A facile preparation of 2-bromodifluoromethyl benzo-1,3-diazoles and its application in the synthesis of gem-difluoromethylene linked aryl ether compounds

A facile preparation of 2-bromodifluoromethyl benzo-1,3-diazoles as novel CF2Br-containing heterocyclic building blocks has been developed through a one-pot process of reaction of 2-OH, 2-SH, or 2-NH2 substituted aniline with bromodifluoroacetic acid in the presence of 3 molar equivalents of CBr4 and Ph3P in refluxing toluene. 2-Bromodifluoromethyl benzo-1,3-thiazole (2b) was successfully utilized in the preparation of gem-difluoromethylene linked aryl ether compounds through the reaction with phenolates or thiophenolate in DMF in good yields.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A facile one-pot preparation of 2-bromodifluoromethyl benzo-1,3-diazoles was disclosed. ► CF2Br-containing heterocyclic building blocks were rarely reported in the past. ► The reaction mechanism involves the formation imidoyl bromide and intramolecular ring-closure reaction. ► The 2-bromodifluoromethyl benzo-1,3-thiazole building block was successfully utilized. ► gem-Difluoromethylene linked benzothiazole-containing aryl ethers were synthesized.