A fully continuous flow process for the preparation of pyridate

Abstract

The application discloses a kind of full continuous flow preparation methods of pyriproxyfen.The chloro o-nitroaniline solution and hydrogen are transported to fixed bed reactor to carry out continuous catalytic hydrogenation reaction, and the 4-chloro o-phenylenediamine reaction mixture obtained is transported to microchannel mixer and reactor with ethyl glyoxylic acid solution to carry out continuous cyclization reaction, and the 2-hydroxy-6-chloroquinoxaline suspension obtained is entered into continuous online filtering device, and the mixture is transported to micro-mixer and continuous flow reactor with phosphorus oxychloride by peristaltic pump, and the effluent reaction liquid and hydroquinone / catalyst mixture are transported to another fixed bed reactor to carry out continuous etherification;Reaction mixture and (S)-2-chloropropionic acid ethyl ester are entered into fixed bed reactor to carry out continuous etherification reaction;Product pyriproxyfen is obtained;Compared with traditional batch kettle type synthesis method, the method has short reaction time, high product yield, high degree of automation, high process continuous efficiency, high space-time yield, low energy consumption and easy industrial amplification application.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of pesticide synthesis, and particularly relates to a full continuous flow preparation method of quizalofop-P-ethyl. BACKGROUND

[0002] Quizalofop-P-ethyl, also known as quizalofop-P, is an aryloxyphenoxypropionate herbicide developed by Japan's Nippon Shokubai Co., Ltd., and its chemical name is (R)-2-[4-(6-chloroquinoxalin-2-yloxy)]propionic acid ethyl ester, and its specific structure is as follows:

[0003] .

[0004] The current traditional industrial route is as follows: 4-chloro-o-nitroaniline and diketene are used as raw materials to obtain quizalofop-P-ethyl through condensation, ring formation, reduction, chlorination, and etherification with p-benzenediol in two steps. In the process of ring formation and etherification, a strong alkaline aqueous solution is needed, which generates a large amount of waste salt, and the environmental protection cost is high; the ring formation and etherification processes are both heterogeneous reactions, and solid by-products are generated, which requires high continuous flow equipment and long reaction time. SUMMARY

[0005] In order to overcome the shortcomings of long reaction time, high safety risk, high energy consumption, and low efficiency of the traditional batch kettle synthesis method, the purpose of the present application is to provide a full continuous flow preparation method of quizalofop-P-ethyl. The reaction time of the method is greatly shortened, the yield and production efficiency of the product quizalofop-P-ethyl are greatly improved, the automation degree of the process is significantly improved, the energy consumption is greatly reduced, the safety is greatly improved, the environmental protection cost is reduced, and the method is easy to be applied in industry.

[0006] The specific technical scheme is as follows:

[0007] A full continuous flow preparation method of quizalofop-P-ethyl, the specific steps are as follows:

[0008] (1) The chloro-o-nitroaniline solution and hydrogen are mixed in the first micro-mixer, and then enter the first fixed bed reactor containing a metal catalyst, to carry out a continuous hydrogenation reaction, and obtain 4-chloro-phenylenediamine material, which enters the first receiving tank;

[0009] (2) The 4-chloro-phenylenediamine material flowing out of the first receiving tank in step (1) is mixed with the ethyl glyoxylate solution in the second micro-mixer, and then enters the first micro-reactor to carry out a continuous cyclization reaction, and the product suspension liquid flowing out is treated by mixing with toluene through an online filtering device to obtain a toluene suspension liquid of 2-hydroxy-6-chloroquinoxaline;

[0010] (3) the 2-hydroxy-6-chloroquinoxaline toluene suspension solution from the online filter device in step (2) and the phosphorus oxychloride solution are respectively fed into a third micromixer for mixing, and then fed into a second microreactor for continuous chlorination reaction; after neutralization of the product with a base in the third microreactor, the product is extracted and separated by a continuous extractor to obtain a 2,6-dichloroquinoxaline toluene solution;

[0011] (4) the 2,6-dichloroquinoxaline toluene solution is fed into a solvent switching device for solvent switching to obtain a 2,6-dichloroquinoxaline N,N-dimethylformamide solution;

[0012] (5) the 2,6-dichloroquinoxaline N,N-dimethylformamide solution from the solvent switching device in step (4) is fed into a fifth micromixer for mixing with hydroquinone / catalyst, and then fed into a second fixed bed reactor containing potassium carbonate for continuous etherification reaction to obtain a 4-(6-chloro-2 quinoxalinyloxy) phenol material;

[0013] (6) the 4-(6-chloro-2 quinoxalinyloxy) phenol material from the second fixed bed reactor in step (5) is fed into a sixth micromixer for mixing with a catalyst / (S)-2-chloropropionic acid ethyl ester reaction solution, and then fed into a third fixed bed reactor for continuous etherification reaction to obtain a fipronil solution.

[0014] Further, the chlorinated o-nitroaniline in step (1) is 4-chloro-2-nitroaniline or 5-chloro-2-nitroaniline; the solvent in the chlorinated o-nitroaniline solution is any one of methanol, ethanol, and isopropanol; and the metal catalyst is a Raney Nickel catalyst.

[0015] Further, in step (1), the flow rate of the chlorinated o-nitroaniline solution fed into the first fixed bed reactor is controlled to be in the range of 1.5-2.5 mL / min; the hydrogen flow rate fed into the first micromixer is controlled to be in the range of 35-50 sccm; the temperature in the first fixed bed reactor is controlled to be in the range of 15-35 ℃; the residence time of the mixed reaction material in the first fixed bed reactor is 30-60 s; and the back pressure during the reaction is 0.5-2.0 MPa.

[0016] Further, in step (2), the ethyl glyoxylate solution is ethyl glyoxylate dissolved in methanol or ethanol, and the flow rate ratio of the 4-chloro-ortho-phenylenediamine solution obtained in step (1) to the ethyl glyoxylate solution delivered into the first micro-reactor is controlled so that the molar ratio of 4-chloro-ortho-phenylenediamine to ethyl glyoxylate is in the range of 1:1.05-1.2; the temperature in the first micro-reactor is controlled in the range of 60-100 ℃; the residence time of the mixed reactants in the first micro-reactor is 10-20 min; and the back pressure during the reaction is 0.2-1 MPa.

[0017] Further, in step (3), the flow rate ratio of the 2-hydroxy-6-chloro-quinoxaline methylbenzene suspension solution obtained in step (2) to the phosphorus oxychloride solution delivered into the second micro-reactor is controlled so that the molar ratio of 2-hydroxy-6-chloro-quinoxaline to phosphorus oxychloride is in the range of 1:0.8-1.5; the temperature in the third micro-mixer and the second micro-reactor is controlled in the range of 80-105 ℃; the residence time of the mixed reactants in the second micro-reactor is 5-10 min; the residence time of the crude product mixture in the continuous extraction separator is 0.1-20 min; and the temperature in the continuous extraction separator is controlled in the range of 30-50 ℃.

[0018] Further, in step (4), the temperature in the solvent switching device is controlled in the range of 110-115 ℃, and nitrogen is introduced for purging; the toluene vapor is recovered through a reflux device, and N,N-dimethylformamide is introduced to obtain a 2,6-dichloro-quinoxaline N,N-dimethylformamide solution;

[0019] Further, in step (5), the flow rate ratio of the 2,6-dichloro-quinoxaline solution obtained in step (4) to the mixed solution of catalyst / hydroquinone delivered into the second fixed-bed reactor is controlled so that the molar ratio of 2,6-dichloro-quinoxaline to hydroquinone is in the range of 1:1.1-1.5; the temperature in the second fixed-bed reactor is controlled in the range of 100-130 ℃; and the residence time of the mixed material in the second fixed-bed reactor is 2.5-6.7 min.

[0020] Further, in step (6), the flow rate ratio of the 4-(6-chloro-2-quinoxalinyloxy)phenol solution obtained in step (4) to the mixed solution of catalyst / (S)-2-chloropropionic acid ethyl ester delivered into the third fixed-bed reactor is controlled so that the molar ratio of 4-(6-chloro-2-quinoxalinyloxy)phenol to (S)-2-chloropropionic acid ethyl ester is in the range of 1:1.2-1.8; the temperature in the third fixed-bed reactor is controlled in the range of 75-120 ℃; and the residence time of the mixed material in the third fixed-bed reactor is 3.0-13.0 min.

[0021] Further, the inner filler of the second fixed bed reactor and the third fixed bed reactor is any one of potassium carbonate, sodium hydroxide and potassium hydroxide, and the catalysts in the step (5) and the step (6) are tetrabutylammonium chloride or tetrabutylammonium bromide.

[0022] Further, the first micro-mixer, the second micro-mixer, the third micro-mixer, the fourth micro-mixer, the fifth micro-mixer and the sixth micro-mixer are any one of a T-shaped micro-mixer, a Y-shaped micro-mixer and a cross-shaped micro-mixer.

[0023] Advantages of the present application

[0024] (1) The new process is selected by abandoning the traditional industrial route and choosing a shorter synthetic route, so that the reaction is more environmentally friendly, the solvent can be recycled, the economic benefit is higher, and the industrialization potential is higher.

[0025] (2) The continuous flow micro-channel reaction system has excellent mass transfer, heat transfer and material molecular mixing performance, so that the reaction time is greatly shortened, and the reaction efficiency is greatly improved, and the full synthesis of the pyridylcarbamic acid ester can be completed in about 2 hours from the traditional batch kettle reaction of several days;

[0026] (3) The continuous liquid-liquid quenching, continuous liquid-liquid extraction and continuous liquid-liquid separation of the reaction liquid are simple to operate in the continuous flow process, the quenching speed is fast, the process is safe, the separation effect is good, the extraction efficiency is high, the separation yield is close to the reaction yield, the reaction process and the liquid-liquid extraction and separation process are continuous, so that the total process efficiency is greatly improved, and the purity of the obtained product is high;

[0027] (4) The continuous synthesis from raw materials to products is realized, the process is continuous and uninterrupted, the degree of automation is high, no external intervention is needed, the space-time efficiency is high, the number of operating workers and the labor intensity are greatly reduced, and the production cost is significantly reduced;

[0028] (5) The use of the continuous flow micro-channel chemical process can realize the multiphase mixing of the reaction process, the mass transfer and the reaction process in the micro-mixer and the micro-channel reactor, the conditions are mild, the operation is simple, no stirring device is needed, the process energy consumption is greatly reduced, and the industrial production can be quickly realized. BRIEF DESCRIPTION OF DRAWINGS

[0029] Figure 1 The flowchart of the present application

[0030] In the figure: 1, first micromixer; 2, first fixed bed reactor; 3, gas-liquid separator; 4, first receiving tank; 5, second micromixer; 6, first microreactor; 7, online filtering device; 8, third micromixer; 9, second microreactor; 10, fourth micromixer; 11, third microreactor; 12, continuous extraction device; 13, solvent switching device; 14, second receiving tank; 15, fifth micromixer; 16, second fixed bed reactor; 17, sixth micromixer; 18, third fixed bed reactor. DETAILED DESCRIPTION

[0031] To make the technical content, structural features, purposes and effects of the technical scheme clear, the following further describes the embodiments in combination with the drawings. The embodiments are implemented on the premise of the technical scheme of the present application, and give detailed implementation modes and specific operation processes, but the protection scope of the present application is not limited to the following embodiments.

[0032] The reaction equation of the present application is as follows:

[0033]

[0034] The reaction process is as shown in Figure 1 , including the following steps:

[0035] The chloro-o-nitroaniline and hydrogen source are mixed by the first micromixer 1 and then fed into the first fixed bed reactor 2 containing a metal catalyst, Raney Nickel, for reaction. The reaction product is separated by the gas-liquid separator 3, and the separated 4-chloro-ortho-phenylenediamine is fed into the first receiving tank 4. The 4-chloro-ortho-phenylenediamine in the first receiving tank 4 is mixed with ethyl glyoxylate by the second micromixer 5 and then fed into the first microreactor 6 for reaction. The reaction product is mixed with toluene by the online filter 7 to obtain a 2-hydroxy-6-chloro-quinoxaline toluene suspension. The 2-hydroxy-6-chloro-quinoxaline toluene suspension is mixed with a phosphorus oxychloride solution by the third micromixer 8 and then fed into the second microreactor 9 for reaction. The reaction product is mixed with sodium hydroxide by the fourth micromixer 10 and then fed into the third microreactor 11 for neutralization. The mixture is fed into the continuous extraction separator 12. The aqueous phase is discharged from the heavy phase outlet of the continuous extraction separator 12. The organic phase containing the product 2,6-dichloroquinoxaline is discharged from the light phase outlet of the continuous extraction separator 12 and then fed into the solvent switching device 13. Nitrogen is introduced for purging. Toluene vapor is recovered by the reflux device. N,N-dimethylformamide is introduced as the solvent to obtain a 2,6-dichloroquinoxaline N,N-dimethylformamide solution. The 2,6-dichloroquinoxaline N,N-dimethylformamide solution is collected in the second receiving tank 14. The 2,6-dichloroquinoxaline N,N-dimethylformamide solution in the second receiving tank 14 is mixed with a catalyst (5 mol%) / hydroquinone N,N-dimethylformamide mixed solution by the fifth micromixer 15 and then fed into the second fixed bed reactor 16 for reaction to obtain a 4-(6-chloro-2-quinoxalinyloxy)phenol N,N-dimethylformamide solution. The 4-(6-chloro-2-quinoxalinyloxy)phenol N,N-dimethylformamide solution is mixed with a catalyst / (S)-2-chloropropionic acid ethyl ester N,N-dimethylformamide mixed solution by the sixth micromixer 17 and then fed into the third fixed bed reactor 18 for reaction to obtain the product, cyhalofop-butyl.

[0036] Example 1: Full continuous flow synthesis of cyhalofop-butyl

[0037] The micromixer in this example is a T-type micromixer

[0038] A methanol solution (0.2 M) of 4-chloro-2-nitroaniline is simultaneously fed into the first micromixer 1 at a flow rate of 2.5 mL / min and hydrogen gas (50 sccm) at the same time. The mixture is then fed into the first fixed bed reactor 2 (the reaction volume is 10.0 ml, and the reactor is filled with 15 g of Raney Nickel catalyst). The back pressure valve is set to 1.0 Mpa, and the temperature of the first fixed bed reactor 2 is controlled at 25°C. After 60 s of reaction (i.e., the residence time of the mixed reaction material in the first fixed bed reactor 2 is 60 s), the mixed reaction material is discharged from the outlet of the first fixed bed reactor 2, separated by the gas-liquid separator 3, and collected in the first receiving tank 4. The conversion rate of 4-chloro-2-nitroaniline is 100%, and a methanol solution (0.2 M) of 4-chloro-ortho-phenylenediamine is obtained.

[0039] The methanol solution of 4-chloro-o-phenylenediamine obtained in the previous step (0.2 M) and the methanol solution of ethyl glyoxylate (1.2 equivalents, 0.24 M) were fed into the second micromixer 5, mixed and then fed into the first microractor, to perform the cyclization reaction. The back pressure valve was set at 0.5 MPa, and the temperature of the microractor was controlled at 90 ℃. After 15 min of reaction (i.e. the residence time of the mixed reactants in the first microractor 6 was 15 min), the mixed reactants flowed out of the outlet, were mixed with toluene by the online filtering device 7, and 2-hydroxy-6-chloro-quinoxaline toluene suspension was obtained.

[0040] The 2-hydroxy-6-chloro-quinoxaline toluene suspension obtained in the previous step was fed into the third micromixer 8 by a peristaltic pump, and the phosphorus oxychloride toluene solution was fed into the third micromixer 8 by a polytetrafluoroethylene plunger pump. The two streams were mixed and then fed into the second microractor 9. By calibrating the flow rate of the peristaltic pump, the molar ratio of 2-hydroxy-6-chloro-quinoxaline to phosphorus oxychloride was controlled at 1:1.2. The temperature of the third micromixer 8 and the second microractor 9 was controlled at 95 ℃. After 10 min of reaction (i.e. the residence time of the mixed reactants in the second microractor 9 was 10 min), the mixed reactants flowed out of the second microractor 9, were mixed with 5 M sodium hydroxide solution in the fourth micromixer 10, and then fed into the third microractor 11 to perform the neutralization. The mixed solution was fed into the continuous extraction separator 12, and the temperature in the continuous extraction separator was controlled at 30 ℃. The liquid was kept in the continuous extraction separator for 10 min. The aqueous phase flowed out of the heavy phase outlet of the continuous extraction separator 12, and the organic phase containing the product 2,6-dichloro-quinoxaline flowed out of the light phase outlet of the continuous extraction separator 12.

[0041] The 2,6-dichloro-quinoxaline organic phase obtained in the previous step was fed into the solvent switching device 13, and the temperature in the solvent switching device 13 was controlled at 110-115 ℃. Nitrogen was introduced to purge the solvent switching device 13, and toluene vapor was recovered by refluxing. N,N-dimethylformamide was introduced into the solvent switching device 13 to obtain a 2,6-dichloro-quinoxaline N,N-dimethylformamide solution (0.2 M)

[0042] The 2,6-dichloro-quinoxaline N,N-dimethylformamide solution obtained in the previous step (1.0 equivalent, 0.2 M) and the N,N-dimethylformamide mixed solution of tetrabutylammonium chloride (5 mol%) and hydroquinone (1.2 equivalents, 0.24 M) were fed into the fifth micromixer 15, mixed, and then fed into the second fixed bed reactor 16 (filled with potassium carbonate). The temperature in the second fixed bed reactor 16 was controlled at 120 ℃. After 6 min of reaction (i.e. the residence time of the mixed reactants in the second fixed bed reactor 16 was 6 min), the mixed reactants flowed out of the second fixed bed reactor 16, and a 4-(6-chloro-2-quinoxalinyloxy)phenol N,N-dimethylformamide solution (0.2 M) was obtained.

[0043] The 4-(6-chloro-2-quinoxalinyloxy)phenol N,N-dimethylformamide solution from the previous step (1.0 eq, 0.2 M) and tetrabutylammonium chloride (5 mol%) / (S)-ethyl 2-chloropropionate N,N-dimethylformamide mixed solution (1.5 eq, 0.3 M) were fed into the sixth micromixer 17 respectively, mixed, and then entered into the third fixed bed reactor 18 (filled with potassium carbonate). The temperature in the third fixed bed reactor 18 was controlled at 100 °C. After 12 min of reaction (i.e., the residence time of the mixed reactant in the third fixed bed reactor 18 was 12 min), the reaction solution was collected in the product storage buffer tank. The collected reaction solution was purified to obtain the fenclorim. The total yield of the multi-step micro-reaction continuous flow was 45%, and the optical purity of the product was 91%. ee .

[0044] Example 2

[0045] The operation of this example is the same as that of Example 1, except that the micro-mixer used in the reaction in this example is a Y-type micro-mixer, and the starting material is 5-chloro-2-nitroaniline. The total yield of the product fenclorim obtained in this example is 45%, and the optical purity of the product is 91%. ee .

[0046] Example 3

[0047] The operation of this example is the same as that of Example 1, except that the 4-chloro-2-nitroaniline solution and the ethyl glyoxylate solution in this example are ethanol solutions. The total yield of the product fenclorim obtained in this example is 42%, and the optical purity of the product is 92%. ee .

[0048] Example 4

[0049] The operation of this example is the same as that of Example 1, except that the catalyst in this example is tetrabutylammonium bromide instead of tetrabutylammonium chloride. The total yield of the product fenclorim obtained in this example is 47%, and the optical purity of the product is 88%. ee .

[0050] Example 5

[0051] The operation of this example is the same as that of Example 1, except that the fillers in the second fixed bed reactor 16 and the third fixed bed reactor 18 in this example are sodium hydroxide. The total yield of the product fenclorim obtained in this example is 40%, and the optical purity of the product is 82%. ee ee .

[0052] Finally, it should be noted that the above examples are merely intended to illustrate the technical solutions of the present application and not to limit the protection scope of the present application. Although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application can be modified or equivalently replaced without departing from the essence and scope of the technical solutions of the present application.

Claims

1. A fully continuous flow process for the preparation of pyriofenone, characterized in that, The specific steps are as follows: (1) the chloro-o-nitroaniline solution and hydrogen are mixed in the first micro-mixer (1) and then enter the first fixed bed reactor (2) provided with a metal catalyst to perform continuous hydrogenation reaction, thereby obtaining 4-chloro-ortho-phenylenediamine material, which enters the first receiving tank (4); (2) the 4-chloro-ortho-phenylenediamine material flowing out of the first receiving tank (4) in step (1) is mixed with the ethyl glyoxylate solution in the second micro-mixer (5), and then enters the first micro-reactor (6) to perform continuous cyclization reaction, and the product suspension is mixed with toluene by the online filtering device (7) to obtain 2-hydroxy-6-chloro-quinoxaline toluene suspension; (3) the 2-hydroxy-6-chloro-quinoxaline toluene suspension flowing out of the online filtering device (7) in step (2) is mixed with the phosphorus oxychloride solution in the third micro-mixer (8), and then enters the second micro-reactor (9) to perform continuous chlorination reaction; after neutralization of the product in the third micro-reactor (11) with an alkali, the product is extracted and separated by the continuous extraction separator (12) to obtain 2,6-dichloro-quinoxaline toluene solution; (4) the 2,6-dichloro-quinoxaline toluene solution flows into the solvent switching device (13) to perform solvent switching to obtain 2,6-dichloro-quinoxaline N,N-dimethylformamide solution; (5) the 2,6-dichloro-quinoxaline N,N-dimethylformamide solution flowing out of the solvent switching device (13) in step (4) is mixed with the hydroquinone / catalyst in the fifth micro-mixer (15), and then enters the second fixed bed reactor (16) provided with potassium carbonate to perform continuous etherification reaction, thereby obtaining 4-(6-chloro-2 quinoxaline oxy) phenol material; (6) the 4-(6-chloro-2 quinoxaline oxy) phenol material flowing out of the second fixed bed reactor (16) in step (5) is mixed with the catalyst / (S)-2-chloropropionic acid ethyl ester reaction solution in the sixth micro-mixer (17), and then enters the third fixed bed reactor (18) to perform continuous etherification reaction, thereby obtaining the target product pyroxasulfone solution; The chloro-o-nitroaniline is 4-chloro-2-nitroaniline or 5-chloro-2-nitroaniline; The temperature in the first fixed bed reactor (2) is controlled at 15-35 ℃; the residence time of the mixed reaction material in the first fixed bed reactor (2) is 30-60 s; The temperature in the first micro-reactor (6) is controlled at 60-100 ℃; the residence time of the mixed reaction material in the first micro-reactor (6) is 10-20 min; The temperature in the third micro-mixer (8) and the second micro-reactor (9) is controlled in the range of 80-105 ℃; the residence time of the mixed reaction material in the second micro-reactor (9) is 5-10 min; the residence time of the crude product mixed solution in the continuous extraction separator (12) is 0.1-20 min; The temperature in the second fixed bed reactor (16) is controlled at 100-130 ℃; the residence time of the mixture in the second fixed bed reactor (16) is 2.5-6.7 min; The temperature in the third fixed bed reactor (18) is controlled at 75-120 ℃; the residence time of the mixture in the third fixed bed reactor (18) is 3.0-13.0 min; The packing in the second fixed bed reactor (16) and the third fixed bed reactor (18) is potassium carbonate, and the catalyst in step (5) and step (6) is tetrabutylammonium chloride or tetrabutylammonium bromide.

2. A fully continuous flow process for the preparation of pyriofenone according to claim 1, characterized in that, The solvent in the chloro-o-nitroaniline solution in step (1) is any one of methanol, ethanol, and isopropanol; and the metal catalyst is Raney Nickel catalyst.

3. A fully continuous flow process for the preparation of pyriofenone according to claim 1, characterized in that, In step (1), the flow rate of the chloro-o-nitroaniline solution delivered into the first fixed bed reactor (2) is controlled so that the flow rate of the liquid is in the range of 1.5-2.5 mL / min; the flow rate of hydrogen delivered into the first micro-mixer (1) is controlled so that the flow rate of hydrogen is in the range of 35-50 sccm; and the back pressure during the reaction is 0.5-2.0 MPa.

4. A fully continuous flow process for the preparation of pyriofenone according to claim 1, characterized in that, In step (2), the ethyl glyoxylate solution is ethyl glyoxylate dissolved in methanol or ethanol; the flow rate ratio of the 4-chloro-ortho-phenylenediamine solution obtained in step (1) to the ethyl glyoxylate solution delivered into the first micro-reactor (6) is controlled so that the molar ratio of 4-chloro-ortho-phenylenediamine to ethyl glyoxylate is in the range of 1:1.05-1.2; and the back pressure during the reaction is 0.2-1 MPa.

5. A fully continuous flow process for the preparation of pyriofenone according to claim 1, characterized in that, In step (3), the flow rate ratio of the 2-hydroxy-6-chloro-quinoxaline methylbenzene suspension solution obtained in step (2) to the phosphorus oxychloride solution delivered into the second micro-reactor (9) is controlled so that the molar ratio of 2-hydroxy-6-chloro-quinoxaline to phosphorus oxychloride is in the range of 1:0.8-1.5; and the temperature in the continuous extraction separator (12) is controlled at 30-50 ℃.

6. A fully continuous flow process for the preparation of pyriofenone according to claim 1, characterized in that, In step (4), the temperature in the solvent switching device (13) is controlled at 110-115 ℃, and nitrogen is introduced for purging at the same time; the toluene vapor is recovered through a reflux device, and N,N-dimethylformamide is introduced as the solvent to obtain a 2,6-dichloro-quinoxaline N,N-dimethylformamide solution.

7. A fully continuous flow process for the preparation of pyriofenone according to claim 1, characterized in that, In step (5), the flow rate ratio of the 2,6-dichloro-quinoxaline solution obtained in step (4) to the mixed solution of the catalyst and hydroquinone delivered into the second fixed bed reactor (16) is controlled so that the molar ratio of 2,6-dichloro-quinoxaline to hydroquinone is in the range of 1:1.1-1.

5.

8. A fully continuous flow process for the preparation of pyriofenone according to claim 1, characterized in that, In step (6), the flow rate ratio of the 4-(6-chloro-2-quinoxalinyloxy)phenol solution obtained in step (4) to the mixed solution of the catalyst and (S)-2-chloropropionic acid ethyl ester delivered into the third fixed bed reactor (18) is controlled so that the molar ratio of 4-(6-chloro-2-quinoxalinyloxy)phenol to (S)-2-chloropropionic acid ethyl ester is in the range of 1:1.2-1.

8.

9. A fully continuous flow process for the preparation of pyriofenone according to claim 1, characterized in that, The first micromixer (1), the second micromixer (5), the third micromixer (8), the fourth micromixer (10), the fifth micromixer (15) and the sixth micromixer (17) are any one of a T-shaped micromixer, a Y-shaped micromixer, a cross-shaped micromixer.

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