When is a trifluoromethyl group more lipophilic than a methyl group? Partition coefficients and selected chemical shifts of aliphatic alcohols and trifluoroalcohols.
Octanol-water partition coefficients were determined for 12 trifluoromethylated aliphatic alcohols and their unfluorinated counterparts. The latter values were derived from measurements using the benzyl alcohol-water solvent system after developing an appropriate correlation equation. Incidentally, an empirical equation was found which allows the partition coefficient of an unsubstituted alcohol to be estimated given the molecular formula and boiling point. Trifluorination strongly enhances lipophilicity only when the trifluoromethyl group is in the alpha-position. The enhancement is barely measurable for the beta- and gamma-(trifluoromethyl) alcohols, while the delta- and epsilon-(trifluoromethyl) compounds are considerably more hydrophilic than their parent compounds. Chemical shift comparisons suggest that the changes in relative lipophilicity are controlled primarily by the inductive effect of the trifluoromethyl group on the acidity-basicity of the hydroxyl group. New synthetic procedures for obtaining some of the alcohols are presented.
D000438:Alcohols / Q000032:analysis*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006845:Hydrocarbons, Fluorinated / Q000032:analysis*; D008055:Lipids; D009682:Magnetic Resonance Spectroscopy; D012995:Solubility
D000438:Alcohols; D006845:Hydrocarbons, Fluorinated; D008055:Lipids