Core Concepts
In this tutorial on the Friedel-Crafts alkylation and acylation reactions, you will learn about the purposes of both reactions. Furthermore, you will learn about the way resonance stabilization affects the reaction mechanism. We will also discuss the similarities and differences between Friedel-Crafts acylation and Friedel-Crafts alkylation.
Topics Covered in Other Articles
- Carbonyl Functional Group
- Electrophiles
- Lewis Dot Structures
- Carbocation Stability
- Resonance Structures
- Leaving Groups
History of the Friedel-Crafts Reactions
In 1877, Charles Friedel and James M. Crafts published “Sur une Nouvelle Méthode Générale de Synthèse d’Hydrocarbures, d’Acétones, etc” or “On a New Method to Synthesis Hydrocarbons, Acetones, etc.,” which included the two Friedel-Crafts reactions – the alkylation and acylation reactions. Both turned out to be examples of electrophilic aromatic substitution.
Friedel-Crafts Acylation
The purpose of the Friedel-Crafts acylation reaction is to synthesize a monoacylated aromatic ring. This reaction occurs when a carboxylic acid chloride (R-COCl) reacts with an aromatic ring in the presence of a Lewis acid, like aluminum chloride (AlCl3) or iron chloride (FeCl3). This reaction can only occur when the aromatic ring is not substituted with electron-withdrawing groups (also called meta-directing groups).
To understand the mechanism of the Friedel-Crafts acylation reaction, let’s use benzene and acetyl chloride as example substrates. In the presence of an aluminum chloride catalyst, these compounds react to form acetophenone.
Friedel-Crafts Acylation Mechanism
The mechanism for this reaction, also, consists of two steps: the formation of the acyl cation, followed by acylation.
In the first step, chlorine forms a Lewis acid-base complex with aluminum chloride, which then acts as a leaving group. This forms a resonance-stabilized acyl cation.
During acylation, the acyl cation reacts with benzene. A benzene π-bond acts as a nucleophile, forming a new C-C bond with the electrophilic acyl carbon. To re-form the aromatic double bond, AlCl4– abstracts the hydrogen (a beta-hydride elimination). This regenerates the aluminum chloride catalyst and generates HCl.
Friedel-Crafts Alkylation
The purpose of the Friedel-Crafts alkylation reaction is to synthesize aromatic alkanes. This reaction occurs when an alkyl chloride reacts with an aromatic ring in the presence of a Lewis acid, like aluminum chloride (AlCl3) or iron chloride (FeCl3). Due to the formation of carbocations, rearrangements occur to ensure the formation of a more stable carbocation.
To understand the mechanism of the Friedel-Craft alkylation reaction, let’s use benzene and n-propyl chloride as example substrates. In the presence of an aluminum chloride catalyst, these compounds react to form cumene.
Friedel-Crafts Alkylation Mechanism
The mechanism for this reaction consists of two steps: the formation of the more stable carbocation, then alkylation.
In the first step, chlorine forms a Lewis acid-base complex with aluminum chloride, which then acts as a leaving group. This forms a carbocation that undergoes a hydride shift to form a more stable carbocation.
During the process of alkylation, the carbocation reacts with benzene. A benzene π-bond acts as a nucleophile, forming a new C-C bond with the electrophilic carbocation. To re-form the aromatic double bond, AlCl4– abstracts the hydrogen (a beta-hydride elimination). This regenerates the aluminum chloride catalyst and generates HCl.
Due to the rearrangement, Friedel-Craft alkylation reactions have major and minor products. The major organic product is the result of the rearrangement, forming from the more stable carbocation. Rearrangement does not occur in the formation of the minor product.
Comparison of Friedel-Crafts Acylation and Alkylation Reactions
Both types of Friedel-Crafts reaction fail when a strong electron-withdrawing group is present. This is because the aromatic π-bonds require a certain degree of electron density to engage in a nucleophilic attack on the acyl/alkyl cation, which they do not have in the presence of a withdrawing group. Therefore, a ring can only be acylated once, as acyl groups are electron-withdrawing. This differs from the alkylation reaction, which often polyalkyates the aromatic ring. Because alkyl groups are electron-donating, products of Friedel-Crafts alkylation reactions are generally better substrates than the starting material.
The acylation reaction does not result in a carbocation rearrangement because the acyl cation in the Friedel-Crafts acylation reaction is resonance stabilized. Conversely, the alkyl cation in Friedel-Crafts alkylations is not resonance-stabilized and will readily rearrange.
Determine the Major Product
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