Aromatic Compounds

Nature presents us with a wide array of naturally occurring

substances. Some structural subtypes occur with high frequency
among the millions of know naturally occurring substances.

One frequently occurring structural subtype is a six-membered ring

with three double bonds. This subtype has been extensively
explored over the past 150 years, and found to possess unusual
stability. It is believed that this stability is due to a particular
property of possessing a closed circle of pi orbitals possessing six
pi electrons.

As we shall see, these cyclic, unsaturated systems seem to

possess some unusual chemical stability. More examples of
such stabilized cyclic systems are shown below.

Pyrrole

Furan

Aromatic Systems are Characterized

by Their Chemical Stability

Note the chemical stability of the

aromatic systems to the reaction
conditions in the following slides

Note aromatic systems stability toward

hydrogenation

Note aromatic systems stability toward strong

reducing agent LiAlH4

Note the (two) aromatic systems stability

toward Br2

Note the aryl iodides stability toward SN2

substitution
(SN2 substitution occurs at the sp3 hybridized
carbon)

Note the aryl iodides stability toward the strong

base (potassium tert-butoxide) used to effect
elimination

It is important to understand that, in heterocyclic ring

systems, the lone pair of electrons on the heteroatom may be
required as part of the aromatic sextet, in which case, the
heteroatom is not basic nor nucleophilic.

In the case of pyrrole, the nitrogen is not basic nor

nucleophilic, since the nitrogen lone pair is part of the
aromatic sextet.

Or, it may be that the lone pair of the heteroatom is not required for
the aromatic sextet, in which case the heteroatom may be basic and
nucleophilic.

In the case of pyridine, above, the lone pair is not a part of

the aromatic sextet, and is basic and nucleophilic.

Another important system is imidazole, shown below, the

heterocyclic system of the amino acid histidine.

One of the nitrogen atoms is basic, while the other is not.

Reactions of Aromatic Systems:

Electrophilic Aromatic
Substitution

Notice that cyclohexene (right, green box) is quite reactive

toward strong acids, bromine, and strong oxidizing agents.

Under these same conditions, benzene, blue box to right, does not
react.
However, benzene can be made to react under forcing conditions
shown at left. But the products (from benzene reaction) are different
from what one might expect, using the reactivity of cyclohexene as a
predictive model.

Mechanism of Electrophilic Aromatic Substitution by attack of

electrophile (E+) on the benzene ring

The FriedelCrafts Reaction

Sometimes, substituents on the aromatic ring may direct

the incoming electrophile to attack specific carbon atoms
of the aromatic ring, as shown in the following examples.

Notice that substituents that stabilize an adjacent carbocation (either

by resonance or by electronegativity) activate the aromatic ring
toward electrophilic substitution.

Notice that electron-withdrawing groups deactivate the ring

toward electrophilic substitution (reduce its reactivity toward
electrophiles).

Nucleophilic Substitution at the

Benzene Ring

Recall that nucleophilic substitution at sp3 hybridized carbon

usually occurs much more rapidly (loss of the benzylic chloride)
than substitution an (sp2-hybridized) aryl halide itself, as shown in
the example below.

But, in certain very specific conditions, substitution of

an aryl halide can occur.
The two most common mechanisms for substitution of
an aryl halide are:
The Benzyne Mechanism (under strongly basic
conditions) and
The Addition-Elimination Mechanism (when the arylhalide has electron-withdrawing groups oriented orthoand para- to the halide.

Treatment of Aryl Halides with Extremely strong

bases (amide anions, NaNH2, pKa of ammonia =
38) can cause substitution reactions

(note that the above table shows the conjugate acids only)

But the mechanism involves a two-step process of

elimination-addition.

Treatment of aryl halides having strongly

electron-withdrawing substituents (at the 2and the 4-position) can also cause substitution
reactions
But

The mechanism involves additionelimination.

Reactions of Side
Chains and Attached
Functionality on
Aromatic Compounds

Recall that aryl nitro compounds are readily available by

electrophilic substitution, using nitric acid.

These product aryl-nitro compounds are synthetically useful, since

the nitro group can be easily reduced to an amino group.

Likewise aryl amino compounds are synthetically valuable, since the

NH2 group can be transformed into an aryl diazonium salt, which is a
useful intermediate for substitution at an aromatic carbon.

Treatment of amines with nitrous acid (HONO) generates

diazonium salts

Aryl Diazonium salts are useful in

substitution reactions

The Sandmeyer
Reaction
Swiss chemist (1854-1922) after whom
reaction is named

Benzylic Positions Can be Selectively Oxidized

(all the way to the carboxylic acid) by
Potassium Permanganate

The benzylic position can be readily halogenated via a free-radical

process, as shown below.

The Clemmensen Reduction

Hydrogenolysis of Benzyl
Esters
and Benzyl Ethers

It is possible to reduce a benzene ring to a 1,4cyclohexadiene, using a reduction protocol known as the
Birch Reduction

The mechanism of the Birch Reduction involves successive one

electron transfers as shown below. The alkali metal serves as a
source of electrons. The solvent is usually liquid ammonia.