Chapter 20: Carboxylic Acid Derivatives. Nucleophilic Acyl Substitution

Nucleophilic Acyl Substitution : Reactive Systems

• If either of the reaction components are reactive, for example anionic nucleophiles (e.g. HO^- etc.) or the electrophile is a  more reactive carboxylic acid derivative (e.g. acyl chlorides or acid anhydrides) then the reaction can occur directly as described  below.
• This mechanism is similar to that seen previously for the reactions for epoxides (Chapter 16) and aldehydes / ketones (Chapter 17) with stronger nucleophiles.

Step 1: The nucleophile adds to the electrophilic C in the polar carbonyl group, electrons from the C=O move to the electronegative O creating the tetrahedral intermediate.
Step 2: The intermediate collapses, reforming the strong C=O bond results in the loss of the leaving group, leading to the new carbonyl containing system.

© Dr. Ian Hunt, Department of Chemistry