CN104356075B - 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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- CN104356075B CN104356075B CN201410629018.8A CN201410629018A CN104356075B CN 104356075 B CN104356075 B CN 104356075B CN 201410629018 A CN201410629018 A CN 201410629018A CN 104356075 B CN104356075 B CN 104356075B
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- sulfadiazine
- refining method
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- fluidity
- bulk density
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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 pharmaceutical technology field, and in particular to a kind of to improve sulfadiazine heap density and mobility
Process for purification
Background technology
Sulfadiazine (SD) belongs to median acting sulfonamide class medicine.Molecular formula C10H10N4O2S, molecular weight 250.28, its chemical name
Referred to as：Sulfadiazine.Chemical structural formula is：
Sulfadiazine is one of larger product of yield in sulfa drugss, domestic to adopt propilolic alcohol method or vinyl second
Ether method synthesizes.The process for purification of sulfadiazine crude product is that sulfadiazine is prepared into calcium salt first by reactive crystallization, adds activity
Charcoal adsorption-edulcoration, is precipitated with acetic acid after filtration and obtains finished product.Obtained product quality is light in this way, and heap density exists
0.34g/mL～0.45g/mL, granularity are little, and main granularity is generally less than 100 μm, characterize generally higher than 43 ° of the angle of repose of mobility,
Dust from flying in production process, wastes larger.Foreign countries are that sulfadiazine crude product and ammonium hydroxide are made ammonium salt, through decolourizing
Afterwards, carbon dioxide precipitates are passed through or sulfadiazine fine work is prepared using decompression ammonia excretion method.But sulfadiazine ammonium salt leads to
Enter carbon dioxide precipitates not exclusively, yield is low, and using decompression ammonia excretion method as the ammonia excretion time is long, often product color be rubescent,
Affect quality.Reagent dosage for occurring in sulfadiazine subtractive process is more, power consumption, the problems such as product quality is bad, this
Bright to be intended to propose a kind of new process for purification, improve product quality makes whole technological process simple.
The content of the invention
It is an object of the invention to provide a kind of reducing energy consumption, reduces solvent load, sulfadiazine heap density and grain are improved
The process for purification of degree.
The technical solution adopted for the present invention to solve the technical problems is：It is a kind of to improve sulfadiazine heap density and mobility
Process for purification, processing step is：Add in the reactor sulfadiazine crude product and the organic solvent, organic solvent can be：N-
Methyl pyrrolidone NMP, dimethylformamide DMF, dimethyl sulfoxide DMSO；Sulfadiazine with the mass ratio of organic solvent is：
1：2～7, at 40 DEG C～70 DEG C, optimum is stirred at 50 DEG C～60 DEG C steady temperature, adds sulfadiazine mass fraction 1%
Activated carbon decolorizing, after filtration, adds water toward filtrate, water and Zhi Liang Bi≤1 of organic solvent, after adding water, drops whole system
Temperature is cooled to final temperature for 0～30 DEG C, filters, be drying to obtain sulfadiazine crystal after stablizing.
Author Ding Xue by force document heavy sulfadiazine development it is medium mention, the refined sulfanilamide of reaction-crystallization method is phonetic
Pyridine, the solvent load of needs are 25～35 times of crude product quality, and system needs to be warmed up to more than 80 DEG C and could react complete, in order to
Reducing energy consumption, reduces solvent, and reactive crystallization is changed into dilution crystallization by the present invention, it is to avoid high temperature, substantially reduce the number solvent load.
Sulfadiazine with the mass ratio of N-Methyl pyrrolidone is：1：2～7, 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 conventional process high temperature reactive crystallization with dissolved crystallisation by cooling, not only make institute
Obtain crystal heap density and granularity is greatly increased, and reduce energy consumption, reduce solvent load, technological operation letter
It is single, it is easy to control.In drug manufacture, the heap density of particle, particle size, mobility have to the post processing processing characteristics of medicine
Very big impact.The increase of heap density, mobility improve storage, the transport for being conducive to product；Be also beneficial to active constituents of medicine with it is auxiliary
The mixing of material, also helps the subsequent processes such as tabletting or pelletize, so it is critically important one of subtractive process to improve particle propertiess
Item index.By the process for refining in the present invention, the heap density of sulfadiazine can bring up to more than 0.6g/mL, and main granularity can
To reach 200 microns, and there is good mobility, 35 ° can be reached angle of repose.
Description of the drawings
Process for refining schematic flow sheet of the accompanying drawing 1 for the present invention；
Microphotograph of the accompanying drawing 2 for 1 products obtained therefrom of embodiment；
XRD powder diagram of the accompanying drawing 3 for 1 products obtained therefrom of embodiment；
Particle size distribution figure of the accompanying drawing 4 for 1 products obtained therefrom of embodiment.
Specific embodiment
Below by by the specific embodiment of embodiment form, the above of the present invention is made further specifically
It is bright.But this scope for being interpreted as above-mentioned theme of the invention should not be only limitted to following examples.It is all above-mentioned interior based on the present invention
Hold realized technology and belong to the scope of the present invention.
Embodiment 1
By the 24gN- methyl pyrrolidones of 6g sulfadiazines dissolving crude product to 50 DEG C；Sulfadiazine quality is added after dissolving
1% activated carbon, decolourizes 30 minutes；Filter；By filtrate constant temperature after 60 DEG C, add water in filtrate dissolved, with constant in 2 hours
Speed adds 24g deionized waters, separates out crystal；After dripping water, system is cooled to into 30 DEG C through 1h, constant temperature 20 minutes；Cross
Filter, washing, is drying to obtain sulfadiazine crystal.
Detect that the angle of repose of product is 36 ° according to GB11986-89 methods describeds, the heap density of product is 0.62g/mL, main
207.9 μm of granularity.The microphotograph of product, XRD 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 pyrrolidones of 5g sulfadiazines dissolving crude product to 70 DEG C；Add the work of sulfadiazine quality 1%
Property charcoal, decolourize 20 minutes；Filter；By filtrate constant temperature after 70 DEG C, add water in filtrate dissolved, is added with constant speed in 3 hours
Enter 30g deionized waters, separate out crystal；After dripping water, system is cooled to into 20 DEG C through 1h, constant temperature 20 minutes；Filter, wash
Wash, be drying to obtain sulfadiazine crystal.
Detect that the angle of repose of product is 35.2 ° according to GB11986-89 methods describeds, the heap density of product is 0.64g/mL,
235.5 μm of main granularity.
Embodiment 3
By the 28gN- methyl pyrrolidones of 4g sulfadiazines dissolving crude product to 40 DEG C；Add the work of sulfadiazine quality 1%
Property charcoal, decolourize 40 minutes；Filter；By filtrate constant temperature after 40 DEG C, add water in filtrate dissolved, is added with constant speed in 4 hours
Enter 42g deionized waters, separate out crystal；After dripping water, system is cooled to into 0 DEG C through 1h, constant temperature 20 minutes；Filter, washing,
It is drying to obtain sulfadiazine crystal.
Detect that the angle of repose of product is 38.4 ° according to GB11986-89 methods describeds, the heap density of product is 0.57g/mL,
193.5 μm of main granularity.
Embodiment 4
By the 40gN- methyl pyrrolidones of 10g sulfadiazines dissolving crude product to 60 DEG C；Add sulfadiazine quality 1%
Activated carbon, decolourizes 30 minutes；Filter；By filtrate constant temperature after 60 DEG C, add water in filtrate dissolved, with constant speed in 5 hours
80g deionized waters are added, crystal is separated out；After dripping water, system is cooled to into 20 DEG C through 1h, constant temperature 30 minutes；Filter, wash
Wash, be drying to obtain sulfadiazine crystal.
Detect that the angle of repose of product is 34.6 ° according to GB11986-89 methods describeds, the heap density of product is 0.67g/mL,
246.7 μm of main granularity.
Embodiment 5
By the 25g dimethylformamide DMF of 7g sulfadiazines dissolving crude product to 40 DEG C；Add sulfadiazine quality 1%
Activated carbon, decolourizes 30 minutes；Filter；By filtrate constant temperature after 40 DEG C, add water in filtrate dissolved, with constant speed in 2.5 hours
Degree adds 50g deionized waters, separates out crystal；After dripping water, system is cooled to into 20 DEG C through 0.5h, constant temperature 30 minutes；Cross
Filter, washing, is drying to obtain sulfadiazine crystal.
Detect that the angle of repose of product is 36.3 ° according to GB11986-89 methods describeds, the heap density of product is 0.61g/mL,
189.6 μm of main granularity.
Embodiment 6
By the 33g dimethyl sulfoxide DMSO of 11g sulfadiazines dissolving crude product to 55 DEG C；Add sulfadiazine quality 1%
Activated carbon, decolourizes 20 minutes；Filter；By filtrate constant temperature after 55 DEG C, add water in filtrate dissolved, with constant speed in 4 hours
100g deionized waters are added, crystal is separated out；After dripping water, system is cooled to into 10 DEG C through 0.5h, constant temperature 30 minutes；Cross
Filter, washing, is drying to obtain sulfadiazine crystal.
Detect that the angle of repose of product is 35.5 ° according to GB11986-89 methods describeds, the heap density of product is 0.63g/mL,
204.5 μm of main granularity.
Embodiment 7
By the 30g dimethyl sulfoxide DMSO of 15g sulfadiazines dissolving crude product to 65 DEG C；Add sulfadiazine quality 1%
Activated carbon, decolourizes 10 minutes；Filter；By filtrate constant temperature after 65 DEG C, add water in filtrate dissolved, with constant speed in 2 hours
50g deionized waters are added, crystal is separated out；After dripping water, system is cooled to into 10 DEG C through 1h, constant temperature 30 minutes；Filter, wash
Wash, be drying to obtain sulfadiazine crystal.
Detect that the angle of repose of product is 35.5 ° according to GB11986-89 methods describeds, the heap density of product is 0.63g/mL,
204.5 μm of main granularity.
Claims (3)
1. a kind of method of the refined sulfadiazine for improving sulfadiazine heap density and mobility, is characterized in that adding in reactor
Enter sulfadiazine crude product and organic solvent, stirring and dissolving under steady temperature, solution temperature are 40 DEG C～70 DEG C, add activated carbon to take off
Color, after filtration, adds water toward filtrate, filters, be drying to obtain sulfadiazine crystal after being cooled to 0～30 DEG C；Wherein organic solvent
It is N-Methyl pyrrolidone or dimethylformamide or dimethyl sulfoxide；Sulfadiazine crude product is 1 with the mass ratio of organic solvent：
2～7；Mass ratio≤1 of N-Methyl pyrrolidone or dimethylformamide or dimethyl sulfoxide and water.
2. a kind of as claimed in claim 1 method of the refined sulfadiazine for improving sulfadiazine heap density and mobility, which is special
It is 50 DEG C～60 DEG C to levy the solution temperature described in being.
3. a kind of as claimed in claim 1 method of the refined sulfadiazine for improving sulfadiazine heap density and mobility, which is special
The cooling final temperature described in being is levied at 15 DEG C～25 DEG C.
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| CN201410629018.8A CN104356075B (en) | 2014-11-10 | 2014-11-10 | Refining method for increasing bulk density and fluidity of sulfadiazine |
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| CN104356075A CN104356075A (en) | 2015-02-18 |
| CN104356075B true CN104356075B (en) | 2017-04-12 |
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| 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 |
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