Compounds containing aromatic groups are widespread in nature, and for this reason chemists who aim to synthesize naturally occurring compounds in the laboratory often need to introduce substituents to aromatic rings.   In the organic synthesis laboratory, electrophilic aromatic substitutions which result in the formation of new carbon-carbon bonds are called ‘Friedel-Crafts’  alkylations and acylations, named for Charles Friedel of France and James Crafts of the United States, who together developed the procedures in 1877.   The Friedel-Crafts reactions are an important part of a synthetic chemist’s toolbox to this day.

Friedel Crafts reactions, like their biochemical counterparts, require reactive electrophiles with significant carbocation character.  One of the most common ways to alkylate an aromatic ring is to use an alkyl chloride electrophile that is activated by the addition of aluminum or iron trichloride.  The metal chloride serves as a Lewis acid, accepting electron density from the alkyl chloride.  This has the effect of magnifying the carbon-chlorine dipole, making the carbon end more electropositive – and thus more electrophilic – even to the point where the bond breaks and an ion-pair is formed.

An alternative method for carrying out a Friedel-Crafts alkylation is to start with an alkene, which is protonated by a strong acid such as H₂SO₄ to generate a carbocation.

Limitations of Friedel-Crafts Alkylation

1. Carbocation Rearrangement – Only certain alkylbenzenes can be made due to the tendency of cations to rearrange.
2. Compound Limitations – Friedel-Crafts fails when used with compounds such as nitrobenzene and other strongly deactivated aromatics.
3. Polyalkylation – Products of Friedel-Crafts alkylations are even more reactive than starting material. Alkyl groups produced in Friedel-Crafts Alkylation are electron-donating substituents meaning that the products are more susceptible to electrophilic attack than what we began with. For synthetic purposes, this is a big disappointment, because the reaction is hard to stop with just a single alkylation.

To remedy some of these limitations (1 and 3), Friedel-Crafts acylation is often used instead, followed by reduction of the ketone product.

The Friedel-Crafts acylation reaction is essentially an acyl substitution  reaction with an aromatic π bond serving as the nucleophile.  As in many other laboratory acyl transfer reactions, acyl chlorides are used as activated carboxylic acids.  Because of the low reactivity of the aromatic π bond nucleophile, however, the acyl chloride electrophile in a Friedel-Crafts acylation must be further activated with a Lewis acid reagent such as aluminum chloride, which again serves to polarize the carbon-chlorine bond and increase the electrophilicity of the acyl carbon.  The activated electrophile in Friedel-Crafts acylations is often depicted as an ionic species.

The resultant aryl ketone can be reduced to CH₃CH₂Ph (ethylbenzene) using H₂/Pd on C, or Zn(Hg) and HCl.