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EAS-Acylation

Acylation (Friedel-Crafts Acylation)

Friedel-Crafts acylation is another crucial Electrophilic Aromatic Substitution (EAS) reaction, which involves the introduction of an acyl group (corresponding to a carbonyl-containing group, RCO−) onto an aromatic ring. This reaction provides a method to add carbon-carbon bonds to aromatic systems, enabling the synthesis of ketones, which are valuable in various chemical industries, including pharmaceuticals and materials science. Friedel-Crafts acylation uses an acyl halide (RCOCl) and a Lewis acid catalyst, such as aluminum chloride (AlCl3), to facilitate the reaction.

Friedel-Crafts Acylation of Benzene: A Step-by-Step Mechanism

  1. Formation of the Electrophile: The reaction starts with the acyl chloride (RCOCl) reacting with the Lewis acid catalyst (AlCl3). The Lewis acid coordinates to the chlorine atom, making the carbonyl carbon more electrophilic and facilitating the departure of the chloride ion. This results in the formation of an acylium ion (RCO+), which serves as the electrophile in the reaction.

  2. Electrophilic Attack and Formation of the Sigma Complex: The acylium ion (RCO+) then attacks the π\pi electrons of the aromatic ring, forming a high-energy carbocation intermediate known as the sigma complex or arenium ion. This intermediate is stabilized by resonance, allowing the positive charge to be delocalized across the ring.

  3. Deprotonation and Restoration of Aromaticity: A base, often the chloride ion (Cl−) from the AlCl4− complex, abstracts a proton (H+) from the carbon adjacent to the newly attached acyl group. This step restores the aromaticity of the ring by re-establishing the conjugated π electron system, resulting in the formation of the acylated aromatic compound.

  4. Regeneration of the Catalyst: In the final step, the Lewis acid catalyst is regenerated when the AlCl4− releases a Cl− ion and recovers AlCl3, making it available to catalyze additional reactions.

Friedel-Crafts acylation offers several advantages over alkylation, including the avoidance of carbocation rearrangement (since acylium ions are less prone to rearrangement) and the ability to introduce a wide variety of acyl groups, thus offering greater control over the product's functionality. This reaction is instrumental in the synthesis of aromatic ketones, serving as a key step in the production of fine chemicals, pharmaceuticals, and agrochemicals.

 

The acylation reaction does not have the limitations as Friedel-Crafts alkylation.  Since it uses AlCl3 it does have compatibility issues with aromatics with a nitro (NO2) group.

1) Carbocation rearrangement is not an issue with acylium ions.

2) Over acylation is not an issue since the acyl group deactivates the ring so further acylation does not occur.  We will see soon that an acyl group is an EWG (Electron Withdrawing Group).  This is easily shown by considering the resonance structures for acetophenone below.  Notice how the curved arrows show the electrons being pulled from the aromatic ring, resulting in a positive charge in the ring.

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Reduction of Aromatic ketones

Aryl ketones and aldehydes can be reduced to the corresponding alkyl groups by way of the Clemmenson reduction.  Recall that propylbenzene would be difficult to synthesize with a Friedel-Crafts alkylation since rearrangement would occur and overalkylation is a problem.  This acylation/reduction sequence is useful for creating difficult alkyl arenes.