Fischer Esterification

The Fischer esterification is a coupling reaction between a carboxylic acid and an alcohol in the presence of an acid catalyst.

General features: 1. The Fischer esterification is straightforward. Acidic conditions can be used if acid-sensitive functional groups are not an issue. 2. The main by-product is water. 3. Less environmental impact by reducing waste (atom economy) and the harmfulness of the reagents when compared to other procedures using acid chlorides, alkyl halides, or acid anhydrides. 4. The reaction is a thermodynamically controlled process; the more stable ester tends to be the main product. 5. The primary disadvantages of the Fischer esterification routes are its thermodynamic reversibility and relatively slow reaction rates.

In a round-bottom flask, the carboxylic acid (466 μmol, 1.0 eq) was dissolved in 10 mL of methanol and H2SO4 (3.0 eq) was added. The reaction mixture was heated under reflux overnight. Water and NaHCO3 were added to the flask, and the solution was extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4, filtered, and the solvent evaporated. The crude product was purified by crystallization with DCM and MeOH to deliver the desired methyl ester (45% yield).