CN102382077A - Method for preparing pharmaceutical grade DM (accelerator) with industrial grade DM - Google Patents
Method for preparing pharmaceutical grade DM (accelerator) with industrial grade DM Download PDFInfo
- Publication number
- CN102382077A CN102382077A CN2011102801000A CN201110280100A CN102382077A CN 102382077 A CN102382077 A CN 102382077A CN 2011102801000 A CN2011102801000 A CN 2011102801000A CN 201110280100 A CN201110280100 A CN 201110280100A CN 102382077 A CN102382077 A CN 102382077A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical grade
- grade
- solvent
- isolate
- pharmaceutical
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for preparing pharmaceutical grade DM (accelerator) with industrial grade DM. The weight ratio of the industrial grade DM to alcoholic solvent is 1:10 to 1:25. The method includes steps of enabling the industrial grade DM to dissolve in a dissolution kettle with the solvent at the temperature ranging from 80 DEG C to 180 DEG C, filtering to separate out impurities insoluble in the solvent by utilizing a filter screen with more than 200 meshes, cooling the liquor to the temperature ranging from 0 DEG C to 60 DEG C so that DM separates out by crystallization, filtering the liquor to separate out pharmaceutical grade DM, washing the pharmaceutical grade DM with filtered purified liquor, removing the residual dissolve on the pharmaceutical grade DM surface, and drying the pharmaceutical grade DM in a vacuum drier to obtain a finished product. Utilizing isopropanol to substitute for methylbenzene and tetrachloroethylene as dissolves has non-toxic side effect on a human body, is safe, reliable, high in flashing point, small in explosion dangers and high in process safety. The pharmaceutical grade DM prepared by the method is high in product purity with melting point reaching more than 178 DEG C and purity reaching more than 99%.
Description
Technical field
The invention belongs to the method for preparing DM, particularly a kind of method for preparing pharmaceutical grade DM with technical grade DM.
Background technology
Pharmaceutical grade DM (dibenzothiazole disulfide) is a raw material of producing active fat (2-(2-amino-4-thiazolyl)-2-(methoxyimino) the acetate sulfo-benzothiazole ester) product of medicine intermediate-AE, and the active fat prod of AE is a raw material of producing cephalosporin analog antibiotic.Cephalosporin analog antibiotic development in recent years is very fast, has spurred pharmaceutical grade DM.In patent 200810139264 (a kind of method for preparing pharmaceutical grade DM with technical grade DM), make referrals to; At present China production pharmaceutical grade DM is to be raw material with technical grade DM (dibenzothiazole disulfide); With toluene or zellon is solvent, obtains pharmaceutical grade DM through recrystallization.The shortcoming of this technology is:
1, use deleterious toluene or zellon as solvent.To toxic effects such as human body skin, mucous membrane, respiratory system, neural system, livers.
2, process safety is poor, and toluene is inflammable and explosive, and its steam and air can form explosive mixture, and chance naked light, high heat energy cause combustion explosion.The zellon flash-point is low, and is inflammable, and chance naked light, high heat energy cause burning.
Summary of the invention
The present invention is in order to remedy the deficiency of prior art, and a kind of nontoxic, pollution-free, safe method for preparing pharmaceutical grade DM with technical grade DM is provided.
The present invention realizes through following technical scheme:
Of the present inventionly a kind ofly prepare the method for pharmaceutical grade DM with technical grade DM, the weight ratio of technical grade DM and alcoholic solvent is 1: 10～25, under 80～180 ℃ condition, dissolves in dissolution kettle with solvent; Filtration is to isolate the impurity that is insoluble to solvent, and filter screen order number is greater than 200 orders, to leach insolubles; Solution is cooled to 0～60 ℃, and the DM crystallization is separated out; Solution is being filtered to isolate pharmaceutical grade DM; Pharmaceutical grade DM after filtering is used purified solution washing, remove the solvent of pharmaceutical grade DM remained on surface; Medical DM is carried out the dry finished product that gets in vacuum drier.
Described alcoholic solvent is Virahol, n-hexyl alcohol, secondary hexyl alcohol, n-Heptyl alcohol or 2-enanthol etc.
Specify as follows:
(1) dissolving: with technical grade DM is raw material, is solvent with Virahol (or n-hexyl alcohol, secondary hexyl alcohol, n-Heptyl alcohol, 2-enanthol), in dissolution kettle, under 80-180 ℃ condition, dissolves, and the weight ratio of technical grade DM and n-hexyl alcohol is 1: 10-25;
(2) filter: above-mentioned solution is filtered to isolate the impurity that is insoluble to Virahol, and filter screen order number is greater than 200 orders, to leach insolubles;
(3) crystallization: above-mentioned solution is cooled to 0-60 ℃, and the DM crystallization is separated out;
(4) filter: above-mentioned solution is being filtered to isolate pharmaceutical grade DM;
(5) washing: the pharmaceutical grade DM after will filtering washs with purified n-hexyl alcohol, removes the solvent of pharmaceutical grade DM remained on surface;
(6) drying: in vacuum drier, isolated pharmaceutical grade DM is carried out the dry finished product that gets.
The present invention prepares the method for pharmaceutical grade DM with technical grade DM, and step (6) back is further comprising the steps of:
(7) distillation: Virahol is reclaimed in the filtrating distillation that will isolate behind the pharmaceutical grade DM, and Virahol is used for reusing.
The invention has the beneficial effects as follows that to the human non-toxic spinoff, safe and reliable, flash-point is high as solvent for use Virahol replacement toluene, zellon, explosion hazard is little, and process safety is good.Product purity is high, and fusing point reaches more than 178 ℃, and purity reaches more than 99%.
Embodiment
Through concrete embodiment the present invention is made further detailed description below:
Following examples can make those skilled in the art more comprehensively understand the present invention, but do not limit the present invention in any way.
Embodiment 1
The present invention may further comprise the steps with the method that technical grade DM prepares pharmaceutical grade DM:
(1) dissolving: in dissolution kettle, drop into 100g technical grade DM, 1000g n-Heptyl alcohol (with technical grade DM weight ratio be 10: 1), under 180 ℃ condition, dissolve;
(2) filter: above-mentioned solution is filtered to isolate the impurity that is insoluble to n-Heptyl alcohol, filter screen 300 orders;
(3) crystallization: above-mentioned solution is cooled to 20 ℃, and the DM crystallization is separated out;
(4) filter: above-mentioned solution is being filtered to isolate pharmaceutical grade DM;
(5) washing: the pharmaceutical grade DM after will filtering washs with purified n-Heptyl alcohol, removes the solvent of pharmaceutical grade DM remained on surface;
(6) drying: in vacuum drier, isolated pharmaceutical grade DM is carried out dry getting finished product, 150 ℃ of drying temperatures, vacuum tightness 0.04Mp, 5 hours time; Obtain pharmaceutical grade DM97g, 178.5 ℃ of fusing points, purity 99.2%.
(7) distillation: n-Heptyl alcohol is reclaimed in the filtrating distillation that will isolate behind the pharmaceutical grade DM, and the distillation recovered temperature is 180 ℃, and n-Heptyl alcohol is used for reusing.
This method is to the human non-toxic spinoff, and is safe and reliable, and flash-point is high, and explosion hazard is little, and process safety is good.Product purity is high.
Embodiment 2:
The present invention may further comprise the steps with the method that technical grade DM prepares pharmaceutical grade DM:
(1) dissolving: in dissolution kettle, drop into technical grade DM100g, 2500g Virahol (with technical grade DM weight ratio be 25: 1), under 80 ℃ condition, dissolve;
(2) filter: above-mentioned solution is filtered to isolate the impurity that is insoluble to Virahol, several 200 orders of filter screen order;
(3) crystallization: above-mentioned solution is cooled to 0 ℃, and the DM crystallization is separated out;
(4) filter: above-mentioned solution is being filtered to isolate pharmaceutical grade DM;
(5) washing: the pharmaceutical grade DM after will filtering uses purified washed with isopropyl alcohol, removes the solvent of pharmaceutical grade DM remained on surface;
(6) drying: in vacuum drier, isolated pharmaceutical grade DM is carried out dry getting finished product, 160 ℃ of drying temperatures, vacuum tightness 0.09Mp, 4 hours time; Obtain pharmaceutical grade DM98g, 178.1 ℃ of fusing points, purity reaches more than 99.1%.
(7) distillation: Virahol is reclaimed in the filtrating distillation that will isolate behind the pharmaceutical grade DM, and the distillation recovered temperature is 83 ℃, and Virahol is used for reusing.
This method is to the human non-toxic spinoff, and is safe and reliable, and flash-point is high, and explosion hazard is little, and process safety is good.Product purity is high.
Embodiment 3:
The present invention may further comprise the steps with the method that technical grade DM prepares pharmaceutical grade DM:
(1) dissolving: in dissolution kettle, drop into technical grade DM100g, 1800g n-hexyl alcohol (with technical grade DM weight ratio be 18: 1), under 150 ℃ condition, dissolve;
(2) filter: above-mentioned solution is filtered to isolate the impurity that is insoluble to n-hexyl alcohol, filter screen 400 orders;
(3) crystallization: above-mentioned solution is cooled to 50 ℃, and the DM crystallization is separated out;
(4) filter: above-mentioned solution is being filtered to isolate pharmaceutical grade DM;
(5) washing: the pharmaceutical grade DM after will filtering washs with purified n-hexyl alcohol, removes the solvent of pharmaceutical grade DM remained on surface;
(6) drying: in vacuum drier, isolated pharmaceutical grade DM is carried out dry getting finished product, drying temperature 150-160 ℃, vacuum tightness 0.06Mp, 3 hours time; Obtain pharmaceutical grade DM98.5g, fusing point is more than 180 ℃, purity 99.5%.
(7) distillation: n-hexyl alcohol is reclaimed in the filtrating distillation that will isolate behind the pharmaceutical grade DM, and the distillation recovered temperature is 157 ℃, and n-hexyl alcohol is used for reusing.
This method is to the human non-toxic spinoff, and is safe and reliable, and flash-point is high, and explosion hazard is little, and process safety is good.Product purity is high.
Although the preferred embodiments of the present invention are described in conjunction with accompanying drawing; But the present invention is not limited to above-mentioned embodiment, and above-mentioned embodiment only is schematically, is not restrictive; Those of ordinary skill in the art is under enlightenment of the present invention; Not breaking away under the scope situation that aim of the present invention and claim protect, can also make the concrete conversion of a lot of forms, these all belong within protection scope of the present invention.
Claims (2)
1. method for preparing pharmaceutical grade DM with technical grade DM, it is characterized in that: the weight ratio of technical grade DM and alcoholic solvent is 1: 10～25, under 80～180 ℃ condition, dissolves in dissolution kettle with solvent; Filtration is to isolate the impurity that is insoluble to solvent, and filter screen order number is greater than 200 orders, to leach insolubles; Solution is cooled to 0～60 ℃, and the DM crystallization is separated out; Solution is being filtered to isolate pharmaceutical grade DM; Pharmaceutical grade DM after filtering is used purified solution washing, remove the solvent of pharmaceutical grade DM remained on surface; Medical DM is carried out the dry finished product that gets in vacuum drier.
2. the method for claim 1 is characterized in that described alcoholic solvent is Virahol, n-hexyl alcohol, secondary hexyl alcohol, n-Heptyl alcohol or 2-enanthol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102801000A CN102382077A (en) | 2011-09-20 | 2011-09-20 | Method for preparing pharmaceutical grade DM (accelerator) with industrial grade DM |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011102801000A CN102382077A (en) | 2011-09-20 | 2011-09-20 | Method for preparing pharmaceutical grade DM (accelerator) with industrial grade DM |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102382077A true CN102382077A (en) | 2012-03-21 |
Family
ID=45821969
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011102801000A Pending CN102382077A (en) | 2011-09-20 | 2011-09-20 | Method for preparing pharmaceutical grade DM (accelerator) with industrial grade DM |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102382077A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103145642A (en) * | 2013-03-29 | 2013-06-12 | 贾占军 | Refining method of mercaptobenzothiazole disulfide |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101168531A (en) * | 2007-11-27 | 2008-04-30 | 南京大学 | Method for synthesizing rubber accelerator DZ |
| CN101343255A (en) * | 2008-08-26 | 2009-01-14 | 山东省单县化工有限公司 | Method for preparing medicine grade DM with technical grade DM |
-
2011
- 2011-09-20 CN CN2011102801000A patent/CN102382077A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101168531A (en) * | 2007-11-27 | 2008-04-30 | 南京大学 | Method for synthesizing rubber accelerator DZ |
| CN101343255A (en) * | 2008-08-26 | 2009-01-14 | 山东省单县化工有限公司 | Method for preparing medicine grade DM with technical grade DM |
Non-Patent Citations (1)
| Title |
|---|
| 宋玉叶等: "2,2-二硫代二苯并噻唑的精制", 《江苏化工》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103145642A (en) * | 2013-03-29 | 2013-06-12 | 贾占军 | Refining method of mercaptobenzothiazole disulfide |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2722165C (en) | Crystalline form of tenofovir disoproxil and a process for its preparation | |
| US8609844B2 (en) | Method for extracting and purifying bisbenzylisoquinolines | |
| CN103724261A (en) | Novel industrial production method for hydroxychloroquine sulfate | |
| CN104292094B (en) | A kind of extracting method of high purity Phloretin | |
| CN104119270A (en) | Method for preparing Montelukast sodium | |
| JP2008524125A (en) | Method for producing galantamine hydrobromide | |
| CN102399200B (en) | Suspension crystallization method for preparing crystal form I of linezolid | |
| CN102382077A (en) | Method for preparing pharmaceutical grade DM (accelerator) with industrial grade DM | |
| WO2022122028A1 (en) | Method and device for back-extraction purification of crude product obtained by sublimation of maltol or ethyl maltol | |
| CN101717376A (en) | Method for directly extracting and purifying rubber vulcanization accelerator MBT granules by methylbenzene | |
| RU2539393C1 (en) | Method of obtaining sanguinarine and chelerythrine sulphates | |
| CN103130699A (en) | Food-grade high-content lutein ester and preparation method thereof | |
| CN110343108B (en) | Synthesis method of dimenhydrinate | |
| CN102363611A (en) | Method for producing pharmaceutical grade dibenzothiazyl disulfide (DM) by using sodium nitrite as oxidant | |
| CN101343255B (en) | Method for preparing medicine grade DM with technical grade DM | |
| CN108272834A (en) | A kind of Processing methods technique of resina liquidamberis medicinal material | |
| CN102690312A (en) | Purification method for lanolin cholesterol | |
| CN102952074A (en) | Method of recycling dextromethorphan from crystallization mother liquor | |
| CN106946811B (en) | Industrial preparation method of environment-friendly 2-cyanophenothiazine | |
| CN102718728A (en) | Refining process of rubber vulcanization accelerator MBT | |
| JPS621396B2 (en) | ||
| CN106279281B (en) | The process for purification of oxazolidone antibiotics safe ground azoles amine phosphate | |
| US1365024A (en) | Method of purifying benzanthrone | |
| CN108794562A (en) | A kind of processing technology of sapindoside extract | |
| CN102485740A (en) | Technology for extracting chenodeoxycholic acid from poultry bile |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120321 |