A kind of preparation method of 2-amino-4,6-dimethoxypyrimidine

Abstract

A preparation method of 2-amino-4,6-dimethoxypyrimidine, using malononitrile and methanol as raw materials, using one of toluene, xylene, chlorobenzene, and dichloroethane as a solvent, through hydrogen chloride The aeration reaction generates 1,3-dimethoxypropanediimine dihydrochloride without filtration and other post-treatment operations. Add a water-insoluble organic base dropwise to the reaction system to adjust the pH of the reaction system to 6-8, and then add The solid reaction of cyanamide generates 3-amino-3-methoxy-N-nitrile-2-propionamidine, and then the heating reaction generates 2-amino-4,6-dimethoxypyrimidine product. The invention utilizes a one-pot method to prepare 2-amino-4,6-dimethoxypyrimidine, the reaction conditions are mild, safe and environmentally friendly, the process operation is simplified, the amount of three wastes is small, and the total synthesis yield of the four-step reaction can reach 80%. Above, the product content can reach more than 99%, which is suitable for green industrial production.

Description

technical field [0001] The invention belongs to the technical field of synthesis of important intermediates of pesticides, in particular to a preparation method of 2-amino-4,6-dimethoxypyrimidine. Background technique [0002] Sulfonylurea herbicides were mainly developed in the 1980s. They are broad-spectrum and high-efficiency herbicides for rice, corn and soybean fields. They have the characteristics of high activity, low dosage and low toxicity. They are widely used in the world. It is recognized as an efficient and environmentally friendly green pesticide. [0003] Pyrimidines are a class of important biologically active substances, which are widely used in pesticides, herbicides, fungicides, in the production of sulfonylurea herbicides, 2-amino-4,6-dimethoxy Pyrimidine is a very important intermediate in its synthesis, and there are many varieties of sulfonylurea herbicides prepared from it, such as nicosulfuron, bensulfuron, pyrazosulfuron, rimsulfuron, and rimsulfur...

AI Technical Summary

Problems solved by technology

[0004] There are many synthetic methods for 2-amino-4,6-dimethoxypyrimidine intermediates: Spencer (Journal ofLabelled Compounds and Radiopharmaceuticals.1989,4(5):433-436.) with 2,4,6-trichloro Pyrimidine and ammonium chloride are used as raw materials, and 2-amino-4,6-dichloropyrimidine is obtained by reacting at -78°C, and then etherified with sodium methoxide to obtain the product. This method has low reaction temperature and harsh reaction conditions. The yield is only about 32%; Japanese patent JP6135941 uses 4,6-dimethoxy-2-pyrimidine methanesulfonate as a raw material, reacts with ammonia water for 72 hours at room temperature to obtain the target product, although the reaction conditions are easy to achieve in the synthesis method, But the reaction time is too long, the raw material is not easy to get, it is unfavorable for industrialized production; Pyrimidine is used as the raw material, and diazomethane is used as the synthesis route of the methylating reagent. Although the steps are short, diazomethane is a poisonous gas with a strong irritant and a musty smell. If it is mishandled, it will explode violently. It will decompose quickly when it encounters water, so the operation is relatively difficult and it is not easy to industrialize

[0010] However, the first step reaction of this process route requires absolute anhydrous conditions to prepare the dihydrochloride of the intermediate 1,3-dimethylpropanediamidine, and the yield is not high, and the conventional process also needs to filter and separate the intermediate, because There is a large amount of hydrogen chloride in the reaction system, and the intermediate 1,3-dimethoxypropanediimine dihydrochloride is extremely unstable to humid air and temperature, and is easily hydrolyzed into monoamide impurities, malonamide, malonic acid, etc. The reaction also needs to be neutralized with sodium bicarbonate in an aqueous environment, and the cyanamide reaction in the aqueous solution is used to prepare 3-amino-3-methoxy-N-cyano-2-propionamidine, which needs to be dried and removed for the ring-closing reaction in the later stage. Water, the process operation is cumbersome, the industrialization requirements are very high, and the final yield is not high, the actual industrial yield is only about 65%

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