Continuous flow synthesis process of tromethamine

Abstract

The invention relates to the technical field of tromethamine synthesis, in particular to a continuous flow synthesis process of tromethamine. Comprising the following steps: adding nitromethane and a solvent A into a container A to obtain a solution A; adding a depolymerizing agent, a solvent B and paraformaldehyde into a container B to obtain a solution B; the first feeding pump and the second feeding pump respectively convey the solution A and the solution B to a micro-channel reactor at the same time for condensation reaction to obtain condensation reaction liquid; transferring the condensation reaction solution to an acidification kettle, and adding a quenching solution for reaction to obtain a quenching reaction solution; diluting the quenching reaction solution, adding a decolorizing agent, and filtering to obtain a decolorizing reaction solution; adding the decolorization reaction liquid and a solvent C into a hydrogenation reaction system by using a circulating pump, and carrying out hydrogenation reaction under the action of hydrogen and a catalyst to obtain hydrogenation reaction liquid; concentrating the hydrogenation reaction liquid to remove the solvent to obtain a tromethamine crude product, and refining the tromethamine crude product to obtain a tromethamine finished product. The method has the effects of low safety risk, continuous and smooth continuous flow pipeline and high product yield and purity.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of synthesis of TTM, in particular to a continuous flow synthesis process of TTM. BACKGROUND

[0002] TTM is also known as tris-hydroxymethyl aminomethane, and its molecular formula is TTM is widely used in acute metabolic and respiratory acidosis, and is a basic buffer agent, which has good buffering effect on metabolic acidosis and enzyme activity, and is also an important pharmaceutical intermediate.

[0003] At present, the two-step method of nitromethane and polyformaldehyde condensation-hydrogenation is mostly used for the intermittent synthesis of TTM in industry, such as the synthesis method of tris-hydroxymethyl aminomethane in Chinese patent No. 200610037713.0, which discloses slowly adding nitromethane to the polyformaldehyde solution for condensation reaction. However, since the condensation reaction is an exothermic reaction, nitromethane will decompose and produce a large amount of gas under the condition of high temperature and alkaline environment, which has the risk of explosion. This slow dropping method cannot well control the dropping point of nitromethane and the reaction temperature near it, and the local high reaction temperature still has the risk of nitromethane explosion, and is easy to catalyze the occurrence of side reactions, which brings problems of subsequent yield and purification.

[0004] Therefore, in view of the above related technologies, the current TTM synthesis process has the problems of high safety risk and side reactions. SUMMARY

[0005] In order to improve the problems of high safety risk and side reactions in the current TTM synthesis process, the purpose of the present application is to provide a continuous flow synthesis process of TTM, which can safely, efficiently and simply synthesize TTM.

[0006] In order to achieve the purpose of the present application, the present application provides a continuous flow synthesis process of TTM, which adopts the following technical scheme: A continuous flow synthesis process of TTM, comprising the following steps: S1, adding nitromethane and solvent A into container A, stirring and mixing uniformly to obtain solution A; S2, adding depolymerization agent, solvent B and polyformaldehyde into container B, stirring and mixing until the system is clear to obtain solution B; S3, using a first feeding pump to deliver the solution A into a microchannel reactor, and using a second feeding pump to deliver the solution B into the microchannel reactor, and performing condensation reaction to obtain a condensation reaction liquid; S4, transferring the condensation reaction liquid to an acidification kettle, adding a quenching solution to perform reaction, and obtaining a quenching reaction liquid; S5, the quenched reaction solution is diluted and a decolorizing agent is added, and after filtration, a decolorized reaction solution is obtained; S6, the decolorized reaction solution and solvent C are added to a hydrogenation reaction system using a circulating pump, and a hydrogenation reaction is carried out under the action of hydrogen and a catalyst to obtain a hydrogenation reaction solution; S7, the hydrogenation reaction solution is refined to obtain an ammel product.

[0007] Implementations can include any or all of the following features.

[0008] In an embodiment, in the step S6, the decolorized reaction solution is added to a front reactor of the hydrogenation reaction system using a first circulating pump, and solvent C is added to another front reactor of the hydrogenation reaction system using a second circulating pump, and the materials in the two front reactors are mixed online and mixed with the hydrogen.

[0009] In an embodiment, the solvent A, the solvent B, and the solvent C are the same organic alcohol solvent.

[0010] In an embodiment, the solvent A or the solvent B or the solvent C is one or a mixture of two or more of methanol, ethanol, n-propanol, and isopropanol.

[0011] In an embodiment, the quenching solution is a mixture of an inorganic acid and solvent A or solvent B, and the concentration of the quenching solution is 5% to 30%.

[0012] In an embodiment, the quenched reaction solution is diluted with the solvent A or the solvent B before the decolorizing agent is added, and a trihydroxynitromethane solution is obtained, and the mass concentration of trihydroxynitromethane in the trihydroxynitromethane solution is 1% to 30%.

[0013] In an embodiment, the condensation reaction temperature is controlled in the range of 20°C to 60°C, and the condensation reaction system pressure is controlled in the range of 0.1 Mpa to 5.0 Mpa.

[0014] In an embodiment, the mass concentration of the solution A is 5% to 40%, the mass concentration of the solution B is 5% to 80%, the molar ratio of nitromethane to polyformaldehyde is 1.0:2.5 to 5.0, and the molar ratio of nitromethane to depolymerization agent is 1.0:0.01 to 1.5.

[0015] In an embodiment, the flow rate of the first feed pump is 0.5 ml / min to 50 ml / min, and the flow rate of the second feed pump is 0.5 ml / min to 50 ml / min.

[0016] In an embodiment, the flow rate of the first circulating pump is 0.1 ml / min-30 ml / min, the flow rate of the second circulating pump is 0.1 ml / min-50 ml / min, the hydrogenation pressure of the hydrogenation reaction is 0.1 Mpa-5.0 Mpa, and the hydrogen flow rate is 5 ml / min-50 ml / min.

[0017] In summary, the present application provides a continuous flow synthesis process of amiloride, which has the following beneficial effects: First, the continuous flow synthesis process is adopted in the condensation reaction and hydrogenation reaction, the flow rate of the material is accurately controlled, the amount of instantaneous contact of the reaction liquid is reduced, the heat release amount of the instantaneous reaction is reduced, the reaction time is prolonged, the heat released in the continuous flow synthesis process can be efficiently removed, the problem of local overheating of the reaction liquid is avoided, and the risk of explosion caused by too fast heat release is avoided.

[0018] Second, before the polyformaldehyde enters the continuous flow reaction channel, the polyformaldehyde is first treated by depolymerization agent to form a uniform solution, which is beneficial to the subsequent efficient reaction of polyformaldehyde and nitromethane raw materials, and avoids the blockage of the continuous flow reaction channel by unsolved polyformaldehyde.

[0019] Third, after the condensation reaction and before the hydrogenation reaction starts, the operation of quenching is carried out to terminate the condensation reaction, reduce the occurrence of side reactions in the subsequent reaction, provide a stable reaction system for the subsequent reaction, and eliminate the risk of explosion of the intermediate product trihydroxynitromethane in the alkaline high-temperature environment.

[0020] Fourth, the decolorization and filtration operations after quenching can increase the purity of the intermediate product by about 2% compared with before decolorization, and can filter out solid impurities such as decolorizing agent and generated inorganic salt in the reaction liquid, so that the reaction liquid after decolorization will not block the continuous flow pipeline when used in the next hydrogenation reaction, promoting the smooth continuous flow reaction of the next reaction material, simplifying the purification of the subsequent product, avoiding the possibility of inorganic salt adsorbed on the surface layer of Raney nickel catalyst, and ensuring the hydrogenation effect of the subsequent Raney nickel catalyst.

[0021] Fifth, while the decolorized reaction liquid continuously enters the hydrogenation reaction system, an organic solvent is used to continuously dilute the decolorized reaction liquid, avoiding the blockage of the continuous flow channel due to the precipitation of solids in the continuous flow channel caused by high concentration of the reaction liquid, and the organic solvent can also continuously dissolve the decolorized reaction liquid that may be precipitated in the continuous flow channel, reducing the waste of substrate and helping to improve the yield of the product. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 The flow chart of the continuous flow synthesis process of amiloride; Figure 2 Chromatogram of the tromethamine product synthesized in Example 1. DETAILED DESCRIPTION

[0023] Other advantages and embodiments of the present application will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings, and myriad of further adaptations of the embodiments discussed will be apparent upon consideration of the specification or practice of the application. It is intended that all such adaptations be within the scope of the application. Like reference numerals in the drawings are denoted by like reference numerals in all the various figures, in which:

[0024] The batch reactor synthesis process of nitromethane dropwise into the mixture of all reaction amounts of paraformaldehyde and base, as nitromethane is continuously added, the first drop of nitromethane will instantaneously react with excess paraformaldehyde, resulting in local instantaneous heat release at the drop point and its vicinity. Due to the limited mixing and heat transfer efficiency of the reactor, the local temperature will be too high, increasing the safety risk of subsequent nitromethane dropwise addition. The local high temperature at the drop point and its vicinity is prone to catalyze side reactions, causing problems in subsequent yield and purity.

[0025] Reference Figure 1 The present application discloses a continuous flow synthesis process of tromethamine, comprising the following steps: S1, adding nitromethane and solvent A into container A, stirring and mixing uniformly to obtain solution A; S2, adding depolymerization agent, solvent B and paraformaldehyde into container B, stirring and mixing until the system is clear to obtain solution B; S3, using a first feed pump to deliver the solution A to a microchannel reactor, and using a second feed pump to deliver the solution B to the microchannel reactor, to perform condensation reaction and obtain a condensation reaction liquid; S4, transferring the condensation reaction liquid to an acidification kettle, adding a quenching solution to perform reaction, and obtaining a quenching reaction liquid; S5, diluting the quenching reaction liquid and adding a decolorizing agent, and then filtering to obtain a decolorizing reaction liquid; S6, using a circulating pump to add the decolorizing reaction liquid and solvent C into a hydrogenation reaction system, and performing hydrogenation reaction under the action of hydrogen and catalyst to obtain a hydrogenation reaction liquid; S7, concentrating the hydrogenation reaction liquid to remove the solvent to obtain tromethamine crude product, and refining the tromethamine crude product to obtain tromethamine product.

[0026] In the step S1, the container A can be a storage tank, and the solvent A can be an organic solvent, further can be an organic alcohol solvent, such as one or two or more than two kinds of mixture of methanol, ethanol, n-propanol, isopropanol. The step controls the mass concentration of nitromethane in the solution A to be 5%~40%.

[0027] In the step S2, the container B can be a storage tank, and the solvent B can be an organic solvent, further can be an organic alcohol solvent, such as one or two or more than two kinds of mixture of methanol, ethanol, n-propanol, isopropanol. In order to introduce less material into the reaction system, reduce the possibility of side reactions, the solvent A and the solvent B are preferably the same organic alcohol solvent. The depolymerization agent is a basic substance, preferably an inorganic strong base, such as potassium hydroxide, sodium hydroxide, and the addition of the depolymerization agent by the mixing of step S2 makes the polyformaldehyde fully depolymerized under alkaline conditions, reducing the problem of polyformaldehyde blocking the continuous flow reaction channel. The stirring mixing in the step S2 can be carried out at a certain temperature, such as stirring mixing at 20℃~30℃, promoting efficient and thorough depolymerization of polyformaldehyde. The step controls the mass concentration of solution B to be 5%~80%. In this embodiment, taking nitromethane as the reference substance, the molar ratio of nitromethane to polyformaldehyde is 1.0:2.5~5.0, and the molar ratio of nitromethane to depolymerization agent is 1.0:0.01~1.5.

[0028] In the step S3, the condensation reaction temperature is controlled to be 20℃~60℃, the whole condensation system pressure is maintained to be 0.1 Mpa~5.0Mpa, and the flow rate of the first feed pump and the second feed pump is 0.5ml / min~50ml / min for continuous flow condensation reaction. Among them, the microchannel reactor adopts a commercially available commercial continuous flow microchannel reactor.

[0029] In the step S4, the quenching solution is an acidic solution mixed by inorganic acid and solvent A or solvent B, and the concentration of the quenching solution is 5%~30%, wherein the inorganic acid is sulfuric acid, and the solvent A and the solvent B are the same organic alcohol solvent, such as methanol, and the quenching solution is 5%~30% sulfuric acid methanol solution. The pH of the basic condensation reaction liquid is adjusted to 3~9 by the acidic quenching solution, the temperature of the liquid is controlled to be 1℃~60℃, and the condensation reaction is quenched.

[0030] In the step S5, the obtained quenched reaction solution is diluted by adding an organic solvent to obtain a solution of trihydroxynitromethane, and the mass concentration of trihydroxynitromethane in the diluted solution is controlled to be 1% to 30%. The organic solvent used for dilution in this step is the same as the solvent A and the solvent B described above, and is an organic alcohol solvent, such as methanol. A decolorizing agent is added to the diluted solution of trihydroxynitromethane, and the solution is decolorized at 40°C to 45°C for about 2 hours. The decolorizing agent is preferably a solid decolorizing agent that can be filtered, such as activated carbon. The decolorized reaction solution is filtered to obtain a decolorized reaction solution.

[0031] In the step S6, the decolorized reaction solution obtained in the step S5 is added to a pre-reactor of a hydrogenation reaction system by using a first circulating pump, and the flow rate of the first circulating pump is 0.1 ml / min to 30 ml / min. The pre-reactor can be a hydrogenation raw material pre-heater, and the decolorized reaction solution is pre-heated to 10°C to 60°C. Solvent C is added to another pre-reactor of the hydrogenation reaction system by using a second circulating pump, and the flow rate of the second circulating pump is 0.1 ml / min to 50 ml / min. The other pre-reactor can be a hydrogenation circulating temperature controller, and the solvent C is controlled to a temperature of 10°C to 60°C. The solvent C is used to dilute the decolorized reaction solution, so as to avoid the continuous flow channel from being blocked by solid precipitated due to high concentration of the reaction solution. The solvent C can be an organic alcohol solvent, such as one of methanol, ethanol, n-propanol, and isopropanol. The two streams of materials in the two pre-reactors are mixed online, and then enter a gas-liquid mixer of the hydrogenation reaction system to be mixed with hydrogen. The hydrogen is also continuously added to the gas-liquid mixer of the hydrogenation reaction system by using a pump, and the flow rate of the hydrogen is controlled to be 5 ml / min to 50 ml / min. Further, the gas-liquid two-phase mixture after being mixed with hydrogen enters a catalyst bed of the hydrogenation reaction system, and the temperature of the catalyst bed of the hydrogenation reaction system is controlled to be below 80°C. The hydrogenation reaction is carried out on the surface of a hydrogenation catalyst under a hydrogenation pressure of 0.1 MPa to 5.0 MPa, and the hydrogenation catalyst is Raney nickel catalyst. The hydrogenation reaction system can be a hydrogenation reactor having multiple material pipelines and reactors.

[0032] In the step S7, the hydrogenated reaction solution obtained in the hydrogenation is transferred to a concentration and crystallization kettle, and the concentration is stopped after crystals are precipitated at 20°C to 60°C. A crude trometamol is obtained. According to the mass of the raw material in the raw material solution before concentration, 0.9 times the mass of the raw material in the raw material solution before concentration is added to the obtained crude trometamol as an organic solvent D. The mixture is stirred and slowly cooled to -5°C to 20°C to precipitate crystals. The crystallization stirring is maintained for 3 hours to 24 hours. The crystallization solution is centrifuged, and the wet product is dried at 30°C to 80°C until the weight is constant, to obtain a finished product of trometamol. The organic solvent D can be an organic alcohol solvent, such as one of methanol, ethanol, n-propanol, and isopropanol.

[0033] The continuous flow synthesis process of the embodiment can accurately control the flow rate of the reactants, realize efficient mixing of the reactants on a microscale, continuously occur reactions in the continuous flow process, and does not have a position-determined local reaction point. By controlling the instantaneous contact amount of the reactants, the reaction exothermic quantity and the required pressure can be controlled within a small range, thereby reducing the risk of explosion of the condensation reaction and the hydrogenation reaction.

[0034] The patency of the continuous flow reaction channel in the continuous flow synthesis process has an important influence on the implementation results. In the embodiment, corresponding operations are taken before the condensation reaction, between the condensation reaction and the hydrogenation reaction, and during the hydrogenation reaction, so as to maintain the patency of the continuous flow reaction channel during the entire continuous flow synthesis process of tromethamine. In the S2 step, the polyformaldehyde is completely depolymerized using a depolymerizing agent before the reactant enters the continuous flow reaction channel, so as to avoid that the macromolecular polymer blocks the continuous flow reaction channel. In the S4 and S5 steps, the intermediate reaction liquid is quenched, decolorized, and filtered after the condensation reaction ends and before the hydrogenation reaction starts, so as to reduce the impurity content in the intermediate reaction liquid and avoid that the impurities are adsorbed and deposited in the continuous flow pipeline to cause blockage. In the S6 step, the decolorized reaction liquid is continuously diluted using the organic solvent C while the decolorized reaction liquid continuously enters the hydrogenation reaction system, so as to avoid that solid is precipitated in the continuous flow channel due to the high concentration of the reaction liquid and the continuous flow channel is blocked. At the same time, maintaining the patency of the continuous flow reaction channel during the entire continuous flow synthesis process of tromethamine can reduce the waste caused by the deposition of the reactant in the continuous flow channel, ensure that the raw materials and intermediate reaction substances can enter the continuous flow channel as much as possible for product synthesis, and obtain a relatively high product yield. For example, in the embodiment, the organic solvent C can continuously dissolve the decolorized reaction liquid that may be precipitated in the continuous flow channel while continuously diluting the decolorized reaction liquid in the continuous flow, so as to reduce the waste of the reactant and help to improve the product yield.

[0035] The continuous flow synthesis process of tromethamine of the present application will be further described in detail below in combination with specific embodiments and comparative examples.

[0036] Embodiment 1 A methanol solution was added to the storage tank A, and nitromethane (1.0 eq, 810.00 g) was stirred and uniformly mixed to obtain solution A, and the mass concentration of solution A was 20%; potassium hydroxide (0.01 eq) and methanol were added to the storage tank B, stirred and dissolved, and then polyformaldehyde (3.0 eq) was added. The system was stirred at 30°C until it was dissolved, and solution B was prepared, and the mass concentration of solution B was 25%.

[0037] The first feed pump with a flow rate of 4.00 ml / min is used to transport solution A in the storage tank A to the micro-channel reactor, and the second feed pump with a flow rate of 3.00 ml / min is used to transport solution B in the storage tank B to the same micro-channel reactor, and the continuous condensation reaction of solution A and solution B is carried out in the micro-channel reactor, the condensation reaction temperature is controlled at 30℃, the pressure of the whole condensation system is kept at 0.1 Mpa, and the condensation reaction liquid is obtained.

[0038] The condensation reaction liquid is transferred to an acidification kettle, the pH is adjusted to 3-4 by using 10% concentrated sulfuric acid methanol, the liquid temperature is controlled at 30℃, the quenched quenching reaction liquid is obtained, the quenching reaction liquid is diluted by adding methanol to obtain a solution with a mass concentration of 5% of the diluted trihydroxy nitromethane, activated carbon is added, and the solution is decolorized at 40-45℃ for 2h, and then the decolorized reaction liquid is obtained by cooling and filtering.

[0039] In one material channel, the decolorized reaction liquid is continuously fed into the hydrogenation raw material preheater of the hydrogenation reactor through the first circulating pump with a flow rate of 0.3 ml / min, and is preheated to 30℃. In another material channel, methanol is continuously fed into the hydrogenation circulating temperature controller of the hydrogenation reactor through the second circulating pump with a flow rate of 0.5 ml / min, and is temperature-controlled to 30℃. The two streams are mixed online and then enter the gas-liquid mixer of the hydrogenation reactor, and hydrogen is continuously fed into the gas-liquid mixer at a flow rate of 10 ml / min to mix with the decolorized reaction liquid and methanol. The mixed gas-liquid two-phase continuously enters the Raney nickel catalyst bed, and hydrogenation reduction reaction is carried out on the surface of the Raney nickel catalyst. The temperature of the Raney nickel catalyst bed is controlled at 50℃, and the hydrogenation pressure is controlled at 1.5 Mpa.

[0040] The hydrogenated solution is transferred to a concentration crystallization kettle, and concentrated at 30℃ until crystals precipitate, and then the concentration is stopped. The crude tromethamine is obtained. 1 times mass of isopropyl alcohol is added to the crude tromethamine (calculated based on the mass of the raw material in the raw material liquid before concentration), and the mixture is slowly cooled to -5-10℃ while stirring to precipitate crystals. The crystallization is stirred for 24 hours to obtain a crystallization solution. The crystallization solution is centrifuged, and the wet product is dried at 30℃ until the weight is constant. Thus, 1255.15 grams of finished tromethamine is obtained, with a total yield of 78.0%, a purity of 99.72%, and a chromatographic detection spectrum of the finished tromethamine as shown in Figure 2 The specific data of each signal corresponding to the chromatographic detection spectrum is shown in Table 1.

[0041] Table 1 Chromatographic detection signals of the finished tromethamine

[0042] The same experimental procedures as in Example 1 are used to implement Examples 2-10, and the experimental conditions and results of Examples 1-10 are summarized in Table 2.

[0043] Table 2 Experimental conditions and experimental results table of Example 1-Example 10

[0044] Comparative Example 1-4 The same experimental procedure as Example 1 was used to implement Comparative Example 1-4, and the experimental conditions and experimental results of Comparative Example 1-Comparative Example 4 are shown in Table 3.

[0045] Comparative Example 5 Comparative Example 5 differs from Example 1 only in that during the hydrogenation reaction, the decolorization reaction liquid is not diluted online, and only one material channel is used. The decolorization reaction liquid continuously enters the hydrogenation reactor's hydrogen feed preheater through the material channel at a flow rate of 0.3 ml / min, is preheated to 30°C, and then enters the gas-liquid mixer of the hydrogenation reactor. At the same time, hydrogen gas continuously enters the gas-liquid mixer at a flow rate of 10 ml / min and mixes with the decolorization reaction liquid. Subsequent process steps are carried out according to the same experimental procedure and experimental conditions as Example 1. The experimental conditions and experimental results of Example 5 are summarized in Table 3.

[0046] Table 3 Experimental conditions and experimental results table of Comparative Example 1-Comparative Example 5

[0047] As can be seen from the comparison of the experimental data of Example 1-10 and the experimental data of Comparative Example 1-4 in Table 1, through the optimization of various reaction conditions in the continuous flow synthesis process of tromethamine, the purity and yield of the product are significantly improved. And through the optimization of various reaction conditions, Examples 1-4 can still obtain relatively high product purity and yield under the conditions of low condensation reaction temperature, condensation system pressure and hydrogenation pressure, significantly improving the safety of the production process.

[0048] As can be seen from the comparison of the experimental data of Example 1 in Table 1 and the experimental data of Comparative Example 5 in Table 2, by continuously diluting the reaction liquid online during the hydrogenation reaction in the continuous flow synthesis process of tromethamine, the purity and yield of the product tromethamine can be improved.

[0049] Finally, it should be noted that the above-described embodiments are merely specific embodiments of the present application, which are used to illustrate the technical solutions of the present application, but not to limit the present application, and the protection scope of the present application is not limited thereto. Although the present application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that any person skilled in the art can still make modifications or easily think of changes to the technical solutions recorded in the foregoing embodiments, or make equivalent replacements to some technical features therein, within the technical range disclosed by the present application, and these modifications, changes or replacements do not make the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application, and all should be covered within the protection scope of the present application. Therefore, the protection scope of the present application should be subject to the protection scope of the claims.

Claims

1. A continuous flow synthesis process for tromethamine, characterized in that, Includes the following steps: S1, add nitromethane and solvent A to container A, stir and mix evenly to obtain solution A; S2, add depolymerizing agent, solvent B and paraformaldehyde to container B, stir and mix until the system is clear, to obtain solution B; S3, the first feed pump is used to deliver the solution A to the microchannel reactor, and the second feed pump is used to deliver the solution B to the microchannel reactor to carry out the condensation reaction and obtain the condensation reaction solution; S4, the condensation reaction solution is transferred to the acidification vessel, and a quenching solution is added to carry out the reaction to obtain a quenching reaction solution; S5, the quenching reaction solution is diluted and a decolorizing agent is added, and the solution is filtered to obtain a decolorizing reaction solution; S6, the decolorizing reaction solution and solvent C are added to the hydrogenation reaction system using a circulating pump, and the hydrogenation reaction is carried out under the action of hydrogen and catalyst to obtain the hydrogenation reaction solution; S7. The hydrogenation reaction solution is concentrated to remove the solvent to obtain crude tromethamine, and the crude tromethamine is purified to obtain the finished tromethamine.

2. The continuous flow synthesis process of tromethamine as described in claim 1, characterized in that, In step S6, the decolorizing reaction solution is added to the preceding reactor of the hydrogenation reaction system using a first circulation pump, and solvent C is added to another preceding reactor of the hydrogenation reaction system using a second circulation pump. The materials in the two preceding reactors are mixed online and then mixed with the hydrogen gas.

3. The continuous flow synthesis process of tromethamine as described in claim 2, characterized in that, Solvent A, solvent B, and solvent C are all organic alcohol solvents.

4. The continuous flow synthesis process of tromethamine as described in claim 3, characterized in that, Solvent A, solvent B, or solvent C is one or a mixture of two or more of methanol, ethanol, n-propanol, and isopropanol.

5. The continuous flow synthesis process of tromethamine as described in claim 1, characterized in that, The quenching solution is a mixture of inorganic acid and solvent A or solvent B, and the concentration of the quenching solution is 5% to 30%.

6. The continuous flow synthesis process of tromethamine as described in claim 1, characterized in that, The quenching reaction solution is diluted with solvent A or solvent B before the decolorizing agent is added to obtain a trihydroxynitromethane solution, wherein the mass concentration of trihydroxynitromethane in the trihydroxynitromethane solution is 1% to 30%.

7. The continuous flow synthesis process of tromethamine as described in claim 1, characterized in that, The condensation reaction temperature is controlled within the range of 20℃ to 60℃, and the condensation reaction system pressure is controlled within the range of 0.1 MPa to 5.0 MPa.

8. The continuous flow synthesis process of tromethamine as described in claim 1, characterized in that, The mass concentration of solution A is 5%~40%, the mass concentration of solution B is 5%~80%, the molar ratio of nitromethane to paraformaldehyde is 1.0:2.5~5.0, and the molar ratio of nitromethane to depolymerizing agent is 1.0:0.01~1.

5.

9. The continuous flow synthesis process of tromethamine as described in claim 1, characterized in that, The flow rate of the first feed pump is 0.5 ml / min to 50 ml / min, and the flow rate of the second feed pump is 0.5 ml / min to 50 ml / min.

10. The continuous flow synthesis process of tromethamine as described in claim 2, characterized in that, The flow rate of the first circulation pump is 0.1 ml / min to 30 ml / min, the flow rate of the second circulation pump is 0.1 ml / min to 50 ml / min, the hydrogenation pressure of the hydrogenation reaction is 0.1 MPa to 5.0 MPa, and the hydrogen flow rate is 5 ml / min to 50 ml / min.

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