A continuous preparation method for cyclopropanation reaction by using a microreactor

Abstract

The application discloses a continuous preparation method for cyclopropanation reaction by using a microreactor. The method adopts a three-stage series connection bottom-spraying microreactor system, realizes efficient and safe cyclopropanation reaction through gradient catalysis design and precise temperature control. The reaction system comprises olefins, diazomethane precursors, lye and solvents, wherein the catalyst adopts single-atom palladium gradient distribution design loaded on SBA-15 and CeO2. The three-stage series connection bottom-spraying microreactors are controlled at different temperatures respectively. The process is simple, high conversion rate is realized, safety is high, and cost is reduced.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and particularly relates to a continuous preparation method for cyclopropaneation reaction using a microreactor. Background Technology

[0002] Cyclopropane and its derivatives are important chemical intermediates, widely used in pharmaceuticals, pesticides, fragrances, and polymer materials. Traditional cyclopropane production processes primarily rely on batch reactors, utilizing pathways such as the Simmons-Smith reaction, carbene insertion reaction, or metal-catalyzed cyclization, with reactions using diazomethane as a carbene precursor being widely employed. However, existing technologies suffer from several key issues that severely limit the economic efficiency and safety of their industrial application.

[0003] In current technological developments, batch reactor processes often employ highly active catalysts (such as organopalladium compounds or supported palladium) and react in batches within organic solvents. Diazomethane precursors require slow, dropwise addition to avoid violent exothermic reactions. After the reaction, additional quenching and separation are necessary, making the process complex. Furthermore, this reaction faces challenges related to exothermic and mass transfer technologies; cyclopropanation is a strongly exothermic reaction, and batch reactors are prone to localized overheating, posing a risk of runaway temperatures.

[0004] While fixed-bed continuous flow processes exist, they face challenges such as catalyst deactivation and low mass transfer efficiency. Furthermore, the explosion risk of diazomethane remains unresolved, necessitating high dilution ratios to mitigate the danger.

[0005] The high risk associated with diazomethane remains a concern in current reaction processes. Diazomethane is extremely unstable and prone to explosion, requiring strict temperature control and low-concentration operation in traditional processes, which limits production efficiency. Furthermore, side reactions are difficult to control, leading to decreased selectivity.

[0006] Low catalyst efficiency also restricts production. Traditional supported palladium catalysts are prone to sintering and carbon buildup, requiring frequent regeneration, and have low metal utilization.

[0007] In the chemical industry, the production of cyclopropane typically involves cyclopropanation reactions, which are often characterized by strong exothermic reactions, rapid reactions, and unstable intermediates. Microreactors are well-suited for such reactions due to their advantages of efficient mass / heat transfer, precise temperature control, and high safety.

[0008] In heterogeneous catalysis research, an efficient catalyst not only requires a large specific surface area and a high concentration of active species, but also should be able to achieve rapid mass transfer. Mesoporous materials, with their large specific surface area, uniform pore size distribution, and ordered pore structure, are very suitable as catalysts and catalyst supports. Furthermore, mesoporous molecular sieves can significantly improve the dispersibility of palladium particles, thereby enhancing their catalytic activity. This type of catalyst exhibits good dispersibility, high activity, excellent stability, and can be recycled.

[0009] SBA-15 has a hexagonal channel structure, but with a larger pore size (4.6-30 nm). Unlike typical MCM-41, which contains only mesopores, typical SBA-15 has many micropores on its pore walls, with sizes ranging from 1 to 3 nm. Due to the large and abundant mesopore size of SBA-15, it has advantages such as higher thermal and hydrothermal stability and a larger pore size distribution. Summary of the Invention

[0010] The technical problem solved by this invention is the low mass transfer efficiency, easy catalyst deactivation, and high risk of diazomethane in the existing batch reactor process and fixed bed continuous flow reaction process.

[0011] In view of the technical problems existing in the prior art, this invention designs a continuous preparation method for cyclopropaneation reaction using a microreactor. To address the aforementioned problems, this study designs a gradient catalytic three-stage microreactor system: utilizing continuous flow chemistry, the millisecond-level mixing and efficient heat transfer of the microreactor solve the exothermic problem. Accumulated risks are avoided through the mesoporous confinement effect of SBA-15 and the precise activation of single-atom Pd / CeO2. The reaction volume is greatly reduced, diazomethane is generated online and consumed immediately, and the extremely low residual amount reduces the danger of the reaction.

[0012] It should be noted that, in this invention, unless otherwise specified, the specific meaning of "comprising" in relation to composition definition and description includes both open-ended meanings such as "comprising," "including," etc., and closed-ended meanings such as "composed of," etc., and similar meanings.

[0013] Furthermore, the terms "first" and "second" are used only to distinguish descriptions and should not be interpreted as indicating or implying relative importance.

[0014] To solve the aforementioned technical problems, the present invention adopts the following solution:

[0015] [The first technical solution]

[0016] A continuous preparation method for cyclopropanation reaction using a microreactor, characterized by comprising the following steps:

[0017] Step 1: The olefin, alkali solution, solvent, and diazomethane precursor are fed into a microreactor for reaction; wherein the microreactor is a three-stage series bottom-splash microreactor, and the reaction rate is controlled by setting temperature gradients in the first-stage reactor, the second-stage reactor, and the third-stage reactor; different catalysts are filled in the first-stage reactor, the second-stage reactor, and the third-stage reactor of the three-stage series bottom-splash microreactor;

[0018] Step 2: After the reaction is completed, the reaction product of Step 1 is quenched by the quenching unit and flows out. After separating the organic phase and the aqueous phase, the organic phase is separated and purified to obtain the cyclopropane product.

[0019] Furthermore, in the aforementioned three-stage series bottom-splashed microreactor, the catalysts filled are as follows:

[0020] First-stage reactor: filled with single-atom palladium catalyst supported on SBA-15 mesoporous molecular sieve, used to milden the reaction;

[0021] Second-stage reactor: packed with cerium oxide-supported single-atom palladium catalyst, used for the stabilization of carbene intermediates and preliminary cyclopropanation;

[0022] The third-stage reactor is filled with a highly dispersed Pd / CeO2 catalyst supported on SBA-15, which is used to efficiently complete the cyclopropaneation reaction.

[0023] Furthermore, the three-stage series bottom-splash microreactor adopts a fractal channel design, with each stage of the reactor having independent temperature control. The temperature gradient is as follows: first stage reactor: 10-15℃; second stage reactor: 15-20℃; third stage reactor: 20-35℃.

[0024] Further, the alkaline solution in step 1 is an aqueous solution of potassium hydroxide or sodium hydroxide with a concentration of 25wt%-45wt%.

[0025] The solvent is one of tetrahydrofuran, xylene, diethyl ether, or ethylene glycol monomethyl ether;

[0026] The diazomethane precursor is N-methyl-N-nitrosourea or N-nitroso-N-methyl-p-toluenesulfonamide;

[0027] The weak acid in the quenching unit is acetic acid or citric acid, and the injection amount is 3-8 vol of the reaction stream.

[0028] Furthermore, in the catalyst of the first-stage reactor, the single-atom palladium catalyst is loaded onto the surface of the support by impregnation to form active sites; wherein the loading amount of single-atom palladium is 0.1-0.3 wt%.

[0029] Furthermore, in the second-stage reactor, the cerium oxide-supported palladium catalyst is filled with a palladium content of 0.5-1.0 wt% based on the total mass of the cerium oxide-supported palladium catalyst.

[0030] [Second Technical Solution]

[0031] This invention also provides a method for preparing a cerium oxide-supported single-atom palladium catalyst:

[0032] The cerium oxide-supported single-atom palladium catalyst was prepared according to the following method:

[0033] An ammonium citrate solution and a palladium salt solution were mixed to obtain a metal-organic complex solution;

[0034] The carrier is dispersed in the first solvent to obtain the first dispersion;

[0035] The first dispersion and the organometallic complex solution were mixed and reacted to obtain the precursor.

[0036] The precursor is calcined in a reducing atmosphere to obtain the cerium oxide-supported single-atom palladium catalyst.

[0037] Furthermore, the molar ratio of ammonium citrate in the ammonium citrate solution to palladium salt in the palladium salt solution is greater than 0 and less than or equal to 3;

[0038] The first solvent includes water and / or alcohol;

[0039] The roasting temperature is 100-300℃ and the time is 2-4 h.

[0040] Furthermore, in the third-stage reactor, an SBA-15 supported highly dispersed Pd / CeO2 catalyst is packed, wherein the Pd loading is 1-1.5 wt% and the CeO2 loading is 5-10 wt%.

[0041] The SBA-15 supported highly dispersed Pd / CeO2 catalyst was prepared according to the following method:

[0042] SBA-15 was dispersed in water, and ammonia was added to adjust the pH of the solution to 8–9. Then, cerium nitrate was added to the solution, and the reaction yielded CeO2 / SBA-15.

[0043] The mass ratio of cerium nitrate to SBA-15 is 8-16:100;

[0044] The CeO2 / SBA-15 above was dispersed in water, and hydrochloric acid was added to control the pH of the solution at 2-5 to obtain the first solution;

[0045] Subsequently, chloropalladium acid was dissolved in water, and hydrochloric acid was added to adjust its pH to 3, thus obtaining the second solution;

[0046] Under vigorous stirring, the second solution was slowly injected into the first solution, and after the reaction, the catalyst precursor was separated and dried.

[0047] The catalyst precursor is calcined in a reducing atmosphere to obtain the highly dispersed Pd / CeO2 catalyst supported on SBA-15, which is the Pd / CeO2@SBA-15 catalyst.

[0048] The mass ratio of the chloropalladium acid to SBA-15 is 3-5:100.

[0049] [The third technical solution]

[0050] The present invention also provides an application of the above-mentioned continuous preparation method for cyclopropanation reaction using a microreactor in the production of cyclopropane products.

[0051] This application method can effectively improve the conversion rate of cyclopropane products, while also shortening the reaction time and improving the safety of the reaction.

[0052] [Fourth technical solution]

[0053] The present invention also provides a three-stage series bottom-splashed microreactor, which can be used to implement the above-described preparation method, comprising:

[0054] Each reactor stage is equipped with high-speed splash nozzles at the bottom to create turbulence.

[0055] The reactor is made of Hastelloy or 316L stainless steel.

[0056] It can also be further integrated with an online infrared monitoring system to regulate the diazomethane generation rate in real time.

[0057] In the reaction of this invention, a continuous series of bottom-splashed microreactors are used, combined with a catalyst-packed structure design. The specific advantages of this approach can be explained from the perspectives of reaction mechanism and engineering safety as follows:

[0058] First, the advantages that can be obtained from the reaction mechanism are as follows:

[0059] Firstly, it can further achieve toxicity control and safety assurance for diazomethane:

[0060] In traditional batch reactor processes, diazomethane is highly toxic and explosive, requiring slow, drip-feeding addition in conventional batch reactions, posing an extremely high risk. In fixed-bed continuous flow reactor processes, diazomethane needs to be rapidly and uniformly mixed with the substrate to achieve cyclopropanation. If mixing is insufficient or residence time is too long, unreacted diazomethane may enter downstream equipment, causing a leakage risk.

[0061] The design and use of microreactors enable the in-situ generation and immediate consumption of diazomethane: within the microreactor, the diazomethane precursor reacts rapidly with alkali in the first reaction unit to generate diazomethane, which then reacts with olefins in subsequent units, preventing accumulation. Furthermore, the entire reaction system is sealed, and the microreactor is small in size; even if a leak occurs, it will only contain trace amounts of diazomethane, significantly reducing the risk of exposure.

[0062] Series microreactors can achieve low-temperature operation: Series microreactors can control the temperature in stages to suppress the decomposition of diazomethane (the decomposition product is an explosive CH2 free radical).

[0063] Secondly, it can further achieve precise control over the alkali solution.

[0064] During the reaction, an excess of alkali solution can lead to side reactions (such as olefin isomerization), while an insufficient amount will result in incomplete formation of diazomethane.

[0065] The series microreactors can achieve multi-stage alkali distribution: alkali is injected in stages (e.g., 80% is injected in the first unit and 20% is added in the third unit), and the pH sensor feedback adjustment ensures that the diazonium methane generation rate matches the consumption rate.

[0066] Meanwhile, the series microreactors can achieve efficient local mixing: their bottom splashing structure allows the alkali solution and precursor to form a thin liquid film on the catalyst surface, resulting in a short mass transfer distance and avoiding excessively high local pH.

[0067] Third, it can further enable control over the reaction rate.

[0068] Cyclopropaneation is a rapid exothermic reaction, and traditional reactions are prone to local overheating and byproducts due to uneven mixing.

[0069] The series microreactors can achieve the unique "pulsating" flow of the series reactors: each splashing unit is equivalent to a miniature continuous stirred tank reactor. The fluid is deflected between the units to form turbulence, which ensures that the reactants are fully renewed and avoids backmixing. Furthermore, the cascade design gradually reduces the concentration of reactants and suppresses over-reaction.

[0070] Secondly, the advantages that can be obtained from the perspective of engineering design and safety enhancement are as follows:

[0071] Firstly, the design of the bottom spray structure has special significance.

[0072] It can achieve highly efficient dispersion—the reactants are vertically sprayed into the catalyst bed from the bottom nozzle, forming a strong shear contact between "microdroplets and catalyst", which improves the mass transfer efficiency by 5–10 times compared with traditional packed beds.

[0073] It can achieve dynamic interface updates—splash flow continuously refreshes the active sites on the catalyst surface, preventing passivation, especially for easily deactivated metal catalysts.

[0074] Secondly, the safety design of series reactors has special significance.

[0075] It can achieve graded pressure release—each unit is equipped with an independent pressure relief valve. If a unit experiences overpressure due to the decomposition of diazonium methane, only that unit will trigger the release, without affecting the overall system. Simultaneously, it can achieve integrated quenching; the outlet of the last unit is directly injected with a weak acid to quench residual diazonium methane, achieving a quenching efficiency >99.9%.

[0076] In this invention, a dynamic equilibrium of reactant generation and consumption is achieved through multi-stage series connection, avoiding the accumulation of hazardous intermediates. The gradient distribution of alkali and catalyst matches the reaction kinetics requirements. The sputtering structure and microscale effects maximize mass / heat transfer efficiency, while this modular design combines safety with scale-up potential.

[0077] In the reaction of this invention, a composite catalyst of single-atom palladium (Pd) and cerium oxide supported on SBA-15 mesoporous molecular sieve is selected and combined with a continuous series bottom-splashed microreactor, which has the characteristics of higher efficiency and greater safety. The mechanism lies in both the catalyst structural characteristics and the synergistic effect of reaction engineering:

[0078] Firstly, the unique structure and advantages of the Pd / CeO2@SBA-15 catalyst.

[0079] Regarding the structural advantages of SBA-15 mesoporous molecular sieves:

[0080] Highly ordered mesoporous structure (2-50 nm): provides high specific surface area, ensuring highly dispersed active sites. Mesoporous channels can act as nanoreactors, restricting the diffusion paths of reactants and intermediates, and improving selectivity.

[0081] Surface silanol (Si-OH) modifiability: facilitates anchoring of Pd single atoms and CeO2 nanoparticles, preventing metal agglomeration.

[0082] Advantages of single-atom palladium loading:

[0083] Atomic-scale dispersed Pd active centers: Each Pd atom is exposed on the mesoporous surface, maximizing atomic utilization, while the utilization rate of traditional Pd nanoparticles is only 10–20%.

[0084] The electronic structure of single-atom Pd is regulated by the carrier cerium oxide, forming Pd-O-Ce active sites, which enhance the activation ability of diazomethane.

[0085] Suppressing Pd catalytic side reactions: Traditional Pd nanoparticles readily catalyze olefin polymerization, while single-atom Pd selectively promotes the cyclopropanation of carbene-inserted olefins.

[0086] Regarding the synergistic effect of cerium oxide:

[0087] Oxygen vacancies (Ov) in cerium oxide regulate electron transfer: Ce 3+ / Ce 4+ The redox pair can stabilize Pd single atoms and promote the decomposition of diazomethane to form carbene.

[0088] Cerium oxide's oxygen storage capacity: It can quench free radicals generated by side reactions and reduce coke formation.

[0089] Secondly, the synergistic effect mechanism between the continuous series bottom-splashed microreactor and its advantages.

[0090] Regarding mass transfer enhancement effects: mesoporous confinement effect and microreactor turbulence

[0091] The mesoporous channels of SBA-15 restrict reactant diffusion paths, leading to high-concentration aggregation of diazomethane and olefins near the Pd active sites. The strong shear flow of the splash-type microreactor breaks the diffusion layer limitations of traditional packed beds, allowing reactants to rapidly renew to the catalyst surface. The synergistic result is a more precise match between the residence time of reactants within the nanopores and the reaction time, preventing over-reaction.

[0092] On reaction kinetics optimization: gradient catalysis and stepwise consumption

[0093] Regarding the cascade design of the series reactors in this invention:

[0094] First-stage diazomethane generation: Efficient and controllable carbene generation, avoiding accumulation.

[0095] Second-stage carbene activation: promotes initial contact between carbene and olefins, reducing side reactions.

[0096] The third-order main reaction: maximizing the rate and selectivity of cyclopropanation.

[0097] The rapid heat transfer in the microreactor avoids localized hot spots. The low loading of single-atom Pd reduces the exothermic intensity, while the high loading of traditional Pd nanoparticles easily leads to runaway reactions.

[0098] The reaction in this invention can achieve excellent conversion rates while greatly improving safety, for the following two reasons:

[0099] From the perspective of catalysts, the mesoporous SBA-15 support utilizes the uniform pore size to exert a confinement effect, forming an enrichment of reactants and intermediates near the active sites within the pores. Combined with the highly selective activation of single-atom Pd and the stabilization of the reaction pathway by cerium oxide, the reaction efficiency is improved in three aspects.

[0100] From a reactor perspective, the splash-type microreactor enhances mass and heat transfer, and its series design achieves integrated reaction and quenching. Simultaneously, the microreactor's small size, combined with the intrinsically safe low-load of single-atom Pd, effectively mitigates the risk of diazomethane explosion.

[0101] In this invention, the choice to design a catalyst gradient distribution has unique significance:

[0102] In the design of multi-stage tandem microreactors for cyclopropaneation, conversion rate, selectivity, and safety can be significantly improved through gradient catalyst distribution and reaction stage optimization.

[0103] Catalyst gradient design for first- and third-stage tandem microreactors:

[0104] First stage: SBA-15 + low-loaded Pd, where Pd: 0.1-0.3wt%. In the initial stage of the reaction, it mildly catalyzes the decomposition of diazomethane, avoiding violent exothermic reactions. At the same time, it utilizes the mesoporous structure of SBA-15 to promote mass transfer.

[0105] Second stage: Cerium oxide supports single-atom Pd, where Pd: 0.5-1wt%. In this stage, the oxygen vacancies of cerium oxide are used to stabilize carbene, and the active sites of single-atom Pd promote the initial bonding of carbene to olefins.

[0106] Third stage: SBA-15 + highly dispersed Pd / CeO2, where Pd: 1-1.5wt%. In this stage, cyclopropanization is completed with high activity, and the confinement effect of SBA-15 improves selectivity.

[0107] Second, the mechanism and optimization basis of catalysts at each stage.

[0108] Level 1: SBA-15 + low-load Pd (0.1-0.3wt%)

[0109] Diazomethane decomposes into carbene under alkaline conditions; this reaction requires mild catalysis to avoid explosive side reactions.

[0110] SBA-15’s mesoporous structure provides a high specific surface area, ensuring uniform dispersion of reactants.

[0111] Low Pd loading (0.1-0.3 wt%) avoids excessive exothermic reactions while ensuring sufficient active sites. When the Pd loading is too high, the decomposition rate of diazomethane is too fast, which can easily lead to local overheating; while when the loading is too low, the reaction is incomplete.

[0112] Second stage: Cerium oxide supported on single-atom Pd (0.5-1wt%)

[0113] The oxygen vacancies (Ov) in cerium oxide stabilize the carbene intermediate, preventing its self-decomposition. Single-atom Pd provides highly active sites, promoting the initial bonding of the carbene with the olefin to form a cyclopropane precursor.

[0114] Third stage: SBA-15 + highly dispersed Pd / CeO2 (1-1.5wt%)

[0115] At this stage, the reactant concentration has decreased, and the mesoporous confinement effect of SBA-15 increases the enrichment concentration of intermediates. The high loading of Pd accelerates the cyclopropanation main reaction, ensuring the complete reaction.

[0116] Third, security

[0117] Graded temperature control: Level 1 (10-15℃) → Level 2 (15-20℃) → Level 3 (20-35℃), gradually increasing the temperature. The low temperature stage suppresses side reactions, while the high temperature stage promotes the complete reaction.

[0118] Pressure staged release: Each stage is equipped with an independent pressure relief valve to avoid chain overpressure, and the anti-carbon deposit performance of SBA-15 can extend the service life of the catalyst.

[0119] The present invention has the following beneficial effects:

[0120] 1. The gradient catalyst loading design of this invention reduces the amount of precious metals used and scientifically allocates active sites. By controlling the Pd loading in stages, active sites are concentrated in key steps. The first stage only requires a low Pd loading to achieve the mild generation and conversion decomposition of diazomethane, avoiding excessive waste of precious metals. The oxygen vacancies of cerium oxide stabilize the carbene intermediate, reducing dependence on high Pd loading and further reducing costs.

[0121] 2. The three-stage series microreactor of this invention provides efficient mass and heat transfer, suppressing side reactions and pollution. The short residence time and precise temperature control of the microreactor can suppress the random decomposition of diazonium methane or carbene insertion side reactions, improving reaction selectivity. The acid quenching layer immediately neutralizes residual carbene, preventing toxic intermediates from entering downstream processes, reducing the content of harmful substances in waste liquid, and meeting the requirements of green chemical engineering.

[0122] 3. In the design of a three-stage tandem microreactor for the cyclopropane reaction, this invention significantly improves conversion rate, selectivity, and safety through gradient catalyst distribution and reaction stage optimization. The design of the microreactor and the corresponding catalyst type and dosage of this invention can achieve a cyclopropane yield of >95%.

[0123] 4. The modular design of this invention improves reactor efficiency and scalability. It can be flexibly adapted to the reaction stage, and each reactor can be optimized independently. It is convenient to adjust parameters when scaling up production and avoids the "scale-up effect" of traditional fixed beds.

[0124] 5. The catalyst designed in this invention offers extended lifespan and convenient regeneration. The mesoporous structure and highly dispersed Pd / CeO2 design of SBA-15 prevent metal agglomeration, while the oxygen vacancies of cerium oxide adsorb byproducts, extending catalyst lifespan. Furthermore, if a stage of the catalyst deactivates, that module can be replaced individually without requiring a complete shutdown, reducing maintenance costs. Attached Figure Description

[0125] Figure 1 This is a schematic diagram of the bottom-jet three-stage series microreactor of the present invention;

[0126] Figure 2 This is a schematic diagram of the continuous preparation method of cyclopropaneation reaction using a microreactor according to the present invention.

[0127] Figure 3 This is a schematic diagram showing the distribution of propanation products of dicyclopentadiene in the product obtained in Example 1 of the present invention. Detailed Implementation

[0128] The present invention will be further described below with reference to specific embodiments and accompanying drawings:

[0129] Example 1:

[0130] Step 1: A mixture of 10% N-methyl-N-nitrosourea tetrahydrofuran (flow rate 19.5 mL / min), a 35% potassium hydroxide aqueous solution (flow rate 3 mL / min), and a 50% dicyclopentadiene tetrahydrofuran mixture (flow rate 2 mL / min) are simultaneously fed into a three-stage series bottom-splash microreactor.

[0131] The first-stage reactor is filled with 20 mL of SBA-15 supported single-atom palladium catalyst (Pd loading 0.3 wt%) at a temperature of 10 °C, and is used for the mild generation and conversion of diazomethane.

[0132] The second-stage reactor was filled with 30 mL of cerium oxide-supported single-atom palladium catalyst (Pd loading 0.8 wt%) at 15 °C for the stabilization of the carbene intermediate and preliminary cyclopropanation.

[0133] The third-stage reactor was filled with 50 mL of SBA-15-supported Pd / CeO2 catalyst (Pd and CeO2 loadings of 1.3 wt% and 7 wt%, respectively) at 20 °C to achieve efficient cyclopropanation.

[0134] The highly dispersed Pd / CeO2 catalyst supported on SBA-15 was prepared as follows: 100g of SBA-15 was dispersed in water, and ammonia was added to adjust the pH of the solution to 8-9. Then, 12g of cerium nitrate was added to the solution, and CeO2 / SBA-15 was obtained by reaction. The CeO2 / SBA-15 was dispersed in water, and hydrochloric acid was added to control the pH of the solution to 2-5 to obtain the first solution. Then, 4g of palladium chloroacetic acid was dissolved in water, and hydrochloric acid was added to adjust its pH to 3 to obtain the second solution. Under vigorous stirring, the second solution was slowly injected into the first solution, and the catalyst precursor was obtained after reaction by separation and drying.

[0135] The catalyst precursor was calcined in a reducing atmosphere at a temperature of 220°C for 3 hours to obtain the highly dispersed Pd / CeO2 catalyst supported on SBA-15, which is the Pd / CeO2@SBA-15 catalyst.

[0136] Step 2: The reaction effluent was quenched with 5 vol% acetic acid, held for 10 min, and then separated. The organic phase was then distilled to obtain the product, such as... Figure 3 As shown, the content of dicyclopentadiene monocyclopropane product is 59.2%, the content of dicyclopentadiene dicyclopropane product is 40.5%, the conversion rate of raw material dicyclopentadiene is greater than 99.9%, no local overheating occurs during the reaction process, and the catalyst can be reused.

[0137] Example 2

[0138] Step 1: A mixture of 10% N-methyl-N-nitrosourea xylene (flow rate 19.5 mL / min), 25% sodium hydroxide aqueous solution (flow rate 2.5 mL / min), and 50% dicyclopentadiene xylene (flow rate 2 mL / min) is fed into a three-stage series bottom-splash microreactor.

[0139] The first-stage reactor consisted of 10 mL of SBA-15 single-atom palladium catalyst (Pd 0.2wt%) at a temperature of 15℃.

[0140] Second-stage reactor: 20 mL cerium oxide single-atom palladium catalyst (Pd 1wt%), temperature 20℃.

[0141] The third-stage reactor used 30 mL of Pd / CeO2@SBA-15 catalyst (Pd and CeO2 loadings of 1.5 wt% and 5 wt%, respectively) at a temperature of 25°C. The catalyst preparation method was the same as in Example 1, except that 8 g of cerium nitrate and 5 g of palladium chloroacetic acid were added.

[0142] Step 2: The reaction effluent was quenched with 3 vol% acetic acid, held for 10 min, and then separated. Organic phase distillation yielded a product containing 76.4% dicyclopentadiene and 23.4% dicyclopentadiene and dicyclopropane. The conversion rate of the dicyclopentadiene feedstock was greater than 99.9%. No localized overheating occurred during the reaction, and the catalyst could be reused.

[0143] Example 3

[0144] Step 1: A mixture of 15% N-nitroso-N-methyl-p-toluenesulfonamide diethyl ether (flow rate 31.5 mL / min), a 45% potassium hydroxide aqueous solution (flow rate 3 mL / min, delivered to the bottom of the first and third reactors at ratios of 80% and 20% respectively), and a 50% myrcene diethyl ether mixture (flow rate 1 mL / min) are delivered to a three-stage series bottom-splash microreactor.

[0145] The first-stage reactor consisted of 30 mL of SBA-15 single-atom palladium catalyst (Pd 0.3 wt%) at a temperature of 10℃.

[0146] Second-stage reactor: 40 mL cerium oxide single-atom palladium catalyst (Pd 1.0 wt%), temperature 15℃.

[0147] The third-stage reactor used 60 mL of Pd / CeO2@SBA-15 catalyst (Pd and CeO2 loadings of 1 wt% and 10 wt%, respectively) at a temperature of 35°C. The catalyst preparation method was the same as in Example 1, except that 16 g of cerium nitrate and 3 g of palladium chloroacetic acid were added.

[0148] Step 2: The reaction effluent was quenched with 8 vol% citric acid, held for 10 min, and then separated. After organic phase distillation, the product contained 25.6% myrcene tricyclopropane, 56.2% myrcene dicyclopropane, and 18.0% myrcene monocyclopropane. The conversion rate of the raw material myrcene was greater than 99.9%. No local overheating occurred during the reaction, and the catalyst could be reused.

[0149] Example 4

[0150] Step 1: A mixture of 30% N-methyl-N-nitrosourea glycol monomethyl ether (flow rate 32.1 mL / min), 30% sodium hydroxide aqueous solution (flow rate 6 mL / min), and 55% myrcene glycol monomethyl ether (flow rate 2 mL / min) is fed into a three-stage series bottom-splash microreactor.

[0151] The first-stage reactor consisted of 15 mL of SBA-15 single-atom palladium catalyst (Pd 0.1 wt%) at a temperature of 12℃.

[0152] Second-stage reactor: 25 mL cerium oxide single-atom palladium catalyst (Pd 0.5 wt%), temperature 18℃.

[0153] The third-stage reactor used 40 mL of Pd / CeO2@SBA-15 catalyst (Pd and CeO2 loadings of 1.5 wt% and 6 wt%, respectively) at a temperature of 32°C. The catalyst preparation method was the same as in Example 1, except that 10 g of cerium nitrate and 5 g of palladium chloroacetic acid were added.

[0154] Step 2: The reaction effluent was quenched with 6 vol% acetic acid, held for 10 min, and then separated. After organic phase distillation, the product contained 12.2% myrcene tricyclopropane, 64.2% myrcene dicyclopropane, and 23.3% myrcene monocyclopropane. The conversion rate of the raw material myrcene was greater than 99.9%. No local overheating occurred during the reaction, and the catalyst could be reused.

[0155] Comparative Example 1: Traditional batch reactor and conventional catalyst system

[0156] This comparative example uses a conventional batch reactor for the cyclopropanation reaction of cyclohexene. The reaction system is consistent with that of Example 1: the catalyst is a commonly used industrial 5 wt% Pd / C (palladium on carbon catalyst), with a loading of more than 5 times the total Pd content in Example 1.

[0157] Operating conditions: The reaction was carried out in a 500 mL glass reactor equipped with mechanical stirring (500 rpm) and a low-temperature circulating bath for temperature control; the reaction temperature was controlled at 22 °C (the same as the first stage temperature in Example 1); the diazomethane precursor was added slowly (over 1 hour) to avoid violent exothermic reactions; after a total reaction time of 2 hours, 3 vol% acetic acid was injected to quench the reaction.

[0158] Test results: The yield of the monocyclopropane product was 78%, significantly lower than the >99% of Example 1;

[0159] Local overheating occurred during the reaction, with a temperature difference ΔT reaching 12℃, requiring an additional ice bath for temperature control.

[0160] Catalyst stability: The activity of Pd / C catalyst decreases by 40% after one use, requiring regeneration. More importantly, the total reaction time increases significantly.

[0161] Comparative Example 2: Fixed-bed reactor and conventional catalyst system

[0162] In this comparative example, the reaction system was consistent with that of Example 1: the mixture was simultaneously fed into a fixed-bed reactor; the fixed-bed reactor was packed with 100 ml of Pd / SiO2 with a palladium mass loading of 10 wt%, a catalyst, and the organic phase was hydrogenated and distilled to obtain dicyclopentadiene monocyclopropane product, with a monocyclopropane product yield of 90%. Local overheating occurred during this reaction process, and the catalyst was prone to deactivation.

[0163] Compared with traditional processes, the three-stage series bottom-splash microreactor of this patent can greatly improve the yield, shorten the total reaction time, and enhance safety. From the perspective of catalyst, the amount of precious metals used is reduced, which also effectively reduces costs.

[0164] The present invention has been described above by way of example with reference to the embodiments and accompanying drawings. Obviously, the implementation of the present invention is not limited to the above-described manner. Any improvements made by adopting the inventive concept and technical solution of the present invention, or the direct application of the inventive concept and technical solution of the present invention to other occasions without modification, are all within the protection scope of the present invention.

Claims

1. A continuous preparation method for cyclopropanation reaction using a microreactor, characterized in that, Includes the following steps: Step 1: The olefin, alkali solution, solvent, and diazomethane precursor are fed into a microreactor for reaction; wherein the microreactor is a three-stage series bottom-splash microreactor, and the reaction rate is controlled by setting temperature gradients in the first-stage reactor, the second-stage reactor, and the third-stage reactor; different catalysts are filled in the first-stage reactor, the second-stage reactor, and the third-stage reactor of the three-stage series bottom-splash microreactor; Step 2: After the reaction is completed, the reaction product of Step 1 is quenched by the quenching unit and flows out. After separating the organic phase and the aqueous phase, the organic phase is separated and purified to obtain the cyclopropane product. In the aforementioned three-stage tandem bottom-splashed microreactor, the catalysts filled are as follows: First-stage reactor: filled with single-atom palladium catalyst supported on SBA-15 mesoporous molecular sieve, used to milden the reaction; Second-stage reactor: packed with cerium oxide-supported single-atom palladium catalyst, used for the stabilization of carbene intermediates and preliminary cyclopropanation; The third-stage reactor is filled with a highly dispersed Pd / CeO2 catalyst supported on SBA-15, which is used to efficiently complete the cyclopropaneation reaction. The aforementioned three-stage series bottom-splash microreactor adopts a fractal channel design, with each stage reactor having independent temperature control. The temperature gradient is as follows: first stage reactor: 10-15℃; second stage reactor: 15-20℃; third stage reactor: 20-35℃. The alkaline solution in step 1 is an aqueous solution of potassium hydroxide or sodium hydroxide with a concentration of 25wt%-45wt%. The solvent is one of tetrahydrofuran, xylene, diethyl ether, or ethylene glycol monomethyl ether; The diazomethane precursor is N-methyl-N-nitrosourea or N-nitroso-N-methyl-p-toluenesulfonamide; The weak acid in the quenching unit is acetic acid or citric acid, and the injection amount is 3-8% of the reaction stream. In the catalyst of the first-stage reactor, a single-atom palladium catalyst is loaded onto the surface of a support by an impregnation method to form active sites; wherein the loading amount of single-atom palladium is 0.1-0.3 wt%. In the second-stage reactor, the cerium oxide-supported palladium single-atom catalyst is packed with a palladium single-atom content of 0.5-1.0 wt% based on the total mass of the cerium oxide-supported palladium single-atom catalyst. In the third-stage reactor, an SBA-15 supported highly dispersed Pd / CeO2 catalyst is packed, wherein the Pd loading is 1-1.5 wt% and the CeO2 loading is 5-10 wt%. The olefin mentioned in step 1 is dicyclopentadiene or myrcene; When the olefin is dicyclopentadiene, the cyclopropanation product in step 2 is dicyclopentadiene monocyclopropane and dicyclopentadiene dicyclopropane. When the olefin is myrcene, the cyclopropanation products in step 2 are myrcene monocyclopropane, myrcene bicyclopropane, and myrcene tricyclopropane.

2. The continuous preparation method for cyclopropaneation reaction using a microreactor according to claim 1, characterized in that: The cerium oxide-supported single-atom palladium catalyst was prepared according to the following method: An ammonium citrate solution and a palladium salt solution were mixed to obtain a metal-organic complex solution; The carrier is dispersed in the first solvent to obtain the first dispersion; The first dispersion and the organometallic complex solution were mixed and reacted to obtain the precursor. The precursor is calcined in a reducing atmosphere to obtain the cerium oxide-supported single-atom palladium catalyst.

3. The continuous preparation method for cyclopropanation reaction using a microreactor according to claim 2, characterized in that: The molar ratio of ammonium citrate in the ammonium citrate solution to palladium salt in the palladium salt solution is greater than 0 and less than or equal to 3. The first solvent includes water and / or alcohol; The roasting temperature is 100-300℃ and the time is 2-4 h.

4. The application of the continuous preparation method of cyclopropanation reaction using a microreactor as described in any one of claims 1-3 in the production of cyclopropane products.

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