Notes on Carbodiimides and Their Use

DCC is an inexpensive brittle solid, melting point 34-35°C, that must be crushed or warmed to a viscous liquid to withdraw it from a container. It generates a very bulky A. V -dialkylurca that is insoluble in organic solvents, and, hence, it may interfere with mixing. Filtration removes most of the urea, but it is soluble enough in the usual solvents that its complete removal can be problematic. It is least soluble in water, hexane, or acetone cooling a solution of a product in acetone for a few 

FIGURE 7.1 A carbodiimide reacts with a carboxylic acid (A) to give the O-acylisourea, which may rearrange (B) to the A-acylurea. It also reacts with amino groups (C) to produce guanidines if no carboxyl group is available. 

DIC is a moderately expensive liquid that is employed in solid-phase synthesis to avoid the obstacles presented by the use of DCC. Both the reagent and the corresponding urea are soluble in organic solvents, and hence there is no bulky precipitate to contend with. The urea cannot be removed from an organic solution by aqueous extraction however, it is soluble enough in water that final traces can be removed from a precipitated peptide by washing the latter with a water-ether mixture. Clean up of spills of DIC can cause temporary blindness if utmost care is not exercised. 

BS Jacobson, KF Fairman. A colorimetric assay for carbodiimides commonly usd in peptide synthesis and carboxyl group modification. Anal Biochem 106, 114, 1980. 

NL Benoiton, FMF Chen, C Williams. Determination of carnitine by HPLC as carnitinyl-anisidine. Proc Fed Am Soc Exp Biol, Abstract 50775, 1987. 

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