CHAPTER 12
Substituted Benzene
12.1
Alkylbenzenes (Ar-R)
Bezylic carbons:
CH3
1
CH2CH3
CH(CH3)2
Reactions of Alkylbenzens
1. Free Radical Halogenation
CH2CH3
Br2
hv
2
Br
CHCH3
2- Oxidation
CH3
KMnO4
hot
CH2CH3
MnO4hot
R
CO2H
KMnO4
hot
CO2H
CO2H
CH2CH3
CHCH3
3
MnO4hot
CO2H
CH3
Notice:
CCH3
CH3
MnO4hot
No Reaction
Benzylic carbon has no hydrogen
CH3
CH3
MnO4hot
MnO4hot
CO2H
HO2C
CO2H
CO2H
4
Phenols (ArOH)
A phenol has a hydroxyl group directly attached
to the benzene ring
SP2- hybridized carbon
OH
C---O bond is not easily broken
R-OH + HBr
5
 No substitution or elimination reaction
 RBr + H2O
Ar-OH + HBr  No reaction
SN1 or SN2
Acidity of Phenols
CH3CH2O- Na+
+ NaOH
CH3CH2OH
pKa= 16
H2O
Not favored
pKa=15.7
OH
+ NaOH
O- Na+
+
H2O
favored
pKa= 15.7
pKa= 10
O- + R X
6
+
a phenoxide ion
SN2
OR
+
X-
Esterfication of phenols
O
OH
+ CH3C
O
O
OCCH3
OCCH3
+ CH3CO2H
7
The Kolbe Reaction
OH
1) OH2) CO2
OH
3) H+
CO2H
Mechanism
OH
OH-
O-
+ O C O
O
H
C O
O-
OH
H+
OH
8
Salicylic acid
CO2H
CO2-
Importance of Kolbe Reaction
To Synthesize aspirin
OH
+
CO2H
O O
CH3COCCH3
O
OCCH3
CO2H
Acetylsalicylic acid
(Aspirin)
9
The Reimer-Tiemann Reaction
The reaction of phenol with chloroform in the
presence of base.
OH
10
OH- ,
1)
CHCl3,
2)
H2O, H+

70 C
OH
CH
O
Salicylaldehyde
Mechanism:
OH-
H CCl3
+
- H2O
H
O-
CCl3
CCl2
CCl2
dichlorocarbene
..CCl
2
+
Cl-
CHCl2
O
OOHO
O
H
11
H
OH
H
H+
O-
O
CHCl
O-
Oxidation of phenols: phenol resists
oxidation
Oxidation of hydroquinones (1,4-dimethoxy benzenes)
O
OH
O
+
2
H+
+
2e
-
H
O
OH
hydroquinone
1.4-benzoquinone
OH
O
(quinone)
O
+
OH
H
O
1.2-benzoquinone
12
2
H+
+
2e
Preparation of Aniline
HNO3
H2SO4
NO2
Fe, HCl
NO2
N+H3Cl-
H2, Pd/C or Pt
13
OH-
NH2
Benzenediazonium Salts
NH2
NaNO2, HCl, 0O C
+ N ClN
+ H2O
benzenediazonium chloride
Excellent leaving abilty of N2 gas
very reactive
+
N N
14
_ N
2
+
Nu -
Nu
Reactions of benzenediazinium Salts
Br
Cl
CuCl
CuBr
1) HNO3, H2SO4
2) H2, Pt
NH2
NaNO 2, HCl,
O
CuCN, KCN
+
N N Cl-
KI
0C
H3PO2
H2O,
1)
H+
2)
H
OH
15
CN
I
HBF4
heat
F
Coupling reactions
+
N
+
N N
N
+
N N +
OH
CO2H
N N
OH
Azo compound
NH2
O
NaNO2, HCl, 0 C
CO2H
16
+
N N +
NHCH3
N N
NHCH3
Synthesis involving diazonium salts
?
CH3
?
?
?
CH3
HNO3, H2SO4
CH3
CuCN, KCN
NO2
1)
C N
Fe, HCl
2) OH
N2+ Cl-
CH3
NaNO2 ,
O
CH3
17
NH2
HCl, O C
Nucleophilic Aromatic Substitution
X
But
+
X
Nu
+
-
No SN1 or SN2 reaction
Nu
-
Nucleophilic Aromatic Substitution
18
Nu
+ X-
Examples
10%
Cl
NaOH
OH
o
350 300 atm
increasing O2N
reactivity
toward Nu -
Cl
10% NaOH
O2N
o
160
P-nitrophenol
NO2
NO2
O2N
Cl
NO2
19
OH
H2O
warm
O2N
OH
NO2
Other nucleophiles
NO2
NO2
O2N
Cl
NO2
O2N
20
Cl
NH3
heat
O2N
NH2
NO2
CH3CH2Sheat
O2N
SCH2CH3
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
OHslow
O2N
Cl
OH
O2N
-
Cl
Carbanion intermediate
21
fast
O2N
OH
Carbanion intermediate is stabilized by resonance
OO-
O2 N
OH
Cl
O+
N
O-
Cl
OH
Cl
O+
N
O-
22
OH
N+
OH
Cl
Benzyne Mechanism:
If there is no electron withdrawing substituent on the
ring.
Cl
NH2 , NH3
NH2
Mechanism
Cl
H
- HCl
NH2-
NH2-
23
NH3
Benzyne
NH2-
NH2
+
NH2
Benzyne
H
H
H
24
H
Syntheses of substituted benzene compounds
Cl
•
How would you synthesize
NO2
HNO3
Cl2
H2SO4
•
NO2
FeCl3
NO2
But IF YOU START WITH CHLORINATION
Cl
Cl2
FeCl3
Cl
HNO3
H2SO4
o,p-director
25
Cl
Cl
NO2
+
NO2
Syntheses
? ?
Br
?
NH2
HNO3
H2SO4
1)
Fe, HCl
NO2
)
OH
2
Br2, FeBr3
Br
NO2
26
Note: Nitro group can be converted to arylamines which in turn can also
be converted to aryldiazonium salts,=> making a diversity of substituted
products
1)
NO2
Fe, HCl
NaNO2, HCl
2) OH-
m-director
NH2
0o
o,p-director
Nu
N2+
Nu
easily 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
27
+
AlCl3
Al-Cl3
N+H2
strongly deactivating
Nitrobenzene does not undergo Friedel-Crafts
reactions
NO2
O
RX or RCX
AlX3
No aromatic substitution
Notice: An amino group is o,p-director, but an ammonium
group ( -NR3+) is an m-director and deactivating.
NH2
o,p-director
28
+ HNO3
N+H3 NO3m-director
Sulfonic acid group (-SO3H)
The sulfonic acid group is easily removed and can be displaced by a
variety of reagents.
SO3H
SO3H
29
H2O, H+
1)
Fused NaOH
+
)
H
O,
H
2
2
+
H2SO4
OH
? ?
?
Br
OH
Br2, FeBr3
H2O, H+
Br
HNO3
H2SO4
Br
NO2
30
1)
Fe, HCl
2)
OH-
Br
NH2 NaNO2,HCl
0o
Br
N2+
Br
? ?
?
Br
HNO3
H2SO4
CuBr
NO2
Br2, FeBr3
Br
NO2
31
Br
Br
1)
2)
Fe, HCl
OH-
NH2
NaNO2,HCl
0
N2+
? ? ? ?
CO2H
NH2
CH3CH2Cl,
AlCl3
KMnO4
heat
CH2CH3
HNO3, H2SO4
CH2CH3
NO2
1)
Fe, HCl
2) OH
CH2CH3
NH2
32
? ? ? ?
OCH3
CH3I
HNO3, H2SO4
O-
NO2
NaOH
H2,Pd/C
NH2
33
OH
1)
NaNO2,HCl
2)
H2O, H+
Cl
? ? ? ?
CH3
CO2H
KMno4, heat
Cl2, FeCl3
CO2H
34
Cl
? ? ? ?
CH3
CH3
HNO3, H2SO4
H3PO2
O2N
CH3
H2,Pd/C
H2N
1)
CH3 2)
35
Cl2, FeCl3
NaNO2, HCl
Cl-
N2
+
Cl
CH3