Fischer esterification of a carboxylic acid is a nucleophilic acyl substitution reaction entailing the nucleophilic addition of alcohol and elimination of a water molecule as the leaving group.

The first step involves acid-catalyzed protonation of the carbonyl oxygen atom. This results in a resonance stabilized protonated acid with increased electrophilicity of the carbonyl carbon atom.

Consequently, a nucleophilic attack by the alcohol followed by deprotonation yields a tetrahedral intermediate.

The tetrahedral intermediate is unstable and immediately protonated to convert the –OH group into a better leaving group. This results in the loss of a water molecule to form a protonated ester. Finally, deprotonation yields the ester as the desired product.

The mechanism was studied via isotope labeling experiments using an ¹⁸O labeled alcohol. The yield of radioisotope-enriched esters proves that the acyl C–O bond of the acid is cleaved rather than the O–H bond.

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

The mechanism of this reaction was confirmed by Robert and Urey (1938) through a radioisotope labeling experiment, whereesterification of a carboxylic acid was carried out using ¹⁸O-labeled alcohol. The resulting ester was found to be labeled with an¹⁸O atom, establishing the fact that the –OH group of the carboxylic acid was replaced bythe –OR group from the alcohol.

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

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