Fischer Esterification-百灵威

The Fischer esterification uses a catalytic acid to convert a carboxylic acid and alcohol to an ester. Protonation of the carbonyl oxygen activates the carboxylic acid to nucleophilic attack by the alcohol, producing a tetrahedral intermediate with two hydroxyl groups. Ester formation occurs when a proton is transferred to one of the hydroxyl groups, converting it to a good leaving group that is released when the carbonyl group is restored.

Lab Tips:

Fisher esterification works well for 1° or 2° alcohols. Carboxylate alkylation by halides or sulfonates may be a better method for the preparation of hindered esters. ^[1] Moreover, sterically hindered esters can be prepared from the corresponding acyl chlorides and alcohols in the presence of silver cyanide. ^[2]
As a reversible reaction, ester formation can be favored when a large excess of alcohol is used as a solvent, which is feasible for simple and relatively inexpensive alcohols such as methanol, ethanol, and propanol. ^[1,3] Irreversible removal of water (azeotropic distillation is one method for this) can also drive ester formation forward.^[1]
Alternatively, Brönsted acidic ionic liquids can be used as an efficient and reusable catalyst and reaction medium, affording good ester yields. ^[4]
Note that intramolecular esterification is also possible in some cases. ^[3]

_{1. Carey, F.A., Sundberg, R.J. (2001). Advanced Organic Chemistry Part B: Reactions and Synthesis (4th ed.). New York: Kluwer Academic/Plenum Publishers.
2. Takimoto, S., Inanaga, J., Katsuki, T., Yamaguchi, M. Preparation of hindered esters from acid chlorides and alcohols in the presence of silver cyanide. Bulletin of the Chemical Society of Japan 1976, 49(8), 2335-2336.
3. McMurry, J. (2000). Organic Chemistry (5th ed.). Pacific Grove, CA: Brooks/Cole.
4. Joseph, T., Sahoo, S., Halligudi, S.B. Brӧnsted acidic ionic liquids: a green, efficient and reusable catalyst system and reaction medium for fischer esterification. Journal of Molecular Catalysis A: Chemical 2005, 234(1), 107-110.}