Ag-Catalyzed Synthesis of Pyrazoles from Propargyl N-Sulfonylhydrazones

Significance

The reported reaction procures 1,3,5-trisubstituted pyrazoles in good to excellent yields from propargyl N-sulfonylhydrazones, which are easily accessible from propargyl bromides, aldehydes and N-tosyl hydrazine. Silver hexafluoroantimonate was found to be the best catalyst, in comparison to other metals; for example, a gold salt did not furnish any products and with a platinum salt the reaction was much slower (55% yield after 18 h at 80 ˚C). Interestingly, the reaction shows an unprecedented 1,3-tosyl group migration. The same migration was observed with an N-mesyl derivative; however, N-phenyl or -benzoyl derivatives showed no reaction. A mechanism was proposed based on deuterium-labeling and cross-over experiments.

Comment

Pyrazoles have received considerable attention due to their application in pharmaceutical and agrochemical industries (J. A. Pfefferkorn et al. J. Med. Chem. 2008, 51, 31). The reported method is simple and valuable due to its efficiency, functional group compatibility, mild reaction conditions and practicality. It is also the first reported silver-catalyzed formation of pyrazoles from propargyl N-sulfonylhydrazones, even though a similar two-step reaction was reported four decades ago, effected in the presence of base with tosylhydrazones as diazo precursors, which underwent further reaction with alkynes to form pyrazoles (T. Sato, S. Watanabe Bull. Chem. Soc. Jpn. 1968, 41, 3017). Further extension of the methodology towards other nitrogen-containing heterocycles is anticipated.