Nucleophilic acyl substitution

A reaction in which a nucleophile replaces a leaving group attached to an acyl carbon, typically through addition to the carbonyl followed by elimination.

Tetrahedral intermediate: A transient species with a tetrahedral carbon bearing four single bonds, formed when a nucleophile adds to a carbonyl. It forms when the incoming nucleophile attacks the acyl carbon.
Carboxylic acid derivative: A compound derived from a carboxylic acid by replacing its hydroxyl group with another atom or group. These compounds are the principal substrates for acyl substitution.
Esterification: A reaction that forms an ester, commonly by combining a carboxylic acid with an alcohol. Acyl substitution provides a route from activated acids to esters.
Nucleophilic addition: A reaction in which a nucleophile adds to a multiple bond without replacing a substituent. Unlike acyl substitution, carbonyl addition ends without expelling a leaving group.
Carbonyl addition: A reaction in which a nucleophile forms a bond to a carbonyl carbon, converting the carbonyl π bond into a C–O bond. This is the first step before the leaving group can depart.
Acyl halide: A carboxylic acid derivative in which a halogen is bonded to the acyl carbon. Its halide leaving group makes it especially reactive toward nucleophiles.
Amide coupling: A reaction that forms an amide bond between a carboxylic acid-derived acyl group and an amine. It uses activated acyl compounds to build amide bonds in synthesis.
Aldehyde: A carbonyl compound whose carbonyl carbon is bonded to hydrogen and an organic group. Aldehydes lack the attached leaving group typical of acyl-substitution substrates.
Leaving group: An atom or group that departs with the bonding electron pair during a chemical reaction. Its ability to depart determines whether the tetrahedral intermediate collapses.
Acid anhydride: A compound containing two acyl groups joined by an oxygen atom. Anhydrides undergo substitution by expelling a carboxylate group.

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