A method for continuously preparing O,S-dimethyl phosphorothioamidate based on a microchannel reactor

Abstract

This application relates to the field of the preparation of O,S-dimethyl phosphorothioamidate, and specifically discloses a method for continuously preparing O,S-dimethyl phosphorothioamidate based on a microchannel reactor. The method for continuously preparing O,S-dimethyl phosphorothioamidate in this application comprises the following steps: Step S1, introducing O,O-dimethyl phosphorothioamidate, a solution of dimethyl sulfate or dimethyl sulfate and the catalyst tributylphosphine-nickel halide into a reactor, and reacting under the conditions of a temperature of 10-34 °C and a flow rate of 1-600 mL / min; Step S2, further introducing the product obtained in Step S1 into a microchannel reactor and further reacting under the conditions of a temperature of 35-75 °C and a flow rate of 1-450 mL / min; Step S3, stirring the reaction solution of O,S-dimethyl phosphorothioamidate and controlling the temperature below 15 °C to obtain liquid O,S-dimethyl phosphorothioamidate. The preparation method of this application has the effect of improving the reaction rate while ensuring a relatively high yield of O,S-dimethyl phosphorothioamidate.

Description

Technical Field

[0001] The present application relates to the field of the preparation of O,S-dimethyl phosphorothioamidate, and more specifically, it relates to a method for continuously preparing O,S-dimethyl phosphorothioamidate based on a microchannel reactor. Background Art

[0002] O,S-dimethyl phosphorothioamidate is an intermediate of a highly effective and low-toxic pesticide and a broad-spectrum and highly effective insecticide. The pesticides prepared therefrom have better control effects on aphids, mites, rice leafhoppers, and rice planthoppers than parathion and malathion, and can also be used to control cotton bollworms, armyworms, yellow rice borers, rice leaf rollers, and underground pests such as mole crickets and grubs; control corn borers.

[0003] In the related art, a Chinese patent application with the application number 201510023044.0 discloses a method for continuously synthesizing O,S-dimethyl phosphorothioamidate based on a tubular reaction device. This method uses O,O-dimethyl phosphorothioamidate and dimethyl sulfate as raw materials to continuously synthesize O,S-dimethyl phosphorothioamidate through a tubular reaction device; the tubular reaction device includes two series-connected tubular reactors. When the reaction is carried out, an appropriate temperature is set in the tubular reactor; O,O-dimethyl phosphorothioamidate and dimethyl sulfate are continuously metered and fed into the first tubular reactor for mixing and reaction for 0.1 - 1 h, and then flow through the second tubular reactor for further reaction for 3 - 8 h, and the O,S-dimethyl phosphorothioamidate product is continuously obtained from the material outlet of the second tubular reactor. There is also a Chinese patent application with the application number 202180010044.0, which also uses a similar method to prepare the O,S-dimethyl phosphorothioamidate product.

[0004] In view of the above related art, in the process of preparing O,S-dimethyl phosphorothioamidate, the reaction rate is relatively low, resulting in a low conversion rate of the stage reaction and reducing the production efficiency. Summary of the Invention

[0005] In order to improve the reaction rate while ensuring a relatively high yield of O,S-dimethyl phosphorothioamidate, the present application provides a method for continuously preparing O,S-dimethyl phosphorothioamidate based on a microchannel reactor.

[0006] A method for continuously preparing O,S-dimethyl phosphorothioamidate based on a microchannel reactor includes the following steps:

[0007] Step S1, feeding O,O-dimethyl phosphorothioamidate, dimethyl sulfate solution or dimethyl sulfate and the catalyst tributylphosphine-nickel halide into a reactor, maintaining the temperature of the reaction raw materials at 10 - 34 °C, and flowing through the reactor at a flow rate of 1 - 600 mL / min;

[0008] Step S2: Continuously introduce the product obtained in Step S1 into a microchannel reactor for reaction. Control the reaction temperature at 35 - 75°C and let it flow through the microchannel reactor at a flow rate of 1 - 450 mL / min for further reaction. Continuously obtain the O,S-dimethylthiophosphoramide reaction solution from the outlet of the microchannel reactor.

[0009] Step S3: Stir the O,S-dimethylthiophosphoramide reaction solution and control the temperature below 15°C to obtain liquid O,S-dimethylthiophosphoramide.

[0010] By adopting the above technical solution, since the chemical formula of dimethyl sulfate is written as (CH3)2SO4, (CH3)2SO4 generally exists in the ionic form CH3 + … - O‒SO2‒OCH3. When it meets O,O-dimethylthiophosphoramide, CH3 + … - In O‒SO2‒OCH3, the positive and negative atomic groups tend to dissociate. Eventually, the positive and negative atomic groups dissociate and attach to both ends of the P=S bond in O,O-dimethylthiophosphoramide to form O,S-dimethylthiophosphoramide. And tributylphosphine-nickel halide can attract S and O in CH3 + … - O‒SO2‒OCH3, as well as P and S in O,O-dimethylthiophosphoramide, which promotes the separation of the positive and negative atomic groups in CH3 + … - O‒SO2‒OCH3, causing the P=S double bond to break into single bonds. However, the adsorption force of tributylphosphine-nickel halide is limited and will not affect the formation of the P=O bond in the final product O,S-dimethylthiophosphoramide. Therefore, adding tributylphosphine-nickel halide to the solution of O,O-dimethylthiophosphoramide and dimethyl sulfate can, while ensuring a relatively high yield of O,S-dimethylthiophosphoramide, improve the reaction rate of preparing O,S-dimethylthiophosphoramide from O,O-dimethylthiophosphoramide and dimethyl sulfate solution, increase the stage conversion rate, and improve production efficiency.

[0011] Combined with the conditions of the first step with a temperature of 10 - 34°C and a flow rate of 1 - 600 mL / min; the second step with a temperature of 35 - 75°C and a flow rate of 1 - 450 mL / min; and Step S3 adding a stirring and cooling step compared with the traditional preparation method, it can ensure a high reaction rate while also improving the yield of O,S-dimethylthiophosphoramide.

[0012] Optionally, in the catalyst tributylphosphine-nickel halide, the molar ratio of tributylphosphine to nickel halide is (3.5 - 4.5):1.

[0013] By adopting the above technical solution, since the reaction intermediate process of O, O-dimethylthiophosphoramide and dimethyl sulfate is difficult to control, it is necessary to promote the dissociation of positive and negative atomic groups in CH3 + … - O‒SO2‒OCH3, promote the transformation of P=S bond into P‒S bond, and at the same time ensure the smooth formation of P=O bond. Therefore, it is necessary to strictly control the molar mass of tributylphosphine and nickel halide to ensure the smooth progress of this reaction and ensure a high reaction rate and yield.

[0014] Optionally, the mass of the catalyst tributylphosphine-nickel halide accounts for 0.15 - 0.25% of the mass of O, O-dimethylthiophosphoramide.

[0015] By adopting the above technical solution, reacting the catalyst tributylphosphine-nickel halide with O, O-dimethylthiophosphoramide and dimethyl sulfate in an appropriate ratio can ensure that the catalyst tributylphosphine-nickel halide can stably catalyze the reaction of O, O-dimethylthiophosphoramide and dimethyl sulfate, while ensuring a high yield of O, S-dimethylthiophosphoramide and improving production efficiency.

[0016] Optionally, the nickel halide is nickel chloride.

[0017] By adopting the above technical solution, nickel chloride is combined with tributylphosphine as a catalyst for the reaction of O, O-dimethylthiophosphoramide and dimethyl sulfate, which has a good catalytic effect on the reaction of O, O-dimethylthiophosphoramide and dimethyl sulfate, can improve the reaction rate, and improve the production efficiency of O, S-dimethylthiophosphoramide.

[0018] Optionally, the dimethyl sulfate and O, O-dimethylthiophosphoramide are introduced into the tubular reactor at a mass ratio of (5 - 10) : 100.

[0019] By adopting the above technical solution, on the basis of coordinating the reaction principle of O, O-dimethylthiophosphoramide, dimethyl sulfate solution and tributylphosphine-nickel halide, controlling the weight ratio of dimethyl sulfate to O, O-dimethylthiophosphoramide within the range of (5 - 10) : 100 can improve the production efficiency of O, S-dimethylthiophosphoramide.

[0020] Optionally, in step S1, the temperature of the reaction raw materials is maintained at 10 - 25°C.

[0021] By adopting the above technical solution, 10 - 25°C is a reaction temperature that can be achieved at room temperature, which is very different from the reaction temperature in the prior art. The reason is that with the preparation process and raw materials of this application, the reaction can be carried out without heating, saving energy consumption.

[0022] Optionally, in the step S1, the flow time of O, O-dimethylthiophosphoramide, dimethyl sulfate solution or dimethyl sulfate and the catalyst tributylphosphine-nickel halide in the reactor is 0.018 - 15 min.

[0023] By adopting the above technical solution, in this application, since the reaction efficiency of O, O-dimethylthiophosphoramide and dimethyl sulfate is relatively high, the reaction time in the reactor is shorter than that of the first step of the traditional reactor, thus shortening the time for preparing O, S-dimethylthiophosphoramide and improving the efficiency.

[0024] Optionally, in the step S2, the flow time of the product obtained in the step S1 in the microchannel reactor is 1.02 - 120 min.

[0025] By adopting the above technical solution, since this application adopts the combined reaction mode of a reactor and a microchannel reactor, and in this application, compared with the traditional method for preparing O, S-dimethylthiophosphoramide, the catalyst tributylphosphine-nickel halide is added, so that the second step reaction only requires 1.02 - 120 min, saving time compared with the 3 - 8 h of the traditional second step reaction and improving the production efficiency.

[0026] Optionally, in the dimethyl sulfate solution, the solvent of dimethyl sulfate is any one or a combination of dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, petroleum ether, aromatic solvents, ester solvents, nitrile solvents, ether solvents.

[0027] Optionally, the solvent is dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, petroleum ether, toluene or methyl tert-butyl ether.

[0028] By adopting the above technical solution, the above solvents can all dissolve dimethyl sulfate well, increasing the contact area between dimethyl sulfate and O, O-dimethylthiophosphoramide and the catalyst tributylphosphine-nickel halide, promoting the improvement of the efficiency of generating O, S-dimethylthiophosphoramide from dimethyl sulfate and O, O-dimethylthiophosphoramide, and ensuring a high yield of O, S-dimethylthiophosphoramide.

[0029] Optionally, the reactor in the step S1 is a tubular reactor or a microchannel reactor.

[0030] By adopting the above technical solution, in this application, the scheme of adding the catalyst tributylphosphine-nickel halide to promote the reaction of O, O-dimethylthiophosphoramide and dimethyl sulfate is better. Therefore, whether the combination mode of a tubular reactor - microchannel reactor or a microchannel reactor - microchannel reactor is selected, the effects of high reaction efficiency and high reaction yield can be obtained.

[0031] Optionally, arc baffles, spiral baffles, baffle plates with a folded flow pattern, or perforated baffles are fixedly connected to the inner walls of the tubular reactor and the microchannel reactor.

[0032] Optionally, the arc baffle is in the shape of a tile.

[0033] By adopting the above technical solution, due to the special structures of the above tubular reactor and microchannel reactor, both the tubular reactor and the microchannel reactor have a very large specific surface area, with very high mass transfer and heat transfer efficiencies, that is, they can achieve precise control of the reaction temperature and instantaneously mix, flow, and react the reaction materials in the tubular reactor and the microchannel reactor in precise proportions, thereby improving production efficiency, increasing the yield, and obtaining high-quality products.

[0034] Optionally, the feeding metering devices for O,O-dimethylthiophosphoramide, dimethyl sulfate solution, and copper bromide in steps S1 and S2 are syringe pumps, peristaltic pumps, or diaphragm pumps.

[0035] By adopting the above technical solution, through a syringe pump, peristaltic pump, or diaphragm pump, O,O-dimethylthiophosphoramide, dimethyl sulfate solution, or dimethyl sulfate and the catalyst tributylphosphine-nickel halide can be smoothly and uniformly injected into the tubular reactor or the microchannel reactor.

[0036] Optionally, a jacketed pipe is provided outside the tubular reactor and the microchannel reactor, or the tubular reactor and the microchannel reactor are immersed in a container filled with a cooling medium.

[0037] By adopting the above technical solution, since the reaction for generating O,S-dimethylthiophosphoramide is an exothermic reaction, cooling the tubular reactor and the microchannel reactor while the reaction raw materials are reacting can promote the improvement of the reaction efficiency, and can increase the product conversion rate of O,S-dimethylthiophosphoramide, ultimately increasing the yield.

[0038] In summary, the present application has the following beneficial effects:

[0039] 1. In the present application, by adding the catalyst tributylphosphine-nickel halide to O,O-dimethylthiophosphoramide and dimethyl sulfate solution or dimethyl sulfate, while ensuring a relatively high yield of O,S-dimethylthiophosphoramide, the reaction rate of preparing O,S-dimethylthiophosphoramide from O,O-dimethylthiophosphoramide and dimethyl sulfate can be increased, the stage conversion rate can be increased, and the production efficiency can be improved;

[0040] 2. In the present application, to promote CH3 + … -In SO3‒OCH3, the dissociation of positive and negative atomic groups promotes the transformation of the P=S bond into a P‒S bond while ensuring the smooth formation of the P=O bond. Therefore, it is necessary to strictly control the molar ratio of tributylphosphine to nickel halide to ensure the smooth progress of this reaction and to ensure a high reaction rate and yield.

[0041] 3. In this application, the reaction efficiency of O,O-dimethylthiophosphoramide and dimethyl sulfate is relatively high. Therefore, the reaction time in the reactor is shorter than that of the first step in the traditional reactor, shortening the time for preparing O,S-dimethylthiophosphoramide and improving the efficiency. Brief Description of the Drawings

[0042] Figure 1 It is a schematic diagram showing that the first-stage reactor is a microchannel reactor;

[0043] Figure 2 It is a schematic diagram showing that the first-stage reactor is a tubular reactor;

[0044] Figure 3 It is a schematic diagram showing the internal structure of a tubular reactor or a microchannel reactor;

[0045] Figure 4 It is an HPLC chromatogram showing the O,S-dimethylthiophosphoramide prepared in Example 10. Detailed Description of the Invention

[0046] The present application will be further described in detail below with reference to examples and comparative examples.

[0047] The raw material sources for the following examples and comparative examples are provided: The raw materials for the examples and comparative examples are all commercially available. Nickel chloride, particle size, 200 - 300 mesh, manufacturer, Taicang Xinglong Chemical Trading Co., Ltd.; Tributylphosphine, purity 98%; O,O-dimethylthiophosphoramide, purity 98%; Dimethyl sulfate, purity 98%.

[0048] Preparation Example of the Catalyst Tributylphosphine-Nickel Halide

[0049] Preparation Example 1

[0050] Inject 3.5 mol of tributylphosphine into a reaction flask containing 1 mol of nickel chloride with a particle size of 200 - 300 mesh. Under nitrogen protection, stir at a speed of 20 rpm for 30 min to obtain the liquid catalyst tributylphosphine-nickel chloride.

[0051] Preparation Example 2

[0052] Inject 4.5 mol of tributylphosphine into a reaction flask containing 1 mol of nickel chloride with a mesh size of 200 - 300. Under nitrogen protection, stir at a speed of 20 rpm for 30 min to obtain the liquid catalyst tributylphosphine - nickel chloride.

[0053] Preparation Example 3

[0054] Inject 4 mol of tributylphosphine into a reaction flask containing 1 mol of nickel chloride with a mesh size of 200 - 300. Under nitrogen protection, stir at a speed of 20 rpm for 30 min to obtain the liquid catalyst tributylphosphine - nickel chloride.

[0055] Preparation Example 4

[0056] Inject 1 mol of tributylphosphine into a reaction flask containing 1 mol of nickel chloride with a mesh size of 200 - 300. Under nitrogen protection, stir at a speed of 20 rpm for 30 min to obtain the liquid catalyst tributylphosphine - nickel chloride.

[0057] Preparation Example 5

[0058] Inject 6 mol of tributylphosphine into a reaction flask containing 1 mol of nickel chloride with a mesh size of 200 - 300. Under nitrogen protection, stir at a speed of 20 rpm for 30 min to obtain the liquid catalyst tributylphosphine - nickel chloride.

[0059] Preparation Example 6

[0060] The difference from Preparation Example 3 is that the nickel chloride in Preparation Example 3 is replaced with an equimolar amount of nickel bromide.

[0061] Preparation Example 7

[0062] The difference from Preparation Example 3 is that the nickel chloride in Preparation Example 3 is replaced with an equimolar amount of nickel iodide.

[0063] Preparation Example 8

[0064] The difference from Preparation Example 3 is that the nickel chloride in Preparation Example 3 is replaced with an equimolar amount of nickel fluoride.

[0065] Comparative Preparation Example 1

[0066] The difference from Preparation Example 3 is that the liquid catalyst tributylphosphine - nickel halide in Preparation Example 3 is replaced with an equimolar amount of methyl methanesulfonate.

[0067] Comparative Preparation Example 2

[0068] Add 5 mol of nickel chloride with a mesh size of 200 - 300 to 330 g of deionized water, and stir at a speed of 20 rpm for 30 min to obtain the liquid catalyst nickel chloride.

[0069] Comparative Preparation Example 3

[0070] Take 5 mol of tributylphosphine and stir it evenly at a speed of 20 rpm for 30 min to obtain the liquid catalyst tributylphosphine.

[0071] Examples of Preparing O,S-Dimethyl Thiophosphoramidate

[0072] Example 1

[0073] A method for preparing O,S-dimethyl thiophosphoramidate, as Figure 1 shown, includes the following steps:

[0074] Step S1: Use a high-pressure infusion pump to introduce the chloroform solution of O,O-dimethyl thiophosphoramidate and dimethyl sulfate and the catalyst tributylphosphine-nickel chloride prepared in Preparation Example 1 into the first-stage microchannel reactor. The reactor is immersed in a cooling medium with a flowing cycle; the mass ratio of O,O-dimethyl thiophosphoramidate to dimethyl sulfate is 100:10, and the catalyst tributylphosphine-nickel chloride accounts for 0.2% of the mass of O,O-dimethyl thiophosphoramidate; the flow rate of the chloroform solution of O,O-dimethyl thiophosphoramidate, dimethyl sulfate and the catalyst tributylphosphine-nickel chloride prepared in Preparation Example 1 in the first-stage microchannel reactor is 45 mL / min, the residence time is 1 min, and the temperature of the first-stage microchannel reactor is 24 - 25°C; as Figure 3 shown, the inside of the first-stage microchannel reactor is fixedly connected with tile-shaped arc-shaped baffles;

[0075] Step S2: Continuously introduce the product obtained in Step S1 into the second-stage microchannel reactor with a high-pressure infusion pump for reaction, with a flow rate of 0.9 mL / min and a residence time of 50 min. The temperature of the second-stage microchannel reactor is 59 - 60°C, and the O,S-dimethyl thiophosphoramidate reaction solution is continuously obtained from the outlet of the second-stage microchannel reactor; as Figure 3 shown, the inside of the second-stage microchannel reactor is fixedly connected with tile-shaped arc-shaped baffles;

[0076] Step S3: Directly introduce the O,S-dimethyl thiophosphoramidate reaction solution into a stirred cooling kettle, control the temperature at 10 - 15°C, and stir at a speed of 100 rpm for 30 min to obtain liquid O,S-dimethyl thiophosphoramidate.

[0077] Example 2

[0078] The difference from Example 1 is that in Step S1, the catalyst tributylphosphine-nickel chloride prepared in Preparation Example 2 is used.

[0079] Example 3

[0080] The difference from Example 1 is that in step S1, the catalyst tributylphosphine-nickel chloride prepared in Preparation Example 3 is used.

[0081] Example 4

[0082] The difference from Example 1 is that in step S1, the catalyst tributylphosphine-nickel chloride prepared in Preparation Example 4 is used.

[0083] Example 5

[0084] The difference from Example 1 is that in step S1, the catalyst tributylphosphine-nickel chloride prepared in Preparation Example 5 is used.

[0085] Example 6

[0086] The difference from Example 1 is that in step S1, the catalyst tributylphosphine-nickel bromide prepared in Preparation Example 6 is used.

[0087] Example 7

[0088] The difference from Example 1 is that in step S1, the catalyst tributylphosphine-nickel iodide prepared in Preparation Example 7 is used.

[0089] Example 8

[0090] The difference from Example 1 is that in step S1, the catalyst tributylphosphine-nickel fluoride prepared in Preparation Example 8 is used.

[0091] Example 9

[0092] The difference from Example 3 is that in step S1, the catalyst tributylphosphine-nickel halide accounts for 0.25% of the mass of O,O-dimethylthiophosphoramide.

[0093] Example 10

[0094] The difference from Example 3 is that in step S1, the catalyst tributylphosphine-nickel halide accounts for 0.15% of the mass of O,O-dimethylthiophosphoramide.

[0095] Example 11

[0096] The difference from Example 3 is that in step S1, the catalyst tributylphosphine-nickel halide accounts for 0.4% of the mass of O,O-dimethylthiophosphoramide.

[0097] Example 12

[0098] The difference from Example 3 is that in step S1, the mass ratio of O,O-dimethylthiophosphoramide to dimethyl sulfate is 100:5.

[0099] Example 13

[0100] The difference from Example 3 is that in step S1, the mass ratio of O,O-dimethylthiophosphoramide to dimethyl sulfate is 100:8.

[0101] Example 14

[0102] A method for preparing O,S-dimethylthiophosphoramide, as Figure 1 shown, includes the following steps:

[0103] Step S1, use a high-pressure infusion pump to introduce the chloroform solutions of O,O-dimethylthiophosphoramide and dimethyl sulfate and the catalyst tributylphosphine-nickel chloride prepared in Preparation Example 3 into the first-stage microchannel reactor. The reactor is immersed in a cooling medium with flowing circulation; the mass ratio of O,O-dimethylthiophosphoramide to dimethyl sulfate is 100:5, and the catalyst tributylphosphine-nickel chloride accounts for 0.2% of the mass of O,O-dimethylthiophosphoramide; the flow rate of the chloroform solutions of O,O-dimethylthiophosphoramide and dimethyl sulfate and the catalyst tributylphosphine-nickel chloride prepared in Preparation Example 3 in the first-stage microchannel reactor is 5 mL / min, the residence time is 0.018 min, and the temperature of the first-stage microchannel reactor is 12 - 13 °C; as Figure 3 shown, a spiral arc-shaped baffle is fixedly connected inside the first-stage microchannel reactor;

[0104] Step S2, continue to introduce the product obtained in step S1 into the second-stage microchannel reactor with a high-pressure infusion pump for reaction, with a flow rate of 5 mL / min and a residence time of 2 min. The temperature of the second-stage microchannel reactor is 36 - 38 °C, and the O,S-dimethylthiophosphoramide reaction solution is continuously obtained from the outlet of the second-stage microchannel reactor; as Figure 3 shown, a spiral arc-shaped baffle is fixedly connected inside the second-stage microchannel reactor;

[0105] Step S3, directly introduce the O,S-dimethylthiophosphoramide reaction solution into a cooling kettle with stirring, control the temperature at 10 - 15 °C, and stir at a speed of 100 rpm for 30 min to obtain liquid O,S-dimethylthiophosphoramide.

[0106] Example 15

[0107] A method for preparing O,S-dimethylthiophosphoramide, as Figure 2 shown, includes the following steps:

[0108] Step S1: Use a high-pressure infusion pump to introduce the chloroform solution of O,O-dimethylthiophosphoramide and dimethyl sulfate and the catalyst tributylphosphine-nickel chloride prepared in Preparation Example 3 into the first-stage tubular reactor. The tubular reactor is immersed in a cooling medium with flowing circulation; the mass ratio of O,O-dimethylthiophosphoramide to dimethyl sulfate is 100:5, and the catalyst tributylphosphine-nickel chloride accounts for 0.2% of the mass of O,O-dimethylthiophosphoramide; the flow rate of the chloroform solution of O,O-dimethylthiophosphoramide, dimethyl sulfate and the catalyst tributylphosphine-nickel chloride prepared in Preparation Example 3 in the first-stage tubular reactor is 600 mL / min, the residence time is 15 min, and the temperature of the first-stage tubular reactor is 33 - 34 °C; as Figure 3 shown, the inside of the first-stage tubular reactor is fixedly connected with tile-shaped arc baffles;

[0109] Step S2: Continue to introduce the product obtained in Step S1 into the second-stage microchannel reactor using a high-pressure infusion pump for reaction, with a flow rate of 450 mL / min and a residence time of 120 min. The temperature of the second-stage microchannel reactor is 74 - 75 °C, and the O,S-dimethylthiophosphoramide reaction solution is continuously obtained from the outlet of the second-stage microchannel reactor; as Figure 3 shown, the inside of the second-stage microchannel reactor is fixedly connected with spiral arc baffles;

[0110] Step S3: Directly introduce the O,S-dimethylthiophosphoramide reaction solution into a stirred cooling kettle, control the temperature at 5 - 15 °C, and stir at a speed of 100 rpm for 30 min to obtain liquid O,S-dimethylthiophosphoramide.

[0111] Comparative Example 1

[0112] The difference from Example 3 is that in Step S1, the catalyst methyl methanesulfonate prepared in Comparative Preparation Example 1 is used.

[0113] Comparative Example 2

[0114] The difference from Example 3 is that in Step S1, the catalyst nickel chloride prepared in Comparative Preparation Example 2 is used.

[0115] Comparative Example 3

[0116] The difference from Example 3 is that in Step S1, the catalyst tributylphosphine prepared in Comparative Preparation Example 3 is used.

[0117] Comparative Example 4

[0118] The difference from Example 3 is that in Step S1, the catalyst tributylphosphine-nickel chloride is not added.

[0119] Performance Detection Test

[0120] The content and yield of O,S-dimethyl phosphoramidothioate prepared in Examples 1 to 15 and Comparative Examples 1 to 4 were calculated; the yield calculation method: (mass of the prepared liquid O,S-dimethyl phosphoramidothioate × content of O,S-dimethyl phosphoramidothioate by external standard quantification) / (mass of the O,O-dimethyl phosphorothioate reaction solution × content of O,O-dimethyl phosphorothioate) × 100% = yield. The test results are shown in Table 1;

[0121] Content (%) Yield (%) Example 1 68.0 86.8 Example 2 68.2 87.1 Example 3 69.5 88.5 Example 4 66.5 85.2 Example 5 66.3 85.1 Example 6 66.7 85.3 Example 7 66.5 85.1 Example 8 66.2 84.3 Example 9 67.2 86.7 Example 10 67.0 86.4 Example 11 66.7 85.5 Example 12 71.3 92.3 Example 13 67.9 87.3 Example 14 68.1 86.5 Example 15 97.8 86.3 Comparative Example 1 61.2 79.6 Comparative Example 2 52.6 68.3 Comparative Example 3 61.1 78.6 Comparative Example 4 63.1 82.1

[0122] Combined with Examples 1 to 5, it can be seen that in Examples 1 - 5, only the raw material ratio of tributylphosphine to nickel chloride was changed. The yields of O,S-dimethyl phosphoramidothioate prepared in Examples 1 - 3 were all greater than 86.8%; the yields of O,S-dimethyl phosphoramidothioate prepared in Examples 4 - 5 were both about 85%. It is proved that the optimal range of the molar ratio of tributylphosphine to nickel chloride is (3.5 - 4.5):1.

[0123] Combined with Example 3 and Examples 6, 7, 8, and Comparative Examples 1 to 3, it can be seen that when nickel chloride was replaced with nickel bromide, nickel iodide, and nickel fluoride, the yields of O,S-dimethyl phosphoramidothioate prepared decreased from 88.5% to 85.3%, 85.1%, and 84.3% respectively. It is proved that among the nickel halides, nickel chloride is the best choice; in Comparative Example 1, methyl methanesulfonate was used to replace the catalyst tributylphosphine-nickel chloride, in Comparative Example 2, tributylphosphine was used to replace the catalyst tributylphosphine-nickel chloride; in Comparative Example 3, nickel chloride was used to replace the catalyst tributylphosphine-nickel chloride, and the yields of Comparative Examples 1, 2, and 3 were all lower than 80%; it is proved that the selection of the catalyst is extremely important for the synthesis of O,S-dimethyl phosphoramidothioate.

[0124] Combined with Example 3 and Examples 9, 10, 11, it can be seen that the yield of O,S-dimethyl phosphoramidothioate in Example 3 was greater than that in Examples 9 and 10, and the yields of Examples 3, 9, and 10 were greater than that in Example 11. It is proved that when the mass of the catalyst tributylphosphine-nickel halide is in the range of 0.15 - 0.25% of the mass of O,O-dimethyl phosphorothioate, the highest yield of O,S-dimethyl phosphoramidothioate can be obtained.

[0125] Combined with Example 3 and Examples 12 and 13, the mass ratios of O,O-dimethyl phosphorothioate to dimethyl sulfate were 100:10, 100:5, and 100:8 respectively. It can be seen that when the mass ratio of O,O-dimethyl phosphorothioate to dimethyl sulfate is 100:5, the highest yield of O,S-dimethyl phosphoramidothioate can be obtained.

[0126] Combined with Example 14 and Example 15, it can be seen that in Example 14 and Example 15, the temperature and raw material flow rate ranges in the claims are supported, and the two combination modes of tubular reactor - microchannel reactor and microchannel reactor - microchannel reactor are supported, which proves that the protection scope of the claims of this application is reasonable.

[0127] Combined with Example 3 and Comparative Example 4, it can be seen that when the catalyst tributylphosphine - nickel chloride is not added to the reaction raw materials, the yield of O,S - dimethylthiophosphoramide prepared is reduced significantly, which proves that the addition of the catalyst tributylphosphine - nickel chloride is very important for the preparation effect of O,S - dimethylthiophosphoramide.

[0128] This specific embodiment is only an interpretation of this application, and it does not limit this application. After reading this specification, those skilled in the art can make modifications to this embodiment without creative contributions as needed, but as long as it is within the scope of the claims of this application, it is protected by the patent law.

Claims

1. A method for continuously preparing O,S-dimethyl phosphorothioamidate based on a microchannel reactor, characterized in that, It includes the following steps: Step S1: Feed O,O-dimethylthiophosphoramide, dimethyl sulfate solution and the catalyst tributylphosphine-nickel chloride into a microchannel reactor, keep the temperature of the reaction raw materials at 10 - 25 °C, and flow through the reactor at a flow rate of 1 - 600 mL / min. Step S2: Continuously feed the product obtained in Step S1 into the microchannel reactor for reaction, control the reaction temperature at 35 - 75 °C, and flow through the microchannel reactor at a flow rate of 1 - 450 mL / min for further reaction, and continuously obtain the O,S-dimethylthiophosphoramide reaction solution from the outlet of the microchannel reactor. Step S3: Stir the O,S-dimethylthiophosphoramide reaction solution and control the temperature below 15 °C to obtain liquid O,S-dimethylthiophosphoramide. In Step S1, the flow time of O,O-dimethylthiophosphoramide, dimethyl sulfate solution and the catalyst tributylphosphine-nickel chloride in the reactor is 0.018 - 15 min. In Step S2, the flow time of the product obtained in Step S1 in the microchannel reactor is 1.02 - 120 min. In the catalyst tributylphosphine-nickel chloride, the molar ratio of tributylphosphine to nickel chloride is (3.5 - 4.5):

1. The mass of the catalyst tributylphosphine-nickel chloride accounts for 0.15 - 0.25% of the mass of O,O-dimethylthiophosphoramide. In the dimethyl sulfate solution, the solvent of dimethyl sulfate is any one or combination of dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, petroleum ether, aromatic solvents, ester solvents, nitrile solvents, ether solvents.

2. The method for continuously preparing O,S-dimethyl phosphorothioamidate based on a microchannel reactor according to claim 1, characterized in that, Dimethyl sulfate and O,O-dimethylthiophosphoramide are fed into the microchannel reactor at a mass ratio of (5 - 10):

100.

3. A method for continuously preparing O,S-dimethyl phosphorothioamidate based on a microchannel reactor according to any one of claims 1-2, characterized in that, The inner wall of the microchannel reactor is fixedly connected with an arc-shaped baffle, a spiral baffle, a baffle with a folded flow pattern or a perforated baffle.

4. A method for continuously preparing O,S-dimethyl phosphorothioamidate based on a microchannel reactor according to claim 3, characterized in that, The arc-shaped baffle is in a tile structure.

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