5-Bromo-2-nitropyridine

500 L of glacial acetic acid and 150 L of acetic acid recovered in were charged into a 1000 L autoclave, and the circulating water was stirred and stirred. After homogeneous mixing, 120 kg of 2-amino-5-bromopyridine was slowly added and the temperature was controlled at 20C. , Stirring 30min, slowly dropping 300kg peracetic acid, when dropping to about 50kg, the temperature began to slowly rise, stop dropping, when the temperature does not rise began to decline, and then dropping the remaining amount, until the peracetic acid plus Finished, the whole process temperature control at 30 . After completion of the dropwise addition, the temperature was controlled at 40 ° C and the reaction was carried out at constant temperature for 20 hours. When the reaction is complete, vacuum distillation, steaming about 600L acetic acid, to stop the distillation. The remaining liquid cooling to 25 , and then add 500L of water, with 40percent sodium hydroxide solution to adjust the pH value of the material to 8, cooled to -20 , filtration, drying, 125kg solid, crude The yield was 89.3percent. The recrystallized product was 120.5kg and the yield was 86.1percent.Add 1000ml of 30percent hydrogen peroxide solution to a 1000ml three-neck reaction flask, cool down to 15 °C with a low temperature reaction bath, and drop 320ml of 98percent concentrated sulfuric acid into the hydrogen peroxide water in the reaction bottle with a constant pressure dropping funnel. The temperature of the solution in the bottle is controlled at 5 In the range of -15 ° C, the solution B was added dropwise. At the same time, 160ml of 98percent concentrated sulfuric acid was added to another 1000ml three-neck reaction flask, and 60.00g of 2-amino-5-bromopyridine was added in batches by a low temperature reaction bath, and the temperature was controlled within the range of 5-15 °C.The solution A was obtained after the addition.The A and B solutions are all prepared, and the solution B is added dropwise to the solution A by a constant pressure dropping funnel, and the temperature of the reaction bottle is controlled by the low temperature reaction bath in the range of 0-10 ° C, and the optimum temperature is 5 ° C. The temperature change value was not more than 3 ° C. After the dropwise addition was completed, the reaction liquid was slowly heated to 50 ° C, the reaction was continued for 3 hours, and the sample was taken for TLC analysis to disappear.Add 5000 ml of water to a 5000 ml three-neck reaction flask, and cool to within 15 ° C. The above reaction solution is added to water with a constant pressure dropping funnel while stirring, and the temperature is controlled within a range of -15 ° C. After the dropwise addition is completed, Continue stirring for 18-20 minutes. At 5-15 ° C, 720 g of 30percent liquid alkali was added, stirring was continued for 0.5 hours, then filtered under reduced pressure, washed with 100 ml of water, and the filter cake was neutralized with a dilute alkali to pH = 7 and filtered again. The resulting solid was recrystallized from methanol and filtered hot.Dry to give a pale yellow solid of 51.13 g of product.Yield 73.4percent, The purity of the product liquid chromatography is greater than 99percent.Reference 5-Bromo-2-nitro-pyridine. A solution of 2-amino-5-bromo-pyridine (5 g, 28.9 mmol) in cone, sulfuric acid (10 mL) was added dropwise to a cold (0