Phosphorus oxychloride → 2,3-Dichloro-5-(4-phenoxyphenyl)isonicotinonitrile

Participants

Reaction Conditions

Reaction Steps

A suspension of 3-chloro-4-cyano-5-(4-phenoxyphenyl)pyridine 1-oxide (0.3068 g, 0.951 mmol) in phosphorus oxychloride (5 mL, 53.6 mmol) was heated to 100° C. for 1 h. The mixture was concentrated, diluted with ethyl acetate (100 mL), washed with saturated sodium bicarbonate (30 mL) and brine (30 mL), dried (MgSO4) and concentrated. Silica gel chromatography, loading with toluene and eluting with 5-15% ethyl acetate in hexanes, gave 2,3-dichloro-5-(4-phenoxyphenyl)isonicotinonitrile (156.6 mg), 2,5-dichloro-3-(4-phenoxyphenyl)isonicotinonitrile (89.4 mg) and a 2:3 mixture of the two isomers (65.4 mg). Characterization of 2,3-dichloro-5-(4-pherioxyphenyl)isonicotinonitrile: 1H NMR (400 MHz, CDCl3) δ ppm 8.49 (1H, s), 7.48-7.59 (2H, m), 7.35-7.46 (2H, m), 7.21 (1H, t, J=7.40 Hz), 7.05-7.18 (4H, m); MS (ES+) m/z: 341 (M+H); LC retention time: 4.601 min (analytical HPLC Method A). Characterization of 2,5-dichloro-3-(4-phenoxyphenyl)isonicotinonitrile: 1H NMR (400 MHz, CDCl3) δ ppm 8.56 (1H, s), 7.33-7.48 (4H, m), 7.21 (1H, t, J=7.40 Hz), 7.07-7.18 (4H, m); MS (ES+) m/z: 341 (M+H); LC retention time: 4.438 min (analytical HPLC Method A).

Provenance & Evidence