Amide Hydrolysis: Videos & Practice Problems

In acidic hydrolysis of amides, the reaction occurs in the presence of aqueous acid, typically hydrochloric acid, and heat. The carbonyl carbon of the amide gains a hydroxyl group (OH), transforming into a carboxylic acid. Simultaneously, the nitrogen atom in the amide gains two hydrogen atoms, forming an ammonium ion. The overall reaction can be summarized as:

${R-\mathrm{CONH}}_2+{H-\mathrm{Cl}}_2+H{O}_2\to {R-\mathrm{COOH}}_2+{\mathrm{NH}}_4+{\mathrm{Cl}}_2$

In basic hydrolysis of amides, the reaction occurs with hydroxide ions (OH^-) in water and heat. The amide bond is cleaved, resulting in the formation of a carboxylate anion and a neutral amine. The carbonyl carbon gains an oxygen atom with a negative charge (O^-), forming the carboxylate anion, while the nitrogen gains one hydrogen atom, forming a neutral amine. The overall reaction can be summarized as:

${R-\mathrm{CONH}}_2+{\mathrm{OH}}_{\mathrm{-}}+H{O}_2\to {R-\mathrm{COO}}_{\mathrm{-}}+{\mathrm{NH}}_3$

Acidic hydrolysis of amides involves the use of aqueous acid (e.g., HCl) and heat, resulting in the formation of a carboxylic acid and an ammonium ion. The carbonyl carbon gains a hydroxyl group (OH), and the nitrogen gains two hydrogen atoms, forming an ammonium ion. In contrast, basic hydrolysis uses hydroxide ions (OH^-) and heat, producing a carboxylate anion and a neutral amine. The carbonyl carbon gains an oxygen atom with a negative charge (O^-), and the nitrogen gains one hydrogen atom, forming a neutral amine. The key difference lies in the products: acidic hydrolysis yields a carboxylic acid and ammonium ion, while basic hydrolysis yields a carboxylate anion and a neutral amine.

The hydrolysis of amides can occur under either acidic or basic conditions, both requiring heat. For acidic hydrolysis, an aqueous acid such as hydrochloric acid (HCl) is used. The reaction produces a carboxylic acid and an ammonium ion. For basic hydrolysis, an aqueous solution of hydroxide ions (OH^-), such as sodium hydroxide (NaOH), is used. This reaction produces a carboxylate anion and a neutral amine. In both cases, heat is necessary to facilitate the reaction and ensure the amide bond is cleaved effectively.

Heat is necessary for the hydrolysis of amides because it provides the energy required to break the strong amide bond. The amide bond is relatively stable and requires significant energy to be cleaved. In both acidic and basic hydrolysis, heat helps to accelerate the reaction by increasing the kinetic energy of the molecules, thereby facilitating the interaction between the amide and the hydrolyzing agents (acid or base). Without sufficient heat, the reaction would proceed very slowly or might not occur at all.