Green protocol for the synthesis of 2-amino-4-chromene-3-carbonitrile derivatives utilizing pyridine-2-carboxylic acid as a rapid catalyst.

This study investigates the green synthesis of 2-amino-4-chromene-3-carbonitrile derivatives using pyridine-2-carboxylic acid (P2CA) as a sustainable and rapid catalyst. The reaction employs a one-pot multicomponent approach, combining various substituted aldehydes, malononitrile, and dimedone in a water-EtOH (1 : 1) solvent mixture under reflux conditions. Optimization of the reaction conditions revealed that P2CA (15 mol%) facilitated high yields of up to 98% in short reaction times while adhering to green chemistry principles. Control experiments, mechanistic studies and plausible mechanisms demonstrated the catalyst's dual acid-base behaviour, which drives the formation of intermediates and the selective generation of products. The process showed significant green metrics, including a high Atom Economy (AE) (99.36%) and a low -factor (16.68), confirming its greenness with EcoScale of 82 (>75, excellent synthesis). Furthermore, gram-scale synthesis validated the method's scalability and potential for industrial applications, instilling confidence in its practicality and widespread use. The catalyst's recyclability was established, with consistent performance observed over four cycles. A comparative analysis with previously reported catalysts highlighted P2CA's competitive efficiency and industrial applicability. This work underscores the utility of P2CA as a versatile and sustainable catalyst, contributing to the development of eco-efficient methodologies for synthesizing 4-chromene derivatives. The potential impact of this research is inspiring as it paves the way for more sustainable chemical synthesis practices.