N-Difluoromethylindazoles

Abstract

Aim. To study the possibility of the N-difluoromethylation and separation of 1-difluoromethyl and 2-difluoromethyl isomers of C-substituted indazoles, as well as some possibilities of functionalization of such molecules. Results and discussion. The N-difluoromethylation of indazole derivatives containing bromine, iodine, and nitro groups in various positions of the heterocyclic ring was studied. In all cases, the conditions for the separation of isomers – N-difluoromethylation products – in positions 1 and 2 were found. The corresponding amines, esters of carboxylic and boric acids were obtained as a result of further functionalization of 1- and 2-difluoromethylindazole derivatives. Experimental part. The structure of the compounds synthesized was proven by 1H and 19F NMR spectroscopy methods, as well as by the elemental analysis. The structure of isomeric difluoromethylindazoles was finally confirmed by the SELNOESY and 1H-13C HMBC experiments. Conclusions. A convenient method for the difluoromethylation of substituted indazoles has been found; difluoromethyl derivatives in positions 1 and 2 of the indazole ring have been obtained in high yields. The method for the efficient separation of isomeric difluoromethylindazoles has been found; some possibilities of their further functionalization have been described.

Keywords

• indazoles
• n-difluoromethylation
• isomer separation