M. Koyama et al., SYNTHESIS OF FLUORINE ANALOGS OF VITAMIN-E .4. SYNTHESIS OF BIS(TRIFLUOROMETHYL)TOCOPHEROLS, Chemical and Pharmaceutical Bulletin, 43(9), 1995, pp. 1466-1474
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.