Improved Protocol for Thorpe Reaction: Synthesis of 4‐Amino‐1‐arylpyrazole using Solid–Liquid Phase‐Transfer Conditions

Abstract

Solid–liquid phase‐transfer conditions were employed for the first time in the Thorpe reaction to synthesize 4‐amino‐1‐aryl‐3,5‐substituted‐1H‐pyrazoles 3. Aryl amines were diazotized and coupled with various active methylene compounds such as cyano acetamide, cyanoacetophenone, malononitrile, and ethyl cyanoacetate, resulting into α‐arylhydrazononitriles 1. Cyclization of 1 using α‐bromo ketones or esters resulted in compounds 3.

Keywords:

• 4‐amino‐1‐arylpyrazole
• α‐arylhydrazononitriles
• 18‐crown‐6
• phase‐transfer catalyst
• Thorpe reaction

Acknowledgment

We thank the Regional Sophisticated Instrumentation Center, Central Drug Research Institute, Lucknow and Chandigarh, India, for ¹H NMR and mass spectral analysis and the principal and director of the Loyola Center for R & D, St. Xavier's College, Ahmedabad, India, for the facility to carry out this work.