Synthesis process of 4,6-dichloropyrimidine

Abstract

The invention provides a synthesis process of 4,6-dichloropyrimidine. The synthesis process takes thionyl chloride as a chlorinating agent and solvent for reactions, 4,6-dihydroxypyrimidine as a raw material, and N, N-dimethyl aniline as a catalyst. Compared with the prior art, thionyl chloride is used as a chlorinating agent and a solvent for reactions during the preparation process of 4,6-dichloropyrimidine, and no other organic solvent is introduced, so that the influence of other solvents on the product is reduced. According to the invention, less wastewater is generated; the finally generated wastewater is mainly composed of a salt solution of sodium sulfite and sodium chloride; excessive thionyl chloride is recycled in a rectification mode, the part of generated wastewater is only limited to the consumed thionyl chloride part, about 6-7 kg of wastewater is generated from 1 kg of 4,6-dichloropyrimidine product, and solid salt is obtained through concentration and crystallization in wastewater after treatment.

Description

technical field [0001] The invention relates to the synthesis of a drug intermediate raw material, in particular to a synthesis process of 4,6-dichloropyrimidine, which belongs to the field of organic chemistry. Background technique [0002] 4,6-Dichloropyrimidine is a heterocyclic compound. Due to its special structure, it is widely used in medicine and pesticides. It is an important intermediate for the synthesis of sulfonamides and the fungicide azoxystrobin. Due to the large market demand, the research on 4,6-dichloropyrimidine should be increased to improve the industrial production level. [0003] At present, there are mainly three existing techniques for synthesizing 4,6-dichloropyrimidine, which are respectively one: 4,6-dihydroxypyrimidine reacts with phosphorus oxychloride under the action of an organic base to obtain 4,6-dichloropyrimidine; : 4,6-dihydroxypyrimidine reacts with phosphorus oxychloride, phosphorus trichloride and chlorine to obtain 4,6-dichloropyri...

AI Technical Summary

Problems solved by technology

The process of the first method is relatively simple, the main disadvantage is that a large amount of phosphorus-containing wastewater is generated, the wastewater treatment is difficult, the investment is large, and it does not conform to the concept of environmental protection

The second method greatly reduces the amount of wastewater, but a large amount of phosphorus oxychloride is used as a solvent in the process, and the reaction process will consume phosphorus oxychloride to generate impurities, resulting in waste of resources and increasing the cost of post-treatment

The third method does not produce a large amount of waste water during the reaction process, and the by-products are easy to treat and have high purity. However, because the reaction is a two-phase reaction, the conversion rate of raw materials is low, and there are also great difficulties in the use and transportation of raw materials.

The patent introduces dichloroethane as a solvent, and the solvent loss is relatively large in the process of desolventization and product crystallization and purification; dichloroethane is a highly toxic chemical and is very dangerous; in the preparation of 4,6-dichloropyrimidine In the reaction, the addition of thionyl chloride is excessive, because the boiling point of thionyl chloride is slightly lower than dichloroethane, it is not easy to separate the excess thionyl chloride earlier by distillation, and the excess oxychloride The sulfone needs to be digested, and the treatment method is generally to add alkaline water, or thermal decomposition to generate gas for reabsorption, which will generate a large amount of waste water; the product is purified by crystallization, and the steps are relatively cumbersome

[0006] Those of ordinary skill in the art generally believe that when 4,6-dihydroxypyrimidine is chlorinated by thionyl chloride to prepare 4,6-dichloropyrimidine, an additional organic solvent needs to be added to promote the reaction and increase product content and yield , only adding chlorinating agents and catalysts, without adding organic solvents, tends to reduce product content and yield