A highly efficient composite catalyst for Michael addition reactions and its application methods

Abstract

A highly efficient composite catalyst for the Michael addition reaction and its application method are disclosed, relating to the field of catalytic chemistry. The composite catalyst comprises a main catalyst system, a co-catalytic modifier, and a reaction terminator. The main catalyst system is a composite of Lewis base catalyst A and metal salt catalyst B. The co-catalytic modifier works synergistically with the main catalyst system to enhance catalytic performance. In application, through steps such as raw material pretreatment, catalyst preparation, isothermal dropwise addition, temperature-controlled reaction, and termination treatment, this composite catalyst is used in the Michael addition step of the synthesis of 2-chloro-5-chloromethylpyridine, achieving synergistic optimization of catalytic activity and selectivity, providing a reliable technical solution for the efficient synthesis of related pesticide intermediates.

Description

Technical Field

[0001] This invention belongs to the field of catalytic chemistry, specifically relating to a highly efficient composite catalyst for Michael addition reactions and its application method. Background Technology

[0002] In the field of catalytic chemistry, the Michael addition reaction is one of the core reactions for constructing carbon-carbon bonds and is widely used in the synthesis of fine chemicals such as pesticides and pharmaceuticals. 2-Chloro-5-chloromethylpyridine, as a key intermediate in neonicotinoid pesticides, requires optimized synthesis for significant advancements in the pesticide industry. Currently, the industrial synthesis of this intermediate primarily utilizes the dicyclopentadiene route, which involves multiple reaction steps. The third step, the Michael addition reaction, is crucial in determining the overall synthesis efficiency, directly impacting the yield and quality of the final product.

[0003] Currently, most catalytic systems used for this Michael addition reaction are single catalysts with limited catalytic activity, resulting in low reaction yields that fail to meet the efficiency requirements of industrial production. Furthermore, single catalyst systems often require large dosages to maintain basic catalytic performance, increasing production costs and generating significant residues due to incomplete reactions, thus increasing the burden on waste treatment. In addition, existing catalytic systems suffer from insufficient selectivity, easily triggering side reactions that further reduce the yield of the target product, limiting their potential application in industrial production.

[0004] While some existing composite catalytic systems are used in Michael addition reactions, they primarily focus on the synthesis of non-pesticide intermediates. The selection and proportioning of catalytic components are often ill-suited to the specific reaction system in the synthesis of 2-chloro-5-chloromethylpyridine. Furthermore, these composite systems lack synergistic enhancement of activity and selectivity and are not optimized for industrial needs such as waste reduction and cost control during the reaction process. Therefore, developing a composite catalytic system with strong adaptability, high catalytic efficiency, and reduced catalyst usage and waste generation has become a pressing technical challenge in this field. Summary of the Invention

[0005] In order to overcome the above-mentioned defects of the prior art, the embodiments of the present invention provide a composite catalyst for the Michael addition reaction with high efficiency and its application method, which solves the problems of insufficient catalytic activity and selectivity, large amount of catalyst, large amount of waste generated and poor adaptability in the prior art.

[0006] To address the above problems, the present invention provides the following technical solution:

[0007] A highly efficient composite catalyst for the Michael addition reaction includes a main catalyst system, a co-catalytic regulating component, and a reaction terminator. The main catalyst system is composed of a Lewis base catalyst A and a metal salt catalyst B in a molar ratio of 0.53:1. The Lewis base catalyst A is a synergistic compound system of an organic base and an inorganic base. The amount of Lewis base catalyst A is 0.45% to 0.75% of the total mass of the main reactants. The molar ratio of the metal salt catalyst B to cycloheptan-2-aldehyde-5-ene in the main reactants is 0.011:1. The amount of the co-catalytic regulating component is 10% to 20% of the mass of Lewis base catalyst A. The molar ratio of the reaction terminator to cycloheptan-2-aldehyde-5-ene is 0.058:1.

[0008] Further, the organic base is selected from at least one of N,N-diisopropylethylamine, 4-dimethylaminopyridine, and 1,8-diazabicyclo[5.4.0]undec-7-ene, and the inorganic base is selected from at least one of cesium carbonate, potassium bicarbonate, and disodium hydrogen phosphate. The molar ratio of the organic base to the inorganic base is 1.2:1 to 2.8:1. During the compounding process, the organic base is first mixed and dissolved with anhydrous ethanol at a mass ratio of 1:5, and then the inorganic base, ground to a particle size of less than 50 μm, is slowly added. The stirring rate is 500 r / min to 800 r / min, and the stirring time is 30 min to 60 min. The molar ratio of the organic base to the inorganic base and the compounding process parameters are specified here to ensure that the two base components are fully integrated to form a stable synergistic system, avoiding the problem of insufficient catalytic efficiency of a single base component. At the same time, by controlling the specific stirring rate and time, it is ensured that the inorganic base is uniformly dispersed in the organic base solution, ensuring the stability and repeatability of the catalytic performance.

[0009] Furthermore, the metal salt catalyst B is a hydrated metal chloride, selected from at least one of zinc chloride hexahydrate, ferric chloride hexahydrate, and copper chloride dihydrate. The purity of metal salt catalyst B is not less than 99.5%, and it is vacuum dried at 120°C for 4-6 hours before use to remove water of crystallization. Here, the specific type of metal salt catalyst B is defined as a hydrated metal chloride, whose metal ions can form synergistic catalytic sites with Lewis base catalyst A, enhancing the catalytic activity for the reaction. Clearly defining the purity requirements of catalyst B and the vacuum drying process before use removes impurities and water of crystallization from interfering with the catalytic system, avoiding side reactions initiated by impurities or damage to the catalytic active sites by water of crystallization, ensuring that catalyst B always maintains highly efficient catalytic performance.

[0010] Furthermore, the co-catalytic regulating component is an organophosphorus compound selected from at least one of triphenylphosphine, tributylphosphine, and diphenylmethylphosphine. The introduction of organophosphorus co-catalytic regulating components allows for the optimization of the spatial structure of the catalytic active center by regulating the electron cloud density of the main catalyst system, thereby improving selectivity for the target reaction and reducing side reactions. Limiting the specific type of co-catalytic regulating component ensures its compatibility with the main catalyst system, preventing a decrease in catalytic efficiency due to component mismatch.

[0011] Furthermore, the reaction terminator is a Lewis acid, selected from at least one of anhydrous aluminum trichloride, anhydrous ferric chloride, and antimony pentachloride. The particle size of the reaction terminator is controlled within the range of 20 μm to 40 μm, and it is activated at 80°C for 2 hours under a nitrogen atmosphere before use. It is explicitly stated here that the specific type of reaction terminator is a Lewis acid, which can rapidly react with the active component in the catalytic system to terminate the Michael addition reaction and avoid excessive reaction and side reactions. Limiting the particle size range and activation process of the reaction terminator improves its contact efficiency with the reaction system, ensuring rapid and complete termination of the reaction. Simultaneously, the activation treatment under a nitrogen atmosphere removes moisture and impurities adsorbed on the surface of the Lewis acid, preventing them from affecting the stability of the reaction system and the purity of the target product.

[0012] The present invention provides a highly efficient composite catalyst for the Michael addition reaction, with the core objective of improving the catalytic efficiency of the Michael addition reaction in the synthesis of 2-chloro-5-chloromethylpyridine. This is achieved by constructing a main catalyst system consisting of a Lewis base catalyst A and a metal salt catalyst B, combined with an organophosphorus co-catalytic modulator and a Lewis acid reaction terminator. The synergistic effect between these components optimizes the electronic environment and spatial structure of the catalytic active center. Simultaneously, the precise determination of the dosage ratio, specific type, and pretreatment process of each component enables a simultaneous improvement in catalytic activity and selectivity, reducing catalyst usage and waste generation, and adapting to the specific requirements of the target reaction system.

[0013] As a general inventive concept, this invention provides a method for applying the highly efficient composite catalyst for Michael addition reactions as described above, comprising the following steps:

[0014] S1. Select a four-necked reaction flask equipped with a mechanical stirrer, a double dropping funnel, a precision thermometer, and a reflux condenser as the reaction vessel. Add a solvent to the reaction vessel. The solvent is selected from anhydrous toluene, anhydrous xylene, and anhydrous acetonitrile. The water content of the solvent is not higher than 0.05%. The mass ratio of the solvent to cyclohepta-2-al-5-ene is 3.2:1 to 4.8:1.

[0015] S2. Accurately measure the two raw materials according to the molar ratio of cyclohepta-2-aldehyde-5-ene to acrylonitrile of 1:2. After filtering the two raw materials through a 5μm filter membrane, add them to a closed mixing container and mix at a stirring rate of 300r / min~400r / min for 15min~20min to prepare a homogeneous mixture of reaction raw materials.

[0016] S3. Prepare a solution of metal salt catalyst B. The solvent used is the same anhydrous solvent as in step S1. The mass ratio of metal salt catalyst B to solvent is 1:12 to 1:18. Ultrasonic assistance is used during the dissolution process. The ultrasonic power is 100W to 200W and the ultrasonic time is 15min to 25min to ensure complete dissolution.

[0017] S4. Add Lewis base catalyst A and co-catalytic adjustment component sequentially to the reaction vessel of step S1, turn on mechanical stirring at a stirring rate of 400 r / min to 600 r / min, and simultaneously adjust the temperature of the reaction system to 28℃ to 38℃ using a constant temperature water bath, with temperature fluctuation controlled within ±0.5℃, and perform constant temperature pretreatment for 10 min to 15 min.

[0018] S5. Add the metal salt catalyst B solution prepared in step S3 and the reaction raw material mixture prepared in step S2 to two dropping funnels respectively. Under the constant temperature condition in step S4, start dropping them simultaneously into the four-necked reaction flask. The dropping rate of the metal salt catalyst B solution is 0.6 mL / min to 1.8 mL / min, and the dropping rate of the reaction raw material mixture is 1.2 mL / min to 2.8 mL / min. Control the dropping rate with a precision flow meter to ensure that the metal salt catalyst B solution is dropped completely first, and the reaction raw material mixture is dropped completely within 2 minutes after the metal salt catalyst B solution is dropped.

[0019] S6. After the addition is complete, maintain the temperature of the reaction system at 28℃~38℃ and the stirring speed at 400r / min~600r / min for 20min. Record the temperature and pressure of the reaction system every 5min during the reaction.

[0020] S7. After the heat preservation reaction is completed, the reaction terminator is prepared into a 0.5 mol / L solution using the anhydrous solvent in step S1. It is then slowly added to the reaction system at a stirring rate of 500 r / min to 700 r / min, with a dropping rate of 0.3 mL / min to 0.8 mL / min. After the addition is complete, the reaction is stirred for another 6 min to 9 min to complete the Michael addition reaction.

[0021] Furthermore, in step S1, the volume of the four-necked reaction flask is 1.5 to 2 times the total volume of the reaction system. Before use, the reaction vessel is baked at 120°C for 2 hours, cooled, and then purged with nitrogen 3 to 5 times, with a nitrogen purity of not less than 99.99%. This limitation on the volume ratio of the four-necked reaction flask provides sufficient reaction space for the reaction system, avoiding uneven material mixing or excessive pressure fluctuations due to insufficient volume. The baking and nitrogen purging processes remove residual moisture and air from the vessel, preventing moisture and air from damaging the active centers of the catalytic system. The high purity requirement of nitrogen further ensures the stability of the reaction environment and prevents impurities from interfering with the smooth progress of the target reaction.

[0022] Furthermore, in step S2, the purity of cycloheptane-2-aldehyde-5-ene is not less than 99.0%, the purity of acrylonitrile is not less than 99.5%, and the moisture content of both raw materials is not higher than 0.03%. The purity and moisture content standards for cycloheptane-2-aldehyde-5-ene and acrylonitrile are specified here. High-purity raw materials can reduce side reactions caused by impurities and decrease the inhibitory effect of impurities on the activity of the catalytic system. Strict control of the moisture content of the raw materials can prevent the interaction between moisture and catalyst components, prevent the deactivation of catalytic active centers, ensure the reactivity of the raw materials during the reaction process, and ensure the yield efficiency and purity of the target product.

[0023] Furthermore, in step S5, the pressure of the reaction system during the dropwise addition process is controlled between 0.1 MPa and 0.12 MPa. If the pressure exceeds this range, pressure compensation is achieved by adjusting the nitrogen gas introduction rate, which is between 10 mL / min and 30 mL / min. This clearly defines the pressure range of the reaction system during the dropwise addition process. A stable pressure environment ensures the structural stability of the catalytic active centers, preventing abnormal pressure from causing a decrease in catalytic efficiency or an increase in side reactions. Pressure compensation through nitrogen gas introduction rate adjustment allows for precise control of pressure fluctuations in the reaction system. Simultaneously, the introduction of nitrogen gas isolates the system from air, preventing air components from affecting the reaction process and ensuring the stability of the dropwise addition process and the repeatability of the reaction results.

[0024] Furthermore, the preparation of the reaction terminator solution in step S7 is carried out under nitrogen protection to prevent the Lewis acid from hydrolyzing due to contact with moisture in the air. The requirement that the reaction terminator solution be prepared under nitrogen protection effectively prevents the Lewis acid from hydrolyzing due to contact with moisture in the air, preventing hydrolysis products from affecting the activity of the terminator; maintaining the high efficiency of the terminator ensures its rapid and complete reaction with the active components in the catalytic system, accurately terminating the Michael addition reaction, avoiding over-reaction and side reactions, and ensuring the purity and yield stability of the target product.

[0025] The present invention discloses a method for applying a highly efficient composite catalyst for the Michael addition reaction. By optimizing the pretreatment process of the reaction vessel, raw materials, and catalyst solution, precisely controlling key parameters such as reaction temperature, pressure, and stirring rate, rationally designing the matching relationship between the droplet order and rate, and combining nitrogen protection and precise use of terminator, a stable and controllable reaction environment is constructed. This ensures that the synergistic catalytic effect of each component of the composite catalyst is fully exerted, reduces side reactions, and improves reaction repeatability, thereby meeting the industrial requirements of high efficiency emission reduction and cost control.

[0026] Compared with the prior art, the advantages of the present invention are as follows:

[0027] (1) This invention optimizes the electronic environment and spatial structure of the catalytic active center by combining Lewis base catalyst A and metal salt catalyst B with organophosphorus co-catalytic adjustment components, thereby enhancing the activation ability of the reaction substrate and significantly improving the catalytic efficiency of Michael addition reaction, thus meeting the specific reaction system requirements for the synthesis of 2-chloro-5-chloromethylpyridine.

[0028] (2) The precise regulation of the co-catalytic regulating component and the compatibility design of each catalyst component in this invention effectively suppress the occurrence of side reactions, improve the selectivity of the target product, reduce the generation of impurities, and ensure the stability of product purity.

[0029] (3) The synergistic effect of the main catalyst system of the present invention reduces the amount of single catalyst used. At the same time, the precise parameter design of raw material pretreatment, catalyst preparation and reaction process reduces material loss, and achieves effective control of production cost from both catalyst consumption and raw material utilization.

[0030] (4) The improved catalytic efficiency and optimized reaction selectivity of this invention make the reaction more thorough, reduce the generation of solid waste such as reactor residue, and at the same time, the controllability of the process reduces the emission of pollutants during the reaction, thus alleviating the pressure of environmental protection treatment.

[0031] (5) The present invention has constructed a stable and controllable reaction environment by pretreatment of reaction vessel, nitrogen protection, precise limitation of key process parameters and optimization of pretreatment process of each component, avoiding interference of moisture, impurities and external condition fluctuations on the reaction, and ensuring the consistency and repeatability of reaction results of different batches.

[0032] (6) The process design of this invention meets the needs of industrial production. The parameters of each step are clear and easy to control. The catalyst components are easy to obtain, the pretreatment process is simple, the reaction conditions are mild, no special equipment is required, and it can be directly adapted to the existing production system for promotion and application. Attached Figure Description

[0033] Figure 1 This is a flowchart of a composite catalyst for highly efficient Michael addition reaction and its application method according to the present invention. Detailed Implementation

[0034] To facilitate understanding of the present invention, the invention will be described more fully and in detail below with reference to the accompanying drawings and preferred embodiments, but the scope of protection of the present invention is not limited to the following specific embodiments.

[0035] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by those skilled in the art. The technical terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the scope of the invention.

[0036] Unless otherwise specified, all raw materials, reagents, instruments and equipment used in this invention can be purchased from the market or prepared by existing methods.

[0037] Example 1

[0038] refer to Figure 1 A highly efficient composite catalyst for the Michael addition reaction of the present invention comprises a main catalyst system, a co-catalytic regulating component, and a reaction terminator. The main catalyst system is composed of a Lewis base catalyst A and a metal salt catalyst B in a molar ratio of 0.53:1. The amount of Lewis base catalyst A is 0.6% of the total mass of the main reactants. The molar ratio of metal salt catalyst B to cyclohepta-2-aldehyde-5-ene in the main reactants is 0.011:1. The amount of co-catalytic regulating component is 15% of the mass of Lewis base catalyst A. The molar ratio of the reaction terminator to cyclohepta-2-aldehyde-5-ene is 0.058:1. Catalyst A is a synergistic compound system of N,N-diisopropylethylamine and cesium carbonate in a molar ratio of 2:1. During the compounding process, N,N-diisopropylethylamine and anhydrous ethanol are first mixed and dissolved at a mass ratio of 1:5, and then cesium carbonate, ground to a particle size of 40 μm, is slowly added. The stirring rate is 650 r / min and the stirring time is 45 min. Metal salt catalyst B is zinc chloride hexahydrate with a purity of 99.8%, which is dried under vacuum at 120℃ for 5 h to remove water of crystallization before use. The co-catalytic regulating component is triphenylphosphine. The reaction terminator is anhydrous aluminum trichloride with a particle size controlled at 30 μm, which is activated at 80℃ for 2 h under a nitrogen atmosphere before use.

[0039] The application method of the highly efficient composite catalyst for the Michael addition reaction in this embodiment includes the following steps.

[0040] S1. A four-necked reaction flask equipped with a mechanical stirrer, a double dropping funnel, a precision thermometer, and a reflux condenser was selected as the reaction vessel. The volume of the four-necked reaction flask was 1.8 times the total volume of the reaction system. Before use, the reaction vessel was baked at 120°C for 2 hours and then purged with 99.99% pure nitrogen four times. Anhydrous toluene was added to the reaction vessel as solvent. The water content of the solvent was 0.03%, and the mass ratio of the solvent to cyclohepta-2-al-5-ene was 4:1.

[0041] S2. The cyclohepta-2-aldehyde-5-ene and acrylonitrile were precisely measured at a molar ratio of 1:2. The purity of cyclohepta-2-aldehyde-5-ene was 99.2%, the purity of acrylonitrile was 99.7%, and the moisture content of both raw materials was 0.02%. After filtering the two raw materials through a 5μm filter membrane, they were added to a sealed mixing container and mixed at a stirring rate of 350r / min for 18min to prepare a homogeneous mixture of reaction raw materials.

[0042] S3. Prepare a solution of metal salt catalyst B. Anhydrous toluene is used as the solvent. The mass ratio of metal salt catalyst B to solvent is 1:15. Ultrasonic assistance is used during the dissolution process. The ultrasonic power is 150W and the ultrasonic time is 20min to ensure complete dissolution.

[0043] S4. Add Lewis base catalyst A and co-catalytic adjustment component sequentially to the reaction vessel of step S1, start mechanical stirring at a stirring rate of 500 r / min, and simultaneously adjust the temperature of the reaction system to 33℃ using a constant temperature water bath, with temperature fluctuation controlled within ±0.5℃, and perform constant temperature pretreatment for 12 min.

[0044] S5. Add the metal salt catalyst B solution prepared in step S3 and the reaction mixture prepared in step S2 to two dropping funnels respectively. Under the constant temperature conditions of step S4, start dropping them simultaneously into the four-necked reaction flask. The dropping rate of the metal salt catalyst B solution is 1.2 mL / min, and the dropping rate of the reaction mixture is 2 mL / min. Control the dropping rate with a precision flow meter to ensure that the metal salt catalyst B solution is added first, and the reaction mixture is added within 2 minutes after the metal salt catalyst B solution is added. During the dropping process, the pressure of the reaction system is controlled at 0.11 MPa. If the pressure exceeds the range, the pressure is compensated by adjusting the nitrogen gas introduction rate, which is 20 mL / min.

[0045] S6. After the addition is complete, maintain the reaction system temperature at 33℃ and the stirring rate at 500r / min for 20min. Record the temperature and pressure of the reaction system every 5min during the reaction.

[0046] S7. After the heat preservation reaction is completed, the reaction terminator is prepared into a 0.5 mol / L solution with anhydrous toluene. The preparation process is carried out under nitrogen protection to avoid the Lewis acid from contacting moisture in the air and causing hydrolysis. The solution is slowly added to the reaction system at a stirring rate of 600 r / min and a dropping rate of 0.5 mL / min. After the addition is complete, the reaction is stirred for another 7 min to complete the Michael addition reaction.

[0047] Example 2

[0048] The difference between this embodiment and Example 1 is that Lewis base catalyst A is replaced with a compound system of 4-dimethylaminopyridine and potassium bicarbonate in a molar ratio of 2:1. In the compounding process, 4-dimethylaminopyridine and anhydrous ethanol are first mixed and dissolved in a mass ratio of 1:5, and then potassium bicarbonate ground to a particle size of 45 μm is slowly added. The stirring rate is controlled at 600 r / min, and the mixture is stirred continuously for 40 min to obtain the compound system. The remaining process steps and parameters are the same as in Example 1.

[0049] Example 3

[0050] The difference between this embodiment and Example 1 is that the metal salt catalyst B is replaced with ferric chloride hexahydrate with a purity of 99.6%; the co-catalytic regulating component is replaced with tributylphosphine; the remaining process steps and parameters are the same as in Example 1.

[0051] Example 4

[0052] The difference between this embodiment and Example 1 is that the reaction temperature is adjusted to 35°C, the stirring rate is 550 r / min, the dropping rate of the metal salt catalyst B solution is 1.5 mL / min, the dropping rate of the reaction raw material mixture is 2.5 mL / min, and the amount of the co-catalytic adjustment component is 18% of the mass of Lewis base catalyst A. The remaining process steps and parameters are the same as in Example 1.

[0053] Example 5

[0054] The difference between this embodiment and Embodiment 1 is that the nitrogen protection and raw material filtration pretreatment steps are omitted during the reaction process, while the remaining process steps and parameters are the same as in Embodiment 1.

[0055] Example 6

[0056] The difference between this embodiment and Example 1 is that the organic base of Lewis base catalyst A is replaced with 1,8-diazabicyclo[5.4.0]undec-7-ene, while the inorganic base remains cesium carbonate, with a molar ratio of 2:1. In the compounding process, 1,8-diazabicyclo[5.4.0]undec-7-ene and anhydrous ethanol are first mixed and dissolved at a mass ratio of 1:5, and then cesium carbonate ground to a particle size of 40 μm is slowly added. The stirring rate is controlled at 650 r / min, and the mixture is stirred continuously for 45 min to obtain the compounding system. The remaining process steps and parameters are the same as in Example 1.

[0057] Example 7

[0058] The difference between this embodiment and Example 1 is that the organic base is still N,N-diisopropylethylamine, and the inorganic base of Lewis base catalyst A is replaced with disodium hydrogen phosphate, with a molar ratio of 2:1. In the compounding process, N,N-diisopropylethylamine and anhydrous ethanol are first mixed and dissolved at a mass ratio of 1:5, and then disodium hydrogen phosphate ground to a particle size of 48 μm is slowly added. The stirring rate is controlled at 650 r / min, and the mixture is stirred continuously for 45 min to obtain the compounding system. The remaining process steps and parameters are the same as in Example 1.

[0059] Example 8

[0060] The difference between this embodiment and Example 1 is that the metal salt catalyst B is replaced with copper chloride dihydrate with a purity of 99.6%. Before use, it is vacuum dried at 120°C for 5 hours to remove water of crystallization. The remaining process steps and parameters are the same as in Example 1.

[0061] Example 9

[0062] The difference between this embodiment and Example 1 is that the co-catalytic regulating component is replaced with diphenylmethylphosphine, and its dosage is 15% of the mass of Lewis base catalyst A. The remaining process steps and parameters are the same as in Example 1.

[0063] Example 10

[0064] The difference between this embodiment and Example 1 is that the reaction terminator is replaced with anhydrous ferric chloride, the particle size of which is controlled at 32 μm. Before use, it is activated at 80°C for 2 hours under a nitrogen atmosphere. The molar ratio of ferric chloride to cyclohepta-2-al-5-ene is still 0.058:1. The remaining process steps and parameters are the same as in Example 1.

[0065] Example 11

[0066] The difference between this embodiment and Example 1 is that the reaction terminator is replaced with antimony pentachloride, the particle size of which is controlled at 28 μm. Before use, it is activated at 80°C for 2 hours under a nitrogen atmosphere. The molar ratio of antimony pentachloride to antimony pentachloride is still 0.058:1. The remaining process steps and parameters are the same as in Example 1.

[0067] Comparative Example 1

[0068] The difference between this comparative example and Example 1 is that only metal salt catalyst B is used as a single catalyst, while the other process parameters remain the same as in Example 1.

[0069] Comparative Example 2

[0070] The difference between this comparative example and Example 1 is that the Lewis base catalyst A and metal salt catalyst B are retained, the co-catalytic adjustment component is removed, and the remaining components and process parameters are consistent with those of Example 1.

[0071] Comparative Example 3

[0072] The difference between this comparative example and Example 1 is that the amount of Lewis base catalyst A is 1%, the molar ratio of metal salt catalyst B to cyclohepta-2-al-5-ene is adjusted to 0.02:1, and the remaining components and process parameters are the same as in Example 1.

[0073] Comparative Example 4

[0074] The difference between this comparative example and Example 1 is that it uses a conventional triethylamine-lithium chloride composite catalytic system for the Michael addition reaction, which is suitable for the synthesis of pharmaceutical intermediates and other non-pesticide intermediates. The conventional process is applied to the Michael addition reaction of cyclohepta-2-aldehyde-5-ene, with triethylamine accounting for 5% of the molar amount of cyclohepta-2-aldehyde-5-ene, lithium chloride accounting for 3% of the molar amount of cyclohepta-2-aldehyde-5-ene, reaction temperature of 40°C, stirring speed of 300 r / min throughout the process, no nitrogen protection or pressure compensation control during the dropping process, a reaction holding time of 60 min, and anhydrous aluminum trichloride as the reaction terminator, which is added directly to the reaction system in solid form. This process is applied to the Michael addition reaction of cyclohepta-2-aldehyde-5-ene and acrylonitrile in this invention.

[0075] The testing method is as follows:

[0076] 1. Reaction yield: The reaction products were quantitatively analyzed by gas chromatography, and the yield was calculated as the percentage of the actual amount of the target product generated to the theoretical amount.

[0077] 2. Purity of the target product: The content of the target compound in the reaction product is determined by high performance liquid chromatography, and the purity is expressed as the mass percentage of the total product.

[0078] 3. Catalyst dosage reduction rate: The reduction rate is calculated by comparing the actual dosage of the composite catalyst of the present invention with that of the existing conventional catalytic system, using (conventional dosage - dosage of the present invention) / conventional dosage × 100%.

[0079] 4. Reduction rate of reactor residue generation: After the reaction is completed, the reactor residue is collected by filtration and dried to constant weight. The reactor residue mass of the present invention is compared with that of the existing process. The reduction rate is calculated as (reactor residue of the existing process - reactor residue of the present invention) / reactor residue of the existing process × 100%.

[0080] Table 1: Experimental Results of Examples 1-11 and Comparative Examples 1-4

[0081]

[0082] In summary, referring to Table 1, the reaction yield, target product purity, catalyst dosage reduction rate, and residue reduction rate of the examples are all significantly better than those of the comparative examples.

[0083] Comparative Example 1, using only a single metal salt catalyst, lacks the synergistic effect of the Lewis base catalyst and the co-catalytic adjustment component, resulting in insufficient catalytic activity and selectivity, leading to low reaction yield and product purity, and no effect on reducing catalyst dosage or residue. Comparative Example 2, lacking the co-catalytic adjustment component, cannot optimize the electronic environment and spatial structure of the catalytic active center, resulting in poor side reaction suppression; therefore, its yield, purity, catalyst dosage reduction rate, and residue reduction rate are all lower than those of the Example. In Comparative Example 3, the dosage of Lewis base catalyst A exceeds the limit, and the molar ratio of metal salt catalyst B to reactants is unreasonable, disrupting the synergistic balance of the main catalyst system, leading to a decrease in catalytic efficiency, and limiting the catalyst dosage reduction rate and residue reduction rate. The existing composite catalytic system used in Comparative Example 4 is suitable for non-pesticide intermediate synthesis scenarios, but is incompatible with the target reaction system of this invention; its catalytic activity and selectivity are difficult to meet the requirements, therefore, all performance indicators are inferior to those of the Example.

[0084] Example 1 achieves the maximum synergistic effect of each component by optimizing the ratio of each catalyst component and precisely controlling the process parameters, thus obtaining the best reaction yield, product purity and emission reduction and consumption reduction effect.

[0085] In Example 2, due to the adjustment of the compound system type of Lewis base catalyst A, although the catalytic performance was maintained, the synergistic efficiency decreased slightly, resulting in a slightly lower yield, purity, and related reduction rate indicators compared to Example 1.

[0086] The metal salt catalyst B replaced in Example 3 showed good compatibility with the co-catalytic adjustment component, further optimizing the catalytic active center. Therefore, the reaction yield and product purity were slightly higher than those in Example 1.

[0087] In Example 4, the adjusted reaction temperature, stirring rate, and dropping speed were within a reasonable range, ensuring the stable operation of the catalytic system, and thus all indicators remained at an excellent level.

[0088] Example 5 omitted the nitrogen protection and raw material filtration pretreatment steps, which resulted in the reaction system being affected by moisture and impurities, thus impacting the catalytic synergy effect. Consequently, the performance indicators were lower than those of other examples.

[0089] In Example 6, the organic base was replaced with 1,8-diazabicyclo[5.4.0]undec-7-ene, which has a slightly weaker ability to synergistically optimize the electronic environment with cesium carbonate than N,N-diisopropylethylamine, resulting in a slight decrease in catalytic synergy efficiency. Therefore, all indicators are slightly lower than in Example 1.

[0090] In Example 7, the inorganic base was replaced with disodium hydrogen phosphate, which is less alkaline than cesium carbonate. When combined with an organic base, its ability to regulate the electronic activity of the catalytic active center is weakened, and its synergy is poor. Therefore, all indicators are worse than those in Example 1.

[0091] In Example 8, metal salt catalyst B was replaced with copper chloride dihydrate. The ability of copper ions to form synergistic catalytic sites with the main catalytic system was slightly inferior to that of zinc ions, but the compatibility was good, and the catalytic efficiency was greatly improved, with all indicators approaching those of Example 1.

[0092] In Example 9, the co-catalytic regulating component was replaced with diphenylmethylphosphine. Its ability to regulate electron cloud density is similar to that of triphenylphosphine, with only a difference in steric hindrance. The catalytic selectivity did not change significantly, so the various indicators only showed slight changes.

[0093] In Example 10, the reaction terminator was replaced with anhydrous ferric chloride, which has excellent compatibility with the quenching of the catalytic system and can quickly and completely terminate the reaction to avoid side reactions. Therefore, the various indicators are close to those of Example 1.

[0094] In Example 11, the reaction terminator was replaced with antimony pentachloride, which has high quenching activity but is less compatible with the organic phase reaction system than aluminum-iron Lewis acids, resulting in a slight weakening of the quenching effect. Therefore, all indicators decreased slightly compared to Example 1.

Claims

1. A composite catalyst for highly efficient Michael addition reactions, characterized in that: The reaction mixture includes a main catalyst system, a co-catalytic regulating component, and a reaction terminator. The main catalyst system is a mixture of Lewis base catalyst A and metal salt catalyst B in a molar ratio of 0.53:

1. Lewis base catalyst A is a synergistic mixture of an organic base and an inorganic base. The organic base is selected from at least one of N,N-diisopropylethylamine, 4-dimethylaminopyridine, and 1,8-diazabicyclo[5.4.0]undec-7-ene. The inorganic base is selected from at least one of cesium carbonate, potassium bicarbonate, and disodium hydrogen phosphate. The amount of Lewis base catalyst A is 0.45% to 0.75% of the total mass of the main reactants. The metal salt catalyst B is water. The catalyst is a metal chloride, selected from at least one of zinc chloride hexahydrate, ferric chloride hexahydrate, and copper chloride dihydrate, wherein the molar ratio of the metal salt catalyst B to cyclohepta-2-aldehyde-5-ene in the main reactant is 0.011:1; the co-catalytic regulating component is an organophosphorus compound, selected from at least one of triphenylphosphine, tributylphosphine, and diphenylmethylphosphine, wherein the amount of the co-catalytic regulating component is 10% to 20% of the mass of Lewis base catalyst A; the reaction terminator is a Lewis acid, selected from at least one of anhydrous aluminum trichloride, anhydrous ferric chloride, and antimony pentachloride, wherein the molar ratio of the reaction terminator to cyclohepta-2-aldehyde-5-ene is 0.058:

1.

2. The composite catalyst for highly efficient Michael addition reaction according to claim 1, characterized in that: The molar ratio of the organic base to the inorganic base is 1.2:1 to 2.8:

1. During the compounding process, the organic base is first mixed and dissolved with anhydrous ethanol at a mass ratio of 1:5, and then the inorganic base, which has been ground to a particle size of less than 50 μm, is slowly added. The stirring speed is 500 r / min to 800 r / min, and the stirring time is 30 min to 60 min.

3. The composite catalyst for highly efficient Michael addition reaction according to claim 1, characterized in that: The purity of the metal salt catalyst B is not less than 99.5%, and it is dried under vacuum at 120°C for 4 to 6 hours before use to remove water of crystallization.

4. The composite catalyst for highly efficient Michael addition reaction according to claim 1, characterized in that: The particle size of the reaction terminator is controlled between 20 μm and 40 μm, and it is activated at 80°C for 2 hours under a nitrogen atmosphere before use.

5. The application of the composite catalyst according to any one of claims 1-4 in the highly efficient catalytic Michael addition reaction, characterized in that: Includes the following steps, S1. Select a four-necked reaction flask equipped with a mechanical stirrer, a double dropping funnel, a precision thermometer, and a reflux condenser as the reaction vessel. Add a solvent to the reaction vessel. The solvent is selected from anhydrous toluene, anhydrous xylene, and anhydrous acetonitrile. The water content of the solvent is not higher than 0.05%. The mass ratio of the solvent to cyclohepta-2-al-5-ene is 3.2:1 to 4.8:

1. S2. Accurately measure the two raw materials according to the molar ratio of cyclohepta-2-aldehyde-5-ene to acrylonitrile of 1:

2. After filtering the two raw materials through a 5μm filter membrane, add them to a closed mixing container and mix at a stirring rate of 300r / min~400r / min for 15min~20min to prepare a homogeneous mixture of reaction raw materials. S3. Prepare a solution of metal salt catalyst B. The solvent used is the same anhydrous solvent as in step S1. The mass ratio of metal salt catalyst B to solvent is 1:12 to 1:

18. Ultrasonic assistance is used during the dissolution process. The ultrasonic power is 100W to 200W and the ultrasonic time is 15min to 25min to ensure complete dissolution. S4. Add Lewis base catalyst A and co-catalytic adjustment component sequentially to the reaction vessel of step S1, turn on mechanical stirring at a stirring rate of 400 r / min to 600 r / min, and simultaneously adjust the temperature of the reaction system to 28℃ to 38℃ using a constant temperature water bath, with temperature fluctuation controlled within ±0.5℃, and perform constant temperature pretreatment for 10 min to 15 min. S5. Add the metal salt catalyst B solution prepared in step S3 and the reaction raw material mixture prepared in step S2 to two dropping funnels respectively. Under the constant temperature condition in step S4, start dropping them simultaneously into the four-necked reaction flask. The dropping rate of the metal salt catalyst B solution is 0.6 mL / min to 1.8 mL / min, and the dropping rate of the reaction raw material mixture is 1.2 mL / min to 2.8 mL / min. Control the dropping rate with a precision flow meter to ensure that the metal salt catalyst B solution is dropped completely first, and the reaction raw material mixture is dropped completely within 2 minutes after the metal salt catalyst B solution is dropped. S6. After the addition is complete, maintain the temperature of the reaction system at 28℃~38℃ and the stirring speed at 400r / min~600r / min for 20min. Record the temperature and pressure of the reaction system every 5min during the reaction. S7. After the heat preservation reaction is completed, the reaction terminator is prepared into a 0.5 mol / L solution using the anhydrous solvent in step S1. It is then slowly added to the reaction system at a stirring rate of 500 r / min to 700 r / min, with a dropping rate of 0.3 mL / min to 0.8 mL / min. After the addition is complete, the reaction is stirred for another 6 min to 9 min to complete the Michael addition reaction.

6. The application of the composite catalyst according to claim 5 in the highly efficient catalytic Michael addition reaction, characterized in that: In step S1, the volume of the four-necked reaction flask is 1.5 to 2 times the total volume of the reaction system. Before use, the reaction vessel is baked at 120°C for 2 hours and then cooled and purged with nitrogen 3 to 5 times. The purity of the nitrogen is not less than 99.99%.

7. The application of the composite catalyst according to claim 5 in the highly efficient catalytic Michael addition reaction, characterized in that: In step S2, the purity of cycloheptane-2-aldehyde-5-ene is not less than 99.0%, the purity of acrylonitrile is not less than 99.5%, and the moisture content of both raw materials is not higher than 0.03%.

8. The application of the composite catalyst according to claim 5 in the highly efficient catalytic Michael addition reaction, characterized in that: In step S5, the pressure of the reaction system during the dropwise addition process is controlled at 0.1 MPa to 0.12 MPa. If the pressure exceeds the range, pressure compensation is performed by adjusting the nitrogen gas introduction rate, which is 10 mL / min to 30 mL / min.

9. The application of the composite catalyst according to claim 5 in the highly efficient catalytic Michael addition reaction, characterized in that: The preparation of the reaction terminator solution in step S7 is carried out under nitrogen protection to prevent the Lewis acid from hydrolyzing due to contact with moisture in the air.

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