Base‐Promoted Multicomponent Synthesis of 4‐Phosphorylated‐2 H ‐Phenylchromenes and Antibacterial Activity Evaluation

ABSTRACT An efficient synthesis of a series of 4‐phosphorylated‐2 H ‐chromenes has been developed via one‐pot multicomponent reaction of salicylaldehyde, β ‐nitrostyrene, and H ‐phosphonates/ H ‐phosphine oxide using DABCO as a base, delivering the desired products within a short reaction time of 5–20 min. This method demonstrates broad substrate scope and affords excellent yields ranging from 70%–92%. The resulting compounds were characterized by 1 H, 13 C, and 31 P NMR and HRMS analysis. The compounds were evaluated for their in vitro antibacterial activity against three pathogenic bacterial strains E. coli , S. aureus , and K. pneumoniae . Among all the tested compounds, 4p and 4q showed antibacterial activity comparable to the standard antibiotic novobiocin against all tested strains with corresponding MIC values of 2 µg/mL for each. Additionally, in silico molecular docking studies revealed compound 4s has strong binding affinity of −10.2 kCal/mol against S. aureus and compound 4j exhibited a docking score of ‐9.0 kCal/mol against E. coli . Further DFT analyses of compounds 4c , 4j , 4p , 4q , 4o, and 4t were performed to elucidate the electronic stability. Owing to its operational simplicity, high efficiency and metal‐free nature, this protocol provides a valuable synthetic platform for accessing novel phosphorus‐containing heterocycles, which may hold potential for future drug discovery.