Friedel-Crafts Acylation of Benzene

Reaction type: Electrophilic Aromatic Substitution

Summary.

• Overall transformation :  Ar-H to Ar-COR (a ketone)
• Named after Friedel and Crafts who discovered the reaction.
• Reagent : normally the acyl halide (e.g. usually RCOCl) with aluminum trichloride, AlCl₃, a Lewis acid catalyst
• The AlCl₃ enhances the electrophilicity of the acyl halide by complexing with the halide
• Electrophilic species : the acyl cation or acylium ion (i.e. RCO ⁺ ) formed by the "removal" of the halide by the Lewis acid catalyst
• The acylium ion is stabilized by resonance as shown below. This extra stability prevents the problems associated with the rearrangement of simple carbocations:

• The reduction of acylation products can be used to give the equivalent of alkylation but avoids the problems of rearrangement  (more details)
• Friedel-Crafts reactions are limited to arenes more reactive than mono-halobenzenes
• Other sources of acylium can also be used such as acid anhydrides with AlCl₃

MECHANISM FOR THE FRIEDEL-CRAFTS ACYLATION OF BENZENE
Step 1: The acyl halide reacts with the Lewis acid to form a more electrophilic C, an acylium ion
Step 2: The p electrons of the aromatic C=C act as a nucleophile, attacking the electrophilic C+. This step destroys the aromaticity giving the cyclohexadienyl cation intermediate.
Step 3: Removal of the proton from the sp3 C bearing the acyl- group reforms the C=C and the aromatic system, generating HCl and regenerating the active catalyst.

Limitations of Friedel-Crafts reactions

There are two types of Friedel-Crafts reactions, alkylation and acylation:

Reaction type: Electrophilic Aromatic Substitutions

However there are certain limitations:

• The halide must be either  an alkyl halide or an acyl halide. Vinyl or aryl halides do not react.
• Alkylation reactions are prone to carbocation rearrangements.
• Deactivated benzenes are not reactive to Friedel-Crafts conditions, the benzene needs to be as or more reactive than a mono-halobenzene (see substituent effects)
• Multiple alkylation can be a problem since the product is more reactive than the starting material.
• The Lewis acid catalyst AlCl₃ often complexes to aryl amines making them very unreactive.

Why aren't acylation reactions as prone to over acylation ? 

Alkylation = Acylation then reduction

Clemmensen Reduction (acidic conditions)

• Zn(Hg) in HCl reduced the C=O into -CH₂-

• NH₂NH₂ / KOH / ethylene glycol (a high boiling solvent)  reduces the C=O into -CH₂-

• These reduction methods do not reduce C=C or CºC nor -CO₂H
• The combination of either one of these methods after a Friedel-Crafts acylation gives the equivalent of alkylation but without the problems and complications associated with carbocations rearrangement.
• The choice of method should be made based on the tolerance of other functional groups to the acidic or basic reaction conditions.

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