Electrophilic Aromatic Substitution - UNAMdepa.fquim.unam.mx/amyd/archivero/SEA1_21979.pdfnitration,...

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Electrophilic Aromatic Substitution H E + E Y + H Y δ+ δ

Transcript of Electrophilic Aromatic Substitution - UNAMdepa.fquim.unam.mx/amyd/archivero/SEA1_21979.pdfnitration,...

  • Electrophilic Aromatic Substitution

    H

    E + E Y + H Y δ+ δ–

  • H

    E + E Y + H Y δ+ δ–

    Electrophilic aromatic substitutions include:

    Nitration Sulfonation Halogenation Friedel-Crafts Alkylation Friedel-Crafts Acylation

  • H

    Nitration of Benzene

    + + H2O

    H2SO4 HONO2

    NO2

    Nitrobenzene (95%)

  • H

    Sulfonation of Benzene

    + + H2O

    heat HOSO2OH

    SO2OH

    Benzenesulfonic acid (100%)

  • H

    Halogenation of Benzene

    + + HBr

    FeBr3 Br2

    Br

    Bromobenzene (65-75%)

  • H

    Friedel-Crafts Alkylation of Benzene

    + + HCl

    AlCl3

    C(CH3)3

    tert-Butylbenzene (60%)

    (CH3)3CCl

  • H

    Friedel-Crafts Acylation of Benzene

    + + HCl

    AlCl3

    1-Phenyl-1-propanone (88%)

    O

    CH3CH2CCl

    CCH2CH3

    O

  • Mechanistic Principles

    of Electrophilic Aromatic Substitution

  • Step 1: attack of electrophile on π-electron system of aromatic ring

    H H

    H H H H

    E+

    H H

    H H

    H H E +

    highly endothermic carbocation is allylic, but not aromatic

  • Step 2: loss of a proton from the carbocation intermediate

    H H

    H H

    H H E +

    highly exothermic this step restores aromaticity of ring

    H H

    H E H H

    H+

  • H H

    H H

    H + E+

    H E

    H

    H H

    H + H+

    H

    H H

    H H

    H H 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

  • Nitration of Benzene

  • H

    Nitration of Benzene

    + + H2O

    H2SO4 HONO2

    NO2

    Electrophile is nitronium ion

    O N O ••

    + ••

    • • • •

  • Step 1: attack of nitronium cation on π-electron system of aromatic ring

    H H

    H H H H

    NO2+

    H H

    H H

    H H NO2 +

  • Step 2: loss of a proton from the carbocation intermediate

    H H

    H H

    H H NO2 +

    H H

    H NO2 H H

    H+

  • Where does nitronium ion come from?

    H2SO4 O

    N

    H

    O

    O

    + •• ••

    •• • •

    • • • • ••

    – O N

    H

    O

    O

    + •• ••

    ••

    • • • • ••

    H +

    O N O ••

    + ••

    • • • • + H O •• H

    ••

  • Sulfonation of Benzene

  • H

    Sulfonation of Benzene

    + + H2O

    heat HOSO2OH

    SO2OH

    Several electrophiles present: a major one is sulfur trioxide

    O S

    O

    O

    + •• ••

    •• • •

    • • • • ••

  • Step 1: attack of sulfur trioxide on π-electron system of aromatic ring

    H H

    H H H H

    SO3

    H H

    H H

    H H SO3–

    +

  • Step 2: loss of a proton from the carbocation intermediate

    H H

    H H

    H H SO3–

    +

    H H

    H SO3– H H

    H+

  • Step 3: protonation of benzenesulfonate ion

    H H

    H SO3– H H

    H2SO4

    H H

    H SO3H H H

  • Halogenation of Benzene

  • H

    Halogenation of Benzene

    + + HBr

    FeBr3 Br2

    Br

    Electrophile is a Lewis acid-Lewis base complex between FeBr3 and Br2.

  • The Br2-FeBr3 Complex

    + • • Br Br • • •• ••

    •• ••

    Lewis base Lewis acid

    FeBr3

    Br Br • • •• ••

    •• •• FeBr3 – +

    Complex

    The Br2-FeBr3 complex is more electrophilic than Br2 alone.

  • Step 1: attack of Br2-FeBr3 complex on π-electron system of aromatic ring

    H H

    H H H H

    Br Br FeBr3

    – +

    H H

    H H

    H H Br +

    + FeBr4–

  • Step 2: loss of a proton from the carbocation intermediate

    H H

    H H

    H H Br +

    H H

    H Br H H

    H+

  • Friedel-Crafts Alkylation of Benzene

  • H

    Friedel-Crafts Alkylation of Benzene

    + + HCl

    AlCl3

    C(CH3)3 (CH3)3CCl

    Electrophile is tert-butyl cation C CH3

    H3C

    H3C +

  • acts as a Lewis acid to promote ionization of the alkyl halide

    Role of AlCl3

    (CH3)3C Cl • • ••

    •• + AlCl3

    + (CH3)3C Cl

    ••

    •• AlCl3 –

    (CH3)3C +

    Cl ••

    •• AlCl3 –

    • • +

  • Step 1: attack of tert-butyl cation on π-electron system of aromatic ring

    H H

    H H H H

    H H

    H H

    H H C(CH3)3 +

    C(CH3)3 +

  • Step 2: loss of a proton from the carbocation intermediate

    H H

    H H

    H H C(CH3)3 +

    H H

    H C(CH3)3 H H

    H+

  • Rearrangements in Friedel-Crafts Alkylation

    Carbocations are intermediates. Therefore, rearrangements can occur

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    (CH3)2CHCH2Cl AlCl3

    Isobutyl chloride tert-Butylbenzene (66%)

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    +

  • H

    Rearrangements in Friedel-Crafts Alkylation

    Isobutyl chloride is the alkyl halide. But tert-butyl cation is the electrophile.

    (CH3)2CHCH2Cl AlCl3

    Isobutyl chloride tert-Butylbenzene (66%)

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    +

  • Rearrangements in Friedel-Crafts Alkylation

    C CH2 H3C

    CH3

    H

    Cl ••

    •• AlCl3

    + –

    C CH2 H3C

    CH3

    H +

    + Cl ••

    •• AlCl3 –

    • •

  • H

    Reactions Related to Friedel-Crafts Alkylation

    H2SO4 +

    Cyclohexylbenzene (65-68%)

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

  • Friedel-Crafts Acylation of Benzene

  • H

    Friedel-Crafts Acylation of Benzene

    + + HCl

    AlCl3 O

    CH3CH2CCl

    CCH2CH3

    O

    Electrophile is an acyl cation

    •• CH3CH2C O • •

    + CH3CH2C O • •

    +

  • Step 1: attack of the acyl cation on π-electron system of aromatic ring

    H H

    H H H H

    O

    CCH2CH3 +

    H H

    H H

    H H

    +

    O

    CCH2CH3

  • Step 2: loss of a proton from the carbocation intermediate

    H H

    H H H

    H+

    O

    CCH2CH3

    H H

    H H

    H H

    +

    O

    CCH2CH3

  • can be used instead of acyl chlorides

    H

    Acid Anhydrides

    Acetophenone (76-83%)

    AlCl3

    O

    CCH3 O

    CH3COCCH3

    O

    +

    O

    CH3COH +

  • Acylation-Reduction

  • Reduction of aldehyde and ketone carbonyl groups using Zn(Hg) and HCl is called the Clemmensen reduction.

    Acylation-Reduction

    H O

    CR

    AlCl3

    RCCl

    O

    Zn(Hg), HCl

    CH2R

    permits primary alkyl groups to be attached to an aromatic ring

  • Reduction of aldehyde and ketone carbonyl groups by heating with H2NNH2 and KOH is called the Wolff-Kishner reduction.

    Acylation-Reduction

    H O

    CR H2NNH2, KOH, triethylene glycol, heat

    AlCl3

    RCCl

    O

    CH2R

    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.

    (CH3)2CHCH2Cl

    AlCl3

    CH2CH(CH3)3

  • Recall

    (CH3)2CHCH2Cl AlCl3

    Isobutyl chloride tert-Butylbenzene (66%)

    C(CH3)3 +

  • Use Acylation-Reduction Instead

    +

    (CH3)2CHCCl

    O

    AlCl3

    O

    CCH(CH3)2

    Zn(Hg) HCl

    CH2CH(CH3)3