Improved Methods for the Oxidation of Secondary Amines to Nitroxides

Abstract

Biologically active spin labeled compounds have recently gained significant prominance as molecular probes in several areas of research^1–4. The most generally useful method described in the literature for oxidizing a secondary amine to a stable nitroxyl free radical requires the use of a water solution of hydrogen peroxide with a catalytic amount of sodium tungstate⁴. Unfortunately, this procedure fails in the case of secondary amines with minimal water solubility. A number of alternative oxidative procedures have been described in the literature. For example, the oxides of lead, mercury and silver as well as an alkaline solution of potassium ferricyanide have been employed⁵. In the case of aromatic amines, which are not generally oxidized by tungstate salts, t-butyl hydroperoxide (in the presence of catalytic amounts of cobalt stearate) as well as p-nitroperbenzoic acid in dioxane⁶ have given the desired product.