ABSTRACT
Dialkylcarbodiimides are efficient peptide-bond-forming reagents (see Section 1.12) that react with carboxyl groups to give the O-acylisourea (Figure 7.1, path A). The acyl (RC=O) of the intermediate is immediately transferred to an amino group, to a second molecule of the acid, or to its own basic nitrogen atom (=NR4) to give the N-acylurea (path B; see Sections 2.2-2.4). The net result is dehydration. They also react with amino groups to form guanidines (path C) if no carboxylic acid is available, so if amino groups are present, the carbodiimide should always be added to a reaction mixture after the acid. There are three popular carbodiimides, dicyclohexylcarbodiimide (DCC), ethyl(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), and diisopropylcarbodiimide (DIC). Each has its unique characteristics, but all are skin irritants and allergenic, so protective glasses and gloves should be worn when they are handled. They are not sensitive to water, so with the exception of EDC, they cannot be removed from an organic solvent by washing the solution with aqueous acid or base. A judicious approach is to add acetic acid after completion of a reaction with a few minutes delay before work-up to destroy any carbodiimide that has not been consumed. 1-Hydroxybenzotriazole, the common additive for carbodiimides (see Sections 2.12 and 2.25), is usually obtained as the hydrate; the water has no deleterious effect.
