The regioselectivity in the fluorination of dibenzofuran, diphenylether and biphenyl with N-F type of reagents

Abstract

Dibenzofuran, diphenylether and biphenyl were used as a target molecules in an investigation of the effect of N-F type of reagent structure and reaction conditions on the fluorination process. The yields of fluorinated products formed and the regioselectivity depend on the reagent used, and in the reactions with dibenzofuran three products were formed. The ratios of 2-fluorodibenzofuran ( 4) and 3-fluorodibenzofuran ( 5) formed were: 1.3 for 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (NFTh, 1b), 1.4 for 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (F-TEDA, 1a), and 1.8 for N-fluoro-2,6-dichloropyridinium tetrafluoroborate (FPD-B, 1c). Ortho regioselectivity predominated for all reagents in the fluorination of biphenyl (ortho : para ratio varied from 4.8 to 1.2), while para attack prevailed for diphenylether (ortho : para = 0.9 – 0.7); however substitution of a phenyl ring by a methyl group enhanced the amount of 2-fluoroanisole. Second order rate constants for the fluorination of aromatic molecules with F-TEDA in acetonitrile at 65°C were established: anisole 4.8×10 −3 Lmol −1s −1, diphenylether 6.0×10 −4 Lmol −1s −1, dibenzofuran 2.5×10 −4 Lmol −1s −1 and biphenyl 1.0×10 −4 Lmol −1s −1.