Fischer–Speier esterification

Contrary to common misconception found in organic chemistry textbooks, phenols can also be esterified to give good to near quantitative yield of products.

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,[5] molecular sieves, or a large amount of certain acids as catalyst in the reaction mixture).

Fischer esterification is an acyl substitution reaction based on the electrophilicity of the carbonyl carbon and the nucleophilicity of an alcohol.

Acid chlorides evolve hydrogen chloride gas upon contact with atmospheric moisture, are corrosive, react vigorously with water and other nucleophiles (sometimes dangerously); they are easily quenched by other nucleophiles besides the desired alcohol; their most common synthesis routes involve the evolution of toxic carbon monoxide or sulfur dioxide gases (depending on the synthesis process used).

Examples of this[contradictory] include the common undergraduate organic lab experiment involving the acetylation of salicylic acid to yield aspirin.

Fischer esterification is primarily a thermodynamically-controlled process: because of its slowness, the most stable ester tends to be the major product.

A more inconvenient scenario is if the reagents have a lower boiling point than either the ester product or water, in which case the reaction mixture must be capped[clarification needed] and refluxed and a large excess of starting material added.

In this case anhydrous salts, such as copper(II) sulfate or potassium pyrosulfate, can also be added to sequester the water by forming hydrates, shifting the equilibrium towards ester products.

[5] The reaction mixture containing the product can then be decanted or filtered to remove the drying agent prior to the final workup.