CN103145642A - Refining method of mercaptobenzothiazole disulfide - Google Patents
Refining method of mercaptobenzothiazole disulfide Download PDFInfo
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- CN103145642A CN103145642A CN2013101044271A CN201310104427A CN103145642A CN 103145642 A CN103145642 A CN 103145642A CN 2013101044271 A CN2013101044271 A CN 2013101044271A CN 201310104427 A CN201310104427 A CN 201310104427A CN 103145642 A CN103145642 A CN 103145642A
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Abstract
The invention relates to a refining method of mercaptobenzothiazole disulfide (DM). The refining method is characterized by comprising the following steps of: soakingindustrial grade DM with a solvent A, stirring for 10-30 hours at the temperature of 10-35 DEG C; stopping stirring, solid-liquid separating, washing the solid with a solvent B, and drying the solid, thereby obtaining the mercaptobenzothiazole disulfide. The refining method has the advantages of being low in material consumption, low in energy consumption, low in investment, high in output, safe, reliable and capable of greatly decreasing the production cost, thereby obtaining good social benefit.
Description
Technical field
[0001] the invention belongs to the process for purification of medicine intermediate, particularly a kind of process for purification of dibenzothiazyl disulfide.
Background technology
Dibenzothiazyl disulfide is called for short in the industry DM, and technical grade DM is mainly used in rubber industry, is the crosslinked efficient promotor of the vulcanization of rubber, and outward appearance is light yellow crystalline powder.Because this product has higher thermostability, the stability of acid and alkali-resistance environment, and be used for high-grade rubber item.After DM is purified, i.e. pharmaceutical grade elaboration DM is important intermediate and the bulk drug of the bulk drug 2-(2-amino-4-thiazolyl) that produces cephalosporins medicine-2-(methoxyimino) acetic acid sulfo-benzothiazole ester (the active fat of AE-).The major impurity of technical grade DM is mainly monomer whose 2-mercaptobenzothiazole (captax), and the production of pharmaceutical grade elaboration DM is at present purified, mainly by following methods:
CN1827608 discloses a kind of method of purification of dibenzothiazyl disulfide, and it adopts toluene high temperature recrystallization.Disclosing the later DM purity of resulting purification in patent is 92-95%.But there is the three aspects: defective in this method, is that toluene is little to the solubleness of DM on the one hand, causes batch output to be told somebody what one's real intentions are.On the other hand, because the quality requirement to pharmaceutical grade DM is higher in the world, require just fusing point higher than 180 ℃, purity is higher than 99%, can not meet the demands with the method for toluene recrystallization.The third aspect, because need high-temperature digestion in dissolving, solvent is volatile, solvent consumption is high.As making solvent with toluene, one ton of pharmaceutical grade elaboration DM of every production namely consumes toluene 250-300 kilogram.These toluene evaporate into and cause atmospheric pollution in atmosphere, exist set off an explosion, Hazard Factor that fire, worker are poisoning and the hidden danger of security incident.CN102285938 discloses a kind of process for purification of pharmaceutical dibenzothiazyl disulfide, and it adopts ethyl acetate and ethyl alcohol recrystallization dissolving, adds decolorization and impurity removal by active carbon, and recrystallization obtains.Although purity reaches more than 99%, because charcoal absorption does not have selectivity, gac not only adsorbs the impurity in DM, the DM that also adsorbs some amount, the mixture of generation gac and DM becomes waste material, increase the consumption of DM, therefore can affect the recrystallization yield.
Therefore, invent the process for purification of the dibenzothiazyl disulfide of a kind of environmental protection and low consumption high yield, become particularly important.
Summary of the invention
The object of the present invention is to provide a kind of process for purification of dibenzothiazyl disulfide, the defects that exists to overcome prior art reaches consumption low, less energy consumption, less investment, output is high, safe and reliable, can decrease production cost, obtain the advantage of fine social benefit.
The present invention adopts following technical scheme:
A kind of process for purification of dibenzothiazyl disulfide is characterized in that, comprises the steps:
(1) soak technical grade DM with solvent orange 2 A, stir 10-30h under 10-35 ℃;
(2) stop stirring, solid-liquid separation, solid washs with solvent B, and drying both gets.
As a further improvement on the present invention, wherein solvent orange 2 A is selected from acetone, ethyl acetate, methylene dichloride, chloroform, ethanol, methyl alcohol and alkaline aqueous solution.
As a further improvement on the present invention, wherein, when solvent orange 2 A was selected from acetone, ethyl acetate, methylene dichloride, chloroform, ethanol, methyl alcohol, solvent B was selected from acetone, ethyl acetate, methylene dichloride, chloroform, ethanol, methyl alcohol; When solvent orange 2 A was alkaline aqueous solution, solvent B was water.
As a further improvement on the present invention, wherein the concentration of alkaline aqueous solution is 0.05-2%.
As a further improvement on the present invention, wherein alkaline aqueous solution is aqueous sodium hydroxide solution, potassium hydroxide aqueous solution, aqueous sodium carbonate or wet chemical.
As a further improvement on the present invention, wherein solid-liquid separation is selected from filtration, centrifugal or press filtration.
As a further improvement on the present invention, wherein the mass ratio of the volume of solvent orange 2 A and DM is 1-10:1.
Further improve as of the present invention, present method is for using any solvent in acetone, ethyl acetate, methylene dichloride, chloroform, ethanol, methyl alcohol, directly soak technical grade DM, stir in 25 ℃ and soak 24h, DM powder and solution separating with after soaking obtain pressed powder DM, then use any solvent wash pressed powder DM in acetone, ethyl acetate, methylene dichloride, chloroform, ethanol, methyl alcohol, drying had both obtained pharmaceutical grade elaboration DM.
Further improve as of the present invention, present method is for using sodium hydroxide solution, directly soak technical grade DM, stir in 25 ℃ and soak 24h, with DM powder and the sodium hydroxide solution separating and filtering after soaking, the pressed powder DM that obtains is washed with water three times, and dry cake had both obtained pharmaceutical grade elaboration DM.
As a further improvement on the present invention, comprise that step (3) merges the solvent after solid-liquid separation and solvent B, reclaims respectively M and solvent.
Because the impurity in technical grade DM is mainly captax, the present invention utilizes technical grade DM different from the physical properties of captax, and both are separated.The present invention utilizes technical grade DM different from the solvability of captax, uses energy dissolution accelerator M can not dissolve solvent acetone, ethyl acetate, methylene dichloride, chloroform, ethanol, the methyl alcohol of DM, and both are separated.The present invention utilize captax slightly acidic, make captax change salt into by the acid-base reaction of using alkaline aqueous solution, because it possesses water-soluble physical properties, and DM is water insoluble, therefore also can reach the effect of solid-liquid separation.
It is pharmaceutical grade DM that the present invention separates the solid that obtains, when solvent orange 2 A was selected from acetone, ethyl acetate, methylene dichloride, chloroform, ethanol, methyl alcohol, the liquid of resulting separation can distill, the gained solvent can recycle, and the gained enriched material is captax.If when solvent orange 2 A is alkaline aqueous solution, gained liquid can neutralize with hydrochloric acid, and the pH value is transferred to neutrality.The captax that dissolves in immersion liquid can be separated out, and refilters, and can obtain high-quality captax again after drying.Extract the captax rear solution and can be used as the boiler flue dedusting, dry cooling follows Hua Shui, and directly discharging can be to environment yet.
The beneficial effect that the present invention produces is:
1, the present invention uses and has avoided the use charcoal absorption, reduces the consumption of primary industry level DM.2, the present invention utilizes envrionment temperature 10-35 ℃, there is no high-temperature digestion, and the decrease temperature crystalline process reduces the consumption of heat, the energy, electric power.3, the low volatilization of also having avoided solvent of temperature of the present invention.Environmentally friendly.4, for gained filtrate, after simple process, can obtain byproduct, avoid waste, increase output.In sum, the present invention consumes low, less energy consumption, and less investment, output is high, and is safe and reliable, and energy decrease production cost can be obtained fine social benefit and considerable economic benefit.
Description of drawings
Fig. 1 is the rectification flow figure of solvent orange 2 A when being acetone, ethyl acetate, methylene dichloride, chloroform, ethanol, methyl alcohol.
Fig. 2 is the rectification flow figure of solvent orange 2 A when being alkaline aqueous solution.
Embodiment
Embodiment 1 pharmaceutical grade DM's is refining
Sodium hydroxide solution 5L with 0.5%, directly soak technical grade DM 5 kg, stir in 25 ℃ and soak 24h, with DM powder and the sodium hydroxide solution separating and filtering after soaking, the pressed powder DM that obtains is washed three times with 100ml, dry cake namely obtains pharmaceutical grade elaboration DM(yield 90%, purity 99.3%).
Embodiment 2 pharmaceutical grade DM's is refining
Sodium carbonate solution 50L with 0.02%, directly soak technical grade DM 5 kg, stir in 30 ℃ and soak 10h, with DM powder and the sodium carbonate solution separating and filtering after soaking, the pressed powder DM that obtains is washed three times with 100ml, dry cake namely obtains pharmaceutical grade elaboration DM(yield 91%, purity 99.2%).
Embodiment 3 pharmaceutical grade DM's is refining
Potassium hydroxide solution 25L with 2%, directly soak technical grade DM 5 kg, stir in 10 ℃ and soak 30h, with DM powder and the potassium hydroxide solution separating and filtering after soaking, the pressed powder DM that obtains is washed three times with 100ml, dry cake namely obtains pharmaceutical grade elaboration DM(yield 90%, purity 99.4%).
Embodiment 4 pharmaceutical grade DM's is refining
Use acetone soln 5L, directly soak technical grade DM 5 kg, stir in 10 ℃ and soak 10h, with DM powder and the acetone soln separating and filtering after soaking, the pressed powder DM that obtains is washed three times dry cake with 100ml acetone, namely obtain pharmaceutical grade elaboration DM(yield 89%, purity 99.4%).
Embodiment 5 pharmaceutical grade DM's is refining
Use ethyl acetate solution 50L, directly soak technical grade DM 5 kg, stir in 25 ℃ and soak 25h, with DM powder and the ethyl acetate solution separating and filtering after soaking, the pressed powder DM that obtains is washed three times with the 100ml ethyl acetate solution, dry cake namely obtains pharmaceutical grade elaboration DM(yield 89%, purity 99.4%).
Embodiment 6 pharmaceutical grade DM's is refining
Use dichloromethane solution 50L, directly soak technical grade DM 5 kg, stir in 15 ℃ and soak 25h, with DM powder and the dichloromethane solution separating and filtering after soaking, the pressed powder DM that obtains is washed three times with the 100ml dichloromethane solution, dry cake namely obtains pharmaceutical grade elaboration DM(yield 90%, purity 99.6%).
Embodiment 7 pharmaceutical grade DM's is refining
Use methanol solution 20L, directly soak technical grade DM 5 kg, stir in 25 ℃ and soak 24h, with DM powder and the methanol solution separating and filtering after soaking, the pressed powder DM that obtains is washed three times dry cake with the 100ml methanol solution, namely obtain pharmaceutical grade elaboration DM(yield 89%, purity 99.2%).
Embodiment 8 pharmaceutical grade DM's is refining
Use ethanolic soln 30L, directly soak technical grade DM 5 kg, stir in 30 ℃ and soak 15h, with DM powder and the ethanolic soln separating and filtering after soaking, the pressed powder DM that obtains is washed three times dry cake with the 100ml ethanolic soln, namely obtain pharmaceutical grade elaboration DM(yield 91%, purity 99.4%).
Embodiment 9 pharmaceutical grade DM's is refining
Use chloroformic solution 15L, directly soak technical grade DM 5 kg, stir in 35 ℃ and soak 10h, with DM powder and the chloroformic solution separating and filtering after soaking, the pressed powder DM that obtains is washed three times with 100ml chloroform ester solution, dry cake namely obtains pharmaceutical grade elaboration DM(yield 92%, purity 99.3%).
Embodiment 10 filtrates are reclaimed
Concentrated distillation embodiment 4 separates the acetone filtrate that obtains, and obtains by product M, reclaims solvent and obtains acetone 5.1L.
The purification of embodiment 11 captaxs
Embodiment 1 gained filtrate is neutralized with 5% hydrochloric acid, and the pH value is transferred to neutrality, separates out captax, filters, and obtains high quality M.
Certainly so-called known in those skilled in the art, to invade the bubble churning time passable in order to reduce, and takes the mode that heats.In order to shorten the time of drying of pharmaceutical grade elaboration DM, can add a small amount of alcohol wash, to take away moisture.
Above embodiment is only unrestricted in order to technical scheme of the present invention to be described, although with reference to preferred embodiment, the present invention is had been described in detail, those of ordinary skill in the art is to be understood that, can modify or be equal to replacement technical scheme of the present invention, and not breaking away from the spirit and scope of technical solution of the present invention, it all should be encompassed in the middle of claim scope of the present invention.
Claims (10)
1. the process for purification of a dibenzothiazyl disulfide, is characterized in that, comprises the steps:
Soak technical grade DM with solvent orange 2 A, stir 10-30h under 10-35 ℃;
Stop stirring, solid-liquid separation, solid washs with solvent B, and drying both gets.
2. the process for purification of a kind of dibenzothiazyl disulfide as claimed in claim 1, is characterized in that, described solvent orange 2 A is selected from acetone, ethyl acetate, methylene dichloride, chloroform, ethanol, methyl alcohol and alkaline aqueous solution.
3. the process for purification of a kind of dibenzothiazyl disulfide as claimed in claim 1 or 2, it is characterized in that, when solvent orange 2 A was selected from acetone, ethyl acetate, methylene dichloride, chloroform, ethanol, methyl alcohol, solvent B was selected from acetone, ethyl acetate, methylene dichloride, chloroform, ethanol, methyl alcohol; When solvent orange 2 A was alkaline aqueous solution, solvent B was water.
4. the process for purification of a kind of dibenzothiazyl disulfide as claimed in claim 2, is characterized in that, the concentration of described alkaline aqueous solution is 0.05-2%.
5. as the process for purification of claim 2 or 4 described a kind of dibenzothiazyl disulfides, it is characterized in that, described alkaline aqueous solution is aqueous sodium hydroxide solution, potassium hydroxide aqueous solution, aqueous sodium carbonate or wet chemical.
6. the process for purification of a kind of dibenzothiazyl disulfide as claimed in claim 1, is characterized in that, described solid-liquid separation is selected from filtration, centrifugal or press filtration.
7. the process for purification of a kind of dibenzothiazyl disulfide as claimed in claim 1, is characterized in that, the mass ratio of the volume of described solvent orange 2 A and technical grade DM is 1-10:1.
8. the process for purification of a kind of dibenzothiazyl disulfide as claimed in claim 1, it is characterized in that, with any solvent in acetone, ethyl acetate, methylene dichloride, chloroform, ethanol, methyl alcohol, directly soak technical grade DM, stir in 25 ℃ and soak 24h, with DM powder and the solution separating after soaking, obtain pressed powder DM, use any solvent wash pressed powder DM in acetone, ethyl acetate, methylene dichloride, chloroform, ethanol, methyl alcohol, drying had both obtained pharmaceutical grade elaboration DM again.
9. the process for purification of a kind of dibenzothiazyl disulfide as claimed in claim 1, it is characterized in that, use sodium hydroxide solution, directly soak technical grade DM, stir in 25 ℃ and soak 24h, DM powder and sodium hydroxide solution separating and filtering with after soaking wash the pressed powder DM that obtains three times with water, dry cake had both obtained pharmaceutical grade elaboration DM.
10. the process for purification of a kind of dibenzothiazyl disulfide as claimed in claim 1, is characterized in that, comprises that step (3) merges the solution after solid-liquid separation and solvent B, reclaims respectively M and solvent.
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| CN2013101044271A CN103145642A (en) | 2013-03-29 | 2013-03-29 | Refining method of mercaptobenzothiazole disulfide |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020055640A1 (en) * | 2000-11-08 | 2002-05-09 | Wolfgang Wolber | Process for the production of dithiazolyl disulfides |
| CN102167686A (en) * | 2011-03-17 | 2011-08-31 | 郑州大学 | Method for preparing 2,2'-dibenzothiazyl disulfide by catalyzing oxidation through molecular oxygen |
| CN102382077A (en) * | 2011-09-20 | 2012-03-21 | 科迈化工股份有限公司 | Method for preparing pharmaceutical grade DM (accelerator) with industrial grade DM |
| CN102838558A (en) * | 2012-09-25 | 2012-12-26 | 科迈化工股份有限公司 | Method for preparing rubber accelerator DM (2,2'-dithiobis(benzothiazole)) from 2-mercaptobenzothiazole coarse product as raw material |
-
2013
- 2013-03-29 CN CN2013101044271A patent/CN103145642A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020055640A1 (en) * | 2000-11-08 | 2002-05-09 | Wolfgang Wolber | Process for the production of dithiazolyl disulfides |
| CN102167686A (en) * | 2011-03-17 | 2011-08-31 | 郑州大学 | Method for preparing 2,2'-dibenzothiazyl disulfide by catalyzing oxidation through molecular oxygen |
| CN102382077A (en) * | 2011-09-20 | 2012-03-21 | 科迈化工股份有限公司 | Method for preparing pharmaceutical grade DM (accelerator) with industrial grade DM |
| CN102838558A (en) * | 2012-09-25 | 2012-12-26 | 科迈化工股份有限公司 | Method for preparing rubber accelerator DM (2,2'-dithiobis(benzothiazole)) from 2-mercaptobenzothiazole coarse product as raw material |
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》 * |
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Application publication date: 20130612 |