CN103965073A - Refining method of oxyclozanide - Google Patents
Refining method of oxyclozanide Download PDFInfo
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- CN103965073A CN103965073A CN201410178139.5A CN201410178139A CN103965073A CN 103965073 A CN103965073 A CN 103965073A CN 201410178139 A CN201410178139 A CN 201410178139A CN 103965073 A CN103965073 A CN 103965073A
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Abstract
The invention discloses a refining method of oxyclozanide, which comprises the following steps: (1) dissolving oxyclozanide crude products in a solvent, heating and reflowing till clarifying, and then carrying out suction filtration; (2) cooling the filtrate to be 40-55 DEG C, adding a reducing decolorising agent, and keeping the temperature for 0.5-2 h; (3) dropwise adding water in a destaining solution to separate out crystals, sufficiently mixing, cooling to the room temperature, carrying out suction filtration, washing, and drying to obtain the product. The refining method has the advantages that the reducing decolorising agent is adopted to decolor oxyclozanide, the refined product is better in appearance and is buff; the HPLC content of the refined product is larger than 99.7%, the individual impurity content of the refined product is smaller than 0.2%, and the yield of the refined product is can be higher than 93%.
Description
Technical field
The present invention relates to a kind of process for purification, be specifically related to the decolouring novel method of Zanil.
Background technology
Zanil (Oxyclozanide), have another name called Oxyclozanide, oxyclozanide and oxyclozanide, belonging to halo salicylanilide compounds, is a kind of Salicylanilide insect repellent, is mainly used at present the trematodiasis of the animals such as treatment and control cattle and sheep.
The synthetic key intermediate of Zanil is 2-amino-4,6-chlorophenesic acid, in this intermediate structure, contain amino and phenolic hydroxyl group, in reaction process, easily oxidation by air is nitro or even the coloured material of azo band, cause final finished with pink or brown, instead of original light yellow, and the colored oxide compound generating in this building-up process, due to more approximate with finished product in structure and polarity, if adopt conventional refining step to be difficult to remove at later separation leaching process, can affect the appearance color of the finished product.
The appearance color of medicine is one of project of drug standard, has reflected to a certain extent the purity of medicine.Now, also more and more higher to the color appearance requirement of medicine in the world, the bulk drug of particularly directly taking and inject class medicine requires also stricter.Therefore, investigate medicine decoloring method and also become the emphasis of research.At present, industrial conventional decolouring means are mainly used charcoal absorption decolouring, shortcoming to be, this method can only be adsorbed and is insoluble to the fine particle of solvent and not obvious to its material adsorption effect, can not be from basic solution pigment residue problem.Patent CN101891646A has reported that weight ratio is that the methyl alcohol of 6.4 times of Zanil crude products makees solvent, and 5% gac is as discoloring agent, and yield is too low, only has 64.7%.Therefore, be necessary to invent a kind of new process for purification, adopt new solvent and discoloring agent, optimize solvent burden ratio, improve refining yield and decolorizing effect, fundamentally solve pigment residue problem.
Summary of the invention
The object of this invention is to provide a kind of simple to operate, refining effect good, yield is higher Zanil process for purification.In order to solve the problems of the technologies described above, concrete technical scheme is as follows:
A process for purification for Zanil, comprises the following steps in order:
(1) by Zanil dissolving crude product in solvent, reflux to molten clear after suction filtration;
(2) above-mentioned filtrate is cooled to 40～55 DEG C, adds reductibility discoloring agent, be incubated 0.5～2 hour;
(3) in destainer, drip water crystallize out, fully stir, be cooled to after room temperature, suction filtration, washing, the dry product that obtains.
Solvent described in step (1) is selected from a kind of of ethanol, Virahol, butanone, acetone, pimelinketone, methyl butyl ketone, methyl iso-butyl ketone (MIBK) or their mixture, preferred alcohol, butanone, the consumption of described solvent is 1～10 times of Zanil weight ratio, preferably 3～6 times.
In step (2), reductibility discoloring agent is selected from following reagent: any one of thiourea peroxide, sodium bisulfite, oxalic acid, S-WAT, Sulfothiorine, ferrous ammonium sulphate, xitix, be preferably thiourea peroxide or S-WAT, the consumption of described discoloring agent is 0.1%～10% of Zanil weight ratio, preferably 0.5～3%.
In step (3), the consumption of water is 1.5～5 times of Zanil weight ratio.
Beneficial effect of the present invention is:
1, adopt reductibility discoloring agent to Zanil crude product refining, overcome the drawback of traditional active carbon discoloring agent, the product appearance of refining out is better, for light yellow.
Outward appearance contrast table:
| Crude product | Fine work 1 | Fine work 2 | |
| Process for purification | / | Absorbent charcoal fine purification | Reductibility discoloring agent is refining |
| Outward appearance | Brown | Yellow | Light yellow |
2, adopt process for purification of the present invention, the Zanil fine work HPLC content making is greater than 99.7%, and single mixing is less than 0.2%, and yield reaches more than 93%.
3, process for purification of the present invention is effective, easy to operate, is applicable to industrial application.
Embodiment
The following specific embodiment of passing through, is described in detail the present invention, and following examples are used for explaining the present invention, instead of limitation of the present invention.
Embodiment 1
In four-hole boiling flask at 500ml with thermometer and whipping appts, add peach Zanil crude product 60g, the butanone of 4 times of weight ratios, open and stir, temperature rising reflux is to molten clear, suction filtration, filtrate is cooled to 50 DEG C, adding weight ratio is the thiourea peroxide of 0.1% times of Zanil crude product, insulated and stirred 1 hour, dripping weight ratio is the water of 1.5 times of Zanil crude products, dropwise, be cooled to 20 DEG C, stir 1h, suction filtration, 30ml butanone washing for filter cake, dry at 95 DEG C after draining, obtain light yellow solid 56.5g, yield approximately 94.2%, HPLC content is 99.8%.
Embodiment 2
In four-hole boiling flask at 500ml with thermometer and whipping appts, add the Zanil crude product 60g of brown, the acetone of 9 times of weight ratios, open and stir, temperature rising reflux is to molten clear, suction filtration, filtrate is cooled to 50 DEG C, adding weight ratio is the sodium bisulfite of 10% times of Zanil crude product, insulated and stirred 2 hours, dripping weight ratio is the water of 5 times of Zanil crude products, dropwise, be cooled to 20 DEG C, stir 1h, suction filtration, 30ml for filter cake (acetone/water=1:1) washing, dry at 95 DEG C after draining, obtain light yellow solid 55.8g, yield approximately 93%, HPLC content is 99.7%.
Embodiment 3
In four-hole boiling flask at 500ml with thermometer and whipping appts, add the Zanil crude product 60g of brown, the methyl alcohol of 3 times of weight ratios, opens and stirs, and temperature rising reflux is to molten clear, suction filtration, filtrate is cooled to 50 DEG C, and adding weight ratio is the xitix of 3% times of Zanil crude product, insulated and stirred 2 hours, dripping weight ratio is the water of 3 times of Zanil crude products, dropwise, be cooled to 20 DEG C, stir 1h, suction filtration, filter cake 30ml methanol wash, dry at 95 DEG C after draining, obtain light yellow solid 57g, yield approximately 95%, HPLC content is 99.8%.
The invention is not restricted to above-described embodiment, that all foundations technical spirit of the present invention is done above-described embodiment is any simple, equivalent variations or modification, all belongs within the scope of the technology of the present invention.
Claims (6)
1. a process for purification for Zanil, is characterized in that comprising the following steps:
(1) by Zanil dissolving crude product in solvent, reflux to molten clear after suction filtration;
(2) above-mentioned filtrate is cooled to 40～55 DEG C, adds reductibility discoloring agent, be incubated 0.5～2 hour;
(3) in destainer, drip water crystallize out, fully stir, be cooled to after room temperature, suction filtration, washing, the dry product that obtains.
2. according to the process for purification of the Zanil described in claim 1, it is characterized in that, solvent described in step (1) is selected from a kind of of ethanol, Virahol, butanone, acetone, pimelinketone, methyl butyl ketone, methyl iso-butyl ketone (MIBK) or their mixture, and the consumption of described solvent is 1～10 times of Zanil weight ratio.
3. the process for purification of Zanil according to claim 2, is characterized in that, the solvent described in step (1) is ethanol or butanone, and the consumption of solvent is 3～6 times of Zanil weight ratio.
4. according to the process for purification of the Zanil described in claim 1, it is characterized in that, in step (2), reductibility discoloring agent is selected from following reagent: any one of thiourea peroxide, sodium bisulfite, oxalic acid, S-WAT, Sulfothiorine, ferrous ammonium sulphate, xitix, the consumption of described discoloring agent is 0.1%～10% of Zanil weight ratio.
5. according to the process for purification of the Zanil described in claim 4, it is characterized in that, reductibility discoloring agent is thiourea peroxide or S-WAT, and the consumption of described discoloring agent is 0.5～3% of Zanil weight ratio.
6. according to the process for purification of the Zanil described in claim 1, it is characterized in that, in step (3), the consumption of water is 1.5～5 times of Zanil weight ratio.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410178139.5A CN103965073B (en) | 2014-04-29 | 2014-04-29 | A kind of process for purification of Zanil |
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| CN201410178139.5A CN103965073B (en) | 2014-04-29 | 2014-04-29 | A kind of process for purification of Zanil |
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| CN103965073A true CN103965073A (en) | 2014-08-06 |
| CN103965073B CN103965073B (en) | 2015-12-02 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105534895A (en) * | 2016-01-18 | 2016-05-04 | 中国农业科学院兰州畜牧与兽药研究所 | Oxyclozanide suspension and preparation method thereof |
| CN108863822A (en) * | 2017-05-09 | 2018-11-23 | 武汉武药制药有限公司 | A method of purification isoprenaline hydrochloride |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3349090A (en) * | 1963-08-14 | 1967-10-24 | Ici Ltd | Polyhalogenated di-hydroxybenzanilide derivatives |
| GB1139989A (en) * | 1966-08-29 | 1969-01-15 | Parke Davis & Co | New benzanilide compounds and methods for their production |
| FR2658192A1 (en) * | 1990-02-12 | 1991-08-16 | Blum Jean | New process for the preparation of benzanilides |
| CN101891646A (en) * | 2010-07-06 | 2010-11-24 | 常州亚邦齐晖医药化工有限公司 | Preparation method of oxyclozanide |
-
2014
- 2014-04-29 CN CN201410178139.5A patent/CN103965073B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3349090A (en) * | 1963-08-14 | 1967-10-24 | Ici Ltd | Polyhalogenated di-hydroxybenzanilide derivatives |
| GB1139989A (en) * | 1966-08-29 | 1969-01-15 | Parke Davis & Co | New benzanilide compounds and methods for their production |
| FR2658192A1 (en) * | 1990-02-12 | 1991-08-16 | Blum Jean | New process for the preparation of benzanilides |
| CN101891646A (en) * | 2010-07-06 | 2010-11-24 | 常州亚邦齐晖医药化工有限公司 | Preparation method of oxyclozanide |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105534895A (en) * | 2016-01-18 | 2016-05-04 | 中国农业科学院兰州畜牧与兽药研究所 | Oxyclozanide suspension and preparation method thereof |
| CN105534895B (en) * | 2016-01-18 | 2018-08-10 | 中国农业科学院兰州畜牧与兽药研究所 | A kind of oxyclozanide suspension and preparation method thereof |
| CN108863822A (en) * | 2017-05-09 | 2018-11-23 | 武汉武药制药有限公司 | A method of purification isoprenaline hydrochloride |
| CN108863822B (en) * | 2017-05-09 | 2021-09-21 | 武汉武药制药有限公司 | Method for refining isoproterenol hydrochloride |
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| CN103965073B (en) | 2015-12-02 |
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Address after: 213127 Jiangsu province Changzhou City North Industrial Park Chunjiang Town New District Jinlong Road, No. 18 Applicant after: Changzhou Qi Hui pharmaceutcal corporation, Ltd Address before: 213127 Jiangsu province Changzhou City North Industrial Park Chunjiang Town New District Jinlong Road, No. 18 Applicant before: Changzhou Yabang Qihui Fine Chemicals Co., Ltd. |
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