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

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.