When electron-donating substituents are added, multiple substitution is always a threat. The principal reaction where multiple substitution is a genuine problem is the Friedel–Crafts alkyl ation reaction. Here’s an example: preparation of diphenylmethane from benzene and benzyl chloride is a useful reaction but the product has two benzene rings, each more reactive than benzene itself. A 50% yield is the best we can do and that requires a large excess of benzene to ensure that it competes successfully for the reagent with the reactive, electron-rich product.

Multiple substitution is just one of the potential pitfalls of Friedel–Crafts alkylations. The other is important to be aware of too: Friedel–Crafts alkylations work well only with stable cations. This is what happens when we try a Friedel–Crafts reaction with n-propyl chloride.

Recall from Chapter 15 that primary halides don’t form cations easily, so the Friedel–Crafts reaction with n-propyl chloride has to go via an SN2 mechanism.

So where does the major product of the reaction come from? The three carbons are arranged not as an n-propyl group but as an iso-propyl group: a rearrangement has occurred. This is the mechanism:

The green hydrogen migrates to allow a secondary rather than a primary alkyl cation to be formed, and iso-propylbenzene results. This leaves us with a problem.

مواضيع ذات صلة

Reaction conditions

Conjugated alkenes can be electrophilic

Alkenes conjugated with carbonyl groups

Two or more substituents may cooperate or compete

Phenols react rapidly with bromine

Alkyl and acyl substituents can be added to a benzene ring by the Friedel–Crafts reaction

Sulfonation of benzene

Nitration of benzene

Benzene and its reactions with electrophiles

enols and phenols

Reactions of silyl enol ethers with halogen and sulfur electrophiles

Reactions of enol ethers Hydrolysis of enol ethers