Chromatographic purification of N–H ketimines via suppression of hydrolysis using dried silica gel and Et3N

Abstract

Chromatographic purification of N–H ketimines is often difficult because these compounds readily undergo hydrolysis on silica gel, regenerating the corresponding ketones during column chromatography. Combining silica gel pre-dried at 120 °C under vacuum with triethylamine (Et₃N) markedly reduces hydrolysis during chromatographic handling and establishes practical operating conditions for purification. Under the optimized conditions, hydrolysis of N–H diaryl ketimines was completely suppressed, allowing their recovery in high purity. Furthermore, a variety of N–H ketimines, including hydrolysis-sensitive alkyl derivatives, were recovered in high purity with only minimal hydrolysis. These conditions also enable isolation of N–H ketimines from mixtures containing the corresponding ketones. The conditions additionally showed a suppressive effect on the decomposition of N–R ketimines. Because the procedure requires only pre-dried silica gel and addition of Et₃N, it provides a simple and practical solution for the chromatographic purification of hydrolysis-sensitive imines.