3-Methoxy-4-nitrobenzonitrile → 4-Amino-3-methoxybenzonitrile

To a cooled solution of 3-methoxybenzonitrile (10 g, 75 mmol) in acetic anhydride (150 ml) was added 70% nitric acid (60 mL) at a rate that kept the reaction mixture below 50° C. After 1 h the reaction mixture was poured onto ice (400 cc) and extracted with ethyl acetate. The ethyl acetate layer was washed with water, and dried (Na2SO4). Concentration under reduced pressure and chromatography with ethyl acetate/hexanes gave 2.69 g (20%) of 3-methoxy-4-nitrobenzonitrile: 1H NMR (DMSO-d6): δ 8.04 (d, 1H), 7.93 (d, 1H), 7.61 (dd, 1H), 3.97 (s, 3H). 3-Methoxy-4-nitrobenzonitrile (2.6 g, 14.6 mmol) was suspended in ethanol(100 mL) and added to a mixture of 5% platinum on carbon (250 mg) in ethanol (150 mL). The reaction mixture was stirred under a hydrogen gas atmosphere. After 24 h the reaction was filtered, concentrated, and chromatographed (ethyl acetate/hexanes, 25/75) to yield 1.3 g (60%) of 4-amino-3-methoxybenzonitrile: 1H NMR (DMSO-d6): δ 7.1 (m, 2H), 6.65 (d, 1H), 5.77 (br s, 2H), 3.79 (s, 3H). 4-Amino-3-methoxybenzonitrile (1.3 g, 8.77 mmol) and 3,4-diethoxy-3-cyclobutene-1,2-dione (1.5 g, 8.82 mmol) in ethanol (50 mL) was heated in an oil bath at 110°-115° C. for 3 days. The reaction mixture was filtered hot, and the filtrate was reduced to half its volume. Filtration gave 0.58 g (24%) of a yellow solid: mp 159°-161° C.; 1H NMR (DMSO-d6): δ 10.42 (br s, 1H), 7.54 (d, 1H), 7.44 (dd, 1H), 7.39 (d, 1H), 4.70 (q, 2H), 3.86 (s, 3H), 1.36 (t, 3H). IR (KBr): 3413, 3026, 2650, 2576, 2439, 1719, 1630, 1548 cm-1 ; MS (m/z) 272 (M+).

1. filtrationAfter 24 h the reaction was filtered
2. concentrationconcentrated
3. customchromatographed (ethyl acetate/hexanes, 25/75)

ORD record

ord-fc3d0231cf6e41e69462b151e7c3eea1

Source dataset

uspto-grants-1996_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05506252