electrophilic aromatic substitution - unamdepa.fquim.unam.mx/amyd/archivero/sea1_21979.pdfnitration,...
TRANSCRIPT
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Electrophilic Aromatic Substitution
H
E + E Y + H Y δ+ δ–
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H
E + E Y + H Y δ+ δ–
Electrophilic aromatic substitutions include:
Nitration Sulfonation Halogenation Friedel-Crafts Alkylation Friedel-Crafts Acylation
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H
Nitration of Benzene
+ + H2O
H2SO4 HONO2
NO2
Nitrobenzene (95%)
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H
Sulfonation of Benzene
+ + H2O
heat HOSO2OH
SO2OH
Benzenesulfonic acid (100%)
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H
Halogenation of Benzene
+ + HBr
FeBr3 Br2
Br
Bromobenzene (65-75%)
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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
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Mechanistic Principles
of Electrophilic Aromatic Substitution
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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
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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+
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H H
H H
H + E+
H E
H
H H
H + H+
H
H H
H H
H H E +
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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
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Nitration of Benzene
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H
Nitration of Benzene
+ + H2O
H2SO4 HONO2
NO2
Electrophile is nitronium ion
O N O ••
+ ••
• • • •
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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 +
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Step 2: loss of a proton from the carbocation intermediate
H H
H H
H H NO2 +
H H
H NO2 H H
H+
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Where does nitronium ion come from?
H2SO4 O
N
H
O
O
+ •• ••
•• • •
• • • • ••
– O N
H
O
O
+ •• ••
••
• • • • ••
–
H +
O N O ••
+ ••
• • • • + H O •• H
••
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Sulfonation of Benzene
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H
Sulfonation of Benzene
+ + H2O
heat HOSO2OH
SO2OH
Several electrophiles present: a major one is sulfur trioxide
O S
O
O
+ •• ••
•• • •
• • • • ••
–
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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–
+
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Step 2: loss of a proton from the carbocation intermediate
H H
H H
H H SO3–
+
H H
H SO3– H H
H+
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Step 3: protonation of benzenesulfonate ion
H H
H SO3– H H
H2SO4
H H
H SO3H H H
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Halogenation of Benzene
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H
Halogenation of Benzene
+ + HBr
FeBr3 Br2
Br
Electrophile is a Lewis acid-Lewis base complex between FeBr3 and Br2.
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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.
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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–
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Step 2: loss of a proton from the carbocation intermediate
H H
H H
H H Br +
H H
H Br H H
H+
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Friedel-Crafts Alkylation of Benzene
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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 –
• • +
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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 +
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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+
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Rearrangements in Friedel-Crafts Alkylation
Carbocations are intermediates. Therefore, rearrangements can occur
The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. H
(CH3)2CHCH2Cl AlCl3
Isobutyl chloride tert-Butylbenzene (66%)
The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. C(CH3)3
+
-
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%)
The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. C(CH3)3
+
-
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
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Friedel-Crafts Acylation of Benzene
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H
Friedel-Crafts Acylation of Benzene
+ + HCl
AlCl3 O
CH3CH2CCl
CCH2CH3
O
Electrophile is an acyl cation
•• CH3CH2C O • •
+ CH3CH2C O • •
+
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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
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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 +
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Acylation-Reduction
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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
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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
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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 +
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Use Acylation-Reduction Instead
+
(CH3)2CHCCl
O
AlCl3
O
CCH(CH3)2
Zn(Hg) HCl
CH2CH(CH3)3