ABSTRACT
The possibility of functionalization of 2-(polyfluorophenyl)-4H-chromen-4-ones, with them having different numbers of fluorine atoms, with 1,2,4-triazole or imidazole under conditions of base-promoted nucleophilic aromatic substitution has been shown. A high selectivity of mono-substitution was found with the use of an azole (1.5 equiv.)/NaOBut(1.5 equiv.)/MeCN system. The structural features of fluorinated mono(azolyl)-substituted flavones in crystals were established using XRD analysis. The ability of penta- and tetrafluoroflavones to form persubstituted products with triazole under azole (6 equiv.)/NaOBut(6 equiv.)/DMF conditions was found in contrast to similar transformations with imidazole. On the basis of mono(azolyl)-containing polyfluoroflavones in reactions with triazole and pyrazole, polynuclear hybrid compounds containing various azole fragments were obtained. For poly(pyrazolyl)-substituted flavones, green emission in the solid state under UV-irradiation was found, and for some derivatives, weak fungistatic activity was found.
ABSTRACT
A simple and convenient method for the synthesis of new methyl 2-(4-methoxyphenyl)- and 2-(3,4-dimethoxyphenyl)-4-oxo-4H-polyfluorochromen-3-carboxylates as analogs of natural methoxy-containing flavones is proposed. As a result of their directed modification under basic conditions, 7-imidazolyl-substituted derivatives were obtained. In aqueous-organic medium under basic conditions, 5,6,7,8-tetrafluoro-3-(methoxycarbonyl)flavones were transformed into 6,8-difluoro-5-hydroxy-7-(1H-imidazol-1-yl)-3-(methoxycarbonyl)flavones as a result of flavone-5-hydroxyflavone rearrangement, while 6,7,8-trifluorinated analogs underwent a flavone-coumarin rearrangement to give 6,8-difluoro-3-(hydroxyarylidene)-7-(1H-imidazol-1-yl)coumarins under the same conditions. Acid hydrolysis of methyl polyfluoroflavone-3-carboxylates allowed to obtain 2-aryl-4H-polyfluorochromen-4-ones. Evaluation of the antiviral activity of the synthesized compounds against influenza A (H1N1) and Coxsackie B3 viruses showed that 2-(3,4-dimethoxyphenyl)-5,6,8-trifluoro-7-(1H-imidazol-1-yl)-4H-chromene-4-one has the most promising properties.
