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

Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Mechanism
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Organic Chemistry
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JoVE Core Organic Chemistry
Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Mechanism

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01:13 min
May 22, 2025

Overview

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.

Esterification process equation, acid-catalyzed reaction diagram, shows ester and water formation.

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.

Esterification reaction formula, chemical equation diagram, alcohol and carboxylic acid reaction process.

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

Chemical reaction scheme for esterification; cyclopropane carboxylic acid with methanol, 81% yield.

Transcript

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.

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