The mechanism of base-promoted HF elimination from 4-fluoro-4-(4′-nitrophenyl)butan-2-one:: A multiple isotope effect study including the leaving group 18F/19F KIE

Leaving-group fluorine as well as the primary and secondary deuterium kinetic isotope effects (KIEs)) have been determined for the base-promoted elimination of hydrogen fluoride from 4-fluoro-4-(4'-nitrophenyl)-butan-2-one in aqueous solution. The elimination was studied for formate, acetate, and imidazole as the catalyzing base. The fluorine KIEs were determined using the accelerator-produced short-lived radionuclide F-18 in combination with natural F-19. The F-19 substrate was labeled with C-14 in a remote position to enable radioactivity measurement of both isotopic substrates. The elimination reaction exhibits large primary deuterium KIEs: 3.2, 3.7; and 7.5 for formate: acetate, and imidazole, respectively, thus excluding the El mechanism. The corresponding C-4-secondary deuterium KIEs are 1.038, 1.050 and 1.014 and the leaving group fluorine KIEs are 1.0037, 1.0047 and 1.0013, respectively. The size of the fluorine KIEs corresponds to 5-15% of the estimated maximum of 1.03 for complete C-F bond breakage. No H/D exchange is observed during the reaction. The size and trends of the KIEs for the different bases are consistent with an E1cB like E2 or an E1cB(ip) mechanism.