Synthesis of Fluorine Analogs of Vitamin E. IV. Synthesis of Bis(trifluoromethyl)tocopherols.

Abstract

We previously synthesized mono(trifluoromethyl)tocopherols, which were used for investigation of the mobility and orientation of tocopherol in Iliposomes by 19F-NMR. For more precise investigation of the behavior of vitamin E in liposomes, tocopherols having two trifluoromethyl groups, one on the prenyl side chain and the other on the chromanol ring, were synthesized. Thusn, dimethylhydroquinones were treated with 6-chloro-3-methyl-2-hexenol in the presence of zinc chloride to give 2-(3-chloropropyl)trimethylchromanol derivatives. These were converted to phosphonium salts, which, upon condensation with trifluoromethylated ketones followed by hydrogenation, gave tocopherols with a trifluoromethyl group on the side chain and a hydrogen on the chromanol part. These were halogenated on the chromanol part and treated with trifluoromethyl iodide and copper powder to give the title compounds.