Acidic hydrolysis of amides and nitriles: practice and mechanism
Boiling with acid cleaves amides (and nitriles via the amide) all the way to the carboxylic acid; N leaves as NH₄⁺.
Example
Amides are very stable and only cleaved by heating with acid, giving the carboxylic acid and ammonium. Nitriles are likewise hydrolysed via the amide all the way to the carboxylic acid.
Mechanism step by step
- 1
The acid protonates the amide carbonyl oxygen.
- 2
Water attacks the carbonyl carbon; after proton transfer the nitrogen is protonated.
- 3
NH₃ leaves (and immediately becomes NH₄⁺), C=O re-forms: carboxylic acid. Nitriles go via the amide.
Practice tasks
Which product forms, which reagent is needed? After each answer you see the explanation.
Which main product forms?
Typical mistakes
- The amide is only the intermediate. Under the harsh conditions (acid, heat) it is hydrolysed further to the carboxylic acid.
- An amine forms by reduction (LiAlH₄), not by hydrolysis. Water and acid cleave the C–N bond.
- A nitrile would come from removing water. Here water is added: you end up with the carboxylic acid.
- An aldehyde would be a reduction. Hydrolysis does not change the oxidation level: the amide becomes the carboxylic acid.
- An aldehyde only forms from nitriles by reduction with DIBAL-H. Acidic hydrolysis goes all the way to the carboxylic acid.
Often confused with: Reduction with lithium aluminium hydride · Amide from acyl chloride
Frequently asked questions
Why such harsh conditions?
Amides are the most stable acid derivatives (resonance with N); NH₂⁻ is a very poor leaving group.
Why does this matter in biology?
Peptide bonds are amides; their stability holds proteins together. Enzymes (proteases) still cleave them quickly.