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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 system’s stability toward hydrogenation
Note aromatic systems’ stability toward strong reducing agent
LiAlH4
Note the (two) aromatic systems’ stability toward Br2
Note the aryl iodide’s stability toward SN2 substitution
(SN2 substitution occurs at the sp3 hybridized carbon)
Note the aryl iodide’s 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 Friedel-Crafts
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 aryl-halide has
electron-withdrawing groups oriented ortho- and 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 electronwithdrawing substituents (at the 2- and the 4-position) can
also cause substitution reactions
But…
The mechanism involves addition-elimination.
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 1,4-cyclohexadiene, 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.