CN1034719A - A kind of method of producing sulfapyrimidine - Google Patents
A kind of method of producing sulfapyrimidine Download PDFInfo
- Publication number
- CN1034719A CN1034719A CN 89100054 CN89100054A CN1034719A CN 1034719 A CN1034719 A CN 1034719A CN 89100054 CN89100054 CN 89100054 CN 89100054 A CN89100054 A CN 89100054A CN 1034719 A CN1034719 A CN 1034719A
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- CN
- China
- Prior art keywords
- acid
- producing
- sulfanilylguanidine
- reaction
- sulphadiazine sodium
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Abstract
A kind of method of producing Sulphadiazine Sodium relates to the production method of benzenesulfonamido-pyrimidines.The production structure formula is
Compound, adopt N, N-two substituted formamides, phosphorus trichloride, the acetaldehyde glycol CH that contracts
3CH (OR)
2(R is CH
3-, C
2H
5-, C
3H
7-) for raw material carries out addition reaction, obtain addition oil; Ring-closure reaction acquisition raw product takes place in sulfanilylguanidine and addition oil in containing R ' OH of NaOR ' (R ' for straight chained alkyl) then; Through decolouring, acid out, filtration can obtain finished product.This technology is simple and direct, and operation is easily gone, and is dangerous few, the recovery rate height, and through a decolorizing and refining, final product quality can reach 1980 editions British Pharmacopoeia standard-requireds.
Description
The present invention relates to the production method of pyrimidines, specially refer to the production method of benzenesulfonamido-pyrimidines.
Before the present invention proposes, West Germany BAFS (Badische Anilin-Soda Fabrik Akt-Ges) claims in its obtained English Patent [(Brit 860,423 (1961)]: with dimethyl formamide photoreactive gas (COCl
2) in benzene, mix and add in the ethyl vinyl ether; This solution cooling back and NaoMe, NSC 2020 adds among the MeOH simultaneously; Heating is filtered said mixture and is removed and desolvates that can to obtain fusing point be that 38～39 ℃ 2-aminopyrimidine yield is 81%.Adopt similar means then can prepare Sulphadiazine Sodium, its yield is 80%.The formal name used at school of Sulphadiazine Sodium is 2-(p-amino benzene sulfonyl) pyrimidine, and its structural formula is
Adopt this production method also need react by pellet type catalyst and obtain ethyl vinyl ether at 145～150 ℃.Beaded catalyst potassium hydroxide, ethanol, lime is made.The method of this production Sulphadiazine Sodium need be used deleterious phosgene, inflammable and explosive acetylene and alcohol vapour, brought difficulty for production technology and production operation, careless slightly will working the mischief becomes a significant problem in the safety in production.Production will be from the preparation of ethyl vinyl ether, and it is tediously long that whole technological process just seems, the production cycle is also long.Temperature of reaction height during preparation, catalyzer can not regenerating reactivating.The thick product needed of being produced by this method of Sulphadiazine Sodium just can reach standards of pharmacopoeia through twice decolouring, has further elongated the production course, has increased trouble to operation.
The objective of the invention is to overcome above-mentioned weak point of the prior art provides a kind of technology simple and direct, and operation is easily gone, and yield is higher, the production method of the Sulphadiazine Sodium that quality product is new preferably.
Purpose of the present invention can realize by following technical measures: with N, N-two substituted formamides and phosphorus trichloride drop into acetaldehyde and contract in the glycol, and the contract chemical general formula of glycol of acetaldehyde is CH
3CH (OR)
2, R is CH in the formula
3-, C
2H
5-, C
3H
7-; Above-mentioned substance carries out addition reaction under suitable temperature, and diluting adduct with R ' OH becomes addition oil.Above-mentioned addition oil and sulfanilylguanidine input are contained among R ' OH of NaOR ' (R ' be straight chained alkyl), the formal name used at school of sulfanilylguanidine is the p-amino benzene sulfonyl carbonamidine, structural formula is
Under the certain temperature condition, carry out ring-closure reaction.Reflux then to reclaim amine and alcohol, carry out the thick product that the acid out after-filtration can obtain Sulphadiazine Sodium with mineral acid.Utilize basic oxide and porous mass that thick product is decoloured, carry out acid out with weak acid behind this porous mass of elimination, promptly obtain the Sulphadiazine Sodium finished product through washing and filtration again.
Send out at once carrying out addition, 0.35～1.1 part N, the phosphorus trichloride of N '-two substituted formamides and 0.5～1.3 part drop into 0.4～1.2 part of (being part by weight) acetaldehyde glycol CH that contracts
3CH (OR)
2[R is CH
3-, C
2H
5-, C
3H
7-] in, the three reacts in 10～100 ℃ of temperature ranges, obtains adduct, and dilutes this adduct with R ' OH (R ' be straight chained alkyl) and become addition oil.Addition send out should in more excellent proportioning be: the acetaldehyde glycol CH that contracts
3CH (OR)
2: phosphorus trioxide: N, N-two substituted formamides=(0.5～0.8): (0.7～0.9): (0.4～0.7) (weight ratio).More excellent temperature range is 20～80 ℃.
When carrying out ring-closure reaction, sulfanilylguanidine and above-mentioned addition oil are dropped among the R ' OH that contains NaOR ' simultaneously (R ' be straight chained alkyl).Sulfanilylguanidine and the acetaldehyde glycol CH that contracts
3CH (OR)
2Ratio be 1: (0.4～1.2) (weight ratio); In 30～90 ℃ of scopes, carry out ring-closure reaction.Reclaim amine and alcohol with reflow method.The adding mineral acid carries out acid out makes PH reach 4.5～5.5, obtains the thick product of Sulphadiazine Sodium after filtering and washing.
With the thick product Jia Shui of ring-closure reaction gained and add basic oxide, make PH reach 10～12, adsorb with porous mass, remove by filter and carry out acid out with weak acid behind this porous mass and make PH=4.5～5.5, reach dry back more after filtration and just can obtain the Sulphadiazine Sodium product.This treating process is very common in the prior art.
This Sulphadiazine Sodium product can reach 99.2～99.9% through chemical examination content, and fusing point is 254.5～257.5, and solution color and luster＜GY6 meets 1980 years version British Pharmacopoeia standards fully.Product is through infrared spectrum analysis; Conform to fully with the standard infrared spectra curve of Sulphadiazine Sodium.
The present invention has following advantage compared to existing technology: have only addition in this production method, and cyclization, refining three phases, catalyzer that need be special not, the simple and direct and convenient operation and control of technology is easily gone; And the catalyst of employed production ethyl vinyl ether once only can use 200 hours in the prior art, so that operating procedure, need make process long and complicated from the preparation catalyzer.This production method does not need deleterious phosgene, does not need inflammable and explosive acetylene and alcohol vapour yet, has increased the security that operation is produced greatly.The product yield of this production method is higher, and total recovery only 70% in the prior art, and recovery rate is 80% (for sulfanilylguanidine) only, and the total recovery of present method can reach 76%, and recovery rate reaches 91-92% (for sulfanilylguanidine).By this production method products obtained therefrom purity good quality height, coarse products only needs can meet the British Pharmacopoeia standard through once decolouring.
The present invention is described in further detail in conjunction with the embodiments:
In the exsiccant there-necked flask, drop into acetal CH
3CH (OC
2H
5)
217 grams drop into dimethyl formamide 16 grams and phosphorus trioxide 20 grams then, react under 20-80 ℃, and reaction finishes with methyl alcohol dilution becoming addition oil.
In another exsiccant there-necked flask, drop into the methyl alcohol that contains sodium methylate, when adding sulfanilylguanidine 30 grams, drop into whole above-mentioned addition oil, be warmed up to 50～85 ℃ ring-closure reaction takes place.Reflow method is dissolved in water after reclaiming amine and methyl alcohol, with hydrochloric acid PH is aligned 5.5, filters the back and obtains the thick product of Sulphadiazine Sodium.
Water is injected thick product, add lime levelling PH to 10～11, add gac and adsorb, elimination charcoal end.Carry out acid out with acetic acid and make PH reach 5.5, can obtain Sulphadiazine Sodium finished product 27.5 grams behind the filtration drying, recovery rate reaches 91.5%, and total recovery reaches 75%.Product meets version British Pharmacopoeia standard-required in 1980.
Claims (4)
1. method of producing Sulphadiazine Sodium relates to the production method of pyrimidine compound, specially refers to the production method of benzenesulfonamido-pyrimidines, produces to have structural formula and be
Compound, adopt N, N-two substituted formamides, sulfanilylguanidine are raw material, and with basic oxide and porous mass raw product are decoloured, and carry out acid out with weak acid, filter the back and obtain product, it is characterized in that:
I) N, N-two substituted formamides, phosphorus trichloride and structural formula are CH
3CH (OR)
2(R is CH
3-, C
2H
5-, C
3H
7-) acetaldehyde contract glycol generation addition send out should, and to dilute with R ' OH (R ' be straight chained alkyl) be addition oil;
Ii) above-mentioned addition oil and sulfanilylguanidine drop among the R ' OH that contains NaOR ' (R ' be straight chained alkyl) simultaneously, and ring-closure reaction takes place, and reclaim amine, behind the alcohol, through the mineral acid acid out, filter the back and obtain thick product.
2. the described a kind of method of producing Sulphadiazine Sodium of claim 1 is characterized in that: N in addition reaction, N-two substituted formamides: phosphorus trichloride: the acetaldehyde glycol [CH that contracts
3CH (OR)
2]=(0.35～1.1): (0.5～1.3): (0.4～1.2) (weight ratio); Temperature of reaction is 10～100 ℃.
3. the described a kind of method of producing Sulphadiazine Sodium of claim 1 is characterized in that: sulfanilylguanidine in ring-closure reaction: the acetaldehyde glycol [CH that contracts
3CH (OR)
2]=1: (0.4～1.2) (weight ratio); Temperature of reaction is 30-90 ℃.
4. the described a kind of method of producing Sulphadiazine Sodium of claim 1, it is characterized in that: described mineral acid is a hydrochloric acid, and weak acid is acetic acid, and basic oxide are calcium oxide, and porous mass is an activated carbon.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 89100054 CN1034719A (en) | 1988-12-29 | 1988-12-29 | A kind of method of producing sulfapyrimidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 89100054 CN1034719A (en) | 1988-12-29 | 1988-12-29 | A kind of method of producing sulfapyrimidine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1034719A true CN1034719A (en) | 1989-08-16 |
Family
ID=4853675
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 89100054 Pending CN1034719A (en) | 1988-12-29 | 1988-12-29 | A kind of method of producing sulfapyrimidine |
Country Status (1)
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|---|---|
| CN (1) | CN1034719A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103012224A (en) * | 2012-12-30 | 2013-04-03 | 湖南尔康制药股份有限公司 | Production process of medicinal sulphaguanidine |
| CN105254575A (en) * | 2015-11-17 | 2016-01-20 | 湖南湘易康制药有限公司 | Synthetic method for sulfadiazine |
| CN106316904A (en) * | 2015-06-25 | 2017-01-11 | 北大方正集团有限公司 | Method for recovering dimethylamine wastewater |
| CN107602412A (en) * | 2017-09-04 | 2018-01-19 | 吉林北沙制药有限公司 | A kind of preparation of aldehyde oil methanol solution and method of purification |
| CN111087350A (en) * | 2019-12-17 | 2020-05-01 | 重庆康乐制药有限公司 | Sulfadiazine refining method adopting food-grade calcium hydroxide as alkalizing agent |
-
1988
- 1988-12-29 CN CN 89100054 patent/CN1034719A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103012224A (en) * | 2012-12-30 | 2013-04-03 | 湖南尔康制药股份有限公司 | Production process of medicinal sulphaguanidine |
| CN103012224B (en) * | 2012-12-30 | 2013-12-04 | 湖南尔康制药股份有限公司 | Production process of medicinal sulphaguanidine |
| CN106316904A (en) * | 2015-06-25 | 2017-01-11 | 北大方正集团有限公司 | Method for recovering dimethylamine wastewater |
| CN105254575A (en) * | 2015-11-17 | 2016-01-20 | 湖南湘易康制药有限公司 | Synthetic method for sulfadiazine |
| CN105254575B (en) * | 2015-11-17 | 2018-01-02 | 湖南湘易康制药有限公司 | A kind of synthetic method of sulphadiazine |
| CN107602412A (en) * | 2017-09-04 | 2018-01-19 | 吉林北沙制药有限公司 | A kind of preparation of aldehyde oil methanol solution and method of purification |
| CN107602412B (en) * | 2017-09-04 | 2020-04-03 | 吉林北沙制药有限公司 | Preparation and purification method of aldehyde oil methanol solution |
| CN111087350A (en) * | 2019-12-17 | 2020-05-01 | 重庆康乐制药有限公司 | Sulfadiazine refining method adopting food-grade calcium hydroxide as alkalizing agent |
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