A Rapid and Convenient Isolation and Methyl Esterification of Water-Soluble Acids Using Diazomethane Of the numerous methods for preparing methyl esters of carboxylic acids (HARRISON, H. R., HAYNES,W. M., ARTHUR, P., A N D EISENBRAUN, E. J., Chem. Ind. (London), 1568 (1968)), the diazomethane procedure (MOORE,J. E., AND REED,D. E., Org. Syn., 41, 16 (1961)) is superior because of the absence of side reactions and the rapidity and completeness of the esterification. The diazomethane procedure becomes less useful for the water-soluble acids since a troublesome and time-consuming continuous-extraction process is required to make the acids available for the esterification. To avoid this extraction step, we have developed a technique which permits esterification with diazomethane and rapid extraction in a single operation. The diazomethane reaction rapidly converts the carboxylic acid to the methyl ester. In this method, a cooled (an ice bath is recommended to reduce loss of diazomethane) magnetically stirred solution containing the water-soluble acid is acidified to pH 3 4 with hydrochloric acid. Excess acid is to be avoided but does not interfere since hydrochloric acid reacts with diazomethane to form methyl chloride. An ether solution of diazomethane is added a t such rate as to avoid loss from frothing (from rapid nitrogen evolution) until a permanent yellow tint of excess diazomethane is observed. Acetic acid is added to destroy the surplus diazometha~le,or it is allowed to escape from the ether layer upon standing. The ether layer is then separated and the methyl ester is isolated from it. Because this technique has been successfully applied to small quantities, it is particularly useful in preparing methyl esters of water-soluble acids for gas chromatography. Trial studies with 0.001 mole of oxalic acid showed that while most of the dimethyl oxalate was found in the ether layer, there was some unidentified material in the water layer. Succinic acid was esterified and the dimethyl ester was completely extracted from the water layer. Tartaric was converted to the dimethyl ester, mp 484g°C, but most of i t remained in the water layer. A smaller sample of succinic acid (4.0 mg) was successfully esterified, extracted, and identified by glpc studies as dimethyl succinate. The technique is capable of utilizing considerably smaller samples. This extraction and esterification technique is a potentially useful starting point for undergraduate laboratory instruction since it involves preparation of the very useful diazomethane, instructs in phase distribution, and as noted, can be extended to glpc studies.
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lournal of Chemical Education
