Selective Reduction of Doxyl and Proxyl Nitroxide Carboxylic Acids to the Corresponding Alcohols with Borane Methyl Sulfide

Abstract

Doxyl² (4,4-dimethyloxazolidine-N-oxy1) nitroxides and the more recently introduced proxyl³ (for example, 8) nitroxides are important stable free radicals for the study of biological systems using the spin labeling technique.⁴ Chemical transformations on molecules already bearing a nitroxide grouping lead to new nitroxide spin labels, providing of course, that the synthetic steps do not destroy the somewhat sensitive nitroxide grouping.⁴ We wish to report that nitroxide carboxylic acids can be smoothly reduced to the corresponding nitroxide alcohols in high yield using borane methyl sulfide⁵ in ether solution at 25°C. Heretofore, LiAlH₄ has been employed for this reduction.⁶ Since borane methyl sulfide and LiAlH₄ differ considerably in their reactivity toward other functional groups⁵, the borane methyl sulfide reagent constitutes a valuable alternative to LiAlH₄ for chemically modifying nitroxide carboxylic acids which also bear other functional groups susceptible toward reduction by LiAlH₄.