Microwave-assisted one-pot lemon-juice-catalyzed synthesis of trifluoromethyl coumarin-based 4H-Pyran hybrids and their antimicrobial evaluation

A green and efficient microwave-assisted one-pot multicomponent strategy was developed for the synthesis of novel trifluoromethyl coumarin-based 4H-pyran hybrids using freshly extracted lemon juice as a natural biocatalyst. The reaction of 7-hydroxy-4-(trifluoromethyl)coumarin, malononitrile, and various aromatic/heteroaromatic aldehydes in an ethanol:water (1:1) medium under microwave irradiation afforded a series of 2-amino-8-oxo-4-aryl-6-(trifluoromethyl)-4,8-dihydropyrano[3,2-g]chromene-3-carbonitrile derivatives (4a-p) in excellent yields (86-94%) within 4-8 min. Optimization studies identified lemon juice (5 mL) under 300 W microwave irradiation as the most effective and environmentally benign catalytic system. Kinetic studies revealed pseudo-first-order behaviour, confirming the high efficiency of the lemon juice-microwave protocol. All synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, 19F-NMR, mass spectrometry, and elemental analysis. Biological screening demonstrated promising antibacterial and antifungal activities, with compounds (4l), (4m), and (4i) exhibiting the highest potency and MIC values comparable to standard drugs against selected microbial strains. Structure-activity relationship studies revealed that electron-withdrawing substituents on the aryl ring significantly enhanced antimicrobial activity. Overall, this sustainable methodology offers rapid access to biologically relevant fluorinated heterocycles and identifies promising lead molecules for the development of new antimicrobial agents.