CN1569843A - Preparation method for sulfadoxine - Google Patents
Preparation method for sulfadoxine Download PDFInfo
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- CN1569843A CN1569843A CN 200410014838 CN200410014838A CN1569843A CN 1569843 A CN1569843 A CN 1569843A CN 200410014838 CN200410014838 CN 200410014838 CN 200410014838 A CN200410014838 A CN 200410014838A CN 1569843 A CN1569843 A CN 1569843A
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- sulphormethoxine
- sulfanilamide
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- sodium salt
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Abstract
Disclosed is the preparation method for sulfadoxine consisting a condensation reaction and a methyl oxidation reaction, wherein the former consists of charging N,N-dimethyl formamide, sulfonamide sodium salt, chloride into dried reaction container proportionally, then charging sulfonamide sodium salt, solid caustic soda, measuring pH=10, elevating the temperature and measuring pH=10 again, then carrying out in turn heating, heat preservation, recovering, dissolving, diluting, adjusting pH, cooling down, separating, acidifying, adjusting pH, dewatering, scouring and drying.
Description
Technical field
The present invention relates to a kind of preparation method of sulphormethoxine, is to existing sulphormethoxine preparation method's improvement, belongs to the sulfa drugs preparing technical field.
Background technology
Sulphormethoxine (fanasil) is white or off-white color crystalline powder, mildly bitter flavor, odorless, chance light gradual change look, is slightly soluble in water, methyl alcohol, ethanol, is insoluble to ether, dissolves in sodium hydroxide and the diluted mineral acid, belongs to sulfonamides.Can be in order to treatment pulmonary tuberculosis, lymphoid tuberculosis, Malaria etc., China lists it in " Chinese new high-tech product export list " (2003)
[7]In.
The result shows by literature search: Chinese Zhejiang Yuyao City Rec biotechnology company limited, Changshu, Chinese Jiangsu gold cypress doctorization Products Co., Ltd, Chinese Ningbo of Zhejiang gold reveal atomizer chemical industry You Xiangongsi ﹠amp; All there are the sulphormethoxine of production product in gold dew biotechnology company limited, the three-dimensional drugmaker of Chinese Shanghai Zhangjiang Fine Chemical Works, the bright hi-tech of Chinese Shanghai Group Co.,Ltd.Wherein the preparation method that sulphormethoxine adopted of Yuyao City Rec biotechnology company limited production all adopts a complete set of Technology in " Shanghai pharmaceutical prod production technique compilation ", meets British Pharmacopoeia 98 editions and American Pharmacopeia 24 editions.Its leading indicator is: content 99.00～101.00%, heavy metal≤0.002%, weight loss on drying≤0.5%, residue on ignition≤0.1%; And the sulphormethoxine that the golden cypress doctorization in aforesaid Changshu Products Co., Ltd produces meets British Pharmacopoeia 2000 editions (BP2000) and American Pharmacopeias 25 editions (USP25).Its leading indicator is: content (Sulphadoxine) 100.60%, heavy metal≤0.002%, 198 ℃ of fusing points, weight loss on drying 0.16%, residue on ignition 0.03%.
The heavy metal content of above-mentioned sulphormethoxine is higher, and heavy metal has hazardness to human body after taking in.The applicant finds: in the condensation reaction of sulphormethoxine production technique, by changing the souring temperature of pH value, can improve the content and the fusing point of reaction intermediate 4-sulfanilamide (SN) 5-methoxyl group 6-chloropyrimide; In the methoxy reaction, use deionized water, can avoid bringing into impurity, thereby content, fusing point, heavy metal content, the weight loss on drying of sulphormethoxine, the overall target of blazing ash are changed.
Summary of the invention
Task of the present invention is the preparation method that a kind of sulphormethoxine will be provided, and with the sulphormethoxine product of this method preparation, can reduce the content of heavy metal, improves overall target.
Task of the present invention is finished like this, a kind of preparation method of sulphormethoxine, and it comprises condensation reaction and methoxy reaction, characteristics are:
(1) condensation reaction is to add 3～3.2 parts N in the dry reaction container, the muriate of N dimethyl formamide and 1～1.2 part of sulfanilamide (SN) sodium salt and 0.9～1 part, in reaction vessel, drop into 1～1.2 part and 0.12～0.13 part solid caustic soda of sulfanilamide (SN) sodium salt again with aforementioned equivalent part, measure PH10, naturally be warming up to 55～60 ℃, measure PH10 once more, be warming up to 85～90 ℃, kept 85～95 minutes, reclaim N then, the N dimethyl formamide, to the N that reclaims, add 95 ℃～100 ℃ pure water in the N dimethyl formamide, treat that being pressed into cooling pan after solids dissolves fully dilutes, and adjusting PH7.2～7.3, be cooled to 15～20 ℃, with suction clarifying kettle behind the pure water rinsing separation sulfanilamide (SN), controlled temperature is made acidification with 15%HCL for 68～70 ℃, and control PH3.8～4.1, after centrifugal dewatering, washing, dry and 4-sulfanilamide (SN) 5-methoxyl group 6-chloropyrimide;
(2) the methoxy reaction be with the resulting 4-sulfanilamide (SN) of condensation reaction 5-methoxyl group 6-chloropyrimide put into 3.48 times to its methyl alcohol and 1.87 times in the solvent system that its sodium methylate is formed, continue 210～270 minutes down at 68～70 ℃, then reclaim anhydrous methanol to solid and add water continuation recovery, stop during to 90～95 ℃ of kettle temperatures reclaiming, then feed liquid is pressed into the dilution pot, dilute with reverse osmosis high purity water, adding activated carbon then decoloured 50～70 minutes down at 75～80 ℃, again feed liquid is pressed into clarifying kettle, be neutralized to PH5.1 with high-purity hydrochloric acid, centrifuge dehydration, washing obtains work in-process and adds Decolouring pot, with the reverse osmosis high purity water dilution, then through insulation, decolouring, filtration is pressed into clarifying kettle, 68～70 ℃ of adding Glacial acetic acid precipitations, and transfer PH to 5.1, after dehydration, washing, dry finished product sulphormethoxine.
Sulfanilamide (SN) sodium salt of the present invention is the White streptocide sodium salt.
Muriate of the present invention is 5-methoxyl group-46-dichloro pyrimidine.
Reverse osmosis high purity water of the present invention is no ion pure water.
High-purity hydrochloric acid of the present invention is that concentration is 38% colourless HCL.
The resulting sulphormethoxine of preparation method of the present invention, heavy metal content, weight loss on drying, blazing ash all are lower than with the sulphormethoxine that the technology preparation is arranged.
Embodiment
Embodiment:
(1) 250KgN, N dimethyl formamide (DMF) are dropped in the dry reaction pot, add 80Kg White streptocide sodium salt while stirring, drop into the 80Kg5-methoxyl group-46-dichloro pyrimidine that not only can make by oneself but also can commercially availablely buy again, and then drop into the 80Kg White streptocide, and add the 10Kg solid caustic soda.Screw pot cover, measure pH value 10, naturally be warmed up to 60 ℃, measure PH10 again, be warmed up to 90 ℃, be incubated 90 minutes, open high pressure vacuum pump reclaim under reduced pressure N, N dimethyl formamide (DMF), to reclaiming the 230KgN that obtains, add 100 ℃ of pure water 300Kg in the N dimethyl formamide (DMF), treat that material all is pressed into cooling pan after the dissolving, be diluted to 1500 liters, regulate PH to 7.2 with pure water, separate sulfanilamide (SN) when being cooled to 15 ℃ then, use pure water rinsing again, reach 2000 until mother liquor and only be upgraded to the suction clarifying kettle, at 70 ℃ of hcl acidifyings with concentration 15%, the control pH value is put into filtering element (cartridge) machine separating and dehydrating then 3.8～4.1, and through 60～80 ℃ of hot washes, dry, advance baking with 110 ℃, 4-sulfanilamide (SN) 5-methoxyl group 6-chloropyrimide dry product 115Kg;
(2) the 4-sulfanilamide (SN) 5-methoxyl group 6-chloropyrimide with 230Kg joins in the solvent system of being made up of 800Kg methyl alcohol and 430Kg sodium methylate, be warming up to 70 ℃, continue 240 minutes, anhydrous methanol to be recycled adds 800Kg water behind solid, continue to reclaim, when 95 ℃ of kettle temperatures, stop to reclaim, then feed liquid is pressed into the dilution pot and is diluted to 3000 liters with no ion pure water, add the 20Kg activated carbon, 80 ℃ of insulation decolourings 60 minutes, feed liquid is pressed into clarifying kettle through pressure filter, colourless hydrochloric acid with 38% under 70 ℃ is neutralized to PH5.1, through centrifuge dehydration, wash to the state of cooling with pure water and to obtain the sulphormethoxine work in-process, work in-process are added Decolouring pot, add no ion pure water and be diluted to 3000 liters, then through 80 ℃ of insulations, decolouring, filtration is pressed into clarifying kettle, add 30% Glacial acetic acid precipitation at 70 ℃, and transfer PH to 5.1, after dehydration, washing, oven dry obtains sulphormethoxine 195Kg.Its leading indicator after testing: content (Sulphadoxine) 100.3%, 198 ℃ of fusing points, heavy metal content≤0.001%, weight loss on drying≤0.15%, blazing ash (0.06%.
Claims (5)
1, a kind of preparation method of sulphormethoxine, it comprises condensation reaction and methoxy reaction, it is characterized in that:
(1) condensation reaction is to add 3～3.2 parts N in the dry reaction container, the muriate of N dimethyl formamide and 1～1.2 part of sulfanilamide (SN) sodium salt and 0.9～1 part, in reaction vessel, drop into 1～1.2 part and 0.12～0.13 part solid caustic soda of sulfanilamide (SN) sodium salt again with aforementioned equivalent part, measure PH10, naturally be warming up to 55～60 ℃, measure PH10 once more, be warming up to 85～90 ℃, kept 85～95 minutes, reclaim N then, the N dimethyl formamide, to the N that reclaims, add 95 ℃～100 ℃ pure water in the N dimethyl formamide, treat that being pressed into cooling pan after solids dissolves fully dilutes, and adjusting PH7.2～7.3, be cooled to 15～20 ℃, with suction clarifying kettle behind the pure water rinsing separation sulfanilamide (SN), controlled temperature is made acidification with 15%HCL for 68～70 ℃, and control PH3.8～4.1, after centrifugal dewatering, washing, dry and 4-sulfanilamide (SN) 5-methoxyl group 6-chloropyrimide;
(2) the methoxy reaction be with the resulting 4-sulfanilamide (SN) of condensation reaction 5-methoxyl group 6-chloropyrimide put into 3.48 times to its methyl alcohol and 1.87 times in the solvent system that its sodium methylate is formed, continue 210～270 minutes down at 68～70 ℃, then reclaim anhydrous methanol to solid and add water continuation recovery, stop during to 90～95 ℃ of kettle temperatures reclaiming, then feed liquid is pressed into the dilution pot, dilute with reverse osmosis high purity water, adding activated carbon then decoloured 50～70 minutes down at 75～80 ℃, again feed liquid is pressed into clarifying kettle, be neutralized to PH5.1 with high-purity hydrochloric acid, centrifuge dehydration, washing obtains work in-process and adds Decolouring pot, with the reverse osmosis high purity water dilution, then through insulation, decolouring, filtration is pressed into clarifying kettle, 68～70 ℃ of adding Glacial acetic acid precipitations, and transfer PH to 5.1, after dehydration, washing, dry finished product sulphormethoxine
2, the preparation method of sulphormethoxine according to claim 1 is characterized in that described sulfanilamide (SN) sodium salt is the White streptocide sodium salt.
3, the preparation method of sulphormethoxine according to claim 1 is characterized in that described muriate is 5-methoxyl group-46-dichloro pyrimidine.
4, the preparation method of sulphormethoxine according to claim 1 is characterized in that described reverse osmosis high purity water is no ion pure water.
5, the preparation method of sulphormethoxine according to claim 1 is characterized in that described high-purity hydrochloric acid is that concentration is 38% colourless HCL.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN 200410014838 CN1272327C (en) | 2004-04-29 | 2004-04-29 | Preparation method for sulfadoxine |
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| CN 200410014838 CN1272327C (en) | 2004-04-29 | 2004-04-29 | Preparation method for sulfadoxine |
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| CN1569843A true CN1569843A (en) | 2005-01-26 |
| CN1272327C CN1272327C (en) | 2006-08-30 |
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| CN 200410014838 Expired - Fee Related CN1272327C (en) | 2004-04-29 | 2004-04-29 | Preparation method for sulfadoxine |
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Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102304095A (en) * | 2011-09-23 | 2012-01-04 | 常熟市南湖实业化工有限公司 | Preparation method of sulfadoxine |
| CN102304094A (en) * | 2011-09-23 | 2012-01-04 | 常熟市南湖实业化工有限公司 | Preparation method of sulfadoxine and intermediate thereof |
| CN102311393A (en) * | 2011-09-23 | 2012-01-11 | 常熟市金申医化制品有限责任公司 | Preparation method of sulfadoxine |
| CN102391189A (en) * | 2011-09-23 | 2012-03-28 | 常熟市南湖实业化工有限公司 | Preparation method of sulfadoxine |
| CN102391190A (en) * | 2011-09-30 | 2012-03-28 | 常熟市金申医化制品有限责任公司 | Method for preparing sulfadoxine |
| CN102432550A (en) * | 2011-09-23 | 2012-05-02 | 常熟市南湖实业化工有限公司 | Methods for preparing sulfadoxine and intermediate of sulfadoxine |
| CN102516183A (en) * | 2011-09-23 | 2012-06-27 | 常熟市南湖实业化工有限公司 | Method for preparing sulfadoxine and its intermediate |
| CN103910686A (en) * | 2014-03-10 | 2014-07-09 | 常熟市南湖实业化工有限公司 | Method used for preparing sulfadimoxine from 4-(p-anilinesulfonamide)-5-methoxy-6 chloropyrimidine |
| CN103910687A (en) * | 2014-03-10 | 2014-07-09 | 常熟市南湖实业化工有限公司 | Preparation method of 4-(p-anilinesulfonamide)-5-methoxy-6 chloropyrimidine |
| CN103910685A (en) * | 2014-03-10 | 2014-07-09 | 常熟市南湖实业化工有限公司 | Method used for purifying sulfadimoxine |
| CN104447578A (en) * | 2014-12-13 | 2015-03-25 | 常熟市金申医化制品有限责任公司 | Method for preparing sulfadoxine |
| CN105153044A (en) * | 2015-09-15 | 2015-12-16 | 桂林南药股份有限公司 | Method for one-pot synthesis of sulfadoxine by monitoring reaction progress through HPLC |
| CN114948993A (en) * | 2022-03-29 | 2022-08-30 | 罗露曦 | Preparation method and application of skin gel for treating tinea capitis, skin eczema and acne |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114874148A (en) * | 2022-03-09 | 2022-08-09 | 江苏金申医药科技有限公司 | Sulfadoxine fine processing technology |
-
2004
- 2004-04-29 CN CN 200410014838 patent/CN1272327C/en not_active Expired - Fee Related
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102304094B (en) * | 2011-09-23 | 2014-03-26 | 常熟市南湖实业化工有限公司 | Preparation method of sulfadoxine and intermediate thereof |
| CN102304094A (en) * | 2011-09-23 | 2012-01-04 | 常熟市南湖实业化工有限公司 | Preparation method of sulfadoxine and intermediate thereof |
| CN102311393A (en) * | 2011-09-23 | 2012-01-11 | 常熟市金申医化制品有限责任公司 | Preparation method of sulfadoxine |
| CN102391189A (en) * | 2011-09-23 | 2012-03-28 | 常熟市南湖实业化工有限公司 | Preparation method of sulfadoxine |
| CN102304095A (en) * | 2011-09-23 | 2012-01-04 | 常熟市南湖实业化工有限公司 | Preparation method of sulfadoxine |
| CN102432550A (en) * | 2011-09-23 | 2012-05-02 | 常熟市南湖实业化工有限公司 | Methods for preparing sulfadoxine and intermediate of sulfadoxine |
| CN102516183A (en) * | 2011-09-23 | 2012-06-27 | 常熟市南湖实业化工有限公司 | Method for preparing sulfadoxine and its intermediate |
| CN102311393B (en) * | 2011-09-23 | 2013-03-13 | 常熟市金申医化制品有限责任公司 | Preparation method of sulfadoxine |
| CN102304095B (en) * | 2011-09-23 | 2013-10-16 | 常熟市南湖实业化工有限公司 | Preparation method of sulfadoxine |
| CN102391190A (en) * | 2011-09-30 | 2012-03-28 | 常熟市金申医化制品有限责任公司 | Method for preparing sulfadoxine |
| CN103910686A (en) * | 2014-03-10 | 2014-07-09 | 常熟市南湖实业化工有限公司 | Method used for preparing sulfadimoxine from 4-(p-anilinesulfonamide)-5-methoxy-6 chloropyrimidine |
| CN103910687A (en) * | 2014-03-10 | 2014-07-09 | 常熟市南湖实业化工有限公司 | Preparation method of 4-(p-anilinesulfonamide)-5-methoxy-6 chloropyrimidine |
| CN103910685A (en) * | 2014-03-10 | 2014-07-09 | 常熟市南湖实业化工有限公司 | Method used for purifying sulfadimoxine |
| CN103910686B (en) * | 2014-03-10 | 2016-05-11 | 常熟市南湖实业化工有限公司 | Utilize 4-(p-amino benzene sulfonyl)-5-methoxyl group-6 chlorine pyrimidine to prepare the method for sulfamethoxine |
| CN104447578A (en) * | 2014-12-13 | 2015-03-25 | 常熟市金申医化制品有限责任公司 | Method for preparing sulfadoxine |
| CN105153044A (en) * | 2015-09-15 | 2015-12-16 | 桂林南药股份有限公司 | Method for one-pot synthesis of sulfadoxine by monitoring reaction progress through HPLC |
| CN114948993A (en) * | 2022-03-29 | 2022-08-30 | 罗露曦 | Preparation method and application of skin gel for treating tinea capitis, skin eczema and acne |
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| CN1272327C (en) | 2006-08-30 |
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Effective date of registration: 20090306 Address after: Nanhu farm, Changshou City, Jiangsu Patentee after: Changshu Nanhu Industrial Chemical Co., Ltd Address before: Nanhu farm, Changshou City, Jiangsu Patentee before: Changshu City Nan-hu Industrial Factory |
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Owner name: CHANGSHU NANHU INDUSTRIAL CHEMICAL CO., LTD. Free format text: FORMER OWNER: CHANGSHU NANHU INDUSTRIAL CHEMICAL PLANT Effective date: 20090306 |
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Assignee: Taicang Pharmaceutical Factory Assignor: Changshu Nanhu Industrial Chemical Co., Ltd Contract record no.: 2010320001199 Denomination of invention: Preparation method for sulfadoxine Granted publication date: 20060830 License type: Exclusive License Open date: 20050126 Record date: 20101122 |
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