Chapter 14faperta.ugm.ac.id/download/bahan_kuliah/tutik_dw/Kimia_Organik/CH... · Organic Chemistry...
Transcript of Chapter 14faperta.ugm.ac.id/download/bahan_kuliah/tutik_dw/Kimia_Organik/CH... · Organic Chemistry...
Organic Chemistry OnLine ©2000
Chapter 14
Electrophilic Aromatic Substitution-II
© 2000, Paul R. YoungUniversity of Illinois at Chicago
All Rights Reserved
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Electrophilic Aromatic Substitution
Acylation
Alkylation
Sulfonation
Nitration
Halogenation
C
O
R
R
SO3H
NO2
X X+
NO2+ HSO3
+ R+
RC O+
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Br2/FeBr3
Br
Fe
Br
Br
Br
Br Brδ δ
FeBr3 functions as a Lewis Acid, binding Br2 andcreating a source of the bromonium cation, Br+
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Br
Br
H
Br
H
H
Br
Br loss of H+
...the driving force for loss of H+ is therestoration of the aromatic system.
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Br
H
Br
H
H
Br
An electrostatic potential map showing chargedistribution in the cyclohexadienyl cation intermediate.
Electron donatingsubstituents at these
positions will stabilizethe cationic
intermediate.
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Cl2/FeCl3
ClCl
H
II
HI2
CuCl2
I
...CuCl2/I2 serves to generate I+
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NO2
NO2+
NO2
H
H2SO4 + HNO3 H2O + NO2+
Nitration
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SO3H
H
H2SO4 + SO3 SO3H+
+ HSO4-
SO3H+
SO3H
Sulfonation
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Friedel-Crafts Alkylation
CH3
CH3
HCH3
Cl
AlCl3
δ
δ
δδ
CH3 Cl AlCl3CH3Cl + AlCl3
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Limitations of the Friedel-Crafts Alkylation
1. Reaction limited to alkyl halides; aryl or vinyl halides donot react.
2. Reaction does not occur on rings containing strongelectron withdrawing substituents.
3. Multiple substitutions often occur.
4. Carbocation rearrangements can occur, particularly with1˚ alkyl halides.
NO2 CN SO3H CHO COR
COOH COOR NR3+
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O
CH3H
O
CH3
CH3
O
Friedel-Crafts Acylation
Cl AlCl3
CH3
O δ δ
ClH3C
O
+ AlCl3
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Friedel-Crafts Acylation
1. Multiple substitutions do not occur.
2. Carbocation rearrangements do not occur.
3. Reaction does not occur on rings containing strongelectron withdrawing substituents.
4. Acid anhydrides can also be used.
O
CH3
...ring is deactived after mono-substitution;multiple substitutions do not occur.
H3C O CH3
O O
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1. Predict the products of the following reactions.
AlCl3
AlCl3
Cl
Cl
O
HNO3/H2SO4
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1. Predict the products of the following reactions.
AlCl3
AlCl3
Cl
Cl
O
HNO3/H2SO4
O
CH3
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1. Predict the products of the following reactions.
AlCl3
AlCl3
Cl
Cl
O
HNO3/H2SO4
O
CH3
NO2
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1. Predict the products of the following reactions.
AlCl3
AlCl3
Cl
Cl
O
HNO3/H2SO4
O
CH3
NO2
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1.(con't) Predict the products of the following reactions.
AlCl3
O
O O
FeCl3
Cl2
SO3/H2SO4
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1.(con't) Predict the products of the following reactions.
AlCl3
O
O O
FeCl3
Cl2
SO3/H2SO4
Cl
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1.(con't) Predict the products of the following reactions.
AlCl3
O
O O
FeCl3
Cl2
SO3/H2SO4
Cl
SO3H
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1.(con't) Predict the products of the following reactions.
AlCl3
O
O O
FeCl3
Cl2
SO3/H2SO4
Cl
SO3H
O
CH2CH3
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H2/Pd25˚ C, 1 atm
Catalytic Reduction of AromaticCompounds
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H2/Pd25˚ C, 1 atm
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H2/Pd25˚ C, 1 atm
H2, Pt/C 25˚ C2000 psi
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H2/Pd25˚ C, 1 atm
H2, Rh/C25˚ C; 1 atm
H2, Pt/C 25˚ C2000 psi
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The Reduction of Aryl Nitro Groups and ArylKetones
O
H2/Pd25˚ C, 1 atm
NO2
H2/Pd25˚ C, 1 atm
NH2
...or...SnCl2/H3O
+
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+
O
Zn(Hg)H3O
+
Aryl ketones can also be reduced to thehydrocarbon using the Clemmensen Reduction.
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Suggest a synthesis of propylbenzene, beginning with benzene.
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AlCl3CH3CH2CH2Cl
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AlCl3CH3CH2CH2Cl
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Cl AlCl3 AlCl3CH3CH2CH2Cl
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1,2-hydride shift
Cl AlCl3
Cl AlCl3 AlCl3CH3CH2CH2Cl
H
H
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1,2-hydride shift
Cl AlCl3
Cl AlCl3 AlCl3CH3CH2CH2Cl
H
H
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Suggest a synthesis of propylbenzene, beginning with benzene.
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O
CH3CH2 C
O
Cl
AlCl3
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AlCl3
H2/Pd25˚ C, 1 atm
CH3CH2 C
O
Cl
O
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Reactions of Arylamines
H2/Pd25˚ C, 1 atm
NO2NH2
...or...SnCl2/H3O
+
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Reactions of Arylamines
H2/Pd25˚ C, 1 atm
NO2NH2
...or...SnCl2/H3O
+
NH2 N
N
HNO2H2SO4
A diazonium salt.
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H3PO2, H 2O
HCl, CuCl
HBr, CuBr
KI
N2+
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H3PO2, H 2O
HCl, CuCl
HBr, CuBr
KI
N2+
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H3PO2, H 2O
HCl, CuCl
HBr, CuBr
KI
N2+
Cl
Sandmeyer Reaction
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H3PO2, H 2O
HCl, CuCl
HBr, CuBr
KI
N2+
Cl
Br
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H3PO2, H 2O
HCl, CuCl
HBr, CuBr
KI
N2+
Cl
Br
I
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KCN, CuCN
H+/H2O
OH
N
CH3
CH3
N2+
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KCN, CuCN
H+/H2O
OH
N
CH3
CH3
N2+
CN
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KCN, CuCN
H+/H2O
OH
N
CH3
CH3
N2+
CN
OH
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KCN, CuCN
H+/H2O
OH
N
CH3
CH3
N2+
CN
OH
NN
OH
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OH
The oxygen atom in phenol is electron-releasing by resonance,activating the ring to electrophilic aromatic substitutionortho- and para- to the oxygen.
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OH
The oxygen atom in phenol is electron-releasing by resonance,activating the ring to electrophilic aromatic substitutionortho- and para- to the oxygen.
OH
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OH
The oxygen atom in phenol is electron-releasing by resonance,activating the ring to electrophilic aromatic substitutionortho- and para- to the oxygen.
OH
OH
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OH OH
OHOH
The oxygen atom in phenol is electron-releasing by resonance,activating the ring to electrophilic aromatic substitutionortho- and para- to the oxygen.
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OHδ
δ δ
Because of the increased electron density, an electrophile willattack the phenol ring preferentially at these positions.
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OHδ
δ δ
Because of the increased electron density, an electrophile willattack the phenol ring preferentially at these positions.
NN
A diazonium salt acting asan electrophile.
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NN
OH
OHδ
δ δ
NN
H+
OH
NN
HH
Because of the increased electron density, an electrophile willattack the phenol ring preferentially at these positions.
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NN
OH
OHδ
δ δ
NN
H+
OH
NN
HH
Because of the increased electron density, an electrophile willattack the phenol ring preferentially at these positions.
A diazonium“coupling” product.
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KCN, CuCN
H+/H2O
OH
N
CH3
CH3
N2+
CN
OH
NN
OH
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KCN, CuCN
H+/H2O
OH
N
CH3
CH3
N2+
CN
OH
NN
OH
NN
N
CH3
CH3
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NH2 NH2
Br
Br
Br
Br2
OH
OH
Br
Br
Br
Br2
Arylamines and Phenols are so highly activated towardselectrophilic aromatic substitution that they react withbromine in the absence of a catalyst to give tribromo adducts.
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Reactivity of Substituted Benzenes
1. Substituents effect the reactivity of aromatic rings.
2. Substituents also effect the orientation orregiochemistry of the reaction.
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NO2CN
SO3H
CHO
CORCOOHCOOR
NR3+
NH2
OCH3
OH
N
H
C
O
CH3CH3
F
BrCl
I
H
stronglyactivating
stronglydeactivating
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Electrostatic potential maps clearly show the effect ofsubstituents on electron density in a substituted benzene ring.
Aniline, stronglyactivating
Benzene Benzonitrile,strongly deactivating
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Electrostatic potential maps clearly show the effect ofsubstituents on electron density in a substituted benzene ring.
Aniline, stronglyactivating
Benzene Benzonitrile,strongly deactivating
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Electrostatic potential maps clearly show the effect ofsubstituents on electron density in a substituted benzene ring.
Aniline, stronglyactivating
Benzene Benzonitrile,strongly deactivating
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Electrostatic potential maps clearly show the effect ofsubstituents on electron density in a substituted benzene ring.
Aniline, stronglyactivating
Benzene Benzonitrile,strongly deactivating
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δ
OCH3
δ
δ
δ
E
OCH3
OCH3 OCH3 OCH3
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Br
H
Br
H
H
Br
Electron donatingsubstituents at these
positions will stabilizethe cationic
intermediate.
Recall that positive charge in the cyclohexadienyl cationintermediate is delocalized to the ortho- and para- positions.
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δ
OCH3
δ
δ
δ
E
Because of this, attack to form the cationic intermediate willoccur predominately ortho- and para- to an electron donatingsubstituent.
Electron donatingsubstituents at these
positions will stabilizethe cationic
intermediate.
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ortho ¶
directing
NO2CN
SO3H
CHO
CORCOOHCOOR
NR3+
NH2
OCH3
OH
N
H
C
O
CH3CH3
F
BrCl
I
H
stronglyactivating
stronglydeactivating
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Cl
Cl Cl Cl
δ
Cl
δ
δ
δ
E ...halogens are deactivating inductively,but activate the ring through resonance.
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CH3
HNO3/H2SO4
CH3
NO2
CH3
NO2
CH3
NO2
63% 3%
34%
...the alkyl group is activating and increases electron densityin the ortho and para positions; thus, nitration generates
predominately ortho and para products.
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CH3
H
E
CH3
E
H
CH3
E
H
CH3
+
E
a tertiarycarbocation
...alkyl groups activate ortho and para because the sigma-complex intermediates yield more stable tertiary carbocations.
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CN
HNO3/H2SO4
CN
NO2
CN
NO2
CN
NO2
17% 81%
2%
...the cyano group is deactivating; nitration generatespredominately meta product.
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δ
δ
δ
δNO2
NOO
NOO
NOO
E
NOO
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Recall that electron donatingsubstituents ortho- and para-
to the sigma intermediate willstabilize the cationic
intermediate.
Deactivating meta-directing groups...
δ
δ
δ
δNO2
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When electron withdrawing substituentsare present ortho- or para- to the sigma
intermediate substitution is forced meta-because there is reduced electron density in
the other positions.
Deactivating meta-directing groups...
δ
δ
δ
δNO2
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NOO
E
NOO
NOO
NOO
NO2
δ
δ
δ
δ
...electrophilic attack occurs at the metapositions because the ortho and para
positions are electron deficient.
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ortho- ¶-
directing
NO2CN
SO3H
CHO
CORCOOHCOOR
NR3+
NH2
OCH3
OH
N
H
C
O
CH3CH3
F
BrCl
I
H
stronglyactivating
stronglydeactivating
meta-directing
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CH3
NO2
HNO3/H2SO4
Orientation Effects in Disubstituted Benzenes
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CH3
NO2
HNO3/H2SO4
CH3
NO2
NO2
CH3
NO2
NO2O2N
methyl directs ortho
nitro directs meta
Trinitrotoluene
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CH3
NO2
HNO3/H2SO4
CH3
NO2
NO2
CH3
NO2
NO2O2N
methyl directs ortho
nitro directs meta
TriNitroToluene
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CH3
OCH3
Br2/FeBr3
Orientation Effects in Disubstituted Benzenes
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CH3
OCH3
Br2/FeBr3
CH3
OCH3
Br
...when substituents direct to different positions, themost powerful group will dominate.
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CH3
Cl
Cl2/FeCl3
Orientation Effects in Disubstituted Benzenes
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CH3
Cl
Cl2/FeCl3
CH3
Cl
Cl
CH3
Cl
Cl
CH3
Cl
Cl
+
...product not observed;too hindered
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Nucleophilic Aromatic Substitution
F
NO2
NO2
HO-
OH
NO2
NO2
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F
NO2
O2N
HO-
...SN2 attack is not possible;SN1 would generate the unstable aryl cation.
F
NO2
NO2
NO2
NO2
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F
NO2
NO2
HO-
NO2
NO2
OHF
NO2
NO2
OH
NO2
NO2
OHF
...addition
...elimination
The Addition-Elimination Mechanism
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N
NO2
OHF O
ON
NO2
OHF O
O
...the carbanion at the ortho- position is stabilizedbyresonance with the oxygens of the nitro group
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N
NO2
OHF O
ON
NO2
OHF O
O
+ F
NO2
OH
N
O
O
elimination
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CH3
SO3H
NO2
Br2/FeBr3
I2/CuCl2
Cl2/FeCl3
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CH3
SO3H
NO2
Br2/FeBr3
I2/CuCl2
Cl2/FeCl3CH3
Cl + ortho isomer
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CH3
SO3H
NO2
Br2/FeBr3
I2/CuCl2
Cl2/FeCl3CH3
Cl
SO3HBr
+ ortho isomer
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CH3
SO3H
NO2
Br2/FeBr3
I2/CuCl2
Cl2/FeCl3CH3
Cl
SO3HBr
NO2I
+ ortho isomer
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CH3
CH(CH3)2
ClSO3/H2SO4
excess HNO3/H2SO4
Cl
O
C
AlCl3
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CH3
CH(CH3)2
ClSO3/H2SO4
excess HNO3/H2SO4
Cl
O
C
AlCl3
Cl
HO3S+ ortho isomer
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CH3
CH(CH3)2
ClSO3/H2SO4
excess HNO3/H2SO4
Cl
O
C
AlCl3
CH3
NO2
O2N NO2
Cl
HO3S+ ortho isomer
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CH3
CH(CH3)2
ClSO3/H2SO4
excess HNO3/H2SO4
Cl
O
C
AlCl3
CH3
NO2
O2N NO2
CH(CH3)2
O
Cl
HO3S+ ortho isomer