Regioselectivity and relative substrate activity of difluoroquinolines containing fluorine atoms in benzene ring in reaction with sodium methoxide

Methoxydefluorination of 5,7-, 6,7-, 6,8-, and 5,8-difluoroquinoline (1-4) by the action of sodium methoxide has been studied in liquid ammonia and Me2SO. The regioselectivity of methoxydefluorination of 1 and 2 in the temperature interval 218-240 K in liquid ammonia and 1 and 4 in the interval 298-378 K in Me2SO as well as the activity correlation of individual reaction centers in different substrates have been established as enthalpically controlled. The overall pattern of relative reactivity is consistent with the ab initio (RHF/6-31G*) calculated relative stabilities and electronic structures of the σ-complexes formed by the substrates with the hydroxide anion as a model nucleophile.