Conjugate addition with organometallics and nitration of nitroxide (aminoxyl) free radicals. Synthesis of potentially useful cross-linking spin label reagents

Abstract

3-Methoxycarbonyl-2,2,5,5-tetramethyl-2,5-dihydropyrrol-1-oxyl (1) was converted with PhMgBr–Cul in a conjugate addition into 3-methoxycarbonyl-2,2,5,5-tetramethyl-4-phenylpyrrolidin-1-oxyl (2). Compound (2) was nitrated with concentrated H₂SO₄/HNO₃ to give the para-nitrophenyl derivative (5). Nitration of other phenyl substituted nitroxides was also investigated. The reaction in strong acids could be carried out in the presence of an acid-sensitive nitroxide free radical. An alkyl nitro compound has also been prepared: a conjugate addition of nitromethane to (1) gave 3-methoxycarbonyl-2,2,5,5-tetramethyl-4-nitromethylpyrrolidin-1-oxyl (20). Both (2) and (20) could be transformed by transfer hydrogenation to amino compounds and then in several steps to potentially useful cross-linking spin label reagents.