chemistry paper : 05 , organic chemistry -ii (reaction

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
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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
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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
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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
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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
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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
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The electrophiles can be generated in various ways, examples are shown below:
Fig. 6: Generation of electrophiles for electrophilic aromatic substitution
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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
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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.
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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
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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
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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
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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
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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.
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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.
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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.
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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.
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chemistry paper : 05 , organic chemistry -ii (reaction

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