CN102329251A - Method for chemically synthesizing p-guanidinobenzoic acid - Google Patents
Method for chemically synthesizing p-guanidinobenzoic acid Download PDFInfo
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- CN102329251A CN102329251A CN201110210851A CN201110210851A CN102329251A CN 102329251 A CN102329251 A CN 102329251A CN 201110210851 A CN201110210851 A CN 201110210851A CN 201110210851 A CN201110210851 A CN 201110210851A CN 102329251 A CN102329251 A CN 102329251A
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Abstract
The invention discloses a method for chemically synthesizing p-guanidinobenzoic acid. The method comprises the following steps of: firstly, putting isopropanol, p-aminobenzoic acid and hydrochloric acid into a reaction vessel, increasing temperature, and stirring for a period of time to obtain a mixed solution; secondly, dropwise-adding a cyanamide solution into the mixed solution, and cooling down to the normal temperature after stirring and reflowing for a period of time; thirdly, putting sodium hydroxide into the reaction vessel, stirring for a period of time, regulating the pH value to be neutral, and then depressurizing, suction-filtering, water-scrubbing and drying to obtain a p-guanidinobenzoic acid crude product; and fourthly, putting the p-guanidinobenzoic acid crude product, ethanol and water in the reaction vessel, increasing temperature, and stirring for a period of time, and then depressurizing, concentrating, suction-filtering, water-scrubbing and drying to obtain p-guanidinobenzoic acid. The method for chemically synthesizing the p-guanidinobenzoic acid provided by the invention is suitable for large-scale industrial production and is favorable for cyclic development of production, the cost is saved, and the pollution to the environment caused by industrial waste materials is reduced.
Description
Technical field
The present invention relates to chemical synthesis process to guanidinobenzoic acid.
Background technology
To guanidinobenzoic acid is a kind of white or off-white color crystalline powder, and main application is the synthetic aspect of a machine raw material, is mainly used in Synthesis Card Mo Tate mesylate.The Ka Motate mesylate is the suppressor factor of multiple protein lytic enzyme, and it can relieve chronic pancreatitis acute symptom.The starting raw material of Ka Motate mesylate is the suppressor factor of acrosomal protease to the guanidinobenzoic acid hydrochloride; It also is the important intermediate of synthetic many other proteinase inhibitor; It has wide practical use in the antifertility field, is expected to develop into the contraceptive bian series product.
Summary of the invention
The invention provides chemical synthesis process, be fit to industrial-scale production, help the cycle development of producing simultaneously, practice thrift cost, and reduce the trade waste pollution on the environment guanidinobenzoic acid.
The present invention has adopted following technical scheme: to the chemical synthesis process of guanidinobenzoic acid, it may further comprise the steps: step 1, in reaction kettle, drop into Virahol, para-amino benzoic acid and hydrochloric acid, and heat up and stirring for some time, obtain mixing solutions; Step 2, to mixed solution and dripping cyanamide solution, stirring and refluxing is cooled to normal temperature after for some time; Step 3 drops into sodium hydroxide in reaction kettle, stir for some time, regulates pH to neutral; Suction filtration, washing, oven dry are carried out in decompression then, obtain the guanidinobenzoic acid bullion; Step 4 drops in reaction kettle guanidinobenzoic acid bullion, second alcohol and water, and intensification is also carried out concentrating under reduced pressure, suction filtration, washing, oven dry after stirring for some time, obtains guanidinobenzoic acid.
Para-amino benzoic acid and Virahol and hydrochloric acid mass ratio are 1: 3: 1 in the said step 1, are warming up to 50 ℃ and stirred 30 minutes during reaction; Para-amino benzoic acid and cyanamide mol ratio are 1: 1 in the said step 2, slowly drip cyanamide after, be warming up to 80 ℃, stirring and refluxing 6.5 hours; Para-amino benzoic acid and sodium hydroxide mol ratio are 1: 1 in the said step 3, and churning time is 3 hours; Be 1: 0.3: 1.5 to guanidinobenzoic acid bullion and water and ethanol mass ratio in the said step 4, stirred 45 minutes after being warming up to 40 ℃.
The present invention has following beneficial effect: the chemical synthesis process to guanidinobenzoic acid provided by the invention; Be fit to industrial-scale production; Help the cycle development of producing simultaneously; Practice thrift cost, and reduce the trade waste pollution on the environment, synthetic is 99.34% to HPLC content in the guanidinobenzoic acid simultaneously.
Embodiment
The invention provides chemical synthesis process to guanidinobenzoic acid; It may further comprise the steps: step 1; In reaction kettle, drop into Virahol, para-amino benzoic acid and hydrochloric acid; Para-amino benzoic acid and Virahol and hydrochloric acid mass ratio are 1: 3: 1, are warming up to 50 ℃ and stirred 30 minutes, obtain mixing solutions; Step 2, to mixed solution and dripping cyanamide solution, para-amino benzoic acid and cyanamide mol ratio are 1: 1, slowly drip cyanamide after, be warming up to 80 ℃, stirring and refluxing is cooled to normal temperature after 6.5 hours; Step 3 drops into sodium hydroxide in reaction kettle, para-amino benzoic acid and sodium hydroxide mol ratio are 1: 1, stirs at normal temperatures 3 hours, regulates pH to neutral; Be evaporated to starchiness then, carry out suction filtration, use water rinse, 60 ℃ of oven dry of filter cake decompression obtain the guanidinobenzoic acid bullion; Step 4; In reaction kettle, drop into guanidinobenzoic acid bullion, second alcohol and water; To guanidinobenzoic acid bullion and water and ethanol mass ratio is 1: 0.3: 1.5, stirs after being warming up to 40 ℃ and carries out concentrating under reduced pressure then in 45 minutes, steams most of solvent to starchiness; Be cooled to and carry out suction filtration, washing, 60 ℃ of oven dry of decompression below 5 ℃, obtain guanidinobenzoic acid.
Embodiment
1, salt-forming reaction
In the 300ml reaction kettle, drop into 150g Virahol and 50 gram para-amino benzoic acid and 50g hydrochloric acid, be warming up to 50 ℃, stirred 30 minutes.
2, substitution reaction
Slow Dropwise 5 0% cyanamide solution 31g in reaction kettle, temperature of reaction rises to 80 ℃ by 50 ℃, and stirring and refluxing 6.5 hours is cooled to normal temperature.
3, neutralization reaction
In reaction kettle, behind the input 14.4g sodium hydroxide, stirring at room 3 hours is regulated pH to neutral, is evaporated to starchiness, carries out suction filtration, washes with 15ml water, and 60 ℃ of oven dry of filter cake decompression obtain guanidinobenzoic acid bullion 72g.
4, the refining extraction
In the 300L reaction kettle, drop into guanidinobenzoic acid bullion 72g and ethanol 108g and water 21.6g, be warming up to 40 ℃, stirred 45 minutes; Concentrating under reduced pressure steams most of solvent, to starchiness, is cooled to below 5 ℃; Suction filtration is used the 10ml water rinse, obtains wet to guanidinobenzoic acid 68.3g; The 60 ℃ of oven dry of reducing pressure obtain to guanidinobenzoic acid 65.2g HPLC content 99.34%.
Claims (5)
1. to the chemical synthesis process of guanidinobenzoic acid, it is characterized in that it may further comprise the steps:
Step 1 drops into Virahol, para-amino benzoic acid and hydrochloric acid in reaction kettle, heat up and stirring for some time, obtains mixing solutions;
Step 2, to mixed solution and dripping cyanamide solution, stirring and refluxing is cooled to normal temperature after for some time;
Step 3 drops into sodium hydroxide in reaction kettle, stir for some time, regulates pH to neutral; Suction filtration, washing, oven dry are carried out in decompression then, obtain the guanidinobenzoic acid bullion;
Step 4 drops in reaction kettle guanidinobenzoic acid bullion, second alcohol and water, and intensification is also carried out concentrating under reduced pressure, suction filtration, washing, oven dry after stirring for some time, obtains guanidinobenzoic acid.
2. the chemical synthesis process to guanidinobenzoic acid according to claim 1 is characterized in that para-amino benzoic acid and Virahol and hydrochloric acid mass ratio are 1: 3: 1 in the said step 1, is warming up to 50 ℃ and stirred 30 minutes during reaction.
3. the chemical synthesis process to guanidinobenzoic acid according to claim 1 is characterized in that para-amino benzoic acid and cyanamide mol ratio are 1: 1 in the said step 2, slowly drip cyanamide after, be warming up to 80 ℃, stirring and refluxing 6.5 hours.
4. the chemical synthesis process to guanidinobenzoic acid according to claim 1 is characterized in that para-amino benzoic acid and sodium hydroxide mol ratio are 1: 1 in the said step 3, and churning time is 3 hours.
5. the chemical synthesis process to guanidinobenzoic acid according to claim 1 is characterized in that in the said step 4 that to guanidinobenzoic acid bullion and water and ethanol mass ratio be 1: 0.3: 1.5, stirs 45 minutes after being warming up to 40 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110210851A CN102329251A (en) | 2011-07-22 | 2011-07-22 | Method for chemically synthesizing p-guanidinobenzoic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110210851A CN102329251A (en) | 2011-07-22 | 2011-07-22 | Method for chemically synthesizing p-guanidinobenzoic acid |
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| CN102329251A true CN102329251A (en) | 2012-01-25 |
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| CN201110210851A Pending CN102329251A (en) | 2011-07-22 | 2011-07-22 | Method for chemically synthesizing p-guanidinobenzoic acid |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103641749A (en) * | 2013-12-02 | 2014-03-19 | 山东永泰化工有限公司 | Preparation method of nafamostat mesylate |
| CN106543041A (en) * | 2016-05-22 | 2017-03-29 | 上海清松制药有限公司 | A kind of synthetic method of p -guanidinobenzoic acid hydrochlorate |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1253945A (en) * | 1998-09-10 | 2000-05-24 | Basf公司 | Method for preparing creatine or creatine-hydrate |
| CN101462983A (en) * | 2007-12-21 | 2009-06-24 | 上海浩洲化工有限公司 | Preparation of glycocyamine |
-
2011
- 2011-07-22 CN CN201110210851A patent/CN102329251A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1253945A (en) * | 1998-09-10 | 2000-05-24 | Basf公司 | Method for preparing creatine or creatine-hydrate |
| CN101462983A (en) * | 2007-12-21 | 2009-06-24 | 上海浩洲化工有限公司 | Preparation of glycocyamine |
Non-Patent Citations (2)
| Title |
|---|
| KAZUYUKI SAGI ET AL.: "Optimization of a coagulation factor VIIa inhibitor found in factor Xa inhibitor library", 《BIOORGANIC & MEDICINAL CHEMISTRY》, vol. 13, 18 January 2005 (2005-01-18), pages 1487 - 1496 * |
| 王晓天等: "对胍基苯甲酸盐酸盐的制备及衍生物卡莫他特磺酸盐的合成", 《精细化工》, vol. 21, no. 8, 31 August 2004 (2004-08-31), pages 597 - 599 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103641749A (en) * | 2013-12-02 | 2014-03-19 | 山东永泰化工有限公司 | Preparation method of nafamostat mesylate |
| CN103641749B (en) * | 2013-12-02 | 2016-02-10 | 山东永泰化工有限公司 | A kind of preparation method of nafamostat mesylate |
| CN106543041A (en) * | 2016-05-22 | 2017-03-29 | 上海清松制药有限公司 | A kind of synthetic method of p -guanidinobenzoic acid hydrochlorate |
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