acylations

Acylation is a chemical reaction in which an acyl group (R-CO-) is introduced into a substrate. The acyl group can be transferred to heteroatoms such as oxygen or nitrogen or to carbon on an aromatic ring, producing esters, amides, or ketones depending on the substrate.

Nucleophilic acylation occurs when nucleophiles such as alcohols or amines attack a reactive acylating agent. Typical reagents include acyl chlorides, anhydrides, or mixed anhydrides. The mechanism proceeds via nucleophilic acyl substitution, forming tetrahedral intermediates and releasing a leaving group (usually Cl- or R'COO-).

Friedel–Crafts acylation is an electrophilic acylation of arenes, using acylium ions generated from acyl chlorides in the presence of a Lewis acid catalyst (e.g., AlCl3). The arene attacks the acylium ion to yield a ketone after workup. The reaction typically deactivates the ring and directs substitution to meta or para positions depending on substituents.

Common acylating agents include acetyl chloride, benzoyl chloride, acetic anhydride, and other acid chlorides or anhydrides. Carboxylic acids can also be converted to esters or amides with coupling reagents or activators. Protective groups such as acetyl or benzoyl are frequently used to mask functionality during multi-step syntheses.

Applications include the synthesis of esters, amides, and aryl ketones in pharmaceuticals and materials. Examples include the acetylation of aniline to give acetanilide, the acetylation of salicylic acid to form aspirin, and Friedel–Crafts acetylation of benzene to yield acetophenone. In biology, acetylation modulates protein function and gene regulation.