SYNTHESIS OF FLUORINE ANALOGS OF VITAMIN-E .4. SYNTHESIS OF BIS(TRIFLUOROMETHYL)TOCOPHEROLS

We previously synthesized mono(trifluoromethyl)tocopherols, which were used for investigation of the mobility and orientation of tocopherol in liposomes by F-19-NMR. For more precise investigation of the behavi or of vitamin E in liposomes, tocopherols having two trifluoromethyl g roups, one on the prenyl side chain and the other on the chromanol rin g, were synthesized. Thus, dimethylhydroquinones were treated with 6-c hloro-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 k etones followed by hydrogenation, gave tocopherols with a trifluoromet hyl group on the side chain and a hydrogen on the chromanol part. Thes e were halogenated on the chromanol part and treated with trifluoromet hyl iodide and copper powder to give the title compounds.