Chapter 20: Carboxylic Acid Derivatives. NucleophilicAcyl Substitution

Hydrolysis of Nitriles

Summary

• Nitriles, RC≡N, can be hydrolysedto carboxylic acids, RCO₂H via the amide, RCONH₂.
• Reagents : Strong acid (e.g. H₂SO₄) or strongbase (e.g. NaOH) / heat.

• Hydrolysis of Esters and Amides
• Hydration of Alkynes

MECHANISM OF THE ACID CATALYSED HYDROLYSIS OF NITRILES
Step 1: An acid/base reaction. Since we only have a weak nucleophile so activate the nitrile, protonation makes it more electrophilic.
Step 2: The water O functions as the nucleophile attacking the electrophilic C in the C≡N, with the electrons moving towards the positive center.
Step 3: An acid/base reaction. Deprotonate the oxygen that came from the watermolecule. The remaining task is a tautomerisation at N and O centers.
Step 4: An acid/base reaction. Protonate the N gives us the -NH2 we need....
Step 5: Use the electrons of an adjacent O to neutralise the positive at the N and form the π bond in the C=O.
Step 6: An acid/base reaction. Deprotonation of the oxonium ion reveals the carbonyl in the amide intermediate....halfway to the acid.....  What about the rest ?

© Dr. Ian Hunt, Department of Chemistry