ion electrophile. NO 2 + then forms a sigma complex with benzene, loses H + to form nitrobenzene. =>

8. Chapter 178 Sulfonation Sulfur trioxide, SO 3, in fuming sulfuric acid is the electrophile. =>

9. Chapter 179 Desulfonation All steps are reversible, so sulfonic acid group can be removed by heating in dilute sulfuric acid. This process is used to place deuterium in place of hydrogen on benzene ring. Benzene-d 6 =>

10. Chapter 1710 Nitration of Toluene Toluene reacts 25 times faster than benzene. The methyl group is an activator. The product mix contains mostly ortho and para substituted molecules. =>

11. Chapter 1711 Sigma Complex Intermediate is more stable if nitration occurs at the ortho or para position. =>

12. Chapter 1712 Energy Diagram =>

13. Chapter 1713 Activating, O-, P- Directing Substituents Alkyl groups stabilize the sigma complex by induction, donating electron density through the sigma bond. Substituents with a lone pair of electrons stabilize the sigma complex by resonance. =>

14. Chapter 1714 Nitration of Anisole Ortho attack Meta attack Para attack =>

15. Chapter 1715 The Amino Group Aniline reacts with bromine water (without a catalyst) to yield the tribromide. Sodium bicarbonate is added to neutralize the HBr that’s also formed. =>

16. Chapter 1716 Summary of Activators =>

17. Chapter 1717 Deactivating Meta- Directing Substituents Electrophilic substitution reactions for nitrobenzene are 100,000 times slower than for benzene. The product mix contains mostly the meta isomer, only small amounts of the ortho and para isomers. Meta-directors deactivate all positions on the ring, but the meta position is less deactivated. =>

18. Chapter 1718 Ortho Substitution on Nitrobenzene =>

19. Chapter 1719 Para Substitution on Nitrobenzene =>

20. Chapter 1720 Meta Substitution on Nitrobenzene =>

21. Chapter 1721 Energy Diagram =>

22. Chapter 1722 Structure of Meta- Directing Deactivators The atom attached to the aromatic ring will have a partial positive charge. Electron density is withdrawn inductively along the sigma bond, so the ring is less electron-rich than benzene. =>

23. Chapter 1723 Summary of Deactivators =>

24. Chapter 1724 More Deactivators =>

25. Chapter 1725 Halobenzenes Halogens are deactivating toward electrophilic substitution, but are ortho, para-directing! Since halogens are very electronegative, they withdraw electron density from the ring inductively along the sigma bond. But halogens have lone pairs of electrons that can stabilize the sigma complex by resonance. =>

26. Chapter 1726 Sigma Complex for Bromobenzene Ortho and para attacks produce a bromonium ion and other resonance structures. => No bromonium ion possible with meta attack.

27. Chapter 1727 Energy Diagram =>

28. Chapter 1728 Summary of Directing Effects =>

29. Chapter 1729 Multiple Substituents The most strongly activating substituent will determine the position of the next substitution. May have mixtures. =>

30. Chapter 1730 Friedel-Crafts Alkylation Synthesis of alkyl benzenes from alkyl halides and a Lewis acid, usually AlCl 3. Reactions of alkyl halide with Lewis acid produces a carbocation which is the electrophile. Other sources of carbocations: alkenes + HF or alcohols + BF 3. =>

31. Chapter 1731 Examples of Carbocation Formation =>

32. Chapter 1732 Formation of Alkyl Benzene => + -

33. Chapter 1733 Limitations of Friedel-Crafts Reaction fails if benzene has a substituent that is more deactivating than halogen. Carbocations rearrange. Reaction of benzene with n-propyl chloride and AlCl 3 produces isopropylbenzene. The alkylbenzene product is more reactive than benzene, so polyalkylation occurs. =>

34. Chapter 1734 Friedel-Crafts Acylation Acyl chloride is used in place of alkyl chloride. The acylium ion intermediate is resonance stabilized and does not rearrange like a carbocation. The product is a phenyl ketone that is less reactive than benzene. =>

35. Chapter 1735 Mechanism of Acylation =>

36. Chapter 1736 Clemmensen Reduction Acylbenzenes can be converted to alkylbenzenes by treatment with aqueous HCl and amalgamated zinc. =>

37. Chapter 1737 Gatterman-Koch Formylation Formyl chloride is unstable. Use a high pressure mixture of CO, HCl, and catalyst. Product is benzaldehyde. =>

38. Chapter 1738 Nucleophilic Aromatic Substitution A nucleophile replaces a leaving group on the aromatic ring. Electron-withdrawing substituents activate the ring for nucleophilic substitution. =>

39. Chapter 1739 Examples of Nucleophilic Substitution =>

40. Chapter 1740 Addition-Elimination Mechanism =>

41. Chapter 1741 Benzyne Mechanism Reactant is halobenzene with no electron- withdrawing groups on the ring. Use a very strong base like NaNH 2. =>

42. Chapter 1742 Benzyne Intermediate =>

43. Chapter 1743 Chlorination of Benzene Addition to the benzene ring may occur with high heat and pressure (or light). The first Cl 2 addition is difficult, but the next 2 moles add rapidly. The product, benzene hexachloride, is an insecticide. =>

44. Chapter 1744 Catalytic Hydrogenation Elevated heat and pressure is required. Possible catalysts: Pt, Pd, Ni, Ru, Rh. Reduction cannot be stopped at an intermediate stage. =>

45. Chapter 1745 Birch Reduction: Regiospecific A carbon with an e - -withdrawing group is reduced. A carbon with an e - -releasing group is not reduced. =>

46. Chapter 1746 Birch Mechanism =>

47. Chapter 1747 Side-Chain Oxidation Alkylbenzenes are oxidized to benzoic acid by hot KMnO 4 or Na 2 Cr 2 O 7 /H 2 SO 4. =>

48. Chapter 1748 Side-Chain Halogenation Benzylic position is the most reactive. Chlorination is not as selective as bromination, results in mixtures. Br 2 reacts only at the benzylic position. =>

49. Chapter 1749 S N 1 Reactions Benzylic carbocations are resonance- stabilized, easily formed. Benzyl halides undergo S N 1 reactions. =>

50. Chapter 1750 S N 2 Reactions Benzylic halides are 100 times more reactive than primary halides via S N 2. Transition state is stabilized by ring. =>

51. Chapter 1751 Reactions of Phenols Some reactions like aliphatic alcohols:  phenol + carboxylic acid  ester  phenol + aq. NaOH  phenoxide ion Oxidation to quinones: 1,4-diketones. =>

52. Chapter 1752 Quinones Hydroquinone is used as a developer for film. It reacts with light-sensitized AgBr grains, converting it to black Ag. Coenzyme Q is an oxidizing agent found in the mitochondria of cells. =>

53. Chapter 1753 Electrophilic Substitution of Phenols Phenols and phenoxides are highly reactive. Only a weak catalyst (HF) required for Friedel-Crafts reaction. Tribromination occurs without catalyst. Even reacts with CO 2. =>

54. Chapter 1754 End of Chapter 17