Overview

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.

Procedure

Amides can be prepared from carboxylic acids or their derivatives.

Carboxylic acids react with amines in the presence of DCC or dicyclohexylcarbodiimide, a dehydrating reagent, to give amides.

The mechanism begins with the protonation of DCC by carboxylic acid, making it a better acceptor.

Next, the carboxylate adds to the protonated carbodiimide, forming a reactive acylating agent.

Subsequently, amine exerts a nucleophilic attack at the acylating agent, forming a tetrahedral intermediate.

Finally, the departure of dicyclohexylurea gives an amide.

Similarly, acid halides or anhydrides react with ammonia or amines to give amides.

Ammonia yields primary amides, whereas primary and secondary amines give secondary and tertiary amides.

The reaction requires two equivalents of ammonia or amine, one for the nucleophilic attack and the second to act as a base.

Acid halides being the most reactive derivative, provide the best yield of amides.

Esters also react with ammonia or amines to form amides. However, esters being less reactive, require heat or a high concentration of amines.