Impact of fluorine substituents on the rates of nucleophilic aliphatic substitution and β-elimination

A measure of the quantitative effect of proximate fluorine substituents on the rates of SN2 and E2 reactions has been obtained through a study mainly of reactions of fluorinated n-alkyl bromides with weak base, strong nucleophile azide ion and strong base/nucleophile methoxide ion in the protic solvent methanol and the aprotic solvent, DMSO. The order of reactivity for SN2 reactions of azide in methanol at 50 °C was found to be: n-alkyl-Br > n-alkyl-CHFBr > n-perfluoroalkyl-CH2CH2Br ≫ n-perfluoroalkyl-CH2Br > n-alkyl-CF2Br. Approximate relative rates of reaction were: 1, 0.20, 0.12, 1 × 10−4, <7.7 × 10−5. The order of reactivity for E2 reactions was found to be: n-perfluoroalkyl-CH2CH2Br ≫ n-alkyl-CF2Br > n-alkyl-CHFBr > n-alkyl-Br. The approximate relative rates for reaction of methoxide in methanol at 50 °C were: 1100, 4.4, 1.9, 1.

α,α or -Fluorine substitution can have a profound effect upon the rates of substitution or elimination of an alkyl halide.Figure optionsDownload as PowerPoint slideHighlights
► Rates of bimolecular substitution by azide and methoxide are reported for a series of partially fluorinated alkyl bromides.
► Rates of β-elimination by methoxide are reported for a series of partially fluorinated alkyl bromides.
► Rates of substitution by azide and methoxide are reported for bromodifluoromethylbenzene.
► Fluorine in the vicinity of a carbon–halogen bond has a significant effect on its rates of either substitution or elimination.