Continuous preparation system and method of pyroxasulfone

Abstract

The invention provides a continuous preparation system and method of pyroxasulfone. The continuous preparation system comprises a mixing device, a continuous oxidation reaction device, a continuous quenching device, a continuous devitrification device, a continuous solid-liquid separation device and a continuous drying device. Compared with intermittent preparation of pyroxasulfone, the continuous preparation system disclosed by the invention has the advantages that the reaction can be more stable, and the reaction temperature can be more accurately controlled, so that the problems of large heat release and high process risk in batch reaction can be effectively solved. Moreover, compared with a tank reactor, the continuous oxidation reaction device filled with the catalyst bed layer can improve the oxidation reaction rate, shorten the oxidation reaction time and improve the yield and selectivity of oxidation products.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a continuous preparation system and method of sulfonepyraclostrobin. Background Art

[0002] Pyroxasulfone is a new soil treatment herbicide that can be used to control grass and broadleaf weeds in corn, soybean, and wheat fields. Its mechanism of action is that after being absorbed by the young roots and shoots of weeds, it destroys the meristem and coleoptile of the seedlings. It is a potential inhibitor of the biosynthesis of VLCFA (very long side chain fatty acids, with 20 to 30 carbon atoms) in plants. It has received widespread attention due to its broad spectrum, high efficiency, and environmental friendliness.

[0003] At present, the production process of sulfonepyraclostrobin is as follows:

[0004] .

[0005] In the presence of a catalyst, the raw material 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole is oxidized with an oxidant in a solvent to obtain the product sulfonepyrazoline. However, this process route has the following technical problems: (1) The oxidation reaction is a high-risk process with high heat release and violent reaction, involving the use of controlled materials and high process risks; (2) The reaction involves a catalyst, which is expensive and environmentally unfriendly; (3) The oxidation reaction takes a long time, usually 5 to 24 hours, and the production efficiency is low.

[0006] On this basis, it is necessary to study and develop a more green, efficient and safe continuous preparation system and method of sulfonepyraclostrobin, which is helpful to improve reaction safety, reduce catalyst cost and shorten oxidation reaction time. Summary of the invention

[0007] The main purpose of the present invention is to provide a continuous preparation system and method of sulfonepyraclostrobin to solve the problems of high risk of oxidation section, high catalyst cost and long oxidation reaction time in the preparation process of sulfonepyraclostrobin in the prior art.

[0008] In order to achieve the above-mentioned objectives, the present invention provides a continuous preparation system of sulfonepyraclostrobin, which comprises: a mixing device, a continuous oxidation reaction device, a continuous quenching device, a continuous crystallization device, a continuous solid-liquid separation device and a continuous drying device. The mixing device is used to mix 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole with a solvent to obtain a raw material liquid; the mixing device is provided with a raw material inlet, a solvent inlet and a raw material liquid outlet; the continuous oxidation reaction device is used to react 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole with an oxidant under the catalysis of a catalyst to obtain an oxidation product system; the continuous oxidation reaction device is provided with a raw material liquid inlet, an oxidant inlet and an oxidation product system outlet; the raw material liquid inlet is connected to the raw material liquid outlet; a catalyst bed is provided inside the continuous oxidation reaction device, and the catalyst is loaded in the catalyst bed; the continuous quenching The quenching device is provided with a quenching agent inlet, an oxidation product system inlet and a quenching system outlet, and the oxidation product system inlet is connected to the oxidation product system outlet; the continuous quenching device is used to continuously quench the oxidation product system with a quenching agent to obtain a quenching system; the continuous crystallization device is provided with a quenching system inlet and a solid-liquid mixing system outlet, and the quenching system inlet is connected to the quenching system outlet; the continuous crystallization device is used to continuously crystallize the quenching system to obtain a solid-liquid mixing system; the continuous solid-liquid separation device is provided with a solid-liquid mixing system inlet and a solid-phase product outlet, and the solid-liquid mixing system inlet is connected to the solid-liquid mixing system outlet; the continuous drying device is provided with a solid-phase product inlet and a sulfonepyraclostrobin outlet, and the solid-phase product inlet is connected to the solid-phase product outlet; the continuous drying device is used to continuously dry the solid-phase product outputted from the solid-phase product outlet to obtain sulfonepyraclostrobin.

[0009] Furthermore, in the continuous oxidation reaction device, the loading amount of the catalyst is 50 to 80 vol%.

[0010] Furthermore, the catalyst is a supported catalyst, and preferably the active ingredient in the supported catalyst is selected from oxides formed by one or more of ruthenium, titanium, and vanadium, and the carrier in the supported catalyst is selected from one or more of alumina, silica, and activated carbon, preferably activated carbon.

[0011] Furthermore, the loading amount of the active component in the supported catalyst is 5 to 15 wt %.

[0012] Furthermore, the raw material liquid inlet and the raw material liquid outlet are connected through a raw material liquid delivery pipeline, and a first plunger pump is arranged on the raw material liquid delivery pipeline.

[0013] Furthermore, the continuous preparation system also includes an oxidant supply device, which is connected to the oxidant inlet through an oxidant delivery pipeline; a second plunger pump is arranged on the oxidant delivery pipeline.

[0014] Furthermore, the continuous oxidation reaction device is also equipped with a heating component, preferably the heating component is a jacket, and preferably a heat transfer medium is passed through the jacket.

[0015] Furthermore, the continuous oxidation reaction device is selected from a tubular reactor.

[0016] Furthermore, the continuous oxidation reaction device comprises 1 to 3 tubular reactors arranged in series in the liquid phase.

[0017] Furthermore, the above-mentioned continuous preparation system also includes a continuous washing device, which is used to wash the solid phase product to remove impurities and obtain a washing product; the continuous drying device is provided with a washing product inlet, and the washing product inlet is connected to the washing product outlet; preferably, the continuous washing device is provided with a spray component.

[0018] In order to achieve the above-mentioned purpose, another aspect of the present invention further provides a continuous preparation method of sulfonepyraclostrobin, using the above-mentioned continuous preparation system of sulfonepyraclostrobin provided by the present application to prepare sulfonepyraclostrobin, the continuous preparation method comprising: step S1, using a mixing device to mix 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole with a solvent to obtain a raw material liquid; step S2, passing the raw material liquid and an oxidant into a continuous oxidation reaction Step S3, passing the oxidation product system into a continuous quenching device and performing continuous quenching treatment with a quenching agent to obtain a quenching system; Step S4, passing the quenching system into a continuous crystallization device for continuous crystallization treatment to obtain a solid-liquid mixed system; Step S5, performing continuous solid-liquid separation treatment on the solid-liquid mixed system with a continuous solid-liquid separation device to obtain a solid phase product; Step S6, performing continuous drying treatment on the solid phase product with a continuous drying device to obtain pyraclostrobin.

[0019] Furthermore, the weight ratio of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole to the solvent is 1:(2-5).

[0020] Furthermore, in step S2, the feed rate ratio of the raw material liquid to the oxidant is (2-10):1.

[0021] Furthermore, in step S2, the feed rate of the raw material liquid is 1-50 g / min, the material residence time is 30-200 min, the feed rate of the oxidant is 1-13 g / min, and the material residence time is 30-200 min.

[0022] Furthermore, the temperature of the continuous oxidation reaction is 10 to 80°C, preferably 20 to 70°C.

[0023] Furthermore, the solvent is selected from one or more of tetrahydrofuran, methanol, acetonitrile, dichloromethane, dichloroethane and chloroform.

[0024] Furthermore, the oxidant is selected from one or more of hydrogen peroxide, ozone and sodium hypochlorite.

[0025] Furthermore, in step S3, the ratio of the feed rate of the oxidation product system to the feed rate of the quenching agent is 1:(1-5).

[0026] Furthermore, in step S3, the feed rate of the oxidation product system is 10-100 g / min, the material residence time is 5-30 min, the feed rate of the quenching agent is 1-50 g / min, and the material residence time is 5-30 min.

[0027] Furthermore, in step S4, the feed rate of the quenching system is 1 to 50 g / min, and the material residence time is 30 to 120 min.

[0028] Furthermore, in step S4, the temperature of the continuous crystallization treatment is 5 to 30°C.

[0029] Furthermore, in step S5, the feed rate of the solid-liquid mixing system is 1 to 50 g / min, and the material residence time is 10 to 30 min.

[0030] Furthermore, between step S5 and step S6, a washing agent is used to continuously wash the solid phase product to remove impurities to obtain a washed product; and step S6 includes continuously drying the washed product to obtain pyraclostrobin.

[0031] Furthermore, the continuous solid-liquid separation process is filtration or centrifugation.

[0032] Furthermore, the continuous washing treatment is performed by a leaching method.

[0033] Furthermore, the detergent is selected from one or more of water, n-heptane, methanol, isopropanol and ethanol.

[0034] Furthermore, in step S6, the feed rate of the washed product is 1 to 50 g / min, and the material residence time is 5 to 30 min.

[0035] Furthermore, the temperature of the continuous drying process is 20-80°C.

[0036] By applying the technical solution of the present invention, compared with adding the reaction raw materials and the solvent separately into the continuous oxidation reaction device, the present application adopts a mixing device to mix the solid reaction raw material 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole with the solvent to obtain a raw material liquid, which is convenient for continuous preparation; then the raw material liquid is passed into the continuous oxidation reaction device for continuous oxidation reaction with the oxidant, which is convenient for continuous preparation; the raw material liquid is passed into the continuous oxidation reaction device for continuous oxidation reaction with the oxidant to obtain an oxidation product system; the oxidation product system is continuously quenched by a quencher to terminate the reaction to obtain a quenched system, and then the quenched system is continuously crystallized to precipitate the solid matter containing sulfonepyrazoline to obtain a solid-liquid mixed system; after the solid-liquid mixed system is continuously solid-liquid separated, the solid phase product and the liquid phase product are separated; after the solid phase product is continuously dried, the solvent component therein can be removed, thereby obtaining sulfonepyrazoline.

[0037] Compared with the intermittent preparation of sulfonepyraclostrobin, the continuous preparation system used in the present application can make the reaction more stable and facilitate more accurate control of the reaction temperature, thereby effectively solving the problems of large heat release and high process risk in batch reactions. Moreover, compared with a kettle reactor, the continuous oxidation reaction device filled with a catalyst bed can increase the oxidation reaction rate, shorten the oxidation reaction time, and improve the yield and selectivity of the oxidation product. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] The drawings constituting a part of the present application are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0039] Figure 1 A schematic structural diagram of a continuous preparation system of sulfonepyraclostrobin in a preferred embodiment is shown;

[0040] Figure 2 A schematic structural diagram of a continuous preparation system of sulfonepyraclostrobin in another preferred embodiment is shown.

[0041] The above drawings include the following reference numerals:

[0042] 100, mixing device; 101, raw material inlet; 102, solvent inlet; 103, raw material liquid outlet; 200, continuous oxidation reaction device; 201, raw material liquid inlet; 202, oxidant inlet; 300, continuous quenching device; 301, quenching agent inlet; 400, continuous crystallization device; 500, continuous solid-liquid separation device; 600, continuous drying device; 700, oxidant supply device; 800, continuous washing device. DETAILED DESCRIPTION

[0043] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present invention will be described in detail below in conjunction with the embodiments.

[0044] As described in the background art, the existing preparation process of sulfonepyraclostrobin has the problems of high risk in the oxidation process, high catalyst cost and long oxidation reaction time. In order to solve the above technical problems, the first aspect of the present application provides a continuous preparation system of sulfonepyraclostrobin, such as Figure 1As shown, the continuous preparation system of sulfonepyraclostrobin includes a mixing device 100, a continuous oxidation reaction device 200, a continuous quenching device 300, a continuous crystallization device 400, a continuous solid-liquid separation device 500 and a continuous drying device 600. The mixing device 100 is used to mix 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole with a solvent to obtain a raw material liquid; the mixing device 100 is provided with a raw material inlet 101, a solvent inlet 102 and a raw material liquid outlet 103; the continuous oxidation reaction device 200 is used to react 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole with an oxidant under the catalysis of a catalyst to obtain an oxidation product system; the continuous oxidation reaction device 200 is provided with a raw material liquid inlet 201, an oxidant inlet 202 and an oxidation product system outlet; the raw material liquid inlet 201 is connected to the raw material liquid outlet 103; a catalyst bed is provided inside the continuous oxidation reaction device 200, and the catalyst is loaded on the catalyst bed. layer; the continuous quenching device 300 is provided with a quenching agent inlet 301, an oxidation product system inlet and a quenching system outlet, and the oxidation product system inlet is connected to the oxidation product system outlet; the continuous quenching device 300 is used to continuously quench the oxidation product system with a quenching agent to obtain a quenching system; the continuous crystallization device 400 is provided with a quenching system inlet and a solid-liquid mixing system outlet, and the quenching system inlet is connected to the quenching system outlet; the continuous crystallization device 400 is used to continuously crystallize the quenching system to obtain a solid-liquid mixing system; the continuous solid-liquid separation device 500 is provided with a solid-liquid mixing system inlet and a solid-phase product outlet, and the solid-liquid mixing system inlet is connected to the solid-liquid mixing system outlet; the continuous drying device 600 is provided with a solid-phase product inlet and a sulfonepyraclostrobin outlet, and the solid-phase product inlet is connected to the solid-phase product outlet; the continuous drying device 600 is used to continuously dry the solid-phase product outputted from the solid-phase product outlet to obtain sulfonepyraclostrobin.

[0045] Compared with adding the reaction raw materials and the solvent separately into the continuous oxidation reaction device 200, the present application adopts a mixing device 100 to mix the solid reaction raw material 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole with the solvent to obtain a raw material liquid, which is convenient for continuous preparation; then the raw material liquid is passed into the continuous oxidation reaction device 200 to carry out a continuous oxidation reaction with the oxidant, which is convenient for realizing continuous preparation; the raw material liquid The product is introduced into a continuous oxidation reaction device 200 to carry out a continuous oxidation reaction with an oxidant to obtain an oxidation product system; a quenching agent is used to continuously quench the oxidation product system to terminate the reaction to obtain a quenched system, and then the quenched system is continuously crystallized to precipitate a solid substance containing sulfonepyraclostrobin to obtain a solid-liquid mixed system; the solid-liquid mixed system is continuously subjected to a solid-liquid separation treatment to separate a solid phase product from a liquid phase product; the solid phase product is continuously dried to remove the solvent component therein, thereby obtaining sulfonepyraclostrobin.

[0046] Compared with the intermittent preparation of sulfonepyraclostrobin, the above-mentioned continuous preparation system used in the present application can make the reaction more stable and facilitate more accurate control of the reaction temperature, thereby effectively solving the problems of large heat release and high process risk in batch reactions. Moreover, compared with a kettle reactor, the continuous oxidation reaction device 200 filled with a catalyst bed can increase the oxidation reaction rate, shorten the oxidation reaction time, and improve the yield and selectivity of the oxidation product.

[0047] In a preferred embodiment, in the continuous oxidation reaction device 200, the loading amount of the catalyst is 50-80 vol%. The filling rate of the catalyst bed includes but is not limited to the above range. Limiting it within the above range is beneficial to improving the oxidation reaction rate, and is beneficial to improving the yield and selectivity of the oxidation product.

[0048] In order to further increase the oxidation reaction rate and further improve the yield and selectivity of the oxidation product, preferably, the catalyst is a supported catalyst.

[0049] In a preferred embodiment, the active ingredients in the supported catalyst include, but are not limited to, oxides formed by one or more of ruthenium, titanium, and vanadium, and the carrier in the supported catalyst includes, but is not limited to, one or more of alumina, silicon dioxide, and activated carbon, preferably activated carbon. Compared with other types, the use of the above-mentioned supported catalyst is conducive to further improving the oxidation reaction rate, and is conducive to further improving the yield and selectivity of the oxidation product; at the same time, compared with traditional catalyst types, the cost of the above-mentioned supported catalyst is lower, which is conducive to reducing costs.

[0050] In order to further increase the oxidation reaction rate and further improve the yield and selectivity of the oxidation product, preferably, the loading amount of the active component in the supported catalyst is 5 to 15 wt %.

[0051] In a preferred embodiment, the raw material liquid inlet 201 is connected to the raw material liquid outlet 103 through a raw material liquid delivery pipeline, and a first plunger pump is provided on the raw material liquid delivery pipeline. Providing a plunger pump on the raw material liquid delivery pipeline is conducive to accurately controlling the feed rate of the raw material liquid, thereby facilitating the control of the oxidation reaction rate, making the oxidation reaction more thorough, and reducing the waste of raw materials; at the same time, it is also conducive to reducing the risk of the reaction and making the reaction process safer.

[0052] In a preferred embodiment, Figure 2 As shown, the continuous preparation system also includes an oxidant supply device 700, which is connected to the oxidant inlet 202 through an oxidant delivery pipeline; a second plunger pump is arranged on the oxidant delivery pipeline. The setting of the oxidant supply device 700 is conducive to inputting the oxidant required for the reaction into the continuous oxidation reaction device 200, and the setting of the plunger pump on the oxidant delivery pipeline is conducive to accurately controlling the feed rate of the oxidant, thereby facilitating the control of the rate of the oxidation reaction, making it easier for the oxidation reaction to proceed more thoroughly, and reducing the waste of raw materials; at the same time, it is also conducive to reducing the risk of the reaction and making the reaction process safer.

[0053] In a preferred embodiment, the continuous oxidation reaction device 200 is further equipped with a heating component. The arrangement of the heating component facilitates providing the temperature required for the continuous oxidation reaction.

[0054] In order to facilitate heating of the reaction system in the continuous oxidation reaction, preferably, the heating component is a jacket, and preferably a heat transfer medium is passed through the jacket. Preferably, the heat transfer medium is water.

[0055] In a preferred embodiment, the continuous oxidation reaction device 200 includes but is not limited to a tubular reactor. Compared with other types of reactors, the use of a tubular reactor is conducive to plug flow operation of materials and inhibits the occurrence of material return.

[0056] In order to improve the reaction capacity and the purity and yield of the reaction system, preferably, the continuous oxidation reaction device 200 includes 1 to 3 tubular reactors arranged in series in the liquid phase.

[0057] In a preferred embodiment, Figure 2As shown, the above-mentioned continuous preparation system also includes a continuous washing device 800, which is used to wash the solid phase product to remove impurities to obtain a washed product; the continuous drying device 600 is provided with a washed product inlet, and the washed product inlet is connected to the washed product outlet. The setting of the continuous washing device 800 is conducive to improving the purity of the finally prepared sulfonepyraclostrobin and reducing the impurity content.

[0058] In a preferred embodiment, the continuous washing device 800 is provided with a spraying component. The provision of the spraying component facilitates spraying the solid phase product to remove impurities, thereby improving the purity of the finally obtained sulfonepyraclostrobin and facilitating the reduction of impurity content.

[0059] The second aspect of the present application also provides a continuous preparation method of sulfonepyraclostrobin, which uses the continuous preparation system of sulfonepyraclostrobin provided by the present application to prepare sulfonepyraclostrobin, and the continuous preparation method comprises: step S1, using a mixing device 100 to mix 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole with a solvent to obtain a raw material liquid; step S2, passing the raw material liquid and an oxidant into a continuous oxidation reaction device 200 for continuous oxidation. Oxidation reaction to obtain an oxidation product system; step S3, passing the oxidation product system into a continuous quenching device 300 and using a quenching agent for continuous quenching treatment to obtain a quenching system; step S4, passing the quenching system into a continuous crystallization device 400 for continuous crystallization treatment to obtain a solid-liquid mixed system; step S5, using a continuous solid-liquid separation device 500 to perform continuous solid-liquid separation treatment on the solid-liquid mixed system to obtain a solid phase product; step S6, using a continuous drying device 600 to continuously dry the solid phase product to obtain pyraclostrobin.

[0060] Compared with adding the raw material and the solvent separately into the continuous oxidation reaction device 200, the present application mixes 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole with a solvent, and then introduces it into the continuous oxidation reaction device 200 in the form of a raw material liquid for continuous oxidation reaction with an oxidant, so as to facilitate continuous preparation; the raw material liquid is introduced into the continuous oxidation reaction device 200 for continuous oxidation reaction with an oxidant to obtain an oxidation product system; the oxidation product system is continuously quenched with a quencher to terminate the reaction to obtain a quenched system, and the quenched system is continuously crystallized to precipitate a solid substance containing sulfonepyraclostrobin to obtain a solid-liquid mixed system; the solid-phase product and the liquid-phase product are separated after continuous solid-liquid separation treatment of the solid-liquid mixed system; the solvent component therein can be removed after continuous drying treatment of the solid-phase product, thereby obtaining sulfonepyraclostrobin.

[0061] Compared with the batch method for preparing sulfonepyraclostrobin, the above-mentioned continuous preparation method adopted in the present application can make the reaction more stable and facilitate more accurate control of the reaction temperature, thereby effectively solving the problem of large heat release and high process risk of batch reaction. Moreover, compared with the kettle reactor, the interior of the continuous oxidation reaction device 200 is filled with a catalyst bed, and the catalytic effect of the catalyst bed can be fully utilized by passing the raw material liquid and the oxidant into the continuous oxidation reaction device 200, thereby increasing the reaction rate of the continuous oxidation reaction and improving the yield and selectivity of the oxidation product.

[0062] In a preferred embodiment, the weight ratio of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole to the solvent is 1:(2-5). Compared with other ranges, limiting the weight ratio of the reaction raw materials in the raw material liquid to the above range is conducive to improving the dispersibility of the reaction raw materials, and is conducive to improving the efficiency of the continuous oxidation reaction, thereby helping to improve the yield of the oxidation product.

[0063] In a preferred embodiment, in step S2, the feed rate ratio of the raw material liquid to the oxidant is (2-10): 1. The feed rate ratio of the raw material liquid to the oxidant includes but is not limited to the above range, and limiting it within the above range is conducive to improving the raw material utilization rate of each reaction raw material, reducing raw material waste, and thus helping to improve the yield of the oxidation product.

[0064] In order to further improve the raw material utilization rate of each reaction raw material, reduce raw material waste, and further improve the yield of oxidation products, preferably, in step S2, the feed rate of the raw material liquid is 1-50 g / min, the material residence time is 30-200 min, the feed rate of the oxidant is 1-13 g / min, and the material residence time is 30-200 min.

[0065] In a preferred embodiment, the temperature of the continuous oxidation reaction is 10 to 80° C. The temperature of the continuous oxidation reaction includes but is not limited to the above range, and limiting it within the above range is conducive to improving the reaction efficiency of the continuous oxidation reaction, allowing each reaction raw material to react more fully, thereby facilitating improving the yield and purity of the oxidation product.

[0066] In order to further improve the reaction efficiency of the continuous oxidation reaction and further improve the yield and purity of the oxidation product, the temperature of the continuous oxidation reaction is 20-70°C.

[0067] In a preferred embodiment, the solvent includes, but is not limited to, one or more of tetrahydrofuran, methanol, acetonitrile, dichloromethane, dichloroethane and chloroform. Compared with other types, the use of the above-mentioned types of solvents is conducive to improving the solubility and dispersibility of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole, thereby helping to improve the reaction efficiency of the continuous oxidation reaction.

[0068] In a preferred embodiment, the oxidant includes but is not limited to one or more of hydrogen peroxide, ozone and sodium hypochlorite. Compared with other types, the use of the above-mentioned oxidants is conducive to improving the efficiency of the continuous oxidation reaction. At the same time, the above-mentioned oxidants are low in cost, easy to purchase, and safe to use.

[0069] In a preferred embodiment, in step S3, the feed rate ratio of the oxidation product system to the quenching agent is 1:(1-5). The feed rate ratio of the oxidation product system to the quenching agent includes but is not limited to the above range, and limiting it within the above range is conducive to improving the quenching efficiency, improving the utilization rate of the quenching agent, and facilitating subsequent post-treatment such as continuous crystallization treatment, thereby facilitating the collection of the target product sulfonepyraclostrobin.

[0070] In order to further improve the quenching efficiency and further improve the utilization rate of the quenching agent, preferably, in step S3, the feed rate of the oxidation product system is 10-100 g / min, the material residence time is 5-30 min, the feed rate of the quenching agent is 1-50 g / min, and the material residence time is 5-30 min.

[0071] In a preferred embodiment, in step S4, the feed rate of the quenching system is 1 to 50 g / min, and the material residence time is 30 to 120 min. The feed rate and material residence time of the quenching system include but are not limited to the above ranges, and limiting them within the above ranges is conducive to improving the efficiency of the continuous crystallization process, thereby facilitating the improvement of the enrichment rate and yield of sulfonepyraclostrobin.

[0072] In a preferred embodiment, in step S4, the temperature of the continuous crystallization treatment is 5 to 30° C. The temperature of the continuous crystallization treatment includes but is not limited to the above range, and limiting it within the above range is conducive to improving the precipitation efficiency of the solid matter containing sulfonepyraclostrobin, thereby facilitating the improvement of the enrichment rate and yield of sulfonepyraclostrobin.

[0073] In a preferred embodiment, in step S5, the feed rate of the solid-liquid mixing system is 1 to 50 g / min, and the material residence time is 10 to 30 min. The feed rate and material residence time of the solid-liquid mixing system include but are not limited to the above ranges, and limiting them within the above ranges is conducive to improving the continuous solid-liquid separation process efficiency, thereby facilitating the improvement of the yield and purity of the subsequently prepared sulfonepyraclostrobin.

[0074] In order to improve the efficiency of the continuous solid-liquid separation process, and thus improve the yield and purity of the subsequently prepared sulfonepyraclostrobin, preferably, the continuous solid-liquid separation process is filtration or centrifugation.

[0075] In a preferred embodiment, between step S5 and step S6, the solid phase product is further subjected to continuous washing treatment with a detergent to remove impurities to obtain a washed product; and step S6 comprises continuously drying the washed product to obtain sulfonepyraclostrobin. Continuously washing the solid phase product is beneficial to improving the purity of sulfonepyraclostrobin and reducing the impurity content therein.

[0076] In order to improve the efficiency of the continuous washing process and the washing effect, preferably, the continuous washing process is carried out by a leaching method.

[0077] In order to improve the efficiency of continuous washing treatment and improve the washing effect, preferably, the detergent includes but is not limited to one or more of water, n-heptane, methanol, isopropanol and ethanol.

[0078] In a preferred embodiment, in step S6, the feed rate of the washed product is 1 to 50 g / min, and the material residence time is 5 to 30 min. The feed rate and material residence time of the washed product include but are not limited to the above ranges, and limiting them within the above ranges is conducive to improving the processing efficiency of the continuous drying process, thereby helping to reduce the solvent content in sulfonepyraclostrobin.

[0079] In order to further reduce the solvent content in pyraclostrobin, preferably, the temperature of the continuous drying process is 20 to 80°C.

[0080] The present application is further described in detail below in conjunction with specific embodiments. These embodiments should not be construed as limiting the scope of protection claimed in the present application.

[0081] It should be noted that in the present application, 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole was purchased from Shandong Zhanhua Yonghao Pharmaceutical Technology Co., Ltd. with a CAS number of 656825-92-2.

[0082] Example 1

[0083] A continuous preparation method of sulfonepyraclostrobin, the synthesis route of which is as follows:

[0084] .

[0085] The continuous preparation method comprises:

[0086] (1) Using a mixing device 100, 50 g of 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole is mixed with 250 mL of acetonitrile to obtain a raw material solution with a mass concentration of 20 wt%; the oxidant supply device 700 is provided with hydrogen peroxide with a mass concentration of 30 wt%;

[0087] (2) A fixed bed reactor is used as the continuous oxidation reaction device 200, wherein a catalyst bed is provided, and a catalyst is loaded in the catalyst bed, and the loading amount of the catalyst is 60 vol%, and the catalyst is a supported catalyst V 2 O 5 / Activated carbon, i.e. the active ingredient is V 2 O 5 , the carrier is activated carbon, and the loading amount of the active ingredient is 10wt%; the temperature of the continuous oxidation reaction device 200 is set to 50-60°C, the above raw material liquid is fed at a feeding rate of 6g / min and the hydrogen peroxide is fed at a feeding rate of 1.5g / min into the continuous oxidation reaction device 200 for continuous oxidation reaction, and the material residence time is 120min to obtain an oxidation product system;

[0088] (3) continuously introducing the oxidation product system into the continuous quenching device 300 at a feed rate of 7.5 g / min, and introducing the quenching agent sodium sulfite at a feed rate of 5.2 g / min to obtain a quenching system;

[0089] (4) continuously introducing the quenching system into the continuous crystallization device 400 at a feed rate of 12.7 g / min, setting the temperature of the continuous crystallization device 400 to 10° C. and the material residence time to 60 min, to obtain a solid-liquid mixed system;

[0090] (5) continuously introducing the solid-liquid mixed system into a continuous solid-liquid separation device 500 (horn centrifuge) at a feed rate of 12.7 g / min, with a material residence time of 10 min, to obtain a solid phase product and a liquid phase product;

[0091] (6) The solid phase product is continuously introduced into a continuous washing device 800 at a feed rate of 1.2 g / min. The continuous washing device 800 is provided with a spraying component. The material residence time is 10 min to obtain a washed product.

[0092] (7) The washed product was continuously introduced into the continuous drying device 600 at a feed rate of 3 g / min, the temperature of the continuous drying device 600 was set to 60° C., and the material residence time was 10 min, to obtain the target product sulfonepyraclostrobin.

[0093] Example 2

[0094] The difference from Example 1 is that the catalyst is a supported catalyst V 2 O 5 / TiO 2 / Activated carbon, i.e. the active ingredient is V 2 O 5 and TiO 2 , the loading amount is 10wt%, where V 2 O 5 With TiO 2 The weight ratio is 1:1.

[0095] Example 3

[0096] The difference from Example 1 is that the catalyst is a supported catalyst RuO 2 / TiO 2 / activated carbon, i.e., the active ingredient is RuO 2 and TiO 2 , the loading amount is 10wt%, of which RuO 2 With TiO 2 The weight ratio is 1:1.

[0097] Example 4

[0098] The difference from Example 1 is that the catalyst is a supported catalyst TiO 2 / Activated carbon, i.e. the active ingredient is TiO 2 , the loading amount is 10wt%.

[0099] Example 5

[0100] The difference from Example 1 is that the catalyst is a supported catalyst RuO 2 / activated carbon, i.e., the active ingredient is RuO 2 , the loading amount is 10wt%.

[0101] Example 6

[0102] The difference from Example 1 is that in the continuous oxidation reaction device 200, the loading amount of the catalyst is 50 vol%.

[0103] Example 7

[0104] The difference from Example 1 is that in the continuous oxidation reaction device 200, the loading amount of the catalyst is 80 vol%.

[0105] Example 8

[0106] The difference from Example 1 is that in the continuous oxidation reaction device 200, the loading amount of the catalyst is 90 vol%.

[0107] Example 9

[0108] The difference from Example 1 is that the loading amount of the active component in the supported catalyst is 5 wt %.

[0109] Example 10

[0110] The difference from Example 1 is that the loading amount of the active component in the supported catalyst is 15 wt %.

[0111] Embodiment 11

[0112] The difference from Example 1 is that the loading amount of the active component in the supported catalyst is 25 wt %.

[0113] Example 12

[0114] The difference from Example 1 is that in step (2), the feed rate of the raw material liquid is 50 g / min, and the feed rate of hydrogen peroxide is 13 g / min.

[0115] Embodiment 13

[0116] The difference from Example 1 is that in step (2), the feed rate of the raw material liquid is 100 g / min, and the feed rate of hydrogen peroxide is 26 g / min.

[0117] Embodiment 14

[0118] The difference from Example 1 is that in step (2), the temperature of the continuous oxidation reaction device 200 is set to 10°C, that is, the temperature of the continuous oxidation reaction is 10°C.

[0119] Embodiment 15

[0120] The difference from Example 1 is that in step (2), the temperature of the continuous oxidation reaction device 200 is set to 80°C, that is, the temperature of the continuous oxidation reaction is 80°C.

[0121] Example 16

[0122] The difference from Example 1 is that in step (2), the temperature of the continuous oxidation reaction device 200 is set to 100°C, that is, the temperature of the continuous oxidation reaction is 100°C.

[0123] Comparative Example 1

[0124] The difference from Example 1 is that the continuous oxidation reaction device 200 is not filled with a catalyst bed, and the continuous oxidation reaction cannot be performed in the absence of a catalyst.

[0125] Comparative Example 2

[0126] The difference from Example 1 is that: a batch process is used to prepare sulfonepyrazoline, and the oxidation reaction section is carried out in a tank reactor, wherein 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole, hydrogen peroxide and supported catalyst V 2 O 5 The molar ratio of activated carbon is 1:4:1.

[0127] Table 1 summarizes the yield and purity of the target product sulfonepyraclostrobin obtained in all the above examples and comparative examples of the present application. In Table 1, " / " means no addition.

[0128] Table 1

[0129]

[0130] From the above description, it can be seen that the above embodiments of the present invention achieve the following technical effects:

[0131] Compared with adding the raw material and the solvent separately into the continuous oxidation reaction device 200, the present application mixes 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole with a solvent, and then introduces it into the continuous oxidation reaction device 200 in the form of a raw material liquid for continuous oxidation reaction with an oxidant, so as to facilitate continuous preparation; the raw material liquid is introduced into the continuous oxidation reaction device 200 for continuous oxidation reaction with an oxidant to obtain an oxidation product system; the oxidation product system is continuously quenched with a quencher to terminate the reaction to obtain a quenched system, and the quenched system is continuously crystallized to precipitate a solid substance containing sulfonepyraclostrobin to obtain a solid-liquid mixed system; the solid-phase product and the liquid-phase product are separated after continuous solid-liquid separation treatment of the solid-liquid mixed system; the solvent component therein can be removed after continuous drying treatment of the solid-phase product, thereby obtaining sulfonepyraclostrobin.

[0132] Compared with the intermittent preparation of sulfonepyraclostrobin, the continuous preparation system used in the present application can make the reaction more stable and facilitate more accurate control of the reaction temperature, thereby effectively solving the problems of large heat release and high process risk in batch reactions. Moreover, compared with a kettle reactor, the continuous oxidation reaction device 200 filled with a catalyst bed can increase the oxidation reaction rate and improve the yield and selectivity of the oxidation product.

[0133] It should be noted that the terms "first", "second", etc. in the specification and claims of the present application are used to distinguish similar objects, and are not necessarily used to describe a specific order or sequence. It should be understood that the terms used in this way can be interchangeable where appropriate, so that the embodiments of the present application described herein can be implemented in an order other than those described herein, for example.

[0134] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A continuous preparation system of sulfonepyraclostrobin, characterized in that: The continuous preparation system of sulfonepyraclostrobin comprises: A mixing device (100) is used for mixing 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole with a solvent to obtain a raw material liquid; the mixing device (100) is provided with a raw material inlet (101), a solvent inlet (102) and a raw material liquid outlet (103); A continuous oxidation reaction device (200) is used for reacting the 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole with an oxidant under the catalysis of a catalyst to obtain an oxidation product system; the continuous oxidation reaction device (200) is provided with a raw material liquid inlet (201), an oxidant inlet (202) and an oxidation product system outlet; the raw material liquid inlet (201) is connected to the raw material liquid outlet (103); a catalyst bed is provided inside the continuous oxidation reaction device (200), and the catalyst is loaded in the catalyst bed; A continuous quenching device (300), wherein the continuous quenching device (300) is provided with a quenching agent inlet (301), an oxidation product system inlet and a quenching system outlet, wherein the oxidation product system inlet is connected to the oxidation product system outlet; the continuous quenching device (300) is used to continuously quench the oxidation product system with the quenching agent to obtain a quenching system; A continuous crystallization device (400), wherein the continuous crystallization device (400) is provided with a quenching system inlet and a solid-liquid mixing system outlet, wherein the quenching system inlet is connected to the quenching system outlet; the continuous crystallization device (400) is used to perform continuous crystallization treatment on the quenching system to obtain a solid-liquid mixing system; A continuous solid-liquid separation device (500), wherein the continuous solid-liquid separation device (500) is provided with a solid-liquid mixing system inlet and a solid phase product outlet, and the solid-liquid mixing system inlet is connected to the solid-liquid mixing system outlet; A continuous drying device (600), wherein the continuous drying device (600) is provided with a solid phase product inlet and a sulfonepyraclostrobin outlet, wherein the solid phase product inlet is connected to the solid phase product outlet; the continuous drying device (600) is used to continuously dry the solid phase product outputted from the solid phase product outlet to obtain the sulfonepyraclostrobin.

2. The continuous preparation system of sulfonepyraclostrobin according to claim 1, characterized in that: In the continuous oxidation reaction device (200), the loading amount of the catalyst is 50 to 80 vol%.

3. The continuous preparation system of sulfonepyraclostrobin according to claim 1 or 2, characterized in that: The catalyst is a supported catalyst, the active component in the supported catalyst is selected from oxides formed by one or more of ruthenium, titanium and vanadium, and the carrier in the supported catalyst is selected from one or more of alumina, silicon dioxide and activated carbon.

4. The continuous preparation system of sulfonepyraclostrobin according to claim 3, characterized in that: The carrier is activated carbon.

5. The continuous preparation system of sulfonepyraclostrobin according to claim 3, characterized in that: The loading amount of the active component in the supported catalyst is 5 to 15 wt %.

6. The continuous preparation system of sulfonepyraclostrobin according to claim 1 or 2, characterized in that: The raw material liquid inlet (201) is connected to the raw material liquid outlet (103) via a raw material liquid delivery pipeline, and a first plunger pump is provided on the raw material liquid delivery pipeline.

7. The continuous preparation system of sulfonepyraclostrobin according to claim 1 or 2, characterized in that: The continuous preparation system further comprises an oxidant supply device (700), wherein the oxidant supply device (700) is connected to the oxidant inlet (202) via an oxidant delivery pipeline; a second plunger pump is arranged on the oxidant delivery pipeline.

8. The continuous preparation system of sulfonepyraclostrobin according to claim 1 or 2, characterized in that: The continuous oxidation reaction device (200) is further equipped with a heating component; and / or the continuous oxidation reaction device (200) is selected from a tubular reactor.

9. The continuous preparation system of sulfonepyraclostrobin according to claim 8, characterized in that: The heating component is a jacket, and a heat transfer medium is passed through the jacket.

10. The continuous preparation system of sulfonepyraclostrobin according to claim 8, characterized in that: The continuous oxidation reaction device (200) comprises 1 to 3 tubular reactors arranged in series in the liquid phase.

11. The continuous preparation system of sulfonepyraclostrobin according to claim 1 or 2, characterized in that: The continuous preparation system further comprises a continuous washing device (800), wherein the continuous washing device (800) is used to wash the solid phase product to remove impurities and obtain a washed product; The continuous drying device (600) is provided with a washing product inlet, the washing product inlet being in communication with the washing product outlet; and the continuous washing device (800) is provided with a spraying component.

12. A continuous preparation method of sulfonepyraclostrobin, characterized in that: The sulfonepyraclostrobin continuous preparation system according to claim 1 is used to prepare the sulfonepyraclostrobin, and the continuous preparation method comprises: Step S1, using a mixing device (100) to mix 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole with a solvent to obtain a raw material liquid; Step S2, introducing the raw material liquid and the oxidant into a continuous oxidation reaction device (200) for continuous oxidation reaction to obtain an oxidation product system; Step S3, passing the oxidation product system into a continuous quenching device (300) and performing continuous quenching treatment with a quenching agent to obtain a quenching system; Step S4, passing the quenching system into a continuous crystallization device (400) for continuous crystallization treatment to obtain a solid-liquid mixed system; Step S5, using a continuous solid-liquid separation device (500) to perform continuous solid-liquid separation on the solid-liquid mixed system to obtain a solid phase product; Step S6, using a continuous drying device (600) to continuously dry the solid phase product to obtain the sulfonepyraclostrobin.

13. The continuous preparation method of sulfonepyraclostrobin according to claim 12, characterized in that: The weight ratio of the 3-[(5-difluoromethoxy-1-methyl-3-trifluoromethylpyrazol-4-yl)-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole to the solvent is 1:(2-5).

14. The continuous preparation method of sulfonepyraclostrobin according to claim 12, characterized in that: In the step S2, the feed rate ratio of the raw material liquid to the oxidant is (2-10):1; and / or, In step S2, the feed rate of the raw material liquid is 1-50 g / min, the material residence time is 30-200 min, the feed rate of the oxidant is 1-13 g / min, and the material residence time is 30-200 min; and / or, The temperature of the continuous oxidation reaction is 10 to 80° C.; and / or, The solvent is selected from one or more of tetrahydrofuran, methanol, acetonitrile, dichloromethane, dichloroethane and chloroform; and / or, The oxidant is selected from one or more of hydrogen peroxide, ozone and sodium hypochlorite.

15. The continuous preparation method of sulfonepyraclostrobin according to claim 14, characterized in that: The temperature of the continuous oxidation reaction is 20-70°C.

16. The continuous preparation method of sulfonepyraclostrobin according to any one of claims 12 to 15, characterized in that: In the step S3, the ratio of the feed rate of the oxidation product system to the feed rate of the quenching agent is 1:(1-5).

17. The continuous preparation method of sulfonepyraclostrobin according to any one of claims 12 to 15, characterized in that: In step S3, the feed rate of the oxidation product system is 10-100 g / min, the material residence time is 5-30 min, the feed rate of the quenching agent is 1-50 g / min, and the material residence time is 5-30 min; and / or, In step S4, the feed rate of the quenching system is 1 to 50 g / min, and the material residence time is 30 to 120 min; and / or, In the step S4, the temperature of the continuous crystallization treatment is 5 to 30° C.; and / or, In the step S5, the feed rate of the solid-liquid mixing system is 1 to 50 g / min, and the material residence time is 10 to 30 min.

18. The continuous preparation method of sulfonepyraclostrobin according to any one of claims 12 to 15, characterized in that: The method between step S5 and step S6 also includes continuously washing the solid phase product with a detergent to remove impurities and obtain a washed product; and step S6 includes continuously drying the washed product to obtain pyraclostrobin.

19. The continuous preparation method of sulfonepyraclostrobin according to claim 18, characterized in that: The continuous solid-liquid separation process is filtration or centrifugation; and / or, The continuous washing treatment is carried out by elution method; and / or, The detergent is selected from one or more of water, n-heptane, methanol, isopropanol and ethanol; and / or, In step S6, the feed rate of the washed product is 1 to 50 g / min, and the material residence time is 5 to 30 min; and / or, The temperature of the continuous drying process is 20-80°C.

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