Chapter 12 Reactions of Arenes: Electrophilic Aromatic Substitution HE+ EY + HY ++++ ––––

12.1 Representative Electrophilic Aromatic Substitution Reactions of BenzeneHE+ EY + HY ++++ ––––

HE+ EY + HY ++++ –––– Electrophilic aromatic substitutions include: NitrationSulfonationHalogenation Friedel-Crafts Alkylation Friedel-Crafts Acylation

H Table 12.1: Nitration of Benzene + + H2OH2OH2OH2O H 2 SO 4 HONO 2 NO 2 Nitrobenzene (95%)

H Table 12.1: Sulfonation of Benzene + + H2OH2OH2OH2O heat HOSO 2 OH SO 2 OH Benzenesulfonic acid (100%)

H Table 12.1: Halogenation of Benzene + + HBr FeBr 3 Br 2 Bromobenzene (65-75%)

H Table 12.1: Friedel-Crafts Alkylation of Benzene + + HCl AlCl 3 C(CH 3 ) 3 tert-Butylbenzene (60%) (CH 3 ) 3 CCl

H Table 12.1: Friedel-Crafts Acylation of Benzene + + HCl AlCl 3 1-Phenyl-1-propanone (88%) O CH 3 CH 2 CCl CCH 2 CH 3 O

12.2 Mechanistic Principles of Electrophilic Aromatic Substitution

Step 1: attack of electrophile on  -electron system of aromatic ring HH HH HH E+E+E+E+ HH H HHHE + highly endothermic carbocation is allylic, but not aromatic

Step 2: loss of a proton from the carbocation intermediate HH HE HH H+H+H+H+ HH H H HH E + highly exothermic this step restores aromaticity of ring

H H HH H + E + H E H HH H + H + H HH H H HH E +

Based on this general mechanism: what remains is to identify the electrophile in nitration, sulfonation, halogenation, Friedel- Crafts alkylation, and Friedel-Crafts acylation to establish the mechanism of specific electrophilic aromatic substitutions

12.3 Nitration of Benzene

H Nitration of Benzene + + H2OH2OH2OH2O H 2 SO 4 HONO 2 NO 2 Electrophile is nitronium ion O N O +

Step 1: attack of nitronium cation on  -electron system of aromatic ring HH HH HH NO 2 + HH H HHH NO 2 +

Step 2: loss of a proton from the carbocation intermediate HH H NO 2 HH H+H+H+H+ HH H H HH +

Where does nitronium ion come from? H 2 SO 4 O N H O O + – O N H O O + –H + O N O + + H O H

12.4 Sulfonation of Benzene

H Sulfonation of Benzene + + H2OH2OH2OH2O heat HOSO 2 OH SO 2 OH Several electrophiles present: a major one is sulfur trioxide O S O O + –

Step 1: attack of sulfur trioxide on  -electron system of aromatic ring HH HH HH SO 3 HH H HHH SO 3 – +

Step 2: loss of a proton from the carbocation intermediate HH H SO 3 – HH H+H+H+H+ HH H H HH +

Step 3: protonation of benzenesulfonate ion HH H SO 3 – HH H 2 SO 4 HH H SO 3 H HH

12.5 Halogenation of Benzene

H Halogenation of Benzene + + HBr FeBr 3 Br 2 Electrophile is a Lewis acid-Lewis base complex between FeBr 3 and Br 2.

The Br 2 -FeBr 3 Complex + BrBr Lewis base Lewis acid FeBr 3 BrBr –+Complex The Br 2 -FeBr 3 complex is more electrophilic than Br 2 alone.

Step 1: attack of Br 2 -FeBr 3 complex on  -electron system of aromatic ring HH HH HH HH H HHHBr + BrBr FeBr 3 – + + FeBr 4 –

Step 2: loss of a proton from the carbocation intermediate HH HBr HH H+H+H+H+ HH H H HH Br +

12.6 Friedel-Crafts Alkylation of Benzene

H Friedel-Crafts Alkylation of Benzene + + HCl AlCl 3 C(CH 3 ) 3 Electrophile is tert-butyl cation (CH 3 ) 3 CCl C CH 3 H3CH3CH3CH3C H3CH3CH3CH3C+

acts as a Lewis acid to promote ionization of the alkyl halide Role of AlCl 3 (CH 3 ) 3 C Cl + AlCl 3 + (CH 3 ) 3 C Cl AlCl 3 –

acts as a Lewis acid to promote ionization of the alkyl halide Role of AlCl 3 (CH 3 ) 3 C Cl + AlCl 3 + (CH 3 ) 3 C Cl AlCl 3 – + (CH 3 ) 3 C Cl AlCl 3 – +

Step 1: attack of tert-butyl cation on  -electron system of aromatic ring HH HH HH HH H HHH C(CH 3 ) 3 + +

Step 2: loss of a proton from the carbocation intermediate HH H C(CH 3 ) 3 HH H+H+H+H+ HH H H HH +

H Rearrangements in Friedel-Crafts Alkylation Carbocations are intermediates. Therefore, rearrangements can occur (CH 3 ) 2 CHCH 2 Cl AlCl 3 Isobutyl chloride tert-Butylbenzene (66%) C(CH 3 ) 3 +

H Rearrangements in Friedel-Crafts Alkylation Isobutyl chloride is the alkyl halide. But tert-butyl cation is the electrophile. (CH 3 ) 2 CHCH 2 Cl AlCl 3 Isobutyl chloride tert-Butylbenzene (66%) C(CH 3 ) 3 +

Rearrangements in Friedel-Crafts Alkylation C CH 2 H3CH3CH3CH3C CH 3 HCl AlCl 3 + – C CH 2 H3CH3CH3CH3C CH 3 H + + Cl AlCl 3 –

H Reactions Related to Friedel-Crafts Alkylation H 2 SO 4 + Cyclohexylbenzene (65-68%) Cyclohexene is protonated by sulfuric acid, giving cyclohexyl cation which attacks the benzene ring

12.7 Friedel-Crafts Acylation of Benzene

H Friedel-Crafts Acylation of Benzene + + HCl AlCl 3 O CH 3 CH 2 CCl CCH 2 CH 3 O Electrophile is an acyl cation CH 3 CH 2 C O + O +

Step 1: attack of the acyl cation on  -electron system of aromatic ring HH HH HH HH H H HH +O CCH 2 CH 3 + O

Step 2: loss of a proton from the carbocation intermediate HH H HH H+H+H+H+ HH H H HH +O CCH 2 CH 3 O

can be used instead of acyl chlorides H Acid Anhydrides Acetophenone (76-83%) AlCl 3 O CCH 3 O CH 3 COCCH 3 O+O CH 3 COH +

12.8 Acylation-Reduction

Reduction of aldehyde and ketone carbonyl groups using Zn(Hg) and HCl is called the Clemmensen reduction. Acylation-ReductionH OCR Zn(Hg), HCl AlCl 3 RCClO CH 2 R permits primary alkyl groups to be attached to an aromatic ring

Reduction of aldehyde and ketone carbonyl groups by heating with H 2 NNH 2 and KOH is called the Wolff-Kishner reduction. Acylation-ReductionH OCR H 2 NNH 2, KOH, triethylene glycol, heat AlCl 3 RCClO CH 2 R permits primary alkyl groups to be attached to an aromatic ring

Example: Prepare isobutylbenzene No! Friedel-Crafts alkylation of benzene using isobutyl chloride fails because of rearrangement. (CH 3 ) 2 CHCH 2 Cl AlCl 3 CH 2 CH(CH 3 ) 3

Recall (CH 3 ) 2 CHCH 2 Cl AlCl 3 Isobutyl chloride tert-Butylbenzene (66%) C(CH 3 ) 3 +

Use Acylation-Reduction Instead + (CH 3 ) 2 CHCCl O AlCl 3 O CCH(CH 3 ) 2 Zn(Hg) HCl CH 2 CH(CH 3 ) 3