Subject Chemistry

Paper No and Title Paper-5, Organic Chemistry-II (Reaction Mechanism-1)

Module No and Title Module-, Aromatic Electrophilic Substitution: Quantitative

treatment of reactivity in substrates and electrophiles.
Module Tag CHE_P5_M30

CHEMISTRY PAPER No:5, Organic Chemistry-II

MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.
 TABLE OF CONTENTS
1. Learning Outcomes
2. Introduction

3. Applicability of Hammett equation for Electrophilic Aromatic Substitution

3.1 Failure of Hammett equation

3.2 Modified Hammett equation for EAS

4. The Selectivity Relationship

6. Summary

CHEMISTRY PAPER No:5, Organic Chemistry-II

MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.
 1. Learning Outcomes

After studying this module, you shall be able to

• Know about Hammett equation and its effect on m- and p- substituents in the aromatic
ring system to the rate of reaction for many different reactions
• Learn about the applicability of Hammett equation for Electrophilic Aromatic
Substitution
• Familiarize with the reasons for failure of Hammett equation in EAS and know about
modified Hammett equation for EAS
• Identify and learn about the selectivity relationship

2. Introduction
The rates of Electrophilic Aromatic Substitutions (EAS) are not same for a set of aromatic ring
systems having different substituents and a given electrophile. One always wonders the way in
which substituents modify the reactivity of the aromatic nucleus. In order to answer (to a certain
extent) such questions, correlations of reactivity have been drawn in which relative reactivity in
different aromatic substitutions can be expressed by equations containing one term characteristic
only of the substituent, and another term which depends only on the reaction. The best known
equation for this is the Hammett equation which was originally deduced for the benzoic acid
ionization equilibrium and defined as:

where, k is the rate or equilibrium constant for a substituted compound in a reaction series;
k0 is the rate or equilibrium constant for the unsubstituted compound in the same reaction
series;
σ is the log(K/K0) for the benzoic acid ionization equilibrium chosen as the standard
reaction series, although many substituent constants have been calculated for other
CHEMISTRY PAPER No:5, Organic Chemistry-II
MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.
 reactions as well. (Ko is the acid dissociation constant for the ionization of benzoic acid
and K is the acid dissociation constant for the ionization of a substituted benzoic acid);
ρ is a dependent variable which is a measure of the susceptibility to substituent effects of
the reaction series under consideration relative to that of the benzoic acid ionization series.

Since log Ko is directly related to the standard free energy change accompanying the ionization of
benzoic acid (ΔGo = -2.303RTlog Ko), and log K is directly related to the standard free energy
change accompanying the ionization of the substituted benzoic acid, the Hammett equation is an
example of Linear Free Energy Relationship (LFER).

Since the K’s depend somewhat upon the temperature and critically upon the nature of the
solvent, σ is defined specifically for water at 25 ᴼC. Also, since the magnitude of the substituent
effect depends upon the position of the subsituent on aromatic ring, there are different substituent
constants for para, meta, and ortho substituents. It should be noted that, by definition, Hammett
substituent constants are relative to hydrogen as a basis of comparison. That is to say, σH = 0.
The sign of σ can tell about the relative effect of substituent:

• If (K/Ko) >1: This implies that the substituent has increased the acidity of the benzoic
acid, σ is positive. Such a substituent is considered to be an electron-withdrawing group
(EWG), because electron density is increased at the reaction site in the product benzoate
anion, and an EWG will favor this change by withdrawing electron density away from
the reaction site. Groups such as m-Cl, p-Cl, m-NO2, p-NO2, etc. which have relatively
large dipole moments oriented with the positive end directed toward the reaction site are
EWGs.
• If (K/Ko) < 1: It implies electron donating groups (groups which tend to increase the
electron density near the reaction site) disfavor the ionization to a negatively charged ion.
These include alkyl groups (at both the meta and para positions), para alkoxy groups,
and p-amino groups.
• The substituent constant σ is a measure of the total polar effect exerted by substituent X
(relative to no substituent) on the reaction centre.

CHEMISTRY PAPER No:5, Organic Chemistry-II

MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.
 • The reaction constant ρ is the slope of the line correlating log k with the σ values of the
substituents.
• The sign of the slope tells whether a reaction rate is accelerated or suppressed by
electron-donating vs. electron withdrawing substituents.
o Negative ρ is diagnostic of the development of positive charge at the reaction
centre in the transition state of the rate-limiting step.
o Positive ρ is diagnostic of the development of negative charge at the reaction
centre in the transition state of the rate-limiting step.
• The magnitude of ρ is a measure of how susceptible a reaction is to the electronic
characteristics of the substituent.

Hammett equation gave fairly good correlations for the effect of m- and p- substituents in the
aromatic ring system to the rate of reaction for many different reactions sush as esterifications,
electrophilic addition to phenyl-alkenes, elimination reactions, nucleophilic substitutions etc. but
failed for o-substituted systems, which was attributed to the steric effect of the o-substituent on
the reaction centre. Also, its applicability for the Electrophilic Aromatic Substitutions is limited
which will be discussed in the proceeding sections.

3. Applicability of Hammett equation for Electrophilic Aromatic

Substitution

3.1 Failure of Hammett Equation

For Aromatic substitution reactions, quantitative rate studies are difficult as there are usually
several hydrogens that can leave, and hence, the measurements of overall rate ratios does not give
a complete picture as they do in nucleophilic substitutions (where it is easy to compare reactants
having only one possible leaving group). Therefore, partial rate factor for a given group and a
given reaction is used which gives the rate of substitution at a single position relative to a single
position in benzene. For example, toluene is acetylated at the ortho position 4.5 times as fast as a

CHEMISTRY PAPER No:5, Organic Chemistry-II

MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.
 single position in benzene, therefore its partial rate factor will be of = 4.5 for the acetylation
reaction. Similarly, mf = 4.8 and pf = 749.

Once partial rate factors for a reaction are known, one can predict the proportions of isomers to be
obtained when two or more groups are present on a ring by making the assumption that the effect
of substituents is independent.

Now, if one applies the Hammett equation for Electrophilic Aromatic Substitution reactions,

the k0 is divided by 6 and, for meta substitution, k is divided by 2, so that comparisons are made
for only one position.

However, while this approach worked fairly well with benzenes containing electron-withdrawing
groups, it failed for those that contain electron donating substituents. This failure arises because
Hammett's original model reaction (the ionization of substituted benzoic acids) does not take
account of the direct resonance interactions between a substituent and the site of reaction. For
example, consider the resonance structures for electrophilic substitutions of anisole, which show
the transition state to be stabilized by direct resonance with the substituent:

CHEMISTRY PAPER No:5, Organic Chemistry-II

MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.
 Since these interactions are impossible when the substituent is attached to the meta position, and
are not operative for even a para resonance-electron withdrawing substituent like nitro or acetyl,
the sigma values of these latter kinds of substituents are still valid and they nicely fall on the
standard Hammett plot.

3.2 Modified Hammett Equation for EAS

After the failure of the classical Hammett equation for the electrophilic aromatic substitutions, it
was suggested that by choosing a different model reaction, in which the direct resonance effects
of substituents contributed, another equation, similar to Hammett's equation, might be devised to
correlate the rates of electrophilic aromatic substitutions.

Brown and his co-workers chose a different model reaction: the solvolysis of substituted
dimethylphenylcarbinyl chlorides (cumyl chlorides) in 90% aq. acetone.

It was thought that because a positive charge develops during the transition state, more
satisfactory correlations can be made, even for electron-donating groups. In the case of p-
substituted substrates, the transition state, represented by the following resonance structures, is
stabilized by direct resonance interaction between the substituent and the site of reaction as
shown below.

CHEMISTRY PAPER No:5, Organic Chemistry-II

MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.
 Using the data for this new reaction (solvolysis of cumylchlorides in 90% aqueous acetone at 25
ᴼC), a plot of Hammett's σ-constants vs the logarithms of the rate constants for the solvolysis of a
series of m-substituted cumylchlorides was plotted.

As expected, m-substituted cumyl chlorides gave a good linear relation while p-susbstituted ones
fall out of the plot. Brown, then modified the Hammett equation as:

Here he introduced σ+ which were determined by extrapolating the originally outlying points
(for the p-substituted cumyl chlorides) to fit into the standard Hammett curve.

CHEMISTRY PAPER No:5, Organic Chemistry-II

MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.
 A look to some of the σ+ values is presented:

For these cases, when σ+ is used to designate the substituent constant, the reaction parameter
should be denoted as ρ+. ρ+ for this new standard reaction is –4.5, the negative sign indicating the
development of positive charge at the reaction site in the transition state.

This modified Hammett equation using the Brown’s σ+ constants gave a fair correlation of the
substituent effects on various electrophilic aromatic substitutions. For example, for nitration

CHEMISTRY PAPER No:5, Organic Chemistry-II

MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.
 reaction of susbtituted benzenes carried at 25 ᴼC in nitromethane or acetic anydride, a plot of log
k/k0 against σ+ produced a ρ+ = –6.53.

Another example is Friedel Craft’s acylation reaction. Here also σ+ valus were used for e-
donating groups and a linear relationship was witnessed, with observed value of ρ+ = –0.49.

CHEMISTRY PAPER No:5, Organic Chemistry-II

MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.
 4. The Selectivity Relationship

Brown also suggested another modification to the Hammett approach called the selectivity
relationship, which is based on the principle that reactivity of a species varies inversely with
selectivity. For example, on comparing the reactivities of toluene relative to benzene in aromatic
substitutions, these were found to be proportional to the ratios in which toluene underwent p- and
m- substitutions as shown in the table below.

Table 1 Relative rates and isomer distribution for substitution in benzene and toluene

This proportionality can be expressed as:

log fp-Me = b log (fp-Me/fm-Me)

where, fp-Me and fm-Me are the partial rate factors for substitution at p- and m-positions,
respectively.

Now, by defining the selectivity factor, Sf as

Sf = log (fp-Me/fm-Me)

the former equation becomes:

log fp-Me = b Sf

This equation is now similar to the Hamett ρ+σ+ equation.

CHEMISTRY PAPER No:5, Organic Chemistry-II

MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.
 b being a parameter whose value depends on the values of σ+ for meta- and para-methyl groups.

Sf is related to ρ+ as

Sf = ρ+ (σp+ – σm+)

The Selectivity factor is a measure of selectivity of an electrophile, which is expressed by the

extent to which it discriminated either between benzene and toluene, or between the meta- and
para-positions in toluene. In simple words, it states that, the more reactive is the electrophile, the
less is its selectivity towards any particular atom/position of the substrate. Through this relation,
selectivity was considered to be related to its reactivity and assumed to not be dominated by other
factors. Thus, powerful electrophiles such that those in Friedel-Crafts' alkylation reactions were
considered to be electrophiles which would be less able to distinguish between substrates and
positions than a weakly electrophilic reagent. Thus, the electrophiles operating in reactions which
have low selectivity factors (Sf) or reaction constants (σ+), are intrinsically more reactive than the
effective electrophiles in reactions which have higher values of these parameters. For example,
bromination reaction of a set of substituted benzenes with Br+ (a reactive electrophile) would
result in lower selectivity than those with relatively less reactive Br2 species.

A series of experiments were done by Olah et al and the effect of substituents on the reactivity
and selectivity of electrophile were determined. Some of the data is represented in Table 2 and
the salient points are discussed as follows:

o It was shown that substituents may affect the substrate selectivity as measured by the
kToluene/kBenzene (kT/kB) ratio. Thus, while electron-donating substituent located at position
ortho and para with respect to the benzylic centre, increase the kT/kB ratio, electron-
withdrawing substituents decrease it.

CHEMISTRY PAPER No:5, Organic Chemistry-II

MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.
 o The acylation of toluene and benzene clearly proved the importance of substituents on the
electrophilicity of the substituting agent, which was reflected by high kT/kB ratios.

o The effect of the nucleophilicity of the aromatic substrate was observed to cause similar
effects; so that with increasingly more basic aromatics, even relatively weak electrophiles
resulted in early transition states resembling more starting materials than intermediates.

Table 2: kt/kb ratios for TiCl4 catalyzed benzylation and AlCl3 catalyzed benzoylation reactions

However, this relationship was found to hold true only under certain cases and under very closely
related conditions. It was observed that this treatment worked well with groups such as methyl
that are not polarizable. As each electrophile makes a different demand for the electrons in the
transition state, with more polarizable groups, the correlations are mostly unsatisfactory. Also, for
more stronger electrophiles, this selectivity relationship was found to be unsatisfactory.

For example, the selectivity relationship is found to hold for nitration in sulphuric acid where the
nature and concentraions of the nitronium ion (electrophile) is well established. However, for

CHEMISTRY PAPER No:5, Organic Chemistry-II

MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.
 mercuration and in Friedel Crafts’s alkylations, many times the slectivity relation breaks down. In
case of mercuration, it was formulated that, reversible formation of a Wheland intermediate takes
place on attack by the electrophile, followed by a loss of electron. However, due to the similar
rate factors of the reversible step-1 and that of step-2, the influence of ring substituents is
nullified and so the slectivity relationship does not hold good.

Also, the selctivity relation was found to be valid for only simple processes where single bond
breaking/formation takes place in the transition state. Similarly, reactions, in which solvation
factors contribute significantly, do not obey this relationship. However, in spite of such
limitations, the empirical reactivity-selectivity relationship has been illustrated for a variety of
electrophilic armoatic substitution reactions (and to other reactions, as well) and provide
experimental support to study their mechanisms.

5. Summary

• Correlations of reactivity have been drawn in the form of Hammett equation in which
relative reactivity in different aromatic substitutions can be expressed by equations
containing one term characteristic only of the substituent, and another term which
depends only on the reaction.

• However, Hammett’s approach worked fairly well with benzenes containing electron-
withdrawing groups, but it failed for those that contain electron donating substituents.

CHEMISTRY PAPER No:5, Organic Chemistry-II

MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.
 • This failure arises because Hammett's original model reaction (the ionization of
substituted benzoic acids) does not take account of the direct resonance interactions
between a substituent and the site of reaction.

• By choosing a different model reaction (solvolysis of substituted cumyl chlorides in 90%

aq. acetone at 25 ᴼC), in which the direct resonance effects of substituents contributed, a
modified Hammett's equation, which used σ+ values, was devised to successfully
correlate the rates of electrophilic aromatic substitutions.

• Brown also suggested another modification to the Hammett approach called the
selectivity relationship, which is based on the principle that reactivity of a species varies
inversely with selectivity.

log fp-Me = b Sf

• The electrophiles operating in reactions which have low selectivity factors (Sf) or reaction
constants (σ+), are intrinsically more reactive than the effective electrophiles in reactions
which have higher values of these parameters.

• A series of experiments under closely monitored conditions validated the concept of

reactivity-selectivity.

• Although the selectivity relationship was found to successfully correlate reactivity as a

function of selectivity in several aromatic electrophilic substitutions, it was found to have
many limitations and would usually work in simple processes and under closely related
systems.

CHEMISTRY PAPER No:5, Organic Chemistry-II

MODULE No. 30 Module-, Aromatic Electrophilic Substitution:
Quantitative treatment of reactivity in substrates and electrophiles.