thumb|The synthesis of [[methyl benzoate by Fischer–Speier esterification]]
Fischer esterification or Fischer–Speier esterification is a special type of esterification by refluxing a carboxylic acid and an alcohol in the presence of an acid catalyst. The reaction was first described by Emil Fischer and Arthur Speier in 1895. Most carboxylic acids are suitable for the reaction, but the alcohol should generally be primary or secondary. Tertiary alcohols are prone to elimination. Contrary to common misconception found in organic chemistry textbooks, phenols can also be esterified to give good to near quantitative yield of products. Commonly used catalysts for a Fischer esterification include sulfuric acid, p-toluenesulfonic acid, and Lewis acids such as scandium(III) triflate. For more valuable or sensitive substrates (for example, biomaterials) other, milder procedures such as Steglich esterification are used. The reaction is often carried out without a solvent (particularly when a large reagent excess of the alcohol reagent is used) or in a non-polar solvent (e.g. toluene, hexane) that can facilitate Dean–Stark distillation to remove the water byproduct. Typical reaction times vary from 1–10 hours at temperatures of 60–110 °C.
Direct acylations of alcohols with carboxylic acids is preferred over acylations with anhydrides (poor atom economy of the reaction) or acid chlorides (moisture sensitive reagents). The main disadvantage of direct acylation is the unfavorable chemical equilibrium that must be remedied (e.g. by a large excess of one of the reagents), or by the removal of water (e.g. by using Dean–Stark distillation or including a drying agent such as anhydrous salts, molecular sieves, or a large amount of certain acids as catalyst in the reaction mixture).
Overview
Fischer esterification is an acyl substitution reaction based on the electrophilicity of the carbonyl carbon and the nucleophilicity of an alcohol. Carboxylic acids tend to be deprotonated by nucleophiles, which gives an unreactive carboxylate. Although kinetically very stable in the absence of catalysts, esters tend to eventually hydrolyse in the presence of water.
Several steps can be taken to turn this unfavourable reaction into a favourable one. It is believed that hydrobromic acid released by TBATB protonates the alcohol rather than the carboxylic acid, making the carboxylate the actual nucleophile. This would be a reversal of the standard esterification mechanism. An example of this method is the acylation of 3-phenylpropanol using glacial acetic acid and TBATB. The reaction generates the ester in 15 minutes in a 95% yield without the need to remove water.
Arthur Speier
Arthur Speier was a German chemist and pharmacist who, along with Emil Fischer, developed Fischer–Speier esterification.
See also
- Fischer glycosidation - the coupling of an alcohol and a sugar