Where Has My Acid Gone? Understanding the Self-Catalyzed Esterification of Maleic Acid in Methanol During Salt Formation

The kinetics of the esterification of maleic acid in methanol have been investigated following the contamination of a batch of an API maleate salt with the corresponding monomethyl maleate salt. The esterification was found to be catalyzed by H+ generated by the ionization of maleic acid, giving rise to an observed rate law with a one-and-a-half-order dependence upon the maleic acid concentration. On the basis of the measured rate constants over a range of temperatures a predictive model has been developed that will estimate the time taken to achieve a given degree of esterification as a function of temperature and maleic acid concentration. Rate constants have also been determined for the maleic acid catalyzed esterification of monomethyl maleate. Neutralization of maleic acid through salt formation with triethylamine reduces the rate of esterification in a manner that is consistent with the degree of neutralization. The potential for the esterification of maleic acid in other alcohols and for the esterification of other carboxylic acids in alcohols is discussed in the light of these findings.