Hydrolysis

Overview

Nitriles can be hydrolysed to carboxylic acids, splitting the old aggregate nitrile-to-amide route into a single functional-group conversion.

Transformation

Nitriles → Carboxylic acids

Equation

R-CN + 2H2O + H+ -> R-CO2H + NH4+

Reagents

dilute HCl(aq) or dilute H2SO4(aq)

Environment

heat under reflux

Reaction class

hydrolysis

Mechanism

hydrolysis

Evidence level

textbook core

Scope and limitations

Scope

Nitriles are hydrolysed under dilute acidic conditions to a carboxylic acid and an ammonium ion.

Limitations

Alkaline hydrolysis gives a carboxylate salt and ammonia as the immediate products; a separate acidification step is required to obtain the carboxylic acid. That alternative is not represented by the displayed equation.

Related reactions

• Cyanation: Chloroalkanes → Nitriles

  Cyanide substitution forms a nitrile and extends the carbon chain by one carbon.

• Cyanation: Bromoalkanes → Nitriles

  Cyanide substitution forms a nitrile and extends the carbon chain by one carbon.

• Cyanation: Iodoalkanes → Nitriles

  Cyanide substitution forms a nitrile and extends the carbon chain by one carbon.

• Oxidation: Alcohols → Carboxylic acids

  Full oxidation of a primary alcohol gives a carboxylic acid.

• Complete oxidation: Primary alcohols → Carboxylic acids

  Full oxidation of a primary alcohol gives a carboxylic acid.

• Reduction: Carboxylic acids → Primary alcohols

  Reduction of a carboxylic acid gives a primary alcohol.

• Oxidation: Aldehydes → Carboxylic acids

  Oxidation of an aldehyde gives a carboxylic acid.

• Reduction: Nitriles → Amines

  Nitriles can be reduced to primary amines, separating the amine feedstock route from later amide or materials chemistry.

• Activation for amide formation: Carboxylic acids → Amide chemistry

  Carboxylic acids or activated acid derivatives connect to amide-bond formation.

• Esterification: Carboxylic acids → Esters

  Carboxylic acids react with alcohols to form esters.

• Hydrolysis: Esters → Carboxylic acids

  Hydrolysis converts esters back into carboxylic acid products.

• Chlorination: Carboxylic acids → Acyl chlorides

  PCl5 converts carboxylic acids into acyl chlorides.

• Chlorination with thionyl chloride: Carboxylic acids → Acyl chlorides

  Thionyl chloride converts carboxylic acids into acyl chlorides with sulfur dioxide and hydrogen chloride as by-products.

• Hydrolysis: Acyl chlorides → Carboxylic acids

  Water hydrolyses acyl chlorides to carboxylic acids, releasing hydrogen chloride.

• Carboxylation: Grignard reagents → Carboxylic acids

  Grignard carboxylation gives carboxylic acids after acidic work-up.

• Grignard carboxylation co reactant: Carbon dioxide → Carboxylic acids

  Carbon dioxide plus a Grignard reagent gives a carboxylic acid after acidic work-up.

References

1. Organic Chemistry: Chemistry of NitrilesJohn McMurry · OpenStax Organic Chemistry · 2023

   Supports nitrile reduction by two hydride additions to imine-anion and aluminium-stabilised dianion intermediates, followed by aqueous work-up to a primary amine; also documents nitrile hydrolysis through amide intermediates.