Friedel-Crafts acylation

Friedel-Crafts Acylation

Friedel-Crafts acylation is a fundamental reaction in organic chemistry that involves the introduction of an acyl group into an aromatic ring. This reaction is named after the chemists Charles Friedel and James Crafts, who first reported it in 1877. It is a key method for the synthesis of aromatic ketones and is widely used in both academic and industrial settings.

Mechanism

The Friedel-Crafts acylation reaction proceeds via an electrophilic aromatic substitution mechanism. The general process involves the following steps:

1. **Formation of the Acyl Cation:** An acyl chloride (RCOCl) or an acid anhydride is treated with a Lewis acid catalyst, typically aluminum chloride (AlCl₃). The Lewis acid coordinates with the acyl chloride, generating a highly reactive acyl cation (RCO⁺).
2. **Electrophilic Attack:** The acyl cation acts as an electrophile and attacks the π-electron-rich aromatic ring, forming a sigma complex (also known as an arenium ion).
3. **Deprotonation:** The sigma complex is deprotonated, restoring the aromaticity of the ring and yielding the acylated aromatic compound.

The overall reaction can be represented as:

C₆H₆ + RCOCl → C₆H₅COR + HCl

Limitations and Considerations

Friedel-Crafts acylation has several limitations and considerations:

• **Reactivity of Substrates:** The reaction is generally limited to aromatic compounds that are not strongly deactivated. Electron-withdrawing groups on the aromatic ring can significantly reduce the reactivity.
• **Catalyst Sensitivity:** The reaction requires a strong Lewis acid catalyst, which can be sensitive to moisture and may lead to side reactions.
• **Polyacylation:** Unlike Friedel-Crafts alkylation, polyacylation is less of a concern because the acyl group is deactivating, reducing the likelihood of further acylation.

Applications

Friedel-Crafts acylation is used in the synthesis of a variety of aromatic ketones, which are important intermediates in the production of dyes, pharmaceuticals, and fragrances. For example, the synthesis of acetophenone from benzene and acetyl chloride is a classic application of this reaction.

Comparison with Friedel-Crafts Alkylation

While both Friedel-Crafts acylation and Friedel-Crafts alkylation involve the introduction of substituents onto an aromatic ring, there are key differences:

• **Reactivity:** Acylation is less prone to rearrangement and polyacylation compared to alkylation.
• **Products:** Acylation results in the formation of ketones, whereas alkylation results in the formation of alkylbenzenes.

See Also

• Electrophilic aromatic substitution
• Lewis acid
• Aromaticity

References

• Smith, M. B.; March, J. (2007). March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. 6th ed. Wiley.
• Carey, F. A.; Sundberg, R. J. (2007). Advanced Organic Chemistry. 5th ed. Springer.