Acid hydrolysis of an amide template

Ethanamide in hot aqueous acid: O-protonation, attack by water, proton transfer to N, loss of NH₃ and its protonation give ethanoic acid and ammonium.

Mechanism step by step

Protonation, water addition and loss of ammonia, which is trapped as NH₄⁺

1. O-Protonation – O, not N: the N lone pair is delocalised
2. Water adds – Tetrahedral intermediate
3. Proton transfer – H⁺ moves from O to N (through the solvent)
4. Loss of NH₃ – An O lone pair pushes out ammonia
5. NH₃ takes H⁺ – NH₄⁺ cannot attack back: the step that makes it irreversible

Key points

• Amides are the least reactive acid derivatives (amide resonance), so prolonged heating with strong acid is needed.
• Acid gives RCOOH + NH₄⁺; alkali gives RCOO⁻ + NH₃ (turns damp red litmus blue).
• Proteins are hydrolysed to amino acids this way (6 M HCl, 110 °C, 24 h).
• Nitriles hydrolyse through the amide, so they end at the same products.

Drawn with 64 atoms, 16 arrows, 7 shapes – every one editable in MolDraw.

Sources

• Clayden, Greeves & Warren, Organic Chemistry, 2nd ed., OUP 2012, ch. 10 Textbook
• Smith, March's Advanced Organic Chemistry, 8th ed., Wiley 2020, ch. 16 Textbook