Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Mechanism

Carboxylic acids react with alcohols to yield esters via an acid-catalyzed condensation reaction called Fischer esterification. This is a nucleophilic acyl substitution reaction that proceeds via a tetrahedral intermediate, where a water molecule is eliminated as the leaving group.

The mechanism of this reaction was confirmed by Robert and Urey (1938) through a radioisotope labeling experiment, where esterification of a carboxylic acid was carried out using ¹⁸O-labeled alcohol. The resulting ester was found to be labeled with an ¹⁸O atom, establishing the fact that the –OH group of the carboxylic acid was replaced by the –OR group from the alcohol.

Modifications of Fischer esterification use either a boron trifluoride ether complex or an organotin complex as the catalyst in an acid-free condition.