CN104356075A - Refining method for increasing bulk density and fluidity of sulfadiazine - Google Patents
Refining method for increasing bulk density and fluidity of sulfadiazine Download PDFInfo
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- CN104356075A CN104356075A CN201410629018.8A CN201410629018A CN104356075A CN 104356075 A CN104356075 A CN 104356075A CN 201410629018 A CN201410629018 A CN 201410629018A CN 104356075 A CN104356075 A CN 104356075A
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- purification
- sulphadiazine sodium
- sulfadiazine
- bulk density
- refining method
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/69—Benzenesulfonamido-pyrimidines
Abstract
The invention relates to a refining method for increasing the bulk density and the fluidity of sulfadiazine. The refining method comprises the following steps: adding rough sulfadiazine and organic solvents into a reaction kettle, wherein the organic solvents include N-methylpyrrolidone NMP, dimethylformamide DMF and dimethyl sulfoxide DMSO; stirring at a constant temperature, and adding activated carbon to carry out decoloration; after filtering, adding water into filtrate, cooling, filtering, and drying so as to obtain sulfadiazine crystals. According to the refining method, a high-temperature reaction cooling crystallization manner in a conventional process is replaced by a dilution crystallization manner by virtue of the organic solvents and water, so that the consumption of the solvents is greatly reduced, the whole technical process is simplified, the consumption and the loss of a great deal of energy caused by the high temperature are avoided, and an obtained sulfadiazine product is large in granularity and relatively good in bulk density and fluidity.
Description
Technical field
The invention belongs to chemical engineering medical art, be specifically related to a kind of process for purification improving Sulphadiazine Sodium bulk density and mobility
Background technology
Sulphadiazine Sodium (SD) belongs to median acting sulfonamide class medicine.Molecular formula C
10h
10n
4o
2s, molecular weight 250.28, its chemical name is: Sulfadiazine.Chemical structural formula is:
Sulphadiazine Sodium is one of product that in sulfa drugs, output is larger, domestic employing propiolic alcohol method or the synthesis of ethyl vinyl ether method.The process for purification of Sulphadiazine Sodium crude product is first Sulphadiazine Sodium is prepared into calcium salt by reactive crystallization, adds charcoal absorption removal of impurities, obtains finished product after filtration by acetic acid precipitation.Adopt lighter in weight obtained in this way, bulk density is at 0.34g/mL ~ 0.45g/mL, and granularity is little, and main granularity is generally less than 100 μm, and the slope of repose characterizing mobility is generally greater than 43 °, dust from flying in production process, wastes larger.Be abroad that Sulphadiazine Sodium crude product and ammonium hydroxide are made ammonium salt, after decolouring, pass into carbon dioxide precipitates or adopt decompression ammonia excretion method and prepare Sulphadiazine Sodium fine work.But it is incomplete that Sulphadiazine Sodium ammonium salt passes into carbon dioxide precipitates, and yield is low, and adopt decompression ammonia excretion method due to the ammonia excretion time long, often product color is rubescent, affects quality.The problems such as, power consumption many for the reagent dosage occurred in Sulphadiazine Sodium treating process, quality product is bad, the invention is intended to propose a kind of new process for purification, improve the quality of products, make whole technical process simple.
Summary of the invention
The object of the present invention is to provide a kind of reduction energy consumption, reduce solvent load, improve the process for purification of Sulphadiazine Sodium bulk density and granularity.
The technical solution adopted for the present invention to solve the technical problems is: a kind of process for purification improving Sulphadiazine Sodium bulk density and mobility, processing step is: in reactor, add Sulphadiazine Sodium crude product and organic solvent, organic solvent can be: N-Methyl pyrrolidone NMP, dimethyl formamide DMF, dimethyl sulfoxide (DMSO) DMSO; The mass ratio of Sulphadiazine Sodium and organic solvent is: 1:2 ~ 7, steady temperature is at 40 DEG C ~ 70 DEG C, optimum stirring at 50 DEG C ~ 60 DEG C, adds the activated carbon decolorizing of Sulphadiazine Sodium massfraction 1%, after filtration, add water in filtrate, water and Zhi Liang Bi≤1 of organic solvent, after water injection, make whole system cooling down be 0 ~ 30 DEG C to outlet temperature, filter after stable, be drying to obtain Sulphadiazine Sodium crystal.
Author Ding Xue mentions the development of document heavy sulfadiazine is medium by force, reaction-crystallization method refines Sulphadiazine Sodium, the solvent load needed is 25 ~ 35 times of crude product quality, system needs to be warmed up to more than 80 DEG C and just can react completely, in order to reduce energy consumption, reduce solvent, reactive crystallization is become dilution crystallization by the present invention, avoid high temperature, substantially reduce the number solvent load.The mass ratio of Sulphadiazine Sodium and N-Methyl pyrrolidone is: 1:2 ~ 7, and the ratio of water and N-Methyl pyrrolidone is more than or equal to 1:1.
The invention has the beneficial effects as follows: replace pyroreaction crystallization in conventional process with dissolved crystallisation by cooling, not only make gained crystal bulk density and granularity be greatly increased, and energy consumption is reduced, reduce solvent load, technological operation is simple, is convenient to control.In drug manufacture, the bulk density of particle, size of particles, the aftertreatment processing characteristics of mobility to medicine have a significant impact.Bulk density increases, mobility improves the storage, the transport that are conducive to product; Also be conducive to mixing of active constituents of medicine and auxiliary material, also help the subsequent process such as compressing tablet or granulation, so improving particle properties is the very important index for the treatment of process.By the process for refining in the present invention, the bulk density of Sulphadiazine Sodium can bring up to more than 0.6g/mL, and main granularity can reach 200 microns, and has good mobility, and slope of repose can reach 35 °.
Accompanying drawing explanation
Accompanying drawing 1 is process for refining schematic flow sheet of the present invention;
Accompanying drawing 2 is the microphotograph of embodiment 1 products obtained therefrom;
Accompanying drawing 3 is the XRD powder diagram of embodiment 1 products obtained therefrom;
Accompanying drawing 4 is the particle size distribution figure of embodiment 1 products obtained therefrom.
Embodiment
Below by the embodiment by embodiment form, foregoing of the present invention is described in further detail.But this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following examples.All technology realized based on foregoing of the present invention all belong to scope of the present invention.
Embodiment 1
By the 24gN-methyl-2-pyrrolidone of 6g Sulphadiazine Sodium dissolving crude product to 50 DEG C; Add the gac of Sulphadiazine Sodium quality 1% after dissolving, decolour 30 minutes; Filter; By filtrate constant temperature after 60 DEG C, add water dissolved in filtrate, adds 24g deionized water, crystallize out in 2 hours with constant speed; After dripping water, system is cooled to 30 DEG C through 1h, constant temperature 20 minutes; Filter, washing, is drying to obtain Sulphadiazine Sodium crystal.
According to GB11986-89, the slope of repose of method testing product is 36 °, and the bulk density of product is 0.62g/mL, main granularity 207.9 μm.The microphotograph of product, XRD figure spectrum and particle size distribution figure are as shown in accompanying drawing 2, accompanying drawing 3 and accompanying drawing 4.
Embodiment 2
By the 15gN-methyl-2-pyrrolidone of 5g Sulphadiazine Sodium dissolving crude product to 70 DEG C; Add the gac of Sulphadiazine Sodium quality 1%, decolour 20 minutes; Filter; By filtrate constant temperature after 70 DEG C, add water dissolved in filtrate, adds 30g deionized water, crystallize out in 3 hours with constant speed; After dripping water, system is cooled to 20 DEG C through 1h, constant temperature 20 minutes; Filter, washing, is drying to obtain Sulphadiazine Sodium crystal.
According to GB11986-89, the slope of repose of method testing product is 35.2 °, and the bulk density of product is 0.64g/mL, main granularity 235.5 μm.
Embodiment 3
By the 28gN-methyl-2-pyrrolidone of 4g Sulphadiazine Sodium dissolving crude product to 40 DEG C; Add the gac of Sulphadiazine Sodium quality 1%, decolour 40 minutes; Filter; By filtrate constant temperature after 40 DEG C, add water dissolved in filtrate, adds 42g deionized water, crystallize out in 4 hours with constant speed; After dripping water, system is cooled to 0 DEG C through 1h, constant temperature 20 minutes; Filter, washing, is drying to obtain Sulphadiazine Sodium crystal.
According to GB11986-89, the slope of repose of method testing product is 38.4 °, and the bulk density of product is 0.57g/mL, main granularity 193.5 μm.
Embodiment 4
By the 40gN-methyl-2-pyrrolidone of 10g Sulphadiazine Sodium dissolving crude product to 60 DEG C; Add the gac of Sulphadiazine Sodium quality 1%, decolour 30 minutes; Filter; By filtrate constant temperature after 60 DEG C, add water dissolved in filtrate, adds 80g deionized water, crystallize out in 5 hours with constant speed; After dripping water, system is cooled to 20 DEG C through 1h, constant temperature 30 minutes; Filter, washing, is drying to obtain Sulphadiazine Sodium crystal.
According to GB11986-89, the slope of repose of method testing product is 34.6 °, and the bulk density of product is 0.67g/mL, main granularity 246.7 μm.
Embodiment 5
By the 25g dimethyl formamide DMF of 7g Sulphadiazine Sodium dissolving crude product to 40 DEG C; Add the gac of Sulphadiazine Sodium quality 1%, decolour 30 minutes; Filter; By filtrate constant temperature after 40 DEG C, add water dissolved in filtrate, adds 50g deionized water, crystallize out in 2.5 hours with constant speed; After dripping water, system is cooled to 20 DEG C through 0.5h, constant temperature 30 minutes; Filter, washing, is drying to obtain Sulphadiazine Sodium crystal.
According to GB11986-89, the slope of repose of method testing product is 36.3 °, and the bulk density of product is 0.61g/mL, main granularity 189.6 μm.
Embodiment 6
By the 33g dimethyl sulfoxide (DMSO) DMSO of 11g Sulphadiazine Sodium dissolving crude product to 55 DEG C; Add the gac of Sulphadiazine Sodium quality 1%, decolour 20 minutes; Filter; By filtrate constant temperature after 55 DEG C, add water dissolved in filtrate, adds 100g deionized water, crystallize out in 4 hours with constant speed; After dripping water, system is cooled to 10 DEG C through 0.5h, constant temperature 30 minutes; Filter, washing, is drying to obtain Sulphadiazine Sodium crystal.
According to GB11986-89, the slope of repose of method testing product is 35.5 °, and the bulk density of product is 0.63g/mL, main granularity 204.5 μm.
Embodiment 7
By the 30g dimethyl sulfoxide (DMSO) DMSO of 15g Sulphadiazine Sodium dissolving crude product to 65 DEG C; Add the gac of Sulphadiazine Sodium quality 1%, decolour 10 minutes; Filter; By filtrate constant temperature after 65 DEG C, add water dissolved in filtrate, adds 50g deionized water, crystallize out in 2 hours with constant speed; After dripping water, system is cooled to 10 DEG C through 1h, constant temperature 30 minutes; Filter, washing, is drying to obtain Sulphadiazine Sodium crystal.
According to GB11986-89, the slope of repose of method testing product is 35.5 °, and the bulk density of product is 0.63g/mL, main granularity 204.5 μm.
Claims (7)
1. one kind is improved the process for purification of Sulphadiazine Sodium bulk density and mobility, it is characterized in that in reactor, add Sulphadiazine Sodium crude product and organic solvent, stirring and dissolving under steady temperature, solvent temperature is 40 DEG C ~ 70 DEG C, add activated carbon decolorizing, after filtration, add water in filtrate, filter after being cooled to 0 ~ 30 DEG C, be drying to obtain Sulphadiazine Sodium crystal.
2. process for purification as claimed in claim 1, is characterized in that described cooling adopts dissolved crystallisation by cooling.
3. process for purification as claimed in claim 1, is characterized in that described organic solvent is: N-Methyl pyrrolidone NMP, dimethyl formamide DMF or dimethyl sulfoxide (DMSO) DMSO.
4. process for purification as claimed in claim 1, is characterized in that the mass ratio of described Sulphadiazine Sodium and organic solvent is: 1:2 ~ 7.
5. process for purification as claimed in claim 3, is characterized in that: mass ratio≤1 of organic solvent and water.
6. process for purification as claimed in claim 1, is characterized in that described solvent temperature is 50 DEG C ~ 60 DEG C.
7. process for purification as claimed in claim 1, is characterized in that described cooling outlet temperature is at 15 DEG C ~ 25 DEG C.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113831322A (en) * | 2021-10-27 | 2021-12-24 | 安徽华星化工有限公司 | Refining method of high-purity rimsulfuron |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2484791A (en) * | 1944-08-24 | 1949-10-11 | American Cyanamid Co | Purification of nu-substituted sulfanilamides |
| CN102603655A (en) * | 2012-03-01 | 2012-07-25 | 上海化工研究院 | Synthetic method of deuterium-marked sulfanilamide |
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2014
- 2014-11-10 CN CN201410629018.8A patent/CN104356075B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2484791A (en) * | 1944-08-24 | 1949-10-11 | American Cyanamid Co | Purification of nu-substituted sulfanilamides |
| CN102603655A (en) * | 2012-03-01 | 2012-07-25 | 上海化工研究院 | Synthetic method of deuterium-marked sulfanilamide |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113831322A (en) * | 2021-10-27 | 2021-12-24 | 安徽华星化工有限公司 | Refining method of high-purity rimsulfuron |
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Address after: 300350 District, Jinnan District, Tianjin Haihe Education Park, 135 beautiful road, Beiyang campus of Tianjin University Patentee after: Tianjin University Address before: 300072 Tianjin City, Nankai District Wei Jin Road No. 92, Tianjin University Patentee before: Tianjin University |