Process and apparatus for the preparation of 2,5-bis(aminomethyl)furan based on the continuous flow method

Abstract

The application provides a method and device for preparing 2,5-di(amino methyl)furan based on a continuous flow method, and belongs to the technical field of organic synthesis. The method for preparing 2,5-di(amino methyl)furan based on the continuous flow method comprises the following steps: providing a liquid phase channel and a gas phase channel, conveying a reaction substrate, an amine compound, a reducing agent and an organic solvent through the liquid phase channel, conveying ammonia through the gas phase channel, respectively conveying them into a mixer, mixing in the mixer and then flowing into a reaction channel provided with a catalyst fixed bed to perform a reaction, and obtaining a reaction liquid containing 2,5-di(amino methyl)furan. The reaction substrate is selected from 2,5-furandicarboxaldehyde, 5-hydroxymethylfurfural and 5-hydroxymethyl-2-furfurylamine, and the amine compound is selected from any one of organic solutions of methylamine or ethylamine, propylamine, butylamine, butanediamine, amylamine, hexylamine and oleylamine.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and particularly relates to a method and apparatus for preparing 2,5-bis(aminomethyl)furan based on a continuous flow method. Background Technology

[0002] With rapid industrialization, pressing environmental problems have prompted researchers to seek new renewable resources and environmentally friendly alternatives to minimize dependence on fossil fuels. After years of research, biomass has emerged as a promising carbon source for future chemical production. 5-Hydroxymethylfurfural (HMF) is considered an intermediate linking biomass resources and the petrochemical industry. The reductive amination of HMF and its derivatives is an important reaction that yields the important organic nitrogen compound, furanyl primary diamine 2,5-di(aminomethyl)furan (BAMF). As a substitute for petroleum-based diamines, furanyl diamines are not only used as key intermediates in the synthesis of pharmaceuticals and agrochemicals but are also widely used in the production of polyamides, polyurethanes, and polyureas. BAMF offers numerous possibilities for constructing novel biopolymers with unique functions. However, the existing technologies for producing BAMF have the following problems: (1) The reductive amination of asymmetric functional groups in HMF is difficult, resulting in low selectivity of BAMF; (2) Hydrogen and ammonia are often used for simultaneous pressurization in industrial production, which poses certain safety risks; (3) BAMF products are difficult to separate and purify.

[0003] Therefore, there is an urgent need to develop a method that is highly selective, safe, and allows for easy product separation during the reductive amination reaction. Summary of the Invention

[0004] In view of the above, and in response to the aforementioned technical problems, the present invention provides an apparatus for preparing 2,5-bis(aminomethyl)furan based on a continuous flow method, in order to at least partially solve the above technical problems. The technical solution provided by the present invention is as follows.

[0005] As a first aspect of the present invention, a method for preparing 2,5-di(aminomethyl)furan based on a continuous flow method is provided, comprising:

[0006] The system provides liquid and gas channels, through which the reaction substrate, amine compound, reducing agent, and organic solvent are delivered to a mixer via the liquid channel and ammonia via the gas channel. After mixing in the mixer, the mixture flows into a reaction channel equipped with a catalyst fixed bed to react and obtain a reaction solution containing 2,5-di(aminomethyl)furan. The reaction substrate is selected from 2,5-furandicarboxaldehyde, 5-hydroxymethylfurfural, and 5-hydroxymethyl-2-furanmethylamine, and the amine compound is selected from any one of organic solutions of methylamine or ethylamine, propylamine, butylamine, butanediamine, pentylamine, hexylamine, and oleylamine.

[0007] As a second aspect of the present invention, an apparatus for preparing 2,5-di(aminomethyl)furan based on a continuous flow method is provided, for performing the above-described method for preparing 2,5-di(aminomethyl)furan based on a continuous flow method, the apparatus comprising:

[0008] A liquid phase channel for feeding liquid phase reactants and a gas phase channel for feeding gaseous ammonia; a mixer connected to the liquid phase channel and the gas phase channel respectively, for mixing the liquid phase reactants and gaseous ammonia in the mixer; and a reaction channel located downstream of the mixer, wherein a catalyst fixed bed is provided in the reaction channel.

[0009] Based on the above technical solution, the method and apparatus for preparing 2,5-di(aminomethyl)furan based on the continuous flow method provided by the present invention have at least one of the following beneficial effects:

[0010] (1) In an embodiment of the present invention, the liquid-phase reactant and the gaseous ammonia material are separated and continuously flowed into a mixer through liquid-phase channels and gas-phase channels, respectively, and mixed in the mixer. After mixing, the mixture flows into a reaction channel for a reducing amination reaction. The liquid-phase reactant and the gaseous ammonia material are continuously mixed in the mixer and react continuously in the reaction channel (microreactor). The reaction channel has a large specific surface area, which enhances the heat and mass transfer performance, improves the conversion rate and selectivity of the reaction, reduces by-products, realizes continuous production, and the continuous flow reaction method facilitates scale-up and purification.

[0011] (2) In an embodiment of the present invention, a continuous flow device is constructed by connecting the liquid phase channel and the gas phase channel to a mixer, and connecting the outlet of the mixer to a reaction channel. The liquid phase reactants and gaseous ammonia materials in the liquid phase channel are continuously fed into the mixer for mixing. After mixing, the mixture continuously flows into the reaction channel equipped with a catalyst fixed bed for continuous reaction, thereby obtaining a product containing 2,5-di(aminomethyl)furan. Furthermore, the reaction device of the present invention has a simple structure, is easy to assemble, and is safer than a reaction vessel. Attached Figure Description

[0012] Figure 1 This is a schematic diagram of the apparatus for preparing 2,5-bis(aminomethyl)furan based on the continuous flow method in an embodiment of the present invention;

[0013] Figure 2 This is the 1H NMR spectrum of the crude 2,5-bis(aminomethyl)furan product prepared by the continuous flow method in Example 1 of this invention;

[0014] Figure 3 This is the 1H NMR spectrum of the pure 2,5-bis(aminomethyl)furan product prepared by the continuous flow method in Example 1 of this invention. Detailed Implementation

[0015] To make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described in detail below with reference to specific embodiments and accompanying drawings.

[0016] To address the challenges of scale-up in the current production of 2,5-bis(aminomethyl)furan (BAMF), including low selectivity and difficulty in product separation, this invention proposes a continuous flow method combined with microchemical processes for the preparation of 2,5-bis(aminomethyl)furan. Microchemical technology, by reducing the dispersion scale of the system, enhancing mixing and transport, and improving the controllability and efficiency of the reaction process, scales up micro-devices based on the principle of "scale-up," allowing laboratory results to be directly applied to industrial processes for continuous large-scale production. Continuous flow microreactors are the core component of microchemical technology. Their characteristic dimensions are much smaller than traditional reactors (such as reaction vessels), and microreactors have a large specific surface area, which enhances heat and mass transfer performance, significantly improving reaction conversion and selectivity. The continuous flow technology enables reactions to occur in a shorter time, improving reaction efficiency and facilitating scale-up.

[0017] Specifically, the present invention provides a method for preparing 2,5-di(aminomethyl)furan based on a continuous flow method, comprising:

[0018] The system provides liquid and gas channels, through which the reaction substrate, amine compound, reducing agent, and organic solvent are delivered to a mixer via the liquid channel and ammonia via the gas channel. After mixing in the mixer, the mixture flows into a reaction channel equipped with a catalyst fixed bed to react and obtain a reaction solution containing 2,5-di(aminomethyl)furan. The reaction substrate is selected from 2,5-furandicarboxaldehyde (DFF), 5-hydroxymethylfurfural (HMF), and 5-hydroxymethyl-2-furanmethylamine (HMFA). The amine compound is selected from any one of organic solutions of methylamine or ethylamine, propylamine, butylamine, butanediamine, pentylamine, hexylamine, and oleylamine.

[0019] In embodiments of the present invention, the liquid-phase reactants and gaseous ammonia are separated and introduced into the mixer through liquid-phase and gas-phase channels, respectively, where they are mixed. The mixture is then continuously fed into the reaction channel (microreactor) for continuous reaction. In the microreactor, the large specific surface area of ​​the reaction channel enhances heat and mass transfer performance, enabling the synthesis of 2,5-di(aminomethyl)furan via reductive amination. Furthermore, the continuous flow technology rapidly improves reaction selectivity and yield in a shorter time, produces fewer byproducts, and enables continuous production, thus accelerating the industrial-scale preparation of furanyl diamine. Moreover, the continuous flow method facilitates reaction scale-up and purification. Additionally, by filling the catalyst in a fixed bed, it is not necessary to remove the catalyst from the product after the reaction, reducing the catalyst's influence on the product, and the catalyst in the fixed bed can be recycled.

[0020] According to embodiments of the present invention, the reducing agent is selected from sodium borohydride or sodium cyanoborohydride. Using a reducing agent instead of the traditional flammable and explosive hydrogen reducing agent ensures experimental safety. Direct contact between the reducing agent, such as sodium borohydride, and the reaction substrate and organic solvent promotes the reduction reaction and allows for flexible control based on the reaction amount. The organic solvent is selected from methanol or tetrahydrofuran. Specifically, the organic solvent in the organic solution of methylamine or ethylamine in the reaction substrate is selected from methanol or tetrahydrofuran, preferably methanol. The reaction substrate is preferably 2,5-furandicarboxaldehyde (DFF). Further, the concentration of the reaction substrate is 0.05–0.5 mol / L, preferably 0.075 mol / L. The amine compound, acting as an aldehyde scavenger, has a concentration of 0.15–1.5 mol / L, preferably 0.2255 mol / L. The amine compound is preferably propylamine or butylamine.

[0021] According to an embodiment of the present invention, the reaction channel is a microreactor, which is much smaller than a traditional reactor, such as a reaction vessel. The microreactor has a larger specific surface area compared to a reaction vessel, thus enhancing heat and mass transfer performance. The reaction channel of the present invention has a spiral structure, with an inner diameter of 1-2 mm, an outer diameter of 3-4 mm, and a tube length of 5-15 m. The preferred dimensions of the reaction channel are 1.5 mm * 3 mm * 10 m. The material of the reaction channel can be stainless steel, or other materials with high temperature resistance (200-300℃), high pressure resistance (8-10 MPa), and corrosion resistance. A fixed bed is arranged inside the reaction channel, and the fixed bed is filled with a catalyst. The catalyst is selected from Raney nickel, Raney cobalt, and Ru / C, preferably Raney nickel. The catalyst dosage is 100-500 mg / L, and the preferred catalyst concentration is 250 mg. In embodiments of the present invention, the reaction channel serves as a microreactor. Designed with a helical structure, the channel's large specific surface area and the eddy current effect created by the liquid significantly improve heat and mass transfer performance and shorten heating time. A fixed bed filled with catalyst within the reaction channel provides a larger contact area between the catalyst, the mixture, and ammonia, enhancing reaction efficiency. Furthermore, the catalyst, packed in the fixed bed, is easily recyclable and retains good catalytic performance even after multiple cycles. Moreover, the catalyst does not need to be removed from the reaction solution, simplifying product processing.

[0022] According to an embodiment of the present invention, the reaction channel (i.e., microreactor) is heated by a heating medium during the reaction process. The heating device can be an oil bath, and the heating medium is selected from dimethyl silicone oil. After heating, the external temperature of the reaction channel is 50-150°C. After the liquid phase material and the gas phase material are mixed, the residence time in the reaction channel is 5-120 min, and the preferred reaction residence time is 30 min.

[0023] The reaction pathways involved in the synthesis of BAMF from HMF and HMFA are as follows:

[0024]

[0025] The reaction pathways involved in the synthesis of BAMF from DFF

[0026]

[0027] According to an embodiment of the present invention, a plunger pump is installed in the liquid phase channel to control the flow rate within the liquid phase channel, which is 0.148–3.54 mL / min. An ammonia storage tank is connected to the gas phase channel to supply ammonia to the gas phase channel. Further, a back pressure valve is installed in the gas phase channel to control the ammonia pressure, which is 0.1–5 MPa, preferably 1.5 MPa. The ammonia storage tank is connected to the back pressure valve via a flow meter to control the ammonia flow rate, which is maintained at a stable flow rate of 5 mL / min.

[0028] According to embodiments of the present invention, the method for preparing 2,5-di(aminomethyl)furan based on a continuous flow method further includes: after the reaction is completed, quenching treatment is performed using a quenching device to obtain a reaction solution containing 2,5-di(aminomethyl)furan; and unreacted ammonia is removed using an ammonia absorption device. The quenching method can be ice bath quenching to terminate the reaction. After quenching, the obtained reaction solution containing 2,5-di(aminomethyl)furan is purified to obtain relatively pure 2,5-di(aminomethyl)furan, and the product is qualitatively and quantitatively analyzed using any one of the following analytical instruments: gas chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy (HMR). The purification method can be: removing organic solvents and low-boiling-point byproducts from the product by vacuum distillation, then extracting the reaction product with deionized water and dichloromethane, extracting the target product into the aqueous phase. Subsequently, water in the aqueous phase is removed by rotary evaporation, and the product is recrystallized to obtain purified 2,5-di(aminomethyl)furan (BAMF). In addition, using an ammonia absorption device to absorb unreacted ammonia reduces ammonia pollution to the environment.

[0029] As a second aspect of the invention, an apparatus for preparing 2,5-di(aminomethyl)furan based on a continuous flow method is provided for performing the method described in the above embodiments. The apparatus includes: a liquid phase channel for feeding liquid reactants and a gas phase channel for feeding gaseous ammonia; a mixer connected to both the liquid phase channel and the gas phase channel; and a reaction channel located downstream of the mixer, wherein a catalyst fixed bed is disposed in the reaction channel. The liquid reactants and gaseous ammonia are mixed in the mixer and then flow into the reaction channel with the catalyst fixed bed to react, yielding a reaction solution containing 2,5-di(aminomethyl)furan.

[0030] In an embodiment of the present invention, a continuous flow device is constructed by connecting the liquid phase channel and the gas phase channel to a mixer, and connecting the outlet of the mixer to a reaction channel. This reaction device has a simple structure, is easy to build, and is safer than a reaction vessel. The liquid phase reactants and gaseous ammonia materials in the liquid phase channel are continuously fed into the mixer for mixing. After mixing, the mixture continuously flows into the reaction channel equipped with a catalyst fixed bed for continuous reaction, thereby obtaining a product containing 2,5-bis(aminomethyl)furan.

[0031] Figure 1 This is a schematic diagram of the apparatus for preparing 2,5-di(aminomethyl)furan based on the continuous flow method in an embodiment of the present invention. The following is in conjunction with... Figure 1 Please provide a detailed explanation.

[0032] like Figure 1 As shown, the apparatus for preparing 2,5-di(aminomethyl)furan based on the continuous flow method of the present invention includes: a liquid phase channel 101, a gas phase channel 102, a mixer 103, a fixed bed 104, a reaction channel 105, and an ammonia storage tank 109.

[0033] The liquid phase channel 101 is used to feed liquid phase reactants and transport them to the mixer 103. The liquid phase reactants include reaction substrates, amine compounds, reducing agents, and organic solvents. The gas phase channel 102 is connected to the ammonia storage tank 109 and is used to feed ammonia gas and transport it to the mixer 103.

[0034] Mixer 103 is connected at one end to liquid phase channel 101 and gas phase channel 102, and at the other end to reaction channel 105. Mixer 103 is a four-way valve micromixer, configured to receive and mix liquid reactants and ammonia gas, then continuously feed the mixture into reaction channel 105 for reductive amination. Reaction channel 104 is a microreactor with a spiral structure. A fixed bed 104 is arranged on the spiral structure, filled with a catalyst for catalyzing the reductive amination reaction. The reaction channel is made of stainless steel, with an inner diameter of 1-2 mm, an outer diameter of 3-4 mm, and a length of 5-15 m. The catalyst is selected from Raney nickel, Raney cobalt, or Ru / C.

[0035] Furthermore, continue as Figure 1 As shown, the apparatus for preparing 2,5-di(aminomethyl)furan based on the continuous flow method further includes: a quenching device (not shown), an ammonia absorption device 106, a purification device (not shown), a heating device, a control device, and an analytical detection device 107.

[0036] A quenching device, connected to the outlet of the reaction channel, is used to quench the reaction; the quenching method can be ice bath quenching. An ammonia absorption device 106, connected to the outlet of the reaction channel 105, is used to remove unreacted ammonia gas from the reaction channel 105. A purification device, connected to the reaction channel 105 or the quenching device, is used to purify the reaction solution containing 2,5-di(aminomethyl)furan to obtain pure 2,5-di(aminomethyl)furan. The control device includes a plunger pump, a flow meter, and a back pressure valve 108. A plunger pump is installed on the liquid phase channel 101 to control the flow rate in the liquid phase channel 101. An ammonia storage tank 109 is connected to the gas phase channel 102 to supply ammonia to the gas phase channel 102. A back pressure valve 108 is installed on the gas phase channel 102 near the mixer 103. A flow meter (not shown) is installed between the ammonia storage tank 109 and the back pressure valve 108 to control the ammonia flow rate in the gas phase channel 102. The flow meter can be a rotor flow meter. The reaction channel 105 is placed inside a heating device configured to heat the reaction channel 105. The heating medium in the heating device is dimethyl silicone oil. An analytical detection device 107 is connected to the outlet of the reaction channel 105 to detect the products of the reductive amination reaction.

[0037] The apparatus for preparing 2,5-di(aminomethyl)furan based on the continuous flow method is as follows: Figure 1 After the framework shown is assembled and connected, methanol and isopropanol cleaning agent are first pumped in to clean the reaction system, followed by purging with N2. The nitrogen cylinder is closed, the ammonia storage tank 109 is opened, and the back pressure valve 108 is fixed to a certain pressure to deliver ammonia to the mixer 103. Simultaneously, a plunger pump is used to pump the reaction solution (reaction substrate, reducing agent, organic solvent, and amine compounds) into the mixer 103. After the liquid and gas phases are mixed, they first enter a fixed bed and undergo a reductive amination reaction for a certain time under the catalysis of a catalyst through a stainless steel microreactor. After the reaction is complete, the reaction solution is recovered, and the reaction mixture is qualitatively and quantitatively analyzed using the analytical detection device 107. Finally, the reaction mixture is purified. The purification steps are as follows: first, the organic solvent and low-boiling-point byproducts are removed by vacuum distillation; then, the reaction product is extracted with deionized water and dichloromethane, and BAMF is extracted into the aqueous phase; then, the aqueous phase is removed by rotary evaporation, and the product is recrystallized to obtain pure BAMF.

[0038] The method and apparatus for preparing 2,5-di(aminomethyl)furan based on the continuous flow method are described in detail below with reference to specific embodiments and accompanying drawings. However, the following embodiments are only used to explain the technical solution of the present invention, and the scope of protection of the present invention is not limited thereto.

[0039] Example 1

[0040] Experiments were conducted in the reaction channel to synthesize BAMF by DFF reductive amination.

[0041] After the reaction apparatus was connected and cleaned, the ammonia storage tank was opened and the back pressure valve was fixed at 0–5 MPa. Then, a mixed solution of 0.075 mol / L DFF, 0.3 mol / L sodium borohydride, and 0.225 mol / L n-butylamine in methanol was pumped in at a flow rate of 0.148–3.54 mL / min. The liquid and gas phases were mixed in a mixer and then passed through a fixed-bed reactor containing Raney nickel. The mixture was introduced into a 1.5 mm * 3 mm * 10 m stainless steel microchannel coil (reaction channel) at 100 °C for 30 minutes. The reaction solution was recovered at the downstream end of the post-processing unit and subjected to qualitative and quantitative analysis. The reaction mixture was then purified. The purification steps were as follows: first, organic solvents and low-boiling-point byproducts were removed by vacuum distillation; then, the reaction product was extracted with deionized water and dichloromethane, and BAMF was extracted into the aqueous phase; the aqueous phase was removed by rotary evaporation, and the product was recrystallized to obtain pure BAMF. Qualitative and quantitative analysis was performed using gas chromatography-mass spectrometry (GC-MS), and the specific test results are shown in Table 1 (rows 1-4). Finally, the crude and pure BAMF samples were analyzed by proton nuclear magnetic resonance (NMR) spectroscopy, as shown in the table below. Figure 2 and Figure 3 As shown.

[0042] The preparation method of DFF is as follows: 25g of glucose, 2.5g of commercial Ru / C catalyst, and 250g of toluene are added to a 500mL reactor. The reactor is then purged three times with a stream of N2, and O2 at a pressure of 10MPa is introduced. The reaction is carried out at 383K for 10h. After the reaction is completed, the reaction solvent is removed by rotary evaporation, and the product DFF is purified by vacuum distillation.

[0043] Example 2:

[0044] Experiments were conducted in the reaction channel to synthesize BAMF by DFF reductive amination.

[0045] After the reaction apparatus was connected and cleaned, the ammonia storage tank was opened and the back pressure valve was fixed at 1 MPa. Then, a mixed solution of DFF (0.05–0.5 mol / L), sodium borohydride (0.3 mol / L), and n-butylamine (0.225 mol / L) in methanol was pumped in at a flow rate of 0.148–3.54 mL / min. The liquid and gas phases were mixed in a mixer and then passed through a fixed-bed reactor containing Raney nickel. The mixture was introduced into a 1.5 mm * 3 mm * 10 m stainless steel microchannel coil (reaction channel) at 100 °C for 30 minutes. The reaction solution was recovered at the downstream end of the post-processing unit and subjected to qualitative and quantitative analysis. The reaction mixture was then purified. The purification steps were as follows: first, organic solvents and low-boiling-point byproducts were removed by vacuum distillation; then, the reaction product was extracted with deionized water and dichloromethane, and BAMF was extracted into the aqueous phase; the aqueous phase was removed by rotary evaporation, and the product was recrystallized to obtain pure BAMF. Qualitative and quantitative detection was performed using gas chromatography-mass spectrometry (GC-MS), and the specific test results are shown in Table 1 (rows 2, 5-7).

[0046] Example 3:

[0047] Experiments were conducted in the reaction channel to synthesize BAMF by DFF reductive amination.

[0048] After the reaction apparatus was connected and cleaned, the ammonia storage tank was opened and the back pressure valve was fixed at 1 MPa. Then, a methanol mixture of 0.075 mol / L DFF, 0.3 mol / L sodium borohydride, and 0.15–1.5 mol / L n-butylamine was pumped in at a flow rate of 0.148–3.54 mL / min. The liquid and gas phases were mixed in a mixer and then passed through a fixed-bed reactor containing Raney nickel. The mixture was then introduced into a 1.5 mm * 3 mm * 10 m stainless steel microchannel tray (reaction channel) at 100 °C for 30 minutes. The reaction solution was recovered at the downstream end of the post-processing unit and subjected to qualitative and quantitative analysis. The reaction mixture was then purified. The purification steps were as follows: first, organic solvents and low-boiling-point byproducts were removed by vacuum distillation; then, the reaction product was extracted with deionized water and dichloromethane, and BAMF was extracted into the aqueous phase; the aqueous phase was removed by rotary evaporation, and the product was recrystallized to obtain pure BAMF. Qualitative and quantitative detection was performed using gas chromatography-mass spectrometry (GC-MS), and the specific test results are shown in Table 1 (rows 2, 8-11).

[0049] Example 4:

[0050] Experiments were conducted in the reaction channel (microreactor) to synthesize BAMF by the reductive amination of DFF.

[0051] After the reaction apparatus was connected and cleaned, the ammonia storage tank was opened and the back pressure valve was fixed at 1 MPa. Then, a mixed solution of 0.075 mol / L DFF, 0.3 mol / L sodium borohydride, and 0.225 mol / L n-butylamine in methanol was pumped in at a flow rate of 0.148–3.54 mL / min. The liquid and gas phases were mixed in a mixer and then passed through a fixed-bed reactor containing Raney nickel. The mixture was then introduced into a stainless steel microchannel coil (reaction channel) with an inner diameter of 1.0–2.0 mm at 100 °C for 30 minutes. The reaction solution was recovered at the downstream end of the post-processing unit and subjected to qualitative and quantitative analysis. The reaction mixture was then purified. The purification steps were as follows: first, organic solvents and low-boiling-point byproducts were removed by vacuum distillation; then, the reaction product was extracted with deionized water and dichloromethane, and BAMF was extracted into the aqueous phase; the aqueous phase was removed by rotary evaporation, and the product was recrystallized to obtain pure BAMF. Qualitative and quantitative detection was performed using gas chromatography-mass spectrometry (GC-MS), and the specific test results are shown in Table 1 (rows 2, 12-13).

[0052] Example 5:

[0053] Experiments were conducted in the reaction channel (microreactor) to synthesize BAMF by DFF reductive amination.

[0054] After the reaction apparatus was connected and cleaned, the ammonia storage tank was opened and the back pressure valve was fixed at 1 MPa. Then, a mixed solution of 0.075 mol / L DFF, 0.3 mol / L sodium borohydride, and 0.225 mol / L n-butylamine in methanol or tetrahydrofuran was pumped in at a flow rate of 0.148–3.54 mL / min. The liquid and gas phases were mixed in a mixer and then passed through a fixed-bed reactor containing Raney nickel. The mixture was introduced into a 1.5 mm * 3 mm * 10 m stainless steel microchannel coil (reaction channel) at 100 °C for 30 minutes. The reaction solution was recovered at the downstream end of the post-processing unit and subjected to qualitative and quantitative analysis. The reaction mixture was then purified. The purification steps were as follows: first, organic solvents and low-boiling-point byproducts were removed by vacuum distillation; then, the reaction product was extracted with deionized water and dichloromethane, and BAMF was extracted into the aqueous phase; the aqueous phase was removed by rotary evaporation, and the product was recrystallized to obtain pure BAMF. Qualitative and quantitative detection was performed using gas chromatography-mass spectrometry (GC-MS), and the specific test results are shown in Table 1 (rows 2 and 14).

[0055] Example 6:

[0056] Experiments were conducted in the reaction channel (microreactor) to synthesize BAMF by DFF reductive amination.

[0057] After the reaction apparatus was connected and cleaned, the ammonia storage tank was opened and the back pressure valve was fixed at 1 MPa. Then, a methanol mixture of 0.075 mol / L DFF, 0.3 mol / L sodium borohydride, and 0.225 mol / L n-butylamine was pumped in at a flow rate of 0.148–3.54 mL / min. The liquid and gas phases were mixed in a mixer and then passed through a fixed-bed reactor equipped with Raney nickel, Raney cobalt, or Ru / C. The mixture was then introduced into a 1.5 mm * 3 mm * 10 m stainless steel microchannel coil (reaction channel) at 100 °C for 30 minutes. The reaction solution was recovered at the downstream end of the post-processing unit and subjected to qualitative and quantitative analysis. The reaction mixture was then purified. The purification steps were as follows: first, organic solvents and low-boiling-point byproducts were removed by vacuum distillation; then, the reaction product was extracted with deionized water and dichloromethane, and BAMF was extracted into the aqueous phase; the aqueous phase was removed by rotary evaporation, and the product was recrystallized to obtain pure BAMF. Qualitative and quantitative detection was performed using gas chromatography-mass spectrometry (GC-MS), and the specific test results are shown in Table 1 (rows 2, 15-16).

[0058] Example 7:

[0059] Experiments were conducted in the reaction channel (microreactor) to synthesize BAMF by DFF reductive amination.

[0060] After the reaction apparatus was connected and cleaned, the ammonia storage tank was opened and the back pressure valve was fixed at 1 MPa. Then, a methanol mixture of 0.075 mol / L DFF, 0.3 mol / L sodium borohydride, and 0.225 mol / L n-butylamine was pumped in at a flow rate of 0.148–3.54 mL / min. The liquid and gas phases were mixed in a mixer and then passed through a fixed-bed reactor equipped with Raney nickel, Raney cobalt, or Ru / C. The mixture was then introduced into a 1.5 mm * 3 mm * 10 m stainless steel microchannel tray (reaction channel) at 25–150 °C for 30 minutes. The reaction solution was recovered at the downstream end of the post-processing unit and subjected to qualitative and quantitative analysis. The reaction mixture was then purified. The purification steps were as follows: first, organic solvents and low-boiling-point byproducts were removed by vacuum distillation; then, the reaction product was extracted with deionized water and dichloromethane, and BAMF was extracted into the aqueous phase; the aqueous phase was removed by rotary evaporation, and the product was recrystallized to obtain pure BAMF. Qualitative and quantitative detection was performed using gas chromatography-mass spectrometry (GC-MS), and the specific test results are shown in Table 1 (rows 2, 17-19).

[0061] Example 8:

[0062] Experiments were conducted in the reaction channel (microreactor) to synthesize BAMF by DFF reductive amination.

[0063] After the reaction apparatus was connected and cleaned, the ammonia storage tank was opened and the back pressure valve was fixed at 1 MPa. Then, a methanol mixture of 0.075 mol / L DFF, 0.3 mol / L sodium borohydride, and 0.225 mol / L n-butylamine was pumped in at a flow rate of 0.148–3.54 mL / min. The liquid and gas phases were mixed in a mixer and then passed through a fixed-bed reactor equipped with Raney nickel, Raney cobalt, or Ru / C. The mixture was introduced at 100°C into a 1.5 mm * 3 mm * 10 m stainless steel microchannel coil (reaction channel) and reacted for 5–120 minutes. The reaction solution was recovered at the downstream end of the post-processing unit and subjected to qualitative and quantitative analysis. The reaction mixture was then purified. The purification steps were as follows: first, organic solvents and low-boiling-point byproducts were removed by vacuum distillation; then, the reaction product was extracted with deionized water and dichloromethane, and BAMF was extracted into the aqueous phase; the aqueous phase was removed by rotary evaporation, and the product was recrystallized to obtain pure BAMF. Qualitative and quantitative detection was performed using gas chromatography-mass spectrometry, and the specific test results are shown in Table 1 (rows 2-22).

[0064] Example 9:

[0065] Experiments were conducted in the reaction channel (microreactor) to synthesize BAMF by DFF reductive amination.

[0066] After the reaction apparatus was connected and cleaned, the ammonia storage tank was opened and the back pressure valve was fixed at 1 MPa. Then, a mixed solution of 0.075 mol / L DFF, 0.3 mol / L sodium borohydride, and 0.225 mol / L aliphatic amines (methylamine in methanol, ethylamine in methanol, propylamine, butylamine, butanediamine, pentylamine, hexylamine, and oleylamine) was pumped in at a flow rate of 0.148–3.54 mL / min. The liquid and gas phases were mixed in a mixer and then passed through a fixed-bed reactor containing Raney nickel. The mixture was then introduced into a 1.5 mm * 3 mm * 10 m stainless steel microchannel coil (reaction channel) at 100 °C for 30 minutes. The reaction solution was recovered at the downstream end of the post-processing unit and subjected to qualitative and quantitative analysis. The reaction mixture was then purified as follows: first, organic solvents and low-boiling-point byproducts were removed by vacuum distillation; then, the reaction product was extracted with deionized water and dichloromethane, and BAMF was extracted into the aqueous phase; the aqueous phase was removed by rotary evaporation, and the product was recrystallized to obtain pure BAMF. Qualitative and quantitative analysis was performed using gas chromatography-mass spectrometry (GC-MS), and the specific test results are shown in Table 1 (rows 23-29).

[0067] Example 10:

[0068] Experiments were conducted in the reaction channel (microreactor) to synthesize BAMF by HMF reduction amination.

[0069] After the reaction apparatus was connected and cleaned, the ammonia storage tank was opened and the back pressure valve was fixed at 1 MPa. Then, a methanol mixture of 0.075 mol / L HMF, 0.3 mol / L sodium borohydride, and 0.225 mol / L n-butylamine was pumped in at a flow rate of 0.148–3.54 mL / min. The liquid and gas phases were mixed in a mixer and then fed into a fixed catalyst bed. The mixture was then subjected to a reaction at a specific temperature through a 1.5 mm * 3 mm * 10 m stainless steel microchannel tray (reaction channel) for 30 minutes. The reaction solution was recovered, and the reaction mixture was qualitatively and quantitatively analyzed. The reaction mixture was then purified. The purification steps were as follows: first, organic solvents and low-boiling-point byproducts were removed by vacuum distillation; then, the reaction product was extracted with deionized water and dichloromethane, and BAMF was extracted into the aqueous phase; finally, the aqueous phase was removed by rotary evaporation, and the product was recrystallized to obtain pure BAMF. Qualitative and quantitative detection was performed using gas chromatography-mass spectrometry, and the specific test results are shown in Table 1 (row 30).

[0070] Example 11:

[0071] An experiment was conducted in the reaction channel (microreactor) to synthesize BAMF by reductive amination of a mixture of HMF and DFF.

[0072] After the reaction apparatus was connected and cleaned, the ammonia storage tank was opened and the back pressure valve was fixed at 1 MPa. Then, a methanol mixture of 0.075 mol / L HMF, 0.3 mol / L sodium borohydride, and 0.225 mol / L n-butylamine was pumped in at a flow rate of 0.148–3.54 mL / min. The liquid and gas phases were mixed in a mixer and then fed into a fixed catalyst bed. The mixture was then subjected to a reaction at a specific temperature through a 1.5 mm * 3 mm * 10 m stainless steel microchannel tray (reaction channel) for 30 minutes. The reaction solution was recovered, and the reaction mixture was qualitatively and quantitatively analyzed. The reaction mixture was then purified. The purification steps were as follows: first, organic solvents and low-boiling-point byproducts were removed by vacuum distillation; then, the reaction product was extracted with deionized water and dichloromethane, and BAMF was extracted into the aqueous phase; finally, the aqueous phase was removed by rotary evaporation, and the product was recrystallized to obtain pure BAMF. Qualitative and quantitative detection was performed using gas chromatography-mass spectrometry, and the specific test results are shown in Table 1 (row 31).

[0073] Example 12:

[0074] Experiments were conducted in the reaction channel (microreactor) to synthesize BAMF by HMFA reductive amination.

[0075] After the reaction apparatus was connected and cleaned, the ammonia storage tank was opened and the back pressure valve was fixed at 1 MPa. Then, a solution of 0.075 mol / L HMFA, 0.3 mol / L sodium borohydride, 0.225 mol / L n-butylamine, and methanol was pumped in at a flow rate of 0.148–3.54 mL / min. The liquid and gas phases were mixed in a mixer and then fed into a fixed catalyst bed. The reaction was carried out at a certain temperature through a 1.5 mm * 3 mm * 10 m stainless steel microchannel tray (reaction channel) for 30 minutes. The reaction solution was recovered, and the reaction mixture was qualitatively and quantitatively analyzed. The reaction mixture was then purified. The purification steps were as follows: first, organic solvents and low-boiling-point byproducts were removed by vacuum distillation; then, the reaction product was extracted with deionized water and dichloromethane, and BAMF was extracted into the aqueous phase; then, the aqueous phase was removed by rotary evaporation, and the product was recrystallized to obtain pure BAMF. Qualitative and quantitative detection was performed using gas chromatography-mass spectrometry, and the specific test results are shown in Table 1 (row 32).

[0076] The preparation method of HMFA is as follows: 1 mmol HMF, 3 mmol butylamine, 120 mg Raney cobalt catalyst, and 14 mL methanol solvent are added to a 500 mL reactor, followed by the addition of 2 mmol sodium borohydride. After purging with N2 three times, NH3 at a certain pressure is added, and the reactor is incubated at 120 °C for 2 h. After the reaction is complete, the reaction mixture is filtered to obtain an HMFA solution.

[0077] Table 1

[0078]

[0079] Comparative Example 1

[0080] Experiments were conducted in a reactor to synthesize BAMF by the reductive amination of DFF.

[0081] 1 mmol DFF, 3 mmol butylamine, 120 mg Raney nickel catalyst, and 14 mL methanol solvent were added to a 25 mL reactor, followed by 2 mmol sodium borohydride. After purging with N2 three times, NH3 was added at a certain pressure, and the reactor was incubated at 100 °C for 10 h. After the reaction was completed, the reaction mixture was filtered and rotary evaporated to obtain the product.

[0082] After the reaction was completed, the resulting organic phase was diluted with ethanol by a certain factor, and the BAMF obtained by vacuum distillation was dissolved in deuterated DMSO and detected by 1H NMR spectroscopy. The yield of BAMF was quantitatively analyzed by gas chromatography, and the yield of BAMF was found to be 88.66%.

[0083] Comparative Example 2

[0084] Experiments were conducted in a reactor to synthesize BAMF by the reductive amination of HMF.

[0085] 1 mmol HMF, 3 mmol butylamine, 120 mg Raney nickel catalyst, and 14 mL methanol solvent were added to a 25 mL reactor, followed by 2 mmol sodium borohydride. After purging three times with N2, NH3 was added at a certain pressure, and the reactor was incubated at 100 °C for 10 h. After the reaction was completed, the reaction mixture was filtered and rotary evaporated to obtain the product.

[0086] After the reaction was completed, the resulting organic phase was diluted with ethanol by a certain factor, and the BAMF after vacuum distillation was dissolved in deuterated DMSO and detected by 1H NMR spectroscopy. The yield of BAMF was quantitatively analyzed by gas chromatography, and the yield of BAMF was found to be 73.01%.

[0087] Comparative Example 3:

[0088] Experiments were conducted in a reactor to synthesize BAMF by the reductive amination of HMFA.

[0089] In a 25 mL reactor, 1 mmol HMFA, 3 mmol butylamine, 120 mg Raney cobalt catalyst, and 15 mL methanol solvent were added, followed by 2 mmol sodium borohydride. After purging three times with N2, NH3 was added at a certain pressure, and the reactor was reacted at 120 °C for 2 h. After the reaction was complete, the reaction mixture was filtered to obtain an HMFA solution. In another reactor, HMFA solution, 120 mg Raney nickel catalyst, and 14 mL methanol solvent were added, followed by 2 mmol sodium borohydride. After purging three times with N2, NH3 was added at a certain pressure, and the reactor was reacted at 160 °C for 6 h. After the reaction was complete, the reaction mixture was filtered and rotary evaporated to obtain the product.

[0090] After the reaction was completed, the resulting organic phase was diluted with ethanol by a certain factor, and the BAMF obtained after vacuum distillation was dissolved in deuterated DMSO and detected by 1H NMR spectroscopy. The yield of BAMF was quantitatively analyzed by gas chromatography, and the yield of BAMF was found to be 86.80%.

[0091] Comparative Example 4:

[0092] Experiments were conducted in a reactor to synthesize BAMF by the reductive amination of DFF.

[0093] 25 mmol DFF, 75 mmol butylamine, 3 g Raney nickel catalyst, and 350 mL methanol solvent were added to a 500 mL reactor, followed by 50 mmol sodium borohydride. After purging three times with N2, NH3 was added at a certain pressure, and the reactor was incubated at 100 °C for 10 h. After the reaction was completed, the reaction mixture was filtered and rotary evaporated to obtain the product.

[0094] After the reaction was completed, the resulting organic phase was diluted with ethanol by a certain factor, and the BAMF obtained by vacuum distillation was dissolved in deuterated DMSO and detected by 1H NMR spectroscopy. The yield of BAMF was quantitatively analyzed by gas chromatography, and the yield of BAMF was found to be 68.69%.

[0095] Comparative Example 5:

[0096] Experiments were conducted in a reactor to synthesize BAMF by the reductive amination of HMF.

[0097] 25 mmol HMF, 75 mmol butylamine, 3 g Raney nickel catalyst, and 350 mL methanol solvent were added to a 500 mL reactor, followed by 50 mmol sodium borohydride. After purging three times with N2, NH3 was added at a certain pressure, and the reactor was incubated at 100 °C for 10 h. After the reaction was completed, the reaction mixture was filtered and rotary evaporated to obtain the product.

[0098] After the reaction was completed, the organic phase of the resulting reaction solution was diluted with ethanol by a certain factor, and the BAMF after vacuum distillation was dissolved in deuterated DMSO and detected by 1H NMR spectroscopy. The yield of BAMF was quantitatively analyzed by gas chromatography, and the yield of BAMF was found to be 58.12%.

[0099] Comparative Example 6:

[0100] Experiments were conducted in a reactor to synthesize BAMF by the reductive amination of HMFA.

[0101] In a 500 mL reactor, 25 mmol HMFA, 75 mmol butylamine, 3 g Raney cobalt catalyst, and 350 mL methanol solvent were added, followed by 50 mmol sodium borohydride. After purging three times with N2, NH3 was added at a certain pressure, and the reactor was reacted at 120 °C for 2 h. After the reaction was complete, the reaction mixture was filtered to obtain an HMFA solution. In another reactor, HMFA solution, 3 g Raney nickel catalyst, and 350 mL methanol solvent were added, followed by 50 mmol sodium borohydride. After purging three times with N2, NH3 was added at a certain pressure, and the reactor was reacted at 160 °C for 6 h. After the reaction was complete, the reaction mixture was filtered and rotary evaporated to obtain the product.

[0102] After the reaction was completed, the resulting organic phase was diluted with ethanol by a certain factor, and the BAMF after vacuum distillation was dissolved in deuterated DMSO and detected by 1H NMR spectroscopy. The yield of BAMF was quantitatively analyzed by gas chromatography, and the yield of BAMF was found to be 60.82%.

[0103] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above descriptions are merely specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing 2,5-bis(aminomethyl)furan based on a continuous flow method, comprising: A liquid phase channel and a gas phase channel are provided. The reaction substrate, amine compound, reducing agent and organic solvent are delivered to the mixer through the liquid phase channel and ammonia gas is delivered through the gas phase channel. After being mixed in the mixer, they flow into the reaction channel equipped with a catalyst fixed bed to react and obtain a reaction solution containing 2,5-bis(aminomethyl)furan. The reaction substrate is selected from 2,5-furandicarboxaldehyde, 5-hydroxymethylfurfural, 5-hydroxymethyl-2-furanmethylamine, and the amine compound is selected from any one of organic solutions of methylamine or ethylamine, propylamine, butylamine, butanediamine, pentylamine, hexylamine, and oleylamine. A plunger pump is installed in the liquid phase channel to control the flow rate in the liquid phase channel to be 0.148~3.54 mL / min; An ammonia storage tank is connected to the gas phase channel. A back pressure valve is installed on the gas phase channel. The ammonia storage tank is connected to the back pressure valve via a flow meter. The back pressure valve controls the ammonia pressure, and the flow meter controls the ammonia flow rate. The ammonia flow rate is 5 mL / min, and the ammonia pressure is 0.1-5 MPa. The reaction channel has a spiral structure, with an inner diameter of 1-2 mm, an outer diameter of 3-4 mm, and a tube length of 5-15 m.

2. The method according to claim 1, further comprising: After the reaction is completed, the reaction solution containing 2,5-bis(aminomethyl)furan is quenched using a quenching device to obtain the reaction solution. as well as Unreacted ammonia is removed using an ammonia absorption device.

3. The method according to claim 1 or 2, further comprising: The obtained reaction solution containing 2,5-bis(aminomethyl)furan was purified.

4. The method according to claim 1, wherein: The reducing agent is selected from sodium borohydride or sodium cyanoborohydride; The organic solvent is selected from methanol or tetrahydrofuran; The catalyst is selected from any one of Raney nickel, Raney cobalt, and Ru / C.

5. The method according to claim 1, wherein: The reaction channel is heated using a heating medium selected from dimethyl silicone oil. The reaction temperature in the reaction channel is 25-150°C, and the residence time in the reaction channel is 5-120 min.

6. The method according to claim 4, wherein: The concentration of the reaction substrate is 0.05~0.5 mol / L, the concentration of the amine compound is 0.15~1.5 mol / L, and the amount of catalyst is 100~500 mg / L.

7. An apparatus for preparing 2,5-bis(aminomethyl)furan using a continuous flow method, for performing the method according to any one of claims 1-6, the apparatus comprising: A liquid phase channel for feeding liquid phase reactants and a gas phase channel for feeding gaseous ammonia, and a mixer connected to the liquid phase channel and the gas phase channel respectively, for mixing the liquid phase reactants and gaseous ammonia in the mixer; and A reaction channel located downstream of the mixer is provided with a catalyst fixed bed.

8. The apparatus according to claim 7, further comprising: Quenching device, used to quench a reaction; An ammonia absorption device, connected to the reaction channel, is used to remove unreacted ammonia from the reaction channel. A purification apparatus for purifying the reaction solution containing 2,5-bis(aminomethyl)furan; The control device includes a plunger pump installed in the liquid phase channel, a back pressure valve for controlling the pressure in the gas phase channel, and a flow meter for controlling the flow rate of ammonia gas delivered from the ammonia storage tank, wherein the ammonia storage tank is connected to the back pressure valve via the flow meter.

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