Continuous production system and continuous production method of butylphenylmorpholine

Abstract

The invention provides a continuous production system and a continuous production method of butylphenylmorpholine. The system comprises a continuous mixing device, a continuous reaction device, a continuous gas-liquid separation device and a continuous rectification device. The continuous mixing device is used for mixing the first mixed solution with the second mixed solution to obtain a raw material solution so as to inhibit deterioration of the raw material solution; the continuous reaction device is used for carrying out continuous reaction on 4-tert-butyl-beta-chloro-alpha-methylcinnamyl aldehyde and 2, 6-dimethylmorpholine under the catalysis of a catalyst and in the presence of an acid-binding agent, hydrogen and a solvent to obtain a product system containing butylphenylmorpholine; the continuous gas-liquid separation device is used for separating a product system containing butylphenylmorpholine to obtain a liquid-phase product; and the continuous rectification device is used for carrying out continuous rectification on the liquid-phase product so as to obtain high-purity butylmorpholine. When the continuous production system is used for production, the continuous production of the butylphenylmorpholine can be realized through a'one-pot method ', the production cost is reduced, and the production efficiency and the production safety are improved.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and in particular to a continuous production system and a continuous production method of fenpropimorph. Background Art

[0002] Fenpropimorph, also known as Fenpropimorph, has a molecular formula of C 20 H 33 NO is a broad-spectrum, systemic morphine fungicide and also an inhibitor of ergosterol biosynthesis. It is mainly used to control powdery mildew, leaf rust, stripe rust of barley and wheat, smut of cereals and damping-off of cotton. It is particularly effective in controlling powdery mildew of cereals and also has a good control effect on rust. Fenpropimorph was first developed and marketed by Dr R.Maag and other companies in 1983, and was later acquired by BASF and became a member of its product line.

[0003] The traditional synthesis route of fenpropimorph is derived from compound patent DE2752135A1, and its process flow is as follows: using tert-butylbenzene as the starting material, 4-tert-butylpropiophenone is generated through Friedel-Crafts acylation reaction; 4-tert-butylpropiophenone reacts with Vilsmeier reagent (mainly composed of phosphorus oxychloride, dimethylformamide and sodium hydroxide) to obtain 4-tert-butyl-β-chloro-α-methylcinnamaldehyde; 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is catalytically hydrogenated and dechlorinated to obtain lily of the valley aldehyde; finally, lily of the valley aldehyde and 2,6-dimethylmorpholine are condensed and catalytically hydrogenated under the catalysis of a catalyst to generate fenpropimorph.

[0004] Although the above-mentioned traditional synthesis method is mature, it has a series of limitations in actual production. For example, in the reaction of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde to generate lily of the valley aldehyde by catalytic hydrogenation and dechlorination, transition reduction is prone to occur, resulting in the generation of more impurity alcohols, thereby resulting in a low yield of lily of the valley aldehyde, and then a low yield of the final product fenpropimorph; at the same time, in batch intermittent processes, especially dangerous reactions such as hydrogenation reactions, the operation is cumbersome and the reaction conditions are difficult to control, which poses a great safety hazard; and the catalyst utilization rate of intermittent kettle reactions is low, and the recovery is complicated, which increases the cost and difficulty of safety control; with the expansion of the reaction system, it becomes difficult to accurately control the reaction parameters, which easily causes differences in product yield and purity between batches, thereby resulting in the problem of a low overall yield of fenpropimorph.

[0005] In summary, researching and developing a continuous production system and method of fenpropimorph is of great significance for improving the yield of fenpropimorph and its production efficiency, reducing safety risks and production costs. Summary of the invention

[0006] The main purpose of the present invention is to provide a continuous production method and a continuous production system of fenpropimorph, so as to solve the problems of complex process flow, poor production safety, low production efficiency, low product yield, unstable yield and purity, and high cost in the production of fenpropimorph in the prior art.

[0007] In order to achieve the above-mentioned object, the present invention provides a continuous production system of fenpropimorph on the one hand, which includes a continuous mixing device, a continuous reaction device, a continuous gas-liquid separation device and a continuous distillation device. The continuous mixing device is used to mix the first mixed liquid with the second mixed liquid to obtain the raw liquid; the continuous mixing device is provided with a raw liquid outlet; the first mixed liquid includes 4-tert-butyl-β-chloro-α-methylcinnamaldehyde and a part of the solvent; the second mixed liquid includes 2,6-dimethylmorpholine, an acid binding agent and another part of the solvent; the continuous reaction device is used to make 4-tert-butyl-β-chloro-α-methylcinnamaldehyde and 2,6-dimethylmorpholine react continuously under the catalysis of the catalyst and the presence of the acid binding agent, hydrogen and the solvent to obtain a product system containing fenpropimorph; the continuous reaction device is provided with a raw liquid inlet, a hydrogen inlet and a product system outlet; the raw liquid inlet is connected to the raw liquid outlet; a catalyst bed is provided inside the continuous reaction device, and the catalyst is loaded in the catalyst bed; the continuous gas-liquid separation device is provided with a product system inlet and a liquid product outlet; the product system inlet is connected to the product system outlet; the continuous distillation device is provided with a liquid product inlet and a fenpropimorph outlet; the liquid product inlet is connected to the liquid product outlet.

[0008] Furthermore, the continuous gas-liquid separation device is also provided with a recovered hydrogen outlet; the recovered hydrogen outlet is connected to the hydrogen inlet.

[0009] Furthermore, the continuous mixing device is a continuous microchannel mixer.

[0010] Furthermore, the continuous reaction device is provided with a temperature control component, and preferably the temperature control component is filled with a heat exchange medium.

[0011] Furthermore, the continuous reaction device is a continuous fixed bed reactor or a continuous fluidized bed reactor.

[0012] Furthermore, the continuous gas-liquid separation device is an inertial separation separator or a filtration separation separator.

[0013] Furthermore, the continuous distillation device is a plate tower or a packed tower.

[0014] Furthermore, the catalyst loading amount is 10 to 90 vol% in terms of volume percentage of the continuous reaction device; preferably, the catalyst is a supported catalyst, and preferably the active ingredient in the supported catalyst is selected from one or more of the group consisting of palladium, platinum, rhodium, nickel and copper; more preferably, the catalyst is selected from one or more of the group consisting of palladium / carbon catalyst, palladium / alumina catalyst and platinum / carbon catalyst.

[0015] Furthermore, the continuous production system of fenpropimorph also includes a first mixing device and a second mixing device; the first mixing device is used to mix 4-tert-butyl-β-chloro-α-methylcinnamaldehyde with a part of the solvent to obtain a first mixed liquid; the outlet of the first mixing device is connected to the inlet of the continuous mixing device; the second mixing device is used to mix 2,6-dimethylmorpholine, an acid binding agent and another part of the solvent to obtain a second mixed liquid; the outlet of the second mixing device is connected to the inlet of the continuous mixing device.

[0016] Furthermore, the raw material liquid inlet and the raw material liquid outlet are connected through a raw material liquid delivery pipeline, and a continuous feed pump is arranged on the raw material liquid delivery pipeline.

[0017] In order to achieve the above-mentioned purpose, another aspect of the present invention further provides a continuous production method of fenpropimorph, which is carried out using the above-mentioned continuous production system provided by the present application. The continuous production method comprises: step S1, using a continuous mixing device to continuously mix a first mixed liquid and a second mixed liquid to obtain a raw material liquid; the first mixed liquid comprises 4-tert-butyl-β-chloro-α-methylcinnamaldehyde and a part of the solvent; the second mixed liquid comprises 2,6-dimethylmorpholine, an acid binding agent and another part of the solvent; step S2, in the presence of a catalyst and hydrogen, passing the raw material liquid into a continuous reaction device for continuous reaction to obtain a product system containing fenpropimorph; step S3, using a continuous gas-liquid separation device to continuously separate the product system into gas and liquid to obtain a liquid product; step S4, using a continuous distillation device to continuously distill the liquid product to obtain fenpropimorph.

[0018] Furthermore, the reaction temperature of the continuous reaction is 70-100° C., and the reaction pressure is 0.1-1.5 MPa.

[0019] Furthermore, in the continuous reaction device, the liquid hourly space velocity of the raw material liquid is 1.34 to 8.01 h -1 ; Preferably, the feed rate ratio of hydrogen to 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is (237~600) mL / min:1.0 g / min.

[0020] Furthermore, the feed rate ratio of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde, 2,6-dimethylmorpholine and the acid binding agent is 1.0:(0.49-0.98):(0.51-0.71).

[0021] Furthermore, in the continuous mixing device, the feed rate ratio of the first mixed liquid to the second mixed liquid is 1:(1-10); preferably, the residence time of the first mixed liquid and the second mixed liquid is independently 2-10 min.

[0022] Furthermore, before step S1, the continuous production method further comprises: using a first mixing device to mix 4-tert-butyl-β-chloro-α-methylcinnamaldehyde with a portion of the solvent to obtain a first mixed solution; preferably, using a second mixing device to mix 2,6-dimethylmorpholine, an acid binding agent and another portion of the solvent to obtain a second mixed solution.

[0023] Furthermore, in the first mixed solution, the mass concentration of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is 16.2-21.2 wt %.

[0024] Furthermore, in the second mixed solution, the mass concentration of the acid binding agent is 7.37-11.6 wt %; preferably, the acid binding agent is an organic base, and more preferably the acid binding agent is one or more selected from the group consisting of triethylamine, pyridine, trimethylamine, diethylamine and ethylenediamine.

[0025] Further, the solvent is selected from one or more of the group consisting of ethanol, methanol, isopropanol, toluene, methyl tert-butyl ether, 1,4-dioxane and ethyl acetate.

[0026] Furthermore, in step S3, after the continuous gas-liquid separation is completed, recovered hydrogen is obtained; preferably, at least part of the recovered hydrogen is returned to step S2.

[0027] By applying the technical solution of the present invention, the present application provides a continuous production system of fenpropimorph, which includes a continuous mixing device, a continuous reaction device, a continuous gas-liquid separation device and a continuous distillation device. The setting of the continuous reaction device enables 4-tert-butyl-β-chloro-α-methylcinnamaldehyde and 2,6-dimethylmorpholine to react continuously in a solvent under the catalysis of a catalyst and in the presence of an acid binding agent and hydrogen to obtain a product system containing fenpropimorph. Compared with the prior art, 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is used as a raw material, and catalytic hydrogenation dechlorination reaction is first performed in two steps to obtain lily of the valley aldehyde; then lily of the valley aldehyde and 2,6-dimethylmorpholine are subjected to condensation and catalytic hydrogenation reaction under the catalysis of a catalyst to generate fenpropimorph. The inventor creatively discovered that the continuous reaction device described above in the present application is used for one-step reaction and the introduction of an acid binding agent in the continuous reaction device can neutralize the acidic substances such as hydrogen chloride generated during the reaction, and inhibit the side reaction of the aldehyde group being reduced to produce hydroxyl impurities under a proton hydrogen environment, thereby improving the conversion rate of the raw materials and the selectivity of the continuous reaction, and then improving the yield of fenpropimorph. The continuous mixing device is set up to pre-mix the above-mentioned raw materials to obtain a raw material liquid, which can achieve the same mixing effect as the batching kettle on the one hand, and can inhibit the various raw materials and the acid binding agent in the batching kettle from being placed for a long time and deteriorating, and the continuous mixing method can improve the reaction efficiency and production efficiency of the continuous reaction, thereby improving the yield of the target product fenpropimorph. The continuous gas-liquid separation device is used to separate the product system containing fenpropimorph to obtain a liquid product. The continuous distillation device is used to continuously distill the liquid product to obtain fenpropimorph with higher purity.

[0028] Compared with the intermittent production system, the continuous production system of fenpropimorph described in the present application can realize the continuous production of fenpropimorph through the "one-pot method", simplify the process flow, and reduce the post-processing process of the multi-step process, thereby reducing material waste, reducing equipment costs, and improving production efficiency; and the use of the above-mentioned continuous production system for production can more accurately control the reaction conditions, improve production safety, and reduce the occurrence of side reactions, improve product selectivity, thereby increasing the yield of fenpropimorph. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] 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:

[0030] Figure 1 A schematic structural diagram of a continuous production system of fenpropimorph in one embodiment of the present application is shown;

[0031] Figure 2A schematic structural diagram of a continuous production system of fenpropimorph in another embodiment of the present application is shown.

[0032] The above drawings include the following reference numerals:

[0033] 100, continuous mixing device; 101, raw liquid outlet; 200, continuous reaction device; 201, raw liquid inlet; 202, hydrogen inlet; 300, continuous gas-liquid separation device; 301, recovered hydrogen outlet; 400, continuous distillation device; 401, fenpropimorph outlet; 500, first mixing device; 600, second mixing device. DETAILED DESCRIPTION

[0034] 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.

[0035] As described in the background technology, the existing production process of fenpropimorph has the problems of complex process flow, low yield, complex operation, poor production safety, low production efficiency, unstable product yield and purity, and high cost. In order to solve the above technical problems, the first aspect of the present application provides a continuous production system of fenpropimorph, such as Figure 1 As shown, the continuous production system includes a continuous mixing device 100, a continuous reaction device 200, a continuous gas-liquid separation device 300 and a continuous distillation device 400. The continuous mixing device 100 is used to mix the first mixed liquid with the second mixed liquid to obtain a raw material liquid; the continuous mixing device 100 is provided with a raw material liquid outlet 101; the first mixed liquid includes 4-tert-butyl-β-chloro-α-methylcinnamaldehyde and a part of the solvent; the second mixed liquid includes 2,6-dimethylmorpholine, an acid binding agent and another part of the solvent; the continuous reaction device 200 is used to make 4-tert-butyl-β-chloro-α-methylcinnamaldehyde and 2,6-dimethylmorpholine react continuously under the catalysis of a catalyst and in the presence of an acid binding agent, hydrogen and a solvent to obtain a raw material liquid. A product system of fenpropimorph; a continuous reaction device 200 is provided with a raw liquid inlet 201, a hydrogen inlet 202 and a product system outlet; the raw liquid inlet 201 is connected to the raw liquid outlet 101; a catalyst bed is provided inside the continuous reaction device 200, and the catalyst is loaded in the catalyst bed; a continuous gas-liquid separation device 300 is provided with a product system inlet and a liquid product outlet; the product system inlet is connected to the product system outlet; a continuous distillation device 400 is provided with a liquid product inlet and a fenpropimorph outlet 401; the liquid product inlet is connected to the liquid product outlet.

[0036] In the continuous production system of the above-mentioned fenpropimorph provided by the present application, the setting of the continuous reaction device 200 can make 4-tert-butyl-β-chloro-α-methylcinnamaldehyde and 2,6-dimethylmorpholine react continuously in a solvent under the catalysis of a catalyst and in the presence of an acid binding agent and hydrogen to obtain a product system containing fenpropimorph. Compared with the prior art, 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is used as a raw material, and catalytic hydrogenation and dechlorination are first performed in two steps to obtain lily of the valley aldehyde; and then lily of the valley aldehyde and 2,6-dimethylmorpholine are condensed and catalytically hydrogenated under the catalysis of a catalyst to generate fenpropimorph. The inventor creatively found that the above-mentioned continuous reaction device 200 of the present application is used for a one-step reaction and the introduction of an acid binding agent in the continuous reaction device 200 can neutralize the acidic substances such as hydrogen chloride generated during the reaction process, and inhibit the side reaction of the aldehyde group being reduced in a proton hydrogen environment to produce hydroxy impurities, thereby improving the conversion rate of the raw material and the selectivity of the continuous reaction, and then improving the yield of fenpropimorph. The continuous mixing device 100 is provided for pre-mixing the above-mentioned raw materials and obtaining a stock liquid, which can achieve the same mixing effect as the batching kettle on the one hand, and can suppress the long-term placement of each raw material and the acid binding agent in the batching kettle and deteriorate on the other hand, and the continuous mixing mode can improve the reaction efficiency and production efficiency of the continuous reaction, thereby improving the yield of the target product fenpropimorph. The continuous gas-liquid separation device 300 is provided for separating the product system containing fenpropimorph, and then obtaining a liquid-phase product. The continuous rectification device 400 is provided for carrying out continuous rectification to the liquid-phase product, to obtain fenpropimorph with higher purity.

[0037] Compared with the intermittent production system, the continuous production system of fenpropimorph described in the present application can realize the continuous production of fenpropimorph through the "one-pot method", thereby simplifying the process flow, and reducing the post-processing process of the multi-step process, thereby reducing material waste, reducing equipment costs, and improving production efficiency; and the use of the above-mentioned continuous production system for production can more accurately control the reaction conditions, improve production safety, and reduce the occurrence of side reactions, improve product selectivity, and thus improve the yield of fenpropimorph.

[0038] In a preferred embodiment, the continuous gas-liquid separation device 300 is further provided with a recovered hydrogen outlet 301; the recovered hydrogen outlet 301 is connected to the hydrogen inlet 202. The continuous gas-liquid separation device 300 is used to separate the liquid product and hydrogen in the product system containing fenpropimorph, and the recovered hydrogen obtained can be returned to the continuous reaction device 200 for recycling, which is beneficial to improve the recovery rate of hydrogen and further help reduce costs.

[0039] In a preferred embodiment, the continuous mixing device 100 is a continuous microchannel mixer. Compared with other types, the continuous mixing device 100 of the above type is conducive to achieving a mixing effect equivalent to that of a batching kettle, and is conducive to inhibiting the deterioration of the raw materials and acid binding agents in the batching kettle due to long-term placement. At the same time, the continuous mixing method is conducive to improving the reaction efficiency and production efficiency of the continuous reaction, thereby helping to improve the yield of the target product fenpropimorph.

[0040] In a preferred embodiment, the continuous reaction device 200 is equipped with a temperature control component. The temperature control component can perform heating and cooling treatment on the continuous reaction device 200, so that the temperature in the continuous reaction device 200 is maintained within a more suitable range. The setting of the temperature control component is conducive to more accurately controlling the temperature in the continuous reaction device 200, thereby helping to improve the reaction efficiency of the continuous reaction, and also helping to improve the stability and safety of the continuous reaction. Preferably, the temperature control component uses microwaves or thermocouples for temperature control.

[0041] In order to improve the efficiency of heat exchange, thereby more accurately controlling the temperature in the continuous reaction device 200, and further improving the reaction efficiency, stability and safety of the continuous reaction, preferably, the temperature control component is filled with a heat exchange medium.

[0042] In a continuous fixed bed reactor, gas or liquid materials can flow through the catalyst bed in a continuous manner, thereby improving the effective contact between them and the catalyst, thereby achieving a higher conversion rate and selectivity. At the same time, its parameters are controllable, the operation is simple and stable, and it is suitable for continuous large-scale industrial production. Continuous fluidized bed reactors suspend solid particles under the action of fluids (usually gas or liquid) to form a fluidized state in the reactor, which helps to improve the efficiency of heat and mass transfer, thereby achieving efficient chemical reactions.

[0043] In a preferred embodiment, the continuous reaction device 200 is a continuous fixed bed reactor or a continuous fluidized bed reactor. Compared with other types, the use of the above-mentioned type of reactor is conducive to improving the use efficiency of the catalyst, the stability and safety of the continuous reaction, and thus the conversion rate of the raw materials and the selectivity of the target product, thereby helping to improve the yield of fenpropimorph, and also helping to improve production efficiency.

[0044] In order to improve the separation efficiency of continuous gas-liquid separation, thereby further improving the recovery rate of hydrogen and further reducing production costs, in a preferred embodiment, the continuous gas-liquid separation device 300 is an inertial separation separator or a filtration separation separator.

[0045] In order to improve the purity of fenpropimorph, in a preferred embodiment, the continuous distillation device 400 includes but is not limited to a plate tower or a packed tower.

[0046] In a preferred embodiment, the loading amount of the catalyst is 10-90 vol%, based on the volume percentage of the continuous reaction device 200. The loading amount of the catalyst includes but is not limited to the above range. Limiting it within the above range is conducive to improving the catalytic efficiency of the catalyst, thereby improving the reaction efficiency of the continuous reaction, improving the conversion rate of the raw materials and the selectivity of fenpropimorph, and also helping to improve the utilization rate of the catalyst, thereby helping to reduce production costs.

[0047] The supported catalyst has the characteristics of high catalytic activity and good stability. In a preferred embodiment, the catalyst is a supported catalyst, and the active ingredients in the preferred supported catalyst include but are not limited to one or more of the group consisting of palladium, platinum, rhodium, nickel and copper. Compared to other types, the catalyst of the above type is conducive to improving its catalytic efficiency to the continuous reaction, thereby helping to improve the conversion rate of raw materials and the selectivity of the target product, and then helping to improve the yield of fenpropimorph.

[0048] In order to further improve the catalytic efficiency of the catalyst for the continuous reaction, thereby further improving the conversion rate of the raw materials and the selectivity of the target product, and then further improving the yield of butyl fenpropimorph, preferably, the catalyst includes but is not limited to one or more of the group consisting of palladium / carbon (Pd / C) catalyst, palladium / alumina (Pd / Al2O3) catalyst and platinum / carbon (Pt / C) catalyst.

[0049] In order to further improve the catalytic activity and selectivity of the catalyst, and thus further improve the reaction efficiency of the continuous reaction, in a preferred embodiment, the ratio of the average particle size of the catalyst to the diameter of the continuous reaction device 200 is 1:(5-20).

[0050] In a preferred embodiment, Figure 2 As shown, the above-mentioned continuous production system of fenpropimorph provided in the present application also includes a first mixing device 500, which is used to mix 4-tert-butyl-β-chloro-α-methylcinnamaldehyde with a part of the solvent to obtain a first mixed solution; the outlet of the first mixing device 500 is connected to the inlet of the continuous mixing device 100. The first mixing device 500 is used to pre-mix 4-tert-butyl-β-chloro-α-methylcinnamaldehyde with the solvent. The setting of the first mixing device 500 is conducive to improving the dispersibility of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde, thereby facilitating the mixing efficiency of subsequent continuous mixing, facilitating the acquisition of the raw material solution, and also conducive to improving production efficiency.

[0051] In a preferred embodiment, Figure 2As shown, the above-mentioned continuous production system of fenpropimorph further includes a second mixing device 600, which is used to mix 2,6-dimethylmorpholine, the acid binding agent and another part of the solvent to obtain a second mixed solution; the outlet of the second mixing device 600 is connected to the inlet of the continuous mixing device 100. The second mixing device 600 is used to pre-mix 2,6-dimethylmorpholine, the acid binding agent and the solvent. The setting of the second mixing device 600 is conducive to improving the dispersibility of 2,6-dimethylmorpholine and the acid binding agent, thereby facilitating the mixing efficiency of subsequent continuous mixing, facilitating the acquisition of the raw material solution, and also conducive to improving production efficiency.

[0052] In order to more accurately control the feed amount and feed rate of the raw material liquid, thereby further improving the reaction efficiency of the continuous reaction, and also to further improve the production efficiency, in a preferred embodiment, as Figure 2 As shown, the raw material liquid inlet 201 is connected to the raw material liquid outlet 101 through a raw material liquid delivery pipeline, and a continuous feed pump is arranged on the raw material liquid delivery pipeline.

[0053] The second aspect of the present application also provides a continuous production method of fenpropimorph, which is carried out using the above-mentioned continuous production system provided by the present application. The continuous production method includes: step S1, using a continuous mixing device 100 to continuously mix a first mixed liquid and a second mixed liquid to obtain a raw material liquid; the first mixed liquid includes 4-tert-butyl-β-chloro-α-methylcinnamaldehyde and a part of the solvent; the second mixed liquid includes 2,6-dimethylmorpholine, an acid binding agent and another part of the solvent; step S2, under the catalysis of a catalyst and the presence of hydrogen, the raw material liquid is passed into a continuous reaction device 200 for continuous reaction to obtain a product system containing fenpropimorph; step S3, using a continuous gas-liquid separation device 300 to continuously separate the product system into gas and liquid to obtain a liquid product; step S4, using a continuous distillation device 400 to continuously distill the liquid product to obtain fenpropimorph.

[0054] The continuous production method of the above-mentioned fenpropimorph provided in the present application enables 4-tert-butyl-β-chloro-α-methylcinnamaldehyde and 2,6-dimethylmorpholine to react continuously in one step under the catalysis of a catalyst and in the presence of an acid-binding agent and hydrogen to obtain a product system containing fenpropimorph. The synthetic route of fenpropimorph in the present application is as follows:

[0055]

[0056] Compared with the prior art, 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is used as a raw material, and lily of the valley aldehyde is first subjected to a catalytic hydrogenation dechlorination reaction in two steps to obtain lily of the valley aldehyde; then lily of the valley aldehyde and 2,6-dimethylmorpholine are subjected to condensation and catalytic hydrogenation reaction under the catalysis of a catalyst to generate fenpropimorph, and the inventor creatively finds that the above-mentioned one-step reaction of the present application and the introduction of an acid binding agent in the continuous reaction can neutralize the acidic substances such as hydrogen chloride generated during the reaction, and suppress the side reaction of hydroxy impurities produced by aldehyde reduction, thereby improving the conversion rate of the raw material and the selectivity of the continuous reaction, and then improving the yield of fenpropimorph. The above-mentioned raw materials are continuously mixed in advance by step S1 to obtain a raw material liquid, and it can be continuously passed into a continuous reaction device 200 for continuous reaction, which can achieve the same mixing effect as the batching kettle on the one hand, and can suppress the long-term placement of each raw material and the acid binding agent in the batching kettle and deteriorate, and the continuous mixing method can improve the reaction efficiency and production efficiency of the continuous reaction, thereby improving the yield of the target product fenpropimorph. The product system containing fenpropimorph is subjected to continuous gas-liquid separation in step S2 to obtain a liquid product. The liquid product is subjected to continuous rectification in step S3 to obtain fenpropimorph with high purity.

[0057] Compared with the batch intermittent production method, the above-mentioned continuous production method of the present application can realize the continuous production of fenpropimorph through the "one-pot method", simplify the process flow, and reduce the post-processing process of the multi-step process, thereby reducing material waste, reducing equipment costs, and improving production efficiency; and the use of the continuous production method for production can more accurately control the reaction conditions, improve production safety, and reduce the occurrence of side reactions, improve product selectivity, thereby increasing the yield of fenpropimorph.

[0058] In a preferred embodiment, the reaction temperature of the continuous reaction is 70-100° C., and the reaction pressure is 0.1-1.5 MPa. The reaction temperature and reaction pressure of the continuous reaction include but are not limited to the above ranges, and limiting them within the above ranges is conducive to improving the reaction efficiency of the continuous reaction, and is conducive to improving the conversion rate of the raw materials and the selectivity of the target product, thereby helping to improve the yield of fenpropimorph.

[0059] Liquid hourly space velocity refers to the volume of liquid phase reactants treated by a unit volume of catalyst per unit time. In a preferred embodiment, the liquid hourly space velocity of the raw material liquid in the continuous reaction device 200 is 1.34 to 8.01 h -1 The liquid hourly space velocity of the raw material liquid includes but is not limited to the above range. Limiting it within the above range is beneficial to improving the reaction efficiency of the continuous reaction, the conversion rate of the raw material and the selectivity of the target product, thereby helping to improve the yield of fenpropimorph.

[0060] In order to improve the utilization efficiency of hydrogen, while improving the reaction efficiency of the continuous reaction, and improving the conversion rate of the raw materials and the selectivity of the target product, in a preferred embodiment, the feed rate ratio of hydrogen to 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is (237-600) mL / min:1.0 g / min.

[0061] In a preferred embodiment, the feed rate ratio of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde, 2,6-dimethylmorpholine and acid binding agent is 1.0:(0.49-0.98):(0.51-0.71). The feed rate ratio of the above raw materials includes but is not limited to the above range. Limiting it within the above range is conducive to introducing an appropriate amount of acid binding agent to timely neutralize acidic substances such as hydrogen chloride generated during the reaction process, thereby facilitating the inhibition of the side reaction of aldehyde groups being reduced to generate hydroxyl impurities in a proton hydrogen environment, reducing the generation of by-products, and improving the reaction efficiency of the continuous reaction, thereby facilitating the improvement of the conversion rate of the raw materials and the selectivity of the continuous reaction, and at the same time, it is also conducive to improving the utilization rate of the raw materials and reducing the production cost.

[0062] In a preferred embodiment, in the continuous mixing device 100, the feed rate ratio of the first mixed liquid to the second mixed liquid is 1:(1-10). The feed rate ratio of the first mixed liquid to the second mixed liquid includes but is not limited to the above range, and limiting it within the above range is conducive to improving the dispersibility of the first mixed liquid and the second mixed liquid, and is also conducive to improving the efficiency of continuous mixing, thereby helping to improve production efficiency.

[0063] In order to further improve the dispersibility of the first mixed liquid and the second mixed liquid and further improve the efficiency of continuous mixing, preferably, the residence time of the first mixed liquid and the second mixed liquid is independently 2 to 10 minutes.

[0064] In a preferred embodiment, before step S1, the above-mentioned continuous production method provided by the present application further includes: using a first mixing device 500 to mix 4-tert-butyl-β-chloro-α-methylcinnamaldehyde with a portion of the solvent to obtain a first mixed solution. Pre-mixing 4-tert-butyl-β-chloro-α-methylcinnamaldehyde with the solvent is beneficial to improving the dispersibility of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde, thereby facilitating the mixing efficiency of subsequent continuous mixing, facilitating the acquisition of a raw material solution, and also beneficial to improving production efficiency.

[0065] In order to improve the dispersibility of 2,6-dimethylmorpholine and the acid binding agent, thereby further improving the mixing efficiency of subsequent continuous mixing and facilitating obtaining a raw material solution, and also to further improve production efficiency, in a preferred embodiment, a second mixing device 600 is used to mix 2,6-dimethylmorpholine, the acid binding agent and another part of the solvent to obtain a second mixed solution.

[0066] In a preferred embodiment, in the first mixed solution, the mass concentration of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is 16.2-21.2wt%. The mass concentration of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde includes but is not limited to the above range, and limiting it within the above range is beneficial to improving the reaction efficiency of the continuous reaction, the conversion rate of the raw materials and the selectivity of the target product, thereby helping to improve the yield of fenpropimorph.

[0067] In order to introduce a more suitable amount of acid binding agent to neutralize the acidic substances such as hydrogen chloride generated during the reaction, thereby further inhibiting the side reaction of aldehyde reduction to generate hydroxyl impurities, and further improving the conversion rate of raw materials and the selectivity of continuous reaction, in a preferred embodiment, the mass concentration of the acid binding agent in the second mixed solution is 7.37-11.6wt%.

[0068] In order to neutralize the acidic substances such as hydrogen chloride generated during the reaction, inhibit the side reaction of aldehyde reduction to generate hydroxy impurities, promote the forward progress of the continuous reaction, thereby improving the conversion rate of the raw materials and the selectivity of the continuous reaction, and then improve the yield of fenpropimorph, in a preferred embodiment, the acid binding agent is an organic base.

[0069] In order to further exert the effect of the acid binding agent, further promote the forward progress of the continuous reaction, and further improve the conversion rate of the raw materials and the selectivity of the continuous reaction, preferably, the acid binding agent includes but is not limited to one or more of the group consisting of triethylamine, pyridine, trimethylamine, diethylamine and ethylenediamine.

[0070] In order to improve the dispersibility of the above raw materials, thereby further improving the reaction efficiency of the continuous reaction, in a preferred embodiment, the solvent includes but is not limited to one or more of the group consisting of ethanol, methanol, isopropanol, toluene, methyl tert-butyl ether, 1,4-dioxane and ethyl acetate.

[0071] In a preferred embodiment, in step S3, after the continuous gas-liquid separation is completed, recycled hydrogen is obtained, and at least part of the recycled hydrogen is returned to step S2. The recycled hydrogen obtained by continuous gas-liquid separation is returned to step S2 for recycling, which is beneficial to improving the recycling rate of hydrogen, thereby helping to reduce production costs.

[0072] In order to improve the separation efficiency of continuous distillation and thus improve the purity of fenpropimorph, in a preferred embodiment, a continuous distillation tower is used to continuously distill the liquid product.

[0073] In order to further improve the separation efficiency of continuous distillation, thereby further improving the purity of fenpropimorph, preferably, the number of plates of the continuous distillation tower is 6 to 10, the top temperature is 50 to 55°C, the bottom temperature is 128 to 162°C, the operating pressure is 0.02 to 0.4 mmHg (millimeters of mercury), and the reflux ratio is (2 to 10):1.

[0074] 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.

[0075] Example 1

[0076] A continuous production method of fenpropimorph, using Figure 2 The continuous production system of fenpropimorph shown in the invention specifically comprises:

[0077] 80 vol% Pd / C catalyst (average particle size of 0.85-2 mm, Pd loading of 5 wt%) was loaded into a continuous fixed bed reactor (reactor volume of 60 mL). After loading, the continuous fixed bed reactor was tested for tightness;

[0078] Mixing 4-tert-butyl-β-chloro-α-methylcinnamaldehyde and ethanol in a mixing kettle to obtain a first mixed solution, wherein the mass concentration of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is 20.2wt%;

[0079] Mixing 2,6-dimethylmorpholine, triethylamine and ethanol in a mixing kettle to obtain a second mixed solution, wherein the mass concentration of triethylamine is 9.83wt%;

[0080] Passing the first mixed liquid and the second mixed liquid into a continuous microchannel mixer (using the continuous microchannel mixer in Chinese patent application CN202320266137.6) for continuous mixing to obtain a raw material liquid; wherein the feed flow rate ratio of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde, 2,6-dimethylmorpholine and triethylamine is 1.0:0.73:0.51, the feed rate ratio of the first mixed liquid to the second mixed liquid is 1:1, and the residence time of the first mixed liquid and the second mixed liquid is 4.5 min;

[0081] Nitrogen was introduced into the continuous fixed bed reactor to replace the air in the reactor. After repeating the operation three times, hydrogen was introduced into the reactor to replace the nitrogen in the reactor. After repeating the operation three times, hydrogen was introduced into the reactor, and the back pressure valve was adjusted to make the pressure in the reactor constant at 0.5 MPa, and then the hydrogen inlet valve was adjusted to make the feed rate ratio of hydrogen to 4-tert-butyl-β-chloro-α-methylcinnamaldehyde be 454 mL / min:1 g / min;

[0082] After the raw material liquid is preheated to 50°C, it is pumped into a continuous fixed bed reactor through a feed pump for continuous reaction to obtain a product system containing fenpropimorph; wherein the reaction temperature of the continuous reaction is 90°C, the reaction pressure is 0.5MPa, and the liquid hourly space velocity of the raw material liquid is 6h -1 ;

[0083] The product system containing fenpropimorph is passed into an inertial separation separator for continuous gas-liquid separation to obtain a liquid product and recovered hydrogen, and the recovered hydrogen is passed into a continuous fixed bed reactor for reuse; wherein the feed rate of the product system is 2.45 g / min, and the residence time is 5 min;

[0084] The liquid product is passed into a continuous distillation tower for continuous distillation to separate fenpropimorph; wherein the feed rate of the liquid product is 2.25 g / min, the residence time is 120 min, the number of plates of the continuous distillation tower is 10, the top temperature is 55°C, the bottom temperature is 165°C, the operating pressure is 0.025 mmHg, and the reflux ratio is 5:1.

[0085] Example 2

[0086] The difference from Example 1 is that in the continuous fixed bed reactor, the liquid hourly space velocity of the raw liquid is 1.34h -1 ; The remaining steps are the same as in Example 1.

[0087] Example 3

[0088] The difference from Example 1 is that in the continuous fixed bed reactor, the liquid hourly space velocity of the raw material liquid is 8.01h -1 ; The remaining steps are the same as in Example 1.

[0089] Example 4

[0090] The difference from Example 1 is that in the continuous fixed bed reactor, the liquid hourly space velocity of the raw material liquid is 10.00h -1 ; The remaining steps are the same as in Example 1.

[0091] Example 5

[0092] The difference from Example 1 is that the reaction temperature of the continuous reaction is 70° C. and the reaction pressure is 1.5 MPa; the remaining steps are the same as Example 1.

[0093] Example 6

[0094] The difference from Example 1 is that the reaction temperature of the continuous reaction is 100° C. and the reaction pressure is 0.1 MPa; the remaining steps are the same as in Example 1.

[0095] Example 7

[0096] The difference from Example 1 is that the reaction temperature of the continuous reaction is 60° C. and the reaction pressure is 1.8 MPa; the remaining steps are the same as in Example 1.

[0097] Example 8

[0098] The difference from Example 1 is that in the first mixed solution, the mass concentration of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is 16.2wt%, in the second mixed solution, the mass concentration of triethylamine is 7.37wt%, and the remaining steps are the same as in Example 1.

[0099] Example 9

[0100] The difference from Example 1 is that in the first mixed solution, the mass concentration of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is 21.1wt%, in the second mixed solution, the mass concentration of triethylamine is 11.60wt%, and the remaining steps are the same as in Example 1.

[0101] Example 10

[0102] The difference from Example 1 is that in the first mixed solution, the mass concentration of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is 14.51wt%, in the second mixed solution, the mass concentration of triethylamine is 5.01wt%, and the remaining steps are the same as in Example 1.

[0103] Embodiment 11

[0104] The difference from Example 1 is that diethylamine (acid binding agent) is used to replace triethylamine, and in the second mixed solution, the mass concentration of diethylamine is 7.37wt%; the remaining steps are the same as in Example 1.

[0105] Example 12

[0106] The difference from Example 1 is that the feed rate ratio of hydrogen to 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is 600 mL / min:1 g / min; the remaining steps are the same as Example 1.

[0107] Example 13

[0108] The difference from Example 1 is that the feed rate ratio of hydrogen to 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is 1183 mL / min:1 g / min; the remaining steps are the same as Example 1.

[0109] Comparative Example 1

[0110] A batch production method of fenpropimorph specifically comprises the following steps:

[0111] (1) Under the catalysis of 51.4 mg of Pd / C catalyst and in the presence of hydrogen, 1028.7 mg of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde was subjected to catalytic hydrogenation dehalogenation reaction in ethanol solvent to obtain 170.4 mg of lily of the valley aldehyde; wherein the reaction temperature was 85° C. and the pressure was 0.8 MPa;

[0112] (2) 1031.7 mg of lily of the valley aldehyde obtained in step (1) and 565.3 mg of 2,6-dimethylmorpholine undergo an aldehyde amine condensation hydrogenation reaction under the catalysis of 234.2 mg of Pd / C catalyst and the action of hydrogen to obtain 582.4 mg of butylfenmorph; wherein the reaction temperature is 100° C. and the pressure is 1 MPa.

[0113] The yields of fenpropimorph produced in all the examples and comparative examples of the present application and the conversion rates of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde are shown in the following Table 1. Among them, the conversion rate of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde refers to the ratio of the weight of the reacted 4-tert-butyl-β-chloro-α-methylcinnamaldehyde to the weight of the initial 4-tert-butyl-β-chloro-α-methylcinnamaldehyde.

[0114] Table 1

[0115]

[0116] From the above description, it can be seen that the above embodiments of the present invention achieve the following technical effects:

[0117] Comparing Example 1 and Comparative Example 1, Comparative Example 1 prepares fenpropimorph using an intermittent two-step method, and alkali is not added during the reaction, so as to cause its reaction selectivity to be low, and the impurity content increases, and then the yield of fenpropimorph is only 9.27%. It can be seen from this that the application introduces an acid binding agent in a continuous reaction to neutralize the acidic substances such as hydrogen chloride generated during the reaction, and suppresses the side reaction of the aldehyde group being reduced to produce hydroxy impurities under a proton hydrogen environment, so as to improve the conversion rate of raw materials and the selectivity of the continuous reaction, and then the yield of fenpropimorph can be improved; at the same time, compared to the batch intermittent production method of Comparative Example 1, the above-mentioned continuous production method of the application is adopted, the post-processing process of multi-step flow is simplified, and the material loss in the production process is reduced, so as to reduce energy consumption and equipment cost, and improve production efficiency; and the reaction conditions can be controlled more accurately, production safety can be improved, and the occurrence of side reactions can be reduced at the same time, the selectivity of the product can be improved, so as to improve the yield of fenpropimorph.

[0118] Comparing Examples 1 to 4, it can be seen that, compared with other ranges, limiting the liquid hourly space velocity of the raw material liquid within the above-mentioned range of the present application is beneficial to improving the reaction efficiency of the continuous reaction, improving the conversion rate of the raw material and the selectivity of the target product, thereby helping to improve the yield of butylfenmorph.

[0119] By comparing Examples 1, 5 to 7, it can be seen that the reaction temperature and reaction pressure of the continuous reaction include but are not limited to the above ranges. Limiting them within the above ranges is beneficial to improving the reaction efficiency of the continuous reaction, improving the conversion rate of the raw materials and the selectivity of the target product, thereby helping to improve the yield of butylfenmorph.

[0120] Comparative Examples 1, 8 to 10 Compared with other ranges, the mass concentration of 4-tert-butyl-β-chloro-α-methylcinnamaldehyde and the mass concentration of the acid binding agent are limited within the above range of the present application. On the one hand, it is beneficial to introduce a more suitable amount of acid binding agent to neutralize the acidic substances such as hydrogen chloride generated during the reaction, thereby helping to inhibit the side reaction of the aldehyde group being reduced to generate hydroxyl impurities under the proton hydrogen environment, and promoting the forward progress of the continuous reaction. On the other hand, it is beneficial to improve the conversion rate of the raw materials and the selectivity of the continuous reaction, improve the reaction efficiency of the continuous reaction, and thus help to improve the yield of fenpropimorph.

[0121] Comparing Examples 1 and 11, it can be seen that, compared with other types, the use of the above-mentioned types of acid-binding agents of the present application is conducive to timely neutralization of acidic substances such as hydrogen chloride generated during the reaction, and is conducive to inhibiting the side reaction of aldehyde groups being reduced to generate hydroxyl impurities in a proton hydrogen environment, thereby facilitating the forward progress of the continuous reaction, and further facilitating the improvement of the conversion rate of the raw materials and the selectivity of the continuous reaction, and is conducive to improving the yield of fenpropimorph.

[0122] By comparing Examples 1, 12 and 13, it can be seen that the feed rate ratio of hydrogen to 4-tert-butyl-β-chloro-α-methylcinnamaldehyde includes but is not limited to the above range. Limiting it within the above range is beneficial to improving the utilization efficiency of hydrogen, while also beneficial to improving the reaction efficiency of the continuous reaction, and is beneficial to improving the conversion rate of the raw material and the selectivity of the target product.

[0123] 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.

[0124] 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 production system of fenpropimorph, characterized in that, The continuous production system comprises: A continuous mixing device (100) is used to mix a first mixed liquid and a second mixed liquid to obtain a raw material liquid; the continuous mixing device (100) is provided with a raw material liquid outlet (101); the first mixed liquid comprises 4-tert-butyl-β-chloro-α-methylcinnamaldehyde and a part of a solvent; the second mixed liquid comprises 2,6-dimethylmorpholine, an acid binding agent and another part of the solvent; A continuous reaction device (200) is used for causing the 4-tert-butyl-β-chloro-α-methylcinnamaldehyde and the 2,6-dimethylmorpholine to react continuously under the catalysis of a catalyst and in the presence of an acid-binding agent, hydrogen and the solvent to obtain a product system containing fenpropimorph; the continuous reaction device (200) is provided with a raw material liquid inlet (201), a hydrogen inlet (202) and a product system outlet; the raw material liquid inlet (201) is connected to the raw material liquid outlet (101); a catalyst bed is provided inside the continuous reaction device (200), and the catalyst is loaded in the catalyst bed; A continuous gas-liquid separation device (300), wherein the continuous gas-liquid separation device (300) is provided with a product system inlet and a liquid product outlet; the product system inlet is connected to the product system outlet; A continuous distillation device (400) is provided with a liquid product inlet and a fenpropimorph outlet (401); the liquid product inlet is connected to the liquid product outlet.

2. The continuous production system of fenpropimorph according to claim 1, characterized in that, The continuous gas-liquid separation device (300) is further provided with a hydrogen recovery outlet (301); the hydrogen recovery outlet (301) is connected to the hydrogen inlet (202); Preferably, the continuous mixing device (100) is a continuous microchannel mixer; Preferably, the continuous reaction device (200) is equipped with a temperature control component, and preferably the temperature control component is filled with a heat exchange medium; Preferably, the continuous reaction device (200) is a continuous fixed bed reactor or a continuous fluidized bed reactor; Preferably, the continuous gas-liquid separation device (300) is an inertial separation separator or a filtration separation separator; Preferably, the continuous distillation device (400) is a plate tower or a packed tower; Preferably, the loading amount of the catalyst is 10 to 90 vol% based on the volume percentage of the continuous reaction device (200); Preferably, the catalyst is a supported catalyst, and preferably the active ingredient in the supported catalyst is selected from one or more of the group consisting of palladium, platinum, rhodium, nickel and copper; more preferably, the catalyst is selected from one or more of the group consisting of palladium / carbon catalyst, palladium / alumina catalyst and platinum / carbon catalyst.

3. The continuous production system of fenpropimorph according to claim 1, characterized in that, The continuous production system of fenpropimorph also includes: A first mixing device (500) is used to mix the 4-tert-butyl-β-chloro-α-methylcinnamaldehyde with a portion of the solvent to obtain a first mixed liquid; the outlet of the first mixing device (500) is connected to the inlet of the continuous mixing device (100); A second mixing device (600) is used to mix the 2,6-dimethylmorpholine, the acid binding agent and another part of the solvent to obtain a second mixed solution; the outlet of the second mixing device (600) is connected to the inlet of the continuous mixing device (100); Preferably, the raw material liquid inlet (201) is connected to the raw material liquid outlet (101) via a raw material liquid delivery pipeline, and a continuous feed pump is provided on the raw material liquid delivery pipeline.

4. A continuous production method of fenpropimorph, characterized in that, The continuous production method is carried out using the continuous production system according to any one of claims 1 to 3, and the continuous production method comprises: Step S1, using a continuous mixing device (100) to continuously mix a first mixed liquid and a second mixed liquid to obtain a raw material liquid; the first mixed liquid comprises 4-tert-butyl-β-chloro-α-methylcinnamaldehyde and a portion of a solvent; the second mixed liquid comprises 2,6-dimethylmorpholine, an acid-binding agent and another portion of the solvent; Step S2, in the presence of a catalyst and hydrogen, the raw material liquid is introduced into a continuous reaction device (200) for continuous reaction to obtain a product system containing fenpropimorph; Step S3, using a continuous gas-liquid separation device (300) to continuously separate the gas and liquid of the product system to obtain a liquid phase product; Step S4, using a continuous distillation device (400) to continuously distill the liquid phase product to obtain the fenpropimorph.

5. The continuous production method of fenpropimorph according to claim 4, characterized in that, The reaction temperature of the continuous reaction is 70-100°C, and the reaction pressure is 0.1-1.5MPa; Preferably, in the continuous reaction device (200), the liquid hourly space velocity of the raw material liquid is 1.34 to 8.01 h -1 ; Preferably, the feed rate ratio of the hydrogen to the 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is (237-600) mL / min:1.0 g / min; Preferably, the feed rate ratio of the 4-tert-butyl-β-chloro-α-methylcinnamaldehyde, the 2,6-dimethylmorpholine and the acid binding agent is 1.0:(0.49-0.98):(0.51-0.71).

6. The continuous production method of fenpropimorph according to claim 4, characterized in that, In the continuous mixing device (100), the feed rate ratio of the first mixed liquid to the second mixed liquid is 1:(1-10); Preferably, the residence time of the first mixed liquid and the second mixed liquid is independently 2 to 10 minutes.

7. The continuous production method of fenpropimorph according to any one of claims 4 to 6, characterized in that, Before step S1, the continuous production method further comprises: using a first mixing device (500) to mix the 4-tert-butyl-β-chloro-α-methylcinnamaldehyde with a portion of the solvent to obtain a first mixed liquid; Preferably, the second mixing device (600) is used to mix the 2,6-dimethylmorpholine, the acid binding agent and another part of the solvent to obtain a second mixed solution.

8. The continuous production method of fenpropimorph according to claim 7, characterized in that, In the first mixed solution, the mass concentration of the 4-tert-butyl-β-chloro-α-methylcinnamaldehyde is 16.2-21.2 wt %.

9. The continuous production method of fenpropimorph according to claim 7, characterized in that, In the second mixed solution, the mass concentration of the acid binding agent is 7.37-11.6wt%; Preferably, the acid binding agent is an organic base, more preferably the acid binding agent is one or more selected from the group consisting of triethylamine, pyridine, trimethylamine, diethylamine and ethylenediamine; Preferably, the solvent is selected from one or more of the group consisting of ethanol, methanol, isopropanol, toluene, methyl tert-butyl ether, 1,4-dioxane and ethyl acetate.

10. The continuous production method of fenpropimorph according to claim 4, characterized in that, In the step S3, after the continuous gas-liquid separation is completed, recycled hydrogen is obtained; preferably, at least part of the recycled hydrogen is returned to the step S2.

Images