Biletska І. Synthesis and properties of 2-(3,3,3-trifluoroacetonyl)chromones

A convenient approach for introducing fluorine-containing fragments into the molecules of 2-alkyl-substituted chromone derivatives is proposed for the first time by their interaction with trifluoroacetic anhydride in the presence of CF3COOK. Methods for the synthesis of 3-trifluoromethyl-5-phenacylpyrazoles, 3- trifluoromethyl-5-phenacylisoxazoles, and 3-trifluoromethylpyrazole-deoxybenzoin hybrids have been developed, opening up the possibility of constructing biologically promising 3-trifluoromethyl derivatives of azoles. Conditions for conducting the Fischer reaction involving 3-trifluoromethyl-5- phenacylpyrazoles and 3-trifluoromethyl-5-phenacylisoxazoles with derivatives of arylhydrazines have been established, which represents a promising method for the synthesis of 3-(3-trifluoromethylpyrazol-5-yl)indoles and 3-(3-trifluoro- methylisoxazol-5-yl)indoles. As a result of the investigation, a focused library on the platform of 3- trifluoromethylpyrazole-deoxybenzoin hybrids, 3-(trifluoromethyl)-5- phenacylpyrazoles, 3-(trifluoromethyl)-5-phenacylisoxazoles, as well as 3-(3- trifluoromethylpyrazol-5-yl)indoles was synthesized. These compounds are promising cyclooxygenase-2 (COX-2) inhibitors due to their structural similarity to known trifluoromethylpyrazole-based inhibitors, as well as plausible antiproliferative activity. The obtained results expand the understanding of the mechanisms and directions of the reaction of chromone derivatives with bidentate nucleophiles.