Nucleophilic acyl substitution

Nucleophile addition to an acyl carbonyl followed by leaving-group elimination, often through a tetrahedral reaction intermediate.

Formation of an ester from an acyl component and an alcohol. Intramolecular esterification of a hydroxy acid makes a lactone. Fischer esterification is the acid-catalysed carboxylic-acid/alcohol case.

Base-promoted bimolecular acyl substitution: nucleophile addition gives a tetrahedral intermediate, then a leaving group departs from the acyl carbon.

Formation of a lactone by intramolecular esterification or acyl substitution. Favourable ring sizes can help trap an intermediate, but do not make the product universally unreactive.

Acid-catalysed ester formation from a carboxylic acid and an alcohol, proceeding through carbonyl addition and elimination with net water formation.

Breaking an ester linkage can proceed by different bonds and mechanisms. Acyl–oxygen and alkyl–oxygen cleavage should be distinguished when explaining protecting-group selectivity.

Breaking the bond between an acyl carbon and the ester alkoxy oxygen. Ordinary hydroxide-promoted ester saponification follows addition–elimination through a tetrahedral intermediate.

Breaking the bond between an ester oxygen and its alkyl substituent. Acid removal of a tert-butyl group can follow this route without requiring water or a tetrahedral acyl-addition intermediate.

Exchange of an ester alkoxy group through reaction with an alcohol, commonly using acid or base catalysis. Excess exchanging alcohol can shift the chemical equilibrium.

For exchange of closely related ester and alcohol groups, an excess alcohol reservoir and dilution of the outgoing alcohol can favour conversion through mixture chemical potentials. Equal molecular stoichiometry does not itself imply a positive standard entropy change; a reaction quotient is needed.