Bromination of Benzene
Mechanism for the Bromination of
Benzene: Preliminary Step
• Before the electrophilic aromatic substitution can take
place, the electrophile must be activated.
• A strong Lewis acid catalyst, such as FeBr3, should be used.
Mechanism for the Bromination of
Benzene: Steps 1 and 2
Step 1: Electrophilic attack and formation of the sigma complex.
Step 2: Loss of a proton to give the products.
Chlorination of Benzene
• Chlorination is similar to bromination. AlCl3
is most often used as catalyst, but FeCl3 will
also work.
Nitration of Benzene
• Sulfuric acid acts as a catalyst, allowing the reaction to be
faster and at lower temperatures.
• HNO3 and H2SO4 react together to form the electrophile of
the reaction: nitronium ion (NO2+).
Mechanism for the Nitration of Benzene:
Preliminary Step
• Formation of the nitronium ion is the
preliminary step of the reaction.
Mechanism for the EAS Nitration of
Benzene
Step 1: Formation of the sigma complex.
Step 2: Loss of a proton gives nitrobenzene.
Friedel–Crafts Alkylation
• Synthesis of alkyl benzenes from alkyl halides and
a Lewis acid, usually AlCl3.
• Reactions of alkyl halide with Lewis acid produces
a carbocation, which is the electrophile.
Mechanism of the Friedel–Crafts Reaction
Step 1
Step 2
Step 3
Rearrangements
Protonation of Alkenes
• An alkene can be protonated by HF.
• This weak acid is preferred because the fluoride
ion is a weak nucleophile and will not attack the
carbocation.
Alcohols and Lewis Acids
• Alcohols can be treated with BF3 to form the
carbocation.
Limitations of Friedel–Crafts
• Reaction fails if benzene has a substituent that
is more deactivating than halogens.
• Rearrangements are possible.
• The alkylbenzene product is more reactive
than benzene, so polyalkylation occurs.
Friedel–Crafts Acylation
• Acyl chloride is used in place of alkyl chloride.
• The product is a phenyl ketone that is less
reactive than benzene.
Mechanism of Acylation
Step 1: Formation of the acylium ion.
Step 2: Electrophilic attack to form the sigma complex.
Mechanism of Acylation (Continued)
Step 3: Loss of a proton to form the product.
The Gattermann-Koch Reaction
Friedel–Crafts acylations are generally
free from rearrangements and multiple
substitution. They do not go on strongly
deactivated rings, however.
Sulfonation of Benzene
• Sulfur trioxide (SO3) is the electrophile in the reaction.
• A 7% mixture of SO3 and H2SO4 is commonly referred to as
“fuming sulfuric acid.”
• The —SO3H group is called a sulfonic acid.
Sulfur Trioxide
• Sulfur trioxide is a strong electrophile, with
three sulfonyl bonds drawing electron
density away from the sulfur atom.
Desulfonation Reaction
• Sulfonation is reversible.
• The sulfonic acid group may be removed from an
aromatic ring by heating in dilute sulfuric acid.
Nitration of Toluene
• Toluene reacts 25 times faster than benzene.
• The methyl group is an activator.
• The product mix contains mostly ortho and para
substituted molecules.
Ortho and Para Substitution
• Ortho and para attacks are preferred because their
resonance structures include one tertiary carbocation.
Energy Diagram
Meta Substitution
• When substitution occurs at the meta position, the
positive charge is not delocalized onto the tertiary carbon,
and the methyl group has a smaller effect on the stability
of the sigma complex.
Alkyl Group Stabilization
• Alkyl groups are activating substituents and ortho, paradirectors.
• This effect is called the inductive effect because alkyl
groups can donate electron density to the ring through
the sigma bond, making them more active.
Anisole
• Anisole undergoes nitration about 10,000 times faster
than benzene and about 400 times faster than toluene.
• This result seems curious because oxygen is a strongly
electronegative group, yet it donates electron density to
stabilize the transition state and the sigma complex.
Substituents with Nonbonding Electrons
Resonance stabilization is provided by a pi bond between
the —OCH3 substituent and the ring.
Meta Attack on Anisole
• Resonance forms show that the methoxy group
cannot stabilize the sigma complex in the meta
substitution.
Bromination of Anisole
• A methoxy group is so strongly activating that
anisole is quickly tribrominated without a catalyst.
Summary of Activators
Activators and Deactivators
• If the substituent on the ring is electron donating, the
ortho and para positions will be activated.
• If the group is electron withdrawing, the ortho and para
positions will be deactivated.
Nitration of Nitrobenzene
• Electrophilic substitution reactions for nitrobenzene are
100,000 times slower than for benzene.
• The product mix contains mostly the meta isomer, and only
small amounts of the ortho and para isomers.
Ortho Substitution of Nitrobenzene
• The nitro group is a strongly deactivating group when
considering its resonance forms. The nitrogen always has a
formal positive charge.
• Ortho or para addition will create an especially unstable
intermediate.
Meta Substitution on Nitrobenzene
• Meta substitution will not put the positive charge
on the same carbon that bears the nitro group.
Energy Diagram
Deactivators and Meta-Directors
• Most electron-withdrawing groups are
deactivators and meta-directors.
• The atom attached to the aromatic ring has a
positive or partial positive charge.
• Electron density is withdrawn inductively along
the sigma bond, so the ring has less electron
density than benzene, and thus it will be slower
to react.
Other Deactivators
Halogens
• Halogens are deactivators since they react slower
than benzene.
• Halogens are ortho, para-directors because the
halogen can stabilize the sigma complex.
Halogens Are Deactivators
• Inductive effect: Halogens are deactivating
because they are electronegative and can
withdraw electron density from the ring along the
sigma bond.
Halogens Are Ortho, Para-Directors
• Resonance effect: The lone pairs on the halogen
can be used to stabilize the sigma complex by
resonance.
Energy Diagram
Summary of Directing Effects
Reduction of the Nitro Group
• Treatment with zinc, tin, or iron in dilute acid will
reduce the nitro to an amino group.
• This is the best method for adding an amino
group to the ring.
Clemmensen Reduction
• The Clemmensen reduction is a way to convert
acylbenzenes to alkylbenzenes by treatment with
aqueous HCl and amalgamated zinc.
Wolff–Kishner Reduction
• Forms hydrazone, then heat with strong base like KOH or
potassium tert-butoxide
• Use a high-boiling solvent: ethylene glycol, diethylene
glycol, or DMSO.
• A molecule of nitrogen is lost in the last steps of the
reaction.
Side-Chain Oxidation
• Alkylbenzenes are oxidized to benzoic acid by heating in
basic KMnO4 or heating in Na2Cr2O7/H2SO4.
• The benzylic carbon will be oxidized to the carboxylic acid.
Side-Chain Halogenation
• The benzylic position is the most reactive.
• Br2 reacts only at the benzylic position.
• Cl2 is not as selective as bromination, so results in
mixtures.