Indium-mediated Reductive Inter-molecular Coupling Reaction of 2-Nitroaniline with Aromatic Aldehydes to Benzimidazoles

2-Nitroaniline and aromatic aldehydes were coupled to give benzimidazoles in high yields in the presence of 2-bromo-2-nitropropane and indium at room temperature.Since the first reported use of indium in organic synthesis in 1975 by Rieke, 1 its application for organic synthesis has been widely developed due to its low ionic potential and aqueous conditions. 2,3 In particular, indium-mediated reactions in aqueous media have been the focus of synthetic applications because of environmental issues and the ease of the reactions, which do not require flammable anhydrous organic solvents or an inert atmosphere. 4 The first ionization potential of indium (5.8 eV) is much lower than that of zinc (9.4 eV) or tin (7.3 eV), and even magnesium (7.6 eV) and thus indium metal should participate readily in SET (single electron transfer) processes and therefore be a potential reducing reagent.Recently, indium has been extensively used in various reductive reactions: reductive coupling of aldimines, 5 reductive elimination of 1,2-dibromides, 6 pinacol couplings, 7 ketone deoxygenation, 8 reductive dehalogenation of α-halocarbonyl compounds, benzyl halides and halomethylcephalosporins, 9 reduction of azides, 10 and N-oxides, 11 reductive coupling of acyl cyanides, 12 reduction of nitrostyrenes, 13 oximes, 14 and other nitro compounds, 2b, 10c, 15, 16d and selective reduction of heterocyclic rings.2d In our continuing study on the application of 2-bromo-2-nitropropane (BNP) and metals to reductive heterocyclization, 16 we examined indium metal as an electron donor and discovered that 2-bromo-2nitropropane and indium are effective to reductive cyclization of 2-substituted nitroarenes to give the corresponding 2,1-benzisoxazoles.16d For the intermolecular ring formation, we examined intermolecular