Substituent-controlled visible light photoisomerization and cyclodimerization of styryl pyrimidinones

Visible light-driven E/Z photoisomerization is an attractive strategy for controlling reactivity and biological activity; however, targeted design of heterocyclic bioactive compounds requires a solid understanding of how substituent effects govern productive isomerization and competing photochemical pathways. Here, a series of 6-methyl-2-styryl-pyrimidine-4(3H)-one derivatives with previously reported antifungal and antimicrobial activity of E-isomers were studied by LED-NMR spectroscopy under visiblelight irradiation at 405-450 nm. Pronounced substituent-dependent differences were observed in the efficiency of E/Z photoisomerization, the stability of the corresponding Z-isomers, and the formation of [2 + 2] cycloaddition products. Derivatives bearing electron-donating groups showed particularly efficient photoresponse, with up to 95% conversion to the Z-isomer within 1-3 h at moderate irradiation power below 1 W. The resulting Z-isomers showed appreciable thermal stability, with half-lives ranging from several hours to several days. Quantum chemical calculations were used to rationalize the observed substituent effects and photoreaction outcomes. Among the computed descriptors, the oscillator strength f _S1 (E) was found to be the most informative. This descriptor represented the absorption-related contribution to photoconversion, and favorable transition intensities were calculated for derivatives bearing OMe-type donor-substituted phenyl groups attached to the vinylene fragment. These results establish substituted 6-methyl-2-styryl-pyrimidine-4(3H)-ones as a visible light-responsive scaffold in which photoconversion, Z-isomer stability, and competing cycloaddition can be tuned by substituent design.