Tandem aqueous extract of onion catalyzed Knoevenagel condensation-Michael addition-cyclization: A green synthesis of 2-amino- 3-cyano-4H-pyran derivatives and their anti-oxidant and molecular docking studies

Abstract

Aqueous extract of onion catalyzed tandem process incorporating Knoevenagel condensation followed by Michael addition-cyclization is revealed using aldehyde 1, malononitrile 2a and an active methylene compound 3. This method caused diverse 2-amino- 3-cyano-4H-pyran annulated heterocyclic scaffolds in excellent yields (up to 98 %). The synthesized compounds 4ah were also analyzed by single-crystal X-ray diffraction. The reactivity of the active methylene compounds and reasonable mechanism for sequential tandem reactions have been described. Also, this methodology has a simple, easy workup, short reaction time, without column chromatography and eco-friendly reaction conditions. Seventeen out of forty-five synthesized pyran derivatives were screened for their in vitro antioxidant studies. Among the compounds 4ai, 4aj, 4al, 4cd, 4ca, 4cb, 4cc, 4cd have shown excellent and 4aa, 4ac, 4ae, 4ah have exhibited comparable antioxidant activity with ascorbic acid standard. Compounds 4ch-4ck exhibited excellent antioxidant activity than standard. Moreover, mushroom tyrosinase (mh-Tyr) has performed molecular docking properties.