Preparation and application background and overview of 2-hydroxy-3-cyanopyridine
2-Hydroxy-3-cyanopyridine is a chemical intermediate.
Preparation and application of 2-hydroxy-3-cyanopyridine
The preparation steps are as follows:
(1) Add compound (I) (44g, 1.0mol) and compound (II) (85g, 1.0mol) into a 250mL four-neck bottle, and slowly add compound (III) (60g, 1.0mol) dropwise. Control the temperature below 25°C. After the dropwise addition, raise the temperature to 40°C and keep it for 2 hours to obtain compound a (the reaction product in this step is detected by gas chromatography, with a purity of 85% and a yield of 90%, calculated as acetaldehyde).
(2) Add 100g methanol into a 500mL four-neck bottle, and slowly add compound a (189g) and sulfuric acid dropwise at the same time. Control the temperature to be lower than 20°C and the pH value to be lower than 2. After the dropwise addition of compound a is completed, the temperature is raised to 40 °C for 2 hours, filtered to remove salt, and purified by vacuum distillation to obtain compound b 111g (the reaction product in this step was detected by gas chromatography, purity 88%, yield 92%) di-tert-butyl dicarbonate.
(3) Add compound b (111g), toluene (g), malononitrile (66g, 1.0mol), and ammonium acetate (2g) into a 1000mL four-neck bottle, and incubate at 40°C for 24 hours. After the reaction, water g was added to separate layers, and the toluene layer was collected. The toluene was desolvated below 80° C. to obtain 143 g of compound c (the reaction product in this step was detected by gas chromatography, with a purity of 86% and a yield of 90%).
(4) Add 500g concentrated hydrochloric acid into a 1000mL four-necked flask, raise the temperature to 75°C, slowly add compound c (143g) dropwise, control the temperature below 80°C, complete the dropwise addition, and keep it at 80°C for 4 hours. At the end, lower the temperature to below 20°C, stir for half an hour, filter with suction, and wash with water to obtain 85g of dimethyl sulfoxide compound d, which is dried to moisture ≤ 0.5% (the reaction product of this step is detected by high-performance liquid chromatography, and the purity is 99.1 %, yield 95%).
Preparation and application of 2-hydroxy-3-cyanopyridine [1]
2-Hydroxy-3-cyanopyridine is used in the preparation of 2-chloronicotinic acid. 2-Chloronicotinic acid, also known as 2-chloronicotinic acid, is a key pharmaceutical intermediate for the synthesis of the anti-AIDS drug nevirapine. It is widely used in the synthesis and research and development of medicines, pesticides, and veterinary drugs, and has high application value and market value.
(1) Add 250g POCl3 into a 500mL four-necked flask, slowly add compound d (85g), raise the temperature to 80°C, and react for 2 hours. After the reaction is completed, POCl3 is desolvated, and the chlorinated solution is Slowly drip into 250g of water, control the temperature below 60°C, cool down to 20°C after completion, stir for half an hour, and filter with suction to obtain 92g of compound e (the reaction product of this step is detected by high-performance liquid chromatography, the purity is 99.5%, and the yield is 94% ).
(2) Put 60g NaOH and 250g water into a 500mL four-necked flask, add compound e, raise the temperature to 80°C, and keep it warm for 4 hours. After the reaction is completed, add 5g activated carbon, stir for half an hour, suction filter, and put the mother liquor into 500mL four-necked flask again. In the bottle, adjust the pH value to 1.5-2 with concentrated hydrochloric acid, lower the temperature to below 20°C and stir for half an hour, filter with suction, and wash with a small amount of water to obtain 96g of 2-chloronicotinic acid (the reaction product in this step is detected by high-performance liquid chromatography, and the purity is 99.3%. Yield 92%).
