DCC(Dicyclohexylcarbodiimide)

Dicyclohexylcarbodiimide (DCC) is a popular coupling reagent used to form amides and esters. The dicyclohexylurea byproduct of coupling is almost insoluble in most solvents and is easily removed by filtration. In forming esters and thioesters from acids and alcohols, addition of a catalytic amount of 4-(N,Ndimethylamino)pyridine (DMAP)  greatly enhances the rate of reaction. When DCC is used in peptide coupling, 1-hydroxybenzotriazole  is added to suppress racemization. DCC coupling is also used to prepare activated esters, such as p-nitrophenyl esters and pentafluorophenyl esters, for peptide synthesis. DCC has been used to prepare carboxylic acid anhydrides1 , ketenes2 , and nitriles from primary amides3 by dehydration. It is also used in combination with dimethylsulfoxide (DMSO) in the Pfitzner-Moffatt oxidation of alcohols to carbonyl compounds under mild conditions.4 DCC is a sensitizer and can cause chemical burns. Wear safety goggles, chemical resistant gloves, and protective garments when using DCC. 

Coupling Using DCC 

1. Dissolve one equivalent of the carboxylic acid and 1 equivalent of the nucleophile (amine, alcohol, etc.) in dichloromethane (DCM). If the nucleophile is an alcohol, add 0.1 equivalent of DMAP. Cool this mixture in an ice bath.

 2. Dissolve 1.1 equivalents of DCC in a minimum amount of DCM. Add this solution with stirring to cooled mixture in the previous step. Equip the flask with a drying tube and stir the mixture until the reaction is complete.

3. Filter the reaction mixture to remove the precipitated dicyclohexylurea. Wash the filtercake with a small amount of DCM. 4. Combine the filtrates and evaporate in vacuo to obtain the crude product.