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Reaction of
Benzene and
its Derivatives
22-1
Reactions of Benzene
FeCl3
Cl + HCl
Chlorobenzene
Contrast to radical
mechanism for
benzylic hyrdogens
Nitration:
H + HNO3
H2 SO4
NO2 + H2 O
Nitrobenzene
22-2
Reactions of Benzene
Sulfonation:
H + SO3
H2 SO4
SO3 H
Benzenesulfonic acid
Alkylation: Friedel Crafts
H + RX
AlX3
R + HX
An alkylbenzene
O
CR + HX
An acylbenzene
22-3
+ E
+ H
22-4
A general mechanism
Step 1:
H + E
Electrophile
+
Step 2:
H
E
fast
slow, rate
determining
E
Resonance-stabilized
cation intermediate
E + H+
Chlorination
Step 1: Generation of the electrophile: a chloronium ion.
Cl
Cl Cl + Fe Cl
Cl
Chlorine Ferric chloride
(a Lewis
(a Lewis
base)
acid)
Cl
Cl
Cl Fe Cl
Cl
A molecular complex
with a positive charge
on chlorine
Cl FeCl4
An ion pair
containing a
chloronium ion
slow, rate
determining
+
+
Cl
Cl
+ Cl
Resonance-stabilized cation intermediate; the positive
charge is delocalized onto three atoms of the ring22-6
Chlorination
Step 3: Proton ejection regenerates the aromatic
character of the ring.
+
H
Cl
Cation
intermediate
+ Cl-FeCl3
fast
Cl + HCl + FeCl3
Chlorobenzene
22-7
Addition vs Substitution
22-8
O
O N
H
O
H
HSO4 +
Nitric
acid
Conjugate acid
of nitric acid
O N
H
O
+ O N O
The nitronium
ion
22-9
Nitration,
Attack of electrophile as before..
Step 1: Attack of the nitronium ion) on the aromatic ring.
H
+
+ O N O
NO2
+
NO2
H
+
NO2
+
Resonance-stabilized cation intermediate
H NO2
O
NO2
+
H
H
O H
22-10
COOH
Ni
(3 atm)
+ 2H2O
NH2
4-Aminobenzoic acid
22-11
Sulfonation
H2 SO4
SO3 H
Benzenesulfonic acid
22-12
Friedel-Crafts Alkylation
Cl
AlCl3
+ HCl
2-Chloropropane
Cumene
(Isopropyl chloride) (Isopropylbenzene)
22-13
Friedel-Crafts Alkylation
Step 1: Formation of an alkyl cation as an ion pair.
R Cl
Cl
Al Cl
Cl
Cl
R Cl Al Cl
Cl
A molecular
complex
+
H
R
+R
A resonance-stabilized cation
+ Cl AlCl3
R + AlCl3 + HCl
22-14
Friedel-Crafts Alkylation
Benzene
CH3
CH3 CHCH2 -Cl
Isobutyl
chloride
+ AlCl3
Isobutyl chloride
AlCl3
+ HCl
tert-Butylbenzene
CH3
+
CH3 C-CH2 -Cl-AlCl3
H
a molecular
complex
CH3
CH3 C+ AlCl4 CH3
an ion pair
22-15
Friedel-Crafts Alkylation
2. F-C alkylation fails on benzene rings bearing one or
more of these strongly electron-withdrawing groups.
Y
+ RX
AlCl3
No reaction
O
CR
SO3 H
C N
CF3
CCl3
O
COH
NO2
O
COR
NR3
O
CNH2
22-16
Friedel-Crafts Alkylation
3. F-C multiple alkylation can occur more rapidly than
monoalkylation. The first alkyl group activates the ring
to the second substitution.
22-17
Friedel-Crafts Acylation
O
AlCl3
Acetyl
chloride
Cl
+ HCl
Acetophenone
O
O
AlCl3
4-Phenylbutanoyl
chloride
+ HCl
-Tetralone
22-18
Friedel-Crafts Acylation
R-C Cl
An acyl
chloride
Cl
+ Al-Cl
Cl
Aluminum
chloride
(1)
O + Cl
(2)
R-C Cl Al Cl
Cl
A molecular complex
with a positive charge
charge on chlorine
O
R-C+ AlCl4An ion pair
containing an
acylium ion
22-19
Friedel-Crafts Acylation
An acylium ion is represented as a resonance hybrid
of two major contributing structures.
O:
+
R-C
complete valence
shells
+
R-C O:
The more important
contributing structure
AlCl3
2-Methylpropanoyl
chloride
O
N2H4, KOH
diethylene
glycol
Isobutylbenzene
2-Methyl-1phenyl-1-propanone
CH3CH=CH2
H3PO4
Propene
Cumene
AlCl3
Benzene Cyclohexene
Phenylcyclohexane
an alkene with a Lewis
acid.
treating
22-22
HO
H3 PO4
2-Methyl-2-propanol
(tert-Butyl alcohol)
+ H2 O
2-Methyl-2phenylpropane
(tert-Butylbenzene)
22-23
Favor
ortho/para
substitution
Favor meta
substitution
meta
-
para
ortho +
para
meta
55
38
99
96
trace
4
30
100
trace
OCH3
CH3
44
58
Cl
70
4
-
Br
37
62
99
COOH
18
80
20
80
CN
19
80
20
80
NO2
6.4
93.2
0.3
6.7
93.2
22-24
Directivity of substituents
22-25
OCH3
NO2
CH3COOH
o-Nitroanisole
(44%)
Anisole
H2 SO4
NO2
100C
OCH3
+
+ H2 O
NO2
p-Nitroanisole
(55%)
COOH
+
+
NO2
o-Nitrobenzoic
acid
(18%)
COOH
m-Nitrobenzoic
acid
(80%)
NO2
p-Nitrobenzoic
acid
(2%) 22-27
Cl :
Br :
Meta Directing
OCAr
R
F:
OCR
NHCAr
NHCR
I:
CH
O
CR
COH
COR
CNH2
NO2
OR
Strongly
deactivating
OH
Moderately
deactivating
NR2
Weakly
deactivating
NHR
:
Weakly
activating
NH2
Moderately
activating
Strongly
activating
Ortho-para Directing
SO3 H
NH3
C N
CF3
CCl3
22-28
Generalizations:
Directivity: Alkyl, phenyl, and all substituents in which
the atom bonded to the ring has an unshared pair of
electrons are ortho-para directing. All other
substituents are meta directing.
22-29
COOH
HNO3
K2 Cr2O7
H2SO4
H2SO4
CH3
K2 Cr2 O7
H2 SO4
NO2
NO2
p-Nitrobenzoic
acid
COOH
COOH
HNO3
H2SO4
NO2
m-Nitrobenzoic
acid
22-30
22-31
22-32
OCH3
+ NO2 +
OCH3
slow
: OCH3
: OCH3
: OCH3
OCH3
+
NO2
(d)
fast
-H+
+
H
NO2
+
H
(e)
NO2
H
(f)
NO2
NO2
(g)
OCH3
+
H
slow
OCH3
+
OCH3
fast
H -H+
NO2
(a)
o,p director
(b)
NO2
+ NO2
OCH3
NO2
(c)
Meta director
slow
COOH
COOH
COOH
COOH
fast
+
-H
H NO2
(d)
H NO2
H NO2
(e)
(f)
The most disfavored
contributing structure
NO2
22-35
slow
COOH
(a)
Meta director
COOH
NO2
NO2
NO2
(b)
COOH
COOH
fast
+
-H
NO2
(c)
22-36
22-38
Activating-Deactivating: Halogens
For the halogens, the inductive and resonance effects
oppose each other. Inductive is somewhat stronger.
Result: halogens are deactivating but ortho-para
directing.
:Cl
H
E
+
:Cl
+E
: :
: :
: Cl
H
E
22-39
22-40
Benzyne Intermediates
Cl
O Na
+ 2NaOH
Chlorobenzene
H2O
o
pressure, 300 C
+ NaCl + H2O
Sodium
phenoxide
22-41
Cl
CH3
CH3
OH
+
OH
2-Methylphenol 3-Methylphenol
(o-Cresol)
(m-Cresol)
+ NaNH2
Cl
NH3 (l)
o
(-33 C)
+ NaCl
+
NH2
NH2
4-Methylaniline 3-Methylaniline
(p-Toluidine)
(m-Toluidine)
22-42
Benzyne Intermediates
-elimination of HX gives a benzyne intermediate, that
then adds the nucleophile to give products.
22-43
Benzyne Intermediates
But wait, do we believe this crazy idea? We need some evidence.
22-44
Benzyne Intermediates
The deuterated fluoride below exchanges the D with
solvent ammonia although the deuterated bromide does
not. This indicates a relatively rapid exchange process for
the fluoro compound.
next
22-45
Benzyne Intermediates
explanation
22-46
Orientation
22-47
Benzyne Intermediates
D
Get
same
product
Explation
next
22-48
Benzyne Intermediates
explanation
22-49
Cl
NO2
Na2 CO3, H2 O
O Na
NO2
100 C
NO2
1-Chloro-2,4dinitrobenzene
NO2
Sodium 2,4-dinitrophenoxide
22-50
Meisenheimer Complex
Reaction involves formation of reactive intermediate
called a Meisenheimer complex.
O
+N
O
slow, rate
determining
Cl + Nu
(1)
NO2
O
+N
O
Cl
Nu
NO2
fast
(2)
O
+N
O
Nu + :Cl
NO2
A Meisenheimer complex
22-51