DCC-Promoted Amide Synthesis

The intermediate in this synthesis does not need to be isolated, and both steps take place at room temperature. Amides are produced in very high yield. In Chapter 24 we shall see how diisopropylcarbodiimide is used in an automated synthesis of peptides. 

TV-Substituted amides and AT -disubstituted amides also undergo hydrolysis in aqueous acid or base. Amide hydrolysis by either method takes place more slowly than the corresponding hydrolysis of an ester. Thus, amide hydrolyses generally require the forcing conditions of heat and strong acid or base. 

The mechanism for acid hydrolysis of an amide is similar to that given in Section 17.7A for the acid hydrolysis of an ester. Water acts as a nucleophile and attacks the protonated amide. The leaving group in the acidic hydrolysis of an amide is ammonia (or an amine). 

The amide carbonyl accepts a proton from the aqueous acid. 

A water molecule attacks the protonated carbonyl to give a tetrahedral intermediate. 

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Acid-Catalyzed Esterification 790 Base-Promoted Hydrolysis of an Ester 793 DCC-Promoted Amide Synthesis 798 Acidic Hydrolysis of an Amide 799 Basic Hydrolysis of an Amide 799 Acidic Hydrolysis of a Nitrile 801 Basic Hydrolysis of a Nitrile 801... 

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