Reactions and Mechanisms: Friedel-Crafts Alkylation

Reaction

Friedel-Crafts alkylation is a reaction in which a benzene ring is modified with an alkyl substituent. Here’s a generic example:

Friedel-Crafts alkylation is a type of electrophilic aromatic substitution: a reaction in which an aromatic molecule (often benzene) reacts with an electrophile, where the electrophile replaces another substituent (typically a hydrogen atom) on the aromatic ring.

In the Friedel-Crafts alkylation reaction, the benzene ring acts as a nucleophile, and an alkyl halide acts as an electrophile. However, benzene is not a very good nucleophile, and cannot react directly with the alkyl halide. To overcome this, a strong Lewis acid is used to help catalyse the reaction. A Lewis acid is a molecule with an empty orbital that can accept an electron pair from a Lewis base; in this reaction, the halogen atom in the alkyl halide acts as a Lewis base. The Lewis acid helps to “pull” the halogen atom off of the alkyl halide, forming a carbocation, which is a much better electrophile. Common Lewis acids for this reaction are aluminum chloride (AlCl₃) and ferric chloride (FeCl₃).

Mechanism

Let’s consider the mechanism of the following Friedel-Crafts alkylation reaction, using benzene, the alkyl halide 2-chloro-2-methylpropane, and the Lewis acid catalyst ferric chloride (FeCl₃):

In the first step of the Friedel-Crafts alkylation mechanism, the halogen atom of the alkyl halide donates a lone pair to an empty orbital on the iron atom of FeCl₃:

Now, this makes it easier to break the carbon-chlorine bond. As the chlorine atom is now positively charged (which is not ideal for an electronegative atom like chlorine), it wants to regain electrons. Therefore, the carbon-chlorine bond cleaves, with the electrons from the bond going onto the chlorine. As the carbon has lost both electrons from this bond, it is now positively charged. For this particular alkyl halide, this generates a tertiary carbocation, which is reasonably stable.

The stability of carbocations generally improves with the number of alkyl substituents. For this reason, you will typically see Friedel-Crafts alkylation reactions with more highly substituted alkyl halides which generate stable carbocations. Keep in mind that, however, that unstable carbocations can undergo rearrangement reactions to generate more stable carbocations.

The carbocation we’ve generated is a much better electrophile than the original alkyl halide. Now, the π electrons of the benzene ring (that is, the electrons drawn as double bonds) nucleophilically attack the carbocation:

The use of the benzene π-electrons to make the carbon-carbon bond disrupts the aromaticity of the benzene ring. As aromatic rings are quite energetically stable, there is a strong drive for the benzene ring to regain aromaticity. To do so, the benzene ring must lose the hydrogen atom on the carbon that is bonded to the new alkyl substituent. This can be accomplished by a base; in this reaction, we can use one of the chloride ions which is coordinated to the iron in ferric chloride:

This last step forms the alkylated benzene product and regenerates the ferric chloride catalyst. The mechanism of this final step is similar to the unimolecular elimination (E1) reactions seen for alkyl halides, in which a base removes a proton on a carbon adjacent to a carbocation, forming a double bond.

Related Topics

One of the major disadvantages of the Friedel-Crafts alkylation reaction is that multiple alkylation reactions can occur. The new alkyl group on the ring actually makes the benzene more reactive, promoting further reactions. One way this can be overcome is by  using the Friedel-Crafts acylation reaction. In this reaction, the benzene ring is acylated instead of alkylated, which deactivates the ring for further reactions. Then, in a subsequent reaction, the ketone can be reduced, resulting in an alkyl substituted benzene.

As mentioned above, Friedel-Crafts alkylation is an electrophilic aromatic substitution reaction. As such, the mechanism for this reaction is very similar to several other reactions. It’s worth focusing on the similarities between these mechanisms. This will help minimize the amount of memorization needed, and will also allow you to predict the mechanisms of reactions you haven’t seen before.

Here are the general reactions of three types of electrophilic aromatic substitution reactions: Friedel-Crafts alkylation, Friedel-Crafts acylation, and electrophilic aromatic halogenation.

In all three reactions, a Lewis acid (such as AlCl₃and FeBr₃) helps to activate the electrophile (an alkyl halide, an acyl chloride, or a diatomic halogen molecule) for nucleophilic attack by the aromatic ring.

Summary

Friedel-Crafts alkylation is an electrophilic aromatic substitution reaction, in which an alkyl substituent is placed on an aromatic ring (benzene). These reactions are catalysed by Lewis acids (e.g., AlCl₃, FeCl₃), which help to generate carbocations from alkyl halides. The benzene ring then nucleophilically attacks the carbocation, followed by re-aromatization. This reaction is suitable for alkyl halides that generate stable carbocations; note that carbocation rearrangement reactions can occur. Multiple alkylation reactions can occur, as alkylation activates the benzene ring.