Formation of Amides Using DCC

by James

Description: Treatment of carboxylic acids with amines in the presence of the dehydrating agent N,N’-dicyclohexylcarbodiimide (DCC) leads to the formation of amides. This is particularly useful for peptide synthesis.
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Notes: The byproduct of this reaction is the urea derivative of DCC (see mechanism below).

Examples: 

Notes: The third example shows an example of a peptide coupling.

Mechanism: The first step in this reaction is addition of the carboxylic acid to the carbodiimide (Step 1, arrows A, B, and C). This is followed by a proton transfer from oxygen to nitrogen (Step 2, arrows D and E). This species is now activated towards attack by the amine nitrogen (Step 3, arrows F and G) to give a tetrahedral intermediate, which then results in elimination to give the dicyclohexylurea derivative (Step 4, arrows H and I). Finally, deprotonation at nitrogen (Step 5, arrows J, K, and L) gives the neutral amide product and the final urea byproduct.

Notes: It’s possible to draw slightly different mechanisms for the proton transfer step and also to use a different base for the final deprotonation step. Note how DCC makes the carboxylic acid oxygen into a better leaving group!

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{ 1 comment… read it below or add one }

Dr. Surendra Kumar Nayak

DCC also used as dehydrating agent during reactions between alcohols (R’-OH) and carboxylic acids (R-COOH) to form corresponsding esters (R-COOR’).
However, precaution should be taken during its use because it is a very potent allergen.

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