dicyclohexylcarbodiimide

Dicyclohexylcarbodiimide, commonly abbreviated as DCC, is an organic carbodiimide reagent widely used to promote amide bond formation and esterifications. It is especially prominent in peptide synthesis, where it activates carboxylic acids toward nucleophilic attack by amines under mild conditions.

Chemically, DCC consists of a central carbodiimide group bearing two cyclohexyl substituents. In typical coupling reactions, DCC reacts with a carboxylic acid to form an O-acylisourea intermediate. This intermediate is reactive toward amines and, upon attack, yields the desired amide product while dicyclohexylurea (DCU) precipitates as a byproduct. The DCU byproduct is usually insoluble in many common organic solvents, allowing convenient filtration from the reaction mixture.

DCC is soluble in a range of organic solvents such as dichloromethane, tetrahydrofuran, and dimethylformamide, but is relatively insoluble in water. Reactions employing DCC can be sensitive to moisture and the presence of water competes with amines, reducing coupling efficiency.

While effective, DCC can promote racemization in peptide synthesis and generate byproducts that complicate purification. To mitigate these issues, coupling systems often employ additives such as hydroxybenzotriazole (HBT) or HOAt, or alternative reagents like EDC, DIC with additives, or newer coupling systems that are water-soluble or easier to purify.

Safety considerations include irritation and potential sensitization; DCC should be handled in a well-ventilated area with appropriate protective equipment. It is typically stored dry in a desiccator to minimize hydrolysis and degradation.