BSc ChemistryCHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
Subject Chemistry
Paper No and Title 5, Organic Chemistry-II (Reaction
Mechanism-1)
Module No and Title 28, Arenium ion mechanism in electrophilic
aromatic
substitution, orientation and reactivity, energy profile
diagrams
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
TABLE OF CONTENTS
1. Learning Outcomes
3. Arenium Ion Mechanism
3.1 Steps involved in Arenium Ion Mechanism
3.2 Energy Profile Diagram of the Arenium Ion Mechanism of
Electrophilic
Aromatic Substitution
4. Evidence of Arenium Ion Mechanism
5. Orientation and Reactivity
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
1. Learning Outcomes
Understand why aromatic compounds undergo electrophilic aromatic
substitution
Mechanism of electrophilic aromatic substitution and arenium ion
intermediate/ Wheland
intermediate involved
Isolation of the arenium ion intermediate as a proof of arenium ion
mechanism
The orientation and reactivity of benzene and related aromatics
towards electrophilic
aromatic substitution
The energy profiles or the free energy diagrams associated with
electrophilic aromatic
substitution
2. Introduction
There are two main classes of aromatic substitution. One is
electrophilic substitution and
the other nucleophilic substitution. There are many types of
aromatic systems. Among
them, the chemistry of benzene and its simple derivatives has been
studied in most detail.
Thus, this modules concerns with reaction on a benzene ring and in
particular
electrophilic aromatic substitution.
The attacking electrophile is a positive ion (or positive end of a
dipole or induced dipole).
After the reaction the “leaving group” must depart without its
electrons. The most
common departing group is the proton, H+.
3. Electrophilic Aromatic Substitution
One of the characteristics of benzene derivatives is that they tend
to undergo substitution
at aromatic carbon rather than to undergo substitution at aromatic
carbon rather than
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
addition (to the double bonds). This property aromatic compounds is
mainly due to their
‘aromaticity’. Some common examples of electrophilic aromatic
substitution reactions
are shown in the given figure.
Fig. 1: Some examples of most commonly occurring electrophilic
aromatic
substitution
1. What is the attaching agent?
2. How does it carry out the substitution?
3. How is the reaction influenced by other groups on the benzene
ring?
We shall discuss these concerns in detail now.
4. Arenium Ion Mechanism and Energy Profile Diagrams
4.1 Steps involved in Arenium Ion Mechanism
The mechanism aromatic electrophilic substitution is known as the
arenium ion
mechanism and has two main steps.
Step 1: The initial step is the attack of an electrophile creating
a resonance stabilized
carbocation/intermediate called arenium ion, which is also known as
the Wheland
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
Intermediate. Although the Wheland intermediate or σ-complex or now
popularly known
as arenium ion is stabilized by resonance (with charge dispersal
over the carbons ortho
and para to the site of attachment of the electrophile), this step
is accompanied by loss of
aromaticity, so the energy of activation is high.
This is also the rate-determining step of the reaction because of
the disruption of
aromaticity.
Fig. 2: Rate determining slow step which leads to generation of
arenium ion and its
resonance stabilized forms
Step 2: In the second step the leaving group departs. This leads to
regeneration of
aromatic stabilization. The second step is nearly always faster
than the first, making the
first rate determining, and the reaction is second order.
Fig. 3: Formation of product and regeneration of aromaticity
Note: There is some resemblance of this mechanism to the attack of
nucleophiles on the
carbonyls of esters or amides to give tetrahedral intermediates,
except that the charges are
reversed. If the electrophilic species is not an ion but a molecule
with a polarized
covalent bond, the product must have a negative charge unless part
of the dipole, with its
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
pair of electrons, is broken off somewhere in the process, as in
the conversion of A to B.
Note that when the aromatic ring attacks X, Z may be lost directly
to give B.
Fig. 4: When the attacking electrophile is a molecule instead of an
ion
4.2 Energy Profile Diagram of the Arenium Ion Mechanism of
Electrophilic
Aromatic Substitution
Fig. 5: Free energy diagram of electrophilic aromatic
substitution
The energy diagram of this reaction shows that step 1 is highly
endothermic and has a
large G‡ (1)
The first step requires the loss of aromaticity of the very stable
benzene ring,
which is highly unfavourable
The first step being a slow step, is rate-determining
Step 2 is highly exothermic and has a small G‡ (2)
The ring regains its aromatic stabilization, which is a highly
favorable process
4.3 Generation of Electrophiles (E+)
A B
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
The electrophiles can be generated in various ways, examples are
shown below:
Fig. 6: Generation of electrophiles for electrophilic aromatic
substitution
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
5. Evidence for Arenium Ion Mechanism
The direct evidence for proposed reaction intermediate in aromatic
substitution has been
obtained by Dr. Olah using NMR spectroscopy.
A mixture of mesitylene (1) with an alkyl halide and a good lewis
acid at low
temperatures yielded the intermediate (2). This (2) went on to the
final product (3) at
higher temperature.
There are numerous studies which show that such salts like this
intermediate can exist as
stable species under favourable conditions. Even the simplest
benzonium ion (4) could be
prepared and studied. These types of charged units are sometimes
called as σ complexes.
The evidence for the arenium ion mechanism is mainly of two
kinds:
1. Isotope Effects: If the hydrogen ion departs before the arrival
of the electrophile (SE1
mechanism) or if the arrival and departure are simultaneous, there
should be a substantial
isotope effect (i.e., deuterated substrates should undergo
substitution more slowly than
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
non-deuterated compounds) because, in each case, the C H bond is
broken in the rate-
determining step. However, in the arenium ion mechanism, the C H
bond is not broken
in the rate-determining step, so no isotope effect should be found.
Many such studies
have been carried out and, in most cases, especially in the case of
nitrations, there is no
isotope effect. This result is incompatible with either the SE1 or
the simultaneous
mechanism. However, in many instances, isotope effects have been
found. Since the
values are generally much lower than expected for either the SE1 or
the simultaneous
mechanisms (e.g., 1–3 for kH/kD instead of 6–7), there must be
another explanation. For
the case where hydrogen is the leaving group, the arenium ion
mechanism can be
summarized:
Fig. 7: When hydrogen is the leaving group in electrophilic
aromatic substitution
reaction
The small isotope effects found most likely arise from the
reversibility of step 1 by a
partitioning effect. The rate at which ArHY+ reverts to ArH should
be essentially the
same as that at which ArDY+ (or ArTY+) reverts to ArD (or ArT),
since the Ar H bond is
not cleaving. However, ArHY+ should go to ArY faster than either
ArDY+ or ArTY+,
since the Ar H bond is broken in this step. If k2»k-1, this does
not matter; since a large
majority of the intermediates go to product, the rate is determined
only by the slow step
(k21[ArH][Y+]) and no isotope effect is predicted. However, if k2≤
k-1, reversion to
starting materials is important. If k2 for ArDY+ (or ArTY+) is
<k2 for ArHY+, but k-1 is
the same, then a larger proportion of ArDY+ reverts to starting
compounds. That is, k2/k-1
(the partition factor) for ArDY+ is less than that for ArHY+.
Consequently, the reaction is
slower for ArD than for ArH and an isotope effect is
observed.
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
2. Isolation of Arenium Ion Intermediates: The isolation of arenium
ions in many cases
provides for a very strong evidence for the arenium ion mechanism.
When 10 was heated,
the normal substitution product (11) was obtained. Even the
simplest such ion, the
benzenonium ion (12) has been prepared in HF SbF5 SO2ClF SO2F2 at
-134 °C, where
it could be studied spectrally.
Fig. 8: Isolation of arenium ion intermediates
6. Orientation and Reactivity
When an electrophilic substitution reaction is performed on a
monosubstituted benzene,
the new group may be directed primarily to the ortho, meta, or para
position. Also,
sometimes, a fourth type of substitution may be encountered viz.,
ipso substitution, a
special case of electrophilic aromatic substitution where the
leaving group is not
hydrogen but the original substituent itself.
Fig. 9: Four possibilities of attack on monosubstituted
benzene
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
Note that the substitution may be slower or faster than with
benzene itself. Thus, the
formation of four possible intermediates is dependent not on the
thermodynamic stability
of the products, but on the activation energy necessary to form
each of the four
intermediates. Considering the Hammond postulate, we assume that
the geometry of the
transition state also resembles that of the intermediate and that
anything that increases the
stability of the intermediate will also lower the activation energy
necessary to attain it.
Fig. 10: Reaction coordinate for the first step in various
electrophilic substitutions in
monosubstituted benzene
The group already on the ring determines which position the new
group will take and
whether the reaction will be slower or faster than with benzene.
Groups that increase the
reaction rate are called activating and those that slow it are
deactivating. The groups, R/Z,
according to their influence on both reactivity and orientation are
classified into different
categories. Two properties of R/Z have a major influence, namely,
inductive (I) effects
and resonance (sometimes known by the older term, mesomeric) (Re or
M) effects.
The groups, R/Z, fall into the following categories:
O-, NR2, NHR, NH2, OH, OR, NHCOR, OCOR
NO2, CN, SO3H, CHO, COR, CO2H, CONH2
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
R
CO2 -
+NR3, +NH3, CCl3, CF3
F, Cl, Br, I
Fig. 11: Ortho, meta and para substitution in monosubstituted
benzene and the
possible structures of the corresponding arenium ions formed.
Six common electrophilic aromatic substitution reactions are listed
below:
1. Halogenation: This is done by replacing hydrogen with a bromine
or chlorine.
Both processes bromination and chlorination require a Lewis acid,
which accepts
a pair of electrons to create a permanent bond dipole of the Br-Br
bond or the Cl-
Cl bond. This dipole allows the bromine or chloride to have a
formal positive
charge and therefore allows the group to be electrophilic enough to
overcome the
activation energy caused by the loss of aromaticity of the benzene
ring.
a. Bromonation
b. Chloronation
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
Consider chlorination of nitrobenzene which gives rise to the meta
substituted
product as nitro is an electron withdrawing group.
Fig. 12: Halogenation of nitrobenzene as an example of EAS
2. Nitration: This happens by the replacement of a hydrogen with a
nitro (NO2)
group. Nitration process requires the presence of sulfuric acid
(H2SO4) as a
catalyst. Just like we had to take extra steps to create the
electrophile in
bromination and chlorination (with the help of a Lewis acid), we
must use the
sulfuric acid to protonate the nitric acid, resulting in the
formation of a nitronium
ion. The nitronium ion can then proceed as a general electrophilic
aromatic
substitution. Nitration of toluene gives a para product
predominantly as alkyl
groups are o-/p- directing.
Fig. 13: Nitration of toluene as an example of EAS
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
3. Sulfonation: This occurs by replacing a hydrogen with a sulfonic
acid (SO3).
The sulfonation process is quite similar to nitration because in
general, we create
the electrophile by protonating the SO3 with H2SO4 to make a
stronger
electrophile. The mechanism can then proceed as an electrophilic
aromatic
substitution reaction. The sulphonation of acetophenone gives a
meta substituted
reaction.
Fig. 14: Sulphonation of acetophenone as an example of EAS
4. Friedel-Crafts Acylation: Friedel-Crafts acylation occurs by
replacing a
hydrogen with an acyl group (RC=O). In Friedel-Crafts Acylation, we
form the
acylium ion (the electrophile in the reaction) by using a lone pair
from the
chlorine (of the H3COCl) to fill the open octet of the aluminium
(of the AlCl3). As
a result, the chlorine carbon bond is weakened and Cl+-Al-Cl3
leaves. The
acylium ion acts as an electrophile in the electrophilic aromatic
substitution
mechanism. The hydroxyl group hers is an o-/p- directing group thus
a para
substituted product is formed henceforth.
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
Fig. 15: Friedel-Crafts acylation of phenol as an example of
EAS
5. Friedel-Crafts Alkylation: Friedel-Crafts alkylation replacing a
hydrogen with
an alkyl group (R). In Friedel-Crafts Alkylation, we use the lone
pair of the
chlorine (of the CH3Cl) to fill the open octet of aluminium (of the
AlCl3). As a
result, the ClAl-Cl3 leaves. The (CH3)3C + acts as the electrophile
in the
electrophilic aromatic substitution mechanism. Alkyl group here is
an o-/p-
directing group in toluene, thus a para substituted product is
formed henceforth.
Fig. 16: Friedel-Crafts alkylation of toluene as an example of
EAS
6. Diazotization of a Primary Amine: In this reaction, we react an
acid (like H3O +)
with NO2 - to form a nitrosonium cation (O=N+) which behaves as an
electrophile.
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
Then, we form the N-N bond with the electrophilic attack of the
nitrosonium
cation to the Ph-NH2. Then, through a series of protonation and
deprotonation
steps by water (the proton shuttle) a diazonium cation is
formed.
Fig. 17: Diazotization of phenol as an example of EAS
These conclusions are correct as far as they go, but they do not
lead to the proper results
in all cases. In many cases, there is resonance interaction between
Z and the ring; this
also affects the relative stability, in some cases in the same
direction as the field effect, in
others differently.
7. Summary
SN2 reactions observed with alkanes do not occur with aromatic
compounds as
they are stabilized by ‘aromatic stabilization’ energy. The
concentration of
negative charge above and below the plane of the ring carbon atoms
make the
aromatic systems susceptible to attack by electrophiles.
Arenium ion/ Wheland intermediate/ σ-complex is the name of the
intermediate
involved in the electrophilic susbstitution of aromatic compounds.
Arenium ion
mechanism and has two main steps.
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams
The first step is the rate determining step, involves the attack of
electrophile and
loss of aromaticity. The second step involves departure of the
leaving group
leading to regain of aromaticity.
The first step is highly endothermic and has a large G‡ (1) while
the latter step is
highly exothermic and has a small G‡ (2).
The isotope effects and the isolation of the arenium ion using
various techniques
and their spectral studies form the main evidences for the arenium
ion mechanism
When an electrophilic substitution reaction is performed on a
monosubstituted
benzene, the new group may be directed primarily to the ortho,
meta, or para
position. Also, sometimes, a fourth type of substitution may be
encountered viz.,
ipso substitution, a special case of electrophilic aromatic
substitution where the
leaving group is not hydrogen but the original substituent
itself.
The group already on the ring determines which position the new
group will take
and whether the reaction will be slower or faster than with
benzene. Groups that
increase the reaction rate are called activating (o-/p- directing)
and those that slow
it are deactivating (m- directing).
In many cases, there is resonance interaction between Z and the
ring; this also
affects the relative stability, in some cases in the same direction
as the field effect,
in others differently.
CHEMISTRY
PAPER : 05 , ORGANIC CHEMISTRY-II (Reaction Mechanism- I) MODULE :
28, Arenium ion mechanism in electrophilic aromatic
substitution, orientation and reactivity, energy profile
diagrams