Amide hydrolysis
Acid activates the amide carbonyl for water addition. Proton transfer makes nitrogen a better leaving group before C-N cleavage; the acyl fragment becomes ethanoic acid and the nitrogen ends as ammonium.
- Reagents
- Dilute HCl(aq)
- Conditions
- Prolonged heating under reflux
- Reaction class
- Amide hydrolysis
- Equation
- CH3CONH2 + H2O + HCl -> CH3COOH + NH4Cl
Overview
Acid activates the amide carbonyl for water addition. Proton transfer makes nitrogen a better leaving group before C-N cleavage; the acyl fragment becomes ethanoic acid and the nitrogen ends as ammonium.
Transformation
- Equation
- CH3CONH2 + H2O + HCl -> CH3COOH + NH4Cl
- Reactants
- Acetamide + Water + Hydrogen chloride
- Products
- Ethanoic acid + Ammonium chloride
- Reagents
- Dilute HCl(aq)
- Environment
- Prolonged heating under reflux
- Reaction class
- Amide hydrolysis
- Mechanism
- acid-catalysed nucleophilic acyl substitution
- Evidence level
- source-backed molecular example
Scope and limitations
- Scope
- Complete hydrolysis of a primary amide.
- Limitations
- Nitrogen gives ammonium under acidic conditions; alkaline hydrolysis would give ethanoate.
Related reactions
- Oxidation: Ethanol → Ethanoic acid
Ethanol is oxidised to ethanoic acid.
- Oxidation: Ethanal → Ethanoic acid
Ethanal is oxidised to ethanoic acid.
- Esterification: Ethanoic acid → Ethyl acetate
Ethanoic acid and ethanol combine reversibly to form ethyl acetate and water.
- Acid hydrolysis: Ethyl acetate → Ethanoic acid
Ethyl acetate and water react reversibly to form ethanoic acid and ethanol.
- Amide formation: Acetyl chloride → Acetamide
Ammonia attacks the carbonyl carbon and chloride leaves when the tetrahedral intermediate collapses. Deprotonation gives acetamide, while another ammonia equivalent neutralises the acid to form ammonium chloride.
- Acid hydrolysis: Methyl acetate → Ethanoic acid
Water adds to the protonated ester carbonyl. Proton transfer allows methanol to leave as the carbonyl reforms, producing the acid and alcohol together.
References
- Organic Chemistry: Chemistry of AmidesJohn McMurry · OpenStax Organic Chemistry · 2023
Supports functional-group chemistry used to curate the linked examples. Checked 2026-09-16; named examples are applications of textbook scope, without claimed experimental yields.