ortho-Aryloxylation of N-substituted benzamides: a new oxidizing process induced by the copper(II)/trimethylamine N-oxide system

Abstract

The oxidation of N-(2-hydroxy-4-nitrophenyl)benzamide 1 by the Cu^II/trimethylamine N-oxide couple has been studied. Under experimental conditions where the concentration quotient, α=[1]/[Cu], of starting benzamide to copper is maintained as low as possible, the benzamide is ortho-hydroxylated into the corresponding salicylamide with 88% yield of isolated product. On the other hand, when α is kept as high as possible, a new oxidation process leads to an oxidative cascade: the benzamide is ortho-aryloxylated by the phenolic group of a second molecule of itself to afford a 2-aryloxy-N-(2-hydroxy-4-nitrophenyl)benzamide, which in turn can undergo another ortho-aryloxylation. In intermediate conditions both processes are in competition, thus providing composite compounds such as a 6-aryloxy-2-hydroxy-N-(2-hydroxy-4-nitrophenyl)benzamide. Transitory formation of, respectively, Cu^III-OH and Cu^III-OAr complexes is suggested to be responsible for these ortho-selective oxidizing processes. Finally, these results show that the 2-(N-amido)-5-nitrophenol group (which is the copper ligand) is a good mediator for the oxidation of a covalently linked aromatic nucleus by the Cu^II/TMAO system.