Mild synthesis of 2,3,5,6-tetrafluoropyridine ethers and their reactivity toward imidazole and pyrazole

Abstract

A series of six, 4-substituted 2,3,5,6-tetrafluoropyridine (TFP) hetero ethers have been synthesized via regio-selective, nucleophilic aromatic substitution (SNAr) of pentafluoropyridine with aliphatic alcohols and phenols. Furthermore, the hexyloxy modified TFP substrate also served as a synthetic intermediate for the preparation of 3,5-difluoro-4-(hexyloxy)-2,6-di(1H-imidazol-1-yl)pyridine, as well as 4-(hexyloxy)-2,3,5,6-tetra(1H-pyrazol-1-yl)pyridine, which offers a terpyridine scaffold. This work outlines their synthetic methodology in addition to detailing the TFP intermediates’ unexpected reactivity with imidazole and pyrazole nucleophiles