A method for the synthesis of tranexamic acid

Abstract

The present application relates to a kind of synthetic methods of tranexamic acid.The method of the present application, with terephthalic acid or terephthalate as raw material, through hydrogenation, ammoniation dehydration, hydrogenation and the like step synthesis tranexamic acid.The method for synthesizing tranexamic acid of the present application, raw material cost is low, process is simple, route green, reaction process is less pollution, can be operated continuously, and high efficiency.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical chemical synthesis, and more specifically, to a method for synthesizing tranexamic acid. Background Technology

[0002] Tranexamic acid is an antifibrinolytic drug, primarily used clinically for hemostasis. In recent years, extensive and in-depth research has been conducted in the field of dermatology and cosmetic medicine, confirming that tranexamic acid reduces melanin production, has anti-inflammatory, anti-allergic, and anti-skin aging and photoaging effects. It can be used to treat various skin diseases such as melasma, post-inflammatory hyperpigmentation, urticaria, and angioedema. Currently, the domestic and international demand exceeds thousands of tons.

[0003]

[0004] The current synthesis method of tranexamic acid is shown in reaction formula 1. It mainly uses p-cyanobenzyl chloride as a raw material, which is hydrolyzed and aminated to prepare tranexamic acid. The tranexamic acid is then catalytically hydrogenated to saturate the benzene ring before undergoing transposition to prepare tranexamic acid. P-cyanobenzyl chloride is expensive (>70,000 RMB per ton), resulting in high synthesis costs. In the process of hydrogenating tranexamic acid to prepare tranexamic acid, a large amount of sulfuric acid is generally added to increase the concentration of reactants. Platinum black catalysts are generally used, which are expensive and need to be reused repeatedly to reduce costs, but the catalytic effect is not ideal. The large amount of sulfuric acid used in the hydrogenation step requires the addition of large amounts of barium hydroxide to remove residual sulfuric acid, resulting in the generation of a large amount of waste salt in the transposition step. This process route has high requirements for equipment and generates a large amount of solid waste, increasing production costs.

[0005]

[0006] In summary, the current synthesis of tranexamic acid faces challenges such as high raw material prices, high catalyst costs in the hydrogenation process, and the generation of significant amounts of wastewater and solid waste, resulting in high overall costs. Furthermore, all steps in reaction formula 1 are batch reactions, leading to generally low production efficiency. Therefore, the development of novel and legal methods remains necessary. Summary of the Invention

[0007] To address the problems existing in the prior art, the present invention aims to provide a method for synthesizing tranexamic acid. The method of the present invention uses terephthalic acid or terephthalic ester as raw materials, and synthesizes tranexamic acid through hydrogenation, ammoniation dehydration, hydrogenation, and transposition steps under the action of a catalyst. The method for synthesizing tranexamic acid of the present invention is simple, easy to separate, allows for continuous operation of multiple steps, has a high yield, reduces waste emissions, and is beneficial for industrial production.

[0008] To achieve the above-mentioned objectives of the present invention, according to one aspect of the present invention, a method for synthesizing tranexamic acid represented by the following reaction formula 2 is provided, comprising the following steps:

[0009]

[0010] Reaction 2

[0011] (1) After mixing terephthalic acid or terephthalic ester with an alkaline solution, the mixture is passed into a reactor containing catalyst 1 for hydrogenation reaction. The resulting product is acidified to obtain 1,4-cyclohexanedicarboxylic acid or 1,4-cyclohexanedicarboxylic ester.

[0012] (2) Mix 1,4-cyclohexanedicarboxylic acid or 1,4-cyclohexanedicarboxylic acid ester with an ammonia source and add it to a reactor containing catalyst 2 for ammoniation and dehydration reaction. The product enters a storage tank to obtain p-cyanocyclohexanecarboxylic acid.

[0013] (3) After mixing p-cyanocyclohexanecarboxylic acid with a solvent, the mixture is passed into a reactor containing catalyst 3 for hydrogenation reaction. The product is then distilled to remove the solvent and obtain aminomethyl tranexamic acid.

[0014] Wherein, R is H, C1-C6 alkyl, more preferably C1-C3 alkyl, and most preferably methyl, ethyl, n-propyl or isopropyl.

[0015] In some embodiments, preferably, the catalyst 1 in step (1) is a Raney Ni, Raney Co catalyst or a supported metal catalyst, wherein the metal active component M in the supported metal catalyst is selected from one or more of Pd, Ru, Rh, Pt, Ni, Co, and Cu, and the catalyst support is selected from one or more of activated carbon, γ-Al2O3, SiO2, Nb2O5, and zeolite molecular sieves.

[0016] Preferably, the catalyst 1 in step (1) is a Raney Ni, Raney Co catalyst or a supported metal catalyst, wherein the active metal component in the supported metal catalyst is selected from one or more of Pd, Ru, Rh, Ni, and Co, and the catalyst support is selected from one or more of γ-Al2O3, SiO2, Nb2O5, and zeolite molecular sieves.

[0017] More preferably, the catalyst 1 in step (1) is a Raney Ni, Raney Co catalyst or a supported metal catalyst, wherein the active metal component in the supported metal catalyst is selected from one or more of Pd, Ru, Ni and Co, and the catalyst support is selected from one or more of γ-Al2O3, SiO2 and zeolite molecular sieve.

[0018] The zeolite molecules are selected from one or more of H-ZSM-5, H-ZSM-35, HY, and Hβ.

[0019] In some embodiments, the alkali in step (1) is selected from one or two of sodium hydroxide and potassium hydroxide.

[0020] In some embodiments, the mass concentration of the alkaline solution in step (1) is 10%-50 wt%, preferably 10-30 wt%, and more preferably 15-30 wt%.

[0021] In some embodiments, the molar ratio of the base to terephthalic acid or terephthalic ester in step (1) is 2:1-6:1, preferably 2:1-4:1, and more preferably 2:1-3:1.

[0022] In some embodiments, the reaction temperature in step (1) is 120-250°C, preferably 120-220°C, and more preferably 150-200°C.

[0023] In some embodiments, the reaction pressure in step (1) is 2-8 MPa, preferably 2-6 MPa, and more preferably 3-5 MPa.

[0024] Alternatively, step (1) is carried out as follows: terephthalic acid or terephthalate ester is mixed and dissolved with an alkaline solution in a reaction vessel, and catalyst 1 is added. After the air in the vessel is replaced with hydrogen, a hydrogenation reaction is carried out. After the reaction is completed, catalyst 1 is removed by filtration, and the product is acidified to obtain 1,4-cyclohexanedicarboxylic acid or 1,4-cyclohexanedicarboxylic acid ester.

[0025] In some embodiments, when a reaction vessel is used as a reactor in step (1), the mass ratio of catalyst 1 to terephthalic acid or terephthalic ester is 1:100-30:100, preferably 3:100-20:100, and more preferably 5:100-15:100.

[0026] In some embodiments, when a fixed bed is used as the reactor in step (1), the mass hourly space velocity (MSV) of the terephthalic acid or terephthalate ester is 0.1-5 h⁻¹. -1 Preferably 0.3-3h -1 More preferably 0.5-1.5h -1 .

[0027] Preferably, the reactor in step (2) includes a fixed-bed reactor and a fluidized-bed reactor.

[0028] Preferably, the ammonia source in step (2) is selected from one or more of ammonia gas, ammonia water, urea, ammonium carbonate, and ammonium bicarbonate, and is preferably ammonia gas or urea.

[0029] In some embodiments, the molar ratio of the ammonia source to 1,4-cyclohexanedicarboxylic acid or 1,4-cyclohexanedicarboxylic acid ester in step (2) is 0.9:1 to 1.5:1.

[0030] In some embodiments, the catalyst 2 in step (2) is a solid acid selected from one or more of γ-Al2O3, SiO2, SiO2-Al2O3, ZrO2, CeO2, Nb2O5, and zeolite molecular sieves, wherein the zeolite molecular sieve is selected from one or more of H-ZSM-5, H-ZSM-35, HY, and Hβ.

[0031] In some embodiments, the reaction temperature in step (2) is 250-400°C, preferably 280-350°C, and more preferably 290-350°C.

[0032] In some embodiments, the reaction pressure in step (2) is 0.1-1.0 MPa, preferably 0.1-0.5 MPa, and more preferably 0.1-0.3 MPa. In some embodiments, the mass hourly space velocity (HHSV) of the 1,4-cyclohexanedicarboxylic acid or 1,4-cyclohexanedicarboxylic acid ester in step (2) is 0.05-5 h⁻¹. -1 Preferably 0.1-3h -1 More preferably 0.1-1.0h -1 .

[0033] Preferably, the catalyst 3 in step (3) is a Raney Ni, Raney Co catalyst or a supported metal catalyst, wherein the metal active component M in the supported metal catalyst is selected from one or more of Pd, Ru, Pt, Ni, and Co, and the catalyst support is selected from one or more of activated carbon, γ-Al2O3, SiO2, and zeolite molecular sieve.

[0034] The zeolite molecules are selected from one or more of H-ZSM-5, H-ZSM-35, HY, and Hβ.

[0035] In some embodiments, the reaction solvent in step (3) is selected from one or more of methanol, ethanol, isopropanol, tetrahydrofuran, and 1,4-dioxane.

[0036] In some embodiments, the mass concentration of the raw material in step (3) is 5-40 wt%, preferably 10-30 wt%, and more preferably 20-30 wt%.

[0037] In some embodiments, the reaction temperature in step (3) is 60-200°C, preferably 80-180°C, and more preferably 100-180°C.

[0038] In some embodiments, the reaction pressure in step (3) is 2-8 MPa, preferably 2-6 MPa, and more preferably 3-5 MPa.

[0039] Alternatively, step (3) is carried out as follows: p-cyanocyclohexane carboxylic acid, solvent and catalyst 3 are mixed and added to the reaction vessel. After replacing the air in the vessel with hydrogen, hydrogen is introduced and the temperature is raised to carry out the hydrogenation reaction. After the reaction is completed, catalyst 3 is removed by filtration and solvent is removed by distillation to obtain tranexamic acid.

[0040] In some embodiments, when a reaction vessel is used as a reactor in step (3), the mass ratio of the catalyst 3 to p-cyanocyclohexanecarboxylic acid is 1:100-30:100, preferably 3:100-20:100, and more preferably 3:100-15:100.

[0041] In some embodiments, when a fixed bed is used as the reactor in step (3), the mass hourly space velocity (HSV) of the p-cyanocyclohexane carboxylic acid is 0.05-3 h⁻¹. -1 Preferably 0.1-3h -1 More preferably 0.1-1.0h -1 .

[0042] Beneficial effects:

[0043] This invention provides a method for synthesizing tranexamic acid, which features low raw material costs, a green reaction route, continuous multi-step production, high efficiency, and simple operation. Compared with traditional methods, it is easier to achieve industrial-scale production.

[0044] Instruction manual illustrations

[0045] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0046] Figure 1 The chromatographic detection results of the product 1,4-cyclohexanedicarboxylic acid obtained in step 1 of Example 1 are shown below.

[0047] Figure 2 The chromatographic detection results of the product p-cyanocyclohexanecarboxylic acid obtained in step 2 of Example 1 are shown below.

[0048] Figure 3 The mass spectrometry results of the product obtained in step 2 of Example 1 for the detection of cyanocyclohexanecarboxylic acid;

[0049] Figure 4The chromatographic detection results are for tranexamic acid, the product obtained in step 3 of Example 1. Detailed Implementation

[0050] The present invention will now be described in detail. Before proceeding with the description, it should be understood that the terminology used in this specification and the appended claims should not be construed as limited to its general or dictionary meaning, but rather should be interpreted according to the meaning and concept corresponding to the technical aspects of the invention, based on the principle that the inventors are allowed to appropriately define the terms for the best interpretation. Therefore, the description presented herein is merely a preferred example for illustrative purposes and is not intended to limit the scope of the invention. It should be understood that other equivalents or modifications can be obtained from it without departing from the spirit and scope of the invention.

[0051] Step (1) of the method for synthesizing tranexamic acid according to the present invention can be carried out in a continuous reactor, such as a fixed-bed reactor, or in a batch reactor, such as a reaction vessel. Preferably, step (1) is carried out in a continuous reactor, such as a fixed-bed reactor.

[0052] The alkali used in step (1) is selected from one or both of sodium hydroxide and potassium hydroxide, and the mass concentration of the alkali solution is 10%-50 wt%, preferably 10-30 wt%, and more preferably 15-30 wt%. Although a higher alkali solution concentration is beneficial to the hydrogenation reaction, an excessively high concentration can lead to increased material viscosity, which can easily cause blockage of the reaction equipment and reduced material flowability. Conversely, an excessively low concentration of alkali solution will increase wastewater volume. When the mass concentration of the alkali solution is controlled within the above-mentioned range, the reaction economy can be optimally achieved.

[0053] The molar ratio of the alkali to terephthalic acid or terephthalate in step (1) is 2:1-6:1, preferably 2:1-4:1, and more preferably 2:1-3:1. A higher molar ratio will increase the amount of wastewater, while a lower molar ratio will reduce the solubility of the raw materials.

[0054] The reaction temperature in step (1) is 120-250℃, preferably 120-220℃, and more preferably 150-200℃. Too low a reaction temperature will slow down the reaction rate and prolong the reaction time, while too high a temperature will speed up the reaction rate, but too high a reaction temperature will place higher demands on the heating medium, equipment safety, and energy consumption.

[0055] The reaction pressure in step (1) is 2-8 MPa, preferably 2-6 MPa, and more preferably 3-5 MPa. If the reaction pressure is too low, the reaction time will be prolonged or the reaction will not be complete. If the reaction pressure is too high, the requirements for the equipment will be high and the cost will be high.

[0056] Since step (1) can also be carried out in a batch reactor, step (1) can be carried out as follows: terephthalic acid or terephthalate ester is mixed and dissolved with an alkaline solution in a reactor, and catalyst 1 is added. After the air in the reactor is replaced with hydrogen, a hydrogenation reaction is carried out. After the reaction is completed, catalyst 1 is removed by filtration, and the product is acidified to obtain 1,4-cyclohexanedicarboxylic acid or 1,4-cyclohexanedicarboxylic acid ester.

[0057] When a reaction vessel is used as the reactor in step (1), the mass ratio of catalyst 1 to terephthalic acid or terephthalate ester is 1:100-30:100, preferably 3:100-20:100, and more preferably 5:100-15:100. A ratio that is too low will result in prolonged reaction time or incomplete reaction, while a ratio that is too high will increase the amount of catalyst used and thus the cost.

[0058] In the method for synthesizing tranexamic acid according to the present invention, when a fixed bed reactor is used in step (1), the mass hourly space velocity (HHSV) of the terephthalic acid or terephthalic ester is 0.1-5 h⁻¹. -1 Preferably 0.3-3h -1 More preferably 0.5-1.5h -1 If the space velocity is too high, the conversion rate decreases; if the space velocity is too low, the reactor's processing capacity is wasted. The formula for calculating the mass hourly space velocity is as follows:

[0059]

[0060] The mass flow rate of terephthalic acid or terephthalic ester is expressed in g / min, and the mass of catalyst is expressed in g.

[0061] In addition, the product obtained in step (1) is condensed and separated into gas and liquid and then enters a storage tank. The product in the storage tank is adjusted to pH 1-2 with hydrochloric acid with a mass percentage concentration of 20% to obtain 1,4-cyclohexanedicarboxylic acid or 1,4-cyclohexanedicarboxylic acid ester.

[0062] In step (2) of the method for synthesizing tranexamic acid according to the present invention, 1,4-cyclohexanedicarboxylic acid or 1,4-cyclohexanedicarboxylic acid ester obtained in step (1) is mixed with an ammonia source and added to a reactor containing catalyst 2 for ammoniation and dehydration reaction. The product enters a storage tank to obtain p-cyanocyclohexanecarboxylic acid.

[0063] The reactors mentioned above include fixed-bed reactors and fluidized-bed reactors.

[0064] The ammonia source is selected from one or more of ammonia gas, ammonia water, urea, ammonium carbonate, and ammonium bicarbonate. However, considering economic efficiency and ease of operation, ammonia gas or urea is preferred.

[0065] The molar ratio of the ammonia source to 1,4-cyclohexanedicarboxylic acid or 1,4-cyclohexanedicarboxylic acid ester in step (2) is 0.9:1-1.5:1. If the ratio is too low (i.e., insufficient ammonia source), the conversion rate of the reactants will decrease; if the ratio is too high (i.e., excessive ammonia source), side reactions will increase, raw material consumption will be high, and costs will be high.

[0066] The reaction temperature in step (2) is 250-400℃, preferably 280-350℃, and more preferably 290-350℃. Too low a reaction temperature will slow down the reaction and waste the reactor's processing capacity; too high a temperature will place high demands on the equipment and will generate byproducts, reducing the yield.

[0067] The reaction pressure in step (2) is 0.1-1.0 MPa, preferably 0.1-0.5 MPa, and more preferably 0.1-0.3 MPa. If the reaction pressure is too low, the reaction time will be slower; if the reaction pressure is too high, the requirements for the equipment will be higher, and the cost will be higher.

[0068] In step (2) of the method for synthesizing tranexamic acid according to the present invention, the mass hourly space velocity (HHSV) of the 1,4-cyclohexanedicarboxylic acid or 1,4-cyclohexanedicarboxylic acid ester is 0.05-5 h⁻¹. -1 Preferably 0.1-3h -1 More preferably 0.1-1.0h -1 Excessive space velocity reduces conversion rate; insufficient space velocity wastes reactor capacity. The formula for calculating mass hourly space velocity is as follows:

[0069]

[0070] The mass flow rate of 1,4-cyclohexanedicarboxylic acid or 1,4-cyclohexanedicarboxylic acid ester is expressed in g / min, and the mass of the catalyst is expressed in g.

[0071] In step (3) of the method for synthesizing tranexamic acid according to the present invention, the p-cyanocyclohexanecarboxylic acid obtained in step (2) is mixed with a solvent and then passed into a reactor containing catalyst 3 for hydrogenation reaction. The resulting product is distilled to remove the solvent and obtain tranexamic acid.

[0072] The reaction solvent in step (3) is selected from one or more of methanol, ethanol, isopropanol, tetrahydrofuran, and 1,4-dioxane. However, considering the economic efficiency of the reaction, methanol is preferred.

[0073] The mass concentration of the raw material in step (3) is controlled at 5-40 wt%, preferably 10-30 wt%, and more preferably 20-30 wt%. If the concentration is too low, the amount of solvent used will increase, and the cost will be higher. If the concentration is too high, it may lead to an increase in by-products.

[0074] The reaction temperature in step (3) is 60-200℃, preferably 80-180℃, and more preferably 100-180℃. If the temperature is too low, the reaction rate will be significantly slower; if the temperature is too high, the requirements for the equipment will be higher, increasing the reaction cost.

[0075] The reaction pressure in step (3) is 2-8 MPa, preferably 2-6 MPa, and more preferably 3-5 MPa. Too low a reaction pressure will slow down the reaction time, while too high a reaction pressure will place higher demands on the equipment and increase costs.

[0076] Step (3) can also be carried out in a batch reactor, such as a reaction vessel. Alternatively, step (3) is carried out as follows: p-cyanocyclohexanecarboxylic acid, solvent and catalyst 3 are mixed and added to the reaction vessel, the air in the vessel is replaced with hydrogen and then hydrogen is introduced, the temperature is raised to carry out the hydrogenation reaction, after the reaction is completed, catalyst 3 is removed by filtration, and the solvent is removed by distillation to obtain tranexamic acid.

[0077] When a reaction vessel is used as the reactor in step (3), the mass ratio of catalyst 3 to p-cyanocyclohexanecarboxylic acid is 1:100-30:100, preferably 3:100-20:100, and more preferably 3:100-15:100. If the ratio is too low, the reaction will be slower; if the ratio is too high, the amount of catalyst will increase, and the cost will rise.

[0078] When a fixed bed reactor is used in step (3) of the method for synthesizing tranexamic acid according to the present invention, the mass hourly space velocity (HHSV) of the p-cyanocyclohexanecarboxylic acid is 0.05-3 h⁻¹. -1 Preferably 0.1-3h -1 More preferably 0.1-1.0h -1 Excessive space velocity reduces conversion rate; insufficient space velocity wastes reactor capacity. The formula for calculating mass hourly space velocity is as follows:

[0079]

[0080] The mass flow rate of p-cyanocyclohexanecarboxylic acid is expressed in g / min, and the mass of the catalyst is expressed in g.

[0081] Unless otherwise specified, the raw materials, reagents, and methods used in the embodiments are all conventional raw materials, reagents, and methods in the art.

[0082] In the following examples, deionized water, Ni / γ-Al2O3, Ru / γ-Al2O3, and Ni / SiO2 were prepared in-house; terephthalic acid, sodium hydroxide, potassium hydroxide, methanol, ethanol, and isopropanol were purchased from Sinopharm Chemical Reagent Co., Ltd.; γ-Al2O3 and SiO2 were purchased from Qingdao Hailang Silica Gel Desiccant Co., Ltd.; the zeolite molecular sieves could be purchased from, for example, H-ZSM-5, H-ZSM-35, HY, and Hβ produced by Tianjin Nanhua Catalyst Co., Ltd.; the H-ZSM-5 series molecular sieves were purchased from Tianjin Nanhua Catalyst Co., Ltd.; the Raney Ni catalyst was purchased from Shanghai Xunkai New Material Technology Co., Ltd.; the Raney Co catalyst was purchased from Jiangsu Raney Metal Technology Co., Ltd.; and high-purity nitrogen, high-purity ammonia, and high-purity hydrogen were purchased from Qingdao Dehai Weiye Technology Co., Ltd.

[0083] In the method for synthesizing tranexamic acid according to the present invention, terephthalic acid / terephthalate ester is used as a raw material, and tranexamic acid is synthesized through hydrogenation, ammoniation dehydration, hydrogenation, and transposition steps under the action of a catalyst. The products obtained in each step are filtered through a 0.22 μm filter membrane and analyzed by liquid chromatography. Liquid chromatography detection conditions: Instrument: Shimadzu LC-20A, chromatographic column: Elite AQ 18, mobile phase: water / acetonitrile = 4:1, isocratic elution, column flow rate: 0.6 ml / min, detector wavelength: 210 nm, column temperature: 30 °C. The relevant calculation formulas are as follows:

[0084]

[0085]

[0086]

[0087] Furthermore, in the heterogeneous catalyst according to this disclosure, the carrier on which the bimetallic alloy catalyst is deposited serves to support and disperse the bimetallic alloy catalyst, thereby increasing its surface area, stabilizing the catalyst by preventing sintering, and reducing the price of the bimetallic alloy catalyst. The carrier itself is not active, but it influences the catalyst activity due to the aforementioned functions. Even using the same composition, the difference in catalyst activity varies greatly depending on the degree of metal catalyst loading; therefore, the selection of the carrier is considered very important.

[0088] When using the aforementioned support, heterogeneous catalysts with a loading of 5% by weight or less, preferably from 0.0001% by weight to 5% by weight, can be prepared. Increasing the loading is advantageous, but when used in a production line, reproducibility, physical stability, cost, catalyst activity, and selectivity must also be considered. When the loading is less than the above range, it is difficult to ensure a sufficient level of heterogeneous catalyst activity, while loadings greater than the above range reduce catalyst stability and are difficult to obtain. Therefore, it is appropriate to use amounts within the above range.

[0089] Catalytic activity is affected by factors such as the composition and particle size of the metal used as the catalyst, the type of support, and the loading.

[0090] In this case, the reactor is not particularly limited in the present invention, and can be any reactor selected from known batch reactors, semi-batch reactors, continuous stirred tank reactors, plug flow reactors, fixed phase reactors and fluidized bed reactors, or can be a mixed reactor of two or more of these reactors connected together.

[0091] Furthermore, according to the present invention, the supported catalyst is supported on a support (support component or support), and the metal catalyst is supported and dispersed on the support, thereby increasing the surface area of ​​the catalyst, stabilizing the catalyst by preventing sintering, and reducing the price of the catalyst. The support itself is inactive, but it affects the catalytic activity due to the above-mentioned functions. Even when the catalyst composition is the same, the amount of metal catalyst loaded can result in significant differences in catalyst activity; therefore, the selection of the support should also be considered very important.

[0092] The following embodiments are merely examples illustrating implementations of the present invention and do not constitute any limitation on the present invention. Those skilled in the art will understand that modifications made without departing from the spirit and concept of the present invention fall within the protection scope of the present invention. Unless otherwise specified, the reagents and instruments used in the following embodiments are commercially available products.

[0093] Example 1

[0094]

[0095] 1. A fixed-bed reactor was loaded with 10 g of Ru / γ-Al₂O₃ catalyst (Ru loading 5 wt%). The temperature was raised to 200 °C under a nitrogen flow rate of 50 ml / min, and the system back pressure was increased to 4 MPa. High-purity hydrogen was then introduced at a flow rate of 200 ml / min. A mixture of terephthalic acid and 20 wt% sodium hydroxide aqueous solution (molar ratio of terephthalic acid to sodium hydroxide 1:2.2, stirred for 30 min until completely dissolved) was added at a flow rate of 0.1 h⁻¹. -1The product is pumped into the reactor at mass hourly space velocity (MHSV) for reaction. After condensation and gas-liquid separation, the product is transferred to a storage tank. Concentrated hydrochloric acid (30 wt%) is added to the product in the storage tank to adjust the pH of the system to 1-2. A large amount of white solid will precipitate in the system. After filtration, the product is dried under vacuum at 60°C for 6 hours to obtain 1,4-cyclohexanedicarboxylic acid. The molar yield of this step is 96%.

[0096]

[0097] 2. Add 300g of γ-Al₂O₃ (80-120 mesh) catalyst to a fluidized bed reactor, heat to 330℃ at a fluidizing gas rate of 2L, and maintain for 1h to activate the catalyst. After catalyst activation, reduce the temperature at a rate of 0.2h. -1 A mixture of 1,4-cyclohexanedicarboxylic acid and urea (molar ratio of 1,4-cyclohexanedicarboxylic acid to urea 1:1, melted by heating to 150°C before dropwise addition) was added dropwise to the reactor at a space velocity (based on 1,4-cyclohexanedicarboxylic acid). The product was separated into gas and liquid phases and stored in a storage tank. After the reaction was completed, the product in the storage tank was washed twice with ethanol at twice the mass of the product. The organic phase was then evaporated to dryness to obtain the product p-cyanocyclohexanecarboxylic acid. The molar yield of this step was 91%.

[0098]

[0099] 3. A fixed-bed reactor was loaded with 10 g of Ni / γ-Al₂O₃ catalyst (Ni loading 20 wt%). The temperature was raised to 150 °C under a nitrogen flow rate of 50 ml / min, and the system back pressure was increased to 3 MPa. High-purity hydrogen was then introduced at a flow rate of 200 ml / min. A methanol solution of p-cyanocyclohexanecarboxylic acid (20 wt%) was added at a flow rate of 0.1 h⁻¹. -1 The product is pumped into the reactor at mass hourly space velocity (MHSV) for reaction. After condensation and gas-liquid separation, the product is sent to a storage tank. The obtained product is distilled to recover methanol and obtain tranexamic acid. The molar yield of this step is 93%.

[0100] Example 2

[0101]

[0102] 1. Add 60g of terephthalic acid and 150g of 20wt% sodium hydroxide solution to a 500ml reactor. Stir until the solution is clear, then add 6g of Raney Ni catalyst. Seal the reactor, replace the air in the reactor with nitrogen, and then purge with hydrogen to 4MPa. Maintain this pressure for 30 minutes without leakage, then raise the temperature to 160℃ to start the reaction. During the reaction, continuously add hydrogen until the pressure no longer decreases, then stop the reaction. Cool down, depressurize, replace the hydrogen in the reactor with nitrogen, and then remove the product. Filter to remove the catalyst, adjust the pH to 1-2 with concentrated hydrochloric acid, filter again, and dry the solid under vacuum at 60℃ for 12 hours to obtain the product 1,4-cyclohexanedicarboxylic acid. The molar yield of this step is 95%.

[0103]

[0104] 2. Add 300g of SiO2 (80-120 mesh) catalyst to a fluidized bed reactor, heat to 320℃ at a fluidizing gas rate of 2L, and maintain for 1h to activate the catalyst. After catalyst activation, reduce the temperature at a rate of 0.2h. -1 A mixture of 1,4-cyclohexanedicarboxylic acid and urea (molar ratio of 1,4-cyclohexanedicarboxylic acid to urea 1:1.2, the mixture was heated to 150°C to melt before being added dropwise) was added dropwise to the reactor at a space velocity (based on 1,4-cyclohexanedicarboxylic acid). The product was separated into gas and liquid phases and stored in a storage tank. After the reaction was completed, the product in the storage tank was washed twice with ethanol at twice the mass of the product. The organic phase was then evaporated to dryness to obtain the product p-cyanocyclohexanecarboxylic acid. The molar yield of this step was 90%.

[0105]

[0106] 3. Add 70g of p-cyanocyclohexanecarboxylic acid, 200ml of methanol, and 7g of Raney Ni to a 500ml reactor. Seal the reactor, purge the air inside with nitrogen, then purge with hydrogen to 3MPa and maintain this pressure for 30 minutes without leakage. Heat to 120℃ to start the reaction. During the reaction, continuously add hydrogen until the pressure stops decreasing, then stop the reaction. Cool down, depressurize, purge the hydrogen inside the reactor with nitrogen, remove the product, filter to remove the catalyst, and distill the organic phase to remove methanol to obtain tranexamic acid. The molar yield of this step is 94%.

[0107] Example 3

[0108]

[0109] 1. A fixed-bed reactor was loaded with 10 g of Ni / γ-Al₂O₃ catalyst (Ni loading 20 wt%). The temperature was raised to 200 °C under a nitrogen flow rate of 50 ml / min, and the system back pressure was increased to 4 MPa. High-purity hydrogen was then introduced at a flow rate of 200 ml / min. A mixture of terephthalic acid and 20 wt% sodium hydroxide aqueous solution (molar ratio of terephthalic acid to sodium hydroxide 1:2.2, stirred for 30 min until completely dissolved) was added at a flow rate of 0.1 h⁻¹. -1 The product is pumped into the reactor at mass hourly space velocity (MHSV) for reaction. After condensation and gas-liquid separation, the product is transferred to a storage tank. Concentrated hydrochloric acid (30 wt%) is added to the product in the storage tank to adjust the pH of the system to 1-2. A large amount of white solid will precipitate in the system. After filtration, the product is dried under vacuum at 60°C for 6 hours to obtain 1,4-cyclohexanedicarboxylic acid. The molar yield of this step is 95%.

[0110]

[0111] 2. Add 300g of H-ZSM-5 (80-120 mesh) catalyst to the fluidized bed reactor, heat to 330℃ at a fluidizing gas rate of 2L, and maintain for 1h to activate the catalyst. After catalyst activation, reduce the temperature at a rate of 0.1h. -1 A mixture of 1,4-cyclohexanedicarboxylic acid and urea (molar ratio of 1,4-cyclohexanedicarboxylic acid to urea 1:1, mechanically mixed) was added to the reactor at a space velocity (based on 1,4-cyclohexanedicarboxylic acid). After gas-liquid separation, the product was stored in a storage tank. After the reaction was completed, the product in the storage tank was washed twice with ethanol at twice the mass, and the organic phase was evaporated to dryness to obtain the product p-cyanocyclohexanecarboxylic acid. The molar yield of this step was 93%.

[0112]

[0113] 3. A fixed-bed reactor was loaded with 10 g of Ru / γ-Al₂O₃ catalyst (Ni loading 20 wt%). The temperature was raised to 100 °C under a nitrogen flow rate of 50 ml / min, and the system back pressure was increased to 3 MPa. High-purity hydrogen was then introduced at a flow rate of 200 ml / min. A methanol solution of p-cyanocyclohexanecarboxylic acid (20 wt%) was added at a flow rate of 0.1 h⁻¹. -1 The product is pumped into the reactor at mass hourly space velocity (MHSV) for reaction. After condensation and gas-liquid separation, the product is sent to a storage tank. The obtained product is distilled to recover methanol and obtain tranexamic acid. The molar yield of this step is 95%.

[0114] Example 4

[0115]

[0116] 1. 10 g of Pd / SiO2 catalyst (Pd loading 5 wt%) was loaded into a fixed-bed reactor. The temperature was raised to 200 °C under a nitrogen flow rate of 50 ml / min, and the system back pressure was increased to 4 MPa. High-purity hydrogen was then introduced at a flow rate of 200 ml / min. A mixture of terephthalic acid and 20 wt% sodium hydroxide aqueous solution (molar ratio of terephthalic acid to sodium hydroxide 1:2.2, stirred for 30 min until completely dissolved) was added at a flow rate of 0.1 h. -1 The product is pumped into the reactor at mass hourly space velocity (MHSV) for reaction. After condensation and gas-liquid separation, the product is transferred to a storage tank. Concentrated hydrochloric acid (30 wt%) is added to the product in the storage tank to adjust the pH of the system to 1-2. A large amount of white solid will precipitate in the system. After filtration, the product is dried under vacuum at 60°C for 6 hours to obtain 1,4-cyclohexanedicarboxylic acid. The molar yield of this step is 94%.

[0117]

[0118] 2. Add 300g of Nb₂O₅ (80-120 mesh) catalyst to a fluidized bed reactor, heat to 330℃ at a fluidizing gas rate of 2L, and maintain for 1h to activate the catalyst. After catalyst activation, reduce the temperature at a rate of 0.1h. -1 A mixture of 1,4-cyclohexanedicarboxylic acid and urea (molar ratio of 1,4-cyclohexanedicarboxylic acid to urea 1:1, mechanically mixed) was added to the reactor at a space velocity (based on 1,4-cyclohexanedicarboxylic acid). After gas-liquid separation, the product was stored in a storage tank. After the reaction was completed, the product in the storage tank was washed twice with ethanol at twice the mass, and the organic phase was evaporated to dryness to obtain the product p-cyanocyclohexanecarboxylic acid. The molar yield of this step was 91%.

[0119]

[0120] 3. 10 g of Ni / HZSM5 catalyst (Ni loading 20 wt%) was loaded into a fixed-bed reactor. The temperature was raised to 100 °C under a nitrogen flow rate of 50 ml / min, and the system back pressure was increased to 3 MPa. High-purity hydrogen was then introduced at a flow rate of 200 ml / min. A methanol solution of p-cyanocyclohexanecarboxylic acid (20 wt%) was added at a flow rate of 0.1 h⁻¹. -1 The product is pumped into the reactor at mass hourly space velocity (MHSV) for reaction. After condensation and gas-liquid separation, the product is sent to a storage tank. The obtained product is distilled to recover methanol and obtain tranexamic acid. The molar yield of this step is 94%.

[0121] Example 5

[0122]

[0123] 1. 10 g of Pd / HZSM5 catalyst (Pd loading 5 wt%) was loaded into a fixed-bed reactor. The temperature was raised to 200 °C under a nitrogen flow rate of 50 ml / min, and the system back pressure was increased to 4 MPa. High-purity hydrogen was then introduced at a flow rate of 200 ml / min. A mixture of terephthalic acid and 20 wt% sodium hydroxide aqueous solution (molar ratio of terephthalic acid to sodium hydroxide was 1:2.2; the mixture was stirred for 30 min until completely dissolved) was added at a flow rate of 0.1 h. -1 The product is pumped into the reactor at mass hourly space velocity (MHSV) for reaction. After condensation and gas-liquid separation, the product is transferred to a storage tank. Concentrated hydrochloric acid (30 wt%) is added to the product in the storage tank to adjust the pH of the system to 1-2. A large amount of white solid will precipitate in the system. After filtration, the product is dried under vacuum at 60°C for 6 hours to obtain 1,4-cyclohexanedicarboxylic acid. The molar yield of this step is 96%.

[0124]

[0125] 2. Add 300g of SiO2-Al2O3 (80-120 mesh) catalyst to a fluidized bed reactor, heat to 330℃ at a fluidizing gas rate of 2L, and maintain for 1h to activate the catalyst. After catalyst activation, reduce the temperature at a rate of 0.1h. -1 A mixture of 1,4-cyclohexanedicarboxylic acid and urea (molar ratio of 1,4-cyclohexanedicarboxylic acid to urea 1:1, mechanically mixed) was added to the reactor at a space velocity (based on 1,4-cyclohexanedicarboxylic acid). The product was separated into gas and liquid phases and stored in a storage tank. After the reaction was completed, the product in the storage tank was washed twice with dichloromethane, and the organic phase was evaporated to dryness to obtain the product p-cyanocyclohexanecarboxylic acid. The molar yield of this step was 91%.

[0126]

[0127] 3. 10 g of Ni / HZSM5 catalyst (Ni loading 20 wt%) was loaded into a fixed-bed reactor. The temperature was raised to 100 °C under a nitrogen flow rate of 50 ml / min, and the system back pressure was increased to 3 MPa. High-purity hydrogen was then introduced at a flow rate of 200 ml / min. A methanol solution of p-cyanocyclohexanecarboxylic acid (20 wt%) was added at a flow rate of 0.1 h⁻¹. -1 The product is pumped into the reactor at mass hourly space velocity (MHSV) for reaction. After condensation and gas-liquid separation, the product is sent to a storage tank. The obtained product is distilled to recover methanol and obtain tranexamic acid. The molar yield of this step is 94%.

[0128] Example 6

[0129]

[0130] 1. 10 g of Ru / HZSM5 catalyst (Pd loading 5 wt%) was loaded into a fixed-bed reactor. The temperature was raised to 200 °C under a nitrogen flow rate of 50 ml / min, and the system back pressure was increased to 4 MPa. High-purity hydrogen was then introduced at a flow rate of 200 ml / min. A mixture of terephthalic acid and 20 wt% sodium hydroxide aqueous solution (molar ratio of terephthalic acid to sodium hydroxide was 1:2.2; the mixture was stirred for 30 min until completely dissolved) was added at a flow rate of 0.1 h. -1 The product is pumped into the reactor at mass hourly space velocity (MHSV) for reaction. After condensation and gas-liquid separation, the product is transferred to a storage tank. Concentrated hydrochloric acid (30 wt%) is added to the product in the storage tank to adjust the pH of the system to 1-2. A large amount of white solid will precipitate in the system. After filtration, the product is dried under vacuum at 60°C for 6 hours to obtain 1,4-cyclohexanedicarboxylic acid. The molar yield of this step is 96%.

[0131]

[0132] 2. Add 300g of SiO2 (80-120 mesh) catalyst to a fluidized bed reactor, heat to 330℃ at a fluidizing gas rate of 2L, and maintain for 1h to activate the catalyst. After catalyst activation, reduce the temperature by 0.1h. -1 1,4-cyclohexanedicarboxylic acid was added to the reactor at a space velocity (based on 1,4-cyclohexanedicarboxylic acid), and ammonia gas (65 ml / min, molar ratio of 1,4-cyclohexanedicarboxylic acid to ammonia 1:1) was introduced into the reactor. After gas-liquid separation, the product was stored in a storage tank. After the reaction was completed, the product in the storage tank was washed twice with dichloromethane, and the organic phase was evaporated to dryness to obtain the product p-cyanocyclohexanecarboxylic acid. The molar yield of this step was 91%.

[0133]

[0134] 3. A fixed-bed reactor was loaded with 10 g of Ni / Al₂O₃ catalyst (Ni loading 20 wt%). The temperature was raised to 100 °C under a nitrogen flow rate of 50 ml / min, and the system back pressure was increased to 3 MPa. High-purity hydrogen was then introduced at a flow rate of 200 ml / min. A methanol solution of p-cyanocyclohexanecarboxylic acid (20 wt%) was added at a flow rate of 0.1 h⁻¹. -1 The product is pumped into the reactor at mass hourly space velocity (MHSV) for reaction. After condensation and gas-liquid separation, the product is sent to a storage tank. The obtained product is distilled to recover methanol and obtain tranexamic acid. The molar yield of this step is 94%.

[0135] Example 7

[0136]

[0137] 1. A fixed-bed reactor was loaded with 10 g of Ni / HZSM5 catalyst (Ni loading 20 wt%). The temperature was raised to 200 °C under a nitrogen flow rate of 50 ml / min, and the system back pressure was increased to 4 MPa. High-purity hydrogen was then introduced at a flow rate of 200 ml / min. A mixture of dimethyl terephthalate and 1,4-dioxane (concentration 10 wt%) was added at a flow rate of 0.1 h⁻¹. -1 The product is pumped into the reactor at mass hourly space velocity (MHSV) for reaction. After condensation and gas-liquid separation, the product enters the storage tank. After distillation to remove the solvent, a pale yellow liquid product is obtained. The molar yield of this step is 93%.

[0138]

[0139] 2. Add 20g of SiO2 (20-40 mesh) catalyst to a fixed-bed reactor, heat to 350℃ at a nitrogen gas flow rate of 100ml / min, and maintain for 1h to activate the catalyst. After catalyst activation, reduce the temperature by 0.3h. -1 Dimethyl 1,4-cyclohexanedicarboxylate was added to the reactor at a space velocity (based on methyl 1,4-cyclohexanedicarboxylate) and ammonia gas was introduced (11 ml / min, molar ratio of dimethyl 1,4-cyclohexanedicarboxylate to ammonia 1:1). The product was then separated into gas and liquid phases and stored in a storage tank. After the reaction was completed, the product in the storage tank was distilled to obtain p-cyanocyclohexanecarboxylic acid, with a molar yield of 90% for this step.

[0140]

[0141] 3. A fixed-bed reactor was loaded with 10 g of Ni / Al₂O₃ catalyst (Ni loading 20 wt%). The temperature was raised to 100 °C under a nitrogen flow rate of 50 ml / min, and the system back pressure was increased to 3 MPa. High-purity hydrogen was then introduced at a flow rate of 200 ml / min. A methanol solution of p-cyanocyclohexanecarboxylic acid (20 wt%) was added at a flow rate of 0.1 h⁻¹. -1 The product is pumped into the reactor at mass hourly space velocity (MHSV) for reaction. After condensation and gas-liquid separation, the product is sent to a storage tank. The obtained product is distilled to recover methanol and obtain tranexamic acid. The molar yield of this step is 94%.

[0142] The above embodiments are merely illustrative of the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein, without departing from the spirit and substance defined by the claims of the present invention; and such modifications or substitutions are still within the scope defined by the claims of the present invention.

Claims

1. A method for synthesizing tranexamic acid represented by the following reaction formula 2, comprising the following steps: Reaction 2 (1) After mixing terephthalic acid with an alkaline solution, the mixture is passed into a reactor containing catalyst 1 for hydrogenation reaction. The resulting product is acidified to obtain 1,4-cyclohexanedicarboxylic acid. (2) 1,4-cyclohexanedicarboxylic acid is mixed with an ammonia source and added to a reactor containing catalyst 2 for ammoniation and dehydration reaction. The product is then transferred to a storage tank to obtain p-cyanocyclohexanecarboxylic acid. (3) After mixing p-cyanocyclohexanecarboxylic acid with a solvent, the mixture is passed into a reactor containing catalyst 3 for hydrogenation reaction. The product is then distilled to remove the solvent and obtain aminomethylcarboxylic acid. in, R is hydrogen; The catalyst 1 in step (1) is a Raney Ni, Raney Co catalyst or a supported metal catalyst. The active metal component M in the supported metal catalyst is selected from one or more of Pd, Ru, Rh, Pt, Ni, Co, and Cu. The catalyst support is selected from one or more of activated carbon, γ-Al2O3, SiO2, Nb2O5, and zeolite molecular sieves. The zeolite molecular sieves are selected from one or more of H-ZSM-5, H-ZSM-35, HY, and Hβ. The alkali in step (1) is selected from one or two of sodium hydroxide and potassium hydroxide, and the mass concentration of the alkali solution is 10%-50 wt%. The molar ratio of the base to terephthalic acid in step (1) is 2:1 to 6:1; The reaction temperature in step (1) is 120-250℃; The reaction pressure in step (1) is 2-8 MPa; The ammonia source mentioned in step (2) is selected from one or more of ammonia gas, ammonia water, urea, ammonium carbonate, and ammonium bicarbonate; The molar ratio of the ammonia source to 1,4-cyclohexanedicarboxylic acid in step (2) is 0.9:1-1.5:1; The catalyst 2 in step (2) is a solid acid selected from one or more of γ-Al2O3, SiO2, SiO2-Al2O3, ZrO2, CeO2, Nb2O5, and zeolite molecular sieves, wherein the zeolite molecular sieve is selected from one or more of H-ZSM-5, H-ZSM-35, HY, and Hβ; The reaction temperature in step (2) is 250-400℃; The reaction pressure in step (2) is 0.1-1.0 MPa; The mass hourly space velocity (HHSV) of the 1,4-cyclohexanedicarboxylic acid in step (2) is 0.05-5 h⁻¹. -1 ; The catalyst 3 in step (3) is a Raney Ni, Raney Co catalyst or a supported metal catalyst, wherein the metal active component M in the supported metal catalyst is selected from one or more of Pd, Ru, Pt, Ni, and Co, and the catalyst support is selected from one or more of activated carbon, γ-Al2O3, SiO2, and zeolite molecular sieves; the zeolite molecular sieves are selected from one or more of H-ZSM-5, H-ZSM-35, HY, and Hβ. The reaction solvent in step (3) is selected from one or more of methanol, ethanol, isopropanol, tetrahydrofuran, and 1,4-dioxane; The mass concentration of the raw material in step (3) is 5-40 wt%; The reaction temperature in step (3) is 60-200℃; The reaction pressure in step (3) is 2-8 MPa.

2. The synthesis method according to claim 1, characterized in that, The catalyst 1 in step (1) is a Raney Ni, Raney Co catalyst or a supported metal catalyst. The active metal component in the supported metal catalyst is selected from one or more of Pd, Ru, Rh, Ni and Co, and the catalyst support is selected from one or more of γ-Al2O3, SiO2, Nb2O5 and zeolite molecular sieve.

3. The synthesis method according to claim 1, characterized in that, The catalyst 1 in step (1) is a Raney Ni, Raney Co catalyst or a supported metal catalyst. The active metal component in the supported metal catalyst is selected from one or more of Pd, Ru, Ni and Co, and the catalyst support is selected from one or more of γ-Al2O3, SiO2 and zeolite molecular sieve.

4. The synthesis method according to claim 1, characterized in that, The mass concentration of the alkaline solution in step (1) is 10-30 wt%.

5. The synthesis method according to claim 1, characterized in that, The mass concentration of the alkaline solution in step (1) is 15-30 wt%.

6. The synthesis method according to claim 1, characterized in that, The molar ratio of the base to terephthalic acid in step (1) is 2:1 to 4:

1.

7. The synthesis method according to claim 1, characterized in that, The molar ratio of the base to terephthalic acid in step (1) is 2:1-3:

1.

8. The synthesis method according to claim 1, characterized in that, The reaction temperature in step (1) is 120-220℃.

9. The synthesis method according to claim 1, characterized in that, The reaction temperature in step (1) is 150-200℃.

10. The synthesis method according to claim 1, characterized in that, The reaction pressure in step (1) is 2-6 MPa.

11. The synthesis method according to claim 1, characterized in that, The reaction pressure in step (1) is 3-5 MPa.

12. The synthesis method according to claim 1, characterized in that, Alternatively, step (1) is carried out as follows: terephthalic acid is mixed and dissolved with an alkaline solution in a reaction vessel, and catalyst 1 is added. After the air in the vessel is replaced with hydrogen, a hydrogenation reaction is carried out. After the reaction is completed, catalyst 1 is removed by filtration, and the product is acidified to obtain 1,4-cyclohexanedicarboxylic acid.

13. The synthesis method according to claim 12, characterized in that, When a reaction vessel is used as a reactor in step (1), the mass ratio of catalyst 1 to terephthalic acid is 1:100-30:

100.

14. The synthesis method according to claim 12, characterized in that, When a reaction vessel is used as a reactor in step (1), the mass ratio of catalyst 1 to terephthalic acid is 3:100-20:

100.

15. The synthesis method according to claim 12, characterized in that, When a reaction vessel is used as a reactor in step (1), the mass ratio of catalyst 1 to terephthalic acid is 5:100-15:

100.

16. The synthesis method according to claim 1, characterized in that, When a fixed bed is used as the reactor in step (1), the mass hourly space velocity (MSV) of the terephthalic acid is 0.1-5 h⁻¹. -1 .

17. The synthesis method according to claim 1, characterized in that, When a fixed bed is used as the reactor in step (1), the mass hourly space velocity (MSV) of the terephthalic acid is 0.3-3 h⁻¹. -1 .

18. The synthesis method according to claim 1, characterized in that, When a fixed bed reactor is used in step (1), the mass hourly space velocity (MSV) of the terephthalic acid is 0.5-1.5 h⁻¹. -1 .

19. The synthesis method according to claim 1, characterized in that, The ammonia source mentioned in step (2) is ammonia or urea.

20. The synthesis method according to claim 1, characterized in that, The reactor mentioned in step (2) is selected from fixed bed reactors and fluidized bed reactors.

21. The synthesis method according to claim 1, characterized in that, The reaction temperature in step (2) is 280-350℃.

22. The synthesis method according to claim 1, characterized in that, The reaction temperature in step (2) is 290-350℃.

23. The synthesis method according to claim 1, characterized in that, The reaction pressure in step (2) is 0.1-0.5 MPa.

24. The synthesis method according to claim 1, characterized in that, The reaction pressure in step (2) is 0.1-0.3 MPa.

25. The synthesis method according to claim 1, characterized in that, The mass hourly space velocity (HSV) of the 1,4-cyclohexanedicarboxylic acid in step (2) is 0.1-3 h⁻¹. -1 .

26. The synthesis method according to claim 1, characterized in that, The mass hourly space velocity (HSV) of the 1,4-cyclohexanedicarboxylic acid in step (2) is 0.1-1.0 h⁻¹. -1 .

27. The synthesis method according to claim 1, characterized in that, The mass concentration of the raw material in step (3) is 10-30 wt%.

28. The synthesis method according to claim 1, characterized in that, The mass concentration of the raw material in step (3) is 20-30 wt%.

29. The synthesis method according to claim 1, characterized in that, The reaction temperature in step (3) is 80-180℃.

30. The synthesis method according to claim 1, characterized in that, The reaction temperature in step (3) is 100-180℃.

31. The synthesis method according to claim 1, characterized in that, The reaction pressure in step (3) is 2-6 MPa.

32. The synthesis method according to claim 1, characterized in that, The reaction pressure in step (3) is 3-5 MPa.

33. The synthesis method according to claim 1, characterized in that, Alternatively, step (3) can be carried out as follows: p-cyanocyclohexane carboxylic acid, solvent and catalyst 3 are mixed and added to the reaction vessel. After replacing the air in the vessel with hydrogen, hydrogen is introduced and the temperature is raised to carry out the hydrogenation reaction. After the reaction is completed, catalyst 3 is removed by filtration and solvent is removed by distillation to obtain tranexamic acid.

34. The synthesis method according to claim 33, characterized in that, When a reaction vessel is used as a reactor in step (3), the mass ratio of catalyst 3 to p-cyanocyclohexanecarboxylic acid is 1:100-30:

100.

35. The synthesis method according to claim 33, characterized in that, When a reaction vessel is used as a reactor in step (3), the mass ratio of catalyst 3 to p-cyanocyclohexanecarboxylic acid is 3:100-20:

100.

36. The synthesis method according to claim 33, characterized in that, When a reaction vessel is used as a reactor in step (3), the mass ratio of catalyst 3 to p-cyanocyclohexanecarboxylic acid is 3:100-15:

100.

37. The synthesis method according to claim 1, characterized in that, When a fixed bed is used as the reactor in step (3), the mass hourly space velocity (MSV) of the p-cyanocyclohexane carboxylic acid is 0.05-3 h⁻¹. -1 .

38. The synthesis method according to claim 1, characterized in that, When a fixed bed is used as the reactor in step (3), the mass hourly space velocity (MSV) of the p-cyanocyclohexanecarboxylic acid is 0.1-3 h⁻¹. -1 .

39. The synthesis method according to claim 1, characterized in that, When a fixed bed is used as the reactor in step (3), the mass hourly space velocity (MSV) of the p-cyanocyclohexanecarboxylic acid is 0.1-1.0 h⁻¹. -1 .

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