Preparation method and device of prothioconazole

Abstract

The invention provides a preparation method and device of prothioconazole. The preparation method comprises the following steps: carrying out Grignard reaction on o-chlorobenzyl chloride and magnesium powder in a mixed solvent of toluene and 2-methyltetrahydrofuran; the method comprises the following steps: carrying out Grignard addition reaction on a Grignard reagent and 2-chloro-1-(1-chlorocyclopropyl) ethanone; the preparation method comprises the following steps: carrying out substitution reaction on 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorphenyl) propanol and hydrazine hydrate in an alcohol solvent; the preparation method comprises the following steps: carrying out ring closing reaction on 2-(1-chlorocyclopropyl)-1-(2-chlorphenyl)-3-hydrazino-2-alcohol, a formaldehyde solution, a sodium thiocyanate solution and a sodium hydrogen sulfate solution; the preparation method comprises the following steps: carrying out oxidation reaction on 2-(2-chlorocyclopropyl)-3-(2-chlorphenyl)-2-hydroxypropyl)-1, 2, 4-triazolidine-3-thioketone, air and inorganic alkali, so as to obtain prothioconazole. The method can improve the efficiency of the oxidation reaction and the yield and purity of prothioconazole, and is more suitable for industrial production of prothioconazole.

Description

[0001] This application is based on the Chinese application with CN application number 202311680959.X and application date December 8, 2023, and claims its priority. The public content of the CN application is again introduced as a whole into this application. Technical Field

[0002] The invention relates to the technical field of chemical synthesis, and in particular to a method and a device for preparing prothioconazole. Background Art

[0003] Prothioconazole, molecular formula C 14 H 15 Cl2N3OS, CAS: 178928-70-6. Prothioconazole has low toxicity, no teratogenicity, no mutagenicity, no toxicity to embryos, and is safe for humans and the environment. It is mainly used to prevent and control many diseases of cereal crops such as wheat, barley, rapeseed, peanuts, rice and legumes. It not only has good safety, good disease prevention and treatment effects, but also significantly increases production. Compared with triazole fungicides, prothioconazole has a broader spectrum of fungicidal activity.

[0004] The existing production of prothioconazole mostly adopts an intermittent operation mode, which has high labor intensity and low production efficiency. The synthetic route of prothioconazole mostly uses o-chlorobenzyl chloride as raw material, and the final product is synthesized by preparing Grignard reagent, Grignard addition reaction, epoxidation reaction, substitution reaction, ring closure reaction and oxidation reaction. Among them, the oxidation reaction is that a heterocyclic compound and ferric chloride react to obtain prothioconazole, and ferrous chloride and hydrochloric acid are produced at the same time. According to theoretical calculations, for every ton of prothioconazole synthesized, 945kg of ferric chloride is consumed, 738kg of ferrous chloride and 212kg of hydrogen chloride are produced. The ferrous chloride and waste acid produced in large quantities are difficult to handle, which is unfriendly to the environment and has a high processing cost. Therefore, it is of great significance to develop a preparation method of prothioconazole with low material cost and low three waste output for the industrial production of prothioconazole. Summary of the invention

[0005] The main purpose of the present invention is to provide a method and device for preparing prothioconazole, so as to solve the problem that a large amount of waste is produced in the preparation of prothioconazole in the prior art.

[0006] In order to achieve the above object, according to the first aspect of the present invention, a preparation method of prothioconazole is provided, the preparation method comprising: performing a Grignard reaction on o-chlorobenzyl chloride and magnesium powder in a mixed solvent of toluene and 2-methyltetrahydrofuran to obtain a Grignard reagent; performing a Grignard addition reaction on the Grignard reagent and 2-chloro-1-(1-chlorocyclopropyl)ethanone to obtain 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol; performing a substitution reaction on 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol and hydrazine hydrate in an alcohol solvent to obtain 2-( 1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazino-2-ol; 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazino-2-ol undergoes a ring-closing reaction with a formaldehyde solution, a sodium thiocyanate solution and a sodium bisulfate solution to obtain 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione; 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione undergoes an oxidation reaction with air and an inorganic base to obtain prothioconazole.

[0007] Furthermore, the mass ratio of o-chlorobenzyl chloride, magnesium powder, 2-methyltetrahydrofuran and toluene in the Grignard reaction is 1:0.10-0.20:1.50-2.50:3.30-4.30; preferably, the temperature of the Grignard reaction is -10-40°C; preferably, the time of the Grignard reaction is 40-80 min.

[0008] Furthermore, the mass ratio of the Grignard reagent to 2-chloro-1-(1-chlorocyclopropyl)ethanone in the Grignard addition reaction is 1:0.6-0.9; preferably, the temperature of the Grignard addition reaction is -20-60°C; preferably, the time of the Grignard addition reaction is 10-50 min.

[0009] Furthermore, in the substitution reaction, the mass ratio of 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol, 60-80%wt hydrazine hydrate, and methanol is 1:0.40-1.20:2.30-3.40; preferably, the temperature of the substitution reaction is 60-120°C; preferably, the back pressure of the substitution reaction is 0.3-1.0MPa; preferably, the time of the substitution reaction is 30-120min.

[0010] Furthermore, in the ring-closing reaction, the mass ratio of 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazine-2-ol, formaldehyde solution, sodium thiocyanate solution, and sodium bisulfate solution is 1:0.30-0.40:0.30-0.50:0.40-0.60; preferably, the pH value of the ring-closing reaction is 4.00-5.00; preferably, the temperature of the ring-closing reaction is 20-50° C.; preferably, the time of the ring-closing reaction is 120-180 min; preferably, in terms of mass fraction, the concentration of the formaldehyde solution is 30-37%, the concentration of the sodium thiocyanate solution is 30-40%, and the concentration of the sodium bisulfate solution is 30-40%.

[0011] Furthermore, in the oxidation reaction, the mass ratio of 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione, air and sodium hydroxide solution is 1:0.5-1.0:20-30; preferably, the temperature of the oxidation reaction is -20-5°C; preferably, the time of the oxidation reaction is 20-80min; preferably, the concentration of the sodium hydroxide solution is 3-5% by mass fraction.

[0012] In order to achieve the above-mentioned object, according to a second aspect of the present invention, a preparation device of prothioconazole is provided, the preparation device comprising: a Grignard reagent-Grignard addition reaction unit, a substitution reaction unit, a ring-closure reaction unit and an oxidation reaction unit connected in sequence; and a continuous feeding device, the feeding device is connected in parallel with the Grignard reagent-Grignard addition reaction unit, the substitution reaction unit, the ring-closure reaction unit and the oxidation reaction unit.

[0013] Furthermore, the continuous feeding device includes: a material storage tank, a material feeding module and a control module; the control module is electrically connected to the material feeding module to control the material feeding speed of the material feeding module; the material feeding module includes a first feeding module, a second feeding module, a third feeding module and a fourth feeding module arranged in parallel; the inlets of the first feeding module, the second feeding module, the third feeding module and the fourth feeding module are independently connected to the outlet of the material storage tank; the outlets of the first feeding module, the second feeding module, the third feeding module and the fourth feeding module are respectively connected to the Grignard reagent-Grignard addition reaction unit, the substitution reaction unit, the ring closure reaction unit and the oxidation reaction unit.

[0014] Furthermore, the Grignard reagent-Grignard addition reaction unit comprises a first continuous reaction module and a first continuous post-processing module; the first continuous reaction module comprises a first temperature control module and a first main reactor; the first main reactor comprises a Grignard reactor and a Grignard addition reactor connected in series, and the Grignard reactor and the Grignard addition reactor are full mixed flow-tubular reactors; the full mixed flow-tubular reactor is divided into a material mixing section and a reaction section in sequence along the material flow direction; the first temperature control module is electrically connected to the first main reactor to control the reaction temperature in the first main reactor; the first feeding module comprises a continuous magnesium powder feeding module, a continuous o-chlorobenzyl chloride feeding module, and a continuous 2-methyl The tetrahydrofuran feeding module, the continuous toluene feeding module and the continuous 2-chloro-1-(1-chlorocyclopropyl)ethanone feeding module; the continuous magnesium powder feeding module, the continuous o-chlorobenzyl chloride feeding module, the continuous 2-methyltetrahydrofuran feeding module and the continuous toluene feeding module are independently connected to the material mixing section of the Grignard reactor; the reaction section outlet of the Grignard reactor and the continuous 2-chloro-1-(1-chlorocyclopropyl)ethanone feeding module are connected to the material mixing section of the Grignard addition reactor; the reaction section outlet of the Grignard addition reactor is connected to the inlet of the first continuous post-processing module, and the outlet of the first continuous post-processing module is connected to the inlet of the substitution reaction unit.

[0015] Furthermore, the substitution reaction unit includes a second continuous reaction module and a second continuous post-processing module; the second continuous reaction module includes a second temperature control module and a second main reactor; the second main reactor is divided into a material mixing section and a reaction section according to the material flow direction; the second temperature control module is electrically connected to the second main reactor to control the reaction temperature in the second main reactor; the second feeding module includes a continuous hydrazine hydrate solution feeding module and a continuous alcohol solvent feeding module; along the material flow direction, the outlets of the continuous hydrazine hydrate feeding module and the continuous alcohol solvent feeding module are independently connected to the inlet of the material mixing section of the second main reactor, the outlet of the reaction section of the second main reactor is connected to the inlet of the second continuous post-processing module, and the outlet of the second continuous post-processing module is connected to the inlet of the ring-closing reaction unit.

[0016] Furthermore, the ring-closing reaction unit includes a third continuous reaction module and a third continuous post-processing module; the third continuous reaction module includes a third temperature control module and a third main reactor; the third main reactor is divided into a material mixing section and a reaction section according to the material flow direction; the third temperature control module is electrically connected to the third main reactor to control the reaction temperature in the third main reactor; the third feeding module includes a continuous formaldehyde solution feeding module, a continuous sodium thiocyanate solution feeding module and a continuous sodium bisulfate solution feeding module; along the material flow direction, the outlets of the continuous formaldehyde solution feeding module, the continuous sodium thiocyanate solution feeding module and the continuous sodium bisulfate solution feeding module are each independently connected to the inlet of the material mixing section of the third main reactor, the outlet of the reaction section of the third main reactor is connected to the inlet of the third continuous post-processing module, and the outlet of the third continuous post-processing module is connected to the inlet of the oxidation reaction unit.

[0017] Furthermore, the oxidation reaction unit includes a fourth continuous reaction module and a fourth continuous post-processing module; the fourth continuous reaction module includes a fourth temperature control module and a fourth main reactor; the fourth main reactor is divided into a material mixing section and a reaction section according to the material flow direction; the fourth temperature control module is electrically connected to the fourth main reactor to control the reaction temperature in the fourth main reactor; the fourth feeding module includes an air pump and a continuous inorganic alkali feeding module; along the material flow direction, the air pump and the continuous inorganic alkali feeding module are connected to the inlet of the material mixing section of the fourth main reactor, and the outlet of the reaction section of the fourth main reactor is connected to the inlet of the fourth continuous post-processing module.

[0018] By applying the technical solution of the present invention, the present application synthesizes prothioconazole under air oxidation and inorganic base catalysis, which not only improves the efficiency of the oxidation reaction, but also significantly improves the yield and purity of prothioconazole, while greatly reducing the generation of three wastes, and can obtain prothioconazole in a more environmentally friendly and low-cost manner, which is more suitable for industrial production of prothioconazole. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] 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:

[0020] Figure 1 A schematic diagram of a continuous device for preparing prothioconazole in the present application is shown;

[0021] Figure 2 The schematic diagram of the device structure of the Grignard reagent-Grignard addition reaction unit 105 of the present application is shown;

[0022] Among them, the above Figure 1 The following reference numerals are included:

[0023] 101: material storage tank; 102: material feeding module; 103: control module; 105: Grignard reagent-Grignard addition reaction unit; 106: substitution reaction unit; 107: ring closure reaction unit; 108: oxidation reaction unit; 109: receiving tank;

[0024] Among them, the above Figure 2 The following reference numerals are included:

[0025] 201: material pump; 202: grid reactor; 203: grid addition reactor; 204: jacket inlet; 205: jacket outlet. DETAILED DESCRIPTION

[0026] 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.

[0027] As mentioned in the background technology, the oxidant ferric chloride used in the existing oxidation reaction not only produces a large amount of waste that is difficult to handle during the reaction, but also has the problem of high dosage cost, and there is a large application cost problem in actual industrial production. Therefore, the present application intends to provide a method for preparing prothioconazole that is low in cost and more environmentally friendly while ensuring reaction efficiency.

[0028] In a first typical embodiment of the present application, a preparation method of prothioconazole is provided, the preparation method comprising: performing a Grignard reaction on o-chlorobenzyl chloride and magnesium powder in a mixed solvent of toluene and 2-methyltetrahydrofuran to obtain a Grignard reagent; performing a Grignard addition reaction on the Grignard reagent and 2-chloro-1-(1-chlorocyclopropyl)ethanone to obtain 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol; performing a substitution reaction on 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol and hydrazine hydrate in an alcohol solvent to obtain 2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol; 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazino-2-ol undergoes a ring-closing reaction with a formaldehyde solution, a sodium thiocyanate solution and a sodium bisulfate solution to obtain 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione; 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione undergoes an oxidation reaction with air and an inorganic base to obtain prothioconazole.

[0029] The present application performs prothioconazole synthesis under air oxidation and inorganic base catalysis, which not only improves the efficiency of the oxidation reaction, but also ensures that the yield and purity of prothioconazole are at a good level, while greatly reducing the generation of three wastes. Among them, inorganic bases such as sodium hydroxide can promote the enol interconversion of heterocyclic compounds to generate a form that is more easily oxidized by oxygen, thereby accelerating the oxidation reaction rate and reducing the impact on the environment. By using a protic solvent and adding an appropriate amount of inorganic base, the oxidation reaction can be effectively promoted to achieve the same or even better effect as using a ferric chloride catalyst, and there is no need to deal with toxic byproducts, which significantly improves the greenness and sustainability of the production process.

[0030] In order to obtain a relatively pure 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol product, it is necessary to add dilute hydrochloric acid for quenching. In a preferred embodiment, after the Grignard addition reaction, the process further includes: quenching the product of the Grignard addition reaction with hydrochloric acid, washing with water and concentrating the product in sequence to obtain 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol.

[0031] In order to obtain relatively pure 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazino-2-ol, in a preferred embodiment, the product of the substitution reaction is concentrated, separated and washed with water in sequence to obtain 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazino-2-ol.

[0032] In order to obtain relatively pure 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione, in a preferred embodiment, after the ring-closing reaction, the process further comprises: filtering and washing the product of the ring-closing reaction in sequence to obtain 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione.

[0033] In order to facilitate subsequent use and storage, prothioconazole needs to be dried (temperature is 40-80°C). In a preferred embodiment, after the oxidation reaction, the process further includes: acidifying and crystallizing the product of the oxidation reaction, performing solid-liquid separation and drying in sequence to obtain prothioconazole. Among them, the solubility of prothioconazole in the system is relatively large under strong alkaline conditions, and acid needs to be added to promote the precipitation of prothioconazole.

[0034] In order to efficiently carry out the Grignard reaction, in a preferred embodiment, the mass ratio of o-chlorobenzyl chloride, magnesium powder, 2-methyltetrahydrofuran and toluene in the Grignard reaction is 1:0.10-0.20:1.50-2.50:3.30-4.30; preferably, the temperature of the Grignard reaction is -10-40°C; preferably, the time of the Grignard reaction is 40-80 min.

[0035] In order to efficiently carry out the Grignard addition reaction, in a preferred embodiment, the mass ratio of the Grignard reagent to 2-chloro-1-(1-chlorocyclopropyl)ethanone in the Grignard addition reaction is 1:0.6-0.9; preferably, the temperature of the Grignard addition reaction is -20-60°C; preferably, the time of the Grignard addition reaction is 10-50 min.

[0036] In order to efficiently carry out the substitution reaction, in a preferred embodiment, the mass ratio of 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol, 60-80%wt hydrazine hydrate, and methanol in the substitution reaction is 1:0.40-1.20:2.30-3.40; preferably, the temperature of the substitution reaction is 60-120°C; preferably, the back pressure of the substitution reaction is 0.3-1.0MPa; preferably, the time of the substitution reaction is 30-120min.

[0037] In order to efficiently carry out the ring-closing reaction, in a preferred embodiment, the mass ratio of 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazine-2-ol, formaldehyde solution, sodium thiocyanate solution, and sodium bisulfate solution in the ring-closing reaction is 1:0.30-0.40:0.30-0.50:0.40-0.60; preferably, the pH value of the ring-closing reaction is 4.00-5.00; preferably, the temperature of the ring-closing reaction is 20-50° C.; preferably, the time of the ring-closing reaction is 120-180 min; preferably, in terms of mass fraction, the concentration of the formaldehyde solution is 30-37%, the concentration of the sodium thiocyanate solution is 30-40%, and the concentration of the sodium bisulfate solution is 30-40%.

[0038] In order to efficiently carry out the oxidation reaction, in a preferred embodiment, the mass ratio of 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione to the sodium hydroxide solution in the oxidation reaction is 1:2-3:20-30; preferably, the temperature of the oxidation reaction is -20-5°C; preferably, the oxidation reaction time is 20-80min; preferably, the concentration of the sodium hydroxide solution is 3-5% by mass fraction.

[0039] In a second typical embodiment of the present application, a preparation device for prothioconazole is provided, the preparation device comprising: a Grignard reagent-Grignard addition reaction unit 105, a substitution reaction unit 106, a ring-closing reaction unit 107 and an oxidation reaction unit 108 connected in sequence; and a continuous feeding device, a continuous feeding device connecting the feeding device and the Grignard reagent-Grignard addition reaction unit 105, the substitution reaction unit 106, the ring-closing reaction unit 107 and the oxidation reaction unit 108 respectively connected in parallel.

[0040] In order to more accurately control the specific reaction degree of each stage reaction in the preparation process of prothioconazole, and to perform more detailed control on the reactant feeding of each reaction, in a preferred embodiment, the continuous feeding device includes: a material storage tank 101, a material feeding module 102 and a control module 103; the control module 103 is electrically connected to the material feeding module 102 to control the material feeding speed of the material feeding module 102.

[0041] In order to enable the reactants of each reaction in the preparation of prothioconazole in the present application to independently enter the relevant reaction unit to complete the subsequent reaction, in a preferred embodiment, the material feeding module 102 includes a first feeding module, a second feeding module, a third feeding module and a fourth feeding module arranged in parallel; the inlets of the first feeding module, the second feeding module, the third feeding module and the fourth feeding module are independently connected to the outlet of the material storage tank 101; the outlets of the first feeding module, the second feeding module, the third feeding module and the fourth feeding module are respectively connected to the Grignard reagent-Grignard addition reaction unit 105, the substitution reaction unit 106, the ring-closure reaction unit 107 and the oxidation reaction unit 108.

[0042] In order to better control the degree of completion of the Grignard reaction and the Grignard addition reaction in the continuous preparation of prothioconazole, the reaction temperature can be timely controlled within a suitable range to maintain the reaction efficiency. In a preferred embodiment, the Grignard reagent-Grignard addition reaction unit 105 includes a first continuous reaction module and a first continuous post-processing module; the first continuous reaction module includes a first temperature control module and a first main reactor; the first main reactor includes a Grignard reactor 202 and a Grignard addition reactor 203 connected in series, and the Grignard reactor 202 and the Grignard addition reactor 203 are full mixed flow-tubular reactors (such as Figure 2 As shown); the material pump 201 is used to pass the unreacted material in the Grignard reactor 202 into the Grignard reactor 202 again, and the fully mixed flow-tubular reactor is divided into a material mixing section and a reaction section along the material flow direction; the first temperature control module is electrically connected to the first main reactor to control the reaction temperature in the first main reactor. Among them, the fully mixed flow-tubular reactor is used to carry out Grignard reaction and Grignard addition reaction, and the temperature in the reactor can be adjusted in time by passing the temperature control material into the jacket, and the temperature control material is circulated from the jacket inlet 204 and the jacket outlet 205.

[0043] In order to better perform individual and precise control on each reactant in the Grignard reaction and the Grignard addition reaction, in a preferred embodiment, the first feeding module includes a continuous magnesium powder feeding module, a continuous o-chlorobenzyl chloride feeding module, a continuous 2-methyltetrahydrofuran feeding module, a continuous toluene feeding module and a continuous 2-chloro-1-(1-chlorocyclopropyl)ethanone feeding module; the continuous magnesium powder feeding module, the continuous o-chlorobenzyl chloride feeding module, the continuous 2-methyltetrahydrofuran feeding module and the continuous toluene feeding module are independently connected to the material mixing section of the Grignard reactor 202; the reaction section outlet of the Grignard reactor 202 and the continuous 2-chloro-1-(1-chlorocyclopropyl)ethanone feeding module are connected to the material mixing section of the Grignard addition reactor 203; the reaction section outlet of the Grignard addition reactor 203 is connected to the inlet of the first continuous post-processing module, and the outlet of the first continuous post-processing module is connected to the inlet of the substitution reaction unit 106. And after the obtained product enters the first continuous post-processing module, it can obtain the product 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol with higher purity through post-processing.

[0044] In order to better control the degree of completion of the substitution reaction during the continuous preparation of prothioconazole, the reaction temperature can be timely controlled within a suitable range to maintain the reaction efficiency, in a preferred embodiment, the substitution reaction unit 106 includes a second continuous reaction module and a second continuous post-processing module; the second continuous reaction module includes a second temperature control module and a second main reactor; the second main reactor is divided into a material mixing section and a reaction section according to the material flow direction; the second temperature control module is electrically connected to the second main reactor to control the reaction temperature in the second main reactor.

[0045] In order to better accurately control each reactant in the substitution reaction, in a preferred embodiment, the second feeding module includes a continuous hydrazine hydrate solution feeding module and a continuous alcohol solvent feeding module; along the material flow direction, the outlets of the continuous hydrazine hydrate feeding module and the continuous alcohol solvent feeding module are independently connected to the inlet of the material mixing section of the second main reactor, the outlet of the reaction section of the second main reactor is connected to the inlet of the second continuous post-processing module, and the outlet of the second continuous post-processing module is connected to the inlet of the ring-closing reaction unit 107. The toluene solution of the product 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazine-2-ol obtained by post-processing in the second continuous post-processing module enters the ring-closing reaction unit for the next step of reaction.

[0046] In order to better control the degree of completion of the ring-closing reaction during the continuous preparation of prothioconazole, the reaction temperature can be timely controlled within a suitable range to maintain the reaction efficiency, in a preferred embodiment, the ring-closing reaction unit 107 includes a third continuous reaction module and a third continuous post-processing module; the third continuous reaction module includes a third temperature control module and a third main reactor; the third main reactor is divided into a material mixing section and a reaction section according to the material flow direction; the third temperature control module is electrically connected to the third main reactor to control the reaction temperature in the third main reactor.

[0047] In order to better accurately control each reactant in the ring-closing reaction, in a preferred embodiment, the third feeding module includes a continuous formaldehyde solution feeding module, a continuous sodium thiocyanate solution feeding module and a continuous sodium bisulfate solution feeding module; along the material flow direction, the outlets of the continuous formaldehyde solution feeding module, the continuous sodium thiocyanate solution feeding module and the continuous sodium bisulfate solution feeding module are independently connected to the inlet of the material mixing section of the third main reactor, the outlet of the reaction section of the third main reactor is connected to the inlet of the third continuous post-processing module, and the outlet of the third continuous post-processing module is connected to the inlet of the oxidation reaction unit 108. The product 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione obtained by post-processing in the third continuous post-processing module enters the oxidation reaction unit for the next step of reaction.

[0048] In order to better control the degree of completion of the ring-closing reaction during the continuous preparation of prothioconazole, the reaction temperature can be timely controlled within a suitable range to maintain the reaction efficiency, in a preferred embodiment, the oxidation reaction unit 108 includes a fourth continuous reaction module and a fourth continuous post-processing module; the fourth continuous reaction module includes a fourth temperature control module and a fourth main reactor; the fourth main reactor is divided into a material mixing section and a reaction section according to the material flow direction; the fourth temperature control module is electrically connected to the fourth main reactor to control the reaction temperature in the fourth main reactor.

[0049] In order to further reduce the generation of more waste in the process of preparing prothioconazole, the present application uses air and inorganic base to carry out oxidation reaction. In a preferred embodiment, the fourth feeding module includes an air pump and a continuous inorganic base feeding module; along the material flow direction, the air pump and the continuous inorganic base feeding module are connected to the inlet of the material mixing section of the fourth main reactor, and the outlet of the reaction section of the fourth main reactor is connected to the inlet of the fourth continuous post-processing module. The product prothioconazole obtained by post-processing in the fourth continuous post-processing module is collected and stored in the product storage tank.

[0050] Since the reactants for the continuous reaction of prothioconazole in the present application include solid reactants and liquid reactants, and since the flow rates caused by the solid and liquid feeding forms are different, in order to more specifically monitor and adjust the feeding speeds of the reactants in two different states. In a preferred embodiment, the material storage tank 101 includes a solid material storage tank and a liquid material storage tank, which are the corresponding solid feeding module and liquid feeding module in the material feeding module 102 respectively; preferably, a feeding bin level monitoring device is connected between the solid material storage tank and the material feeding module 102; preferably, a metering system is connected between the liquid material storage tank and the material feeding module 102.

[0051] In order to further control the material feeding speed in a timely and convenient manner, in a preferred embodiment, a material conveying pump is arranged between each feeding module in the material feeding module 102 connected to the corresponding main reactor and the corresponding main reactor, and the control system adjusts the material flow rate delivered by the material conveying pump through the monitoring data of the feeding bin level monitoring device and the metering system.

[0052] In order to further improve the safety of the reaction and the purity of the product, a protective gas atmosphere can be provided to provide a stable reaction environment in each stage of the continuous production of prothioconazole. In a preferred embodiment, each corresponding main reactor also includes a nitrogen protection system to transport nitrogen to the material mixing section and the reaction section.

[0053] 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.

[0054] Example 1 (using Figure 1 The continuous device shown in the figure is used for preparation)

[0055] Grignard reagent-Grignard addition reaction:

[0056] Through the continuous feeding device, the relevant raw materials in the solid material storage tank (material storage tank 101) and the liquid material storage tank are respectively transported to each reaction unit using the solid feeding module (material feeding module 102) and the liquid feeding module, wherein the feeding situation is monitored by the feeding bin level monitoring device and the metering system (control module 103), and the feeding speed of the liquid material is adjusted by adjusting the delivery pump.

[0057] o-Chlorobenzyl chloride, magnesium powder, 2-methyltetrahydrofuran and toluene are respectively fed into the Grignard reactor 202 of the Grignard reagent-Grignard addition reaction unit 105 at mass flow rates of 1.00 kg / h, 0.16 kg / h, 2.00 kg / h and 3.80 kg / h, the reaction temperature is 20°C, the reaction time is 60 min, and the remaining reactants are returned to the Grignard reactor 202 through the material pump 201. After the reaction is completed, there is no o-chlorobenzyl chloride remaining, the reaction molar yield is 98%, and the coupling impurities are less than or equal to 1%. Among them, the reaction molar yield is the total mass of the product actually obtained / the theoretical mass of the product.

[0058] The Grignard reagent obtained from the Grignard reactor 202 of the Grignard reagent-Grignard addition reaction unit 105 is transported to the Grignard addition reaction unit 105 through the first feed module. The Grignard reagent solution and 2-chloro-1-(1-chlorocyclopropyl)ethanone are respectively fed into the Grignard addition reaction unit 203 at a mass flow rate of 6.92kg / h and 5.17kg / h, and the reaction temperature is -5°C and the reaction time is 15min. After the Grignard addition reaction is completed, the reaction product is quenched, separated, washed with water and concentrated in the first continuous post-processing module to obtain 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol. The remaining amount of 2-chloro-1-(1-chlorocyclopropyl)ethanone is ≤1%, and the reaction molar yield is 91% (based on 2-chloro-1-(1-chlorocyclopropyl)ethanone). The reaction temperature of the above-mentioned Grignard reaction and Grignard addition reaction can be adjusted by a temperature control material in the jacket, and the temperature control material flows from the jacket inlet 204 to the jacket outlet 205.

[0059] Substitution reaction: 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol obtained from the Grignard addition reactor 203 of the Grignard reagent-Grignard addition reaction unit 105 and 80%wt hydrazine hydrate and methanol transported to the substitution reaction unit 106 through the second feed module are respectively fed into the main reactor of the substitution reaction unit 106 at mass flow rates of 1.50kg / h, 1.20kg / h, and 4.28kg / h, with a reaction temperature of 100°C, a back pressure of 0.5MPa, and a reaction time of 60min. After the substitution reaction is completed, the reaction product is concentrated, extracted with toluene, and washed with water in the second continuous post-processing module to obtain a toluene solution of 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazine-2-ol. The remaining amount of 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol is ≤3%, and the reaction molar yield is about 90%.

[0060] Ring-closing reaction: The toluene solution of 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazine-2-ol obtained from the substitution reaction unit 106 and the 37%wt formaldehyde solution and 40%wt sodium thiocyanate and 40%wt sodium bisulfate transported to the ring-closing reaction unit 107 through the third feeding module are respectively fed into the main reactor of the ring-closing reaction unit 107 at a mass flow rate of 1.00kg / h, 0.35kg / h, 0.40kg / h, and 0.50kg / h, the reaction temperature is 40°C, the reaction time is 140min, and the pH value is 1-3. After the ring-closing reaction is completed, the reaction product is cooled and crystallized, filtered, and washed in the third continuous post-processing module to obtain 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione. The remaining amount of 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazino-2-ol is ≤2%, and the reaction molar yield is 83%.

[0061] Oxidation reaction: 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione obtained from the ring-closing reaction unit 107 and air and 5%wt sodium hydroxide solution transported to the oxidation reaction unit 108 through the fourth feed module are respectively put into the main reactor of the oxidation reaction unit 108 at a mass flow rate of 1.00kg / h, 1.0kg / h, and 25.00kg / h, the reaction temperature is -15°C, and the reaction time is 50min. After the oxidation reaction is completed, the reaction product is acid-crystallized and dried in the fourth continuous post-processing module to obtain prothioconazole, which is stored in the receiving tank 109 for standby use. The reaction molar yield is 90%.

[0062] Example 2

[0063] Grignard reagent-Grignard addition reaction:

[0064] Through the continuous feeding device, the relevant raw materials in the solid material storage tank (material storage tank 101) and the liquid material storage tank are respectively transported to each reaction unit using the solid feeding module (material feeding module 102) and the liquid feeding module, wherein the feeding situation is monitored by the feeding bin level monitoring device and the metering system (control module 103), and the feeding speed of the liquid material is adjusted by adjusting the delivery pump.

[0065] o-Chlorobenzyl chloride, magnesium powder, 2-methyltetrahydrofuran and toluene are respectively fed into the Grignard reactor 202 of the Grignard reagent-Grignard addition reaction unit 105 at mass flow rates of 1.00 kg / h, 0.16 kg / h, 2.00 kg / h and 3.80 kg / h, the reaction temperature is 40°C, the reaction time is 80 min, and the remaining reactants are returned to the Grignard reactor 202 through the material pump 201. After the reaction is completed, there is no o-chlorobenzyl chloride remaining, the reaction molar yield is 98%, and the coupling impurities are less than or equal to 1%. Among them, the reaction molar yield is the total mass of the product actually obtained / the theoretical mass of the product.

[0066] The Grignard reagent obtained from the Grignard reactor 202 of the Grignard reagent-Grignard addition reaction unit 105 is transported to the Grignard addition reaction unit 105 through the first feed module. The Grignard reagent solution and 2-chloro-1-(1-chlorocyclopropyl)ethanone are respectively fed into the Grignard addition reaction unit 203 at a mass flow rate of 6.92kg / h and 5.17kg / h, and the reaction temperature is 60°C and the reaction time is 50min. After the Grignard addition reaction is completed, the reaction product is quenched, separated, washed with water and concentrated in the first continuous post-processing module to obtain 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol. The remaining amount of 2-chloro-1-(1-chlorocyclopropyl)ethanone is ≤1%, and the reaction molar yield is 90% (based on 2-chloro-1-(1-chlorocyclopropyl)ethanone). The reaction temperature of the above-mentioned Grignard reaction and Grignard addition reaction can be adjusted by a temperature control material in the jacket, and the temperature control material flows from the jacket inlet 204 to the jacket outlet 205.

[0067] Substitution reaction: 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol obtained from the Grignard addition reactor 203 of the Grignard reagent-Grignard addition reaction unit 105 and 80%wt hydrazine hydrate and methanol transported to the substitution reaction unit 106 through the second feed module are respectively fed into the main reactor of the substitution reaction unit 106 at mass flow rates of 1.50kg / h, 1.20kg / h, and 4.28kg / h, with a reaction temperature of 120°C, a back pressure of 1.0MPa, and a reaction time of 120min. After the substitution reaction is completed, the reaction product is concentrated, extracted with toluene, and washed with water in the second continuous post-processing module to obtain a toluene solution of 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazine-2-ol. The remaining amount of 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol is ≤3%, and the reaction molar yield is about 88%.

[0068] Ring-closing reaction: The toluene solution of 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazine-2-ol obtained from the substitution reaction unit 106 and the 37%wt formaldehyde solution, 40%wt sodium thiocyanate and 40%wt sodium bisulfate transported to the ring-closing reaction unit 107 through the third feeding module are fed into the main reactor of the ring-closing reaction unit 107 at a mass flow rate of 1.00kg / h, 0.35kg / h, 0.40kg / h and 0.50kg / h, respectively. The reaction temperature is 50°C, the reaction time is 180min, and the pH value is 1-3. After the ring-closing reaction is completed, the reaction product is cooled and crystallized, filtered and washed in the third continuous post-processing module to obtain 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione. The remaining amount of 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazino-2-ol is ≤2%, and the reaction molar yield is 81%.

[0069] Oxidation reaction: 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione obtained from the ring-closing reaction unit 107 and air and 5%wt sodium hydroxide solution transported to the oxidation reaction unit 108 through the fourth feed module are respectively put into the main reactor of the oxidation reaction unit 108 at a mass flow rate of 1.00kg / h, 1.0kg / h, and 25.00kg / h, the reaction temperature is 5°C, and the reaction time is 80min. After the oxidation reaction is completed, the reaction product is crystallized, washed, filtered and dried in the fourth continuous post-processing module to obtain prothioconazole, which is stored in the receiving tank 109 for standby use. The reaction molar yield is 87%.

[0070] Example 3

[0071] Grignard reagent-Grignard addition reaction:

[0072] Through the continuous feeding device, the relevant raw materials in the solid material storage tank (material storage tank 101) and the liquid material storage tank are respectively transported to each reaction unit using the solid feeding module (material feeding module 102) and the liquid feeding module, wherein the feeding situation is monitored by the feeding bin level monitoring device and the metering system (control module 103), and the feeding speed of the liquid material is adjusted by adjusting the delivery pump.

[0073] o-Chlorobenzyl chloride, magnesium powder, 2-methyltetrahydrofuran and toluene are respectively fed into the Grignard reactor 202 of the Grignard reagent-Grignard addition reaction unit 105 at mass flow rates of 1.00 kg / h, 0.16 kg / h, 2.00 kg / h and 3.80 kg / h, the reaction temperature is -10°C, the reaction time is 40 min, and the remaining reactants are returned to the Grignard reactor 202 through the material pump 201. After the reaction is completed, there is no o-chlorobenzyl chloride remaining, the reaction molar yield is 98%, and the coupling impurities are less than or equal to 1%. Among them, the reaction molar yield is the total mass of the product actually obtained / the theoretical mass of the product.

[0074] The Grignard reagent obtained from the Grignard reactor 202 of the Grignard reagent-Grignard addition reaction unit 105 is transported to the Grignard addition reaction unit 105 through the first feed module. The Grignard reagent and 2-chloro-1-(1-chlorocyclopropyl)ethanone are respectively fed into the Grignard addition reaction unit 203 at a mass flow rate of 6.92kg / h and 5.17kg / h, the reaction temperature is -20°C, and the reaction time is 10min. After the Grignard addition reaction is completed, the reaction product is quenched, separated, washed with water and concentrated in the first continuous post-processing module to obtain 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol. The remaining amount of 2-chloro-1-(1-chlorocyclopropyl)ethanone is ≤1%, and the reaction molar yield is 89% (based on 2-chloro-1-(1-chlorocyclopropyl)ethanone). The reaction temperature of the above-mentioned Grignard reaction and Grignard addition reaction can be adjusted by a temperature control material in the jacket, and the temperature control material flows from the jacket inlet 204 to the jacket outlet 205.

[0075] Substitution reaction: 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol obtained from the Grignard addition reactor of the Grignard reagent-Grignard addition reaction unit 105 and 80%wt hydrazine hydrate and methanol transported to the substitution reaction unit 106 through the second feed module are respectively fed into the main reactor of the substitution reaction unit 106 at mass flow rates of 1.50kg / h, 1.20kg / h, and 4.28kg / h, with a reaction temperature of 60°C, a back pressure of 0.3MPa, and a reaction time of 30min. After the substitution reaction is completed, the reaction product is concentrated, extracted with toluene, and washed with water in the second continuous post-processing module to obtain a toluene solution of 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazine-2-ol. The remaining amount of 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol is ≤3%, and the reaction molar yield is about 89%.

[0076] Ring-closing reaction: The toluene solution of 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazine-2-ol obtained from the substitution reaction unit 106 and the 37%wt formaldehyde solution, 40%wt sodium thiocyanate and 40%wt sodium bisulfate transported to the ring-closing reaction unit 107 through the third feeding module are fed into the main reactor of the ring-closing reaction unit 107 at a mass flow rate of 1.00kg / h, 0.35kg / h, 0.40kg / h and 0.50kg / h, respectively. The reaction temperature is 20°C, the reaction time is 120min, and the pH value is 1-3. After the ring-closing reaction is completed, the reaction product is cooled and crystallized, filtered and washed in the third continuous post-processing module to obtain 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione. The remaining amount of 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazino-2-ol is ≤2%, and the reaction molar yield is 82%.

[0077] Oxidation reaction: 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione obtained from the ring-closing reaction unit 107 and air and 5%wt sodium hydroxide solution transported to the oxidation reaction unit 108 through the fourth feed module are respectively put into the main reactor of the oxidation reaction unit 108 at a mass flow rate of 1.00kg / h, 1.0kg / h, and 25.00kg / h, the reaction temperature is -20°C, and the reaction time is 20min. After the oxidation reaction is completed, the reaction product is crystallized, washed, filtered and dried in the fourth continuous post-processing module to obtain prothioconazole, which is stored in the receiving tank 109 for standby use. The reaction molar yield is 88%.

[0078] Comparative Example 1

[0079] Except that the oxidation reaction in this comparative example is different from that in Example 1, the other operations and conditions are the same as those in Example 1. The specific description of the oxidation reaction in this comparative example 1 is as follows:

[0080] Oxidation reaction: 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione obtained from the ring-closing reaction unit 107 and the air and 5%wt hydrochloric acid solution transported to the oxidation reaction unit 108 through the fourth feed module are respectively put into the main reactor of the oxidation reaction unit 108 at a mass flow rate of 1.00kg / h, 1.0kg / h, and 20.00kg / h, the reaction temperature is -15°C, and the reaction time is 50min. After the oxidation reaction is completed, the reaction product is acid-crystallized and dried in the fourth continuous post-processing module to obtain prothioconazole, which is stored in the receiving tank 109 for standby use. The reaction molar yield is 60%.

[0081] Comparative Example 2

[0082] Except that the oxidation reaction in this comparative example is different from that in Example 1, the other operations and conditions are the same as those in Example 1. The specific description of the oxidation reaction in this comparative example 1 is as follows:

[0083] Oxidation reaction: 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione obtained from the ring-closing reaction unit 107 and 20%wt ferric chloride aqueous solution transported to the oxidation reaction unit 108 through the fourth feed module are respectively put into the main reactor of the oxidation reaction unit 108 at a mass flow rate of 1.00kg / h and 5.16kg / h, the reaction temperature is -15°C, and the reaction time is 50min. After the oxidation reaction is completed, the reaction product is acid-crystallized and dried in the fourth continuous post-processing module to obtain prothioconazole, which is stored in the receiving tank 109 for standby use. The reaction molar yield is 85%.

[0084] The cost calculation of the oxidation reaction of Example 1 and Comparative Examples 1 and 2 is shown in Table 1 below:

[0085] Table 1:

[0086]

[0087]

[0088] From the above description, it can be seen that the above-mentioned embodiments of the present invention achieve the following technical effects: the present application synthesizes prothioconazole under air oxidation and inorganic base catalysis, which not only improves the efficiency of the oxidation reaction, but also significantly improves the yield and purity of prothioconazole, while greatly reducing the generation of three wastes, and can obtain prothioconazole in a more environmentally friendly and low-cost manner; and the use of the continuous synthesis system of the present application to prepare prothioconazole can omit the epoxidation reaction link in the batch reaction of the prior art, simplify the operation, save production time, and improve the efficiency of the reaction, which is more suitable for the industrial preparation of prothioconazole.

[0089] 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 method for preparing prothioconazole, characterized in that: The preparation method comprises: o-Chlorobenzyl chloride and magnesium powder undergo a Grignard reaction in a mixed solvent of toluene and 2-methyltetrahydrofuran to obtain a Grignard reagent; The Grignard reagent and 2-chloro-1-(1-chlorocyclopropyl)ethanone undergo a Grignard addition reaction to obtain 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol; The 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol is subjected to a substitution reaction with hydrazine hydrate in an alcohol solvent to obtain 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazine-2-ol; The 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazinyl-2-ol is subjected to a ring-closing reaction with a formaldehyde solution, a sodium thiocyanate solution and a sodium bisulfate solution to obtain 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione; The 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione is subjected to oxidation reaction with air and inorganic base to obtain the prothioconazole.

2. The preparation method according to claim 1, characterized in that: The mass ratio of the o-chlorobenzyl chloride, the magnesium powder, the 2-methyltetrahydrofuran and the toluene in the Grignard reaction is 1:0.10-0.20:1.50-2.50:3.30-4.30; Preferably, the temperature of the Grignard reaction is -10 to 40°C; Preferably, the Grignard reaction time is 40 to 80 minutes.

3. The preparation method according to claim 1, characterized in that: The mass ratio of the Grignard reagent to the 2-chloro-1-(1-chlorocyclopropyl)ethanone in the Grignard addition reaction is 1:0.6-0.9; Preferably, the temperature of the Grignard addition reaction is -20 to 60°C; Preferably, the Grignard addition reaction time is 10 to 50 minutes.

4. The preparation method according to claim 1, characterized in that: The mass ratio of 1-chloro-2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)propanol, 60-80%wt hydrazine hydrate and methanol in the substitution reaction is 1:0.40-1.20:2.30-3.40; Preferably, the temperature of the substitution reaction is 60 to 120°C; Preferably, the back pressure of the substitution reaction is 0.3-1.0 MPa; Preferably, the substitution reaction time is 30 to 120 minutes.

5. The preparation method according to claim 1, characterized in that: The mass ratio of the 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-hydrazine-2-ol, the formaldehyde solution, the sodium thiocyanate solution, and the sodium bisulfate solution in the ring-closing reaction is 1:0.30-0.40:0.30-0.50:0.40-0.60; Preferably, the pH value of the ring-closing reaction is 4.00-5.00; Preferably, the temperature of the ring-closing reaction is 20 to 50°C; Preferably, the ring-closing reaction time is 120 to 180 minutes; Preferably, in terms of mass fraction, the concentration of the formaldehyde solution is 30-37%, the concentration of the sodium thiocyanate solution is 30-40%, and the concentration of the sodium bisulfate solution is 30-40%.

6. The preparation method according to claim 1, characterized in that: The mass ratio of 2-(2-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl)-1,2,4-triazolidine-3-thione, air and sodium hydroxide solution in the oxidation reaction is 1:0.5-1.0:20-30; Preferably, the temperature of the oxidation reaction is -20 to 5°C; Preferably, the oxidation reaction time is 20 to 80 minutes; Preferably, the concentration of the sodium hydroxide solution is 3-5% by mass fraction.

7. A device for preparing prothioconazole, characterized in that: The preparation device comprises: A Grignard reagent-Grignard addition reaction unit (105), a substitution reaction unit (106), a ring closure reaction unit (107) and an oxidation reaction unit (108) connected in sequence; and A continuous feeding device, wherein the connecting feeding device is connected in parallel with the Grignard reagent-Grignard addition reaction unit (105), the substitution reaction unit (106), the ring closure reaction unit (107) and the oxidation reaction unit (108).

8. The preparation device according to claim 7, characterized in that: The continuous feeding device comprises: A material storage tank (101), a material feeding module (102) and a control module (103); The control module (103) is electrically connected to the material feeding module (102) to control the material feeding speed of the material feeding module (102); The material feeding module (102) comprises a first feeding module, a second feeding module, a third feeding module and a fourth feeding module which are arranged in parallel; The inlets of the first feeding module, the second feeding module, the third feeding module and the fourth feeding module are independently connected to the outlet of the material storage tank (101); The outlets of the first feed module, the second feed module, the third feed module and the fourth feed module are respectively connected to the Grignard reagent-Grignard addition reaction unit (105), the substitution reaction unit (106), the ring-closure reaction unit (107) and the oxidation reaction unit (108).

9. The preparation device according to claim 8, characterized in that: The Grignard reagent-Grignard addition reaction unit (105) comprises a first continuous reaction module and a first continuous post-processing module; The first continuous reaction module includes a first temperature control module and a first main reactor; The first main reactor comprises a Grignard reactor (202) and a Grignard addition reactor (203) which are sequentially connected in series, and the Grignard reactor (202) and the Grignard addition reactor (203) are fully mixed flow-tubular reactors; The fully mixed flow-tubular reactor is divided into a material mixing section and a reaction section in sequence along the material flow direction; The first temperature control module is electrically connected to the first main reactor to control the reaction temperature in the first main reactor; The first feeding module includes a continuous magnesium powder feeding module, a continuous o-chlorobenzyl chloride feeding module, a continuous 2-methyltetrahydrofuran feeding module, a continuous toluene feeding module and a continuous 2-chloro-1-(1-chlorocyclopropyl)ethanone feeding module; The continuous magnesium powder feeding module, the continuous o-chlorobenzyl chloride feeding module, the continuous 2-methyltetrahydrofuran feeding module and the continuous toluene feeding module are each independently connected to the material mixing section of the Grignard reactor (202); The reaction section outlet of the Grignard reactor (202) and the continuous 2-chloro-1-(1-chlorocyclopropyl)ethanone feeding module are connected to the material mixing section of the Grignard addition reactor (203); The outlet of the reaction section of the Grignard addition reactor (203) is connected to the inlet of the first continuous post-treatment module, and the outlet of the first continuous post-treatment module is connected to the inlet of the substitution reaction unit (106).

10. The preparation device according to claim 8, characterized in that: The substitution reaction unit (106) includes a second continuous reaction module and a second continuous post-processing module; The second continuous reaction module includes a second temperature control module and a second main reactor; The second main reactor is divided into a material mixing section and a reaction section according to the material flow direction; The second temperature control module is electrically connected to the second main reactor to control the reaction temperature in the second main reactor; The second feeding module includes a continuous hydrazine hydrate solution feeding module and a continuous alcohol solvent feeding module; Along the material flow direction, the outlets of the continuous hydrazine hydrate feeding module and the continuous alcohol solvent feeding module are each independently connected to the inlet of the material mixing section of the second main reactor, the outlet of the reaction section of the second main reactor is connected to the inlet of the second continuous post-processing module, and the outlet of the second continuous post-processing module is connected to the inlet of the ring-closing reaction unit (107).

11. The preparation device according to claim 8, characterized in that: The ring-closing reaction unit (107) comprises a third continuous reaction module and a third continuous post-processing module; The third continuous reaction module includes a third temperature control module and a third main reactor; The third main reactor is divided into a material mixing section and a reaction section according to the material flow direction; The third temperature control module is electrically connected to the third main reactor to control the reaction temperature in the third main reactor; The third feeding module includes a continuous formaldehyde solution feeding module, a continuous sodium thiocyanate solution feeding module and a continuous sodium bisulfate solution feeding module; Along the material flow direction, the outlets of the continuous formaldehyde solution feeding module, the continuous sodium thiocyanate solution feeding module and the continuous sodium bisulfate solution feeding module are each independently connected to the inlet of the material mixing section of the third main reactor, the outlet of the reaction section of the third main reactor is connected to the inlet of the third continuous post-processing module, and the outlet of the third continuous post-processing module is connected to the inlet of the oxidation reaction unit (108).

12. The preparation device according to claim 8, characterized in that: The oxidation reaction unit (108) includes a fourth continuous reaction module and a fourth continuous post-processing module; The fourth continuous reaction module includes a fourth temperature control module and a fourth main reactor; The fourth main reactor is divided into a material mixing section and a reaction section according to the material flow direction; The fourth temperature control module is electrically connected to the fourth main reactor to control the reaction temperature in the fourth main reactor; The fourth feeding module includes an air pump and a continuous inorganic alkali feeding module; Along the material flow direction, the air pump and the continuous inorganic alkali feeding module are connected to the inlet of the material mixing section of the fourth main reactor, and the outlet of the reaction section of the fourth main reactor is connected to the inlet of the fourth continuous post-processing module.

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