CN101602744A - A kind of preparation method of nitazoxanide - Google Patents
A kind of preparation method of nitazoxanide Download PDFInfo
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- CN101602744A CN101602744A CNA200910016459XA CN200910016459A CN101602744A CN 101602744 A CN101602744 A CN 101602744A CN A200910016459X A CNA200910016459X A CN A200910016459XA CN 200910016459 A CN200910016459 A CN 200910016459A CN 101602744 A CN101602744 A CN 101602744A
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- nitazoxanide
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- nitrothiazole
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Abstract
A kind of preparation method of nitazoxanide is characterized in that 2-amino-5-nitrothiazole and anhydrous propanone are mixed, and adds the solution of being made up of anhydrous propanone and adjacent acetyl bigcatkin willow acyl chlorides in the mixed solution of gained, under agitation slowly drip anhydrous triethylamine then, isothermal reaction behind the dropping anhydrous triethylamine, keeps temperature of reaction to continue to stir, while stirring the gained reaction solution is poured in the frozen water, leave standstill, filter drying, use ethyl alcohol recrystallization, obtain nitazoxanide.The inventive method simple possible, end product yield are about 75%, and reactions steps simplified, and have improved production efficiency.
Description
Technical field
The present invention relates to a kind of preparation method who treats the nitazoxanide of animals and human beings body parasitosis.
Background technology
In recent years, nitazoxanide as the medicine of a kind of efficient, the anti-animals and human beings body of wide spectrum parasite, bacterium and fungi infestation by extensive concern, it is first and unique medicine that is used for the treatment of Cryptosporidium of united states drug and food Surveillance Authority (FDA) approval, also be first kind of new drug ratifying to be used for the treatment of giardia over more than 40 year, in country's listings such as Australia, New Zealand, the U.S., Canada, Mexico, China Ministry of Agriculture is not this equipment registration also at present.
Nitazoxanide is the nitrothiazole amide compound, and chemical name is 2-acetoxyl group-N-(5-nitro-2-thiazole) benzamide [2-(acetolyloxy)-N-(5-nitro-2-thiazolyl) benzamide].In the preparation of nitazoxanide, literature method is earlier with the Whitfield's ointment acetylize, makes carboxylic acid halides again, last and 2-amino-5-nitrothiazole condensation, productive rate 70%.The defective of this method (seeing reaction formula) is that product can be taken off ethanoyl in follow-up reaction, has influenced the yield of nitazoxanide.
Summary of the invention
The preparation method who the purpose of this invention is to provide a kind of more simple and effective nitazoxanide, it is more that it can overcome existing synthetic method reactions steps, reacts more loaded down with trivial details shortcoming.
A kind of preparation method of nitazoxanide is characterized in that 2-amino-5-nitrothiazole and anhydrous propanone are mixed, and adds the solution of being made up of anhydrous propanone and adjacent acetyl bigcatkin willow acyl chlorides in the mixed solution of gained, under agitation slowly drip anhydrous triethylamine then, isothermal reaction behind the dropping anhydrous triethylamine, keeps temperature of reaction to continue to stir, while stirring the gained reaction solution is poured in the frozen water, leave standstill, filter drying, use ethyl alcohol recrystallization, obtain nitazoxanide.
The inventive method simple possible, end product yield are about 75%, and reactions steps simplified, and have improved production efficiency.
Embodiment
2-amino-5-nitrothiazole and anhydrous propanone are mixed, in the mixed solution of gained, add the solution of forming by anhydrous propanone and adjacent acetyl bigcatkin willow acyl chlorides, under agitation slowly drip the catalyzer anhydrous triethylamine again, make two kinds of reactant 2-amino-5-nitrothiazoles and the isothermal reaction of acetyl bigcatkin willow acyl chlorides, after anhydrous triethylamine dropwises, keep temperature of reaction to continue to stir, while stirring the gained reaction solution is poured in the frozen water then, leave standstill, filter, drying is used ethyl alcohol recrystallization, promptly gets nitazoxanide.
Reaction formula of the present invention is shown below:
Embodiment
In the dry four-hole boiling flask of stirring rod, reflux condensing tube, constant pressure funnel and thermometer is housed, add the anhydrous propanone that 12g 2-amino-5-nitrothiazole and 36g processed obtain, mix and obtain mixed solution, in addition the 37.8g anhydrous propanone is dissolved in the adjacent acetyl bigcatkin willow of the 25.2g acyl chlorides and makes solution, under agitation slowly drip anhydrous triethylamine 10.0g to this solution, temperature remains on 25 ℃.Dropwise the back and keep 25 ℃ of temperature to continue to stir 60min, then gained solution is added in the above-mentioned mixed solution; 2-amino-5-nitrothiazole and adjacent acetyl bigcatkin willow acyl chloride reaction are poured the reaction solution of gained in the 285g frozen water into while stirring, leave standstill, and filter, and drying is used ethyl alcohol recrystallization, promptly gets nitazoxanide.
The 2-amino-5-nitrothiazole in the described mixed solution and the mass ratio of anhydrous propanone are 1: 3～3.5; The mass ratio of adjacent acetyl bigcatkin willow acyl chlorides and anhydrous propanone is 1: 1.5～1.8 in the described solution; The mass ratio of 2-amino-5-nitrothiazole and adjacent acetyl bigcatkin willow acyl chlorides is: 1: 2.0～2.5; The mass ratio of anhydrous triethylamine and 2-amino-5-nitrothiazole is: 1: 1.2～1.5.The isothermal reaction temperature is 24-26 ℃; It is 58-62min that anhydrous triethylamine dropwises the back churning time.The volume of pouring frozen water into is 2-3 a times of gained reaction solution; The solvent that recrystallization is used is an ethanol.
Claims (5)
1, a kind of preparation method of nitazoxanide is characterized in that 2-amino-5-nitrothiazole and anhydrous propanone are mixed, and adds the solution of being made up of anhydrous propanone and adjacent acetyl bigcatkin willow acyl chlorides in the mixed solution of gained, under agitation slowly drip anhydrous triethylamine then, isothermal reaction behind the dropping anhydrous triethylamine, keeps temperature of reaction to continue to stir, while stirring the gained reaction solution is poured in the frozen water, leave standstill, filter drying, use ethyl alcohol recrystallization, obtain nitazoxanide.
2, the preparation method of nitazoxanide as claimed in claim 1 is characterized in that the 2-amino-5-nitrothiazole in the described mixed solution and the mass ratio of anhydrous propanone are 1: 3～3.5.
3, the preparation method of nitazoxanide as claimed in claim 1 is characterized in that the mass ratio of adjacent acetyl bigcatkin willow acyl chlorides and anhydrous propanone is 1: 1.5～1.8 in the described solution.
4, the preparation method of nitazoxanide as claimed in claim 1 is characterized in that the mass ratio of described 2-amino-5-nitrothiazole and adjacent acetyl bigcatkin willow acyl chlorides is: 1: 2.0～2.5.
5, the preparation method of nitazoxanide as claimed in claim 1 is characterized in that the mass ratio of described anhydrous triethylamine and 2-amino-5-nitrothiazole is: 1: 1.2～1.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910016459XA CN101602744B (en) | 2009-06-30 | 2009-06-30 | Preparation method of nitazoxanide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910016459XA CN101602744B (en) | 2009-06-30 | 2009-06-30 | Preparation method of nitazoxanide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101602744A true CN101602744A (en) | 2009-12-16 |
| CN101602744B CN101602744B (en) | 2011-06-01 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN200910016459XA Expired - Fee Related CN101602744B (en) | 2009-06-30 | 2009-06-30 | Preparation method of nitazoxanide |
Country Status (1)
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105175352A (en) * | 2015-10-27 | 2015-12-23 | 杭州澳医保灵药业有限公司 | Preparation method of nitazoxanide |
| WO2023058046A1 (en) * | 2021-10-05 | 2023-04-13 | Council Of Scientific And Industrial Research An Indian Registered Body Incorporated Under The Regn. Of Soc. Act (Act Xxi Of 1860) | An improved process for the preparation of nitazoxanide and intermediates thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1437800A (en) * | 1973-08-08 | 1976-06-03 | Phavic Sprl | Derivatives of 2-benzamido-5-nitro-thiazoles |
| CN100465169C (en) * | 2006-08-02 | 2009-03-04 | 杭州欣阳三友精细化工有限公司 | Method for preparing nitazoxanide |
| CN101007792B (en) * | 2007-01-31 | 2010-05-26 | 浙江大学 | Synthesis process of nitro thiazoly benzamide compound |
-
2009
- 2009-06-30 CN CN200910016459XA patent/CN101602744B/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105175352A (en) * | 2015-10-27 | 2015-12-23 | 杭州澳医保灵药业有限公司 | Preparation method of nitazoxanide |
| WO2023058046A1 (en) * | 2021-10-05 | 2023-04-13 | Council Of Scientific And Industrial Research An Indian Registered Body Incorporated Under The Regn. Of Soc. Act (Act Xxi Of 1860) | An improved process for the preparation of nitazoxanide and intermediates thereof |
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| Publication number | Publication date |
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| CN101602744B (en) | 2011-06-01 |
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Address after: 266061 Shandong Province, Qingdao high tech park of Shandong Miao Road Building 6 floor, Room 606, high speed Co-patentee after: Qingdao Agricultural University Patentee after: QINGDAO KDN PHARMACEUTICAL Co.,Ltd. Co-patentee after: QINGDAO KDN BIOTECH Co.,Ltd. Address before: 266061 Shandong Province, Qingdao high tech park of Shandong Miao Road Building 6 floor, Room 606, high speed Co-patentee before: Qingdao Agricultural University Patentee before: Qingdao Vland Biotech INC. Co-patentee before: Qingdao Liuhe Pharmaceuticals Ltd. |
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Address after: 266111 Shandong city of Qingdao province Chengyang Qingda Industrial Park, the first northbound dual Patentee after: QINGDAO VLAND BIOTECH Inc. Patentee after: Qingdao Agricultural University Patentee after: QINGDAO KDN BIOTECH Co.,Ltd. Address before: 266061 Shandong Province, Qingdao high tech park of Shandong Miao Road Building 6 floor, Room 606, high speed Patentee before: QINGDAO KDN PHARMACEUTICAL Co.,Ltd. Patentee before: Qingdao Agricultural University Patentee before: QINGDAO KDN BIOTECH Co.,Ltd. |
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Granted publication date: 20110601 |