CN116947664A - Synthesis method of tranexamic acid - Google Patents

Synthesis method of tranexamic acid Download PDF

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CN116947664A
CN116947664A CN202310948143.4A CN202310948143A CN116947664A CN 116947664 A CN116947664 A CN 116947664A CN 202310948143 A CN202310948143 A CN 202310948143A CN 116947664 A CN116947664 A CN 116947664A
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catalyst
reaction
acid
reactor
product
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刘晓然
张少春
王喜成
牟新东
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Shanghai Suntian Technology Co ltd
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Shanghai Suntian Technology Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/04—Formation of amino groups in compounds containing carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/22—Preparation of carboxylic acid nitriles by reaction of ammonia with carboxylic acids with replacement of carboxyl groups by cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/303—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by hydrogenation of unsaturated carbon-to-carbon bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

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  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention relates to a method for synthesizing tranexamic acid. The method takes terephthalic acid or terephthalic acid ester as raw material, and synthesizes tranexamic acid through the steps of hydrogenation, ammoniation dehydration, hydrogenation and the like. The method for synthesizing the tranexamic acid has the advantages of low raw material cost, simple process, green route, less pollution in the reaction process, continuous operation and high efficiency.

Description

Synthesis method of tranexamic acid
Technical Field
The invention relates to the field of pharmaceutical chemistry synthesis, in particular to a synthesis method of tranexamic acid.
Background
Tranexamic acid is an antiplasmin drug and is mainly used for hemostasis in clinic. In recent years, the skin beauty field has been studied deeply, and it is proved that tranexamic acid has the functions of reducing melanin generation, anti-inflammatory, anti-allergic reaction, anti-natural skin aging and photo-aging, and can be used for treating various skin diseases such as chloasma, post-inflammatory pigmentation, urticaria, angioedema and the like, and the current demand of tranexamic acid at home and abroad is more than thousand tons.
The existing synthesis method of tranexamic acid is shown in the following reaction formula 1, wherein p-cyanoborobenzyl is mainly used as a raw material, tranexamic acid is prepared by hydrolysis and ammoniation, and tranexamic acid is prepared by saturated benzene rings through catalytic hydrogenation. The price of p-cyanobenzyl chloride is high (> 7 ten thousand yuan per ton), resulting in high synthesis costs. In the process of preparing the tranexamic acid by the hydrogenation of the amino toluene acid, a large amount of sulfuric acid is generally required to be added to improve the concentration of reactants, a platinum black catalyst is generally used as a catalyst, the price is high, repeated use is required to reduce the cost, and the catalytic effect is not ideal. The use of large amounts of sulfuric acid in the hydrogenation step requires the addition of large amounts of barium hydroxide to remove residual sulfuric acid, resulting in a large amount of waste salts generated in the metathesis step. The process route has higher requirements on equipment, and a large amount of solid waste can be generated in the production process, so that the production cost is increased.
In summary, the existing synthesis process of tranexamic acid has the problems of high raw material price, high catalyst cost in the hydrogenation process, more wastewater and solid waste in the production process, high comprehensive cost and the like. In addition, each step in the reaction formula 1 is a batch reaction, and the production efficiency is generally low. There is therefore still a need to develop new legal methods.
Disclosure of Invention
In order to solve the problems in the prior art, the invention aims to provide a method for synthesizing tranexamic acid. The method takes terephthalic acid or terephthalic acid ester as raw material, and synthesizes tranexamic acid through the steps of hydrogenation, ammoniation dehydration, hydrogenation, transposition and the like under the action of a catalyst. The method for synthesizing the tranexamic acid has the advantages of simple process, easy separation, continuous operation in multiple steps, high yield, reduction of three-waste discharge and contribution to industrial production.
In order to achieve the above object of the present invention, according to one aspect of the present invention, there is provided a method for synthesizing tranexamic acid represented by the following reaction formula 2, comprising the steps of:
reaction 2
(1) Mixing terephthalic acid or terephthalic acid ester with an alkali solution, introducing the mixture into a reactor filled with a catalyst 1 for hydrogenation reaction, and acidifying the obtained product to obtain 1, 4-cyclohexanedicarboxylic acid or 1, 4-cyclohexanedicarboxylic acid ester;
(2) Mixing 1, 4-cyclohexanedicarboxylic acid or 1, 4-cyclohexanedicarboxylic acid ester with an ammonia source, adding the mixture into a reactor filled with a catalyst 2 for ammonification and dehydration reaction, and allowing a product to enter a storage tank to obtain p-cyano cyclohexanedicarboxylic acid;
(3) Mixing cyanocyclohexanecarboxylic acid with a solvent, introducing the mixture into a reactor filled with a catalyst 3 for hydrogenation reaction, and distilling the obtained product to remove the solvent to obtain tranexamic acid;
wherein R is H, C1-C6 alkyl, more preferably C1-C3 alkyl, most preferably methyl, ethyl, n-propyl or isopropyl.
In some embodiments, preferably, the catalyst 1 in step (1) is Raney Ni, raney Co catalyst or supported metal catalyst, the metal active component M in the supported metal catalyst is selected from one or more of Pd, ru, rh, pt, ni, co, cu, and the catalyst carrier is selected from active carbon and gamma-Al 2 O 3 、SiO 2 、Nb 2 O 5 One or more of zeolite molecular sieves;
preferably, the catalyst 1 of step (1) is Raney Ni, raney Co catalyst or supported metal catalyst,the metal active component in the supported metal catalyst is selected from one or more of Pd, ru, rh, ni, co, and the catalyst carrier is selected from gamma-Al 2 O 3 、SiO 2 、Nb 2 O 5 One or more of zeolite molecular sieves;
more preferably, the catalyst 1 in the step (1) is Raney Ni, raney Co or a supported metal catalyst, the metal active component in the supported metal catalyst is selected from one or more of Pd, ru, ni, co, and the catalyst carrier is selected from gamma-Al 2 O 3 、SiO 2 One or more of zeolite molecular sieves.
The zeolite molecular sieve is selected from one or more of H-ZSM-5, H-ZSM-35, HY and H beta.
In some embodiments, the base of step (1) is selected from one or both of sodium hydroxide, potassium hydroxide.
In some embodiments, the alkaline solution of step (1) has a mass concentration of 10% to 50% by weight, preferably 10% to 30% by weight, more preferably 15% to 30% by weight.
In some embodiments, the molar ratio of the base to terephthalic acid or terephthalate of step (1) is from 2:1 to 6:1, preferably from 2:1 to 4:1, more preferably from 2:1 to 3:1.
In some embodiments, the reaction temperature of step (1) is 120-250 ℃, preferably 120-220 ℃, more preferably 150-200 ℃.
In some embodiments, the reaction pressure of step (1) is 2-8MPa, preferably 2-6MPa, more preferably 3-5MPa.
Alternatively, step (1) is performed as follows: and (3) mixing terephthalic acid or terephthalic acid ester with an alkali solution in a reaction kettle, dissolving, adding a catalyst 1, replacing air in the kettle with hydrogen, performing hydrogenation reaction, filtering to remove the catalyst 1 after the reaction is finished, and acidifying the product to obtain 1, 4-cyclohexanedicarboxylic acid or 1, 4-cyclohexanedicarboxylic acid ester.
In some embodiments, when step (1) uses a reaction vessel as a reactor, the mass ratio of catalyst 1 to terephthalic acid or terephthalate is from 1:100 to 30:100, preferably from 3:100 to 20:100, more preferably from 5:100 to 15:100.
In some embodiments, when step (1) uses a fixed bed as the reactor, the terephthalic acid or terephthalate has a mass space velocity of 0.1 to 5 hours -1 Preferably 0.3-3h -1 More preferably 0.5 to 1.5h -1 。
Preferably, the reactor in step (2) comprises a fixed bed reactor and a fluidized bed reactor.
Preferably, the ammonia source in step (2) is selected from one or more of ammonia, ammonia water, urea, ammonium carbonate, ammonium bicarbonate, preferably ammonia or urea.
In some embodiments, the molar ratio of the ammonia source of step (2) to 1, 4-cyclohexanedicarboxylic acid or 1, 4-cyclohexanedicarboxylate is from 0.9:1 to 1.5:1.
In some embodiments, the catalyst 2 of step (2) is a solid acid selected from gamma-Al 2 O 3 、SiO 2 、SiO 2 -Al 2 O 3 、ZrO 2 、CeO 2 、Nb 2 O 5 One or more of zeolite molecular sieves selected from one or more of H-ZSM-5, H-ZSM-35, HY and H beta.
In some embodiments, the reaction temperature of step (2) is 250-400 ℃, preferably 280-350 ℃, more preferably 290-350 ℃.
In some embodiments, the reaction pressure of step (2) is from 0.1 to 1.0MPa, preferably from 0.1 to 0.5MPa, more preferably from 0.1 to 0.3MPa. In some embodiments, the 1, 4-cyclohexanedicarboxylic acid or 1, 4-cyclohexanedicarboxylate of step (2) has a mass space velocity of from 0.05 to 5 hours -1 Preferably 0.1-3h -1 More preferably 0.1 to 1.0h -1 。
Preferably, the catalyst 3 in the step (3) is Raney Ni, raney Co 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, co, and the catalyst carrier is selected from active carbon and gamma-Al 2 O 3 、SiO 2 One or more of zeolite molecular sievesSeed;
the zeolite molecular sieve is selected from one or more of H-ZSM-5, H-ZSM-35, HY and H beta.
In some embodiments, the reaction solvent of step (3) is selected from one or more of methanol, ethanol, isopropanol, tetrahydrofuran, 1, 4-dioxane.
In some embodiments, the feedstock of step (3) has a mass concentration of 5 to 40wt%, preferably 10 to 30wt%, more preferably 20 to 30wt%.
In some embodiments, the reaction temperature of step (3) is 60 to 200 ℃, preferably 80 to 180 ℃, more preferably 100 to 180 ℃.
In some embodiments, the reaction pressure of step (3) is 2-8MPa, preferably 2-6MPa, more preferably 3-5MPa.
Alternatively, step (3) is performed as follows: mixing the cyanocyclohexanecarboxylic acid, the solvent and the catalyst 3, adding the mixture into a reaction kettle, replacing the air in the kettle with hydrogen, introducing hydrogen, heating for hydrogenation reaction, filtering to remove the catalyst 3 after the reaction is finished, and distilling to remove the solvent to obtain the tranexamic acid.
In some embodiments, when step (3) uses a reaction vessel as a reactor, the mass ratio of catalyst 3 to p-cyanocyclohexanecarboxylic acid is from 1:100 to 30:100, preferably from 3:100 to 20:100, more preferably from 3:100 to 15:100.
In some embodiments, when step (3) uses a fixed bed as the reactor, the mass space velocity of the para-cyanocyclohexanecarboxylic acid is from 0.05 to 3 hours -1 Preferably 0.1-3h -1 More preferably 0.1 to 1.0h -1 。
The beneficial effects are that:
the method for synthesizing the tranexamic acid has the advantages of low raw material cost, green reaction route, continuous production in multiple steps, high efficiency and simple process operation. Compared with the traditional method, the method is easy to realize industrial production.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following description will briefly explain the drawings needed in the embodiments or the prior art, and it is obvious that the drawings in the following description are some embodiments of the present invention and that other drawings can be obtained according to these drawings without inventive effort to a person skilled in the art.
FIG. 1 is a chromatographic test result of 1, 4-cyclohexanedicarboxylic acid, which is the product obtained in step 1 of example 1;
FIG. 2 is a graph showing the results of chromatographic detection of cyanocyclohexanecarboxylic acid from the product obtained in step 2 of example 1;
FIG. 3 is a mass spectrum of the product obtained in step 2 of example 1 versus cyanocyclohexanecarboxylic acid;
FIG. 4 shows the results of chromatographic detection of the product tranexamic acid obtained in step 3 of example 1;
Detailed Description
Hereinafter, the present invention will be described in detail. Before the description, it is to be understood that the terms used in this specification and the appended claims should not be construed as limited to general and dictionary meanings, but interpreted based on the meanings and concepts corresponding to technical aspects of the present invention on the basis of the principle that the inventor is allowed to define terms appropriately for the best explanation. Accordingly, the description set forth herein is merely a preferred example for the purpose of illustration and is not intended to limit the scope of the invention, so that it should be understood that other equivalents or modifications may be made thereto without departing from the spirit and scope of the invention.
Step (1) of the process for synthesizing tranexamic acid according to the present invention may 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 using a continuous reactor, for example a fixed bed reactor.
The alkali in the 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%, preferably 10-30wt%, and more preferably 15-30wt%. Although higher alkali solution concentration is helpful for hydrogenation reaction, too high alkali solution concentration can cause material viscosity to increase, easily cause problems of reaction equipment blockage, material fluidity reduction and the like, and if the alkali solution concentration is too low, the wastewater amount can be increased. When the mass concentration of the alkali solution is controlled within the above range, the reaction economy can be optimally achieved.
The molar ratio of base to terephthalic acid or terephthalate of step (1) is from 2:1 to 6:1, preferably from 2:1 to 4:1, more preferably from 2:1 to 3:1. When the molar ratio is too high, the amount of waste water increases, and when the molar ratio is too low, the solubility in the raw material becomes poor.
The reaction temperature of step (1) is 120-250 ℃, preferably 120-220 ℃, more preferably 150-200 ℃. Too low a reaction temperature may result in a slow reaction rate, an extended time, and an excessively high reaction rate, but too high a reaction temperature may have higher requirements for heating medium, equipment safety, energy consumption, and the like.
The reaction pressure in step (1) is 2 to 8MPa, preferably 2 to 6MPa, more preferably 3 to 5MPa. Too low a reaction pressure may result in prolonged reaction time or insufficient reaction, and too high a reaction pressure may require high equipment and may result in high cost.
Since step (1) may also be performed in a batch reactor, alternatively step (1) may be performed as follows: and (3) mixing terephthalic acid or terephthalic acid ester with an alkali solution in a reaction kettle, dissolving, adding a catalyst 1, replacing air in the kettle with hydrogen, performing hydrogenation reaction, filtering to remove the catalyst 1 after the reaction is finished, and acidifying the product to obtain 1, 4-cyclohexanedicarboxylic acid or 1, 4-cyclohexanedicarboxylic acid ester.
When the reaction kettle is used as the reactor in the step (1), the mass ratio of the catalyst 1 to the terephthalic acid or the terephthalic acid ester is 1:100-30:100, preferably 3:100-20:100, and more preferably 5:100-15:100. Too low a ratio may result in prolonged reaction time or insufficient reaction, and too high a ratio may result in increased catalyst usage and increased costs.
In the method for synthesizing tranexamic acid according to the present invention, when a fixed bed is used as the reactor in step (1), the mass space velocity of terephthalic acid or terephthalate is 0.1 to 5 hours -1 Preferably 0.3-3h -1 More preferably 0.5 to 1.5h -1 . Where the space velocity is too high, the conversion is reduced, and if the space velocity is too low, the processing capacity of the reactor is wasted. Wherein the mass airspeed calculation formula is as follows:
wherein, the mass flow unit of terephthalic acid or terephthalic ester is g/min, and the unit of catalyst mass is g.
In addition, the product obtained in the step (1) enters a storage tank after condensation and gas-liquid separation, and the product in the storage tank is regulated to pH 1-2 by hydrochloric acid with the mass percent concentration of 20% to obtain 1, 4-cyclohexanedicarboxylic acid or 1, 4-cyclohexanedicarboxylic acid ester.
In the step (2) of the method for synthesizing the tranexamic acid, the 1, 4-cyclohexanedicarboxylic acid or the 1, 4-cyclohexanedicarboxylic acid ester obtained in the step (1) is mixed with an ammonia source and then added into a reactor filled with a catalyst 2 for ammonification and dehydration reaction, and the product enters a storage tank to obtain the p-cyano-cyclohexanedicarboxylic acid.
Wherein the reactor comprises a fixed bed reactor and a fluidized bed reactor.
Wherein the ammonia source is selected from one or more of ammonia gas, ammonia water, urea, ammonium carbonate and ammonium bicarbonate. However, ammonia or urea is preferable in view of economy and ease of operation.
The molar ratio of the ammonia source of step (2) to 1, 4-cyclohexanedicarboxylic acid or 1, 4-cyclohexanedicarboxylate is from 0.9:1 to 1.5:1. Too low a ratio (i.e., insufficient ammonia source) can result in reduced reactant conversion; an excessively high proportion (i.e., an excessive ammonia source) causes an increase in side reactions, and is high in raw material consumption and high in cost.
The reaction temperature of step (2) is 250-400 ℃, preferably 280-350 ℃, more preferably 290-350 ℃. Too low a reaction temperature can lead to slow reactions and waste of the processing capacity of the reactor; the too high temperature has high requirements on equipment, byproducts are generated, and the yield is reduced.
The reaction pressure in step (2) is 0.1 to 1.0MPa, preferably 0.1 to 0.5MPa, more preferably 0.1 to 0.3MPa. Too low a reaction pressure may result in a slow reaction time; the requirement on equipment is high due to the excessively high reaction pressure, and the cost becomes high.
The mass space velocity of the 1, 4-cyclohexanedicarboxylic acid or 1, 4-cyclohexanedicarboxylic acid ester in step (2) of the process for the synthesis of tranexamic acid according to the invention is from 0.05 to 5 hours -1 Preferably 0.1-3h -1 More preferably 0.1 to 1.0h -1 . The airspeed is too high, and the conversion rate is reduced; the space velocity is too low, which results in waste of the processing capacity of the reactor. Wherein the mass airspeed calculation formula is as follows:
wherein the mass flow rate unit of the 1, 4-cyclohexanedicarboxylic acid or the 1, 4-cyclohexanedicarboxylic acid ester is g/min, and the mass unit of the catalyst is g.
In the step (3) of the method for synthesizing tranexamic acid according to the present invention, the p-cyanocyclohexanecarboxylic acid obtained in the step (2) is mixed with a solvent, and then introduced into a reactor containing a catalyst 3 for hydrogenation reaction, and the solvent is distilled off from the resultant product to obtain tranexamic acid.
The reaction solvent in the step (3) is one or more selected from methanol, ethanol, isopropanol, tetrahydrofuran and 1, 4-dioxane. However, methanol is preferable in view of economy of the reaction.
The mass concentration of the raw material in the step (3) is controlled to be 5 to 40wt%, preferably 10 to 30wt%, more preferably 20 to 30wt%. Too low a concentration, increased solvent usage, increased cost, and too high a concentration may result in increased byproducts.
The reaction temperature of step (3) is 60 to 200 ℃, preferably 80 to 180 ℃, more preferably 100 to 180 ℃. The temperature is too low, the reaction speed is obviously slowed down, the temperature is too high, the requirement on equipment is high, and the reaction cost is increased.
The reaction pressure in step (3) is 2 to 8MPa, preferably 2 to 6MPa, more preferably 3 to 5MPa. Too low reaction pressure can lead to slow reaction time, too high reaction pressure has high requirements on equipment and high cost.
Step (3) may also be carried out in a batch reactor, for example a reaction vessel. Alternatively, step (3) is performed as follows: mixing the cyanocyclohexanecarboxylic acid, the solvent and the catalyst 3, adding the mixture into a reaction kettle, replacing the air in the kettle with hydrogen, introducing hydrogen, heating for hydrogenation reaction, filtering to remove the catalyst 3 after the reaction is finished, and distilling to remove the solvent to obtain the tranexamic acid.
When the reaction kettle is used as the reactor in the step (3), the mass ratio of the catalyst 3 to the p-cyanocyclohexanecarboxylic acid is 1:100-30:100, preferably 3:100-20:100, and more preferably 3:100-15:100. Too low a ratio, slow reaction, too high a ratio, increased catalyst amount, and increased cost.
In the case of using a fixed bed as a reactor in the step (3) of the method for synthesizing tranexamic acid according to the present invention, the mass space velocity of the p-cyanocyclohexanecarboxylic acid is 0.05 to 3 hours -1 Preferably 0.1-3h -1 More preferably 0.1 to 1.0h -1 . The airspeed is too high, and the conversion rate is reduced; the space velocity is too low, which results in waste of the processing capacity of the reactor. Wherein the mass airspeed calculation formula is as follows:
wherein, the mass flow unit of the p-cyanocyclohexanecarboxylic acid is g/min, and the mass unit of the catalyst is g.
Unless otherwise indicated, all materials, reagents, methods and the like used in the examples are those conventionally used in the art.
In the following examples, deionized water, ni/gamma-Al 2 O 3 ，Ru/γ-Al 2 O 3 ，Ni/SiO 2 For homemade terephthalic acid, sodium hydroxide, potassium hydroxide, methanol, ethanol, isopropanol were purchased from national pharmaceutical community chemical reagent company; gamma-Al 2 O 3 And SiO 2 Purchased from Qingdao sea wave silica gel desiccant Co., ltd; the zeolite molecular sieve is commercially available from, for example, H-ZS manufactured by Tianjin southbound catalyst Co., ltdM-5, H-ZSM-35, HY and H beta; the H-ZSM-5 series molecular sieve is purchased from Tianjin southbound catalyst Co., ltd; raney Ni catalyst was purchased from Shanghai Kaiki New Material technologies Co., ltd; raney Co catalyst was purchased from Jiangsu Raney Metal technologies Co; high purity nitrogen, high purity ammonia, and high purity hydrogen were purchased from Qingdao de Haiwei technology Co.
In the method for synthesizing the tranexamic acid, terephthalic acid/terephthalate is taken as a raw material, and the tranexamic acid is synthesized through the steps of hydrogenation, ammonification and dehydration, hydrogenation, transposition and the like under the action of a catalyst. The product obtained in each step was filtered through a 0.22 μm filter and analyzed by liquid chromatography. Liquid chromatography detection conditions: instrument: shimadzu LC-20A, chromatographic column: irinotecan aq 18, mobile phase: water/acetonitrile=4:1, isocratic elution, column flow 0.6ml/min, detector wavelength: 210nm, column temperature 30 ℃. The correlation calculation formula is as follows:
further, in the heterogeneous catalyst according to the present disclosure, a carrier (carrier) on which the bimetallic alloy catalyst is deposited functions to support and disperse the bimetallic alloy catalyst, thereby increasing its surface area, stabilizing the catalyst by preventing a sintering phenomenon, and reducing the price of the bimetallic alloy catalyst. The carrier itself does not have activity, but since it has the above function to affect the activity of the catalyst, even if the same composition is used, the difference in catalyst activity becomes large depending on the degree of metal catalyst loading, and therefore, the selection of the carrier needs to be regarded as very important.
When the carrier is used, a heterogeneous catalyst having a loading of 5wt% or less, preferably 0.0001 wt% to 5wt% may be prepared. The increase in the loading is advantageous, but reproducibility, physical stability, cost, catalyst activity, selectivity, etc. are also required to be considered when used in a production line. When the loading is less than the above range, it is difficult to ensure a sufficient level of heterogeneous catalyst activity, while a loading greater than the above range reduces catalyst stability and is difficult to obtain, and therefore, the amount within the above range is suitably used.
The catalytic activity is affected by factors such as the composition of the metal used as the catalyst, the particle size, the kind of support, and the loading.
In this case, the reactor is not particularly limited in the present invention, and may be any one reactor selected from known batch reactors, semi-batch reactors, continuous stirred tank reactors, plug flow reactors, stationary phase reactors and fluidized bed reactors, or may be a connected mixed reactor of two or more of these reactors.
In addition, the supported catalyst according to the present invention is supported on a carrier (carrier component or carrier), and the carrier on which the metal catalyst is supported supports and disperses the metal catalyst, thereby serving to increase the surface area of the catalyst, stabilize the catalyst by preventing the sintering phenomenon, and reduce the price of the catalyst. The carrier itself is inactive but affects the catalytic activity due to the above-described function, and exhibits a large difference in catalyst activity by how much metal catalyst is supported even when the composition of the catalysts is the same, so the selection of the carrier should be regarded as very important.
The following examples are merely illustrative of embodiments of the present invention and are not intended to limit the invention in any way, and those skilled in the art will appreciate that modifications may be made without departing from the spirit and scope of the invention. Unless otherwise specified, reagents and equipment used in the following examples are commercially available products.
Example 1
1. 10g Ru/gamma-Al were packed in a fixed bed reactor 2 O 3 The catalyst (Ru loading is 5 wt%) is heated to 200 ℃ under the nitrogen flow rate of 50ml/min, the system back pressure is 4MPa, the high purity hydrogen is switched to, the hydrogen flow rate is 200ml/min, the mixture of terephthalic acid and 20wt% sodium hydroxide aqueous solution (the mole ratio of terephthalic acid to sodium hydroxide is 1:2.2, and the mixture is stirred for 30min to be completely dissolved) is stirred for 0.1h -1 The product is condensed and gas-liquid separated, then enters a storage tank, concentrated hydrochloric acid (the mass percentage concentration is 30 wt%) is added into the product obtained in the storage tank to regulate the pH of the system to be 1-2, a large amount of white solid is precipitated in the system, the product is filtered and dried in vacuum at 60 ℃ for 6 hours, and then the product 1, 4-cyclohexanedicarboxylic acid is obtained, and the molar yield of the step is 96%.
2. 300g of gamma-Al are introduced into a fluidized bed reactor 2 O 3 (80-120 mesh) catalyst, heating to 330 ℃ under 2L fluidization gas speed, maintaining for 1h to activate the catalyst, and after the catalyst activation is finished, heating for 0.2h -1 Dropwise adding a mixture of 1, 4-cyclohexanedicarboxylic acid and urea (the molar ratio of 1, 4-cyclohexanedicarboxylic acid to urea is 1:1) into the reactor (calculated by 1, 4-cyclohexanedicarboxylic acid), mixing the two, heating to 150 ℃ for melting, then dropwise adding, and separating the product from gas and liquid, and then entering a storage tank for storage. After the reaction is finished, adding ethanol with the mass being 2 times to the product in the storage tank for washing, and evaporating the organic phase to dryness to obtain the product p-cyano cyclohexane carboxylic acid, wherein the molar yield of the step is 91%.
3. 10g of Ni/gamma-Al was packed in a fixed bed reactor 2 O 3 The catalyst (Ni loading is 20wt%) is heated to 150 ℃ under the nitrogen flow rate of 50ml/min, the system back pressure is 3MPa, the catalyst is switched into high-purity hydrogen, the hydrogen flow rate is 200ml/min, and the methanol solution (mass concentration of 20wt%) of p-cyanocyclohexanecarboxylic acid is added for 0.1h -1 The product is condensed and gas-liquid separated and then enters a storage tank, and the obtained product is distilled to recover methanol to obtain the tranexamic acid, wherein the molar yield of the step is 93%.
Example 2
1. 60g of terephthalic acid and 150g of sodium hydroxide solution with the concentration of 20wt% are added into a 500ml reaction kettle, after the solution is stirred until clear, 6g of Raney Ni catalyst is added, the reaction kettle is closed, the air in the kettle is replaced by nitrogen, hydrogen is filled to 4MPa, the reaction is started after the reaction kettle is kept for 30min and is heated to 160 ℃, the reaction is stopped after the hydrogen is continuously replenished in the reaction process until the pressure is not continuously reduced, the reaction is stopped after the temperature is reduced and the pressure is relieved, the product is taken out after the hydrogen in the kettle is replaced by nitrogen, the catalyst is removed by filtration, the pH value is adjusted to 1-2 by concentrated hydrochloric acid, the filtration is carried out again, the solid is dried in vacuum at 60 ℃ for 12h, and the molar yield of the step is 95%.
2. 300g of SiO was charged into a fluidized-bed reactor 2 (80-120 mesh) catalyst, heating to 320 deg.C under 2L fluidization gas speed, holding for 1 hr to activate catalyst, and after catalyst activation is completed, heating for 0.2 hr -1 Dropwise adding a mixture of 1, 4-cyclohexanedicarboxylic acid and urea (the molar ratio of 1, 4-cyclohexanedicarboxylic acid to urea is 1:1.2) into the reactor (calculated by 1, 4-cyclohexanedicarboxylic acid), mixing the two, heating to 150 ℃ for melting, then dropwise adding, and separating the product from the gas and the liquid, and then entering a storage tank for storage. After the reaction is finished, the product in the storage tank is fedAfter washing by adding ethanol with the mass of 2 times in two times, the organic phase is evaporated to dryness to obtain the p-cyanocyclohexanecarboxylic acid product, and the molar yield of the step is 90%.
3. 70g of p-cyanocyclohexanecarboxylic acid, 200ml of methanol, 7g of Raney Ni and the like are added into a 500ml reaction kettle, the reaction kettle is closed, the air in the kettle is replaced by nitrogen, then hydrogen is filled to 3MPa, the reaction kettle is kept for 30min and heated to 120 ℃ to start the reaction, the reaction is stopped after the hydrogen is continuously supplemented until the pressure is not continuously reduced, the reaction is stopped after the temperature is reduced and the pressure is relieved, the product is taken out after the hydrogen in the kettle is replaced by nitrogen, the catalyst is removed by filtration, the methanol is removed by distillation of an organic phase, and the tranexamic acid product is obtained, wherein the molar yield of the step is 94%.
Example 3
1. 10g of Ni/gamma-Al was packed in a fixed bed reactor 2 O 3 The catalyst (Ni loading is 20 wt%) is heated to 200 ℃ under the nitrogen flow rate of 50ml/min, the system back pressure is 4MPa, the high purity hydrogen is switched to, the hydrogen flow rate is 200ml/min, the mixture of terephthalic acid and 20wt% sodium hydroxide aqueous solution (the mole ratio of terephthalic acid to sodium hydroxide is 1:2.2, and the mixture is stirred for 30min to be completely dissolved) is stirred for 0.1h -1 The product is condensed and gas-liquid separated, then enters a storage tank, concentrated hydrochloric acid (the mass percentage concentration is 30 wt%) is added into the product obtained in the storage tank to regulate the pH of the system to be 1-2, a large amount of white solid is precipitated in the system, the product is filtered and dried in vacuum at 60 ℃ for 6 hours, and then the product 1, 4-cyclohexanedicarboxylic acid is obtained, and the molar yield of the step is 95%.
2. Adding 300g H-ZSM-5 (80-120 mesh) catalyst into a fluidized bed reactor, heating to 330 ℃ under 2L fluidization gas speed, maintaining for 1h to activate the catalyst, and after the catalyst activation is finished, performing catalyst activation for 0.1h -1 And (3) adding a mixture of 1, 4-cyclohexanedicarboxylic acid and urea (the molar ratio of the 1, 4-cyclohexanedicarboxylic acid to the urea is 1:1) into the reactor (calculated by 1, 4-cyclohexanedicarboxylic acid), and separating the product from the gas and the liquid, and then entering a storage tank for storage. After the reaction is finished, adding ethanol with the mass being 2 times to the product in the storage tank for washing, and evaporating the organic phase to dryness to obtain the product p-cyano cyclohexane carboxylic acid, wherein the molar yield of the step is 93%.
3. 10g Ru/gamma-Al were packed in a fixed bed reactor 2 O 3 The catalyst (Ni loading is 20wt%) is heated to 100deg.C under the flow rate of 50ml/min nitrogen, the back pressure of the system is 3MPa, the catalyst is switched into high purity hydrogen with the flow rate of 200ml/min, and the methanol solution (mass concentration of 20wt%) of p-cyanocyclohexanecarboxylic acid is added for 0.1h -1 The product is condensed and separated from gas and liquid, and then enters a storage tank, and the obtained product is distilled to recover methanol to obtain tranexamic acid, wherein the molar yield of the step is 95%.
Example 4
1. 10g Pd/SiO was charged into a fixed bed reactor 2 The catalyst (Pd loading is 5 wt%) is heated to 200 ℃ under the nitrogen flow rate of 50ml/min, the system back pressure is 4MPa, the high purity hydrogen is switched to, the hydrogen flow rate is 200ml/min, the mixture of terephthalic acid and 20wt% sodium hydroxide aqueous solution (the mole ratio of terephthalic acid to sodium hydroxide is 1:2.2, and the mixture is stirred for 30min to be completely dissolved) is stirred for 0.1h -1 The mass airspeed of (2) is pumped into a reactor for reaction, the product enters a storage tank after condensation and gas-liquid separation,adding concentrated hydrochloric acid (the mass percentage concentration is 30 wt%) into the product obtained in the storage tank to regulate the pH of the system to 1-2, precipitating a large amount of white solid in the system, filtering, and vacuum drying at 60 ℃ for 6 hours to obtain the product 1, 4-cyclohexanedicarboxylic acid, wherein the molar yield of the step is 94%.
2. 300g of Nb was charged into a fluidized-bed reactor 2 O 5 (80-120 mesh) catalyst, heating to 330 ℃ under 2L fluidization gas speed, maintaining for 1h to activate the catalyst, and after the catalyst activation is finished, heating for 0.1h -1 And (3) adding a mixture of 1, 4-cyclohexanedicarboxylic acid and urea (the molar ratio of the 1, 4-cyclohexanedicarboxylic acid to the urea is 1:1) into the reactor (calculated by 1, 4-cyclohexanedicarboxylic acid), and separating the product from the gas and the liquid, and then entering a storage tank for storage. After the reaction is finished, adding ethanol with the mass being 2 times to the product in the storage tank for washing, and evaporating the organic phase to dryness to obtain the product p-cyano cyclohexane carboxylic acid, wherein the molar yield of the step is 91%.
3. 10g of Ni/HZSM5 catalyst (the loading of Ni is 20 wt%) was filled in a fixed bed reactor, the temperature was raised to 100℃at a nitrogen flow rate of 50ml/min, the back pressure of the system was 3MPa, the reactor was switched to high purity hydrogen gas with a hydrogen flow rate of 200ml/min, and a methanol solution (mass concentration of 20 wt%) of p-cyanocyclohexanecarboxylic acid was prepared at a rate of 0.1h -1 The product is condensed and separated from gas and liquid, and then enters a storage tank, and the obtained product is distilled to recover methanol to obtain the tranexamic acid, wherein the molar yield of the step is 94%.
Example 5
1. Filling 10 in a fixed bed reactorg Pd/HZSM5 catalyst (Pd loading is 5 wt%) heating to 200 deg.C under nitrogen flow rate of 50ml/min, back pressure of system is 4MPa, switching to high purity hydrogen gas, hydrogen flow rate is 200ml/min, mixing terephthalic acid and 20wt% sodium hydroxide aqueous solution (molar ratio of terephthalic acid and sodium hydroxide is 1:2.2, mixing them, stirring for 30min to completely dissolve) for 0.1h -1 The product is condensed and gas-liquid separated, then enters a storage tank, concentrated hydrochloric acid (the mass percentage concentration is 30 wt%) is added into the product obtained in the storage tank to regulate the pH of the system to be 1-2, a large amount of white solid is precipitated in the system, the product is filtered and dried in vacuum at 60 ℃ for 6 hours, and then the product 1, 4-cyclohexanedicarboxylic acid is obtained, and the molar yield of the step is 96%.
2. 300g of SiO was charged into a fluidized-bed reactor 2 -Al 2 O 3 (80-120 mesh) catalyst, heating to 330 ℃ under 2L fluidization gas speed, maintaining for 1h to activate the catalyst, and after the catalyst activation is finished, heating for 0.1h -1 And (3) adding a mixture of 1, 4-cyclohexanedicarboxylic acid and urea (the molar ratio of the 1, 4-cyclohexanedicarboxylic acid to the urea is 1:1) into the reactor (calculated by 1, 4-cyclohexanedicarboxylic acid), and separating the product from the gas and the liquid, and then entering a storage tank for storage. After the reaction, the product in the storage tank was washed by adding 2 times of methylene dichloride twice, and the organic phase was evaporated to dryness to obtain the p-cyanocyclohexanecarboxylic acid product, the molar yield in this step was 91%.
3. 10g of Ni/HZSM5 catalyst (the loading of Ni is 20 wt%) was filled in a fixed bed reactor, the temperature was raised to 100℃at a nitrogen flow rate of 50ml/min, the back pressure of the system was 3MPa, the reactor was switched to high purity hydrogen gas with a hydrogen flow rate of 200ml/min, and a methanol solution (mass concentration of 20 wt%) of p-cyanocyclohexanecarboxylic acid was prepared at a rate of 0.1h -1 Is pumped into the reactorAnd (3) carrying out reaction, condensing and gas-liquid separating a product, then entering a storage tank, and distilling the obtained product to recover methanol to obtain tranexamic acid, wherein the molar yield of the step is 94%.
Example 6
1. 10g of Ru/HZSM5 catalyst (Pd loading is 5 wt%) is filled in a fixed bed reactor, the temperature is raised to 200 ℃ under the flow rate of 50ml/min nitrogen, the system back pressure is changed to 4MPa, high-purity hydrogen is switched to, the hydrogen flow rate is 200ml/min, the mixture of terephthalic acid and 20wt% sodium hydroxide aqueous solution (the mol ratio of terephthalic acid to sodium hydroxide is 1:2.2, and the terephthalic acid and sodium hydroxide are mixed and stirred for 30min to be completely dissolved) is added for 0.1h -1 The product is condensed and gas-liquid separated, then enters a storage tank, concentrated hydrochloric acid (the mass percentage concentration is 30 wt%) is added into the product obtained in the storage tank to regulate the pH of the system to be 1-2, a large amount of white solid is precipitated in the system, the product is filtered and dried in vacuum at 60 ℃ for 6 hours, and then the product 1, 4-cyclohexanedicarboxylic acid is obtained, and the molar yield of the step is 96%.
2. 300g of SiO was charged into a fluidized-bed reactor 2 (80-120 mesh) catalyst, heating to 330 ℃ under 2L fluidization gas speed, maintaining for 1h to activate the catalyst, and after the catalyst activation is finished, heating for 0.1h -1 1, 4-cyclohexanedicarboxylic acid is added into the reactor, ammonia gas (65 ml/min, the mol ratio of the 1, 4-cyclohexanedicarboxylic acid to the ammonia gas is 1:1) is introduced into the reactor, and the product is stored in a storage tank after gas-liquid separation. After the reaction, the product in the storage tank was washed by adding 2 times of methylene dichloride twice, and the organic phase was evaporated to dryness to obtain the p-cyanocyclohexanecarboxylic acid product, the molar yield in this step was 91%.
3. 10g of Ni/Al was packed in a fixed bed reactor 2 O 3 The catalyst (Ni loading is 20wt%) is heated to 100deg.C under the flow rate of 50ml/min nitrogen, the back pressure of the system is 3MPa, the catalyst is switched into high purity hydrogen with the flow rate of 200ml/min, and the methanol solution (mass concentration of 20wt%) of p-cyanocyclohexanecarboxylic acid is added for 0.1h -1 The product is condensed and separated from gas and liquid, and then enters a storage tank, and the obtained product is distilled to recover methanol to obtain the tranexamic acid, wherein the molar yield of the step is 94%.
Example 7
1. 10g of Ni/HZSM5 catalyst (the loading of Ni is 20 wt%) was charged in a fixed bed reactor, the temperature was raised to 200℃at a nitrogen flow rate of 50ml/min, the system back pressure was changed to 4MPa, high purity hydrogen was used, the hydrogen flow rate was 200ml/min, and a mixture (concentration of 10 wt%) of dimethyl terephthalate and 1, 4-dioxane was fed to the reactor at a rate of 0.1h -1 The product is condensed and gas-liquid separated, then enters a storage tank, and the solvent is distilled off to obtain a pale yellow liquid product, wherein the molar yield of the step is 93%.
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2. 20g of SiO are introduced into a fixed bed reactor 2 (20-40 mesh) catalyst, heating to 350deg.C under nitrogen gas flow rate of 100ml/min, holding for 1 hr to activate catalyst, and activating catalyst for 0.3 hr -1 1, 4-cyclohexanedicarboxylic acid dimethyl ester is added into the reactor and ammonia gas (11 ml/min, the molar ratio of the 1, 4-cyclohexanedicarboxylic acid dimethyl ester to the ammonia gas is 1:1) is introduced into the reactor, and the product is stored in a storage tank after gas-liquid separation. After the reaction is finished, the product in the storage tank is steamedThe product p-cyanocyclohexanecarboxylic acid was obtained by distillation in a molar yield of 90%.
3. 10g of Ni/Al was packed in a fixed bed reactor 2 O 3 The catalyst (Ni loading is 20wt%) is heated to 100deg.C under the flow rate of 50ml/min nitrogen, the back pressure of the system is 3MPa, the catalyst is switched into high purity hydrogen with the flow rate of 200ml/min, and the methanol solution (mass concentration of 20wt%) of p-cyanocyclohexanecarboxylic acid is added for 0.1h -1 The product is condensed and separated from gas and liquid, and then enters a storage tank, and the obtained product is distilled to recover methanol to obtain the tranexamic acid, wherein the molar yield of the step is 94%.
The above embodiments are only for illustrating the technical solution of the present invention, and are not limited thereto. Although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: modifications may be made to the technical solutions described in the foregoing embodiments, or equivalents may be substituted for some or all of the technical features thereof, without departing from the spirit and scope of the present invention as defined in the claims; and such modifications or substitutions are intended to be within the scope of the present invention as defined by the claims.

Claims (8)

1. A method for synthesizing tranexamic acid represented by the following reaction formula 2, comprising the steps of:
(1) Mixing terephthalic acid or terephthalic acid ester with an alkali solution, introducing the mixture into a reactor filled with a catalyst 1 for hydrogenation reaction, and acidifying the obtained product to obtain 1, 4-cyclohexanedicarboxylic acid or 1, 4-cyclohexanedicarboxylic acid ester;
(2) Mixing 1, 4-cyclohexanedicarboxylic acid or 1, 4-cyclohexanedicarboxylic acid ester with an ammonia source, adding the mixture into a reactor filled with a catalyst 2 for ammonification and dehydration reaction, and allowing a product to enter a storage tank to obtain p-cyano cyclohexanedicarboxylic acid;
(3) Mixing cyanocyclohexanecarboxylic acid with a solvent, introducing the mixture into a reactor filled with a catalyst 3 for hydrogenation reaction, and distilling the obtained product to remove the solvent to obtain tranexamic acid;
wherein R is H, C1-C6 alkyl, more preferably C1-C3 alkyl, most preferably methyl, ethyl, n-propyl or isopropyl.
2. The synthesis method according to claim 1, wherein the catalyst 1 in the step (1) is Raney Ni, raney Co or a supported metal catalyst, the metal active component M in the supported metal catalyst is one or more selected from Pd, ru, rh, pt, ni, co, cu, and the catalyst carrier is selected from activated carbon and gamma-Al 2 O 3 、SiO 2 、Nb 2 O 5 One or more of zeolite molecular sieves;
preferably, the catalyst 1 in the step (1) is Raney Ni, raney Co or a supported metal catalyst, the metal active component in the supported metal catalyst is selected from one or more of Pd, ru, rh, ni, co, and the catalyst carrier is selected from gamma-Al 2 O 3 、SiO 2 、Nb 2 O 5 One or more of zeolite molecular sieves;
more preferably, the catalyst 1 in the step (1) is Raney Ni, raney Co or a supported metal catalyst, the metal active component in the supported metal catalyst is selected from one or more of Pd, ru, ni, co, and the catalyst carrier is selected from gamma-Al 2 O 3 、SiO 2 One or more of zeolite molecular sieves;
the zeolite molecular sieve is selected from one or more of H-ZSM-5, H-ZSM-35, HY and H beta.
3. The synthetic method according to claim 1, wherein the base of step (1) is selected from one or both of sodium hydroxide and potassium hydroxide;
preferably, the mass concentration of the alkaline solution of step (1) is 10-50 wt%, preferably 10-30wt%, more preferably 15-30wt%;
preferably, the molar ratio of the base to terephthalic acid or terephthalate of step (1) is from 2:1 to 6:1, preferably from 2:1 to 4:1, more preferably from 2:1 to 3:1;
preferably, the reaction temperature of step (1) is 120-250 ℃, preferably 120-220 ℃, more preferably 150-200 ℃;
preferably, the reaction pressure of step (1) is from 2 to 8MPa, preferably from 2 to 6MPa, more preferably from 3 to 5MPa.
4. The synthetic method of claim 1, wherein optionally step (1) is performed as follows: mixing terephthalic acid or terephthalic acid ester with alkali solution in a reaction kettle, dissolving, adding a catalyst 1, replacing air in the kettle with hydrogen, performing hydrogenation reaction, filtering after the reaction is finished to remove the catalyst 1, and acidifying the product to obtain 1, 4-cyclohexanedicarboxylic acid or 1, 4-cyclohexanedicarboxylic acid ester;
preferably, when the reaction kettle is used as the reactor in the step (1), the mass ratio of the catalyst 1 to terephthalic acid or terephthalate is 1:100-30:100, preferably 3:100-20:100, more preferably 5:100-15:100;
preferably, when step (1) uses a fixed bed as a reactor, the mass space velocity of terephthalic acid or terephthalate is in the range of 0.1 to 5 hours -1 Preferably 0.3-3h -1 More preferably 0.5 to 1.5h -1 。
5. The synthetic method according to claim 1, wherein the ammonia source in step (2) is selected from one or more of ammonia, ammonia water, urea, ammonium carbonate, ammonium bicarbonate, preferably ammonia or urea;
preferably, the reactor in step (2) is selected from a fixed bed reactor and a fluidized bed reactor;
preferably, the molar ratio of the ammonia source of step (2) to 1, 4-cyclohexanedicarboxylic acid or 1, 4-cyclohexanedicarboxylate is from 0.9:1 to 1.5:1;
preferably, the catalyst 2 of step (2) is a solid acid selected from gamma-Al 2 O 3 、SiO 2 、SiO 2 -Al 2 O 3 、ZrO 2 、CeO 2 、Nb 2 O 5 One or more of zeolite molecular sieves selected from one or more of H-ZSM-5, H-ZSM-35, HY and hβ;
preferably, the reaction temperature of step (2) is from 250 to 400 ℃, preferably from 280 to 350 ℃, more preferably from 290 to 350 ℃;
preferably, the reaction pressure of step (2) is from 0.1 to 1.0MPa, preferably from 0.1 to 0.5MPa, more preferably from 0.1 to 0.3MPa; in some embodiments, the 1, 4-cyclohexanedicarboxylic acid or 1, 4-cyclohexanedicarboxylate of step (2) has a mass space velocity of from 0.05 to 5 hours -1 Preferably 0.1-3h -1 More preferably 0.1 to 1.0h -1 。
6. The synthesis method according to claim 1, wherein the catalyst 3 in the step (3) is Raney Ni, raney Co 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, co, and the catalyst carrier is selected from active carbon and gamma-Al 2 O 3 、SiO 2 One or more of zeolite molecular sieves;
the zeolite molecular sieve is selected from one or more of H-ZSM-5, H-ZSM-35, HY and H beta.
7. The synthetic method according to claim 1, wherein the reaction solvent of step (3) is selected from one or more of methanol, ethanol, isopropanol, tetrahydrofuran, 1, 4-dioxane;
preferably, the mass concentration of the feedstock of step (3) is from 5 to 40wt%, preferably from 10 to 30wt%, more preferably from 20 to 30wt%;
preferably, the reaction temperature of step (3) is from 60 to 200 ℃, preferably from 80 to 180 ℃, more preferably from 100 to 180 ℃;
preferably, the reaction pressure of step (3) is from 2 to 8MPa, preferably from 2 to 6MPa, more preferably from 3 to 5MPa.
8. The synthetic method of claim 1 wherein, optionally, step (3) is performed as follows: mixing the cyanocyclohexanecarboxylic acid, a solvent and the catalyst 3, adding the mixture into a reaction kettle, replacing air in the kettle with hydrogen, introducing hydrogen, heating for hydrogenation reaction, filtering to remove the catalyst 3 after the reaction is finished, and distilling to remove the solvent to obtain tranexamic acid;
preferably, when the reaction kettle is used as the reactor in the step (3), the mass ratio of the catalyst 3 to the p-cyanocyclohexanecarboxylic acid is 1:100-30:100, preferably 3:100-20:100, more preferably 3:100-15:100;
preferably, when step (3) uses a fixed bed as a reactor, the mass space velocity of the p-cyanocyclohexanecarboxylic acid is from 0.05 to 3 hours -1 Preferably 0.1-3h -1 More preferably 0.1 to 1.0h -1 。
CN202310948143.4A 2023-07-31 2023-07-31 Synthesis method of tranexamic acid Pending CN116947664A (en)

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