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Chapter 12
Substituted benzenes
allylic radical
benzylic radical
H
C
C
H
H
C
industrial process
highly regioselective for benzylic position
Cl2
CH3
Toluene
light
or
heat
CH2Cl
Benzyl chloride
CHCl2
(Dichloromethyl)benzene
CCl3
(Trichloromethyl)benzene
Benzylic Bromination
N-Bromosuccinimide (NBS)
CH2Br
CH3
CH2CH3
O
+ Br2
NO2
CCl4, 80
80C
+ HBr
light
NO2
p-Nitrotoluene
CCl4
NBr +
benzoyl
peroxide,
heat
CHCH3
O
NH +
O
p-Nitrobenzyl
bromide (71%)
(87%)
CH3
or
Na2Cr2O7
H2SO4
Oxidation of Alkylbenzenes
CH2R
or
CHR2
H2O
heat
O
COH
Example
Example
O
O
COH
CH(CH3)2
Na2Cr2O7
H2SO4
COH
CH3
Na2Cr2O7
H2SO4
H2O
heat
H2O
heat
CH3
NO2
COH
NO2
p-Nitrotoluene
p-Nitrobenzoic
acid (82
(82--86%)
(45%)
O2N
Nucleophilic Substitution
CH2Cl
O
Mechanism is SN2
in Benzylic Halides
NaOCCH3
acetic acid
O
O2N
CH2OCCH3
(78--82%)
(78
CH3
Cl
CH3
CH3
CH3
Cl
CH3
C+
CH3
CH3
CH3
600
C+
CH3
more stable
t bl
less stable
Compare.
H
C
C
C+
allylic carbocation
C+
+
C
benzylic carbocation
H
+
H
Solvolysis
CH3
Cl
C
H
CH3
+
H
H
H
CH3CH2OH
CH3
C
CH3
OCH2CH3
(87%)
Nomenclature
Phenols
Nomenclature
Nomenclature
OH
OH
CH3
5-Chloro
Chloro--2-methyl
methylphenol
phenol
OH
OH
OH
Cl
OH
OH
1,2--Benzenediol
1,2
1,3--Benzenediol
1,3
1,41,4-Benzenediol
(common name:
(common name:
(common name:
pyrocatechol)
resorcinol)
hydroquinone)
Nomenclature
OH
p-Hydroxybenzoic acid
CO2H
name on basis of benzoic acid as parent
Physical Properties
The OH g
group
p of p
phenols allows hydrogen
y g bonding
g
to other phenol molecules and to water.
Physical Properties
O
Compared to compounds of similar size and
molecular weight, hydrogen bonding in phenol
raises its melting point, boiling point, and
solubility in water.
Physical Properties
C6H5CH3
C6H5OH
C6H5F
Molecular weight
92
94
96
95
43
41
Boiling
point ((C,1 atm)
111
132
85
Solubility in
H2O (g/100 mL,25
mL,25C)
0.05
8.2
0.2
Acidity of Phenols
Compare
H
Ka = 10-10
H
+ +
O
H
CH3CH2O
Ka = 10-16
H
H
+ + CH CH O
H
3
2
H
H
H
H
H
H
+ HO
stronger acid
Substituent Effects
on the
Acidity of Phenols
+ H2O
weaker acid
H
H
OH
Ka:
1 x 10-10
OH
OH
CH3
OCH3
5 x 10-11
6 x 10-11
Effect of electron
electron--withdrawing groups is most
pronounced at ortho and para positions
OH
OH
OH
OH
Ka:
1 x 10-10
OH
OH
Cl
NO2
4 x 10-9
7 x 10-8
OH
OH
NO2
NO2
NO2
O2N
NO2
Ka:
6 x 10-8
4 x 10-9
NO2
NO2
NO2
7 x 10-8
Ka: 7 x 10-8
1 x 10-4
NO2
4 x 10-1
Resonance Depiction
O
N
+
N
+
ONa + RX
SN2
NaX
OR + NaX
ONa + RX
SN2
NaX
OR + NaX
Example
Carboxylation of Phenols
acetone
ONa + CH3I
OCH3
heat
(95%)
O
Aspirin and
the
Kolbe--Schmitt
Kolbe
R
Reaction
ti
OCCH3
COH
O
CH3COCCH3
H2SO4
O
OCCH3
ONa
CO2
125C, 100 atm
125
COH
O
OH
CONa
O
CO2
ONa
stronger base:
pKa of conjugate
acid = 10
weaker base:
pKa of conjugate
acid = 3
O
H
O
how does carboncarbon-carbon bond form?
recall electron delocalization in phenoxide ion
negative charge shared by oxygen and by the
ring carbons that are ortho and para to oxygen
H
H
H
H
CONa
OH
CO2
C
O
O
C
H
C
O
Reimer--Tiemann reaction.
Reimer
Mechanism of ReimerReimer-Tiemann
Reimer--Tiemann rxn
Reimer
O-
OH
OCHCl2
OH- + CHCl3
OH
CHO
H2O + Cl3C:-
Cl- + Cl2C:
CHO
HCl
O-
O-
OCCl2
+ :CCl2
Strong Electrophile
CHCl2
Quinones
The most common examples of phenol oxidations
are the oxidations of 1,2
1,2-- and 1,4
1,4--benzenediols
to give quinones.
OH
Oxidation of Phenols:
Quinones
O
Na2Cr2O7, H2SO4
H2O
OH
(76--81%)
(76
Quinones
The most common examples of phenol oxidations
are the oxidations of 1,2
1,2-- and 1,4
1,4--benzenediols
to give quinones.
OH
OH
OH
OH
Ag2O
diethyl ether
CH3
CH3
(68%)
Alizarin
(red pigment)
O
CH3
CH3O
CH3
CH3
CH3O
n
O
Ubiquinone (Coenzyme Q)
n=6
6--10
involved in biological electron transport
CH3
CH3
CH3
CH3
Vitamin K
(blood-clotting factor)
(blood-
Example:
(CH3)2CH
NaNO2, H2SO4
H2O, 0
0--5C
+
ArN
+
R
fast
slow
+
Ar
NH2
+ N2
(CH3)2CH
+
N
N HSO4
+ N2
H
HNO3, H2SO4
Ar
NO2
NH2
+
N
Cl
Br
Ar
+
N
Ar
Ar
y
y
of a diazonium salt
hydrolysis
Ar
CN
Ar
+
N
Ar
Ar
Ar
Preparation of Phenols
N
H2O,
O heat
OH
OH
Ar
Example
(CH3)2CH
1. NaNO2, H2SO4
H2O, 0
0--5C
Ar
Ar
Cl
Ar
CN
+
N
Ar
Br
Ar
Ar
2. H2O, heat
Ar
OH
(CH3)2CH
Ar
(73%)
OH
Example
NH2
Br
+
N
Ar
N
Ar
Ar
Ar
+
N
Ar
Ar
OH
Ar
Ar
Ar
Ar
Br
Ar
CN
(72--83%)
(72
Br
KI
Ar
1. NaNO2, HCl
H2O, 0
0--5C
+
N
Example
NH2
1 N
1.
NaNO
NO2, HCl,
HCl
H2O, 0
0--5C
CCH2CH3
Br
Ar
Ar
CCH2CH3
3.
3 heat
Ar
(68%)
Ar
Ar
OH
Example
Br
NH2
+
N
+
N
Ar
2. HBF4
Ar
Ar
CN
Ar
Ar
Cl
1 N
1.
NaNO
NO2, HCl,
HCl
H2O, 0
0--5C
NO2
2. CuCl, heat
Cl
NO2
(68--71%)
(68
Example
NH2
Cl
1 N
1.
NaNO
NO2, HBr,
HB
H2O, 0
0--10
10C
Cl
Ar
Br
Cl
CN
Ar
+
N
Ar
2. CuBr, heat
(89--95%)
(89
Ar
Ar
+
N
CH3
N
Ar
OH
Example
NH2
CN
Ar
N
H
Ar
Ar
Br
1 N
1.
NaNO
NO2, HCl,
HCl
H2O, 0
0C
CN
CH3
2. CuCN, heat
(64--70%)
(64
Cl
Ar
+
N
Ar
Ar
Ar
Ar
Ar
Br
Ar
CN
Ar
Ar
CH3
OH
Example
NH2
+
N
NaNO
N NO2, H2SO4,
H3PO2
CH3
(70--75%)
(70
Example
NH2
NH2
Br2
Br
Br
NaNO2, H2SO4,
H2O, CH3CH2OH
H2O
Azo Coupling
Br
Br
Br
(100%)
Br
(74--77%)
(74
Azo Coupling
Diazonium salts are weak electrophiles.
R
React
t with
ith strongly
t
l activated
ti t d aromatic
ti
compounds by electrophilic aromatic
substitution.
Azo Coupling
Diazonium salts are weak electrophiles.
electrophiles.
R
React
t with
ith strongly
t
l activated
ti t d aromatic
ti
compounds by electrophilic aromatic
substitution.
Ar
+
N
N + Ar'
Ar
Ar'
an azo compound
Ar' must bear a strongly electronelectron-releasing group
such as OH, OR, or NR2.
Example
OH
+
+ C6H5N
Cl
Halobenzenes and Nucleophilic
Aromatic Substitution
OH
N
NC6H5
NaOH, 350C
Mechanism:
If the ring is substituted by an electron withdrawing group the
reaction proceeds through a two-step carbanion intermediate.
OH
300 atm.
Cl
Slow
O2N
Cl
O2N
Fast
O2N
OH
OH
OH
O2N
Cl
NaOH, 160C
300 atm.
O2N
OH
NO2
NO2
Cl
O2N
Cl
NO2
H2O, warm
O2N
OH
NO2
-HCl
Slow
NH2-, NH3
NH2