diacylation

Diacylation is a chemical reaction in which two acyl groups (R–C(=O)–) are introduced into a substrate. This can occur either through a single difunctional acylating agent that transfers two acyl units or by using two equivalents of a monofunctional acylating reagent on a substrate that has two reactive sites. Diacylation contrasts with monoacylation, which adds a single acyl group.

Common substrates include amines, alcohols, and diols. When conditions allow, amine or alcohol substrates can be converted to diacylated products such as diamides or diesters, respectively. The use of acid chlorides, anhydrides, or activated esters as acylating agents is typical, often in the presence of a base to promote acyl transfer and to absorb the leaving group.

Mechanistically, diacylation proceeds by nucleophilic attack of the substrate on an activated carbonyl, formation of a tetrahedral intermediate, and departure of a leaving group. If a substrate has two reactive sites or if enough equivalents of the acylating agent are present, second acylation can occur after the first is complete. Factors that influence the outcome include the nucleophilicity of the sites, steric hindrance, solvent, temperature, and the stoichiometry of the reagents. Controlling these parameters allows selective mono- versus diacylation.

Applications of diacylation appear in protecting-group strategies, the synthesis of diamide and diester building blocks, and the preparation of bifunctional acylated materials. The term is mainly used in organic synthesis and polymer chemistry to describe introduction of two acyl moieties into a molecule.