The synthesis of aromatic amines is an active and important area of research.² Many methods are available in the literature for the synthesis of these compounds. Though some of these are widely used, still they have limitations based on safety or handling considerations. For example, catalytic hydrogenation³ of nitro or azido compounds in the presence of metals such as palladium on carbon or Raney nickel require stringent precautions because of their flammable nature in the presence of air. In addition, these methods require compressed hydrogen gas and a vacuum pump to create high pressure within the reaction flask. To overcome these difficulties, several new methods have been reported in the recent literature⁴ involving such reducing agents as decaborane,⁵ electrochemically generated Raney nickel,⁶ dimethyl hydrazine/ferric chloride,⁷ hydrazine hydrate/ferric oxide-magnesium oxide,⁸ diethyl chlorophosphite,⁹ and sodium borohydride-sodium-methoxide in methanol¹⁰ In general, the main drawbacks of these methods are long reaction time and non-chemoselectivity. The submitters¹¹ have also described new methods for the reduction of aromatic nitro compounds and imines to aromatic amines by novel samarium-induced iodine catalyzed and ammonium chloride mediated reduction.¹² While our samarium-induced reduction of aromatic nitro compounds works well in the polycarbocyclic series, similar reaction with several heteroaromatic nitro compounds results in a mixture of products under identical conditions. Moreover, samarium-induced reduction of the nitro compounds requires anhydrous reaction conditions.

The submitters have been actively involved in the use of polyaromatic amines for the development of anticancer agents.¹³ Therefore, the submitters began a research program aimed at developing methods to synthesize several aromatic amines rapidly and in high selectivity, by using ecologically friendly reagents. The present study describes a method for the selective reduction of aromatic nitro compounds to the corresponding amines by indium in the presence of ammonium chloride in aqueous ethanol.¹⁴

The chemistry of indium metal is the subject of current investigation, especially since the reactions induced by it can be performed in aqueous solution.¹⁵ The selective reductions of ethyl 4-nitrobenzoate (entry 1), 2-nitrobenzyl alcohol (entry 2), 1-bromo-4-nitrobenzene (entry 3), 4-nitrocinnamyl alcohol (entry 4), 4-nitrobenzonitrile (entry 5), 4-nitrobenzamide (entry 6), 4-nitroanisole (entry 7), and 2-nitrofluorenone (entry 8) with indium metal in the presence of ammonium chloride using aqueous ethanol were performed and the corresponding amines were produced in good yield. These results indicate a useful selectivity in the reduction procedure. For example, ester, nitrile, bromo, amide, benzylic ketone, benzylic alcohol, aromatic ether, and unsaturated bonds remained unaffected during this transformation. Many of the previous methods produce a mixture of compounds. Other metals like zinc, tin, and iron usually require acid-catalysts for the activation process, with resultant problems of waste disposal.

Because of the non-flammable nature of the process and ready availability of indium and ammonium chloride, the submitters believe this method is practical for the preparation of several aromatic amines. Further, this method is performed in aqueous ethanol, is extremely safe from the environmental point of view, and should prove useful in organic chemistry.