Effects Substituent on the Reactivity and Orientation
of Electrophilic Aromatic Substitution
Substituent groups already on the benzene ring greatly influence
both the reactivity of electrophilic attack, and the site (o,m,p) of
attachment of the incoming electrophile.
Classification of Substituents
Substituents are classified as activating or deactivating relative to the
reactivity of benzene.
Substituents also are classified as ortho/para directing or
meta directing.
There is a fundamental theoretical connection
between the reactivity influence and site
direction of a substituent group.
Activating Groups: Ortho-Para Directors
The methyl and other alkyl groups are in this category.
Example: The Nitration of Toluene
The nitration of toluene proceeds faster than benzene and gives
predominantly ortho and para nitrotoluene products.
CH3
CH3
HNO3
H2SO4
toluene
more reactive
than benzene
CH3
NO2
+
CH3
+
NO2
NO2
o-nitrotoluene
59%
p-nitrotoluene
37%
m-nitrotoluene
4%
Alkyl groups are also activating and ortho/para directing in
other electrophilic aromatic substitutions such as
halogenation, sulfonation, and Friedel-Crafts reactions.
Other Substituent Groups that are Activating
and Ortho/Para Directing
methoxy-
=
OCH3
O
NHCCH3
acetamido-
OH
hydroxy-
NH2
amino-
Deactivating Groups: Meta Directors
The nitro group, -NO2, is an example.
The nitration of nitrobenzene proceeds at rate approximately 10-8
times the rate of nitration of benzene, and the major product is
meta-dintrobenzene.
NO2
NO2
HNO3
H2SO4
NO2
NO2
+
NO2
+
NO2
NO2
nitrobenzene
o-dinitrobenzene p-dinitrobenzene m-dinitrobenzene
much less reactive
1%
6%
93%
than benzene
Other deactivating and meta-directing groups are:
carboxyl-
SO3H
sulfo-
=
COOH
O
C-R
CF3
acyl-
trifluoromethyl-
Halogen Substituents: Deactivating but Ortho/Para Directing
The chloro and bromo substituents are unique in decreasing
reactivity in electrophilic aromatic substitution, but producing
mostly ortho and para products.
Cl
E+
Cl
E
+
+
E
E
chlorobenzene
ortho
Reaction
Cl
Cl
para
meta
________________ % ___________________
chlorination
39
55
6
bromination
nitration
11
30
87
70
2
--
sulfonation
--
100
--
A Summary of Substituent Effects on Electrophilic
Aromatic Substitution Reactions
ortho/para directing
and activating
ortho/para directing
and deactivating
meta directing and
very deactivating
:
-O-H
-Cl:
-O-R
O
-NHCR
-Br:
:
-NO2
+
-NR3
-CF3, CCl3
-F:
: :: :
: :: :: :: :
-NR2
-I:
-Ar
-SO3H
=
-R
-COOH
O
-CR
-C N
::
::
=
:
::
:
The reactivity order of substituted benzenes in electrophilic
aromatic substitution reactions is:
O
all meta
-NR2 > -O-H > -NHCR > -O-R > -R , -Ar > -X: > directors
=
Among the meta directors, the reactivity order is:
O
+
, -COOH, -SO3H > -NO2 , -NR3 , -CF3
-C N , -CR
Theory of Substituent Effects
The reactivity of substituted benzenes in electrophilic aromatic
substitution is determined by the electronic influence of the
substituent on the developing carbocation intermediate-the
arenium ion.
An electrophile attacks o,m, or p to a substituent.
S
S
S
+ E+
S is some
substituent
RDS
+
!+
H
E!+
transition state
H
E
arenium ion
intermediate
[the developing arenium ion}
When S is electron-releasing, it stabilizes the arenium ion
intermediate, and is expected to decrease the energy of the transition
state relative to the reaction of benzene.
When S is electron-withdrawing, it should destabilize the arenium
ion intermediate, and is expected to increase the energy of the
transition state relative to the reaction of benzene.
Since the addition of the electrophile is the RDS, the
reactivities of the arenes are in the order:
NO2
CH 3
>
>
because !GCH3 <
Electronic Influences of Substituent Groups:
Inductive and Resonance Effects
The electronic influences of substituent groups that operate on the
arenium ion (and the transition state leading to the arenium ion)
include both inductive and resonance effects.
The Inductive Effect
The inductive effect of a substitutent S arises from electrostatic
interactions transmitted through polarized sigma bonds.
In a covalent bond where S is more
electronegative than C, there is a permanent
polarization of the sigma electrons towards
the more electronegative atom:
!+
!"
S
C
When S is attached to a benzene ring, the ring carbon with the
substituent is more electropositive than the other carbon atoms.
!" !+
S
Examples of such
electronegative
substituents are the
halogens and other
groups shown:
+
NR3
!+ !"
CX3
ammonium trihalomethyl
-
-
O N=O
+
nitro
O
HO
+
S=O
Y !+ !"
C=O
sulfo
acyl
Addition of an electrophile, E+ , to such a
substituted will benzene be slower than
addition to benzene because of the buildup
of additional positive charge in the ring as
the arenium ion is formed.
!" !+
S
E+
slower
The Resonance Effect
S
:
:
S
S
+
+
S
HE
HE
+
+
HE
:
The resonance effect of a substituent S arises from the additional
resonance structures that are possible because of the electronic
features present in S. For example, nonbonding electron pairs on S
help stabilize the arenium ion through an additional resonance
structure.
HE
usual arenium ion resonance contributors
additional resonance
structure
:
most electrondonating
:OH , :OR > :X:
:
NH2 , NR2 >
:
:
:
The stabilizing influencing of
a nonbonding electron pair on
S is in the order:
least electrondonating
The Orientation of Electrophilic Aromatic Substitution
Meta Substitution: When S is Electron-Withdrawing
Meta substitution arises with substituents that are electron-withdrawing.
When an electrophile adds meta to the substituent, the formed arenium ion
has the most positive charge at positions ortho and para to the carbon of
attachment. This distribution avoids placing additional positive charge on
a ring carbon already electropositive because of S.
CF3
CF3
CF3
CF3
CF3
+
+
+
E
+
H
H
H
H
E
E
E
+E
meta addition
arenium ion
CF3
CF3
E+
+
para addition
H
+
+
+
E
arenium ion
HE
CF3
CF3
CF3
HE
HE
additional positive charge
on electropositive carbon
Ortho addition also leads
to an arenium ion with
additional positive charge
on the electropositive
carbon bonded to the
trifluoromethyl group.
CF3
CF3
E+
+
ortho addition
E
H
arenium ion
Based on the resonance structure descriptions of the distributions of
the positive charge among the carbons centers, the stabilities of the
arenium ions are:
CF3
CF3
+
H
E
more stable
CF3
+
+
H
E
less stable
E
H
Example: The Nitration of Trifluoromethylbenzene
CF3
CF3
HNO3
H2SO4
NO2
m-nitrotrifluoromethylbenzene
~100%
Ortho/Para Directing Groups
When the substituent is electron-donating, ortho/para products are
preferentially formed because of stabilization of the arenium ions
leading to those products. With substituents that have nonbonding
electron pairs, the arenium ions for the ortho/para products allow an
additional resonance structure to be drawn that shows further
distribution of the positive charge onto the substituent.
The following ortho/para directing substituents are all rate
accelerating, except for the halogens.
rate accelerating
:O-R
:
ortho/para
directing
groups
:NR2
:
R
:X:
rate
retarding
A Resonance Structure Analysis of the Site Selectivity
:
+OCH3
+
HE
arenium ion
:OCH3
HE
+
HE
HE
HE
In addition to the three standard three resonance
structures for the arenium ion, a fourth structure
disperses and stabilizes the positive charge
Conclusion
less stable
meta addition
E
H
arenium ion
:
+
:OCH3
:OCH3
:OCH3
E
H
E
H
:
E+
:
:
:
:OCH3
:OCH3
anisole
:
anisole
:OCH3
+
+
para addition
more stable
:OCH3
:
E+
:
:
:
:OCH3
:OCH3
+
+
E
H
+
The arenium ion for meta addition is described
by the three standard resonance structures.
:
:OCH3
:
Ortho addition also
provides an arenium ion
where the distribution of
positive charge allows
additional dispersal onto
the oxygen atom.
:OCH3
E
+H
E+
ortho addition
anisole
arenium ion
Based on the resonance structure descriptions of the distributions of
the positive charge among the carbons centers, the stabilities of the
arenium ions are:
:OCH3
E
+H
HE
more stable
:
+
:
:
:OCH3
:OCH3
+
E
H
less stable
Example: The Nitration of Anisole
anisole
40%
:OCH3
:
:
HNO3
45o C
:OCH3
NO2
+
:
:
:OCH3
:OCH3
+
NO2
58%
NO2
2%
The Halo Groups: Ortho-Para Directing but Rate Retarding.
An Oxymoron?
The apparent contradiction in behavior of the halogen substituents is
explained by opposing electronic influences of the inductive and
resonance effects.
Inductive Effect
!"
:X:
!+
:
The halogens are electronegative
relative to carbon, so they all
withdraw electrons inductively from
the benzene ring. This polarization
deactivates the aromatic ring towards
electrophilic addition.
Resonance Effect
:X:
+
arenium ion
HE
+
HE
HE
meta addition
:X:
:
:
:
+
:X:
+
+
E
H
arenium ion
+
E
H
HE
:
:
an important
contributor
:X:
:X:
E+
:X:
+
HE
:X:
:
:
:X:
+
para addition
+X:
:
E+
:
:
:
:X:
:X:
E
H
E
H
No special resonance stabilization by halogen.
Relative Rates of Nitration of Substituted Benzenes
compound
OH
major product
relative rate
ortho/para
CH3
1000
ortho/para
25
(1)
Cl
ortho/para
=
O
COC2H 5
0.03
meta
0.004
meta
2.6 x 10-5
meta
6 x 10-8
meta
1.2 x 10-8
+
CH2N(CH3) 3
NO2
+N(CH3)3
A reactivity
range of 1011!