A method and system for the continuous production of prothioconazole

Abstract

The present application relates to the technical field of production of prothioconazole, and discloses a method and system for continuously producing prothioconazole. The prothioconazole is prepared by reacting raw material 2-(1-chloro-cycloprop-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thione-1-yl)-propane in the presence of oxidant ferric chloride, and the oxidation reaction and crystallization purification are both carried out in a tubular reactor. The tubular reactor is used to continuously carry out the oxidation reaction and the continuous crystallization operation, the prepared product crystal is a cubic crystal grain, the product particle size is between 100-200 μm, the stability of the product quality and the production efficiency are improved, the ferric chloride can be recycled and reused, almost no three wastes are generated, it is clean and environmentally friendly, the product purity reaches more than 99%, the conversion rate is 100%, the yield is more than 99%, it is suitable for industrial production, and has good economic and social benefits.

Description

Technical Field

[0001] This invention relates to the technical field of prothioconazole production, and more particularly to a method and system for continuous production of prothioconazole. Background Technology

[0002] Prothioconazole is a low-toxicity, highly effective, and broad-spectrum triazole thione fungicide manufactured and developed by Bayer AG, primarily used to control numerous diseases in cereals, wheat, and legumes. Currently, methods for preparing prothioconazole by oxidizing 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane have been reported in the literature. This method requires air, a catalytic amount of sulfur powder, or an excess of sulfur powder as the reaction reagent, and the oxidation reaction is carried out at a relatively high temperature. This reaction generates odorous byproducts, and the product yield is low. Other literature reports the use of excess ferric chloride as the reaction reagent, which generates a large amount of solid waste requiring deep treatment. Furthermore, these methods are mostly intermittent production, resulting in unstable and fluctuating product quality, uneven particle size, and low yield, making them unsuitable for industrial-scale production.

[0003] Currently, a series of continuous production methods have emerged in China. One reported method uses a tubular reactor as the reaction vessel. 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane is dissolved in a solvent, and an oxidant is added to the solvent and mixed. The mixture and oxygen are then simultaneously introduced into the tubular reactor for reaction. After the reaction, the reaction liquid discharged from the reactor outlet is purified and crystallized to obtain high-purity prothioconazole product. However, this process uses oxygen as the oxidant. Because oxygen has excessive oxidizing power, it can lead to the formation of a large amount of over-oxidized products, affecting both product quality and yield.

[0004] Furthermore, currently disclosed continuous production processes for prothioconazole all involve a single oxidation step using tubular or microchannel reactors. These processes require the addition of large amounts of solvent to homogenize the reaction system, and post-oxidation still necessitates traditional batch processing. This results in intermittent fluctuations in the process, low reaction efficiency, difficulty in guaranteeing product quality, and persistent issues with particle size uniformity. Therefore, it is necessary to find a fully continuous process for producing prothioconazole to improve the uniformity of product quality and increase reaction efficiency. Summary of the Invention

[0005] To address the problems of low production efficiency and unstable product quality in existing industrial production processes of prothioconazole, this invention provides a method and system for continuous production of prothioconazole.

[0006] To solve the above-mentioned technical problems, the technical solution provided by the present invention is as follows:

[0007] A method for continuous production of prothioconazole, the method specifically includes the following steps:

[0008] Step a: Add 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane raw material and ferric chloride to the reaction solvent respectively, mix them evenly, and obtain the raw material liquid and ferric chloride solution.

[0009] Step b: The raw material liquid and ferric chloride solution are continuously fed into static mixer I and mixed evenly. The mixture is then continuously fed into tubular reactor I for oxidation reaction to obtain oxidation reaction liquid.

[0010] Step c: After cooling the oxidation reaction solution to 30℃~40℃, it is continuously fed into static mixer II together with the crystallization solvent. After mixing evenly, the mixture is continuously fed into tubular reactor II for crystallization at a crystallization temperature of 20℃~30℃. The crystallized liquid is then separated into solid and liquid components, washed, and crude prothioconazole is obtained.

[0011] Step d: Add a portion of the refining solvent to the refining system, and then simultaneously and continuously add the crude prothioconazole and the remaining refining solvent to the refining system to carry out the refining reaction and obtain the refining reaction solution.

[0012] Step e: The refined reaction solution and crystallization solvent are continuously fed into the static mixer III and mixed evenly. The mixture is then continuously fed into the tubular reactor III for crystallization reaction. The crystallization temperature is 0℃~30℃. After crystallization, the liquid is separated into solid and liquid, washed, and dried to obtain the prothioconazole product.

[0013] In step b, the tubular reactor I is a multi-stage reactor, including a low-temperature reaction section, a heating reaction section, and a high-temperature reaction section; the temperature of the low-temperature reaction section is 20℃~30℃, the temperature of the heating reaction section is increased from 20℃~30℃ to 50℃~70℃, and the temperature of the high-temperature reaction section is 50℃~70℃.

[0014] To address the technical problems in the existing intermittent production process of prothioconazole, particularly the intermittent crystallization operation which leads to unstable product quality and uneven particle size, this invention conducts in-depth research on the production process of prothioconazole, especially on the technical challenge of making the intermittent crystallization reaction process continuous.

[0015] Intermittent crystallization is simple to operate, but the product particle size is uneven and the product quality is unstable. Continuous crystallization requires precise control of the initial crystallization timing, crystallization rate and crystal particle size to avoid crystal bursting and resulting in inconsistent product particle size. At the same time, it is also necessary to control technical issues such as the feeding sequence, material concentration, reaction temperature and reaction selectivity of the oxidation reaction to minimize the occurrence of side reactions and reduce their impact on the crystallization process.

[0016] Compared to existing technologies, the continuous production method of prothioconazole provided by this invention employs a multi-stage tubular reactor for continuous oxidation reaction, controlling the reaction temperature of each stage to ensure sufficient oxidation and reduce side reactions. Furthermore, by selecting a tubular reactor and controlling a specific crystallization temperature for continuous crystallization, combined with a refining system, the prepared prothioconazole product exhibits uniform cubic crystals with a particle size of 100μm–200μm and a concentrated particle size distribution. This effectively improves the quality and particle size uniformity of the prothioconazole product, achieving a purity of over 99%, a raw material conversion rate of 100%, and a product yield of over 99%. Moreover, it significantly improves production efficiency, reduces labor costs, and is conducive to industrial-scale production, making it highly valuable for widespread application.

[0017] It should be noted that the structural formulas of 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane and prothioconazole are shown below:

[0018]

[0019] Further, in step a, the reaction solvent is one or more of acetonitrile, tetrahydrofuran, acetone, methanol, ethanol, n-butanol, isopropanol, or water.

[0020] Further, in step a, the mass concentration of the raw material liquid is 30% to 40%, and the mass concentration of the ferric chloride solution is 40% to 75%.

[0021] Optimal reaction solvent and material concentrations promote the full progress of the oxidation reaction, improve the selectivity of the reaction, and reduce the occurrence of side reactions.

[0022] Further, in step b, the residence time of the low-temperature reaction section is 0.5 min to 20 min, the heating time of the heating reaction section is 0.2 min to 2 min, and the residence time of the high-temperature reaction section is 0.5 min to 5 min.

[0023] Furthermore, in step b, the pressure of the oxidation reaction is 0.4 MPa to 1.0 MPa.

[0024] This invention improves product quality by selecting a multi-stage oxidation reaction and controlling the temperature and time of each stage of the reaction, while ensuring sufficient reaction and avoiding the generation of polymerization impurities. It also effectively reduces the impact of side reaction impurities on the crystallization process.

[0025] Further, in step b, the ferric chloride solution is first introduced into the static mixer I, and after 0.5 min to 1 min, the raw material liquid is then introduced.

[0026] Further, in step b, the molar ratio of the 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane raw material to ferric chloride is 1:2 to 3.

[0027] Further, in step b, the feed rate of the ferric chloride solution is 0.5T / h to 3T / h, and the feed rate of the raw material liquid is 1T / h to 5T / h.

[0028] Optimal material feeding sequence, feeding rate, and material molar ratio are beneficial for ensuring the oxidation reaction proceeds fully and reducing the generation of polymerization impurities.

[0029] Furthermore, in step c, the crystallization solvent is water.

[0030] Further, in step c, the mass ratio of the crystallization solvent to the 2-(1-chloro-cycloprop-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane raw material is 2 to 4:1.

[0031] Furthermore, in step c, the residence time of the mixture in tubular reactor II is 0.5 min to 2 min.

[0032] Furthermore, in step c, the feed rate of the crystallization solvent is 2T / h to 10T / h.

[0033] Further, in step c, the crystallization solvent is first introduced into the static mixer II, and after the oxidation reaction solution is cooled to 30°C to 40°C, the oxidation reaction solution is then introduced.

[0034] By controlling the feed ratio, feed rate, and crystallization temperature of the materials during the crystallization process, crystallization can proceed continuously and stably. This also helps to regulate the growth process of prothioconazole crystals, resulting in uniform cubic prothioconazole crystals. This ensures the quality of the continuously crystallized product and improves the particle size uniformity of the continuously crystallized product.

[0035] Further, in step d, the refining solvent is one or more of acetonitrile, tetrahydrofuran, acetone, methanol, ethanol, n-butanol, isopropanol, toluene, xylene, or chlorobenzene.

[0036] Furthermore, in step d, the portion of the refined solvent is 5% to 20% of the total amount of refined solvent.

[0037] Further, in step d, the total amount of the refining solvent is 1 to 4 times the mass of the 2-(1-chloro-cycloprop-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane raw material.

[0038] Furthermore, in step d, the residence time of the mixture in the tubular reactor III is 0.5 min to 2 min.

[0039] Furthermore, in step d, the purification reaction includes a reduction reaction and an adsorption purification process, and the temperature of the purification reaction is 20℃~30℃.

[0040] In summary, the reducing agent used in the reduction reaction can be a substance with reducing properties commonly used in the art, such as hydrogen, thiosulfate, hydride, aluminum hydride, sulfite, and borohydride.

[0041] The adsorption and impurity removal can be achieved by one or more of the following: activated carbon adsorption, chelating agent adsorption, resin adsorption, or molecular sieve adsorption.

[0042] Furthermore, in step e, the crystallization solvent is water.

[0043] Further, in step e, the mass ratio of the crystallization solvent to the 2-(1-chloro-cycloprop-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane raw material is 2 to 4:1.

[0044] Further, in step e, the residence time of the mixture in the tubular reactor III is 0.5 min to 2 min.

[0045] Further, in step e, the crystallization solvent is first introduced into the static mixer III, and then the purified reaction solution is introduced.

[0046] Optimal refining and crystallization processes can further improve the purity of prothioconazole products.

[0047] Furthermore, it also includes: acidifying, oxidizing, and extracting the crystallization mother liquor obtained from solid-liquid separation in step c, and filtering and concentrating the raffinate, and returning the resulting concentrated liquid to step a as a raw material for ferric chloride solution.

[0048] Based on the above, the filtrate is concentrated to a ferric chloride concentration of 30%–40% and then recycled as a raw material for the synthesis of prothioconazole.

[0049] Recycling ferric chloride not only effectively reduces the generation of hazardous waste, but also effectively lowers the production cost of prothioconazole, making the continuous production process of prothioconazole provided by this invention more in line with the development requirements of green environmental protection, energy conservation and consumption reduction.

[0050] The present invention also provides a system for the continuous production of prothioconazole, the system comprising: a static mixer I, a tubular reactor I, a static mixer II, a tubular reactor II, a purification system, a static mixer III, and a tubular reactor III connected in sequence;

[0051] The static mixer I is provided with an inlet and an outlet for mixing 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane solution and ferric chloride solution.

[0052] The tubular reactor I is a multi-stage tubular reactor, including a low-temperature reaction section, a heating reaction section and a high-temperature reaction section, used to oxidize 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane feed and ferric chloride solution.

[0053] The static mixer II is equipped with two feed inlets for mixing the oxidation reaction solution and the crystallization solvent;

[0054] The tubular reactor II is connected to the outlet of the static mixer and is used to carry out a crystallization reaction of the oxidation reaction liquid to obtain crude prothioconazole.

[0055] The refining system includes several reaction vessels, which are used to sequentially dissolve, reduce and adsorb the crude prothioconazole obtained from crystallization in tubular reactor II.

[0056] The static mixer III is equipped with two feed inlets for mixing the purified reaction solution with the crystallization solvent;

[0057] The tubular reactor III is connected to the outlet of the static mixer III and is used to carry out a crystallization reaction of the refined reaction solution to obtain the prothioconazole product.

[0058] The system for continuous production of prothioconazole provided by this invention can effectively improve the yield and purity of prothioconazole products. At the same time, the purification efficiency and process safety are also greatly improved, resulting in good economic benefits.

[0059] Furthermore, a first centrifuge device, a crude mother liquor tank, and a crude mother liquor refining system are also provided between the tubular reactor II and the refining system;

[0060] The first centrifuge device is used to separate the crystallization reaction liquid in tubular reactor II into solid and liquid components to obtain crude prothioconazole and crude mother liquor.

[0061] The crude mother liquor tank is connected to the outlet of the first centrifuge device and is used to store the crude mother liquor;

[0062] The crude mother liquor refining system, connected to the outlet of the crude mother liquor tank, includes an acidification tank, an oxidation tank, and an extraction tank, and is used to refine the crude mother liquor to obtain refined mother liquor.

[0063] Furthermore, a heat exchanger is also provided between the tubular reactor I and the static mixer II.

[0064] Furthermore, the system also includes a second centrifuge device, a purified mother liquor tank, and a solvent recovery system connected in sequence to the tubular reactor III;

[0065] The second centrifuge device is used to separate the crystallization reaction liquid in tubular reactor III into solid and liquid components to obtain prothioconazole product and refined mother liquor.

[0066] The refined mother liquor tank is connected to the outlet of the second centrifuge device and is used to store the refined mother liquor;

[0067] The solvent recovery system is connected to the outlet of the refined mother liquor tank and is used to recover the solvent in the refined mother liquor.

[0068] The method and system for continuous production of prothioconazole provided by this invention employs a tubular reactor for continuous oxidation and crystallization operations, yielding cubic prothioconazole products with a purity exceeding 99% and a yield exceeding 99%. This significantly improves the purity and yield of prothioconazole products, resulting in higher product quality stability and more uniform particle size. Furthermore, the process is highly automated, reducing labor intensity and the impact of human factors such as operator skill levels, making it suitable for large-scale production applications. Attached Figure Description

[0069] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0070] Figure 1This is a schematic diagram of the process flow for the continuous production of prothioconazole products according to an embodiment of the present invention. Detailed Implementation

[0071] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0072] The embodiments of the present invention will be described in detail below.

[0073] A method for continuous production of prothioconazole, the method specifically includes the following steps:

[0074] Step a, the vinylene carbonate synthesis liquid is sent to the first scraped evaporator and heated for distillation to obtain the top product. Step a, 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane raw material and ferric chloride are added to the reaction solvent respectively and mixed evenly to obtain the raw material liquid and ferric chloride solution.

[0075] Step b: The raw material liquid and ferric chloride solution are continuously fed into static mixer I and mixed evenly. The mixture is then continuously fed into tubular reactor I for oxidation reaction to obtain oxidation reaction liquid.

[0076] Step c: After cooling the oxidation reaction solution to 30℃~40℃, it is continuously fed into static mixer II together with the crystallization solvent. After mixing evenly, the mixture is continuously fed into tubular reactor II for crystallization at a crystallization temperature of 20℃~30℃. The crystallized liquid is then separated into solid and liquid components, washed, and crude prothioconazole is obtained.

[0077] Step d: Add a portion of the refining solvent to the refining system, and then continuously pass the crude prothioconazole and the remaining refining solvent into the refining system simultaneously to carry out the refining reaction and obtain the refined reaction solution.

[0078] Step e: The purified reaction solution and crystallization solvent are continuously fed into static mixer III and mixed evenly. The mixture is then continuously fed into tubular reactor III for crystallization reaction at a temperature of 0℃ to 30℃. After crystallization, the liquid is separated into solid and liquid components, washed, and dried to obtain the prothioconazole product.

[0079] The method for continuous production of prothioconazole provided in this invention not only effectively improves the purity and yield of the product, ensuring stable product characteristics and uniform particle size distribution, but also reduces equipment investment, labor costs, and energy consumption, resulting in low production costs. Furthermore, the production process generates almost no waste, thus avoiding secondary pollution to the environment. It can be widely applied to the large-scale production of prothioconazole products.

[0080] This invention also provides a system for the continuous production of prothioconazole, the system comprising: a static mixer I, a tubular reactor I, a static mixer II, a tubular reactor II, a purification system, a static mixer III, and a tubular reactor III connected in sequence;

[0081] The static mixer I is provided with an inlet and an outlet for mixing 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane solution and ferric chloride solution.

[0082] The tubular reactor I is a multi-stage tubular reactor, including a low-temperature reaction section, a heating reaction section and a high-temperature reaction section, used to oxidize 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane feed and ferric chloride solution.

[0083] The static mixer II is equipped with two feed inlets for mixing the oxidation reaction solution and the crystallization solvent;

[0084] The tubular reactor II is connected to the outlet of the static mixer and is used to carry out a crystallization reaction of the oxidation reaction liquid to obtain crude prothioconazole.

[0085] The refining system includes several reaction vessels, which are used to sequentially dissolve, reduce and oxidize the crude prothioconazole obtained from crystallization in tubular reactor II.

[0086] The static mixer III is equipped with two feed inlets for mixing the purified reaction solution with the crystallization solvent;

[0087] The tubular reactor III is connected to the outlet of the static mixer III and is used to carry out a crystallization reaction of the refined reaction solution to obtain the prothioconazole product.

[0088] The system for continuous production of prothioconazole provided by this invention has a simple equipment structure, high stability, high purification efficiency, and good process safety, and can be widely used in the production of prothioconazole.

[0089] To better illustrate the present invention, further examples are provided below.

[0090] In the following examples and comparative examples, 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane is referred to as Raw Material I.

[0091] Example

[0092] Reference Figure 1 The continuous production system for prothioconazole used in this embodiment consists of a raw material batching tank I, a ferric chloride batching tank, a static mixer I, an oxidation tubular reactor I, a heat exchanger, a crystallization solvent storage tank, a static mixer II, a crystallization tubular reactor II, a centrifugal merging tank I, a centrifuge I, a crude mother liquor tank, a refining system, a static mixer III, a crystallization tubular reactor III, a centrifugal merging tank II, a centrifuge II, a dryer, a temperature control and display system, a feed metering and control system, and related supporting conveying equipment connected by pipelines.

[0093] The metering pumps for ferric chloride and raw material I are connected to their respective mixing tanks. The outlets of these metering pumps are connected to two inlets of static mixer I via a mass flow rate control system. The outlet of static mixer I is connected to the inlet of oxidation tubular reactor I. The outlet of oxidation tubular reactor I is connected to the inlet of a heat exchanger, and the outlet of the heat exchanger is connected to one inlet of static mixer II. The metering pump for the crystallization solvent is connected to a crystallization solvent storage tank. The outlet of this metering pump is connected to the other inlet of static mixer II via a mass flow rate control system. The outlet of static mixer II is connected to the inlet of crystallization tubular reactor II. The outlet of I is connected to centrifugal blending tank I, the outlet of centrifugal blending tank I is connected to centrifuge I, centrifuge I is connected to the purification system and the crude mother liquor tank respectively, the mother liquor in the crude mother liquor tank is purified and then connected to the ferric chloride batching tank, the outlet of the purification system is connected to one inlet of static mixer III, the outlet of the metering pump of the crystallization solvent is connected to the other inlet of static mixer III through the mass flow regulation and control system, the outlet of static mixer III is connected to crystallization tubular reactor III, crystallization tubular reactor III is connected to centrifugal blending tank II, the outlet of centrifugal blending tank II is connected to centrifuge II, and the wet product is dried by a dryer to obtain the prothioconazole finished product.

[0094] The aforementioned refining system includes a dissolving tank, a reduction reaction tank, a feed pump, a filtration device, and a receiving tank. Temperature and pressure displays and automatic control systems are installed at each process node.

[0095] Furthermore, the aforementioned continuous prothioconazole production system consists of three parts in its oxidation tubular reactor I: a low-temperature reaction section, a heating reaction section, and a high-temperature reaction section. Each part has a different controlled temperature. The low-temperature reaction section controls the reaction temperature at 20–30°C, the heating reaction section controls the reaction temperature to gradually increase from 20–30°C to 50–70°C, and the high-temperature reaction section controls the reaction temperature at 50–70°C.

[0096] Specifically, the method for continuous production of prothioconazole using the above system includes:

[0097] Step a: Add the reaction solvent to raw material I and ferric chloride in the mixing tanks of each group, mix them evenly, and obtain a raw material liquid with a mass concentration of 30% to 40% and a ferric chloride solution with a mass concentration of 40% to 75%.

[0098] Step b: First, use a high-precision metering pump to continuously feed the ferric chloride solution into the static mixer I at a feed rate of 0.5T / h to 3T / h. After the ferric chloride solution has been fed for 0.5min to 1min, use the high-precision metering pump to feed the raw material liquid into the static mixer I at a feed rate of 1T / h to 5T / h. After thorough mixing, continuously feed the mixture into the oxidation tubular reactor I for oxidation reaction. Sample testing shows that the raw material I is not detected, indicating that the reaction has reached its endpoint, and the oxidation reaction liquid is obtained.

[0099] The tubular reactor has a low-temperature reaction section with a temperature of 20℃~30℃ and a residence time of 0.5min~20min; a heating reaction section with the temperature raised from 20℃~30℃ to 50℃~70℃ within 0.2min~2min; and a high-temperature reaction section with a temperature of 50℃~70℃ and a residence time of 0.5min~5min.

[0100] Step c: Using a high-precision metering pump, the crystallization solvent is continuously fed into static mixer II at a feed rate of 2T / h to 10T / h. After the crystallization solvent is fed for 0.5min to 1min, the oxidation reaction liquid cooled to 30℃ to 40℃ is continuously fed into static mixer II. After thorough mixing, the mixture is continuously fed into tubular reactor II for crystallization. The crystallization temperature is maintained at 20℃ to 30℃, and the residence time is 0.5min to 2min. The crystallized liquid is continuously introduced into centrifugal blending tank I. After the crystallized liquid in centrifugal blending tank I reaches a fixed volume, the crystallized slurry in centrifugal blending tank I is continuously introduced into centrifuge I. After centrifugation, filtration, and washing, the filter cake is the crude prothioconazole product.

[0101] Step d: First, add 5% to 20% of the total amount of refining solvent to the dissolving tank of the refining system. Then, continuously add crude prothioconazole to the dissolving tank while continuously adding the remaining refining solvent. Stir to promote the dissolution of crude prothioconazole. At the same time, continuously introduce the crude prothioconazole solution dissolved in the upper layer of the dissolving tank into the reduction reaction tank and continuously add reducing agent to carry out the reduction reaction. Then, introduce the reduction reaction liquid in the upper layer of the reduction reaction tank into the adsorption and impurity removal tank for continuous impurity removal. The temperature of the refining reaction is maintained at 30℃ to 50℃ and the residence time is 5 min to 30 min to obtain the refined reaction liquid.

[0102] Step e: Using a high-precision metering pump, the crystallization solvent and the refined reaction solution are simultaneously and continuously fed into the static mixer III. After thorough mixing, the mixture is continuously fed into the tubular reactor III for crystallization reaction. The crystallization temperature is 0℃~30℃, and the residence time is 0.5min~20min. The crystallized liquid is continuously introduced into the centrifugal slurry tank II. When the crystallized slurry in the centrifugal slurry tank II reaches a fixed volume, the crystallized slurry in the centrifugal slurry tank II is continuously introduced into the centrifuge II for centrifugation, filtration, washing, and drying to obtain the prothioconazole product.

[0103] The specific process conditions for Examples 1-9 are shown in Table 1 below.

[0104] Table 1 Process conditions for Examples 1-9

[0105]

[0106]

[0107]

[0108] Comparative Example 1

[0109] This comparative example provides a continuous production method for prothioconazole, comprising the following steps:

[0110] Step a: Add the reaction solvent to raw material I and ferric chloride in the mixing tanks of each group respectively, mix them evenly, and obtain a raw material solution with a mass concentration of 32.04% and a ferric chloride solution with a mass concentration of 51.32%.

[0111] Step b: Using a high-precision metering pump, ferric chloride solution is continuously fed into a static mixer at a feed rate of 0.75 T / h. After 0.5 min of ferric chloride solution feeding, the raw material liquid is then pumped into the static mixer at a feed rate of 2 T / h using the same high-precision metering pump. After thorough mixing, the mixture is continuously fed into an oxidation tubular reactor for oxidation reaction. The oxidation tubular reactor is a single-stage reactor. During the reaction, the temperature is kept constant at 25℃, the residence time is 30 min, and the reaction pressure is 0.7 MPa. Sampling and testing showed that the content of raw material I was 1.36%, and the content of prothioconazole was 98.02%. The reaction was not complete, and solids were precipitated.

[0112] Subsequent steps c-e are the same as in Example 4, and will not be repeated here.

[0113] The final prepared prothioconazole product had a content of 98.35%, a yield of 97.67%, and a particle size mainly of 120μm to 130μm.

[0114] Comparative Example 2

[0115] This comparative example provides a continuous production method for prothioconazole, comprising the following steps:

[0116] Step a: Add the reaction solvent to raw material I and ferric chloride in the mixing tanks of each group respectively, mix them evenly, and obtain a raw material solution with a mass concentration of 32.06% and a ferric chloride solution with a mass concentration of 50.41%.

[0117] Step b: Using a high-precision metering pump, ferric chloride solution is continuously fed into a static mixer at a feed rate of 0.75 T / h. After 1 minute of feeding, the raw material liquid is then pumped into the static mixer at a feed rate of 2 T / h using the same high-precision metering pump. After thorough mixing, the mixture is continuously fed into an oxidation tubular reactor for oxidation reaction. The oxidation tubular reactor is a single-stage reactor. During the reaction, the temperature is kept constant at 65℃, the residence time is 10 minutes, and the reaction pressure is 0.7 MPa. The sample test showed that the content of raw material I was 0.031%, the content of prothioconazole was 97.83%, and the content of new impurities was 1.74%. The reaction was complete, with no solid precipitation, and the liquid color was slightly darker.

[0118] Subsequent steps c-e are the same as in Example 4, and will not be repeated here.

[0119] The final prepared prothioconazole product had a content of 97.66% and a yield of 97.98%. The product particle size was mainly 150μm to 170μm, but a small amount of small spherical solids were produced. The content of prothioconazole in the small spherical substances was 92.38%, and the content of polymeric impurities was 6.81%.

[0120] Comparative Example 3

[0121] This comparative example provides a continuous production method for prothioconazole, comprising the following steps:

[0122] Step a: Add the reaction solvent to raw material I and ferric chloride in the mixing tanks of each group respectively, mix them evenly, and obtain a raw material solution with a mass concentration of 32.04% and a ferric chloride solution with a mass concentration of 50.75%.

[0123] Step b: First, use a high-precision metering pump to continuously feed ferric chloride solution into the static mixer at a feed rate of 0.75T / h. After 0.5 minutes of feeding, use the high-precision metering pump to feed the raw material liquid into the static mixer at a feed rate of 1T / h. After thorough mixing, continuously feed the mixture into the oxidation tubular reactor for oxidation reaction. Sample testing showed that raw material I was not detected, and the content of prothioconazole was 99.06%. The reaction endpoint was reached, and no solid precipitated, resulting in a light yellow oxidation reaction liquid.

[0124] The tubular reactor has a low-temperature reaction section with a temperature of 20℃~25℃ and a residence time of 5min; a heating reaction section with the temperature raised from 20℃~25℃ to 55℃~60℃ within 1min; and a high-temperature reaction section with a temperature of 55℃~60℃ and a residence time of 5min.

[0125] Step c: The oxidation reaction solution is continuously introduced into a tubular reactor and directly cooled to 5℃~10℃ for deep crystallization. The crystallization process is maintained at 5℃~10℃ for 2 minutes. The crystallization reaction solution is then introduced into a centrifugal slurry tank. After the crystallized slurry in the centrifugal slurry tank reaches a fixed volume, the crystallized slurry in the centrifugal slurry tank is continuously introduced into a centrifuge for centrifugation, filtration, and washing. The filter cake is the crude prothioconazole product. The crude product in this step has uneven particle size and is difficult to centrifuge and filter.

[0126] Step d: First, add 5% of the total amount of refining solvent to the dissolving tank of the refining system. Then, continuously add the crude prothioconazole to the dissolving tank, and simultaneously add the remaining refining solvent. The total amount of refining solvent is 2.2 times the mass of raw material I. Stir to dissolve the crude prothioconazole. At the same time, continuously introduce the crude prothioconazole solution dissolved in the upper layer of the dissolving tank into the reduction reaction tank, and continuously add reducing agent to carry out the reduction reaction. Then, introduce the reduction reaction liquid in the upper layer of the reduction reaction tank into the adsorption and impurity removal tank for continuous impurity removal. The temperature of the refining reaction is maintained at 35°C, and the residence time is 20 min to obtain the refined reaction liquid.

[0127] Step e: Using a high-precision metering pump, the refined reaction solution is continuously fed into a tubular reactor for crystallization reaction. The crystallization temperature is 5℃~10℃ and the residence time is 2min. The crystallized solution is continuously introduced into a centrifugal slurry tank. When the crystallized slurry in the centrifugal slurry tank reaches a fixed volume, the crystallized slurry in the centrifugal slurry tank is continuously introduced into a centrifuge for centrifugation, filtration, washing, and drying to obtain the prothioconazole product.

[0128] The prepared prothioconazole product had a content of 99.16% and a yield of 98.98%. The product particle size ranged from 20μm to 500μm, was uneven in size, had no obvious crystal form, and was in an amorphous powder state. The product required a long centrifugation time and had a high dry and wet content.

[0129] Comparative Example 4

[0130] This comparative example provides a continuous production method for prothioconazole, comprising the following steps:

[0131] Steps a and b are the same as in Example 4;

[0132] Step c: Using a high-precision metering pump, primary water is continuously fed into a static mixer at a feed rate of 2T / h. The amount of primary water added is twice the mass of raw material I. After the crystallization solvent is fed in for 0.5 minutes, the oxidation reaction liquid cooled to 45℃ is continuously fed into the static mixer. After thorough mixing, the mixture is continuously fed into a tubular reactor for crystallization. The crystallization temperature is maintained at 35℃, and the residence time is 2 minutes. The crystallized liquid is continuously introduced into a centrifugal slurry tank. After the crystallized liquid in the centrifugal slurry tank reaches a fixed volume, the crystallized slurry in the centrifugal slurry tank is continuously introduced into a centrifuge for centrifugal filtration, washing, and the filter cake is the crude prothioconazole. The crude prothioconazole is a fine powder, amorphous, with a high centrifugal filtration load, and the wet product has a drying weight loss of more than 30%.

[0133] Step d: First, add 5% of the total amount of refining solvent to the dissolving tank of the refining system. Then, continuously add the crude prothioconazole to the dissolving tank, and simultaneously add the remaining refining solvent. The total amount of refining solvent is 2.2 times the mass of raw material I. Stir to dissolve the crude prothioconazole. At the same time, continuously introduce the crude prothioconazole solution dissolved in the upper layer of the dissolving tank into the reduction reaction tank, and continuously add reducing agent to carry out the reduction reaction. Then, introduce the reduction reaction liquid in the upper layer of the reduction reaction tank into the adsorption and impurity removal tank for continuous impurity removal. The temperature of the refining reaction is maintained at 35°C, and the residence time is 20 min to obtain the refined reaction liquid.

[0134] Step e: Using a high-precision metering pump, primary water and refined reaction solution are simultaneously and continuously fed into a static mixer. After thorough mixing, the mixture is continuously fed into a tubular reactor for crystallization reaction. The crystallization temperature is 35°C and the residence time is 2 minutes. The crystallized liquid is continuously introduced into a centrifugal slurry tank. When the crystallized slurry in the centrifugal slurry tank reaches a fixed volume, the crystallized slurry in the centrifugal slurry tank is continuously introduced into centrifuge II for centrifugation, filtration, washing, and drying to obtain the prothioconazole product.

[0135] The prepared prothioconazole product had a content of 98.76% and a yield of 97.83%. The product had a particle size of 5μm to 100μm, was uneven in size, had no obvious crystal form, and was a fine powder. It was amorphous, had a high centrifugal filtration load, and required a long centrifugation time. The dry and wet content of the product reached 34.16%, and the drying energy consumption was high.

[0136] Comparative Example 5

[0137] This comparative example provides a method for the intermittent production of prothioconazole, comprising the following steps:

[0138] Steps a and b are the same as in Example 4;

[0139] Step c: Add primary water directly to the crystallization kettle, the amount of primary water being twice the mass of raw material I. Then, add the oxidation reaction solution cooled to 35°C to the crystallization kettle, maintaining the temperature of the crystallization kettle at 25°C for 30 minutes. Continuously introduce the crystallized liquid into a centrifugal merging tank. Once the crystallized liquid in the centrifugal merging tank reaches a fixed volume, continuously introduce the crystallized slurry from the centrifugal merging tank into a centrifuge for centrifugation, filtration, and washing. The filter cake is the crude prothioconazole product. The crude prothioconazole product has uneven particle size and exhibits clumping.

[0140] Step d: First, add the refining solvent to the dissolving tank of the refining system, then continuously add the crude prothioconazole to the dissolving tank. The total amount of refining solvent is 2.2 times the mass of raw material I. Stir to dissolve the crude prothioconazole. At the same time, continuously introduce the crude prothioconazole solution dissolved in the upper layer of the dissolving tank into the reduction reaction tank, and continuously add reducing agent to carry out the reduction reaction. Then, introduce the reduction reaction liquid in the upper layer of the reduction reaction tank into the adsorption and impurity removal tank for continuous impurity removal. The temperature of the refining reaction is maintained at 35℃ and the residence time is 20min to obtain the refined reaction liquid.

[0141] Step e: Add primary water directly to the crystallization vessel, the amount of primary water being twice the mass of raw material I. Then add the refined reaction solution to the crystallization vessel, control the temperature of the crystallization vessel at 25℃, and maintain the temperature for crystallization for 30 minutes. Continuously introduce the crystallized liquid into a centrifugal slurry tank. When the crystallized slurry in the centrifugal slurry tank reaches a fixed volume, continuously introduce the crystallized slurry in the centrifugal slurry tank into centrifuge II, centrifuge, filter, wash, and dry to obtain the prothioconazole product.

[0142] The prepared prothioconazole product has a content of 99.34% and a yield of 97.59%. The product particle size ranges from 50μm to 2400μm, with uneven size and clumping. It has an irregular cubic crystal form and uneven dry and wet content, with the lowest dry and wet content being 2.16% and the highest reaching 18.14%.

[0143] Comparative Example 6

[0144] This comparative example provides a method for the intermittent production of prothioconazole, comprising the following steps:

[0145] Steps a and b are the same as in Example 4;

[0146] Step c: The oxidation reaction solution is directly added to the crystallization vessel, and then primary water is added to the crystallization vessel. The amount of primary water added is twice the mass of raw material I. The temperature of the crystallization vessel is maintained at 25℃, and the crystallization holding time is 30 minutes. The crystallized liquid is continuously introduced into a centrifugal slurry tank. After the crystallized liquid in the centrifugal slurry tank reaches a fixed volume, the crystallized slurry in the centrifugal slurry tank is continuously introduced into a centrifuge, centrifuged, filtered, washed, and the filter cake is the crude prothioconazole. The crude prothioconazole crystals are not easy to form, and there are particles, powders, uneven particle sizes, and some particles are agglomerated into spheres.

[0147] Step d: First, add the refining solvent to the dissolving tank of the refining system, then continuously add the crude prothioconazole to the dissolving tank. The total amount of refining solvent is 2.2 times the mass of raw material I. Stir to dissolve the crude prothioconazole. At the same time, continuously introduce the crude prothioconazole solution dissolved in the upper layer of the dissolving tank into the reduction reaction tank, and continuously add reducing agent to carry out the reduction reaction. Then, introduce the reduction reaction liquid in the upper layer of the reduction reaction tank into the adsorption and impurity removal tank for continuous impurity removal. The temperature of the refining reaction is maintained at 35℃ and the residence time is 20min to obtain the refined reaction liquid.

[0148] Step e: The refined reaction solution is directly added to the crystallization vessel, and then primary water is added to the crystallization vessel. The amount of primary water added is twice the mass of raw material I. The temperature of the crystallization vessel is controlled at 25°C, and the crystallization time is 30 minutes. The crystallized liquid is continuously introduced into a centrifugal slurry tank. When the crystallized slurry in the centrifugal slurry tank reaches a fixed volume, the crystallized slurry in the centrifugal slurry tank is continuously introduced into centrifuge II. After centrifugation, filtration, washing, and drying, the prothioconazole product is obtained.

[0149] The prepared prothioconazole product had a content of 98.42% and a yield of 98.47%. The product particle size ranged from 20μm to 2400μm, with uneven size and different crystal forms. Some were small spheres, some were irregular cubic crystals, and some were powder. The product was uneven in terms of dryness and wetness, with the lowest dryness and wetness content being 3.38% and the highest reaching 20.32%.

[0150] In summary, the method for continuous production of prothioconazole provided by this invention requires less equipment investment, has high production efficiency, and produces prothioconazole products with a purity of over 99% and a yield of over 99%. Furthermore, the product quality is stable, and the particle size is uniform, making it suitable for industrial and continuous production. This method can significantly enhance the market competitiveness of enterprises and has broad application prospects.

[0151] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for continuous production of prothioconazole, characterized in that, The method specifically includes the following steps: Step a: Add 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane raw material and ferric chloride to the reaction solvent respectively, mix them evenly, and obtain the raw material liquid and ferric chloride solution. Step b: The raw material liquid and ferric chloride solution are continuously fed into static mixer I and mixed evenly. The mixture is then continuously fed into tubular reactor I for oxidation reaction to obtain oxidation reaction liquid. Step c: After cooling the oxidation reaction solution to 30℃~40℃, it is continuously fed into static mixer II together with the crystallization solvent. After mixing evenly, the mixture is continuously fed into tubular reactor II for crystallization at a temperature of 20℃~30℃. The crystallized liquid is then separated into solid and liquid components, washed, and crude prothioconazole is obtained. Step d: Add a portion of the refining solvent to the refining system, and then simultaneously and continuously add the crude prothioconazole and the remaining refining solvent to the refining system to carry out the refining reaction and obtain the refining reaction solution. Step e: The refined reaction solution and crystallization solvent are continuously fed into static mixer III and mixed evenly. The mixture is then continuously fed into tubular reactor III for crystallization reaction. The crystallization temperature is 0℃~30℃. After crystallization, the liquid is separated into solid and liquid, washed, and dried to obtain the prothioconazole product. In step a, the reaction solvent is one or more of acetonitrile, tetrahydrofuran, acetone, methanol, ethanol, n-butanol, isopropanol, or water. In step b, the tubular reactor I is a multi-stage reactor, including a low-temperature reaction section, a heating reaction section, and a high-temperature reaction section; the temperature of the low-temperature reaction section is 20℃~30℃, the temperature of the heating reaction section is increased from 20℃~30℃ to 50℃~70℃, and the temperature of the high-temperature reaction section is 50℃~70℃; the residence time of the low-temperature reaction section is 0.5min~20min, the heating time of the heating reaction section is 0.2min~2min, and the residence time of the high-temperature reaction section is 0.5min~5min.

2. The method for continuous production of prothioconazole as described in claim 1, characterized in that, In step a, the mass concentration of the raw material liquid is 30%~40%, and the mass concentration of the ferric chloride solution is 40%~75%.

3. The method for continuous production of prothioconazole as described in claim 1, characterized in that, In step b, the ferric chloride solution is first passed into static mixer I, and after 0.5 min to 1 min, the raw material liquid is then passed in; and / or In step b, the feed rate of the ferric chloride solution is 0.5T / h to 3T / h, and the feed rate of the raw material liquid is 1T / h to 5T / h.

4. The method for continuous production of prothioconazole as described in claim 1, characterized in that, In step c, the crystallization solvent is water; and / or In step c, the residence time of the mixture in tubular reactor II is 0.5 min to 2 min; and / or In step c, the feed rate of the crystallization solvent is 2T / h to 10T / h; and / or In step c, the crystallization solvent is first introduced into static mixer II, and after the oxidation reaction solution cools down to 30°C~40°C, the oxidation reaction solution is introduced again.

5. The method for continuous production of prothioconazole as described in claim 1, characterized in that, In step d, the refining solvent is one or more of acetonitrile, tetrahydrofuran, acetone, methanol, ethanol, n-butanol, isopropanol, toluene, xylene, or chlorobenzene; and / or In step d, the portion of the refining solvent is 5% to 20% of the total refining solvent; and / or In step d, the total amount of the refining solvent is 1 to 4 times the mass of the 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane feedstock; and / or In step d, the purification reaction includes a reduction reaction and an adsorption process for removing impurities, and the temperature of the purification reaction is 20℃~30℃.

6. The method for continuous production of prothioconazole as described in claim 1, characterized in that, In step e, the crystallization solvent is water; and / or In step e, the mass ratio of the crystallization solvent to the 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane feedstock is 2~4:1; and / or In step e, the residence time of the mixture in tubular reactor III is 0.5 min to 2 min; In step e, the crystallization solvent is first introduced into the static mixer III, and then the purified reaction solution is introduced.

7. The method for continuous production of prothioconazole as described in claim 1, characterized in that, Also includes: The mother liquor obtained from solid-liquid separation in step c is acidified, oxidized, and extracted. The raffinate is then filtered and concentrated. The resulting concentrated solution is recycled back to step a as a raw material for the ferric chloride solution.

8. A system for the continuous production of prothioconazole according to any one of claims 1 to 7, characterized in that, The system comprises, in sequence, a static mixer I, a tubular reactor I, a static mixer II, a tubular reactor II, a purification system, a static mixer III, and a tubular reactor III; The static mixer I is provided with an inlet and an outlet for mixing 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane solution and ferric chloride solution. The tubular reactor I is a multi-stage tubular reactor, including a low-temperature reaction section, a heating reaction section and a high-temperature reaction section, used to oxidize 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)-propane feed and ferric chloride solution. The static mixer II is equipped with two feed inlets for mixing the oxidation reaction solution and the crystallization solvent; The tubular reactor II is connected to the outlet of the static mixer II to carry out a crystallization reaction of the oxidation reaction liquid to obtain crude prothioconazole. The refining system includes several reaction vessels, which are used to sequentially dissolve, reduce and oxidize the crude prothioconazole obtained from crystallization in tubular reactor II. The static mixer III is equipped with two feed inlets for mixing the purified reaction solution with the crystallization solvent; The tubular reactor III is connected to the outlet of the static mixer III and is used to carry out a crystallization reaction of the refined reaction solution to obtain the prothioconazole product.

9. The system as described in claim 8, characterized in that, The tubular reactor II is also connected to the refining system by a first centrifuge device, a crude mother liquor tank, and a crude mother liquor refining system. The first centrifuge device is used to separate the crystallization reaction liquid in tubular reactor II into solid and liquid components to obtain crude prothioconazole and crude mother liquor. The crude mother liquor tank is connected to the outlet of the first centrifuge device and is used to store the crude mother liquor; The crude mother liquor refining system, connected to the outlet of the crude mother liquor tank, includes an acidification tank, an oxidation tank, and an extraction tank, and is used to refine the crude mother liquor to obtain refined mother liquor.

10. The system as described in claim 8, characterized in that, The system also includes a second centrifuge device, a refined mother liquor tank, and a solvent recovery system connected in sequence to tubular reactor III; The second centrifuge device is used to separate the crystallization reaction liquid in tubular reactor III into solid and liquid components to obtain prothioconazole product and refined mother liquor. The refined mother liquor tank is connected to the outlet of the second centrifuge device and is used to store the refined mother liquor; The solvent recovery system is connected to the outlet of the refined mother liquor tank and is used to recover the solvent in the refined mother liquor.

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