Sulfuric Acid → 6-Methoxynaphthalen-2-amine

Participants

Reaction Conditions

Reaction Steps

A 2-necked 100 mL round bottom flask was charged with commercially available 2-acetyl-6-methoxynapthalene(5.0 g, 25 mmol) and trifluoroacetic acid (500 mmol, 38 mL) and fitted with a reflux condenser and a stopper. The solution was heated to 120° C. and sodium azide (3.25 g, 50 mmol) was added over 30 minutes. Each addition resulted in a visible exotherm. Gas evolution ceased 30 minutes after complete addition of the azide. The reaction was cooled and poured into excess saturated aqueous sodium bicarbonate. The resulting mixture was extracted (2×, ethyl acetate). The combined organic extracts were washed (2×, brine), dried (Na2SO4), filtered and concentrated in vacuo to afford a light red solid which was a mixture (~5:1) of the respective N-acetyl-6-methoxynapthylamine and N-methylaminocarbonyl-6-methoxynapthalene. The mixture was carried on without purification. The unpurified solid (4.51 g, 20.9 mmol) was dissolved in hot ethanol (100 mL). Water (15 mL) and concentrated sulfuric acid (2.24 g, 41.9 mmol) were added and the reaction heated at reflux for 24 h during which time a thick precipitate formed. The reaction was cooled to 0° C. and the solid 2-amino-6-methoxynapthalene hydrogen sulfate salt was collected by filtration. The salt was neutralized by partitioning between aqueous sodium hydroxide(15.8 g, 0.396 mmol in 200 mL of water) and ethyl acetate. The layers were separated and the aqueous layer extracted with ethyl acetate (2×). The organic layers were combined, washed (brine, 3×), dried (Na2SO4), filtered and concentrated in vacuo to afford a purple solid. Recrystallization from ethyl acetate and acetone gave the title compound in three fractions (2.64 g, 61%) as a light beige solid. mp 133°-136° C.

Provenance & Evidence