Sustainable, one-pot multicomponent synthesis of 1,4-dihydropyridines, benzylidene malononitriles and tetrahydrobenzo[b]pyrans using copper nanoparticles: Exploration of green chemistry metrics and antioxidant potential

Abstract

Background

Development of one-pot sustainable methodologies are of high interest in organic synthesis and medicinal chemistry. Researchers focused their efforts for the development of one-pot multicomponent reactions (MCRs) to access heterocyclic scaffolds utilising novel nanomaterials. Herein, the catalytic performance of biogenic cuprous oxide nanoparticles (BCONPs) was explored in MCRs along with exploration of green chemistry metrics, ensuring sustainable aspects of reactions.

Methods

Nanocatalyst was synthesized by green co-precipitation method and characterized by variegated characterization techniques including FT-IR, P-XRD, XPS, TEM, FE-SEM, and EDX; and demonstrated excellent catalytic activity. Developed protocols afforded 1,4-dihydropyridines (1,4-DHPs), benzylidene malononitrile, and tetrahydrobenzo[b]pyran (THBP) derivatives. Various green chemistry metrics such as TON, TOF, AE, AEf, RME, OE, and E-factor for each derivative based on electron withdrawing and donating influence was evaluated which proved efficacy, sustainability, and scalability of the processes. Also, EcoScale score was calculated for each developed protocol. In addition, in vitro and in silico antioxidant potential of all compounds was explored.

Significant Findings

Developed methods afforded important heterocyclic scaffolds including 1,4-DHPs, and THBPs along with, benzylidene malononitriles in high yields under mild conditions tolerating various functionalities with exploration of green chemistry metrics. An EcoScale score above 75 % was achieved for each protocol. These BCONPs were applicable for gram scale synthesis and recyclable up to five times, sustaining catalytic function. 1,4-DHPs especially with electron donating functionalities showed excellent antioxidant activity.