Overview of the preparation of 2-amino-5-trifluoromethylpyridine
2-Amino-5-trifluoromethylpyridine is a key intermediate in synthetic medicine (drugs for the treatment of cardiovascular and cerebrovascular diseases). It has good curative effect, rapid effect, and no side effects. It is an indispensable new medicine for cardiovascular and cerebrovascular patients. . Very popular in the international market. 2-Amino-5-trifluoromethylpyridine is not only a new pharmaceutical and pesticide intermediate, but also widely used in the fields of organic synthesis and dyes. In recent years, it has been found that the introduction of trifluoromethyl group into the heterocyclic ring can improve the lipophilicity of the compound. , thereby improving the efficacy of the drug, improving the permeability of biological membranes and tissues and the electron attraction during biological reactions, and enhancing the physiological activity of the compound. At present, 2-amino-5-trifluoromethylpyridine has been widely used in medicine, pesticides, dyes and other fields. Existing technology: 2-amino-5-trifluoromethylpyridine developed by a Japanese company uses 3-trifluoromethylpyridine as the main raw material to undergo a nitrification reduction reaction. Only 60% of the product is produced, and there is a lot of waste acid and waste water. , environmental protection issues are difficult to solve, and the product purity is low, only 96% content.
Preparation of 2-amino-5-trifluoromethylpyridine
The preparation of 2-amino-5-trifluoromethylpyridine is as follows:
(1) Ammonolysis: Pump 1300g of raw materials 2-chloro-5-trifluoromethylsulfoxide pyridine, 1700g of methanol, and 1462g of liquid ammonia into a 5L autoclave, start stirring and raise the temperature, and control the inside of the autoclave Temperature 120-135℃, pressure 2.0-3.5Mpa. , keep the reaction for 16 hours, cool to 60°C, and slowly release the pressure to 0.0Mpa. Blow in air and inflate for more than 2 hours until NH3 is gone. Pump the reaction liquid into the methanol distillation kettle, and evaporate the methanol under normal pressure. When the methanol content in the amino compound is less than 10%, stop distillation, cool down to 50°C, pump a large amount of water into the kettle, wash, stand still, and separate. Obtain the crude amino product and put it into a 5000ml beaker.
(2) Refining: Put the crude amino product into the reduced pressure refining kettle and turn on the vacuum. When the vacuum reaches -0.086Mpa, the refining kettle begins to heat up to 140°C. When there is reflux at the top of the tower, Control the heating and maintain full reflux for 30 minutes, then press extraction: reflux = 1:8, distill under reduced pressure, and the extracted fraction enters the front fraction receiving tank. Sampling is performed once every 10 minutes. Chromatographic tracking analysis is performed. When the content of the main fraction reaches more than 99% , the extracted fraction is cut into the finished product receiving tank. At this time, the reflux ratio is controlled at 1:4. When the kettle temperature rises and the tower top temperature drops, the sodium bicarbonate adjusts the reflux ratio to 1:8, sampling once every 5 minutes, and chromatographic tracking After analysis, when the content of the main fraction is lower than 98%, the extraction is stopped, the temperature is cooled, and the system is vented. After the system is at normal pressure, the vacuum pump is stopped, and the front fraction, finished product, and rear fraction are measured to get the finished product packaged and stored in the warehouse. Product yield is 85%.
