Another useful esterification reagent is the Lewis acid boron trifluoride or the analogous reagent boron trichloride. Boron trifluoride is commercially available as a 14% solution in methanol for forming ester derivatives. Boron trifluoride catalyzed reactions carried out on a water bath are very rapid and can be complete in a few minutes. 1 to 15 mg of the acid are placed in a vial and 1 ml of 14% boron trifluoride in methanol added. The mixture is heated in a water bath for 2 minutes and then cooled. The esters can be extracted into n–heptane by vigorous shaking.
Thionyl chloride is another useful catalyst but should be purified by distilling from linseed oil before use. To 10 to 50 mg of acid, contained in a vial is added 200 ml of dry methanol and cooled in a solid carbon dioxide-acetone cooling bath. 20 ml of thionyl chloride is then added with shaking and the vial warmed to and maintained at 40°C for two hours. The solution is then evaporated to dryness in a stream of nitrogen.
The esterification of an alcohol is the complimentary form of ester derivatization. The most common reagent would be an acid anhydride that also removes the water formed during esterification. 10 to 100 mg of acid contained in a vial is reacted with 1 molar equivalent of the alcohol in the presence of 1.2 to 1.4 equivalents of trifluoroacetic anhydride. The mixture is warmed and the reaction proceeds rapidly and is complete in about 10 minutes.
A popular reagent for the esterification of acids is diazomethane. However, it must be emphasized that diazomethane is carcinogenic and can be extremely unstable. The materials must not be overheated as there is a risk of explosion. Nevertheless, despite the hazards, the reagent is extremely effective and, if its use is restricted to microscale reactions, it is generally safe to use.
Diazomethane is employed as an ethereal solution but, in fact, is a yellow gas. Its reaction with an organic acid is as follows,
R—COOH + CH2N2
R—COO–CH3 + N2
The yellow color persists when the reaction is complete and thus the reagent acts as its own indicator. An apparatus developed by Schlenk and Gellerman (14) for esterification with diazomethane is shown in figure 23. Nitrogen is bubbled through ether and then through a vessel containing a solution of N–methyl–N–Nitroso–p toluene sulfonamide which, when treated with potassium hydroxide generates the diazomethane.
