Synthesis method of 4,6-dichloropyrimidine with 4,6-dihydroxypyrimidine serving as midbody

Abstract

The invention provides a synthesis method of 4,6-dichloropyrimidine with 4,6-dihydroxypyrimidine serving as a midbody. The synthesis method mainly comprises the following steps: adding sodium methylate, dimethyl malonate and formamide into a reaction kettle, fully stirring, then increasing the system temperature, performing heat preservation reaction to remove byproducts, slowly adding sodium methylate drop by drop again, keeping the temperature for half an hour after completion of adding, and performing desolventizing; adding water when the solution is hot, and stirring to cool the solution to realize crystallization; performing centrifugal spin-drying to obtain centrifugal filtrate and crystallized solids, intensively refining and recycling the filtrate, and directly esterifying solid sodium salt; transferring for alkaline hydrolysis, and filtering to obtain a 4,6-dihydroxy pyridine solution; adding trichloromethane and a pyridine catalyst; stirring, slowly feeding phosgene and controlling the reaction temperature; decompressing to distill redundant trichloromethane, and continuously performing suction filtration, concentration and crystallization to obtain white needle-shaped products. The preparation method disclosed by the invention is simple; production of a large amount of wastewater due to multiple acid modulations is avoided; the product yield is high, and the synthesis method is suitable for industrial production.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a method for synthesizing 4,6-dichloropyrimidine using 4,6-dihydroxypyrimidine as an intermediate. Background technique: [0002] As an important biological endogenous substance, pyrimidine heterocycle exists widely in organisms and participates in life activities. Pyrimidine compounds are a class of nitrogen-containing heterocyclic compounds with a special structure, which have the functions of antifungal and promoting plant growth regulation, and can be used to prepare insecticides, herbicides and fungicides. 4,6-dichloropyrimidine is an important intermediate in the synthesis of pyrimidine compounds, and is used in the pharmaceutical industry to produce sulfamotosin, sulfa-6-methoxine and other sulfa drugs. [0003] At present, the synthesis methods of 4,6-dichloropyrimidine mainly include phosphorus oxychloride chlorination method and solid phosgene chlorination method, both...

AI Technical Summary

Problems solved by technology

According to literature reports, the most widely used synthetic method of 4,6-dihydroxypyrimidine is to use dimethyl malonate, sodium methoxide and formamide as raw materials to prepare 4,6-dihydroxypyrimidine through ring closure reaction and multiple acid adjustments 6-dihydroxypyrimidine, but this method is easy to produce a large amount of industrial wastewater, destroys the ecological environment, and is not conducive to industrial production