Aromatic Compounds

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Aromatic Compounds
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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.
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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.
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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.
Furan
Pyrrole
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Aromatic Systems are Characterized by Their
Chemical Stability

• Note the chemical stability of the aromatic
  systems to the reaction conditions in the
  following slides

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Note aromatic systems stability toward
hydrogenation
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Note aromatic systems stability toward strong
reducing agent LiAlH4
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Note the (two) aromatic systems stability toward
Br2
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Note the aryl iodides stability toward SN2
substitution (SN2 substitution occurs at the sp3
hybridized carbon)
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Note the aryl iodides stability toward the
strong base (potassium tert-butoxide) used to
effect elimination
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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.
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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.
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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.
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Reactions of Aromatic Systems Electrophilic
Aromatic Substitution
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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.
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Mechanism of Electrophilic Aromatic Substitution
by attack of electrophile (E) on the benzene ring
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The Friedel-Crafts Reaction
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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.
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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).
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Nucleophilic Substitution at the Benzene Ring
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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.
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• 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.

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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)
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But the mechanism involves a two-step process of
elimination-addition.
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Treatment of aryl halides having strongly
electron-withdrawing substituents (at the 2- and
the 4-position) can also cause substitution
reactions But
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The mechanism involves addition-elimination.
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Reactions of Side Chains and Attached
Functionality on Aromatic Compounds
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Recall that aryl nitro compounds are readily
available by electrophilic substitution, using
nitric acid.
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These product aryl-nitro compounds are
synthetically useful, since the nitro group can
be easily reduced to an amino group.
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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.
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Treatment of amines with nitrous acid (HONO)
generates diazonium salts
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Aryl Diazonium salts are useful in substitution
reactions
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The Sandmeyer Reaction
Swiss chemist (1854-1922) after whom reaction is
named
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Benzylic Positions Can be Selectively Oxidized
(all the way to the carboxylic acid) by Potassium
Permanganate
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The benzylic position can be readily halogenated
via a free-radical process, as shown below.
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The Clemmensen Reduction
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Hydrogenolysis of Benzyl Esters and Benzyl Ethers
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It is possible to reduce a benzene ring to a
1,4-cyclohexadiene, using a reduction protocol
known as the Birch Reduction
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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.
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