Sustainable synthesis of piperazine analogs using varied energy sources in the petasis reaction: A green chemistry perspective

Abstract

The Petasis reaction between substituted boronic acids (1a-c), N-Boc-piperazine, and glyoxylic acid in the conventional method of synthesis needs continuous refluxing for 16 h in a solvent like acetonitrile (ACN) to obtain the products. Using the same reactants, the source of energy was changed to microwave irradiation, ultrasonication, or mechanical energy (Trituration) to obtain good yields of the products consuming much less energy and time. Apart from the use of different sources of energy, the solvents as the media of the reactants were also changed. In microwave synthesis, more than 95% yield was obtained for the products in the presence of ACN/dichloromethane as solvents. In the sonication method, the yield ranged from 76 to 98% while in the trituration method, the yield decreased to 76-82% in the presence of various polar protic/aprotic solvents. Microwave irradiation or ultrasonication provides good alternatives to refluxing the reaction mixture continuously for a long time.. KEYWORDS :Microwave synthesis, Multicomponent reactions, Petasis reaction, Sonication, Trituration.