Regiochemistry and mechanism of oxidation of N-benzyl-N-alkylhydroxylamines to nitrones

The oxidation of various N-(o-, m-, p-substituted benzyl)-N-alkylhydroxylamines and their dideuteriobenzyl (PhCD₂) counterparts was carried out using mercury(II) oxide and p-benzoquinone (p-BQ) as oxidants. An overwhelming preference for the formation of conjugated nitrones is observed in the oxidation of N-benzyl-N-isopropylhydroxylamines. Considerable intra- and intermolecular kinetic isotope effects and negative ρ values in the Hammet plots point towards a mechanistic pathway that involves electron transfer from nitrogen to the oxidant followed by hydrogen abstraction. The conformation of unstable (E)-nitrones, which readily isomerize to the more stable (Z)-nitrones, is deduced from ¹H NMR data. The E ⇌ Z isomerization was found to be a bimolecular process.