Synthesis of N -phenyl- and N -thiazolyl-1 H -indazoles by copper-catalyzed intramolecular N -arylation of ortho -chlorinated arylhydrazones.

The broad application of 1 H -indazoles has prompted the development of several approaches for the synthesis of such compounds, including metal-free, palladium-, or copper-promoted intramolecular N -arylation of in situ-generated or isolated o -haloarylhydrazones. Such methods mainly start from o -bromo derivatives due to the better yield observed when compared to those obtained from o -chloroarylhydrazones. However, the o -chloroarylaldehydes and o -chloroarylketones used to prepare the arylhydrazones are more commercially available and less expensive than brominated analogs. Seeking to cover a lack in the literature, this work reports a convenient protocol for the synthesis of N -phenyl- and N -thiazolyl-1 H -indazoles by copper-catalyzed intramolecular N -arylation of o -chlorinated arylhydrazones. Therefore, a series of seven N -phenyl derivatives and a series of six novel N -thiazolyl derivatives was obtained in 10-70% and 12-35% yield, respectively, after stirring the o -chlorinated arylhydrazones, CuI, KOH, and 1,10-phenantroline for 12-48 hours in DMF at 120 °C. The products were isolated by column chromatography on silica gel. All products were fully characterized by HRMS as well as 1 H and 13 C NMR spectroscopy. Thus, this approach is valuable for promoting the synthesis of N -phenyl-1 H -indazoles in a higher yield than that reported in the literature using copper catalysis and the same substrates. This study also prompted the first reported synthesis of pharmacologically interesting N -thiazolyl derivatives.