3-Aminoquinoline → 3-Fluoroquinoline

Participants

Reaction Conditions

Reaction Steps

23.5 g of 3-aminoquinoline and 12.1 g of sodium nitrite in 20 cm3 of distilled water were added cautiously to 100 cm3 of tetrafluoroboric acid cooled to about 0° C., with vigorous stirring, and the reaction mixture was thus stirred for 30 minutes. The suspension was filtered, spin-filtered, washed with 3 times 30 cm3 of ice-cold tetrafluoroboric acid, 50 cm3 of ice-cold ethanol and 4 times 30 cm3 of diethyl ether. The solid was dried in a desiccator (2 kPa) in the region of 20° C. and then taken up in 200 cm3 of toluene and heated at a temperature in the region of 90° C. for 1 hour with stirring. After cooling to about 20° C., the phases of the reaction mass were separated by settling and the insoluble oil was washed with 3 times 100 cm3 of toluene and taken up in 110 cm3 of water, which was basified by slow addition of sodium hydrogen carbonate so that the pH was at about 8. The aqueous phase was extracted with 5 times 100 cm3 of diethyl ether and the organic phases were combined, washed with twice 50 cm3 of water, dried over magnesium sulfate and taken up with vegetable charcoal (3S), filtered and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 45° C. The oil was taken up in 50 cm3 of a 40-60° C. petroleum ether/ethyl acetate mixture (90/10 by volume) and the insoluble material was filtered off, rinsed with twice 25 cm3 of a 40-60° C. petroleum ether/ethyl acetate mixture (90/10 by volume) and dried in a desiccator under reduced pressure (2 kPa) at a temperature in the region of 20° C. The filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 5 cm; height 45 cm), eluting with a 40-60° C. petroleum ether/ethyl acetate mixture (90/10 by volume) and collecting 100-cm3 fractions. Fractions 20 to 31 were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 13 g of 3-fluoroquinoline were obtained in the form of a colorless liquid.

Provenance & Evidence