Report background and overview of several preparation methods of 3-bromo-2-chloropyridine
3-Bromo-2-chloropyridine is a white to yellow-white organic intermediate of bromopyridine dihydrochloride. It has been reported in the literature that it can be prepared from 3-amino-2-chloropyridine through diazotization reaction or by 2-Chloropyridine-3-carboxylic acid and 2,3-dibromopyridine are prepared through a one-step reaction.
Several preparation methods of 3-bromo-2-chloropyridine reported
Report on several preparation methods of 3-bromo-2-chloropyridine 1.
Water (45ml) and 48% hydrobromic acid (27ml) were added to 3-amino-2-chloropyridine (2.57g, 20mmol) at room temperature. At room temperature, 2,2,6,6-tetramethylpiperidine 1-oxyl (0.31 g, 2 mmol) was added to the mixed solution, and the mixture was cooled to 10°C or lower. Then, sodium nitrite (4.14g) dissolved in water (30ml) was added. After stirring at room temperature for about 2 hours, 10 mol/L sodium hydroxide aqueous solution (40 ml) was added, followed by extraction twice with toluene (300 ml). The toluene layers were combined and washed with water (50 ml). The solvent was distilled off by concentrating the toluene layer under reduced pressure to obtain 3-bromo-2-chloropyridine (7) (3.08 g, 80.1%).
Report 2 on several preparation methods of 3-bromo-2-chloropyridine,
2-Chloropyridine-3-carboxylic acid (0.02 mmol, 3.1 mg) Tri-tert-butylphosphine tetrafluoroborate, Ag2O (0.02 mmol, 4.6 mg) at 110°C ) and tBu3PAuC1 (0.02 mmol, 8.7 mg) was stirred in DMF (0.3 mL) for 3 h. Cool the mixture to 50°C. To the above mixture was added NBS (0.022 mmol, 3.9 mg). Stir the mixture for an hour. The reaction mixture was filtered through cotton wool to obtain 3-bromo-2-chloropyridine.
Report 3 on several preparation methods of 3-bromo-2-chloropyridine,
Under a nitrogen atmosphere, TMSCH2Li (6 mL, 5.52 mmol) was added dropwise to 2-dimethylaminoethanol (1.84 mmol) in hexane (1.84 mmol) cooled to 0°C. 6 mL) solution. The mixture was stirred at 0°C for 30 minutes. A solution of 2,3-dibromopyridine (1.84 mmol) in toluene (2 mL) was added dropwise. The red solution obtained was stirred at 0°C for 30 minutes. Treat dropwise with a solution of C2Cl6 (2.2 mmol) in THF (2 mL) at -20°C. Stir the mixture for 1 hour. Hydrolyze the mixture with water (10 mL). The organic layer was extracted with diethyl ether (10 mL) and dried over MgSO4. The solvent was evaporated from the mixture. The crude product was subjected to GC analysis and purified by column chromatography using a (hexane/AcOEt:8/2) mixture as eluent to obtain 3-bromo-2-chloropyridine.
References
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