Amination of nitrobenzene via nucleophilic aromatic substitution for hydrogen: direct formation of aromatic amide bonds

Abstract

The first example of the direct formation of aromatic amide bonds via nucleophilic aromatic substitution for hydrogen is described. Thus, the reaction of benzamide, tetramethylammonium hydroxide dihydrate, and nitrobenzene under anaerobic conditions generates N-(4-nitrophenyl)-benzamide (1) (98%) and azoxybenzene (30%) in isolated yields. In addition, other substituted benzamides and aliphatic amides are shown to function as nucleophiles in this reaction. A mechanism that is consistent with the simultaneous formation of anilide products and azoxybenzene which requires the oxidation of α-complex intermediates by nitrobenzene initially generating nitrobenzene radical anions is proposed. By contrast, when the reaction is run under aerobic conditions, the formation of azoxybenzene is completely inhibited due to the trapping of nitroarene radicals by O 2 . The ability to prepare (1) in high yield and regioselectivity affotds a nouvel route for the direct amination of nitrobenzene that does not require halogenated intermediated or auxiliary leaving groups. Accordingly, treatment of (1) with methanolic ammonia results in the aminolysis of the amide bond producing 4-nitroaniline and regenerates benzamide