Safe and Scaleable Oxidation of Benzaldoximes to Benzohydroximinoyl Chlorides^†

Abstract

Benzohydroximinoyl chlorides are useful precursors to nitrile oxides used in the preparation of various heterocycles via 1,3-dipolar cycloadditions. These intermediates are typically accessed by oxidation of aldoximes using N -chlorosuccinimide. This simple and efficient reaction is highly exothermic and a significant induction period can be observed. The potential for a sudden and significant heat release makes large-scale reactions difficult to control and potentially hazardous. Herein we describe a thermal analysis of this reaction to determine the heat flow in the presence of common additives to determine the most effective means of safe scale-up. Of the additives screened, aqueous HCl consistently avoided an induction period and enabled a dose-controlled process to be developed.