Method for continuously synthesizing pyroxasulfone intermediate

Abstract

The invention relates to the technical field of organic synthesis, in particular to a method for continuously synthesizing a pyroxasulfone intermediate, which at least comprises the following steps: mixing polyformaldehyde and a compound I to prepare a solution A, respectively introducing the solution A and sulfonyl chloride into a micro-channel reactor for chloromethylation reaction, and after the reaction is finished, carrying out post-treatment to obtain the pyroxasulfone intermediate. The compound I is 1-methyl-3-trifluoromethyl-5-difluoromethoxy-1-H-pyrazole, and the compound II is a compound III. The pyroxasulfone intermediate is 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole, and the structural formula of the pyroxasulfone intermediate is shown in the description. By adopting the microchannel reactor, mass transfer between two-phase fluids can be enhanced, rapid and sufficient mixing of two strands of materials is realized, so that the reaction process is enhanced, the flow rate, the reaction temperature, the reaction time, the pressure and the like are controlled for reaction, and the method has the characteristics of high purity, high yield, simple synthesis process, no pollution and easy treatment of three wastes, and is suitable for industrial production. The industrial application is facilitated.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for continuously synthesizing a sulfonepyraclostrobin intermediate. Background Art

[0002] 1-Methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole is an important intermediate for the synthesis of sulfonepyraclostrobin. In the prior art, for example, CN117777122A discloses a method for preparing sulfonepyraclostrobin using a new intermediate, and the synthetic route is as follows:

[0003]

[0004] This route uses trioxymethylene, thionyl chloride and sulfuric acid as raw materials to prepare sulfonepyraclostrobin intermediates. This method has the disadvantages of low product yield, low formaldehyde utilization, and difficulty in handling three wastes. In addition, due to the low heat and mass transfer efficiency of traditional kettle reactors, not only will the local temperature be high, but also the reaction time will be prolonged and the equipment utilization rate will be low. At the same time, excessive formaldehyde gas in the reaction will cause environmental pollution, which does not meet the requirements of green environmental protection. Summary of the invention

[0005] In order to solve the problems in the prior art, the present invention provides a method for continuously synthesizing a sulfonepyraclostrobin intermediate, which comprises at least the following steps:

[0006] Polyformaldehyde and compound I are mixed to form solution A, and solution A and sulfonyl chloride are respectively introduced into a microchannel reactor for chloromethylation reaction. After the reaction is completed, a sulfonepyraclostrobin intermediate is obtained by post-treatment; the compound I is 1-methyl-3-trifluoromethyl-5-difluoromethoxy-1-H-pyrazole; the sulfonepyraclostrobin intermediate is 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole.

[0007] In one embodiment, the microchannel reactor includes two straight-through modules and one enhanced mass transfer module; a metering pump is respectively arranged on the pipelines connecting the two straight-through modules and the enhanced mass transfer module.

[0008] In one embodiment, the microchannel reactor is made of glass, and the metering pump is made of polytetrafluoroethylene and titanium.

[0009] In one embodiment, the microchannel reactor is a Homag microchannel reactor, model RMCS181003.

[0010] In one embodiment, the chloromethylation reaction in the microchannel reactor comprises the following steps:

[0011] Solution A prepared from polyoxymethylene and 1-methyl-3-trifluoromethyl-5-difluoromethoxy-1-H-pyrazole and sulfonyl chloride are respectively introduced into the straight-through module of the microchannel reactor for temperature control treatment. When the reaction temperature is reached, the temperature-controlled solution A and sulfonyl chloride are synchronously transported to the enhanced mass transfer module by a metering pump for mixing and performing a chloromethylation reaction.

[0012] In one embodiment, the reaction temperature of the chloromethylation reaction is 50-90° C.; the pressure of the chloromethylation reaction is 0-8 bar, and the pressure is not 0; and the reaction residence time of the chloromethylation reaction is 3-10 min.

[0013] In one embodiment, the reaction temperature of the chloromethylation reaction is 50-60° C.; the pressure of the chloromethylation reaction is 0-6 bar, and the pressure is not 0; and the reaction residence time of the chloromethylation reaction is 5-8 min.

[0014] In one embodiment, the flow rates of the metering pump are set as follows: the flow rate of solution A is 5.1 to 14.3 g / min; the flow rate of sulfonyl chloride is 2.2 to 7.3 g / min.

[0015] In one embodiment, the flow rates of the metering pump are set as follows: the flow rate of solution A is 7.1 to 11.5 g / min; the flow rate of sulfonyl chloride is 4.1 to 6.5 g / min.

[0016] In one embodiment, the polyoxymethylene comprises trioxymethylene.

[0017] In one embodiment, the polyoxymethylene is trioxymethylene.

[0018] In one embodiment, the purity of the 1-methyl-3-trifluoromethyl-5-difluoromethoxy-1-H-pyrazole is ≥ 98%, the purity of the sulfonyl chloride is ≥ 98%, and the purity of the polyoxymethylene is ≥ 99%.

[0019] In one embodiment, the mass ratio of 1-methyl-3-trifluoromethyl-5-difluoromethoxy-1-H-pyrazole, polyoxymethylene and sulfonyl chloride is 1:(0.139-0.146):(0.631-0.687).

[0020] In one embodiment, the mass ratio of 1-methyl-3-trifluoromethyl-5-difluoromethoxy-1-H-pyrazole, polyoxymethylene and sulfonyl chloride is 1:(0.140-0.143):(0.643-0.662).

[0021] In one embodiment, the post-processing step comprises:

[0022] After the chloromethylation reaction is completed, the product flows out from the outlet of the microchannel reactor, and the reaction product is quenched into an ice-water mixture, and an organic solvent is added for extraction, layering, water washing, concentration, and distillation to obtain a colorless transparent liquid 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole.

[0023] In one embodiment, the organic solvent includes any one of dichloromethane, chloroform, toluene and dichloroethane.

[0024] In one embodiment, the ethylene dichloride is 1,2-ethylene dichloride.

[0025] Beneficial Effects

[0026] 1. The present invention adopts a microchannel reactor to enhance the mass transfer between the two-phase fluids, realize rapid and sufficient mixing of the two streams of materials, thereby strengthening the reaction process. At the same time, the microchannel has good heat transfer performance, can accurately control the temperature, and remove the heat generated by the reaction in time, avoiding excessive local temperature, so that the conversion rate of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole is greatly improved.

[0027] 2. The present invention strictly controls the flow rate of solution A and sulfonyl chloride, as well as the reaction temperature, reaction time and pressure of the chloromethylation reaction to react, which improves the yield on the one hand, reduces the production of side reactions and tar on the other hand, and also solves the safety problem caused by excessively high local temperature in the autoclave reaction.

[0028] 3. The present invention has the characteristics of simple process, high yield, solvent-free reaction and good treatment of three wastes. The method provided by the present invention can make the molar yield of sulfonepyraclostrobin intermediate more than 97% and the purity more than 98%.

[0029] 4. The microchannel reactor used in the present invention is made of glass, and the metering pump is made of polytetrafluoroethylene and titanium, which have good corrosion resistance and further avoid the serious corrosion problem of conventional equipment.

[0030] 5. In the microchannel reactor of the present invention, the entire process from feeding, heating, cooling, and mixing reaction is a continuous flow reaction, which avoids the safety hazards and environmental pollution caused by leakage during material transfer in conventional production. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 The figure is a flow chart of the continuous synthesis method of the product 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole of Example 1-6.

[0032] Figure 2 This is the GC-MS chart of the target product sulfonepyraclostrobin intermediate in Example 1. DETAILED DESCRIPTION

[0033] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with the examples and drawings. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. The experimental methods for which specific conditions are not specified in the examples are carried out under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used that do not specify the manufacturer are all conventional products that can be purchased commercially.

[0034] Example 1

[0035] This embodiment provides a method for continuously synthesizing a sulfonepyraclostrobin intermediate, comprising the following steps:

[0036] Compound I and trioxymethylene are prepared into a solution in a mass ratio of 50:6.95, denoted as solution A;

[0037] The flow rate of the feed metering pump was set to solution A = 11.39 g / min, sulfonyl chloride = 6.49 g / min, and they were pumped into their respective straight-through modules for heating, the temperature was set to 50°C, and then synchronously pumped into the enhanced mass transfer module for chloromethylation reaction, the reaction pressure was 5 bar, the residence time was 5 min, and the reaction liquid continuously entered the receiving bottle. After the reaction liquid was quenched with ice water, dichloromethane was added for extraction, layering, washing, concentration, and reduced pressure distillation to obtain 59.62 g of colorless transparent liquid, with a content of 98.5% of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole and a yield of 97.9%.

[0038] Figure 2 The mass spectrum of the target product sulfonepyraclostrobin intermediate in Example 1, wherein GC-MS (EI): m / z = 264.0 (M + ), 229.0([M-Cl] + ), 179.0([M-(Cl+CHF2)] + ).

[0039] Example 2

[0040] This embodiment provides a method for continuously synthesizing a sulfonepyraclostrobin intermediate, comprising the following steps:

[0041] Compound I and trioxymethylene are prepared into a solution in a mass ratio of 50:7.08, assuming solution A;

[0042] The flow rate of the feed metering pump was set to solution A = 7.14 g / min, sulfonyl chloride = 4.10 g / min, and they were pumped into their respective straight-through modules for heating, the temperature was set to 55°C, and then synchronously pumped into the enhanced mass transfer module for chloromethylation reaction, the reaction pressure was 3 bar, the residence time was 8 min, and the reaction liquid continuously entered the receiving bottle. After the reaction liquid was quenched with ice water, 1,2-dichloroethane was added for extraction, layering, water washing, concentration, and reduced pressure distillation to obtain 59.32 g of colorless transparent liquid, with a content of 98.3% of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole and a yield of 97.2%.

[0043] Example 3

[0044] This embodiment provides a method for continuously synthesizing a sulfonepyraclostrobin intermediate, comprising the following steps:

[0045] Compound I and trioxymethylene are prepared into a solution in a mass ratio of 50:7.02, assuming solution A;

[0046] The flow rate of the feed metering pump was set to solution A = 9.50 g / min, sulfonyl chloride = 5.41 g / min, and they were pumped into their respective modules for heating, the temperature was set to 58°C, and then synchronously pumped into the enhanced mass transfer module for chloromethylation reaction, the reaction pressure was 4 bar, the residence time was 6 min, and the reaction liquid continuously entered the receiving bottle. After the reaction liquid was quenched with ice water, 1,2-dichloroethane was added for extraction, layering, water washing, concentration, and reduced pressure distillation to obtain 60.05 g of colorless transparent liquid, with a content of 98.2% of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole and a yield of 98.3%.

[0047] Example 4

[0048] This embodiment provides a method for continuously synthesizing a sulfonepyraclostrobin intermediate, comprising the following steps:

[0049] Compound I and trioxymethylene are prepared into solution A in a mass ratio of 50:7.08;

[0050] The flow rate of the feed metering pump was set to solution A = 8.15 g / min, sulfonyl chloride = 4.68 g / min, and they were pumped into their respective straight-through modules for heating, the temperature was set to 60°C, and then synchronously pumped into the enhanced mass transfer module for chloromethylation reaction, the reaction pressure was 3 bar, the residence time was 7 min, and the reaction liquid continuously entered the receiving bottle. After the reaction liquid was quenched with ice water, dichloromethane was added for extraction, layering, washing, concentration, and reduced pressure distillation to obtain 59.75 g of colorless transparent liquid, with a content of 98.1% of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole and a yield of 97.7%.

[0051] Example 5

[0052] This embodiment provides a method for continuously synthesizing a sulfonepyraclostrobin intermediate, comprising the following steps:

[0053] Compound I and trioxymethylene are prepared into solution A in a mass ratio of 50:6.95;

[0054] The flow rate of the feed metering pump was set to solution A = 7.12 g / min, sulfonyl chloride = 4.14 g / min, and they were pumped into their respective straight-through modules for heating, the temperature was set to 53°C, and then synchronously pumped into the enhanced mass transfer module for chloromethylation reaction, the reaction pressure was 3 bar, the residence time was 8 min, and the reaction liquid continuously entered the receiving bottle. After the reaction liquid was quenched with ice water, 1,2-dichloroethane was added for extraction, layering, water washing, concentration, and reduced pressure distillation to obtain 59.75 g of colorless transparent liquid, with a content of 98.3% of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole and a yield of 97.9%.

[0055] Example 6

[0056] This embodiment provides a method for continuously synthesizing a sulfonepyraclostrobin intermediate, comprising the following steps:

[0057] Compound I and trioxymethylene are prepared into solution A in a mass ratio of 50:7.01;

[0058] The flow rate of the feed metering pump was set to solution A = 9.50 g / min, sulfonyl chloride = 5.41 g / min, and they were pumped into their respective straight-through modules for heating, the temperature was set to 56°C, and then synchronously pumped into the enhanced mass transfer module for chloromethylation reaction, the reaction pressure was 4 bar, the residence time was 6 min, and the reaction liquid continuously entered the receiving bottle. After the reaction liquid was quenched with ice water, 1,2-dichloroethane was added for extraction, layering, water washing, concentration, and reduced pressure distillation to obtain 59.87 g of colorless transparent liquid, with a content of 98.4% of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole and a yield of 98.2%.

[0059] Figure 1 The figure is a flow chart of the continuous synthesis method of the product 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole of Example 1-6.

[0060] Comparative Example 1

[0061] This comparative example provides a method for continuously synthesizing a sulfonepyraclostrobin intermediate, comprising the following steps:

[0062] Compound I and trioxymethylene are prepared into solution A in a mass ratio of 50:7.01;

[0063] The flow rate of the feed metering pump was set to solution A = 14.25 g / min, sulfonyl chloride = 8.12 g / min, and they were pumped into their respective straight-through modules for heating, the temperature was set to 65°C, and then synchronously pumped into the enhanced mass transfer module for chloromethylation reaction, the reaction pressure was 8 bar, the residence time was 4 min, and the reaction liquid continuously entered the receiving bottle. After the reaction liquid was quenched with ice water, dichloromethane was added for extraction, layering, water washing, concentration, and reduced pressure distillation to obtain 56.36 g of colorless transparent liquid, with a content of 97.5% of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole and a yield of 91.6%.

[0064] Comparative Example 2

[0065] This comparative example provides a method for continuously synthesizing a sulfonepyraclostrobin intermediate, comprising the following steps:

[0066] Compound I and trioxymethylene are prepared into solution A in a mass ratio of 50:7.01;

[0067] The flow rate of the feed metering pump was set to solution A = 6.33 g / min, sulfonyl chloride = 3.64 g / min, and they were pumped into their respective straight-through modules for heating, the temperature was set to 45°C, and then synchronously pumped into the enhanced mass transfer module for chloromethylation reaction, the reaction pressure was 3 bar, the residence time was 9 min, and the reaction liquid continuously entered the receiving bottle. After the reaction liquid was quenched with ice water, 1,2-dichloroethane was added for extraction, layering, water washing, concentration, and reduced pressure distillation to obtain 53.40 g of colorless transparent liquid, with a content of 98.3% of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole and a yield of 87.5%.

[0068] Comparative Example 3

[0069] This comparative example provides a method for continuously synthesizing a sulfonepyraclostrobin intermediate, comprising the following steps:

[0070] Compound I and paraformaldehyde were prepared into solution A at a mass ratio of 50:7.01;

[0071] The flow rate of the feed metering pump was set to solution A = 9.50 g / min, sulfonyl chloride = 5.52 g / min, and they were pumped into their respective straight-through modules for heating, the temperature was set to 55°C, and then synchronously pumped into the enhanced mass transfer module for chloromethylation reaction, the reaction pressure was 4 bar, the residence time was 6 min, and the reaction liquid continuously entered the receiving bottle. After the reaction liquid was quenched with ice water, 1,2-dichloroethane was added for extraction, layering, water washing, concentration, and reduced pressure distillation to obtain 50.43 g of colorless transparent liquid, with a content of 97.9% of 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole and a yield of 82.3%.

Claims

1. A method for continuously synthesizing a sulfonepyraclostrobin intermediate, characterized in that: At least the following steps are included: Polyformaldehyde and compound I are mixed to form solution A, and solution A and sulfonyl chloride are respectively introduced into a microchannel reactor for chloromethylation reaction. After the reaction is completed, a sulfonepyraclostrobin intermediate is obtained by post-treatment; the compound I is 1-methyl-3-trifluoromethyl-5-difluoromethoxy-1-H-pyrazole; the sulfonepyraclostrobin intermediate is 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole.

2. The method for continuously synthesizing a sulfonepyraclostrobin intermediate according to claim 1, characterized in that: The microchannel reactor comprises two straight-through modules and an enhanced mass transfer module; a metering pump is respectively arranged on the pipelines connecting the two straight-through modules and the enhanced mass transfer module.

3. The method for continuously synthesizing sulfonepyraclostrobin intermediates using a microchannel reactor according to claim 2, characterized in that: The chloromethylation reaction in the microchannel reactor comprises the following steps: Solution A prepared from polyoxymethylene and 1-methyl-3-trifluoromethyl-5-difluoromethoxy-1-H-pyrazole and sulfonyl chloride are respectively introduced into the straight-through module of the microchannel reactor for temperature control treatment. When the reaction temperature is reached, the temperature-controlled solution A and sulfonyl chloride are synchronously transported to the enhanced mass transfer module by a metering pump for mixing and performing a chloromethylation reaction.

4. The method for continuously synthesizing a sulfonepyraclostrobin intermediate according to claim 3, characterized in that: The reaction temperature of the chloromethylation reaction is 50-90° C.; the pressure of the chloromethylation reaction is 0-8 bar, and the pressure is not 0; and the reaction residence time of the chloromethylation reaction is 3-10 min.

5. The method for continuously synthesizing sulfonepyraclostrobin intermediate according to claim 3, characterized in that: The flow rates of the metering pumps are set as follows: the flow rate of solution A is 5.1 to 14.3 g / min; the flow rate of sulfonyl chloride is 2.2 to 7.3 g / min.

6. The method for continuously synthesizing sulfonepyraclostrobin intermediate according to claim 1, characterized in that: The polyoxymethylene includes trioxymethylene.

7. The method for continuously synthesizing sulfonepyraclostrobin intermediate according to claim 1, characterized in that: The purity of the 1-methyl-3-trifluoromethyl-5-difluoromethoxy-1-H-pyrazole is ≥98%, the purity of the sulfonyl chloride is ≥98%, and the purity of the polyoxymethylene is ≥99%.

8. The method for continuously synthesizing sulfonepyraclostrobin intermediate according to claim 1, characterized in that: The mass ratio of the 1-methyl-3-trifluoromethyl-5-difluoromethoxy-1-H-pyrazole, polyoxymethylene and sulfonyl chloride is 1:(0.139-0.146):(0.631-0.687).

9. The method for continuously synthesizing sulfonepyraclostrobin intermediate according to claim 1, characterized in that: The post-processing steps include: After the chloromethylation reaction is completed, the product flows out from the outlet of the microchannel reactor, and the reaction product is quenched into an ice-water mixture, and an organic solvent is added for extraction, layering, water washing, concentration, and distillation to obtain a colorless transparent liquid 1-methyl-3-trifluoromethyl-4-chloromethyl-5-difluoromethoxy-1-H-pyrazole.

10. The method for continuously synthesizing sulfonepyraclostrobin intermediate according to claim 9, characterized in that: The organic solvent includes any one of dichloromethane, chloroform, toluene and dichloroethane.

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