Ultrasound Assisted Synthesis of 1,5-Disubstituted Pyrazole using Cu(I) Catalyst

Abstract

A new efficient and convenient approach towards the synthesis of pyrazole is described. The α,β-unsaturated cyanoesters were obtained from substituted benzaldehyde and ethyl cyanoacetate by reported methods. 1,5-Disubstituted pyrazoles were synthesized from α,β-unsaturated cyanoester and phenyl hydrazine using sodium ethoxide as a base in the presence of 10 mol % Cu(I) catalyst in high yields within 75-90 min under ultrasound irradiation at 60 ºC. The reaction rate is enhanced tremendously under ultrasound irradiation as compare to conventional methods with improved yields are recorded.

Synthetic Strategies and Biological Activities of 1,5-Disubstituted Pyrazoles and 2,5-Disubstituted Thiazoles

“…From a mechanistic perspective, the authors proposed that copper coordinates easily to π-bonds and heteroatoms. This would lead to the formation of the C-N bond via an oxidative addition followed by reductive elimination, similar to that observed in Pd(0) cross coupling reactions [5].…”

“…In another recent report, Cu(I) catalyst, Cu(PPh 3 ) 2 NO 3 was used to synthesize 1,5-disubstituted pyrazoles from hydrazines 22 and α,β-unsaturated cyanoester 23 under ultrasound irradiation (Figure 8) [5]. This efficient route uses short reaction times, moderate temperatures, facile work-ups, high regioselectivity and yields [5].…”