Indium metal has recently drawn increasing attention because of environmental issues and the ease of reactions [1]. Of our special interest was the possibility of utilizing indium promoted reaction for the preparation of various nitrogen containing heterocycles as an extension of our study on reductive cyclizations of 2-nitroarenes [2]. Thus, we examined various reaction conditions using indium to develop efficient and new heterocylization reactions, and found that indium/iodine-mediated reactions could successfully transform 2-nitroaroyls to 2,1-benzisoxazoles in MeOH. However, reductive reactions of N-[(2-nitroaryl)methylene]benzenamines in the presence of indium/iodine in MeOH, mixtures of 2,1-benzisoxazoles and indazoles were produced. Indazole formation was in some way unexpected. As indazoles have attracted much attention for their pharmaceutical activities, such as anti-tumor and anti-HIV, the reductive reactions of N-[(2-nitroaryl)methylene]benzenamines reinvestigated at the point of the indazole formation. Consequently, we found that N-[(2-nitrophenyl)methylene]benzenamine in the presence of indium, iodine, and excess amount of aniline was mainly cyclized to (2-phenyl-2H-indazol-3-yl)phenylamine in THF solution. In general, reductive cyclizations of various N-[(2-nitroaryl)methylene]arenamines were successful using excess amount of corresponding aniline derivatives, which are the subunit of substrate, i.e. bold of Ar-CH=N-Ar (method A). However, substituents of 2- and 3-position of indazoles were mainly dependent upon the nature of added anilines regardless of the nature of subunit of starting substrate. Consequently, reaction of (2-phenyl-2H-indazol-3-yl)phenylamine in the presence of indium, iodine, and excess amount of p-toluidine produced [2-(4-methylphenyl)-2H-indazol-3-yl]-4-methylphenylamine (Method B). Herein, we report synthetic and mechanistic consideration for the indium/iodine-mediated heterocyclizations of 2-nitro-substituted iminobenzenes to indazoles.

[1] H. Yamamoto, K. Oshima, Main Group Metals in Organic Synthesis, Wiley-VCH: Weinheim, 2004; Vol. 1, Ch. 8, pp. 323.

[2] B. H. Kim, Y. Jin, R. Han, W. Baik, B. M. Lee, Tetrahedron Lett. 2000, 41, 2137, 4244 and references cited therein.

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