Chemistry of Benzene
 Reactions of Benzene
 Just like alkenes, benzene has a substantial
amount of electron density due to the p-orbitals.
As a result, benzene also undergoes reactions
with electrophilic species "E+".
 Alkenes undergo electrophilic addition reactions:
H
+ Br2
C C
H3C
Br
H
Br
HC CH2
H
H3C
 Benzene, however undergoes electrophilic substitution reactions:
H
+ Br2
FeBr3
Br
+ HBr
Electrophilic Aromatic Substitution (EAS)
 The general mechanism for all electrophilic aromatic substitution reactions is the
following
2-step for
process:
The general
mechanism
ALL electrophilic aromatic substitution reactions is the following two step process:
B
H
+ H—B
H
E
+
H
E
E
H
-complex
H
 The -complex is a very important intermediate. It is stabilized by delocalization of
the positive charge.
The -complex is a very important intermediate. It is stabilized by delocalization of the positive charge:
H
E
H
H
E
H
H
E
H
Electrophilic Aromatic Substitution
 Substitution
vs. Addition:
Substitution
vs Addition
Br
H
Br+
H
H
Br
H
-complex
-complex
Br
H
Br+
H
H
E
H
Br
H Br
-complex
-complex
E
n
er
g
y
E
ne
rg
y
E
HBr
Reaction Progress
Reaction Progress
Substitution
Addition
H
H
Br
Br
Electrophilic Aromatic Substitution – Electrophiles E+
 EAS reactions differ only in the identity of E+ and
+ how it is generated!!
EAS reactions differ only in the identity of E and how it is generated.
Nitration
+ HNO3
H2SO4
heat
N O
H
+ H2SO4
 Reduction of nitroaromatics
gives anilines.
O
O
O
NO2
H
N O
O
 In the case of nitration, E+ is NO2+.
H
O
+ HSO4 -
N
O
+ H2O
Electrophilic Aromatic Substitution
Sulfonation
+ SO3
SO3H
O
O
S O
O
H2SO4
heat
S OH
+ H2SO4
O
+ HSO4 -
Electrophilic Aromatic Substitution
Halogenation
Br
Fe or
FeBr3
+ Br2
+ Cl2
Fe or
FeCl3
Br Br + FeBr3
+ HBr
Cl
+ HCl
+
Br
Br
FeBr3
Electrophilic Aromatic Substitution
H
H
H3PO4
H
H
O
H3C
C
H
H+
HO
CH3
HO
HO
HO
HO
Bisphenol A
HO
OH
Friedel-Crafts Alkylation
 Alkylation of Aromatic Compounds – The Friedel-Crafts Reaction:
Alkylation of Aromatic Compounds - The Friedel-Crafts Reaction
+ RCl
H3 C
CH
Cl
R
AlCl3
+ AlCl3
H3C
+ HCl
H3 C +
CH Cl
H3C
AlCl3
H3 C
H + AlCl4
C
H3C
When a relatively stable carbocation
In some alkylations, this complex
is possible,
then stable
it is likely
the electrophile
may
In some
alkylations
this
complex
may

When
a relatively
carbocation
is
serve as the alkylating electrophile.
serve as the alkylating electrophile.
possible, then it is likely the electrophile.
Again, the mechanism for this reaction is no different than any other Electrophilic Aromatic Substitution.
Cl
H3 C
H3C
H
C
H
CH3
CH
CH3
 The mechanism is the same as all other EAS reactions
CH3
CH
CH3 + HCl
Friedel-Crafts Alkylation
 Carbocation rearrangements can occur during Friedel-Crafts Alkylations:
Carbocation Rearrangement during Friedel-Crafts Alkylations
+ CH3 CH2CH2Cl
CH2 CH2 CH3
AlCl3
CH3
CH
40%
35°C
5h
CH3
60%
PhH
PhH
H
H3CH 2CH2 C Cl + AlCl3
+
H3C C C
H2
H
Cl
Rearrangements like this
always a problem whe
more stable carbocation
result from a hydride or a
shift.
AlCl3
H3 C
C
H + AlCl4
H3C
 Such rearrangements always compete when a more stable carbocation can result
from a hydride or alkyl shift.
Friedel-Crafts Acylation
Friedel-Crafts Acylation
O
H3 C C Cl
O
C
AlCl3
O
CH3
O
H3 C C Cl + AlCl3
AlCl3
H3 C C+ Cl

An acid chloride.
Mechanism
H3 C C O
O
O
C
H3C
Cl
H
C
O
CH3
H3 C C ClO+ HCl
+ HCl

H3 C C O
The Acylium cation, a resonance
stabilized carbocation, is the
electrophile.
CH 3
The Friedel-Crafts acylation can be used to circumvent the problems of carbocation rearrangement.
O
O
H2NNH 2, KOH
C
AlCl3
CH2CH3 (Wolff-Kishner reduction)
H 3CH2 C C Cl
or
Zn/Hg amalgam, HCl
(Clemmenson reduction)
CH2 CH2 CH3
 The Friedel-Crafts acylation can be used to circumvent the problems of carbocation
rearrangement.
Reactions of Substituted
Benzenes
Electrophilic
Aromatic
Substitution of Substituted Molecules
CH3
CH3
CH3
CH3
NO2
HNO
HNO
3, 3
H
4
Acetic2SO
Acid
+
Toluene
2-Nitrotoluene
Statistical
Statistical
Actual
Actual
40%
40%
60%
60%
+
NO2
NO 2
3-Nitrotoluene 4-Nitrotoluene
40%
40%
20% 20%
3% 3%
37% 37%
This reaction is faster than the corresponding nitration of benzene. Why? And what is
the reason
for this
particular
product distribution?
groups
and several other
 This reaction
is faster
than
the corresponding
reactionAll
of alkyl
benzene.
Why?
substituents show this pattern of reactivity.
NO2
HNO
HNO
3 ,3
HH
2SO
44
2SO
Nitrobenzene
Statistical
Actual
NO2
NO2
NO2
NO2
+
NO2
1,3-Dinitrobenzene
93%40%
Yield
93%
NO2
40%
20%
Minor products
trace
trace
This reaction is much slower than the nitration of benzene. Toluene gives mainly ortho
and paraisproducts
nitrobenzene
gives the
meta product
almost exclusively.
What
 This reaction
slower while
than the
corresponding
nitration
of benzene.
Why?
is it about the substituent that directs the position of the incoming electrophile?
Electrophilic Aromatic Substitution of Substituted Molecules
Cl
Cl
NO2
HNO3,
HNO
3
SO4
HH2SO
2
+
+
4
30%
o-Chloronitrobenzene
Statistical
Cl
Cl
40%
NO2
1%
m-Chloronitrobenzene
40%
NO2
69%
20%
p-Chloronitrobenzene
This reaction is
slower
than the nitration of 30%
Actual
1%
69%
benzene. All of the halogens follow this pattern of reactivity. What's going on?
 This reaction is slower than the corresponding nitration of benzene. Why?
 Why do toluene and chlorobenzene give predominantly ortho and para substitution, while
nitrobenzene gives predominantly meta substitution?
Electrophilic Aromatic Substitution - Activators
Substituent Directing Effects
-Complex Intermediates
CH3
CH3
+ NO2
H
CH3
O
N+
O
+
CH3
CH3
+
NO2
H
CH3
NO2
+
CH3
CH3
NO2
H
+
NO2
H
CH3
+
NO2
H
CH3
CH3
NO2
H
CH3
NO2
CH3
+
+
+
H NO2
H NO2
H NO2
NO2
 Any substituent capable of stabilizing an adjacent positive charge
(resonance or inductive) gives predominantly ortho and para substitution.
Electrophilic Aromatic Substitution – Resonance Activators
:
:
 This includes ANY ATOM THAT CONTAINS A LONE PAIR and is directly attached to
the ring.
+ OH
: OH
+
H
E
 Examples of this type of substituent:
Br
: :
Cl
: :
:
F
: :
: :
:
.. and
thethe
halides:
…and
halides:
:
OH
NHR
O
O C R
O
N C R
H
: :
: :
: :
OR
NR2
:
NH2
:
Z=
:
Z
:
E
I
:
H
 Resonance Activator
Electrophilic Aromatic Substitution - Deactivators
-Complex Intermediates
O
O-
N+
+
O
NO2
O
N+
O
NO2
H
ON+
NO2
H
+
O
O-
N+
O N+ ONO2
H
O
O+
N
O
O+
N
+
+
O
+
O-
N+
O-
N+
NO2
NO2
+
NO2
H
O
NO2
H
NO2
NO2
H
O
O-
N+
NO2
NO2
+
+
H NO2
+
H NO2
H NO2
NO2
 Any substituent which destabilizes an adjacent positive charge gives
predominantly meta substitution.
Electrophilic Aromatic Substitution - Deactivators
 ANY SUBSTITUENT WHICH DESTABILIZES AN ADJACENT POSITIVE
CHARGE WILL BE A META-DIRECTOR.
 All of the following are meta-directors:
O
C
O
Esters
OR
C
O
O
C
C
R
Aldehydes
Ketones
Amides
NR2
O
C
OH
Carboxylic Acids
C
Nitriles
O
Cl
Acid
Halides
S
OH
O
Sulfonic acids
NH3
N
Electrophilic Aromatic Substitution of Substituted Molecules
 Directing Groups and Reaction Rate
 We have seen how substituents can be placed into two classes: those that
are ortho/para-directors and those that are meta-directors. What about the
effect of substituents on the rate of reaction?
We made the following observations:
1.) Benzenes substituted with ortho/para-directors will react more quickly
than benzene itself UNLESS THE SUBSTITUENT IS A HALIDE
(F, Cl, Br, I).
2.) Benzenes substituted with meta-directors ALWAYS REACT MORE
SLOWLY THAN BENZENE ITSELF.
Why?
Why?
 Recall that these substitutions are ELECTROPHILIC, i.e. the attacking species are
attracted by the large amount of electron density circulating in the aromatic ring.
+ CH3
 Alkyl groups are "electron releasing" or "electron donating". This is
how they are able to stabilize adjacent positive charges in EAS
reactions and in other carbocation species. (Recall that 3°
carbocations are more stable than 2° carbocations because they bear
more alkyl substituents.)
Electrophilic Aromatic Substitution of Substituted Molecules
 Substituents with lone pairs on them can delocalize an electron pair into the
aromatic ring thus dramatically increasing the electron density. This is
reflected in the resonance structures for phenol.
:
+ OH
_
+ OH
:
+ OH
:
:
+ :OH
_
_
 In both these cases, electron density is donated by the substituent into the
aromatic ring. Substituents that are capable of doing this are called
ELECTRON DONATING GROUPS. By donating electron density into
the aromatic ring they increase the charge density of the aromatic cloud
making it more attractive to attacking electrophiles. These groups are
therefore said to be ACTIVATING GROUPS as well as being ortho/para
directors.
Electrophilic Aromatic Substitution of Substituted Molecules
_
O
+
N
+
:
: Cl :
O  Meta-directors are electron withdrawing groups. They
suck electron density away from the aromatic electron
cloud making it less attractive to electrophiles. This slows
the reaction between the electrophile and the aromatic ring
as a result. Thus, meta-directors are said to be
DEACTIVATING.
 What about the halides?
Well, the halides strike a unique balance. They are
ortho/para-directors because their lone pairs are capable
of stabilizing an adjacent positive charge in a p-type of
interaction. At the same time, the halogens are
electronegative enough to diminish the electron density
of the ring through the -bond..
+
Electrophilic Aromatic Substitution of Substituted Molecules
Directing
influence
o,p
o,p
o,p
o,p
m
m
Summary
Substituent
-NH2 , -NHR, -NR 2 (amino and aminoalkyl),
-OH (hydroxy)
Effect on Rate
Very Strongly
Activating
-NHCOR (amide), -OR (ether),
-OCOR (ester - O end)
Strongly
Activating
R (alkyl), Aryl, Vinyl
Activating
X = F, Cl, Br, I (Halides)
-CHO (aldehyde), -COR (ketone),
-CO2H (carboxylic acid),
-CO2R (ester), -COCl (acid halide), -CN (nitrile),
-SO3H (sulfonic acid)
-NO2 (nitro)
Deactivating
Strongly
Deactivating
Very Strongly
Deactivating
Functional Group Interconversions of Benzene substituents
O
C
H2
C
NO2
SO3H
H2NNH2, KOH or
Zn/Hg, HCl
H2
C
O
KMnO4, or K2Cr2O7
C
Pd/H2 or Sn/HCl
aq. H2SO4
NH2
H
OH
Functional Group Interconversin of Benzene Substituents
H
The Sandmeyer Reaction
I
N Cl
NH2
N
NaNO2,
HCl, < 5°C
KX, Cu2X2
X = Cl, Br
CuCN
CN
KI
H3PO2
X
BF4
H2O, HSO4, ²
OH
F