WO2023123170A1 - Preparation method for 1,4-butanedisulfonic acid - Google Patents
Preparation method for 1,4-butanedisulfonic acid Download PDFInfo
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- WO2023123170A1 WO2023123170A1 PCT/CN2021/142918 CN2021142918W WO2023123170A1 WO 2023123170 A1 WO2023123170 A1 WO 2023123170A1 CN 2021142918 W CN2021142918 W CN 2021142918W WO 2023123170 A1 WO2023123170 A1 WO 2023123170A1
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- Prior art keywords
- hydrogen chloride
- preparation
- solution
- butanedisulfonic acid
- reaction
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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 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 24
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 21
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 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 abstract description 7
- 238000001914 filtration Methods 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000012141 concentrate Substances 0.000 claims description 5
- -1 1,4-butanedisulfonic acid sodium (I) Chemical compound 0.000 claims description 3
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 claims description 3
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical group Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 claims description 3
- AKPUJVVHYUHGKY-UHFFFAOYSA-N hydron;propan-2-ol;chloride Chemical compound Cl.CC(C)O AKPUJVVHYUHGKY-UHFFFAOYSA-N 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000000243 solution Substances 0.000 abstract description 18
- 239000002904 solvent Substances 0.000 abstract description 13
- 238000000034 method Methods 0.000 abstract description 10
- 239000007864 aqueous solution Substances 0.000 abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 6
- 239000000047 product Substances 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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 2
- 150000001450 anions Chemical group 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000001953 recrystallisation Methods 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 1
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 1
- 229960001570 ademetionine Drugs 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 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
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000000232 gallbladder Anatomy 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
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002156 mixing Methods 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
- 238000007670 refining Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 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
Definitions
- the invention relates to the field of drug synthesis, in particular to a preparation method of 1,4-butanedisulfonic acid (II).
- S-adenosylmethionine is a physiologically active molecule ubiquitous in human tissues and body fluids. It participates in important biochemical reactions in the body. Because of the protection of large anion groups in the body, it has better stability, but it is extremely unstable in vitro and easily Hydrolytic cleavage and racemization reactions occur, and 1,4-butanedisulfonic acid (II), as an anion, can pair with it to form a double salt 1,4-butanedisulfonic acid adenosylmethionine to stabilize its structure.
- 1,4-Butanedisulfonic acid adenosylmethionine is used to prevent intrahepatic cholestasis. It is a first-line product for promoting gallbladder and protecting liver, and occupies a large market share.
- Chinese patent CN104086463 discloses passing hydrogen chloride gas into an organic alcohol solution of 1,4-butanedisulfonic acid sodium (I) until the hydrogen chloride content is greater than 10 wt%. Afterwards, after concentration under reduced pressure to remove hydrogen chloride, the organic acid is crystallized to obtain the crude product of 1,4-butanedisulfonic acid (II), and the crude product is recrystallized in organic acid to obtain the refined product of 1,4-butanedisulfonic acid (II), which is added as a solvent Dubbed into a solution.
- This method (1) needs to continuously feed hydrogen chloride gas in the reaction process, and needs to judge the reaction end point according to the hydrogen chloride content, and the operation is cumbersome; (3) direct decompression distillation after the completion of the reaction, so that a large amount of sodium chloride generated is mixed into the product, and two crystallizations are needed to obtain high-quality 1,4-butanedisulfonic acid (II). It is cumbersome, twice crystallization will lead to low product yield (CN104086463 embodiment 2 calculates its refined yield to be 78%), solvent usage is large, and production cost and operation cost increase.
- the method comprises: mixing 1,4-butanedisulfonic acid sodium (I) and hydrogen chloride solution for reaction, filtering and concentrating after the reaction to obtain 1,4-butanedisulfonic acid (II),
- the hydrogen chloride solution is an aqueous hydrogen chloride solution or an organic alcohol solution of hydrogen chloride.
- the organic alcohol solution of hydrogen chloride is selected from hydrogen chloride methanol solution, hydrogen chloride ethanol solution or hydrogen chloride isopropanol solution.
- the mass percent concentration of the hydrogen chloride solution is 10wt%-37wt%.
- the mass ratio of sodium 1,4-butanedisulfonate (I) to hydrogen chloride solution is 1:1-5, preferably 1:2-5.
- the filtration temperature is 0-30°C.
- the reaction temperature is 20-60°C.
- the reaction time is 2-6 hours.
- water is added to the prepared 1,4-butanedisulfonic acid (II) to obtain a 1,4-butanedisulfonic acid (II) aqueous solution, and the quality of the 1,4-butanedisulfonic acid (II) aqueous solution is The percentage concentration is 30wt%-80wt%.
- the present invention omits crystallization and recrystallization processes, does not need to be purified by obtaining crystalline solids, and does not require the use of organic solvents for post-treatment, which reduces the amount of solvents used, reduces costs, and is environmentally friendly. Therefore, the present invention is easy to operate, and the obtained product can obtain 1,4-butanedisulfonic acid (II) with higher purity than that of the prior art without refining, with high purity and yield, less solvent consumption, low cost and environmental friendliness , is a preparation method that can realize industrial production.
- II 1,4-butanedisulfonic acid
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention provides a preparation method for 1,4-butanedisulfonic acid (II). According to the method, disodium 1,4-butanedisulfonate (I) and a hydrogen chloride solution are mixed for reaction, filtration and concentration are performed after the reaction is finished to obtain 1,4-butanedisulfonic acid (II), and water is added to prepare an aqueous solution of 1,4-butanedisulfonic acid (II). The method is simple and convenient to operate. The obtained product does not need to be refined, and the purity and the yield are high. The amount of solvent used is small, the cost is low, and the method is environmentally friendly.
Description
本发明涉及药物合成领域，具体涉及一种1,4-丁二磺酸(Ⅱ)的制备方法。The invention relates to the field of drug synthesis, in particular to a preparation method of 1,4-butanedisulfonic acid (II).
S-腺苷蛋氨酸是人体组织和体液中普遍存在的一种生理活性分子，参与体内重要的生化反应，在体内由于有大阴离子团的保护，稳定性更好，但在体外极不稳定，易发生水解裂解和消旋反应，而1,4-丁二磺酸(Ⅱ)作为阴离子，能与其配对形成复盐1,4-丁二磺酸腺苷蛋氨酸，达到稳定其结构的作用。1,4-丁二磺酸腺苷蛋氨酸用于防止肝内胆汁淤积，是利胆保肝的一线产品，占有很大的市场份额。S-adenosylmethionine is a physiologically active molecule ubiquitous in human tissues and body fluids. It participates in important biochemical reactions in the body. Because of the protection of large anion groups in the body, it has better stability, but it is extremely unstable in vitro and easily Hydrolytic cleavage and racemization reactions occur, and 1,4-butanedisulfonic acid (II), as an anion, can pair with it to form a double salt 1,4-butanedisulfonic acid adenosylmethionine to stabilize its structure. 1,4-Butanedisulfonic acid adenosylmethionine is used to prevent intrahepatic cholestasis. It is a first-line product for promoting gallbladder and protecting liver, and occupies a large market share.
关于1，4-丁二磺酸(Ⅱ)制备的方法，中国专利CN104086463公开了将氯化氢气体通入1,4-丁二磺酸钠(Ⅰ)的有机醇溶液中，至氯化氢含量大于10wt％后，减压浓缩除去氯化氢后，有机酸结晶得到1，4-丁二磺酸(Ⅱ)粗品，粗品在有机酸中重结晶得到1，4-丁二磺酸(Ⅱ)精品，精品加溶剂配成溶液。该方法(1)需要在反应过程中持续通入氯化氢气体，且需要根据氯化氢含量判断反应终点，操作繁琐；(2)需要使用无水醇多次减压蒸馏带出氯化氢，操作繁琐，且增加了有机溶剂的使用量(3)反应结束后直接减压蒸馏，使生成的大量氯化钠混入产品中，需要两次结晶才能得到高品质的1，4-丁二磺酸(Ⅱ)，操作繁琐，两次结晶会导致产品收率低(CN104086463实施例2计算其精制后的收率为78％)，溶剂使用量大，生产成本和操作成本增加。Regarding the method for preparing 1,4-butanedisulfonic acid (II), Chinese patent CN104086463 discloses passing hydrogen chloride gas into an organic alcohol solution of 1,4-butanedisulfonic acid sodium (I) until the hydrogen chloride content is greater than 10 wt%. Afterwards, after concentration under reduced pressure to remove hydrogen chloride, the organic acid is crystallized to obtain the crude product of 1,4-butanedisulfonic acid (II), and the crude product is recrystallized in organic acid to obtain the refined product of 1,4-butanedisulfonic acid (II), which is added as a solvent Dubbed into a solution. This method (1) needs to continuously feed hydrogen chloride gas in the reaction process, and needs to judge the reaction end point according to the hydrogen chloride content, and the operation is cumbersome; (3) direct decompression distillation after the completion of the reaction, so that a large amount of sodium chloride generated is mixed into the product, and two crystallizations are needed to obtain high-quality 1,4-butanedisulfonic acid (II). It is cumbersome, twice crystallization will lead to low product yield (CN104086463 embodiment 2 calculates its refined yield to be 78%), solvent usage is large, and production cost and operation cost increase.
发明内容Contents of the invention
一种1，4-丁二磺酸(Ⅱ)的制备方法，该方法操作简便，所得产品无需精制，纯度和收率高，溶剂用量少，成本低，环境友好。所述方法包括：将1,4-丁二磺酸钠(Ⅰ)和氯化氢溶液混合进行反应，反应结束后过滤，浓缩，得到1,4-丁二磺酸(Ⅱ)，A preparation method of 1,4-butanedisulfonic acid (II), the method is simple and convenient to operate, the obtained product does not need to be refined, has high purity and yield, less solvent consumption, low cost, and is environmentally friendly. The method comprises: mixing 1,4-butanedisulfonic acid sodium (I) and hydrogen chloride solution for reaction, filtering and concentrating after the reaction to obtain 1,4-butanedisulfonic acid (II),
优选的，所述氯化氢溶液为氯化氢水溶液或氯化氢的有机醇溶液。Preferably, the hydrogen chloride solution is an aqueous hydrogen chloride solution or an organic alcohol solution of hydrogen chloride.
优选的，所述氯化氢的有机醇溶液选自氯化氢甲醇溶液、氯化氢乙醇溶液或氯化氢异丙醇溶液。Preferably, the organic alcohol solution of hydrogen chloride is selected from hydrogen chloride methanol solution, hydrogen chloride ethanol solution or hydrogen chloride isopropanol solution.
优选的，所述氯化氢溶液的质量百分比浓度为10wt％～37wt％。Preferably, the mass percent concentration of the hydrogen chloride solution is 10wt%-37wt%.
优选的，所述的1,4-丁二磺酸钠(Ⅰ)与氯化氢溶液的质量比为1:1～5，优选1:2～5。Preferably, the mass ratio of sodium 1,4-butanedisulfonate (I) to hydrogen chloride solution is 1:1-5, preferably 1:2-5.
优选的，所述过滤的温度为0～30℃。Preferably, the filtration temperature is 0-30°C.
优选的，所述反应的温度为20～60℃。Preferably, the reaction temperature is 20-60°C.
优选的，所述反应的时间为2～6小时。Preferably, the reaction time is 2-6 hours.
优选的，向制备得到的1,4-丁二磺酸(Ⅱ)中加水得1,4-丁二磺酸(Ⅱ)水溶液，所述的1,4-丁二磺酸(Ⅱ)水溶液质量百分比浓度为30wt％～80wt％。Preferably, water is added to the prepared 1,4-butanedisulfonic acid (II) to obtain a 1,4-butanedisulfonic acid (II) aqueous solution, and the quality of the 1,4-butanedisulfonic acid (II) aqueous solution is The percentage concentration is 30wt%-80wt%.
与现有技术CN104086463相比，本发明的有益效果主要体现在：Compared with the prior art CN104086463, the beneficial effects of the present invention are mainly reflected in:
现有技术只能在醇类中进行反应，而本发明可用氯化氢水溶液进行反应。现有技术需要加有机溶剂结晶，而且需要重结晶才能得到高纯度的1，4-丁二磺酸(Ⅱ)；本发明在氯化氢存在的情况下，反应副产物氯化钠将直接析出，此时过滤，将得到纯品溶液，蒸掉溶剂就可以得到1，4-丁二磺酸(Ⅱ)，没有结晶过程。相比而言，本发明省去了结晶和重结晶过程，不需要通过得到结晶固体的方式提纯，后处理也不需要使用有机溶剂，减少了溶剂用量，降低了成本，环境友好。因此，本发明操作简便，所得产品无需精制即能获得比现有技术纯度更高的1，4-丁二磺酸(Ⅱ)，纯度和收率高，溶剂用量少，成本低，环境友好，是一个可实现工业化生产的制备方法。The prior art can only react in alcohols, but the present invention can react with hydrogen chloride aqueous solution. Prior art needs to add organic solvent crystallization, and needs recrystallization just can obtain high-purity 1,4-butanedisulfonic acid (II); Under the situation that hydrogen chloride exists in the present invention, reaction by-product sodium-chlor will directly separate out, and this When filtered, the pure product solution will be obtained, and the solvent can be evaporated to obtain 1,4-butanedisulfonic acid (II), without crystallization process. In contrast, the present invention omits crystallization and recrystallization processes, does not need to be purified by obtaining crystalline solids, and does not require the use of organic solvents for post-treatment, which reduces the amount of solvents used, reduces costs, and is environmentally friendly. Therefore, the present invention is easy to operate, and the obtained product can obtain 1,4-butanedisulfonic acid (II) with higher purity than that of the prior art without refining, with high purity and yield, less solvent consumption, low cost and environmental friendliness , is a preparation method that can realize industrial production.
以下实施例对本发明作进一步说明，但有必要指出以下实施例只用于对发明内容的描述，并不构成对本发明保护范围的限制，本发明保护范围以权利要求为准。The following examples further illustrate the present invention, but it is necessary to point out that the following examples are only used to describe the content of the invention, and do not constitute a limitation to the protection scope of the present invention, and the protection scope of the present invention is as the criterion with claims.
在下列实例中，除非另有指明，所有温度为摄氏温度；除非另有指明，各种起始原料和试剂均来自市售，均不经进一步纯化直接使用；除非另有指明，各种溶剂均为工业级溶剂，不经进一步处理直接使用。In the following examples, all temperatures are in degrees Celsius unless otherwise indicated; unless otherwise indicated, various starting materials and reagents were commercially available and used without further purification; unless otherwise indicated, various solvents were As an industrial grade solvent, it was used directly without further treatment.
实施例1Example 1
向反应瓶中加入1,4-丁二磺酸钠(Ⅰ)100g，37wt％的氯化氢水溶液200g，控制温度在20℃，反应2h，反应结束后，0℃过滤，滤液减压浓缩，蒸干溶剂，得到1,4-丁二磺酸(Ⅱ)，收率93.8％，HPLC含量为98.3％。加入水定容成30wt％的1,4-丁二磺酸(Ⅱ)水溶液。Add 100g of 1,4-butanedisulfonate sodium (I) and 200g of 37wt% aqueous hydrogen chloride solution to the reaction flask, control the temperature at 20°C, and react for 2h. After the reaction, filter at 0°C, concentrate the filtrate under reduced pressure, and evaporate to dryness solvent to obtain 1,4-butanedisulfonic acid (II) with a yield of 93.8% and an HPLC content of 98.3%. Add water to make up to 30wt% 1,4-butanedisulfonic acid (II) aqueous solution.
实施例2Example 2
向反应瓶中加入1,4-丁二磺酸钠(Ⅰ)100g，20wt％的氯化氢甲醇溶液400g，控制温度在40℃，反应6h，反应结束后，10℃过滤，滤液减压浓缩，蒸干溶剂，得到1,4-丁二磺酸(Ⅱ)，收率95.7％，HPLC含量为98.7％。加入水定容成70wt％的1,4-丁二磺酸(Ⅱ)水溶液。Add 100g of 1,4-butanedisulfonate sodium (I) and 400g of 20wt% hydrogen chloride methanol solution to the reaction flask, control the temperature at 40°C, and react for 6h. After the reaction, filter at 10°C, concentrate the filtrate under reduced pressure, and evaporate Dry the solvent to obtain 1,4-butanedisulfonic acid (II) with a yield of 95.7% and an HPLC content of 98.7%. Add water to make up to 70wt% 1,4-butanedisulfonic acid (II) aqueous solution.
实施例3Example 3
向反应瓶中加入1,4-丁二磺酸钠(Ⅰ)100g，28wt％的氯化氢乙醇溶液400g，控制温度 在60℃，反应4h，反应结束后，25℃过滤，滤液减压浓缩，蒸干溶剂，得到1,4-丁二磺酸(Ⅱ)，收率92.8％，HPLC含量为99.2％。加入水定容成50wt％的1,4-丁二磺酸(Ⅱ)水溶液。Add 100g of 1,4-butanedisulfonate sodium (I) and 400g of 28wt% hydrogen chloride ethanol solution to the reaction flask, control the temperature at 60°C, and react for 4h. After the reaction, filter at 25°C, concentrate the filtrate under reduced pressure, and evaporate Dry the solvent to obtain 1,4-butanedisulfonic acid (II) with a yield of 92.8% and an HPLC content of 99.2%. Add water to make up to 50wt% 1,4-butanedisulfonic acid (II) aqueous solution.
实施例4Example 4
向反应瓶中加入1,4-丁二磺酸钠(Ⅰ)100g，10wt％的氯化氢异丙醇溶液500g，控制温度在40℃，反应6h，反应结束后，30℃过滤，滤液减压浓缩，蒸干溶剂，得到1,4-丁二磺酸(Ⅱ)，收率94.2％，HPLC含量为98.4％。加入水定容成80wt％的1,4-丁二磺酸(Ⅱ)水溶液。Add 100g of 1,4-butanedisulfonate sodium (I) and 500g of 10wt% hydrogen chloride in isopropanol solution to the reaction flask, control the temperature at 40°C, and react for 6h. After the reaction, filter at 30°C and concentrate the filtrate under reduced pressure , the solvent was evaporated to dryness to obtain 1,4-butanedisulfonic acid (II) with a yield of 94.2% and an HPLC content of 98.4%. Add water to make up to 80wt% 1,4-butanedisulfonic acid (II) aqueous solution.
Claims (8)
- 一种1,4-丁二磺酸(Ⅱ)的制备方法，其特征在于，将1,4-丁二磺酸钠(Ⅰ)和氯化氢溶液混合进行反应，反应结束后过滤，浓缩，得到1,4-丁二磺酸(Ⅱ)A kind of preparation method of 1,4-butanedisulfonic acid (II), it is characterized in that, 1,4-butanedisulfonic acid sodium (I) and hydrogen chloride solution are mixed and reacted, after reaction is finished, filter, concentrate, obtain 1 ,4-Butanedisulfonic acid (Ⅱ)
- 根据权利要求1所述的制备方法，其特征在于，所述氯化氢溶液为氯化氢水溶液或氯化氢的有机醇溶液。The preparation method according to claim 1, wherein the hydrogen chloride solution is an aqueous hydrogen chloride solution or an organic alcohol solution of hydrogen chloride.
- 根据权利要求2所述的制备方法，其特征在于，所述氯化氢的有机醇溶液选自氯化氢甲醇溶液、氯化氢乙醇溶液或氯化氢异丙醇溶液。The preparation method according to claim 2, wherein the organic alcohol solution of hydrogen chloride is selected from hydrogen chloride methanol solution, hydrogen chloride ethanol solution or hydrogen chloride isopropanol solution.
- 根据权利要求1-3任一项所述的制备方法，其特征在于，所述氯化氢溶液的质量百分比浓度为10wt％～37wt％。The preparation method according to any one of claims 1-3, characterized in that, the mass percent concentration of the hydrogen chloride solution is 10wt%-37wt%.
- 根据权利要求1-4任一项所述的制备方法，其特征在于，所述的1,4-丁二磺酸钠(Ⅰ)与氯化氢溶液的质量比为1:1～5。The preparation method according to any one of claims 1-4, characterized in that the mass ratio of sodium 1,4-butanedisulfonate (I) to hydrogen chloride solution is 1:1-5.
- 根据权利要求1-5任一项所述的制备方法，其特征在于，所述过滤的温度为0～30℃。The preparation method according to any one of claims 1-5, characterized in that the temperature of the filtration is 0-30°C.
- 根据权利要求1-6任一项所述的制备方法，其特征在于，所述反应的温度为20～60℃。The preparation method according to any one of claims 1-6, characterized in that the temperature of the reaction is 20-60°C.
- 根据权利要求1-7任一项所述的制备方法，其特征在于，所述反应的时间为2～6小时。The preparation method according to any one of claims 1-7, characterized in that the reaction time is 2-6 hours.
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