Herman Jelle Wories

On the mechanism of the esterification of a β-hydroxy alkylamide with a carboxylic acid

β-Hydroxy alkylamide reacts with carboxylic acid to form an ester much faster than with a normal alcohol. Many suggestions have been made to describe the mechanism of this reaction, but none of them have been proved. It is clear that this reaction cannot be seen as a normal esterification since it cannot be catalysed by acids or bases. We have prepared model compounds, for which calibration curves have been obtained by means of UV spectroscopy. A technique was developed for separating the starting materials and the expected reaction products by means of HPLC. In this way, quantitative and qualitative information about the reaction mixtures could be obtained as a function of time. This method revealed the existence of an intermediate oxazolinium cation. The formation of this compound plays a key role in the esterification. Apart from the expected ester and the intermediate, various other reaction products were determined. All the reaction products could be obtained in a pure state with the aid of preparative HPLC. The structures of the compounds were studied using 1H NMR spectrometry. A reaction mechanism has been put forward to explain the experimental data.