Chapter 12Chapter 12Reactions of Arenes:Reactions of Arenes:

Electrophilic Aromatic SubstitutionElectrophilic Aromatic Substitution

HH

EE

++ EE YY ++ HH YY++ ––

12.1Representative Electrophilic Aromatic

Substitution Reactions of Benzene

HH

EE

++ EE YY ++ HH YY++ ––

HH

EE

++ EE YY ++ HH YY++ ––

Electrophilic aromatic substitutions include:Electrophilic aromatic substitutions include:

NitrationNitration

SulfonationSulfonation

HalogenationHalogenation

Friedel-Crafts AlkylationFriedel-Crafts Alkylation

Friedel-Crafts AcylationFriedel-Crafts Acylation

HH

Table 12.1: Table 12.1: Nitration of BenzeneNitration of Benzene

++ ++ HH22OO

HH22SOSO44

HOHONONO22

NONO22

NitrobenzeneNitrobenzene(95%)(95%)

HH

Table 12.1: Sulfonation of BenzeneTable 12.1: Sulfonation of Benzene

++ ++ HH22OO

heatheatHOHOSOSO22OHOH

SOSO22OHOH

Benzenesulfonic acidBenzenesulfonic acid(100%)(100%)

HH

Table 12.1: Halogenation of BenzeneTable 12.1: Halogenation of Benzene

++ ++ HHBrBr

FeBrFeBr33

BrBr22

BrBr22

BromobenzeneBromobenzene(65-75%)(65-75%)

HH

Table 12.1: Friedel-Crafts Alkylation of BenzeneTable 12.1: Friedel-Crafts Alkylation of Benzene

++ ++ HHClCl

AlClAlCl33

C(CHC(CH33))33

terttert-Butylbenzene-Butylbenzene(60%)(60%)

(CH(CH33))33CCClCl

HH

Table 12.1: Friedel-Crafts Acylation of BenzeneTable 12.1: Friedel-Crafts Acylation of Benzene

++ ++ HHClCl

AlClAlCl33

1-Phenyl-1-propanone1-Phenyl-1-propanone(88%)(88%)

OO

CHCH33CHCH22CCClCl

CCHCCH22CHCH33

OO

12.212.2Mechanistic PrinciplesMechanistic Principles

ofofElectrophilic Aromatic SubstitutionElectrophilic Aromatic Substitution

Step 1: attack of electrophileStep 1: attack of electrophileon on -electron system of aromatic ring-electron system of aromatic ring

HH HH

HH HHHH HH

EE++

HH HH

HHHH

HH HH EE

++

highly endothermichighly endothermic

carbocation is allylic, but not aromaticcarbocation is allylic, but not aromatic

Step 2: loss of a proton from the carbocationStep 2: loss of a proton from the carbocationintermediateintermediate

HH HH

HH EEHH HH

HH++ HH HH

HHHH

HH HH EE

++

highly exothermichighly exothermic

this step restores aromaticity of ringthis step restores aromaticity of ring

HH

H H

H + E+

H

EH

H H

H + H+

H

H H

HH

H H E

+

Based on this general mechanism:Based on this general mechanism:

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

12.3Nitration of Benzene

HH

Nitration of BenzeneNitration of Benzene

++ ++ HH22OO

HH22SOSO44

HOHONONO22

NONO22

Electrophile isElectrophile isnitronium ion nitronium ion

OO NN OO••••

++

•••••••• ••••

Step 1: attack of nitronium cationStep 1: attack of nitronium cationon on -electron system of aromatic ring-electron system of aromatic ring

HH HH

HH HHHH HH

NONO22++

HH HH

HHHH

HH HH NONO22

++

Step 2: loss of a proton from the carbocationStep 2: loss of a proton from the carbocationintermediateintermediate

HH HH

HH NONO22

HH HH

HH++ HH HH

HHHH

HH HH NONO22

++

Where does nitronium ion come from?Where does nitronium ion come from?

HH22SOSO44

OONN

HH

OO

OO

++•••• ••••

••••••••

•••• ••••••••

––OO

NN

HH

OO

OO

++•••• ••••

••••

•••• ••••••••

––

HH++

OO NN OO••••

++

•••••••• •••• ++ HH

OO••••HH

••••

12.4Sulfonation of Benzene

HH

Sulfonation of BenzeneSulfonation of Benzene

++ ++ HH22OO

heatheatHOHOSOSO22OHOH

SOSO22OHOH

Several electrophiles present:Several electrophiles present:a major one is sulfur trioxidea major one is sulfur trioxide

OOSS

OO

OO

++•••• ••••

••••••••

•••• ••••••••

––

Step 1: attack of sulfur trioxideStep 1: attack of sulfur trioxideon on -electron system of aromatic ring-electron system of aromatic ring

HH HH

HH HHHH HH

SOSO33

HH HH

HHHH

HH HH SOSO33––

++

Step 2: loss of a proton from the carbocationStep 2: loss of a proton from the carbocationintermediateintermediate

HH HH

HH SOSO33––

HH HH

HH++ HH HH

HHHH

HH HH SOSO33––

++

Step 3: protonation of benzenesulfonate ionStep 3: protonation of benzenesulfonate ion

HH HH

HH SOSO33––

HH HH

HH22SOSO44

HH HH

HH SOSO33HHHH HH

12.5Halogenation of Benzene

HH

Halogenation of BenzeneHalogenation of Benzene

++ ++ HHBrBr

FeBrFeBr33

BrBr22

BrBr22

Electrophile is a Lewis acid-Lewis baseElectrophile is a Lewis acid-Lewis basecomplex between FeBrcomplex between FeBr33 and Br and Br22..

The BrThe Br22-FeBr-FeBr33 Complex Complex

++••••BrBr BrBr•••••••• ••••

•••• ••••

Lewis baseLewis base Lewis acidLewis acid

FeBrFeBr33

BrBr BrBr•••••••• ••••

•••• ••••FeBrFeBr33

––++

ComplexComplex

The BrThe Br22-FeBr-FeBr33 complex is more electrophilic complex is more electrophilic

than Brthan Br22 alone. alone.

Step 1: attack of BrStep 1: attack of Br22-FeBr-FeBr33 complex complex

on on -electron system of aromatic ring-electron system of aromatic ring

HH HH

HH HHHH HH

HH HH

HHHH

HH HH BrBr

++

BrBr BrBr FeBrFeBr33

––++

+ FeBr+ FeBr44––

Step 2: loss of a proton from the carbocationStep 2: loss of a proton from the carbocationintermediateintermediate

HH HH

HH BrBrHH HH

HH++ HH HH

HHHH

HH HH BrBr

++

12.6Friedel-Crafts Alkylation of Benzene

HH

Friedel-Crafts Alkylation of BenzeneFriedel-Crafts Alkylation of Benzene

++ ++ HHClCl

AlClAlCl33

C(CHC(CH33))33

Electrophile is Electrophile is terttert-butyl cation-butyl cation

(CH(CH33))33CClCCl

CC CHCH33

HH33CC

HH33CC++

acts as a Lewis acid to promote ionizationacts as a Lewis acid to promote ionizationof the alkyl halideof the alkyl halide

Role of AlClRole of AlCl33

(CH(CH33))33CC ClCl ••••••••

••••++ AlClAlCl33

++(CH(CH33))33CC ClCl

••••

••••AlClAlCl33––

acts as a Lewis acid to promote ionizationacts as a Lewis acid to promote ionizationof the alkyl halideof the alkyl halide

Role of AlClRole of AlCl33

(CH(CH33))33CC ClCl ••••••••

••••++ AlClAlCl33

++(CH(CH33))33CC ClCl

••••

••••AlClAlCl33––

++(CH(CH33))33CC ClCl

••••

••••AlClAlCl33––

••••++

Step 1: attack of tert-butyl cationStep 1: attack of tert-butyl cationon on -electron system of aromatic ring-electron system of aromatic ring

HH HH

HH HHHH HH

HH HH

HHHH

HH HH C(CHC(CH33))33

++

C(CHC(CH33))33++

Step 2: loss of a proton from the carbocationStep 2: loss of a proton from the carbocationintermediateintermediate

HH HH

HH C(CHC(CH33))33

HH HH

HH++ HH HH

HHHH

HH HH C(CHC(CH33))33

++

HH

Rearrangements in Friedel-Crafts AlkylationRearrangements in Friedel-Crafts Alkylation

Carbocations are intermediates.Carbocations are intermediates.

Therefore, rearrangements can occurTherefore, rearrangements can occur

(CH(CH33))22CHCHCHCH22ClClAlClAlCl33

Isobutyl chlorideIsobutyl chloride terttert-Butylbenzene-Butylbenzene(66%)(66%)

C(CHC(CH33))33

++

HH

Rearrangements in Friedel-Crafts AlkylationRearrangements in Friedel-Crafts Alkylation

Isobutyl chloride is the alkyl halide.Isobutyl chloride is the alkyl halide.

But But terttert-butyl cation is the -butyl cation is the electrophile.electrophile.

(CH(CH33))22CHCHCHCH22ClClAlClAlCl33

Isobutyl chlorideIsobutyl chloride terttert-Butylbenzene-Butylbenzene(66%)(66%)

C(CHC(CH33))33

++

Rearrangements in Friedel-Crafts AlkylationRearrangements in Friedel-Crafts Alkylation

CC CHCH22HH33CC

CHCH33

HH

ClCl••••

••••AlClAlCl33

++ ––

CC CHCH22HH33CC

CHCH33

HH++

++ ClCl••••

••••AlClAlCl33––

••••

HH

Reactions Related to Friedel-Crafts AlkylationReactions Related to Friedel-Crafts Alkylation

HH22SOSO44

++

CyclohexylbenzeneCyclohexylbenzene(65-68%)(65-68%)

Cyclohexene is protonated by sulfuric acid, Cyclohexene is protonated by sulfuric acid, giving cyclohexyl cation which attacks the giving cyclohexyl cation which attacks the benzene ringbenzene ring

12.7Friedel-Crafts Acylation of Benzene

HH

Friedel-Crafts Acylation of BenzeneFriedel-Crafts Acylation of Benzene

++ ++ HHClCl

AlClAlCl33OO

CHCH33CHCH22CClCCl

CCHCCH22CHCH33

OO

Electrophile is an acyl cationElectrophile is an acyl cation

••••CHCH33CHCH22CC OO ••••

++CHCH33CHCH22CC OO ••••

++

Step 1: attack of the acyl cationStep 1: attack of the acyl cationon on -electron system of aromatic ring-electron system of aromatic ring

HH HH

HH HHHH HH

HH HH

HHHH

HH HH

++

OO

CCHCCH22CHCH33++

OO

CCHCCH22CHCH33

Step 2: loss of a proton from the carbocationStep 2: loss of a proton from the carbocationintermediateintermediate

HH HH

HHHH HH

HH++ HH HH

HHHH

HH HH

++

OO

CCHCCH22CHCH33

OO

CCHCCH22CHCH33

can be used instead of acyl chloridescan be used instead of acyl chlorides

HH

Acid AnhydridesAcid Anhydrides

AcetophenoneAcetophenone(76-83%)(76-83%)

AlClAlCl33

OO

CCHCCH33

OO

CHCH33COCCHCOCCH33

OO

++

OO

CHCH33COHCOH++

12.8Acylation-Reduction

Reduction of aldehyde and ketoneReduction of aldehyde and ketone

carbonyl groups using Zn(Hg) and HCl is carbonyl groups using Zn(Hg) and HCl is

called the called the Clemmensen reductionClemmensen reduction..

Acylation-ReductionAcylation-Reduction

HH

OO

CRCR

Zn(Hg), HClZn(Hg), HClAlClAlCl33

RCClRCCl

OO

CHCH22RR

permits primary alkyl groups to be attachedpermits primary alkyl groups to be attachedto an aromatic ringto an aromatic ring

Reduction of aldehyde and ketoneReduction of aldehyde and ketonecarbonyl groups by heating with Hcarbonyl groups by heating with H22NNHNNH22

and KOH is called theand KOH is called the

Wolff-Kishner reductionWolff-Kishner reduction..

Acylation-ReductionAcylation-Reduction

HH

OO

CRCRHH22NNHNNH22, KOH,, KOH,

triethylene glycol,triethylene glycol,

heatheat

AlClAlCl33

RCClRCCl

OO

CHCH22RR

permits primary alkyl groups to be attachedpermits primary alkyl groups to be attachedto an aromatic ringto an aromatic ring

Example: Prepare isobutylbenzeneExample: Prepare isobutylbenzene

No! Friedel-Crafts alkylation of benzene No! Friedel-Crafts alkylation of benzene using isobutyl chloride fails because of using isobutyl chloride fails because of rearrangement.rearrangement.

(CH(CH33))22CHCHCHCH22ClCl

AlClAlCl33

CHCH22CH(CHCH(CH33))33

RecallRecall

(CH(CH33))22CHCHCHCH22ClClAlClAlCl33

Isobutyl chlorideIsobutyl chloride terttert-Butylbenzene-Butylbenzene(66%)(66%)

C(CHC(CH33))33

++

Use Acylation-Reduction InsteadUse Acylation-Reduction Instead

++

(CH(CH33))22CHCClCHCCl

OO

AlClAlCl33

OO

CCH(CHCCH(CH33))22

Zn(Hg)Zn(Hg)HClHCl

CHCH22CH(CHCH(CH33))33