Sulfuric acid mediated heterocyclization of ortho-cyanomethylnitroarenes to benzo[c]isoxazoles and fused benzo[c]isoxazoles

The vicarious nucleophilic substitution of hydrogen (VNS) is used as the key step to convert substituted 5-nitrobenzimidazoles 1a-b into their ortho-cyanomethyl derivatives 2a-b. Conc. sulfuric acid mediated heterocyclization of these intermediates gave the novel 3H-imidazo[4',5':3,4]benzo[c]isoxazole-8-carboxamides 3a-b. To generalize this synthetic strategy for benzo[c]isoxazoles syntheses, the VNS products of para-substituted nitrobenzene 4a-d were successfully converted to the new benzo[c]isoxazoles derivatives 5a-d.