Preparation background and overview of 3,4,5-trichloropyridine
3,4,5-Trichloropyridine can be used as an intermediate for pharmaceutical and chemical synthesis. If 3,4,5-trichloropyridine is inhaled, move the patient to fresh air; if the skin comes in contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel uncomfortable; if the eyes contact If exposed to sunlight, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.
Preparation structure of 3,4,5-trichloropyridine
Preparation and application of 3,4,5-trichloropyridine
3,4,5-Trichloropyridine can be used as an intermediate for pharmaceutical and chemical synthesis, such as preparing 3,5-difluoro-4-[4-(trifluoromethoxy)phenoxy]pyridine, specific steps To prepare a mixture of 3,4,5-trifluoropyridine (135 mg, 1.0 mmol), 4-trifluoromethoxy (200 mg, 1.1 mmol), anhydrous potassium carbonate (210 mg, 1.5 mmol) and anhydrous DMF (2 mL ) and stir at 25°C for 18 hours. The resulting mixture was partitioned between ethyl acetate and water, the organic phase was washed with water, dried (Celite column) and concentrated. The crude product was purified by medium-pressure liquid chromatography on a silica column, eluting with a gradient of 0% to 50% ethyl acetate in hexane, to afford the title compound, synthesized fluorphlogopite as a colorless oil (129 mg) . 19F NMR (CDCl 3) delta -58.33 (s, 3F), -140.27.
Preparation of 3,4,5-trichloropyridine
The preparation of 3,4,5-trichloropyridine is as follows:
Step 1: Heat a stirred solution of 4-pyridinol (1.0 equiv) in acetonitrile (15.0 vol) and water (0.1 vol) to 40°C, then add N-chlorosuccinamide (2.2 equiv) in portions . The reaction mixture was stirred at 45-55°C for 6-8 hours and the reaction progress was monitored by HPLC. After the reaction is complete, the reaction is cooled and stirred for 3-4 hours. The solids were filtered and washed with acetonitrile (1 x 2.0 vol) and water (5.0 vol + 2.0 vol). The product was dried in an oven to constant weight.
Step 2: To a stirred suspension of 3,5-dichloro-4-pyridinol (1.0 equiv) in acetonitrile (5.0 vol) was added POCb (2.0 equiv). The reaction mixture was heated to 50-55°C and stirred for 24 hours. The reaction progress was monitored by HPLC. Bromopyridine dihydrochloride. After the reaction is complete, the mixture is cooled. The reaction mixture was then slowly poured into water (5.0 vol) at 2-10 °C. The mixture was stirred for 20-30 minutes and the pH was adjusted to 9-10 with 50% NaOH (aq). The temperature was raised to 25-30°C and the mixture was extracted with n-heptane (1 x 18.0 vol, 2 x 10.0 vol).
Wash the combined organic layers with water (1 × 5.0 volume), then add activated carbon (15% w/w) and stir for 1-2 hours. The organic phase was filtered through a hyflo bed and the filter cake was washed with heptane (2.0 vol). The collected organic phase is concentrated under vacuum at 40°C or less until up to 1.0 volume is present. The mixture was cooled to 25-30°C and water (2.0 vol) was added. The mixture was concentrated again under vacuum to remove more heptane. Stop concentration when less than 2.0 volume is present. Water (5.0 vol) was added and the mixture was stirred for 2-3 hours. The solid was isolated by filtration and washed with water (2.0 vol). Dry in a vacuum oven at 40-45°C until constant weight. 1H NMR (600MHz, chloroform-d) δ8.52 (s, 2H)
