CN116829534A - Preparation method of 1, 4-butanedisulfonic acid - Google Patents
Preparation method of 1, 4-butanedisulfonic acid Download PDFInfo
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- CN116829534A CN116829534A CN202180065469.1A CN202180065469A CN116829534A CN 116829534 A CN116829534 A CN 116829534A CN 202180065469 A CN202180065469 A CN 202180065469A CN 116829534 A CN116829534 A CN 116829534A
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- CN
- China
- Prior art keywords
- hydrogen chloride
- butanedisulfonic acid
- solution
- reaction
- butanedisulfonic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- VERAMNDAEAQRGS-UHFFFAOYSA-N butane-1,4-disulfonic acid Chemical compound OS(=O)(=O)CCCCS(O)(=O)=O VERAMNDAEAQRGS-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 27
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 16
- 238000001914 filtration Methods 0.000 claims abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- LEUIUWYZAHKPSE-UHFFFAOYSA-L disodium;butane-1,4-disulfonate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)CCCCS([O-])(=O)=O LEUIUWYZAHKPSE-UHFFFAOYSA-L 0.000 claims description 4
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 claims description 2
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 claims description 2
- AKPUJVVHYUHGKY-UHFFFAOYSA-N hydron;propan-2-ol;chloride Chemical compound Cl.CC(C)O AKPUJVVHYUHGKY-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 abstract description 17
- 239000002904 solvent Substances 0.000 abstract description 12
- -1 1, 4-butanedisulfonic acid sodium (I) Chemical compound 0.000 abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 6
- 239000007864 aqueous solution Substances 0.000 abstract description 5
- 238000002156 mixing Methods 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 150000001450 anions Chemical group 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- MEFKEPWMEQBLKI-AIRLBKTGSA-N S-adenosyl-L-methioninate Chemical compound O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H](N)C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-N 0.000 description 2
- 229960001570 ademetionine Drugs 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- DMNNAGLOODQTOQ-HXTWIPGBSA-N [C@@H]1([C@H](O)[C@H](O)[C@@H](CN[C@@H](CCSC)C(=O)O)O1)N1C=NC=2C(N)=NC=NC12.C(CCCS(=O)(=O)O)S(=O)(=O)O Chemical compound [C@@H]1([C@H](O)[C@H](O)[C@@H](CN[C@@H](CCSC)C(=O)O)O1)N1C=NC=2C(N)=NC=NC12.C(CCCS(=O)(=O)O)S(=O)(=O)O DMNNAGLOODQTOQ-HXTWIPGBSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 208000001024 intrahepatic cholestasis Diseases 0.000 description 1
- 230000007872 intrahepatic cholestasis Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/42—Separation; Purification; Stabilisation; Use of additives
- C07C303/44—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/02—Sulfonic acids having sulfo groups bound to acyclic carbon atoms
- C07C309/03—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C309/05—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing at least two sulfo groups bound to the carbon skeleton
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02E—REDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION
- Y02E60/00—Enabling technologies; Technologies with a potential or indirect contribution to GHG emissions mitigation
- Y02E60/10—Energy storage using batteries
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of 1, 4-butanedisulfonic acid (II), which comprises the steps of mixing 1, 4-butanedisulfonic acid sodium (I) with hydrogen chloride solution for reaction, filtering after the reaction is finished, concentrating to obtain 1, 4-butanedisulfonic acid (II), and adding water to prepare 1, 4-butanedisulfonic acid (II) aqueous solution. The method is simple and convenient to operate, the obtained product does not need to be refined, the purity and the yield are high, the solvent consumption is small, the cost is low, and the environment is friendly.
Description
The invention relates to the field of medicine synthesis, in particular to a preparation method of 1, 4-butanedisulfonic acid (II).
S-adenosylmethionine is a physiological active molecule commonly existing in human tissues and body fluid, participates in important biochemical reaction in vivo, has better stability in vivo due to the protection of large anion groups, is extremely unstable in vitro and is easy to generate hydrolytic cleavage and racemization reaction, and 1, 4-butanedisulfonic acid (II) is taken as an anion, can be paired with the anion to form double salt 1, 4-butanedisulfonic acid adenosylmethionine, so as to achieve the effect of stabilizing the structure of the double salt. The 1, 4-butanedisulfonic acid ademetionine is used for preventing intrahepatic cholestasis, is a first-line product for promoting bile flow and protecting liver, and has a great market share.
Regarding a method for preparing 1, 4-butanedisulfonic acid (II), chinese patent CN104086463 discloses that hydrogen chloride gas is introduced into an organic alcohol solution of sodium 1, 4-butanedisulfonate (I) until the hydrogen chloride content is more than 10wt%, then the hydrogen chloride is removed by decompression concentration, the organic acid is crystallized to obtain a crude product of the 1, 4-butanedisulfonic acid (II), the crude product is recrystallized in the organic acid to obtain a refined product of the 1, 4-butanedisulfonic acid (II), and the refined product is dissolved into a solution. The method (1) needs to continuously introduce hydrogen chloride gas in the reaction process, and needs to judge the reaction end point according to the content of the hydrogen chloride, so that the operation is complicated; (2) The anhydrous alcohol is required to be used for carrying out reduced pressure distillation for multiple times to carry out hydrogen chloride, the operation is complicated, the use amount of the organic solvent is increased (3), the reduced pressure distillation is directly carried out after the reaction is finished, a large amount of generated sodium chloride is mixed into the product, two times of crystallization are required to obtain high-quality 1, 4-butanedisulfonic acid (II), the operation is complicated, the product yield is low due to the two times of crystallization (the yield after the refining is 78% as calculated in the CN104086463 embodiment 2), the use amount of the solvent is large, and the production cost and the operation cost are increased.
Disclosure of Invention
The preparation method of the 1, 4-butanedisulfonic acid (II) is simple and convenient to operate, and the obtained product does not need to be refined, and has the advantages of high purity and yield, less solvent consumption, low cost and environmental friendliness. The method comprises the following steps: mixing 1, 4-butanedisulfonic acid sodium (I) with hydrogen chloride solution for reaction, filtering after the reaction is finished, concentrating to obtain 1, 4-butanedisulfonic acid (II),
preferably, the hydrogen chloride solution is an aqueous hydrogen chloride solution or an organic alcohol solution of hydrogen chloride.
Preferably, the organic alcohol solution of hydrogen chloride is selected from the group consisting of a methanol solution of hydrogen chloride, an ethanol solution of hydrogen chloride, and an isopropanol solution of hydrogen chloride.
Preferably, the mass percentage concentration of the hydrogen chloride solution is 10-37 wt%.
Preferably, the mass ratio of the 1, 4-butanedisulfonic acid sodium salt (I) to the hydrogen chloride solution is 1:1-5, preferably 1:2-5.
Preferably, the temperature of the filtration is 0 to 30 ℃.
Preferably, the temperature of the reaction is 20 to 60 ℃.
Preferably, the reaction time is 2 to 6 hours.
Preferably, water is added into the prepared 1, 4-butanedisulfonic acid (II) to obtain an aqueous solution of the 1, 4-butanedisulfonic acid (II), and the mass percentage concentration of the aqueous solution of the 1, 4-butanedisulfonic acid (II) is 30-80 wt%.
Compared with the prior art CN104086463, the invention has the following main beneficial effects:
the prior art can only be carried out in alcohols, whereas the present invention can be carried out with aqueous hydrogen chloride. In the prior art, an organic solvent is needed to be added for crystallization, and recrystallization is needed to obtain the 1, 4-butanedisulfonic acid (II) with high purity; in the presence of hydrogen chloride, the sodium chloride as a reaction byproduct is directly separated out, and then filtered to obtain a pure product solution, and the solvent is evaporated to obtain the 1, 4-butanedisulfonic acid (II) without a crystallization process. Compared with the method, the method omits crystallization and recrystallization processes, does not need to purify in a mode of obtaining crystalline solids, does not need to use organic solvents for post-treatment, reduces the solvent consumption, reduces the cost and is environment-friendly. Therefore, the method is simple and convenient to operate, the obtained product can obtain the 1, 4-butanedisulfonic acid (II) with higher purity than the prior art without refining, the purity and the yield are high, the solvent consumption is less, the cost is low, and the method is environment-friendly, and is a preparation method capable of realizing industrial production.
The following examples further illustrate the invention, but it is necessary to point out that the following examples are given for the purpose of illustration only and are not to be construed as limiting the scope of the invention, which is defined by the claims.
In the following examples, all temperatures are degrees celsius unless otherwise indicated; unless otherwise indicated, the various starting materials and reagents were all from commercial sources and were used without further purification; unless otherwise indicated, each solvent was an industrial grade solvent and was used without further treatment.
Example 1
100g of 1, 4-butanedisulfonic acid sodium (I) and 200g of 37wt% hydrogen chloride aqueous solution are added into a reaction bottle, the temperature is controlled at 20 ℃, the reaction is carried out for 2 hours, after the reaction is finished, the filtration is carried out at 0 ℃, the filtrate is concentrated under reduced pressure, and the solvent is evaporated to dryness, thus obtaining 1, 4-butanedisulfonic acid (II), the yield is 93.8%, and the HPLC content is 98.3%. Water was added to a volume of 30wt% aqueous 1, 4-butanedisulfonic acid (II).
Example 2
100g of 1, 4-butanedisulfonic acid sodium (I) and 400g of 20wt% hydrogen chloride methanol solution are added into a reaction bottle, the temperature is controlled at 40 ℃, the reaction is carried out for 6 hours, after the reaction is finished, the filtration is carried out at 10 ℃, the filtrate is concentrated under reduced pressure, and the solvent is evaporated to dryness, thus obtaining 1, 4-butanedisulfonic acid (II), the yield is 95.7%, and the HPLC content is 98.7%. Water was added to a volume of 70wt% aqueous 1, 4-butanedisulfonic acid (II).
Example 3
100g of 1, 4-butanedisulfonic acid sodium (I) and 400g of 28wt% hydrogen chloride ethanol solution are added into a reaction bottle, the temperature is controlled at 60 ℃, the reaction is carried out for 4 hours, after the reaction is finished, the filtration is carried out at 25 ℃, the filtrate is concentrated under reduced pressure, and the solvent is evaporated to dryness, thus obtaining 1, 4-butanedisulfonic acid (II) with the yield of 92.8% and the HPLC content of 99.2%. Water was added to a volume of 50wt% aqueous 1, 4-butanedisulfonic acid (II).
Example 4
100g of 1, 4-butanedisulfonic acid sodium (I) and 500g of 10wt% hydrogen chloride isopropanol solution are added into a reaction bottle, the temperature is controlled at 40 ℃, the reaction is carried out for 6 hours, after the reaction is finished, the filtration is carried out at 30 ℃, the filtrate is concentrated under reduced pressure, and the solvent is evaporated to dryness, so that 1, 4-butanedisulfonic acid (II) is obtained, the yield is 94.2%, and the HPLC content is 98.4%. Water was added to a volume of 80% by weight of an aqueous solution of 1, 4-butanedisulfonic acid (II).
Claims (8)
- A process for preparing 1, 4-butanedisulfonic acid (II) features that the sodium 1, 4-butanedisulfonate (I) and hydrogen chloride solution are mixed for reaction, and after the reaction is finished, the mixture is filtered and concentrated to obtain 1, 4-butanedisulfonic acid (II)
- The method according to claim 1, wherein the hydrogen chloride solution is an aqueous hydrogen chloride solution or an organic alcohol solution of hydrogen chloride.
- The method according to claim 2, wherein the organic alcohol solution of hydrogen chloride is selected from the group consisting of a hydrogen chloride methanol solution, a hydrogen chloride ethanol solution and a hydrogen chloride isopropanol solution.
- A method according to any one of claims 1 to 3, wherein the hydrogen chloride solution has a mass percentage concentration of 10 to 37wt%.
- The preparation method according to any one of claims 1 to 4, wherein the mass ratio of the sodium 1, 4-butanedisulfonate (I) to the hydrogen chloride solution is 1:1-5.
- The process according to any one of claims 1 to 5, wherein the temperature of the filtration is 0 to 30 ℃.
- The process according to any one of claims 1 to 6, wherein the temperature of the reaction is 20 to 60 ℃.
- The process according to any one of claims 1 to 7, wherein the reaction time is 2 to 6 hours.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CN2021/142918 WO2023123170A1 (en) | 2021-12-30 | 2021-12-30 | Preparation method for 1,4-butanedisulfonic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116829534A true CN116829534A (en) | 2023-09-29 |
Family
ID=86996994
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202180065469.1A Pending CN116829534A (en) | 2021-12-30 | 2021-12-30 | Preparation method of 1, 4-butanedisulfonic acid |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN116829534A (en) |
| WO (1) | WO2023123170A1 (en) |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101450921B (en) * | 2007-12-06 | 2012-08-29 | 浙江海正药业股份有限公司 | Optimization of 1,4-butanedisulfonic acid disodium preparation technology |
| JP5105599B2 (en) * | 2007-12-14 | 2012-12-26 | 竹本油脂株式会社 | Method for treating alkali metal salt of organic sulfonic acid and method for producing organic sulfonic acid ammonium salt type surfactant |
| JP5783769B2 (en) * | 2011-03-30 | 2015-09-24 | 住友精化株式会社 | Method for producing barium alkanedisulfonate and method for producing alkanedisulfonic acid |
| CN102746078A (en) * | 2011-04-18 | 2012-10-24 | 东丽纤维研究所（中国）有限公司 | Preparation method for organic sulfonic acid compound |
| CN104086463B (en) * | 2014-07-14 | 2016-05-11 | 河南豫辰药业股份有限公司 | The preparation method of a kind of Isosorbide-5-Nitrae-Ding disulfonic acid fine work and solution thereof |
| JP6592802B2 (en) * | 2014-11-06 | 2019-10-23 | 国立大学法人富山大学 | Phytosphingosine derivatives with sulfonyl |
| JP6582259B1 (en) * | 2019-03-15 | 2019-10-02 | 竹本油脂株式会社 | Method for treating alkali metal salt or ammonium salt solution of organic sulfonic acid and method for producing organic sulfonic acid solution |
-
2021
- 2021-12-30 WO PCT/CN2021/142918 patent/WO2023123170A1/en active Application Filing
- 2021-12-30 CN CN202180065469.1A patent/CN116829534A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2023123170A1 (en) | 2023-07-06 |
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