α-Heteroatom-Substituted Nitrones. Synthesis and Reactions of Acyclic α-Alkoxynitrones

Article abstract of DOI:10.1021/jo00268a043

A general method was developed for the synthesis of acyclic α-alkoxynitrones (imidate N-oxides), a relatively new class of compounds.Regioselective alkylation of hydroxamic acids under neutral conditions with alkyl trifluoromethanesulfonates (triflates) gave nitrone hydrotriflates, and deprotonation by one of three methods gave the rather unstable nitrones in overall yields from 4 to 85percent.A wide range of substitution was possible, with R = H, Me, or Ar, R1 = Me or t-Bu, and R2 = Me or Et.The reactivity of these nitrones toward examples of various classes of reagents was investigated.Nitrone 3e (R = H, R1 = t-Bu, R2 = Me), the most reactive one studied, gave the following results: (1) with nucleophiles (aniline, n-butylamine, thiophenol, n-butyl mercaptan, and potassium cyanide), substitution of the α-OMe group produced new nitrones with amino, thio, and cyano groups in the α position; (2) with a reducing agent (NaBH4), N-tert-butylnitrone was formed; (3) with an oxidizing agent (m-chloroperbenzoic acid), oxidation and cleavage gave methyl formate and 2-methyl-2-nitrosopropane monomer and dimer; (4) with an electrophilic acylating agent (p-nitrobenzoyl chloride), methyl p-nitrobenzoate, N,O-bis(p-nitrobenzoyl)-N-tert-butylhydroxylamine, and N-tert-butyl-O-(p-nitrobenzoyl)hydroxylamine were produced.In parallel with the similar reactivity of aldo- and ketonitrones to ketones, the present α-alkoxynitrones undergo reactions analogous to those of esters with nucleophilic-type reagents.