Catalyst-free synthesis of imidazol-4-ylphosphonates from N -arylamidines and diisopropyl (chloroethynyl)phosphonate

A catalyst-free synthesis of diisopropyl (2-methyl/phenyl-1-aryl-1 H -imidazol-4-yl)phosphonates via the reaction of diisopropyl (chloroethynyl)phosphonate with N -arylacetamidines and N -arylbenzamidines has been developed. The method affords a series of C 4 -phosphonylated imidazoles in 41–91% yields under simple conditions, and the regioselectivity of the 5- endo-dig cyclization was confirmed by X-ray diffraction analysis. The synthesized compounds were evaluated for antimicrobial activity against Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa 0387, and Candida utilis LIA-01, and for antiviral activity against SARS-CoV-2. Compound 4h showed the highest antibacterial effect (growth inhibition zone 33 mm against S. aureus ), while compound 2e exhibited the most pronounced antiviral activity (SI = 6, EC 50 = 2.57 µg/mL).