A method for efficiently preparing tranexamic acid

Abstract

The application belongs to the technical field of organic synthesis, and more particularly relates to a method for efficiently preparing tranexamic acid. The preparation method comprises the following steps: pretreating aminomethylbenzoic acid, then performing hydrogenation reaction, conversion reaction, decolorization and impurity removal, and crude product concentration. According to the application, the starting material is purified, and the conditions of hydrogenation reaction and conversion reaction are optimized, so that each reaction can be effectively controlled to smoothly proceed, the reaction energy consumption is low, the reaction time is greatly shortened, the purity of the obtained tranexamic acid is high, and the yield is good.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of organic synthesis, and more particularly relates to a method for efficiently preparing tranexamic acid. BACKGROUND

[0002] Tranexamic acid, also known as p-aminomethylcyclohexane carboxylic acid or trans-4-aminomethyl-cyclohexane carboxylic acid, is mainly used for various bleeding caused by acute or chronic, localized or systemic fibrinolysis hyperfunction. Its pharmacological action is related to fibrinolysis, increased vascular permeability and other physiological or pathological states, and also related to the occurrence, development and cure of body reactions caused by fibrinolysis, various bleeding symptoms and allergic reactions, etc. It can inhibit the action of such fibrinolysin, thereby showing hemostatic, anti-allergic and anti-inflammatory effects.

[0003] At present, there are many reported methods for preparing tranexamic acid, among which the method using aminomethylbenzoic acid as a starting material is relatively common. After hydrogenation reduction and conversion, the aminomethylbenzoic acid is refined to obtain tranexamic acid. In this method, aminomethylbenzoic acid is directly catalytically hydrogenated, and many deamination impurities are generated, which are difficult to purify and have low production efficiency. At the same time, highly toxic barium hydroxide is used for production, and the generated barium sulfate is difficult to handle, thereby limiting the economic benefit of the product. In a preparation method of tranexamic acid disclosed in Chinese Patent CN108689870A, aminomethylbenzoic acid is pretreated, but the service life of the platinum catalyst is still not high, the cost is not low, the conversion reaction temperature is high, the time is long, the energy consumption is large, and the excess sulfuric acid and alkali make the waste liquid difficult to handle. In addition, the purity of trans-aminomethylcyclohexane carboxylic acid is only 83.64%. Therefore, it is necessary to develop an efficient and environmentally friendly preparation process of tranexamic acid. SUMMARY

[0004] In view of the above defects or improvement needs of the prior art, the present application provides a method for efficiently preparing tranexamic acid. The preparation method is simple, safe, efficient, low in energy consumption, environmentally friendly, high in product yield and purity, and overcomes the shortcomings of the prior art.

[0005] In order to achieve the above-mentioned purpose, the present application provides a method for efficiently preparing tranexamic acid, comprising the following steps:

[0006] (1) Inject concentrated sulfuric acid into purified water, then add aminomethylbenzoic acid, heat to dissolve, add a pretreatment agent, stir for 1-2 h, filter to obtain a filtrate;

[0007] (2) Add a bimetallic catalyst to the filtrate of step (1), mix uniformly, then pass in hydrogen, heat to 80-100℃, carry out hydrogenation reaction, cool, filter to obtain a hydrogenation liquid;

[0008] (3) Add alkali and purified water to the hydrogenation solution in step (2) under stirring. After mixing evenly, first heat to 140-150℃ and keep it at the temperature for 1-2 hours to carry out pre-translocation. Then continue to heat to 160-170℃ and keep it at the temperature for 2-5 hours to complete the translocation reaction. Cool down to room temperature to obtain the conversion solution.

[0009] (4) Add dilute sulfuric acid to the conversion solution obtained in step (3) to adjust the pH to 4.5-5.0, add activated carbon and stir to decolorize for 0.5-1h, filter, and pass the filtrate through a sulfonic acid cation exchange resin column to obtain the final filtrate;

[0010] (5) The final filtrate obtained in step (4) is concentrated under reduced pressure to a thick slurry, stirred and cooled to below 5°C, crystallized, and then filtered to obtain tranexamic acid.

[0011] This invention uses tranexamic acid as the starting material. After dissolution, a pretreatment agent is used to effectively remove impurities such as iron and organic amines from the raw material, providing pure conditions for subsequent reactions. Then, hydrogenation is performed using a bimetallic catalyst, followed by gradient temperature control for conversion. Finally, decolorization, impurity removal, concentration, and crystallization yield tranexamic acid. This invention, by purifying the starting material and optimizing the conditions of the hydrogenation and conversion reactions, effectively controls the smooth progress of each reaction step, resulting in low energy consumption, significantly shortened reaction time, and the obtained tranexamic acid with high purity and good yield.

[0012] Furthermore, in step (1) of the above technical solution, the mass-volume ratio of aminotranexamic acid, concentrated sulfuric acid, and purified water is 1:0.2-0.75:6-30; and the heating temperature is 80-90℃.

[0013] Furthermore, in step (1) of the above technical solution, the pretreatment agent is a mixture of EDTA and activated carbon in a mass ratio of 1:2-3, and the amount used is 0.5-1.5% of the total mass of the reaction system. By pretreating the raw materials, impurities such as iron and organic amines can be effectively removed, which can prevent them from being adsorbed onto the catalyst and affecting the catalytic efficiency.

[0014] Further, in step (2) of the above technical solution, the bimetallic catalyst is a catalyst obtained by supporting ruthenium and tin on activated carbon in a molar ratio of 1:0.2-0.5, with a loading of 3-5 wt%; the amount used is 3-6% of the mass of the aminotranyl acid. Specifically, RuCl3 and SnCl2 are dissolved in deionized water to prepare a mixed solution with a Ru and Sn molar ratio of 1:0.2-0.5. Then, activated carbon is impregnated in the mixed solution overnight, filtered, dried at 80-120℃ for 10-14 h, and finally calcined at 300-500℃ for 2-5 h, and reduced at atmospheric pressure in a mixed atmosphere of hydrogen and inert gas to obtain the bimetallic catalyst. The bimetallic catalyst used in this technical solution has the electronic effect of the bimetallic interface, which can reduce the reaction energy barrier and improve the hydrogenation efficiency.

[0015] Furthermore, in step (2) of the above technical solution, the pressure of the hydrogenation reaction is 1.5-2.0 MPa, and the hydrogenation reaction is stopped when the pressure inside the reactor no longer decreases within 1 hour.

[0016] Furthermore, in step (3) of the above technical solution, the alkali is a mixture of cesium hydroxide and ethanol in a mass ratio of 1:0.2-0.3, and the amount used is 2-3 times the mass of the aminotoluic acid. In this technical solution, cesium hydroxide is used as the alkali catalyst, which fully utilizes its strong alkali advantage to accelerate the transposition reaction, shorten the reaction time, reduce the reaction temperature, and reduce energy consumption.

[0017] Furthermore, in step (4) of the above technical solution, the mass concentration of the dilute sulfuric acid is 10%; and the cesium ion concentration in the final filtrate is less than 5 ppm.

[0018] Furthermore, in step (2) of the above technical solution, the used bimetallic catalyst is washed with a 5% HNO3 solution and then reused.

[0019] Furthermore, in step (4) of the above technical solution, the sulfonic acid cation exchange resin column after adsorption is eluted with 5% dilute hydrochloric acid to remove cesium ions and then reused, and the eluted cesium ions are recycled.

[0020] Furthermore, the above technical solution also includes mixing the tranexamic acid obtained in step (5) with 1-2 times the volume of purified water, heating to 85-95℃ and stirring for 0.5-1h, cooling to below 5℃, crystallizing, and then filtering to obtain wet tranexamic acid.

[0021] The beneficial effects of this invention are:

[0022] 1. This invention improves the composition of the auxiliary agents and uses a pretreatment agent to treat the starting materials, which can effectively remove impurities from the raw materials. This not only improves the subsequent reaction rate but also prevents iron from adsorbing onto the hydrogenation catalyst, thus extending the catalyst's lifespan. The use of a bimetallic catalyst results in high catalytic efficiency, long lifespan (over 200 cycles), and low cost. The use of strong base cesium hydroxide not only accelerates the transposition reaction and shortens the reaction time but also lowers the conversion temperature, significantly reducing energy consumption.

[0023] 2. This invention improves reaction conditions by employing a gradient temperature-controlled conversion reaction. It first uses a low temperature for pre-reaction to form a thermodynamically unstable intermediate, and then raises the temperature to complete the isomerization. This not only reduces the occurrence of side reactions and improves the selectivity of the trans product, resulting in high conversion efficiency and short time, but also lowers the conversion temperature, reduces energy consumption, and yields a high-purity and high-yield final product. Detailed Implementation

[0024] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Unless otherwise specified, the raw materials used in the following examples are all commercially available products and can be purchased from the market.

[0025] The above-described technical features of the present invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions.

[0026] Example 1:

[0027] A method for efficiently preparing tranexamic acid includes the following steps:

[0028] (1) 70 kg of concentrated sulfuric acid was injected into a glass-lined mixing vessel containing 2400 L of purified water and stirred evenly. Then 100 kg of aminotranic acid was added, heated to 80 °C until dissolved, and 25 kg of pretreatment agent (EDTA and activated carbon in a mass ratio of 1:2) was added. The mixture was stirred and reacted for 2 h, and then filtered to obtain the filtrate.

[0029] (2) The filtered liquid from step (1) is poured into the hydrogenation reactor and 4 kg of bimetallic catalyst (ruthenium and tin in a molar ratio of 1:0.3 supported on activated carbon, with a loading of 4 wt%) is added. After stirring evenly, nitrogen gas is introduced to purge the air in the reactor beforehand, hydrogen gas is introduced, and the temperature is raised to 85°C. At the same time, the pressure is controlled at 2.0 MPa. The hydrogenation reaction is stopped when the pressure in the reactor no longer decreases within 1 hour, indicating that the reaction is over. The temperature is lowered and filtered to obtain the hydrogenation liquid. The bimetallic catalyst is recycled.

[0030] (3) The hydrogenated liquid from step (2) is injected into a reaction vessel lined with polytetrafluoroethylene. Under stirring, 250 kg of alkali (cesium hydroxide and ethanol in a mass ratio of 1:0.2) and 300 kg of purified water are added. After mixing evenly, the temperature is first raised to 140℃ and kept at the temperature for 2 hours for pre-translocation. Then, the temperature is raised to 160℃ and kept at the temperature for 4 hours to complete the translocation reaction. The temperature is then lowered to room temperature to obtain the conversion liquid.

[0031] (4) Add 10% dilute sulfuric acid to the conversion solution obtained in step (3) to adjust the pH to 4.5-5.0, add 2kg activated carbon and stir to decolorize for 0.5h, filter, and pass the filtrate through a sulfonic acid cation exchange resin column (AMBERLITEIR 120H) until the cesium ion concentration is less than 5ppm to obtain the final filtrate; the sulfonic acid cation exchange resin column can be reused after eluting cesium ions with 5% dilute hydrochloric acid, and the eluted cesium ions can be recovered and reused;

[0032] (5) The final filtrate obtained in step (4) was concentrated under reduced pressure to a slurry, stirred and cooled to below 5°C, crystallized, and then filtered to obtain tranexamic acid. The yield of tranexamic acid was calculated to be 92.1%, and the purity of tranexamic acid was determined to be 96.48% by gas chromatography. The bimetallic catalyst can be reused more than 200 times after washing with a 5% HNO3 solution.

[0033] Example 2:

[0034] A method for efficiently preparing tranexamic acid includes the following steps:

[0035] (1) 70 kg of concentrated sulfuric acid was injected into a glass-lined mixing vessel containing 2400 L of purified water and stirred evenly. Then 100 kg of aminotranic acid was added, heated to 85 °C until dissolved, and 25 kg of pretreatment agent (EDTA and activated carbon in a mass ratio of 1:3) was added. The mixture was stirred and reacted for 1.5 h, filtered, and the filtrate was obtained.

[0036] (2) The filtered liquid from step (1) is poured into the hydrogenation reactor and 3 kg of bimetallic catalyst (ruthenium and tin in a molar ratio of 1:0.2 supported on activated carbon, with a loading of 5 wt%) is added. After stirring evenly, nitrogen gas is introduced to purge the air in the reactor beforehand, hydrogen gas is introduced, and the temperature is raised to 90°C. At the same time, the pressure is controlled at 1.8 MPa. The hydrogenation reaction is stopped when the pressure in the reactor no longer decreases within 1 hour, indicating that the reaction is over. The temperature is lowered and filtered to obtain the hydrogenation liquid. The bimetallic catalyst is recycled.

[0037] (3) The hydrogenated liquid from step (2) is injected into a reaction vessel lined with polytetrafluoroethylene. Under stirring, 250 kg of alkali (cesium hydroxide and ethanol in a mass ratio of 1:0.2) and 300 kg of purified water are added. After mixing evenly, the temperature is first raised to 145℃ and kept at the temperature for 1.5 h for pre-translocation. Then, the temperature is raised to 165℃ and kept at the temperature for 3.5 h to complete the translocation reaction. The temperature is then lowered to room temperature to obtain the conversion liquid.

[0038] (4) Add 10% dilute sulfuric acid to the conversion solution obtained in step (3) to adjust the pH to 4.5-5.0, add 2kg activated carbon and stir for decolorization for 1h, filter, and pass the filtrate through a sulfonic acid cation exchange resin column (AMBERLITEIR 120H) until the cesium ion concentration is less than 5ppm to obtain the final filtrate; the sulfonic acid cation exchange resin column can be reused after eluting cesium ions with 5% dilute hydrochloric acid, and the eluted cesium ions can be recovered and reused;

[0039] (5) The final filtrate obtained in step (4) was concentrated under reduced pressure to a thick slurry, stirred and cooled to below 5°C, crystallized, and then filtered to obtain tranexamic acid. The yield of tranexamic acid was calculated to be 93.5%, and the purity of tranexamic acid was determined to be 96.85% by gas chromatography. The bimetallic catalyst can be reused more than 200 times after washing with a 5% HNO3 solution.

[0040] Example 3:

[0041] A method for efficiently preparing tranexamic acid includes the following steps:

[0042] (1) 70 kg of concentrated sulfuric acid was injected into a glass-lined mixing vessel containing 2400 L of purified water and stirred evenly. Then 100 kg of aminotranic acid was added, heated to 90 °C until dissolved, and 25 kg of pretreatment agent (EDTA and activated carbon in a mass ratio of 1:2.5) was added. The mixture was stirred and reacted for 2 h, and then filtered to obtain the filtrate.

[0043] (2) The filtered liquid from step (1) is poured into the hydrogenation reactor and 6 kg of bimetallic catalyst (ruthenium and tin in a molar ratio of 1:0.5 supported on activated carbon, with a loading of 3 wt%) is added. After stirring evenly, nitrogen gas is introduced to purge the air in the reactor beforehand, hydrogen gas is introduced, and the temperature is raised to 100°C while controlling the pressure at 1.5 MPa. The hydrogenation reaction is stopped when the pressure in the reactor no longer decreases within 1 hour, indicating that the reaction is over. The temperature is lowered and filtered to obtain the hydrogenation liquid. The bimetallic catalyst is recycled.

[0044] (3) The hydrogenation liquid from step (2) is injected into a reaction vessel lined with polytetrafluoroethylene. 250 kg of alkali (cesium hydroxide and ethanol in a mass ratio of 1:0.3) and 250 kg of purified water are added under stirring. After mixing evenly, the temperature is first raised to 150°C and kept at that temperature for 1 h for pre-translocation. Then the temperature is raised to 170°C and kept at that temperature for 3 h to complete the translocation reaction. The temperature is then lowered to room temperature to obtain the conversion liquid.

[0045] (4) Add 10% dilute sulfuric acid to the conversion solution obtained in step (3) to adjust the pH to 4.5-5.0, add 2kg activated carbon and stir for decolorization for 1h, filter, and pass the filtrate through a sulfonic acid cation exchange resin column (AMBERLITEIR 120H) until the cesium ion concentration is less than 5ppm to obtain the final filtrate; the sulfonic acid cation exchange resin column can be reused after eluting cesium ions with 5% dilute hydrochloric acid, and the eluted cesium ions can be recovered and reused;

[0046] (5) The final filtrate obtained in step (4) was concentrated under reduced pressure to a slurry, stirred and cooled to below 5°C, crystallized, and then filtered to obtain tranexamic acid. The yield of tranexamic acid was calculated to be 92.8%, and the purity of tranexamic acid was determined to be 97.26% by gas chromatography. The bimetallic catalyst can be reused more than 200 times after washing with a 5% HNO3 solution.

[0047] Example 4:

[0048] A method for efficiently preparing tranexamic acid includes the following steps:

[0049] (1) 70 kg of concentrated sulfuric acid was injected into a glass-lined mixing vessel containing 2400 L of purified water and stirred evenly. Then 100 kg of aminotranic acid was added, heated to 80 °C until dissolved, and 25 kg of pretreatment agent (EDTA and activated carbon in a mass ratio of 1:2) was added. The mixture was stirred and reacted for 2 h, and then filtered to obtain the filtrate.

[0050] (2) The filtered liquid from step (1) is poured into the hydrogenation reactor and 4 kg of bimetallic catalyst (ruthenium and tin in a molar ratio of 1:0.3 supported on activated carbon, with a loading of 4 wt%) is added. After stirring evenly, nitrogen gas is introduced to purge the air in the reactor beforehand, hydrogen gas is introduced, and the temperature is raised to 85°C. At the same time, the pressure is controlled at 2.0 MPa. The hydrogenation reaction is stopped when the pressure in the reactor no longer decreases within 1 hour, indicating that the reaction is over. The temperature is lowered and filtered to obtain the hydrogenation liquid. The bimetallic catalyst is recycled.

[0051] (3) The hydrogenated liquid from step (2) is injected into a reaction vessel lined with polytetrafluoroethylene. Under stirring, 250 kg of alkali (cesium hydroxide and ethanol in a mass ratio of 1:0.2) and 300 kg of purified water are added. After mixing evenly, the temperature is first raised to 140℃ and kept at the temperature for 2 hours for pre-translocation. Then, the temperature is raised to 160℃ and kept at the temperature for 4 hours to complete the translocation reaction. The temperature is then lowered to room temperature to obtain the conversion liquid.

[0052] (4) Add 10% dilute sulfuric acid to the conversion solution obtained in step (3) to adjust the pH to 4.5-5.0, add 2 kg of activated carbon and stir to decolorize for 0.5 h, filter, and pass the filtrate through a sulfonic acid cation exchange resin column (AMBERLITEIR 120H) until the cesium ion concentration is less than 5 ppm to obtain the final filtrate; the sulfonic acid cation exchange resin column can be reused after eluting cesium ions with 5% dilute hydrochloric acid, and the eluted cesium ions can be recovered and reused;

[0053] (5) The final filtrate obtained in step (4) is concentrated under reduced pressure to a thick slurry, stirred and cooled to below 5°C, crystallized, and then filtered to obtain tranexamic acid;

[0054] (6) The tranexamic acid obtained in step (5) was mixed with twice the volume of purified water, heated to 90°C and stirred for 1 hour, then cooled to below 5°C. After crystallization, the mixture was filtered to obtain wet tranexamic acid. The yield of tranexamic acid was calculated to be 91.5%, and the purity of tranexamic acid was determined to be 99.91% by gas chromatography.

[0055] Comparative Example 1:

[0056] A method for efficiently preparing tranexamic acid includes the following steps:

[0057] (1) 70 kg of concentrated sulfuric acid was injected into a glass-lined mixing vessel containing 2400 L of purified water and stirred evenly. Then 100 kg of aminotranic acid was added and heated to 80 °C until dissolved. The solution was then pressed into a hydrogenation reactor and 4 kg of bimetallic catalyst (ruthenium and tin in a molar ratio of 1:0.3 supported on activated carbon, with a loading of 4 wt%) was added. After stirring evenly, nitrogen gas was introduced to purge the air in the reactor beforehand. Hydrogen gas was introduced and the temperature was raised to 85 °C. At the same time, the pressure was controlled at 2.0 MPa. The hydrogenation reaction was stopped when the pressure in the reactor no longer decreased within 1 hour, indicating that the reaction was over. The solution was cooled, filtered, and hydrogenated liquid was obtained.

[0058] (2) The hydrogenated liquid from step (1) is injected into a reaction vessel lined with polytetrafluoroethylene. 250 kg of alkali (cesium hydroxide and ethanol in a mass ratio of 1:0.2) and 300 kg of purified water are added under stirring. After mixing evenly, the temperature is first raised to 140℃ and kept at that temperature for 2 hours for pre-translocation. Then the temperature is raised to 160℃ and kept at that temperature for 4 hours to complete the translocation reaction. The temperature is then lowered to room temperature to obtain the conversion liquid.

[0059] (3) Add 10% dilute sulfuric acid to the conversion solution obtained in step (2) to adjust the pH to 4.5-5.0, add 2kg activated carbon and stir to decolorize for 0.5h, filter, and pass the filtrate through a sulfonic acid cation exchange resin column (AMBERLITEIR 120H) until the cesium ion concentration is less than 5ppm to obtain the final filtrate; the sulfonic acid cation exchange resin column can be reused after eluting cesium ions with 5% dilute hydrochloric acid, and the eluted cesium ions can be recovered and reused;

[0060] (4) The final filtrate obtained in step (3) was concentrated under reduced pressure to a slurry, stirred and cooled to below 5°C, crystallized, and then filtered to obtain tranexamic acid. The yield of tranexamic acid was calculated to be 88.6%, and the purity of tranexamic acid was determined to be 93.65% by gas chromatography. The bimetallic catalyst can be reused 130 times after washing with a 5% HNO3 solution.

[0061] Comparative Example 2:

[0062] A method for efficiently preparing tranexamic acid includes the following steps:

[0063] (1) 70 kg of concentrated sulfuric acid was injected into a glass-lined mixing vessel containing 2400 L of purified water and stirred evenly. Then 100 kg of aminotranic acid was added, heated to 80 °C until dissolved, and 25 kg of pretreatment agent (EDTA and activated carbon in a mass ratio of 1:2) was added. The mixture was stirred and reacted for 2 h, and then filtered to obtain the filtrate.

[0064] (2) The filtered liquid from step (1) is poured into the hydrogenation reactor and 4 kg of catalyst (ruthenium supported on activated carbon, with a loading of 4 wt%) is added. After stirring evenly, nitrogen gas is introduced to purge the air in the reactor beforehand, and hydrogen gas is introduced. The temperature is raised to 85°C, while the pressure is controlled at 2.0 MPa. The hydrogenation reaction is stopped when the pressure in the reactor no longer decreases within 1 hour, indicating that the reaction is over. The temperature is lowered and filtered to obtain the hydrogenation liquid. The bimetallic catalyst is recycled.

[0065] (3) The hydrogenated liquid from step (2) is injected into a reaction vessel lined with polytetrafluoroethylene. Under stirring, 250 kg of alkali (cesium hydroxide and ethanol in a mass ratio of 1:0.2) and 300 kg of purified water are added. After mixing evenly, the temperature is first raised to 140℃ and kept at the temperature for 2 hours for pre-translocation. Then, the temperature is raised to 160℃ and kept at the temperature for 4 hours to complete the translocation reaction. The temperature is then lowered to room temperature to obtain the conversion liquid.

[0066] (4) Add 10% dilute sulfuric acid to the conversion solution obtained in step (3) to adjust the pH to 4.5-5.0, add 2kg activated carbon and stir to decolorize for 0.5h, filter, and pass the filtrate through a sulfonic acid cation exchange resin column (AMBERLITEIR 120H) until the cesium ion concentration is less than 5ppm to obtain the final filtrate; the sulfonic acid cation exchange resin column can be reused after eluting cesium ions with 5% dilute hydrochloric acid, and the eluted cesium ions can be recovered and reused;

[0067] (5) The final filtrate obtained in step (4) was concentrated under reduced pressure to a slurry, stirred and cooled to below 5°C, crystallized, and then filtered to obtain tranexamic acid. The yield of tranexamic acid was calculated to be 84.5%, and the purity of tranexamic acid was determined to be 94.25% by gas chromatography. The catalyst can be reused 105 times after washing with 5% HNO3 solution.

[0068] Comparative Example 3:

[0069] A method for efficiently preparing tranexamic acid includes the following steps:

[0070] (1) 70 kg of concentrated sulfuric acid was injected into a glass-lined mixing vessel containing 2400 L of purified water and stirred evenly. Then 100 kg of aminotranic acid was added, heated to 80 °C until dissolved, and 25 kg of pretreatment agent (EDTA and activated carbon in a mass ratio of 1:2) was added. The mixture was stirred and reacted for 2 h, and then filtered to obtain the filtrate.

[0071] (2) The filtered liquid from step (1) is poured into the hydrogenation reactor and 4 kg of bimetallic catalyst (ruthenium and tin in a molar ratio of 1:0.3 supported on activated carbon, with a loading of 4 wt%) is added. After stirring evenly, nitrogen gas is introduced to purge the air in the reactor beforehand, hydrogen gas is introduced, and the temperature is raised to 85°C. At the same time, the pressure is controlled at 2.0 MPa. The hydrogenation reaction is stopped when the pressure in the reactor no longer decreases within 1 hour, indicating that the reaction is over. The temperature is lowered and filtered to obtain the hydrogenation liquid. The bimetallic catalyst is recycled.

[0072] (3) The hydrogenation liquid from step (2) is injected into a reaction vessel lined with polytetrafluoroethylene. 250 kg of barium hydroxide and 300 kg of purified water are added under stirring. After mixing evenly, the temperature is first raised to 170°C and kept at the temperature for 2 hours for pre-translocation. Then the temperature is raised to 200°C and kept at the temperature for 4 hours to complete the translocation reaction. The temperature is then lowered to room temperature to obtain the conversion liquid.

[0073] (4) The converted liquid obtained in step (3) is injected into the CO2 neutralization vessel and CO2 is introduced. The temperature is raised to 50°C and the reaction is completed when the pH does not change. The mixture is filtered, and the pH of the filtrate is adjusted to 5.5-6.0 with 10% dilute sulfuric acid. 2 kg of activated carbon is added and stirred for decolorization for 0.5 h. The mixture is then filtered.

[0074] (5) The filtrate obtained in step (4) was concentrated under reduced pressure to a thick slurry, stirred and cooled to below 5°C, crystallized, and then filtered to obtain tranexamic acid. The yield of tranexamic acid was calculated to be 76.7%, and the purity of tranexamic acid was determined to be 93.54% by gas chromatography. The bimetallic catalyst can be reused more than 200 times after washing with a 5% HNO3 solution.

[0075] Comparative Example 4:

[0076] A method for efficiently preparing tranexamic acid includes the following steps:

[0077] (1) 70 kg of concentrated sulfuric acid was injected into a glass-lined mixing vessel containing 2400 L of purified water and stirred evenly. Then 100 kg of aminotranic acid was added, heated to 80 °C until dissolved, and 25 kg of pretreatment agent (EDTA and activated carbon in a mass ratio of 1:2) was added. The mixture was stirred and reacted for 2 h, and then filtered to obtain the filtrate.

[0078] (2) The filtered liquid from step (1) is poured into the hydrogenation reactor and 4 kg of bimetallic catalyst (ruthenium and tin in a molar ratio of 1:0.3 supported on activated carbon, with a loading of 4 wt%) is added. After stirring evenly, nitrogen gas is introduced to purge the air in the reactor beforehand, hydrogen gas is introduced, and the temperature is raised to 85°C. At the same time, the pressure is controlled at 2.0 MPa. The hydrogenation reaction is stopped when the pressure in the reactor no longer decreases within 1 hour, indicating that the reaction is over. The temperature is lowered and filtered to obtain the hydrogenation liquid. The bimetallic catalyst is recycled.

[0079] (3) The hydrogenation liquid from step (2) is injected into a reaction vessel lined with polytetrafluoroethylene. 250 kg of alkali (cesium hydroxide and ethanol in a mass ratio of 1:0.2) and 300 kg of purified water are added under stirring. After mixing evenly, the temperature is raised to 160℃ and kept at that temperature for 6 hours to complete the transposition reaction. The temperature is then lowered to room temperature to obtain the conversion liquid.

[0080] (4) Add 10% dilute sulfuric acid to the conversion solution obtained in step (3) to adjust the pH to 4.5-5.0, add 2kg activated carbon and stir to decolorize for 0.5h, filter, and pass the filtrate through a sulfonic acid cation exchange resin column (AMBERLITEIR 120H) until the cesium ion concentration is less than 5ppm to obtain the final filtrate; the sulfonic acid cation exchange resin column can be reused after eluting cesium ions with 5% dilute hydrochloric acid, and the eluted cesium ions can be recovered and reused;

[0081] (5) The final filtrate obtained in step (4) was concentrated under reduced pressure to a slurry, stirred and cooled to below 5°C, crystallized, and then filtered to obtain tranexamic acid. The yield of tranexamic acid was calculated to be 82.4%, and the purity of tranexamic acid was determined to be 93.85% by gas chromatography. The bimetallic catalyst can be reused more than 200 times after washing with a 5% HNO3 solution.

[0082] Results analysis:

[0083] As can be seen from the results of Examples 1-4, the tranexamic acid prepared according to the method of the present invention has a yield of over 92% and a purity of over 96%. After further purification, the purity can reach over 99.9%. The overall preparation time is shortened, especially the conversion reaction time, which only requires 4-6 hours. The reaction temperature is reduced to 160-170℃, the energy consumption is greatly reduced, the catalyst used can be reused more than 200 times, and the cost is low.

[0084] In Comparative Example 1, no pretreatment agent was used to treat the starting materials compared to Example 1, resulting in a decrease in product yield and purity, and a significant reduction in catalyst lifespan. In Comparative Example 2, the hydrogenation reaction catalyst was ruthenium-carbon catalysis, which reduced catalytic efficiency and thus affected product yield. In Comparative Example 3, barium hydroxide was used for catalytic conversion, requiring a reaction temperature above 200°C, which not only resulted in high energy consumption but also low product yield due to short reaction time, and barium hydroxide is toxic and environmentally unfriendly. In Comparative Example 4, the conversion reaction was heated to the target temperature in one step, leading to numerous side reactions, incomplete isomerization, reduced conversion efficiency, and a decrease in both product yield and purity.

[0085] Finally, it should be emphasized that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention can have various changes and modifications. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for efficiently preparing tranexamic acid, characterized in that, Includes the following steps: (1) Concentrated sulfuric acid is injected into purified water, then aminotranexamic acid is added, heated until dissolved, pretreatment agent is added and stirred for 1-2 hours, filtered, and filtrate is obtained; the mass-volume ratio of aminotranexamic acid, concentrated sulfuric acid and purified water is 1:0.2-0.75:6-30; the pretreatment agent is a mixture of EDTA and activated carbon with a mass ratio of 1:2-3. (2) Add the bimetallic catalyst to the filtrate from step (1), mix thoroughly, then introduce hydrogen gas, heat to 80-100℃, carry out the hydrogenation reaction, cool down, and filter to obtain the hydrogenated solution; the bimetallic catalyst is a catalyst obtained by supporting ruthenium and tin on activated carbon in a molar ratio of 1:0.2-0.5, with a loading of 3-5 wt%; (3) Add alkali and purified water to the hydrogenation solution in step (2) under stirring. After mixing evenly, first heat to 140-150℃ and keep it at that temperature for 1-2 hours to perform pre-translocation. Then continue to heat to 160-170℃ and keep it at that temperature for 2-5 hours to complete the translocation reaction. Cool to room temperature to obtain the conversion solution. The alkali is a mixture of cesium hydroxide and ethanol in a mass ratio of 1:0.2-0.

3. (4) Add dilute sulfuric acid to the conversion solution obtained in step (3) to adjust the pH to 4.5-5.0, add activated carbon and stir to decolorize for 0.5-1h, filter, and pass the filtrate through a sulfonic acid cation exchange resin column to obtain the final filtrate; (5) The final filtrate obtained in step (4) is concentrated under reduced pressure to a thick slurry, stirred and cooled to below 5°C, crystallized, and then filtered to obtain tranexamic acid.

2. The method for efficiently preparing tranexamic acid according to claim 1, characterized in that, In step (1), the mass-volume ratio of aminotranexamic acid, concentrated sulfuric acid, and purified water is 1:0.2-0.75:6-30; the heating temperature is 80-90℃.

3. The method for efficiently preparing tranexamic acid according to claim 1, characterized in that, In step (1), the amount of the pretreatment agent used is 0.5-1.5% of the total mass of the reaction system.

4. The method for efficiently preparing tranexamic acid according to claim 1, characterized in that, In step (2), the amount of the bimetallic catalyst used is 3-6% of the mass of the aminotranyl acid.

5. The method for efficiently preparing tranexamic acid according to claim 1, characterized in that, In step (2), the pressure of the hydrogenation reaction is 1.5-2.0 MPa, and the hydrogenation reaction is stopped when the pressure inside the reactor no longer decreases within 1 hour.

6. The method for efficiently preparing tranexamic acid according to claim 1, characterized in that, In step (3), the amount of alkali used is 2-3 times the mass of the aminotranic acid.

7. The method for efficiently preparing tranexamic acid according to claim 1, characterized in that, In step (4), the mass concentration of the dilute sulfuric acid is 10%; the cesium ion concentration in the final filtrate is less than 5 ppm.

8. The method for efficiently preparing tranexamic acid according to claim 1, characterized in that, In step (2), the used bimetallic catalyst is washed with a 5% HNO3 solution and then reused.

9. The method for efficiently preparing tranexamic acid according to claim 1, characterized in that, In step (4), the sulfonic acid cation exchange resin column after adsorption is eluted with 5% dilute hydrochloric acid to remove cesium ions and then reused. The eluted cesium ions are then recycled.

10. The method for efficiently preparing tranexamic acid according to claim 1, characterized in that, It also includes mixing the tranexamic acid obtained in step (5) with 1-2 times the volume of purified water, heating to 85-95℃ and stirring for 0.5-1h, cooling to below 5℃, crystallizing, filtering, and obtaining wet tranexamic acid.