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 FeBr 3 , 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. AlCl 3 is most often used as catalyst, but FeCl 3 will also work.

Nitration of Benzene • • Sulfuric acid acts as a catalyst, allowing the reaction to be faster and at lower temperatures.

HNO 3 and H 2 SO 4 react together to form the electrophile of the reaction: nitronium ion (NO 2 + ).

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 AlCl 3 .

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 BF 3 carbocation.

to form the

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 (SO 3 ) is the electrophile in the reaction.

A 7% mixture of SO 3 and H “fuming sulfuric acid.” 2 SO 4 is commonly referred to as The —SO 3 H 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, para directors.

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 —OCH 3 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 KMnO 4 or heating in Na 2 Cr 2 O 7 /H 2 SO 4 .

The benzylic carbon will be oxidized to the carboxylic acid.

Side-Chain Halogenation • • • The benzylic position is the most reactive.

Br 2 reacts only at the benzylic position.

Cl 2 is not as selective as bromination, so results in mixtures.