14.22: Preparation of Amides
Amides are synthesized by treating carboxylic acids with amines in the presence of dehydrating agents like dicyclohexylcarbodiimide (DCC).
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the final step, dicyclohexylurea departs to give an amide as the final product.
Alternatively, acid halides or acid anhydrides undergo aminolysis to form amides. The reaction requires two equivalents of ammonia or amines, where one equivalent acts as a nucleophile and the second functions as a base to give the substitution product. Interestingly, the best amide yield is obtained from highly reactive acid halides.
Similarly, esters undergo aminolysis to form amides. However, the preparation method involves heating or a high concentration of amines due to the lower reactivity of esters.