1
CHAPTER 12
Substituted Benzene
12.1 Alkylbenzenes (Ar-R)
Bezylic carbons:
CH3 CH2CH3CH(CH3)2
2
Reactions of Alkylbenzens
1. Free Radical Halogenation
CH2CH3Br2
hvCHCH3
Br
3
2 -Oxidation RKMnO4hot
CO2H
CH3 KMnO4hot
CO2HCH2CH3
hotMnO4
-
CO2H
CHCH3
CH2CH3
hotMnO4
- CO2H
4
Notice: CCH3
CH3
CH3 hotMnO4
-
Benzylic carbon has no hydrogen
No Reaction
CH3
CH3hotMnO4
- CO2H
HO2C
hotMnO4
- CO2H
CO2H
5
Phenols (ArOH)
OH
A phenol has a hydroxyl group directly attached to the benzene ring
SP2- hybridized carbon
C---O bond is not easily broken No substitution or elimination reaction
R-OH + HBr RBr + H2O SN1 or SN2
Ar-OH + HBr No reaction
6
Acidity of Phenols
CH3CH2OH + NaOH CH3CH2O- Na++ H2O Not favored
pKa= 16 pKa=15.7
OH + NaOH O- Na+ + H2O favored
pKa= 10pKa= 15.7
O- + R X OR+ X-
SN2
a phenoxide ion
7
Esterfication of phenols
OH + CH3C
O
OCCH3
O
OCCH3
O
+ CH3CO2H
8
The Kolbe Reaction
OH
1) OH-2) CO2
3) H+
OH
CO2H
Mechanism
OHOH- O-
C OO+ -
O
H
C OO-
OH
CO2-
H+OH
CO2HSalicylic acid
9
Importance of Kolbe Reaction
To Synthesize aspirin
OH
CO2H
CH3COCCH3
O O
+CO2H
OCCH3
O
Acetylsalicylic acid
(Aspirin)
10
The Reimer-Tiemann Reaction
The reaction of phenol with chloroform in the presence of base.
OH1) CHCl3, OH-, 70
2) H2O, H+
C
OH
CHO
Salicylaldehyde
11
Mechanism:
OH- H CCl3- H2O
+CCl3
Cl-CCl2
dichlorocarbene
CCl2O-+ O
HCCl2..
O-
CHCl2
OH-
O-
CHClO
H
O-
H
O
H+
OH
H
O
12
Oxidation of phenols: phenol resists oxidation
Oxidation of hydroquinones (1,4-dimethoxy benzenes)OH
OH
O
O
+ 2 H++ 2e-
O
H
hydroquinone1.4-benzoquinone
(quinone)
O
H
OH
OH
O
H
O
O
+ 2 H++ 2e-
1.2-benzoquinone
13
Preparation of Aniline
HNO3
H2SO4
NO2
NO2Fe, HCl N+H3Cl- OH- NH2
H2, Pd/C or Pt
14
Benzenediazonium Salts
NH2NaNO2, HCl, 0
OC N N Cl-+
+ H2O
benzenediazonium chloride
very reactive Excellent leaving abilty of N2 gas
N N+ _ N2+
Nu -Nu
15
Reactions of benzenediazinium Salts
NH2NaNO2, HCl,
0OC
Cl
CuCl
Br
CuBr
CN
CuCN, KCN
IKI
F
1) HBF4
2) heat
OH
H2O, H+
H
H3PO2
HNO3, H2SO41)
2) H2, Pt
N N Cl-+
16
Coupling reactions
N N+
N N+
N N+
OH N N OH+
CO2H
NH2
N N
CO2H
+ NHCH3+ N N NHCH3
NaNO2, HCl, 0 CO
Azo compound
17
Synthesis involving diazonium salts
CH3 C NCH3? ? ? ?
HNO3, H2SO4
CH3 NO2
1) Fe, HCl
2) OH-
CH3 NH2
NaNO2,
HCl, O CO
CH3 N2+ Cl-
CuCN, KCN
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Nucleophilic Aromatic Substitution
X Nu - No SN1 or SN2 reaction+
X Nu -+ Nu + X-But
Nucleophilic Aromatic Substitution
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Examples
Cl10% NaOH
350 300 atmo OH
O2N Cl 10% NaOH
160o
O2N OH
P-nitrophenol
O2N Cl
NO2
NO2
H2Owarm
O2N OH
NO2
NO2
increasingreactivitytoward Nu -
20
Other nucleophiles
O2N Cl
NO2NH3
heat
O2N Cl
NO2CH3CH2S-
heat
O2N NH2
NO2
O2N SCH2CH3
NO2
21
Carbanion Mechanism:If the ring is activated toward nucleophilc substitution by an electron withdrawing group (I,e NO2)
Two steps 1) addition of Nu: to form carbanion
2 (Loss of the halide ion
O2N Clslow
OH-
O2NCl
OH
-
O2N OH
Carbanion intermediate
fast
22
Carbanion intermediate is stabilized by resonance
O2NCl
OH OH
ClN
O
O-
+
NO-
O-
OH
Cl+
OH
ClN
O
O-
+
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Benzyne Mechanism:
If there is no electron withdrawing substituent on the ring.
ClNH2
-, NH3NH2
Cl
H NH2-
- HClNH2
- NH2
NH3
NH2NH2-
+
Mechanism
Benzyne
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Benzyne
HH
H
H
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Syntheses of substituted benzene compounds
• How would you synthesize
• But IF YOU START WITH CHLORINATION
Cl
NO2
HNO3
H2SO4 NO2
Cl
NO2
Cl2FeCl3
Cl
Cl2
FeCl3
HNO3
H2SO4
Cl
NO2
ClNO2
+
o,p-director
26
SynthesesBr
NH2
? ? ?
HNO3H2SO4
NO2
Br2, FeBr3
NO2
Br
1) Fe, HCl
2) OH-
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Note: Nitro group can be converted to arylamines which in turn can also be converted to aryldiazonium salts,=> making a diversity of substituted products
NO2
1) Fe, HCl
2) OH-NH2
NaNO2, HCl0o
N2+
Nu
Nu
m-director o,p-directoreasily displaced
Notice: Amino group does not undergo Friedel-Crafts reaction because an amino group reacts with Lewis acid since it is basic to form strongly deactivating grouo
NH2+
AlCl3N+H2
Al-Cl3
strongly deactivating
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Nitrobenzene does not undergo Friedel-Crafts reactions
NO2
RX or RCXO
AlX3No aromatic substitution
Notice: An amino group is o,p-director, but an ammonium group ( -NR3
+) is an m-director and deactivating.
NH2 HNO3+ N+H3 NO3-
o,p-director m-director
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Sulfonic acid group (-SO3H)
The sulfonic acid group is easily removed and can be displaced by a
variety of reagents.
SO3HH2O, H+ H2SO4+
SO3H OH1) Fused NaOH
2) H2O, H+
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OHBr? ? ?
Br2, FeBr3
Br
HNO3H2SO4
NO2Br 1) Fe, HCl
2) OH-NH2Br NaNO2,HCl
0oN2
+Br
H2O, H+
31
Br
Br? ? ?
HNO3H2SO4
NO2
Br2, FeBr3
NO2
Br1) Fe, HCl
2) OH- NH2
BrNaNO2,HCl
0N2
+
Br
CuBr
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CO2H
NH2
? ? ? ?
CH3CH2Cl,AlCl3
CH2CH3
HNO3, H2SO4
CH2CH3
NO2
1) Fe, HCl
2) OH- CH2CH3
NH2
KMnO4
heat
33
OCH3? ? ? ?
NO2
HNO3, H2SO4
NH2
H2,Pd/C
1) NaNO2,HCl
2) H2O, H+
OH
NaOH
O-
CH3I
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CH3
Cl
CO2H
? ? ? ?
KMno4, heat
CO2H
Cl2, FeCl3
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HNO3, H2SO4
O2N
CH3
H2N
CH3
H2,Pd/C
1) Cl2, FeCl3
2) NaNO2, HCl
Cl- N2+
CH3
Cl
CH3
Cl
CH3
? ? ? ?
H3PO2