A continuous flow process and apparatus for the synthesis of a diene diepoxide

Abstract

The application belongs to the technical field of fine chemical industry, and particularly relates to a continuous flow synthesis method and device of diene diepoxide. The method comprises the following steps: mixing an organic phase containing a diene compound, a catalyst and a pyridine-acetic acid ligand, and an aqueous phase containing hydrogen peroxide and a specific buffer system through a micro-mixer to form a water-in-oil micro-dispersion system; making the micro-dispersion system enter a micro-reactor to perform an epoxidation reaction; then performing cooling treatment on the reaction liquid; removing the aqueous phase through a membrane separator; and obtaining the diene diepoxide through post-treatment. By introducing the buffer system, the pH of the reaction system is stabilized at 10.5-12.0, the decomposition of hydrogen peroxide and the deactivation of methyltrioxorhenium are effectively inhibited; in combination with the continuous flow technology, the reaction process is accurately controlled and intrinsically safe, and the reaction time is significantly shortened; and the conversion rate of the diene compound and the yield of the target epoxide are both significantly improved.

Description

Technical Field

[0001] This invention belongs to the field of fine chemical technology, specifically relating to a continuous flow synthesis method and apparatus for diene diepoxides. Background Technology

[0002] Epoxides are valuable multifunctional intermediates in organic synthetic chemistry and can serve as versatile precursors for the synthesis of many natural products and drug molecules. Divinylbenzene dioxide (DVBDO) can be used as an reactive diluent or as the main epoxy resin matrix in epoxy thermosetting formulations. DVBDO itself has a very low liquid viscosity, making it particularly suitable for preparing low-viscosity epoxy formulations. Epoxy formulations made from DVBDO can be used as intermediates in a variety of other products and are widely used in polymer materials, drug synthesis, and fine chemical production.

[0003] Traditional divinylbenzene epoxidation processes mostly employ batch reactors. Known batch processes include: adding divinylbenzene, hydrogen peroxide, nano-ferric oxide, sodium hydroxide, and acetonitrile, reacting at 32°C for 24 hours, yielding 69.5%; adding divinylbenzene, hydrogen peroxide, acetonitrile, methanol, and sodium silicate, reacting at 40°C for 8 hours, yielding 55%; adding divinylbenzene, hydrogen peroxide, methylrhenium trioxide, 3-methylpyridine, and dichloromethane, reacting at 25°C for 8 hours, yielding 70%. Another example is adding phosphotungstic acid, water, phosphoric acid, hydrogen peroxide, dichloroethane, and methyltrioctylammonium chloride at 20°C, stirring for 30 minutes, then adding divinylbenzene and hydrogen peroxide, reacting at 50°C for 6 hours, yielding 20%. These processes have long reaction times and require large amounts of oxidant, resulting in excessively high local concentrations of hydrogen peroxide, leading to low reaction efficiency, poor selectivity, and significant safety hazards. Continuous flow reactors, due to their higher specific surface area and rapid mass / heat transfer, can overcome these problems. Therefore, in continuous flow epoxidation reactions, shorter reaction times, higher yields and selectivity, and safer operation can be achieved. Chinese patent CN105392781A discloses a continuous flow process using a tubular reactor or CSTR / PFR reactor, which reduces the residence time to 15 minutes through enhanced heat removal. However, this process uses unstable peroxycarboxyimino acid, resulting in poor safety. Its engineering implementation (multi-point, multi-stream feed, pH control) is overly complex and prone to failure, and the overall process is not sufficiently integrated.

[0004] In traditional batch reactor processes, inorganic salts such as sodium silicate and sodium phosphate have been used as buffers. However, these salts are prone to crystallization in continuous flow microreactors due to solubility limitations, leading to microchannel blockage and disrupting stable continuous production. Furthermore, traditional homogeneous buffer systems struggle to precisely control the pH at the reaction interface under rapid mass transfer conditions, thus failing to effectively suppress the deactivation of methylrhenium trioxide (MTO) catalysts and the non-selective decomposition of hydrogen peroxide.

[0005] Therefore, developing an efficient, safe, and scalable process for synthesizing diene diepoxides suitable for continuous flow systems has significant industrial application value. Summary of the Invention

[0006] The purpose of this invention is to overcome the defects of the prior art by providing a continuous flow synthesis method and apparatus for diene diepoxides.

[0007] The objective of this invention can be achieved through the following technical solutions: A continuous flow synthesis method for diene diepoxides includes the following steps: a. An organic phase and an aqueous phase are mixed using a micromixer to form a water-in-oil microdispersion system; wherein the organic phase comprises a diene compound, a catalyst, a ligand, and an organic solvent, and the aqueous phase comprises hydrogen peroxide, a buffer solution, and a phase transfer catalyst; b. The micro-dispersed system is subjected to an epoxidation reaction in a microreactor to obtain a reaction solution containing a double epoxide; c. Cool the reaction solution; d. The cooled reaction solution is separated by a membrane separator to remove the aqueous phase, and then post-processed to obtain diene diepoxide.

[0008] Furthermore, the diene compound is selected from one or more of divinylbenzene, 1,7-octadiene, or 1,5-hexadiene; The concentration of the hydrogen peroxide is 30 wt%; The molar ratio of hydrogen peroxide to diene compounds is 2.5:1 to 5.0:1.

[0009] Further, the buffer solution is an aqueous solution containing sodium hydroxide and disodium ethylenediaminetetraacetate (EDTA-2Na), and the pH value of the buffer solution is 10.5-12.0.

[0010] Furthermore, based on the molar amount of the diene compound, the amount of sodium hydroxide used is 0.2-0.5 equivalents, and the amount of disodium ethylenediaminetetraacetate used is 0.03-0.08 equivalents.

[0011] Furthermore, the phase transfer catalyst is tetrabutylammonium bisulfate (TBAS); based on the molar amount of the diene compound, the amount of the phase transfer catalyst is 0.01-0.05 equivalents.

[0012] Furthermore, the catalyst is methyl rhenium trioxide (MTO); based on the molar amount of the diene compound, the amount of the catalyst is 0.002-0.006 equivalents; The ligand is a mixture of pyridine and acetic acid in a volume ratio of 1:1; The mass ratio of the catalyst to the ligand is from 0.1:1 to 0.2:1.

[0013] Furthermore, the organic solvent is a mixture of toluene and 1,2-dichloroethane, with a volume ratio of toluene to 1,2-dichloroethane of 2:1 to 4:1; the volume ratio of the organic solvent to the diene compound is 5:1 to 9:1.

[0014] Furthermore, in step b, the epoxidation reaction is carried out at a temperature of 50-70°C, a pressure of 5-15 bar, and a residence time of 5-15 min.

[0015] Furthermore, in step c, the cooling treatment involves cooling the reaction solution to 5-15°C to suppress side reactions and protect the stability of the product.

[0016] In step d, the post-treatment is to remove the organic solvent by rotary evaporation under reduced pressure to obtain purified diene diepoxide.

[0017] This invention also provides an apparatus for realizing the continuous flow synthesis method of the diene diepoxide described in any of the above claims, which constructs a microreaction system based on the "buffer capsule" concept, specifically including: A micromixer is used to mix an organic phase with an aqueous phase to form a water-in-oil microdispersion system; the micromixer is a T-junction or a T-type mixer. A microreactor, fluidly connected to the outlet of the micromixer, is used for epoxidation reaction; the microreactor is a coil-type microreactor with an inner diameter of 0.5-2 mm and is made of fluorinated ethylene propylene copolymer (FEP). A cooler, fluidly connected to the outlet of the microreactor, is used to cool the reaction liquid; the cooler is a cooling coil. A membrane separator, fluidly connected to the outlet of the cooler, is used to separate the aqueous phase and obtain the target product, diene diepoxide. The device also includes a back pressure valve, located between the cooler and the membrane separator, to maintain the system reaction pressure.

[0018] The device employs a split-feed strategy, placing the MTO catalyst and substrate in the organic phase and the hydrogen peroxide and "buffer capsule" in the aqueous phase, thus preventing premature contact and deactivation of the catalyst and oxidant. At the outlet, a design is adopted to rapidly cool to 5-15°C before membrane separation, which can suppress side reactions and protect product stability.

[0019] The synthesis of the diene diepoxide of the present invention is as follows: Figure 1 As shown, the core of the olefin epoxidation reaction catalyzed by methyl rhenium trioxide (MTO) and hydrogen peroxide is the reversible generation and oxygen transfer process of rhenium peroxide species, which is specifically divided into three stages: (1) Formation of the active peroxyrhenium species: MTO(CH3ReO3) first reacts with H2O2 to generate a single peroxyrhenium species A; subsequently, A can further react with H2O2 to generate a double peroxyrhenium species B (Re–O2). B is the key epoxidation active intermediate in the reaction, and its structure is a seven-coordinate Re(VII) peroxy complex, which has strong electrophilicity and oxygen transfer ability.

[0020] (2) Epoxidation reaction occurs: In the reaction, one oxygen atom in B attacks the electron-rich double bond of the olefin in a highly electrophilic manner to form a three-membered epoxide, while itself being reduced to a single peroxide species A or MTO.

[0021] (3) Maintenance of the catalytic cycle: The monoperoxide species A generated in the reaction can continue to react with H2O2 and be regenerated into B, thereby maintaining the catalytic cycle.

[0022] Rhenium peroxide species B, as a highly efficient and selective epoxidizing agent, forms a highly efficient and environmentally friendly catalytic cycle system through its formation and regeneration. However, rhenium peroxide species B is extremely sensitive to the pH of the reaction environment: insufficient alkalinity hinders the formation of this active species, while excessive alkalinity easily leads to ring-opening of the epoxide. Furthermore, MTO is easily decomposed and deactivated in a strongly alkaline environment, and H2O2 will rapidly decompose into water and oxygen under strongly alkaline conditions.

[0023] Existing technologies struggle to maintain a precise alkaline environment under continuous flow conditions. This invention addresses the fundamental stability challenge of MTO catalytic systems under alkaline conditions through a "buffer capsule" microdispersion system. Specifically, this invention employs a synergistic buffer system composed of NaOH and EDTA-2Na, working in conjunction with the phase transfer catalyst TBAS to form a stable water-in-oil microdispersion system within microchannels. TBAS combines the dual functions of a phase transfer catalyst and a surfactant: on one hand, it adsorbs at the oil-water interface, significantly reducing interfacial tension and dispersing the aqueous phase into micron-sized droplets under the shearing action of the micromixer; on the other hand, the oleophilic FEP material channel ensures the organic phase remains continuous, and the TBAS adsorbed on the droplet surface prevents droplet aggregation through electrostatic repulsion, ultimately stably encapsulating the alkaline aqueous phase within the organic phase, forming a "water-in-oil" microreaction unit. This structure strictly confines the strongly alkaline environment (pH 10.5-12.0) within the aqueous droplets. The MTO catalyst only momentarily contacts the alkaline environment at the water-oil interface, completing the oxygen transfer reaction before immediately returning to the neutral organic phase. This significantly reduces the alkaline exposure time for both the catalyst and the product, preventing MTO deactivation and ring-opening side reactions of the epoxide products from the outset. Simultaneously, EDTA-2Na effectively inhibits the ineffective decomposition of hydrogen peroxide by chelating trace metal impurities in the reaction system, further enhancing the stability of the reaction environment. Ordinary buffer solutions can only maintain the overall pH range and cannot achieve the dual functions of interfacial isolation and metal ion chelation, thus failing to address the core issues of MTO deactivation and hydrogen peroxide decomposition.

[0024] Compared with the prior art, the essential difference of the present invention lies in three aspects: First, the form in which the alkali exists is different. In the prior art, the alkali (such as potassium carbonate) is dissolved or suspended in the system, and OH... - It can freely diffuse and directly contact the catalyst and hydrogen peroxide, while the alkali of this invention is encapsulated inside aqueous microdroplets, OH - First, the base cannot freely diffuse into the organic phase; second, the mechanism of action of the base is different. Existing technologies adjust the pH of the reaction system globally, while the base of this invention only regulates the reaction through the oil-water interface, without directly contacting the MTO catalyst and substrate, and only transporting the necessary active oxygen species through the phase transfer catalyst; third, the pH control precision is different. Existing technologies control the average pH value of the system, and OH- may still appear locally. - The concentration was too high, but this invention eliminates the local OH groups spatially through physical isolation. - The possibility of excessively high pH levels was minimized, enabling precise pH control of the reaction interface. Maintaining a stable pH between 10.5 and 12.0 ensured sufficient basic ligands to coordinate with MTO, neutralize its acidity, and protect the product, while also preventing localized OH- ions. - Excessive concentration leads to nucleophilic attack on the active site of MTO (generating inactive perrhenate), while simultaneously controlling the dissociation of H2O2 into HO2.- The rate ensures the stable existence and effective utilization of the oxidant.

[0025] Compared with the prior art, the present invention has the following beneficial effects: (1) This invention solves the stability problem of MTO catalytic epoxidation reaction under continuous flow environment. Through the synergistic buffer system composed of NaOH and EDTA-2Na, the dual functions of interface isolation and metal ion chelation are achieved, and the reaction pH is stably controlled in the suitable range of 10.5-12.0, which effectively inhibits catalyst deactivation and ineffective decomposition of hydrogen peroxide.

[0026] (2) The problem of microchannel blockage is avoided from the root: In view of the defect that traditional inorganic salt buffer systems (such as phosphates and silicates) are prone to crystallization and precipitation in microchannels, resulting in blockage, the present invention adopts a buffer system composed of EDTA-2Na and NaOH. The components of this system have good solubility and stable properties, which overcomes the problem of crystallization blockage and provides a reliable guarantee for the long-term stable operation of continuous production.

[0027] (3) The reaction process was enhanced by the “buffer capsule” micro-dispersion system: The present invention innovatively designed a “water-in-oil” micro-dispersion system, which physically confines the alkaline aqueous phase inside the microdroplets, greatly reducing the contact area and time between the alkaline solution and the alkaline-sensitive MTO catalyst and epoxy products, suppressing side reactions such as epoxy ring opening from the source. The conversion rate of divinylbenzene can reach 82.0% and the selective yield of the target diepoxide can reach 77.3% within a residence time of only 10 minutes.

[0028] (4) Significantly improved reaction efficiency and selectivity: With the help of the phase transfer catalysis of TBAS, the efficient transfer of active oxygen species in the aqueous phase to the organic phase is promoted. Combined with the excellent mass transfer performance of the microreactor, the efficient conversion of diene compounds is achieved in a very short reaction time, and the yield is significantly improved compared with the traditional batch process.

[0029] (5) Achieved precise process control and inherent safety: In view of the problems of inaccurate reaction process control and poor safety in existing technologies, the continuous flow microreactor of the present invention provides precise temperature control and efficient heat and mass transfer conditions, eliminating the safety hazards caused by local overheating and excessive hydrogen peroxide concentration that are prone to occur in traditional batch reactors; the reaction pressure is precisely controlled by the back pressure valve, making the reaction process safer and more controllable, which meets the requirements of green chemical industry and process intensification.

[0030] (6) It has good industrial application prospects: The process described in this invention is simple to operate, continuous and stable, and easy to scale up. While ensuring high yield and high selectivity, it significantly shortens the reaction time and reduces safety risks, providing a new, efficient, safe and controllable path for the industrial production of diene diepoxides. Attached Figure Description

[0031] Figure 1 This is a schematic diagram of the methyl rhenium trioxide-catalyzed olefin epoxidation reaction mechanism of the present invention; Figure 2 These are schematic diagrams of the microreaction systems in various embodiments of the present invention; Among them, 1-micro mixer, 2-micro reactor, 3-cooler, 4-back pressure valve, 5-membrane separator; Figure 3 The divinylbenzene diepoxide of Example 1 of this invention 1 1H NMR spectrum (400 MHz, CDCl3); Figure 4 The octadiene diepoxide of Example 2 of this invention 1 1H NMR spectrum (400 MHz, CDCl3); Figure 5 The hexadiene diepoxide of Example 3 of this invention 1 H NMR spectrum (400 MHz, CDCl3). Detailed Implementation

[0032] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments. These embodiments are based on the technical solution of the present invention and provide detailed implementation methods and specific operating procedures. However, the scope of protection of the present invention is not limited to the following embodiments.

[0033] Unless otherwise specified, all raw materials used in this invention are commercially available products.

[0034] This invention mixes an organic phase containing diene compounds, a methyl rhenium trioxide catalyst, and a pyridine-acetic acid ligand with an aqueous phase containing hydrogen peroxide and a specific buffer system to form a water-in-oil microdispersion system. The resulting microdispersion system undergoes a sequential epoxidation reaction, cooling treatment, and removal of the aqueous phase, followed by post-treatment to obtain the target product, diene diepoxide. This invention effectively suppresses the decomposition of hydrogen peroxide and the deactivation of the methyl rhenium trioxide catalyst; combined with continuous flow technology, it achieves precise control and intrinsic safety of the reaction process, significantly shortening the reaction time; compared with traditional batch processes, this invention significantly improves both the conversion rate of diene compounds and the yield of the target epoxide. The apparatus for the continuous flow synthesis method of diene diepoxide is as follows: Figure 2 As shown, it includes: Micromixer 1: used to mix the organic phase and the aqueous phase to form a water-in-oil microdispersion system; the micromixer 1 is a T-type mixer, and the minimum dispersion scale of the T-type micromixer is 100~300µm; Microreactor 2: Fluidly connected to the outlet of the micromixer 1, used for epoxidation reaction; the microreactor 2 is a coil-type microreactor with an inner diameter of 0.5-2 mm and made of FEP. Cooler 3: fluidly connected to the outlet of the microreactor 2, used to cool the reaction liquid; the cooler 3 is a cooling coil; Membrane separator 5: fluidly connected to the outlet of the cooler 3, used to separate the aqueous phase and obtain the target product diene diepoxide; Back pressure valve 4: Located between cooler 3 and membrane separator 5, used to maintain system reaction pressure.

[0035] In the following examples and comparative examples: The micro mixer is a T-type micro mixer (1 / 16 inch, 316L material), manufactured by Kunshan Fuxi Engineering Technology Co., Ltd. The microreactor is a coil-type microreactor (FEP material, 1 mm inner diameter), manufactured by Shenzhen Yizheng Technology Co., Ltd. The cooler is a cooling coil (316L material, 1 mm inner diameter), manufactured by Shenzhen Yizheng Technology Co., Ltd. The back pressure valve (0~100 bar, 316L material, temperature resistance 80℃) is manufactured by Shenzhen Yizheng Technology Co., Ltd. The membrane separator (model: MS-10) is manufactured by Shenzhen Yizheng Technology Co., Ltd.

[0036] Example 1 Dissolve 3.0 mL (0.02 mol) of divinylbenzene in a mixed solvent of 16.5 mL toluene and 5.5 mL 1,2-dichloroethane, and add 0.02 g (8 × 10⁻⁶ mol) of divinylbenzene. -5 0.15 mL of a mixture of methyl rhenium trioxide (mol) and pyridine and acetic acid (pyridine to acetic acid volume ratio of 1:1) was mixed evenly to form organic phase A.

[0037] Dissolve 0.24 g (0.006 mol) sodium hydroxide and 0.37 g (0.001 mol) disodium ethylenediaminetetraacetate in water, adjust the pH to 11.5, then add 6.1 mL of 30% hydrogen peroxide (0.06 mol) and 0.136 g (4 × 10⁻⁶ mol) solution. -4 1 mol) of tetrabutylammonium bisulfate was mixed evenly and used as aqueous phase solution B.

[0038] Two high-pressure plunger pumps delivered feed solutions A and B to a T-type micromixer, respectively, at a flow rate of 0.5 mL / min for solution A and 0.4 mL / min for solution B. At a reaction temperature of 60°C, the two-phase fluids formed a water-in-oil microdispersion system in the micromixer, which then entered a coil-type microreactor made of FEP material. The system pressure was controlled at 10 bar using a back pressure valve, and the reaction residence time was 10 min. After the reaction, the effluent was cooled to 10°C via a cooling coil before entering a membrane separator for oil-water phase separation. The organic phase was collected and the solvent was removed by rotary evaporation under reduced pressure at 50°C (vacuum degree approximately -0.09 MPa), yielding a yellow liquid product, divinylbenzene diepoxide.

[0039] Quantitative analysis by high-performance liquid chromatography (HPLC) showed that the conversion rate of divinylbenzene was 82.0%, and the yield of divinylbenzene diepoxide was 77.3%. The structure of the product was determined by proton nuclear magnetic resonance spectroscopy (NMR). 1 Characterization by H NMR confirmed that its spectrum is as follows: Figure 3 As shown: 1 ¹H NMR (400MHz, CDCl₃) δ 2.7-2.8, 3.1-3.2, 3.8-3.9 (multiple peaks, 3H, epoxide proton), 7.1-7.4 (multiple peaks, 4H, aromatic ring proton).

[0040] Example 2 Dissolve 3.0 mL (0.02 mol) of 1,7-octadiene in a mixed solvent of 16.5 mL toluene and 5.5 mL 1,2-dichloroethane, and add 0.01 g (4 × 10⁻⁶ mol) of 1,7-octadiene. -5 0.08 mL of a mixture of methyl rhenium trioxide (mol) and pyridine and acetic acid (pyridine to acetic acid volume ratio of 1:1) was mixed evenly to form organic phase A.

[0041] Dissolve 0.24 g (0.006 mol) sodium hydroxide and 0.37 g (0.001 mol) disodium ethylenediaminetetraacetate in water, adjust the pH to 11.5, then add 6.1 mL of 30% hydrogen peroxide (0.06 mol) and 0.136 g (4 × 10⁻⁶ mol) solution. -4 1 mol) of tetrabutylammonium bisulfate was mixed evenly and used as aqueous phase solution B.

[0042] Two high-pressure plunger pumps delivered feed solutions A and B to a T-type micromixer, respectively, at a flow rate of 0.7 mL / min for solution A and 0.5 mL / min for solution B. At a reaction temperature of 50°C, the two-phase fluids formed a water-in-oil microdispersion system in the micromixer, which then entered a coil-type microreactor made of FEP material. The system pressure was controlled at 10 bar using a back pressure valve, and the reaction residence time was 7.5 min. After the reaction, the effluent was cooled to 10°C via a cooling coil before entering a membrane separator for oil-water phase separation. The organic phase was collected and the solvent was removed by rotary evaporation under reduced pressure at 50°C (vacuum degree approximately -0.09 MPa), yielding a yellow liquid product, 1,7-octadiene diepoxide.

[0043] HPLC quantitative analysis showed that the conversion rate of 1,7-octadiene was 85.2%, and the yield of 1,7-octadiene diepoxide was 70.0%. The product structure was determined by 1H NMR spectroscopy. 1 Characterization by H NMR confirmed that its spectrum is as follows: Figure 4 As shown: 1 ¹H NMR (400 MHz, CDCl₃) δ 1.2–1.6 (m, 4H, center CH₂), 2.3 (m, 4H, CH₂CH₂ epoxide), 2.4–2.8 (m, 4H, epoxide CH₂), 2.9–3.0 (m, 2H, epoxide CH).

[0044] Example 3 Dissolve 2.5 mL (0.02 mol) of 1,5-hexadiene in a mixed solvent of 16.5 mL toluene and 5.5 mL 1,2-dichloroethane, and add 0.01 g (4 × 10⁻⁶ mol) of 1,5-hexadiene. -5 0.08 mL of a mixture of methyl rhenium trioxide (mol) and pyridine and acetic acid (pyridine to acetic acid volume ratio of 1:1) was mixed evenly to form organic phase A.

[0045] Dissolve 0.24 g (0.006 mol) sodium hydroxide and 0.37 g (0.001 mol) disodium ethylenediaminetetraacetate in water, adjust the pH to 11.5, then add 5.1 mL of 30% hydrogen peroxide (0.05 mol) and 0.136 g (4 × 10⁻⁶ mol) solution. -4 1 mol) of tetrabutylammonium bisulfate was mixed evenly and used as aqueous phase solution B.

[0046] Two high-pressure plunger pumps delivered feed solutions A and B to a T-type micromixer, respectively, at a flow rate of 0.7 mL / min for solution A and 0.5 mL / min for solution B. At a reaction temperature of 50°C, the two-phase fluids formed a water-in-oil microdispersion system in the micromixer, which then entered a coil-type microreactor made of FEP material. The system pressure was controlled at 10 bar using a back pressure valve, and the reaction residence time was 7.5 min. After the reaction, the effluent was cooled to 10°C via a cooling coil before entering a membrane separator for oil-water phase separation. The organic phase was collected and the solvent was removed by rotary evaporation under reduced pressure at 50°C (vacuum degree approximately -0.09 MPa), yielding a yellow liquid product, 1,5-hexadiene diepoxide.

[0047] HPLC quantitative analysis showed that the conversion rate of 1,5-hexadiene was 76.2%, and the yield of 1,5-hexadiene diepoxide was 62.3%. The product structure was determined by 1H NMR spectroscopy. 1 Characterization by H NMR confirmed that its spectrum is as follows: Figure 5 As shown: 1 ¹H NMR (400MHz, CDCl₃) δ 1.6–1.8 (m, 4H, CH₂-epoxy), 2.5–2.7 (m, 4H, epoxy CH₂), 2.9–3.0 (m, 2H, epoxy CH).

[0048] Example 4 Dissolve 3.0 mL (0.02 mol) of divinylbenzene in a mixed solvent of 16.5 mL toluene and 5.5 mL 1,2-dichloroethane, and add 0.03 g (1.2 × 10⁻⁶ mol) of [a specific solvent]. -4 0.19 mL of a mixture of methyl rhenium trioxide (mol) and pyridine and acetic acid (pyridine to acetic acid volume ratio of 1:1) was mixed evenly to form organic phase A.

[0049] Dissolve 0.24 g (0.006 mol) sodium hydroxide and 0.37 g (0.001 mol) disodium ethylenediaminetetraacetate in water, adjust the pH to 11.5, then add 6.1 mL of 30% hydrogen peroxide (0.06 mol) and 0.136 g (4 × 10⁻⁶ mol) solution. -4 1 mol) of tetrabutylammonium bisulfate was mixed evenly and used as aqueous phase solution B.

[0050] Two high-pressure plunger pumps delivered feed solutions A and B to a T-type micromixer, respectively, at a flow rate of 0.5 mL / min for solution A and 0.4 mL / min for solution B. At a reaction temperature of 60°C, the two-phase fluids formed a water-in-oil microdispersion system in the micromixer, which then entered a coil-type microreactor made of FEP material. The system pressure was controlled at 10 bar using a back pressure valve, and the reaction residence time was 10 min. After the reaction, the effluent was cooled to 10°C via a cooling coil before entering a membrane separator for oil-water phase separation. The organic phase was collected and the solvent was removed by rotary evaporation under reduced pressure at 50°C (vacuum degree approximately -0.09 MPa), yielding a yellow liquid product, divinylbenzene diepoxide.

[0051] HPLC analysis showed that the conversion rate of divinylbenzene was 80.3% and the yield of divinylbenzene diepoxide was 75.6%.

[0052] Example 5 Dissolve 3.0 mL (0.02 mol) of divinylbenzene in a mixed solvent of 16.5 mL toluene and 5.5 mL 1,2-dichloroethane, and add 0.02 g (8 × 10⁻⁶ mol) of divinylbenzene. -5 0.15 mL of a mixture of methyl rhenium trioxide (mol) and pyridine and acetic acid (pyridine to acetic acid volume ratio of 1:1) was mixed evenly to form organic phase A.

[0053] Dissolve 0.24 g (0.006 mol) sodium hydroxide and 0.37 g (0.001 mol) disodium ethylenediaminetetraacetate in water, adjust the pH to 11.5, then add 8.1 mL of 30% hydrogen peroxide (0.08 mol) and 0.136 g (4 × 10⁻⁶ mol) solution. -4 1 mol) of tetrabutylammonium bisulfate was mixed evenly and used as aqueous phase solution B.

[0054] Two high-pressure plunger pumps delivered feed solutions A and B to a T-type micromixer, respectively, at a flow rate of 0.5 mL / min for solution A and 0.4 mL / min for solution B. At a reaction temperature of 60°C, the two-phase fluids formed a water-in-oil microdispersion system in the micromixer, which then entered a coil-type microreactor made of FEP material. The system pressure was controlled at 10 bar using a back pressure valve, and the reaction residence time was 10 min. After the reaction, the effluent was cooled to 10°C via a cooling coil before entering a membrane separator for oil-water phase separation. The organic phase was collected and the solvent was removed by rotary evaporation under reduced pressure at 50°C (vacuum degree approximately -0.09 MPa), yielding a yellow liquid product, divinylbenzene diepoxide.

[0055] HPLC analysis showed that the conversion rate of divinylbenzene was 79.9% and the yield of divinylbenzene diepoxide was 72.9%.

[0056] Example 6 Dissolve 3.0 mL (0.02 mol) of divinylbenzene in a mixed solvent of 16.5 mL toluene and 5.5 mL 1,2-dichloroethane, and add 0.02 g (8 × 10⁻⁶ mol) of divinylbenzene. -5 0.15 mL of a mixture of methyl rhenium trioxide (mol) and pyridine and acetic acid (pyridine to acetic acid volume ratio of 1:1) was mixed evenly to form organic phase A.

[0057] Dissolve 0.24 g (0.006 mol) sodium hydroxide and 0.37 g (0.001 mol) disodium ethylenediaminetetraacetate in water, adjust the pH to 11.5, then add 6.1 mL of 30% hydrogen peroxide (0.06 mol) and 0.136 g (4 × 10⁻⁶ mol) solution. -4 1 mol) of tetrabutylammonium bisulfate was mixed evenly and used as aqueous phase solution B.

[0058] Two high-pressure plunger pumps delivered feed solutions A and B to a T-type micromixer, respectively, at a flow rate of 0.67 mL / min for solution A and 0.53 mL / min for solution B. At a reaction temperature of 60°C, the two-phase fluids formed a water-in-oil microdispersion system in the micromixer, which then entered a coil-type microreactor made of FEP material. The system pressure was controlled at 10 bar using a back pressure valve, and the reaction residence time was 10 min. After the reaction, the effluent was cooled to 10°C via a cooling coil before entering a membrane separator for oil-water phase separation. The organic phase was collected and the solvent was removed by rotary evaporation under reduced pressure at 50°C (vacuum degree approximately -0.09 MPa), yielding a yellow liquid product, divinylbenzene diepoxide.

[0059] HPLC analysis showed that the conversion rate of divinylbenzene was 65.2% and the yield of divinylbenzene diepoxide was 58.9%.

[0060] Comparative Example 1 Dissolve 3.0 mL (0.02 mol) of divinylbenzene in a mixed solvent of 16.5 mL toluene and 5.5 mL 1,2-dichloroethane, and add 0.02 g (8 × 10⁻⁶ mol) of divinylbenzene. -5 0.15 mL of a mixture of methyl rhenium trioxide (mol) and pyridine and acetic acid (pyridine to acetic acid volume ratio of 1:1) was mixed evenly to form organic phase A.

[0061] Add a sodium phosphate-sodium hydrogen phosphate buffer solution (pH 11.5) containing 2.20 g sodium phosphate, 0.80 g sodium hydrogen phosphate, and 20.00 mL water. Then add 6.1 mL of 30% hydrogen peroxide (0.06 mol) and 0.136 g (4 × 10⁻⁶ g) of sodium hydrogen peroxide.-4 1 mol) of tetrabutylammonium bisulfate was mixed evenly and used as aqueous phase solution B.

[0062] Two high-pressure plunger pumps delivered feed solutions A and B to a T-type micromixer, respectively, at a flow rate of 0.5 mL / min for solution A and 0.4 mL / min for solution B. At a reaction temperature of 60°C, the two-phase fluids formed a water-in-oil microdispersion system in the micromixer, which then entered a coil-type microreactor made of FEP material. The system pressure was controlled at 10 bar using a back pressure valve, and the reaction residence time was 10 min. After the reaction, the effluent was cooled to 10°C via a cooling coil before entering a membrane separator for oil-water phase separation. The organic phase was collected and the solvent was removed by rotary evaporation under reduced pressure at 50°C (vacuum degree approximately -0.09 MPa), yielding a yellow liquid product, divinylbenzene diepoxide.

[0063] HPLC quantitative analysis showed that the conversion rate of divinylbenzene was 30.5%, and the yield of divinylbenzene diepoxide was 22.8%.

[0064] The results show that when using the traditional sodium phosphate-sodium hydrogen phosphate buffer system, the conversion rate of divinylbenzene and the yield of the target product are significantly lower than those of the sodium hydroxide-disodium ethylenediaminetetraacetate buffer system used in this invention because the traditional sodium phosphate-sodium hydrogen phosphate buffer system cannot effectively inhibit the deactivation of the MTO catalyst and the decomposition of hydrogen peroxide, and the precipitation of inorganic salts may reduce the stability of the reaction system.

[0065] Comparative Example 2 The preparation method of divinylbenzene diepoxide is basically the same as that in Example 1, except that the pH of the aqueous solution of sodium hydroxide and disodium ethylenediaminetetraacetate is adjusted to 9.5.

[0066] HPLC quantitative analysis showed that the conversion rate of divinylbenzene was 35.6%, and the yield of divinylbenzene diepoxide was 28.4%.

[0067] The results show that when the pH of the buffer system is too low, the alkalinity is insufficient to effectively promote the generation of rhenium peroxide active species, resulting in reduced catalytic efficiency and a significant decrease in the yield of the target product.

[0068] Comparative Example 3 The preparation method of divinylbenzene diepoxide is basically the same as that in Example 1, except that the pH of the aqueous solution of sodium hydroxide and disodium ethylenediaminetetraacetate is adjusted to 13.0.

[0069] HPLC quantitative analysis showed that the conversion rate of divinylbenzene was 60.5%, and the yield of divinylbenzene diepoxide was 42.3%. The results show that when the pH of the buffer system is too high, the strongly alkaline environment leads to the deactivation of the MTO catalyst and exacerbates the ring-opening side reaction of the epoxide product. Although the conversion rate of divinylbenzene can still reach 60.5%, the yield of the target diepoxide decreases significantly, far below the yield of Example 1. This also demonstrates the necessity of controlling the reaction pH within the range of 10.5-12.0 in this invention.

[0070] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A continuous flow synthesis method for diene diepoxides, characterized in that, Includes the following steps: a. An organic phase and an aqueous phase are mixed using a micromixer to form a water-in-oil microdispersion system; wherein the organic phase comprises a diene compound, a catalyst, a ligand, and an organic solvent, and the aqueous phase comprises hydrogen peroxide, a buffer solution, and a phase transfer catalyst; b. The micro-dispersed system is subjected to an epoxidation reaction in a microreactor to obtain a reaction solution containing a double epoxide; c. Cool the reaction solution; d. The cooled reaction solution is separated by a membrane separator to remove the aqueous phase, and then post-processed to obtain diene diepoxide.

2. The continuous flow synthesis method of diene diepoxides according to claim 1, characterized in that, The diene compound is selected from one or more of divinylbenzene, 1,7-octadiene, or 1,5-hexadiene; The concentration of the hydrogen peroxide is 30 wt%; The molar ratio of hydrogen peroxide to diene compounds is 2.5:1 to 5.0:

1.

3. The continuous flow synthesis method of diene diepoxides according to claim 1, characterized in that, The buffer solution is an aqueous solution containing sodium hydroxide and disodium ethylenediaminetetraacetate; the pH value of the buffer solution is 10.5-12.

0.

4. The continuous flow synthesis method of diene diepoxide according to claim 3, characterized in that, Based on the molar amount of the diene compound, the amount of sodium hydroxide used is 0.2-0.5 equivalents, and the amount of disodium ethylenediaminetetraacetate used is 0.03-0.08 equivalents.

5. The continuous flow synthesis method of diene diepoxide according to claim 1, characterized in that, The phase transfer catalyst is tetrabutylammonium bisulfate; based on the molar amount of the diene compound, the amount of the phase transfer catalyst is 0.01-0.05 equivalents.

6. The continuous flow synthesis method of diene diepoxide according to claim 1, characterized in that, The catalyst is methyl rhenium trioxide; based on the molar amount of the diene compound, the amount of the catalyst is 0.002-0.006 equivalents; The ligand is a mixture of pyridine and acetic acid; The mass ratio of the catalyst to the ligand is from 0.1:1 to 0.2:

1.

7. The continuous flow synthesis method of diene diepoxide according to claim 1, characterized in that, The organic solvent is a mixture of toluene and 1,2-dichloroethane, with a volume ratio of toluene to 1,2-dichloroethane of 2:1 to 4:1; the volume ratio of the organic solvent to the diene compound is 5:1 to 9:

1.

8. The continuous flow synthesis method of diene diepoxides according to claim 1, characterized in that, In step b, the epoxidation reaction is carried out at a temperature of 50-70°C, a pressure of 5-15 bar, and a residence time of 5-15 min.

9. The continuous flow synthesis method of diene diepoxide according to claim 1, characterized in that, In step c, the cooling process involves cooling the reaction solution to 5-15°C.

10. An apparatus for implementing a continuous flow synthesis method of diene diepoxides as described in any one of claims 1 to 9, characterized in that, include: Micromixers are used to mix organic and aqueous phases to form water-in-oil microdispersion systems; A microreactor, fluidly connected to the outlet of the micromixer, is used for carrying out an epoxidation reaction; A cooler, fluidly connected to the outlet of the microreactor, is used to cool the reaction liquid; A membrane separator, fluidly connected to the outlet of the cooler, is used to separate the aqueous phase and obtain the target product, diene diepoxide.

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