Preparation of 4-chloro-3-nitropyridine_Industrial additives

Preparation background and overview of 4-chloro-3-nitropyridine

Pyridine and its derivatives are important intermediates for the synthesis of heterocyclic compounds, pesticides and medicines. It is known that the benzene ring in a compound may have higher biological activity or lower toxicity after being replaced by a pyridine ring. Therefore, pyridine and its derivatives are potentially important intermediates for the development of new pesticides and medicines.

4-Chloro-3-nitropyridine is a very important class of pyridine derivatives. It can be used as a viscosity regulator and can be used to synthesize the anti-sodium carbonate (decahydrate) ulcer drug pirenzepine and diazepam. Heterozoic anti-AIDS drugs, leukotriene biosynthesis inhibitors, and can be used as drug intermediates for pesticides. Therefore, the research on the synthesis of 4-chloro-3-nitropyridine is of great significance. The currently commonly used method is to use 3-nitropyridine as raw material. First, a chlorination reaction occurs under the action of hydrogen peroxide and hydrochloric acid. This method has a simple reaction, but has many by-products and a low product yield.

Preparation of 4-chloro-3-nitropyridine

The preparation method of 4-chloro-3-nitropyridine includes the following steps:

(1) Mix 5 mol of 4-hydroxypyridine and ionic liquid and stir evenly, add concentrated nitric acid while stirring, continue stirring for 10 minutes, add 1 mol of mesoporous silica, raise the temperature to 95°C, stir for 2 hours, and cool to room temperature. In an ice-salt bath, add concentrated ammonia dropwise while stirring, adjust the pH to 5-7, add desamidomethylpyridinium ionized water, stir until complete precipitation, filter, wash the precipitate with deionized water 2-5 times, and dry it , obtaining 4-hydroxy-3-nitropyridine;

(2) Mix 4 mol of 4-hydroxy-3-nitropyridine and 2 mol of phosphorus oxychloride obtained in step (1) and stir evenly. Add 1 mol of thionyl chloride dropwise. After the dropwise addition is completed, raise the temperature to 90 °C, reflux for 3 hours. After the reflux is completed, add deionized water, extract with dichloromethane, and then remove the dichloromethane under negative pressure to obtain 4-chloro-3-nitropyridine.