Effect of ω-trifluorination on the microsomal metabolism of ethyl and pent-1-yl p-nitrophenyl ether

Abstract

1. p-Nitrophenyl pent-1-yl ether was metabolized (65–70%) in the presence of liver microsomes from phenobarbital-treated rats to give the 4-(major), 3-(minor), and 2-hydroxypent-1-yl (minor) derivatives which were characterized by g.l.c.-mass spectrometry; O-dealkylation (reflecting 1-hydroxylation) and 5-hydroxylation did not occur to a significant extent.

2. 5,5,5-Trifluorination of the pent-1-yl group markedly reduced the extent of metabolism (to ∼10%).

3. p-Nitrophenyl 2,2,2-trifluoroethyl ether was virtually completely resistant to microsomal metabolism under conditions where the ethyl analogue was extensively O-dealkylated.