Preparation of 2-cyanophenthiazine

Abstract

The invention provides a preparation method of 2-cyanophenothiazine. First, a certain amount of industrial-grade 2-chlorophenothiazine, cuprous cyanide, N-methylpyrrolidone, and potassium iodide are added to the reactor, and the temperature is raised to reflux reaction. . The present invention is characterized in that, after the reaction is completed, cool and add a certain amount of water to force out the product and inorganic impurities, filter and dry to obtain a solid mixture, and extract the crude product of 2-cyanophenothiazine with ethyl acetate; 2- The crude product of cyanophenothiazine was dissolved in N, N 1 -In dimethylformamide, add an appropriate amount of phosphorus oxychloride at room temperature for dehydration reaction; then add an appropriate amount of inorganic weak alkali aqueous solution to precipitate the product, and the aqueous solution is weakly alkaline; filter, wash with water, dry, and recrystallize through toluene, The product purity is greater than 99%, the content of impurity amides is less than 0.15%, and the total yield is greater than 85%.

Description

1. Technical field [0001] The invention relates to a preparation method of organic heterocyclic compounds, in particular to a preparation method of 2-cyanophenothiazine. 2. Background technology [0002] 2-cyanophenothiazine is an important pharmaceutical intermediate, the drug prepared by it has a variety of drug functions, especially in antihypertensive, mental stability, analgesia and anticancer. This intermediate is in great demand. 2-cyanophenothiazine structural formula (I) is as follows: [0003] The synthesis of this type of compound generally adopts the synthesis process described in Reaction Formula (II), that is, using 2-chlorophenothiazine and cuprous cyanide as raw materials in high-boiling organic solvents such as quinoline or N-methylpyrrolidone , prepared by reaction under the catalysis of iodine or sodium iodide, potassium iodide. [0004] [0005] In 1978, the Japanese patent first reported the synthesis of this compound. It used 2-chlorophenothiazi...

AI Technical Summary

Problems solved by technology

After adopting the toluene / n-hexane of Japanese patent report to carry out one recrystallization, the content of amide body becomes 3-6%, after recrystallization again, the content of amide body drops to 1.5-3%, although three to four times of recrystallization can make The content of the amide body is less than 1%, but there is still some distance from the goal of the content of the amide body in the Japanese standard product being less than 0.15%, and multiple recrystallizations will reduce the yield, greatly increase the industrial cost, and complicate the operation

[0010] In addition, in the method reported in the above-mentioned patent, the post-treatment step adopts dilute sulfuric acid acidification method, and dilute sulfuric acid will generate highly toxic hydrocyanic acid gas with unreacted copper cyanide, causing great danger to industrial production

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