Table 12.1: Halogenation of Benzene

1. H Br Table 12.1: Halogenation of Benzene FeBr3 + Br2 + HBr Bromobenzene(65-75%)

2. H C(CH3)3 Table 12.1: Friedel-Crafts Alkylation of Benzene AlCl3 + (CH3)3CCl + HCl tert-Butylbenzene(60%)

3. O O H CCH2CH3 CH3CH2CCl Table 12.1: Friedel-Crafts Acylation of Benzene AlCl3 + + HCl 1-Phenyl-1-propanone(88%)

4. H Br Halogenation of Benzene FeBr3 + Br2 + HBr Electrophile is a Lewis acid-Lewis basecomplex between FeBr3 and Br2.

5. + – •• •• •• •• • • • Br Br Br Br FeBr3 • • • •• •• •• •• The Br2-FeBr3 Complex The Br2-FeBr3 complex is more electrophilic than Br2 alone. + FeBr3 Lewis base Lewis acid Complex

6. H H Br H + H H H Step 1: attack of Br2-FeBr3 complex on p-electron system of aromatic ring + – Br Br FeBr3 H H H H H H + FeBr4–

7. Step 2: loss of a proton from the carbocationintermediate H H Br H H H H Br + H H H H H H+

8. 12.6Friedel-Crafts Alkylation of Benzene

9. H C(CH3)3 H3C + CH3 C H3C Friedel-Crafts Alkylation of Benzene AlCl3 + (CH3)3CCl + HCl Electrophile is tert-butyl cation

10. + – •• • AlCl3 (CH3)3C Cl • •• Role of AlCl3 acts as a Lewis acid to promote ionizationof the alkyl halide •• + (CH3)3C Cl AlCl3 ••

11. + – •• • AlCl3 (CH3)3C Cl • •• – •• • AlCl3 Cl • •• Role of AlCl3 acts as a Lewis acid to promote ionizationof the alkyl halide •• + (CH3)3C Cl AlCl3 •• + + (CH3)3C

12. + C(CH3)3 H H C(CH3)3 H + H H H Step 1: attack of tert-butyl cationon p-electron system of aromatic ring H H H H H H

13. Step 2: loss of a proton from the carbocationintermediate H H C(CH3)3 H H H H C(CH3)3 + H H H H H H+

14. H Reactions Related to Friedel-Crafts Alkylation Cyclohexene is protonated by sulfuric acid, giving cyclohexyl cation which attacks the benzene ring H2SO4 + Cyclohexylbenzene(65-68%)

15. 12.7Friedel-Crafts Acylation of Benzene

16. H + + •• • • CH3CH2C O CH3CH2C O • • Friedel-Crafts Acylation of Benzene O O CCH2CH3 AlCl3 + CH3CH2CCl + HCl Electrophile is an acyl cation

17. O O CCH2CH3 + CCH2CH3 Step 1: attack of the acyl cationon p-electron system of aromatic ring H H H H H H H + H H H H H

18. O O CCH2CH3 CCH2CH3 Step 2: loss of a proton from the carbocationintermediate H H H H H H + H H H H H H+

19. O O O H CCH3 CH3COCCH3 O + CH3COH Acid Anhydrides can be used instead of acyl chlorides AlCl3 + Acetophenone(76-83%)

20. 12.8Acylation-Reduction

21. O O H CR Acylation-Reduction permits primary alkyl groups to be attachedto an aromatic ring Reduction of aldehyde and ketonecarbonyl groups using Zn(Hg) and HCl is called the Clemmensen reduction. RCCl AlCl3 Zn(Hg), HCl CH2R

22. O O H CR Acylation-Reduction permits primary alkyl groups to be attachedto an aromatic ring Reduction of aldehyde and ketonecarbonyl groups by heating with H2NNH2and KOH is called theWolff-Kishner reduction. RCCl H2NNH2, KOH,triethylene glycol,heat AlCl3 CH2R

23. H C(CH3)3 AlCl3 Rearrangements in Friedel-Crafts Alkylation Carbocations are intermediates. Therefore, rearrangements can occur + (CH3)2CHCH2Cl Isobutyl chloride tert-Butylbenzene(66%)

24. H C(CH3)3 AlCl3 Rearrangements in Friedel-Crafts Alkylation Isobutyl chloride is the alkyl halide. But tert-butyl cation is the electrophile. + (CH3)2CHCH2Cl Isobutyl chloride tert-Butylbenzene(66%)

25. H •• AlCl3 H3C Cl C CH2 •• CH3 – •• • AlCl3 Cl • •• Rearrangements in Friedel-Crafts Alkylation + – H + + H3C C CH2 CH3

26. Example: Prepare isobutylbenzene No! Friedel-Crafts alkylation of benzene using isobutyl chloride fails because of rearrangement. (CH3)2CHCH2Cl CH2CH(CH3)2 AlCl3

27. C(CH3)3 AlCl3 Recall + (CH3)2CHCH2Cl Isobutyl chloride tert-Butylbenzene(66%)

28. O (CH3)2CHCCl CH2CH(CH3)2 O CCH(CH3)2 Use Acylation-Reduction Instead + AlCl3 Zn(Hg)HCl