Base-Promoted Eco-Friendly Synthesis Of Trisubstituted Pyrazoles Under Metal- And Solvent-Free Condition

Pyrazole is one of the important N-heterocycle broadly found in many natural products and pharmaceutically active molecules and frequently used as useful ligands for metal catalyzed cross-coupling reactions in organic synthesis, biological medicine and material science. Several methods have been reported for the synthesis of substituted pyrazoles by literatures. However, the use of hazardous transition metals, harsh reaction conditions, tedious workup procedures as well as poor regioselectivity are the main drawbacks of many of these methods. To overcome these difficulties, the development of more convenient and efficient synthetic methodologies is still desirable.This paper mainly described a simple, efficient and green method for the synthesis of trisubstituted pyrazoles from α,β-alkynic N-tosylhydrazones under metal- and solvent-free conditions. Only iPr2NH was required as the promotor here and the reaction can be easily performed at room temperature and also in gram scale. It was found that the reaction proceeded smoothly over a wide range of substrates and afforded the corresponding pyrazoles in high yields. This approach displayed some advantages compared to the conventional methods, such as shorter reaction time, mild reaction temperature, high isolated yields as well as regioselectivities, and the ease of purification of the products. In addition, we proposed a possible mechanism of this transformation.On the other hand, we have investigated the Pd-catalyzed coupling reactions of α,β-alkynic hydrazones with benzyl halides. Although a lot of experiments have been performed, the satisfactory results has not yet obtained. Further exploitation is currently underway in our laboratory.