2-Bromo-3-cyanopyridine

20577-27-9

20577-26-8

General procedure for the synthesis of 2-bromo-3-cyanopyridine from 2-oxo-1,2-dihydropyridine-3-carbonitrile: First, 2-chloro-3-cyanopyridine (3.68 mg, 26 mmol) was refluxed in acetic acid (100 mL) for 12 hours. After completion of the reaction, the evaporated residue was dissolved in a solvent mixture of tetrahydrofuran (80 mL) and water (20 mL) and refluxed for 4 hours. Evaporation of the solvent gave 3-cyanopyridin-2-one (3.12 g, quantitative yield) as white crystals with a melting point of 110-114 °C (literature value 13174-175 °C). Its nuclear magnetic resonance hydrogen spectrum (1H NMR) showed δ 6.47 (1H, t, J = 6.6 Hz, 5-H), 7.91 (1H, dd, J = 6.5, 2.1 Hz, 4-H), 8.14 (1H, dd, J = 7.0, 2.1 Hz, 6-H), and 11.48 (1H, s, 1-H); and nuclear magnetic resonance carbon spectrum (13C NMR) showed δ 105.80 (3-C), 124.05 (5-C), 141.87 (CN), 144.50 (6-H), 150.02 (4-C), 154.20 (2-C); mass spectrum (MS) m/z 143.0214 (M + Na)+ (calculated value C6H4N2NaO 143.0222). Next, tetrabutylammonium bromide (Bu4NBr, 8.55 g, 26 mmol) and phosphorus pentoxide (P2O5, 3.67 g, 26 mmol) were heated in toluene (250 mL) at 80 °C for 30 min. Then 3-cyanopyridin-2-one (1.59 g, 13 mmol) prepared above was added and the mixture was refluxed for 12 hours. After completion of the reaction, the mixture was cooled, poured into cold water and extracted twice with ethyl acetate. The organic layers were combined, dried and the solvent was evaporated to give 2-bromo-3-cyanopyridine (2.24 g, 94% yield) as white crystals with a melting point of 114-118 °C (literature values 14 °C, 105 °C). Infrared spectra (IR) showed νmax 2236, 1574, 1550, 1472 cm-1 ; nuclear magnetic resonance hydrogen spectra (1H NMR, CDCl3) showed δ 7.42 (1H, dd, J = 7.7, 4.8 Hz, 5-H), 8.01 (1H, dd, J = 7.8, 2.0 Hz, 4-H), 8.57 (1H, dd, J = 4.9, 2.0 Hz, 6-H); nuclear magnetic resonance carbon spectrum (13C NMR) showed δ 114.27 (3-C), 115.63 (CN), 122.37 (5-C), 142.53 (4-C), 143.84 (2-C), 152.92 (6-C).