Electrophilic aromatic substitution (SEAr) is an organic reaction in which an atom that is

attached to an aromatic system (usually hydrogen) is replaced by an electrophile. Some of

the most important electrophilic aromatic substitutions are aromatic nitration, aromatic
halogenation, aromatic sulfonation, and acylation and alkylating FriedelCrafts reactions.
Contents
[hide]

1 Illustrative reactions

2 Effect of substituent groups

o

2.1 Ortho/para directors

2.2 Meta directors

3 Reaction mechanism

4 Ipso substitution

5 Five membered heterocyclic compounds

6 Asymmetric electrophilic aromatic substitution

7 Other reactions

8 See also

9 External links

10 References

Illustrative reactions[edit]
The most widely practiced example of this reaction is the ethylation of benzene.

Approximately 24,700,000 tons were produced in 1999.[1] (After dehydrogenation and

polymerization, the commodity plastic polystyrene is produced.) In this process, solid
acids are used as catalyst to generate the incipient carbocation. All other electrophilic
reactions of benzene are conducted on much smaller scale, they are valuable routes to

key intermediates. The nitration of benzene is achieved via the action of thenitronium
ion as the electrophile.

Aromatic sulfonation of benzene with fuming sulfuric acid gives benzenesulfonic

acid.

Aromatic halogenation of benzene with bromine, chlorine or iodine gives the

corresponding aryl halogen compounds catalyzed by the corresponding iron or
aluminum trihalide.

The FriedelCrafts reaction can be performed either as an acylation or as

an alkylation. Typically, aluminium trichloride is used, but almost any
strong Lewis acid can be successful. For the acylation reaction
astoichiometric amount of aluminum trichloride must be used instead of
simply a catalytic amount.

Effect of substituent groups[edit]

See also: Arene substitution patterns

Both the regioselectivity and the speed of an electrophilic aromatic

substitution are affected by the substituents already attached to the
benzene ring. In terms of regioselectivity, some groups promote
substitution at the ortho or para positions, while other groups
increase substitution at the meta position. These groups are called
either orthopara directing or meta directing. In addition, some
groups will increase the rate of reaction (activating) while others
will decrease the rate (deactivating). While the patterns of
regioselectivity can be explained with resonance structures, the
influence on kinetics can be explained by both resonance
structures and the inductive effect.
Substituents can generally be divided into two classes regarding
electrophilic substitution: activating(Electron-donating substituents)
and deactivating(Electron-withdrawing substituents) towards the
aromatic ring. Activating substituents or activating
groups stabilize the cationic intermediate formed during the
substitution by donating electrons into the ring system, by
either inductive effect or resonance effects. Examples of activated
aromatic rings are toluene, aniline and phenol.
The extra electron density delivered into the ring by the substituent
is not equally divided over the entire ring, but is concentrated on
atoms 2, 4 and 6 (the ortho and para positions). These positions are
thus the most reactive towards an electron-poor electrophile. The
highest electron density is located on both ortho and para positions,
though this increased reactivity might be off set by steric
hindrance between substituent and electrophile. The final result of
the electrophilic aromatic substitution might thus be hard to predict,
and it is usually only established by doing the reaction and
determining the ratio of ortho versus para substitution.
On the other hand, deactivating substituents destabilize the
intermediate cation and thus decrease the reaction rate. They do so
by withdrawing electron density from the aromatic ring, though the
positions most affected are again the ortho and para ones. This
means that the most reactive positions (or, least unreactive) are the
meta ones (atoms 3 and 5). Examples of deactivated aromatic rings
are nitrobenzene,benzaldehyde and trifluoromethylbenzene. The
deactivation of the aromatic system also means that generally

harsher conditions are required to drive the reaction to completion.

An example of this is the nitration of toluene during the production
of trinitrotoluene (TNT). While the first nitration, on the activated
toluene ring, can be done at room temperature and with dilute acid,
the second one, on the deactivated nitrotoluene ring, already needs
prolonged heating and more concentrated acid, and the third one,
on very strongly deactivated dinitrotoluene, has to be done in boiling
concentrated sulfuric acid.
Functional groups thus usually tend to favor one or two of these
positions above the others; that is, they direct the electrophile to
specific positions. A functional group that tends to direct attacking
electrophiles to themeta position, for example, is said to be metadirecting.

Ortho/para directors[edit]
Groups with unshared pairs of electrons, such as the amino group
of aniline, are strongly activating and ortho/para-directing.
Such activating groups donate those unshared electrons to
the pi system.

When the electrophile attacks the ortho and para positions of

aniline, the nitrogen atom can donate electron density to
the pi system (forming an iminium ion), giving four resonance
structures (as opposed to three in the basic reaction). This
substantially enhances the stability of the cationic intermediate.

Compare this with the case when the electrophile attacks

the meta position. In that case, the nitrogen atom cannot
donate electron density to the pi system, giving only three
resonance contributors. For this reason, the metasubstituted product is produced in much smaller proportion
to the ortho and para products.

Other substituents, such as

the alkyl and aryl substituents, may also donate
electron density to the pi system; however, since they
lack an available unshared pair of electrons, their ability
to do this is rather limited. Thus, they only weakly
activate the ring and do not strongly disfavor
the meta position.
Halogens are ortho/para directors, since they possess
an unshared pair of electrons just as nitrogen does.
However, the stability this provides is offset by the fact
that halogens are substantially
more electronegativethan carbon, and thus draw
electron density away from the pi system. This
destabilizes the cationic intermediate, and EAS occurs
less readily. Halogens are therefore deactivating
groups.
Directed ortho metalation is a special type of EAS with
special ortho directors.

Meta directors[edit]

Non-halogen groups with atoms that are more

electronegative than carbon, such as a carboxylic acid
group (CO2H) draw substantial electron density from
the pi system. These groups are strongly deactivating
groups. Additionally, since the substituted carbon is
already electron-poor, the resonance contributor with a
positive charge on this carbon (produced
by ortho/para attack) is less stable than the others.
Therefore, these electron-withdrawing groups
are meta directing.

Reaction mechanism[edit]
In the first step of the reaction mechanism for this
reaction, the electron-rich aromatic ring, which in the
simplest case is benzene, attacks the electrophile A.
This step leads to the formation of a positively charged
cyclohexadienyl cation, also known as an arenium ion.
This carbocation is unstable, owing both to the positive
charge on the molecule and to the temporary loss
of aromaticity. However, the cyclohexadienyl cation is
partially stabilized by resonance, which allows the
positive charge to be distributed over three carbon
atoms.

In the second stage of the reaction, a Lewis

base B donates electrons to the hydrogen atom at
the point of electrophilic attack, and the electrons
shared by the hydrogen return to the pi system,
restoring aromaticity.
An electrophilic substitution reaction on benzene
does not always result in monosubstitution. While
electrophilic substituents usually withdraw electrons
from the aromatic ring and thus deactivate it
against further reaction, a sufficiently strong
electrophile can perform a second or even a third
substitution. This is especially the case with the use
of catalysts.

Ipso substitution[edit]
The Ipso substitution is a special case of
electrophilic aromatic substitution where the leaving
group is not hydrogen.
A classic example is the reaction of salicylic
acid with a mixture of nitric and sulfuric acid to
form picric acid. The nitration of the 2 position
involves the loss of CO2 as the leaving group.

Desulfonation in which a sulfonyl group is

substituted by a proton is a common example. See
also Hayashi rearrangement.
In aromatics substituted by silicon, the silicon
reacts by ipso substitution.

Five membered heterocyclic

compounds[edit]
Furan, thiophene, pyrrole and their derivatives are
all highly activated compared to benzene. These
compounds all contain an atom with an unshared
pair of electrons (oxygen, sulphur, or nitrogen) as a
member of the aromatic ring, which substantially
increases the stability of the cationic intermediate.
Examples of electrophilic substitutions to pyrrole
are the PictetSpengler reaction and the Bischler
Napieralski reaction.

Asymmetric electrophilic
aromatic substitution[edit]
Electrophilic aromatic substitutions
with prochiral carbon electrophiles have been
adapted for asymmetric synthesis by switching
to chiral Lewis acid catalysts especially in Friedel
Crafts type reactions. An early example concerns
the addition of chloral to phenols catalyzed
by aluminium chloride modified with ()-menthol.
[2]

A glyoxylate compound has been added to N,N-

dimethylaniline with a chiral bisoxazoline ligand

copper(II) triflate catalyst system also in a Friedel
Crafts hydroxyalkylation:[3]

In another alkylation N-methylpyrrole reacts

with crotonaldehyde catalyzed by trifluoroacetic
acid modified with a chiral imidazolidinone:[4]

Indole reacts with an enamide catalyzed by

a chiral BINOL derived phosphoric acid:[5]

In all these reactions the chiral catalyst

load is between 10 to 20% and a new
chiral carbon center is formed with 80
90% ee.

Other reactions[edit]

Other reactions that follow an

electrophilic aromatic substitution
pattern are a group of aromatic
formylation reactions including
the VilsmeierHaack reaction,
the Gattermann Koch reaction and
the ReimerTiemann reaction.

Other electrophiles are

aromatic diazonium
salts in diazonium
couplings, carbon dioxide in
the KolbeSchmitt reaction and
activated carbonyl groups in
the Pechmann condensation.

In the multistep Lehmstedt

Tanasescu reaction, one of the
electrophiles is a N-nitroso
intermediate.

In the TscherniacEinhorn
reaction (named after Joseph
Tscherniac and Alfred Einhorn) the
electrophile is a N-methanol
derivative of an amide [6][7]