Method for preparing secnidazole

Abstract

This invention relates to secnidazole [1-(2-hydroxy group propyl)-2-methyl-5- nitro imidazole] preparation method, it belongs to chemical pharmacy technique field. 2-methyl-5-nitro imidazole and 1-chlorine-2-propyl alcohol are materials, dry acid gas is let in to dissolve solid, then heated, distilled and recover 1-chlorine-2- propanol, pH is adjusted by sig water and cooled to 0 degree centigrade. Then it is filtrated, unreacted 2-methyl-5-nitro imidazole is recovered, filtrate pH value is adjusted to alkality, and then secnidazole crude is got after filtration. Reaction temperature is 85-95 degrees cenrigrade, reaction time is 6.0-7.5 hours, mol ratio of 2-methyl-5-nitro imidazole and 1-chlorine-2-propyl alcohol is 1:3.25-5.30. Compering to existing technique, the reaction preoceudre is only one step, generating period is shortened, and operation is simplified. Reaction whole yield is improved from less than 50 percent reported from document to 56-60 percent, and material mass using is reduced, so generating cost is reduced, generating safty is also improved.

Description

technical field [0001] The invention relates to a preparation method of secnidazole [1-(2-hydroxypropyl)-2-methyl-5-nitroimidazole], belonging to the technical field of chemical pharmacy. Background technique [0002] Secnidazole has a structure as shown in general formula I, and is a highly effective anti-amoeba and anti-trichomonad drug of the 5-nitroimidazole class. It is clinically used to treat various acute and chronic hepatic and intestinal amoebiasis and trichomoniasis such as urethra, female vagina, and male prostate. It is also used for the treatment of giardiasis and anaerobic infection in various parts of the human body. [0003] [0004] Formula I [0005] About the preparation method of secnidazole, current bibliographical information roughly has following several kinds: [0006] 1. Rhone-poulec S.A reported (French patent 1427627 and French patent M3270) that 2-methyl-5-nitroimidazole (1mol) was dissolved in 85% formic acid (7.88 parts), cooled to -14°C, ...

AI Technical Summary

Problems solved by technology

[0012] ① Method 1 uses a large amount of highly corrosive and toxic formic acid, which requires high operation requirements, and there are many subsequent problems in decompression recovery treatment

[0013] ②Method 2 uses expensive sodium borohydride and chloroacetone, and the steps are long, the yield is 3.62% lower; method 3 is also 6.25% lower in yield, and it is difficult to realize industrialization

[0014] ③ Method 4 uses highly corrosive fuming sulfuric acid, which is dangerous to operate, and the steps are long, and the yield is 14.5% lower

[0015] ④ Method 5 requires no water, high requirements for operation and equipment, and difficult to achieve industrialization

After alkalization, the reaction solution must be extracted with a large amount of ethyl acetate, and the recovered ethyl acetate cannot be reused due to its high water content

[0016] ⑤In the above methods using propylene oxide, the propylene oxide used has a very low boiling point (33.9°C), is volatile, difficult to operate, and more dangerous

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