A method for preparing 1,3-bis[(trihydroxymethyl)methylamino]propane

Abstract

The present application provides a method for preparing 1,3-bis[(trimethylol)methylamino]propane, and relates to the technical field of organic compound synthesis. The preparation method includes: subjecting raw materials including tromethamine and malondialdehyde to a condensation reaction; catalytic hydrogenation of the product of the condensation reaction to obtain the 1,3-bis[(trimethylol)methylamino]propane. The present application improves the molar yield and purity of the product by selecting suitable raw materials and process steps, and the preparation method is simple, which greatly reduces the cost. Further, the preparation method of the present application can also be used for continuous and large-scale production, and the product prepared is suitable for application in the field of buffers.

Description

Technical Field

[0001] The present application relates to the technical field of organic compound synthesis, and in particular to a method for preparing 1,3-bis[(trihydroxymethyl)methylamino]propane. Background Art

[0002] 1,3-Bis[(trihydroxymethyl)methylamino]propane (BIS-TRIS propane, or BTP) is a zwitterionic buffer with strong buffering capacity. Therefore, it is often used as a biological buffer in biochemical diagnostic kits, DNA / RNA extraction kits or PCR diagnostic kits. In addition, 1,3-bis[(trihydroxymethyl)methylamino]propane also has broad application prospects in the fields of medicinal chemistry and material chemistry, but there are still many problems in its preparation process, such as low yield and low purity.

[0003] In the preparation method of 1,3-bis[(trihydroxymethyl)methylamino]propane, patent CN200810200543.2 discloses the relevant synthesis and purification process using trihydroxymethylaminomethane and 1,3-dibromopropane as raw materials, wherein the product yield is up to 80%. Patent CN202210106789 discloses a new preparation method, but a large amount of by-products will be produced during the preparation process, and the by-products need to be treated, which increases the preparation cost. Therefore, it is necessary to find a new synthesis preparation method to improve the yield. Summary of the invention

[0004] The purpose of the present application is to provide a method for preparing 1,3-bis[(trihydroxymethyl)methylamino]propane. By using common raw materials and mild reaction conditions, the final product has a high yield, simple post-treatment, and can be produced continuously and on a large scale.

[0005] To achieve the above objectives, the technical solution of this application is as follows:

[0006] The preparation method of 1,3-bis[(trihydroxymethyl)methylamino]propane provided in the present application comprises:

[0007] subjecting raw materials including tromethamine and malondialdehyde to a condensation reaction;

[0008] The product of the condensation reaction is subjected to catalytic hydrogenation to obtain the 1,3-bis[(trihydroxymethyl)methylamino]propane.

[0009] Preferably, the preparation method satisfies at least one of the following conditions:

[0010] a. The raw materials for the condensation reaction also include an organic solvent;

[0011] b. The condensation reaction is carried out in an atmosphere of inert gas;

[0012] c. The molar ratio of tromethamine to malondialdehyde is 2:(1-1.05);

[0013] d. The condensation reaction temperature is 70°C-90°C and the time is 4h-6h.

[0014] More preferably, at least one of the following conditions is also met:

[0015] e. The organic solvent comprises at least one of methanol, ethanol and propanol;

[0016] f. The inert gas comprises at least one of nitrogen, argon and helium;

[0017] g. The molar concentration of tromethamine in the organic solvent is 2mmol / mL-3mmol / mL.

[0018] Preferably, before the hydrogenation, the process comprises:

[0019] The composition of the product of the condensation reaction is detected. If the mass proportion of the residual tromethamine is less than 0.3%, the product of the condensation reaction is cooled to room temperature and a catalyst is added.

[0020] Further preferably, the catalyst includes any one of a platinum-carbon catalyst, a palladium-carbon catalyst, a ruthenium-carbon catalyst, and a Raney nickel catalyst;

[0021] The mass of the catalyst is 0.01 to 0.1 times the mass of the tromethamine.

[0022] Further preferably, the catalyst is a palladium-carbon catalyst containing 5wt%-10wt% of palladium.

[0023] Preferably, the preparation method further satisfies at least one of the following conditions:

[0024] h. The gas pressure of the catalytic hydrogenation is 1MPa-3MPa;

[0025] i. The temperature of the catalytic hydrogenation is 40°C-60°C and the time is 5h-8h.

[0026] Preferably, the condensation reaction and the catalytic hydrogenation are carried out continuously in the same reactor;

[0027] Alternatively, the product of the condensation reaction is added to a fixed bed reactor for the catalytic hydrogenation.

[0028] Further preferably, the flow rate of the product of the condensation reaction added to the fixed bed reactor is 0.1 mL / min-0.5 mL / min.

[0029] Preferably, after the catalytic hydrogenation is completed, the method further comprises:

[0030] The product after the catalytic hydrogenation reaction is subjected to atmospheric distillation, suction filtration, and drying to obtain the 1,3-bis[(trihydroxymethyl)methylamino]propane.

[0031] Beneficial effects of this application:

[0032] The preparation method of 1,3-bis[(trihydroxymethyl)methylamino]propane provided in the present application improves the yield and purity of the product by selecting suitable raw materials and process steps, and the method is simple, greatly reduces the preparation cost, and can be used for continuous production. The purified 1,3-bis[(trihydroxymethyl)methylamino]propane has high purity and is suitable for application in the fields of biological buffers and the like. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the embodiments will be briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present application and therefore should not be regarded as limiting the scope of the present application.

[0034] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of 1,3-bis[(trihydroxymethyl)methylamino]propane prepared in Example 1 in DMSO-d6. DETAILED DESCRIPTION

[0035] As used herein:

[0036] "Prepared from" is synonymous with "comprising." As used herein, the terms "comprising," "including," "having," "containing," or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus comprising the listed elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus. The conjunction "consisting of" excludes any unspecified element, step, or component.

[0037] When an amount, concentration, or other value or parameter is expressed as a range, a preferred range, or a range defined by a series of upper preferred values ​​and lower preferred values, this should be understood as specifically disclosing all ranges formed by any pairing of any range upper limit or preferred value with any range lower limit or preferred value, regardless of whether the range is disclosed separately. For example, when a range of "1 to 5" is disclosed, the described range should be interpreted as including ranges "1 to 4", "1 to 3", "1 to 2", "1 to 2 and 4 to 5", "1 to 3 and 5", etc. When a numerical range is described in this article, unless otherwise stated, the range is intended to include its end values ​​and all integers and fractions within the range.

[0038] In these examples, parts and percentages are by mass unless otherwise indicated.

[0039] "Parts by mass" refers to the basic unit of measurement for expressing the mass ratio of multiple components. 1 part can represent any unit mass, such as 1g or 2.689g. If we say that the mass of component A is a parts and the mass of component B is b parts, it means the ratio of the mass of component A to the mass of component B is a:b. Alternatively, it means that the mass of component A is aK and the mass of component B is bK (K is an arbitrary number, indicating a multiple factor). It should not be misunderstood that, unlike the mass parts, the sum of the mass of all components is not limited to 100 parts.

[0040] "And / or" is used to indicate that one or both of the stated situations may occur, for example, A and / or B includes (A and B) and (A or B).

[0041] The present application provides a method for preparing 1,3-bis[(trihydroxymethyl)methylamino]propane, comprising:

[0042] S1, subjecting raw materials including tromethamine and malondialdehyde to a condensation reaction;

[0043] S2. Catalytically hydrogenating the product of the condensation reaction to obtain the 1,3-bis[(trihydroxymethyl)methylamino]propane.

[0044] It should be noted that the preparation method of the present application uses condensation reaction and hydrogenation reaction for synthesis, and the specific reaction equation is as follows:

[0045]

[0046] In a preferred embodiment, when the condensation reaction is carried out in S1, the required raw materials also include an organic solvent. Specifically, the organic solvent can be added to the mixture of tromethamine and malondialdehyde.

[0047] More preferably, the added organic solvent includes at least one of methanol, ethanol and propanol, more preferably methanol.

[0048] In a preferred embodiment, the condensation reaction in S1 is carried out in an atmosphere containing an inert gas.

[0049] More preferably, the inert gas introduced includes at least one of nitrogen, argon and helium.

[0050] Further preferably, the molar concentration of tromethamine in the organic solvent is 2 mmol / mL-3 mmol / mL, for example, it can be 1 mmol / mL, 1.1 mmol / mL, 1.25 mmol / mL, 1.4 mmol / mL, 1.5 mmol / mL or any value between 1 mmol / mL and 1.5 mmol / mL.

[0051] In a preferred embodiment, the molar ratio of tromethamine to malondialdehyde in S1 is 2:(1-1.05), for example, it can be 2:1, 2:1.01, 2:1.02, 2:1.03, 2:1.04, 2:1.05 or any value between 2:(1-1.05).

[0052] In a preferred embodiment, the condensation reaction temperature in S1 is 70°C-90°C, for example, 70°C, 80°C, 90°C or any value between 70°C-90°C; the reaction time is 4h-6h, for example, 4h, 5h, 6h or any value between 4h-5h. More preferably, the condensation reaction is carried out at 80°C for 5 hours.

[0053] In a preferred embodiment, before hydrogenation, S2 includes: testing the composition of the product of the condensation reaction, and if the mass proportion of residual tromethamine is less than 0.3%, cooling the product of the condensation reaction to room temperature and adding a catalyst.

[0054] Specifically, at the end of the condensation reaction, the proportion of residual raw materials in the product is detected. If the mass proportion of tromethamine in the mixed product after the condensation reaction is less than 0.3%, this indicates that almost all of the tromethamine has undergone a condensation reaction with malondialdehyde. At this time, the temperature of the condensation reaction product can be lowered to room temperature, and then a catalyst is added to promote the reaction of the product with hydrogen.

[0055] In a more preferred embodiment, the catalyst for catalytic hydrogenation comprises any one of a platinum-carbon catalyst, a palladium-carbon catalyst, a ruthenium-carbon catalyst, and a Raney nickel catalyst, wherein the noble metal content in the platinum-carbon, palladium-carbon, and ruthenium-carbon is 5wt%-10wt%.

[0056] Further preferably, the catalyst is a palladium-carbon catalyst containing 5wt%-10wt% of palladium.

[0057] Further preferably, the mass of the added catalyst is 0.01-0.1 times the mass of tromethamine in S1, for example, it can be 0.01, 0.03, 0.05, 0.07, 0.08, 0.09, 0.1 or any value between 0.01 and 0.1.

[0058] In a preferred embodiment, the gas pressure after catalytic hydrogenation in S2 is 1 MPa-3 MPa, more preferably 2 MPa.

[0059] In a preferred embodiment, the temperature after catalytic hydrogenation in S2 is 40°C-60°C, for example, 40°C, 45°C, 50°C, 55°C, 60°C or any value between 40°C-60°C; the time is 5h-8h, for example, 5h, 6h, 7h, 8h or any value between 5h-8h. More preferably, the hydrogenation reaction is carried out at 45°C for 6 hours.

[0060] In a preferred embodiment, the condensation reaction and the catalytic hydrogenation can be carried out continuously in the same reactor. For example, after adding tromethamine, malondialdehyde and an organic solvent into a stainless steel hydrogenation reactor, the hydrogenation reactor is sealed, an inert gas is introduced to replace the air in the reactor, and then the reactor is heated to carry out the condensation reaction. After the reaction is completed and cooled, a catalyst is added to the reactor under negative pressure, and hydrogen is introduced to carry out the hydrogenation reaction.

[0061] It should be noted that when the condensation reaction and catalytic hydrogenation are continuously carried out in the same reactor, especially when the catalyst is added to the reactor, the catalyst can be mixed with a certain amount of organic solvent before adding to the reactor.

[0062] In a preferred embodiment, the condensation reaction can be carried out in a reactor, and the catalytic hydrogenation is carried out in a fixed bed reactor. Specifically, the catalyst can be first filled into the fixed bed reactor, and then the product of the condensation reaction prepared in the reactor is added to the fixed bed reactor, and the temperature required for the catalytic hydrogenation, the flow rate of the raw material product and the pressure of the hydrogen introduced are set, so that continuous production can be achieved and the product after the hydrogenation reaction in the fixed bed reactor can be continuously collected.

[0063] Further preferably, the product flow rate of the condensation reaction added to the fixed bed reactor is 0.1 mL / min-0.5 mL / min, for example, it can be 0.1 mL / min, 0.2 mL / min, 0.3 mL / min, 0.4 mL / min, 0.5 mL / min or any value between 0.1 mL / min and 0.5 mL / min, more preferably 0.4 mL / min.

[0064] In a preferred embodiment, after the catalytic hydrogenation in S2 is completed, the process further comprises: distilling the product after the catalytic hydrogenation reaction under normal pressure, filtering and drying the product to obtain the 1,3-bis[(trihydroxymethyl)methylamino]propane.

[0065] After the catalyst in the catalytic hydrogenation product is recovered, the remaining liquid product is distilled at atmospheric pressure. After 2 / 3 of the organic solvent in the liquid product evaporates, the distillation is stopped, and the remaining product is cooled to 0°C-5°C, and a solid product is precipitated. The remaining product after cooling is filtered and dried to obtain 1,3-bis[(trihydroxymethyl)methylamino]propane.

[0066] The embodiments of the present application will be described in detail below in conjunction with specific examples, but it will be appreciated by those skilled in the art that the following examples are only used to illustrate the present application and should not be considered as limiting the scope of the present application. If specific conditions are not specified in the examples, they are carried out according to normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0067] Example 1

[0068] This embodiment provides a method for preparing 1,3-bis[(trihydroxymethyl)methylamino]propane, which specifically comprises:

[0069] (1) Add 121 g of tromethamine (molecular weight 121, 1.0 mol), 400 mL of methanol, and 36.7 g of malondialdehyde (molecular weight 72, 0.51 mol) into a 1 L stainless steel hydrogenation kettle, seal the hydrogenation kettle, introduce nitrogen, and then heat to 80° C. for condensation reaction for 5 hours;

[0070] (2) After sampling and testing to confirm that the mass proportion of residual tromethamine in the product after the condensation reaction of step (1) is less than 0.3%, the hydrogenation kettle is cooled to room temperature, and 5 g of palladium-carbon catalyst containing 5% palladium is added to 50 mL of methanol, and pumped into the hydrogenation kettle under negative pressure, and hydrogen is introduced to replace the nitrogen therein until the pressure in the kettle reaches 2.0 MPa, and the hydrogenation kettle is heated to 45° C. to carry out hydrogenation reaction for 6 hours;

[0071] (3) After the hydrogenation reaction in step (2) is completed, the hydrogenation kettle is cooled to room temperature to release hydrogen, and the catalyst in the product is filtered out. The remaining liquid is distilled at atmospheric pressure. When 2 / 3 of the methanol is evaporated, the atmospheric distillation is stopped. The remaining distillation product is cooled to between 0 and 5° C., filtered, and dried to obtain a solid product of 1,3-bis[(trihydroxymethyl)methylamino]propane.

[0072] Figure 1 The nuclear magnetic resonance hydrogen spectrum (1H-HMR, 400MHz) of the prepared solid product in DMSO-d6 is given in the figure. From the figure, we can see that there are 4 very obvious absorption peaks, among which the absorption peak corresponding to δ4.25ppm is the hydrogen on the hydroxyl group -OH; the absorption peak corresponding to δ3.25ppm is the hydrogen on the methylene -CH2- connected to the hydroxyl group; the absorption peak corresponding to δ2.6ppm is the hydrogen on the methylene -CH2- connected to the nitrogen; the absorption peak corresponding to δ1.4ppm is the hydrogen on the methylene -CH2- located in the middle and connected to the two methylene groups on the left and right; the number ratios of these four hydrogen atoms are 6:12:4:2, which is basically close to the ratio of the intensities of these four absorption peaks.

[0073] Example 2

[0074] Same as Example 1, except that the catalyst in step (2) is replaced by a palladium-carbon catalyst containing 10% palladium.

[0075] Example 3

[0076] Same as Example 1, except that the catalyst in step (2) is replaced by a platinum-carbon catalyst containing 5% platinum.

[0077] Example 4

[0078] Same as Example 1, except that the catalyst in step (2) is replaced by a platinum-carbon catalyst containing 10% platinum.

[0079] Example 5

[0080] Same as Example 1, except that the catalyst in step (2) is replaced by a ruthenium-carbon catalyst containing 5% ruthenium.

[0081] Example 6

[0082] Same as Example 1, except that the catalyst in step (2) is replaced by a ruthenium-carbon catalyst containing 10% ruthenium.

[0083] Example 7

[0084] Same as Example 1, except that the catalyst in step (2) is replaced by a Raney nickel catalyst.

[0085] Example 8

[0086] Same as Example 1, except that the methanol in step (1) and step (2) is replaced by ethanol.

[0087] Example 9

[0088] Same as Example 3, except that the methanol in step (1) and step (2) is replaced by ethanol.

[0089] Example 10

[0090] Same as Example 5, except that the methanol in step (1) and step (2) is replaced by ethanol.

[0091] Embodiment 11

[0092] Same as Example 7, except that the methanol in step (1) and step (2) is replaced by ethanol.

[0093] Example 12

[0094] This embodiment provides a method for preparing 1,3-bis[(trihydroxymethyl)methylamino]propane, which specifically comprises:

[0095] (1) Add 121 g of tromethamine, 400 mL of methanol, and 36.7 g of malondialdehyde into a 1 L stainless steel hydrogenation kettle, seal the hydrogenation kettle, introduce nitrogen, and then heat to 80° C. for condensation reaction for 5 hours;

[0096] (2) After sampling and testing to confirm that the mass proportion of residual tromethamine in the product after the condensation reaction of step (1) is less than 0.3%, the hydrogenation kettle is cooled to room temperature, and 5g of fixed bed palladium carbon catalyst (the catalyst is a fixed bed catalyst of Xunkai Chemical, model PMCAT-110) is filled into the fixed bed reactor. The temperature of the fixed bed reactor is set to 45°C, the flow rate of the liquid product of the condensation reaction is 0.3mL / min, and the back pressure of the hydrogen introduced is adjusted to 2.0MPa with a back pressure valve, and then the liquid product is collected;

[0097] (3) The liquid product collected in step (2) is subjected to atmospheric distillation. When 2 / 3 of the methanol solvent is evaporated, the atmospheric distillation is stopped, and the remaining product is cooled to between 0 and 5° C., filtered, and dried to obtain a solid product of 1,3-bis[(trihydroxymethyl)methylamino]propane.

[0098] Comparative Example 1

[0099] In this comparative example, the preparation method disclosed in patent CN101376635A was used to prepare 1,3-bis[(trihydroxymethyl)methylamino]propane.

[0100] According to Example 4 in the patent, the experiment was carried out, and the reaction principle was as follows:

[0101]

[0102] Tromethamine and 1,3-dibromopropane in a molar ratio of 6:1 were added to 1500 mL of ethanol solution, reacted under reflux for 12 hours, deep-cold crystallized for 2 hours, filtered with suction, and HBr was added for acidification and crystallization to obtain 1,3-bis[(trihydroxymethyl)methylamino]propane hydrobromide. The product hydrobromide was filtered with suction, ethanol was added, alkalized with NaOH, recrystallized, and dried to obtain crude 1,3-bis[(trihydroxymethyl)methylamino]propane. The crude product was crystallized from ethanol to obtain a pure product with a yield of 79% and a purity of 96%.

[0103] By comparison, it can be found that the amount of tromethamine used as the raw material in the comparative example is much larger than the amount of tromethamine required in the preparation method of the present application.

[0104] Comparative Example 2

[0105] 1,3-bis[(trihydroxymethyl)methylamino]propane was prepared by using the preparation method disclosed in patent CN114591187A.

[0106] Among them, the reaction principle of the patent embodiment 1 is as follows:

[0107]

[0108] Compound 2 needs to be self-made, and the molar ratio of compound 2 to tromethamine needs to reach 1:3. The yield of the crude product is 68%, which is higher than the molar ratio of tromethamine used in the preparation method of the present application, and lower than the yield of the product prepared in the present application.

[0109] The reaction principle of the patent embodiment 7 is as follows:

[0110]

[0111] Obviously, the product sulfite is inevitably generated during the second step of the reaction, so the crude product yield is only 51%, which is much lower than Example 1 of the present application.

[0112] The molar yield and purity of the 1,3-bis[(trihydroxymethyl)methylamino]propane products prepared under different conditions in the above Examples 1-12 and Comparative Examples 1-2 were tested and statistically analyzed, and the results are shown in Table 1.

[0113] Table 1

[0114]

[0115]

[0116] From Table 1, it can be analyzed that the molar yield of the product finally obtained by using methanol as an organic solvent in Examples 1-12 is higher than the molar yield of the product prepared in ethanol. This is because after atmospheric distillation, when precipitated in the remaining 1 / 3 solvent, the solubility of 1,3-bis[(trihydroxymethyl)methylamino]propane product in methanol is worse than that in ethanol. Therefore, under the same conditions, the molar yield of the product prepared using methanol as an organic solvent is slightly higher than the molar yield of the product prepared using ethanol as an organic solvent, but this does not affect the purity of the product after purification. For the influence of the catalyst, the best is to use a palladium carbon catalyst, followed by a Raney nickel catalyst, a ruthenium carbon catalyst, and a platinum carbon catalyst. Because the yields of a palladium carbon catalyst containing 5% palladium and a palladium carbon catalyst containing 10% palladium are close, for cost considerations, it is more reasonable to use a palladium carbon catalyst containing 5% palladium in the process of mass production and preparation.

[0117] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit it. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present application.

[0118] In addition, those skilled in the art will appreciate that, although some embodiments herein include certain features included in other embodiments but not other features, the combination of features of different embodiments is meant to be within the scope of the present application and form different embodiments. For example, any of the above-mentioned claimed embodiments may be used in any combination. The information disclosed in this background technology section is intended only to deepen the understanding of the overall background technology of the present application and should not be regarded as an admission or in any form of implication that the information constitutes prior art known to those skilled in the art.

Claims

1. A method for preparing 1,3-bis[(trihydroxymethyl)methylamino]propane, characterized in that: include: Mixing raw materials consisting of tromethamine, malondialdehyde and an organic solvent and performing a condensation reaction in an inert gas atmosphere; Catalytically hydrogenating the product of the condensation reaction to obtain the 1,3-bis[(trihydroxymethyl)methylamino]propane; The condensation reaction temperature is 70°C-90°C, and the time is 4h-6h; The organic solvent is selected from at least one of methanol, ethanol and isopropanol; The inert gas is selected from at least one of nitrogen, argon and helium; The catalyst includes any one of a platinum-carbon catalyst, a palladium-carbon catalyst, a ruthenium-carbon catalyst, and a Raney nickel catalyst; The condensation reaction and the catalytic hydrogenation are carried out continuously in the same reactor; Alternatively, the product of the condensation reaction is added to a fixed bed reactor for the catalytic hydrogenation.

2. The preparation method according to claim 1, characterized in that The molar ratio of the tromethamine to the malondialdehyde is 2:1-1.

05.

3. The preparation method according to claim 2, characterized in that: The molar concentration of the tromethamine in the organic solvent is 2 mmol / mL-3 mmol / mL.

4. The preparation method according to claim 1, characterized in that: Prior to the hydrogenation, the method comprises: The composition of the product of the condensation reaction is detected. If the mass proportion of the residual tromethamine is less than 0.3%, the product of the condensation reaction is cooled to room temperature and then the catalyst is added.

5. The preparation method according to claim 4, characterized in that: The mass of the catalyst is 0.01 to 0.1 times the mass of the tromethamine.

6. The preparation method according to claim 5, characterized in that: The catalyst is a palladium-carbon catalyst containing 5wt%-10wt% of palladium.

7. The preparation method according to claim 1, characterized in that: At least one of the following conditions is met: h. The gas pressure of the catalytic hydrogenation is 1MPa-3MPa; i. The temperature of the catalytic hydrogenation is 40°C-60°C and the time is 5h-8h.

8. The preparation method according to claim 1, characterized in that: The flow rate of the product of the condensation reaction added to the fixed bed reactor is 0.1 mL / min-0.5 mL / min.

9. The preparation method according to any one of claims 1 to 8, characterized in that: After the catalytic hydrogenation is completed, the following steps are also included: The product after the catalytic hydrogenation reaction is subjected to atmospheric distillation, suction filtration, and drying to obtain the 1,3-bis[(trihydroxymethyl)methylamino]propane.

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