Acid-Catalyzed Amide Hydrolysis and Alcoholysis

Amides react with water to form carboxylic acids and with alcohols to form esters, if the reaction mixture is heated in the presence of an acid. 

The mechanism for the acid-catalyzed hydrolysis of an amide is exactly the same as the mechanism for the acid-catalyzed hydrolysis of an ester shown on page 742. 

Notice again the pattern of the three tetrahedrai intermediates protonated tetrahedrai intermediate neutrai tetrahedrai intermediate protonated tetrahedrai intermediate. 

Let s take a minute to see why an amide cannot be hydrolyzed without a catalyst. In an uncatalyzed reaction, the amide would not be protonated. Therefore, water, a very poor nucleophile, would have to add to a neutral amide that is much less susceptible to nucleophilic addition than a protonated amide would be. More importantly in the uncatalyzed reaction, the NH2 group of the tetrahedral intermediate would not be protonated. Therefore, HO would be eliminated from the tetrahedral intermediate (because HO is a weaker base than NH2), which would re-form the amide. 

When an amide reacts with an alcohol in the presence of acid to form an ester, it follows the same mechanism as it does when it reacts with water to form a carboxylic acid. 

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