5,6-Dimethylpyridin-3-amine → 5-Fluoro-2,3-dimethyl-1-oxidopyridin-1-ium

Participants

Reaction Steps

Sodium nitrite (5.6 g) was added portionwise to a stirred solution of 5-amino-3-methyl-2-picoline (5 g) in conc. hydrochloric acid (25 ml) and water (30 ml) at -5° to 0° over 15 minutes. After a further 15 minutes at this temperature, 65% hexafluorophosphoric acid (25 ml) was added dropwise causing precipitation of the hexafluorophosphate salt which was filtered off, washed with water, ethanol, and ether and dried under vacuum (12.33 g). The salt was added portionwise, with rapid stirring, to petroleum ether (100 ml, b.p. 120°-160°) at 60° over 20 minutes. After a further 5 minutes the mixture was cooled to room temperature, the petroleum ether layer decanted, and extracted with 2N hydrochloric acid. The acidic and oily residues were combined, extracted with ether, basified (NaOH) and extracted again with dichloromethane. After drying (K2CO3), m-chloroperbenzoic acid (8.45 g) was added to the dichloromethane solution and the mixture allowed to stand for 16 hours. Ammonia gas was passed through the solution and the precipitated benzoate salts filtered off. The filtrate was evaporated to dryness to give 2,3-dimethyl-5-fluoropyridine-N-oxide (2.66 g) m.p. indeterminate.

Provenance & Evidence