Full-continuous flow preparation method of quizalofop-p-ethyl

Abstract

The invention discloses a fully continuous flow preparation method of quizalofop-p-ethyl. The method comprises the following steps: conveying a chloro-o-nitroaniline solution and hydrogen into a fixed bed reactor, carrying out a continuous catalytic hydrogenation reaction, conveying an obtained 4-chloro-o-phenylenediamine reaction mixed solution and an ethyl glyoxylate solution into a micro-channel mixer and a reactor, and carrying out a continuous cyclization reaction, the obtained 2-hydroxy-6-chloroquinoxaline turbid liquid enters a continuous online filtering device, the mixed liquid and phosphorus oxychloride are conveyed to a micro-mixer and a continuous flow reactor through a peristaltic pump, and the flowing-out reaction liquid and hydroquinone / catalyst mixed liquid are conveyed to another fixed bed reactor for continuous etherification; a reaction mixed solution and (S)-2-ethyl chloropropionate enter a fixed bed reactor for a continuous etherification reaction; the product quizalofop-p-ethyl is obtained; compared with a traditional intermittent kettle type synthesis method, the method disclosed by the invention is short in reaction time, high in product yield, high in automation degree, high in process continuous efficiency, high in space-time yield, low in energy consumption and easy to industrially amplify and apply.

Description

Technical Field

[0001] The present invention belongs to the technical field of pesticide synthesis, and particularly relates to a fully continuous flow preparation method of quizalofop-P-ethyl. Background Art

[0002] Quizalofop-P-ethyl, also known as quizalofop-P, is an aryloxyphenoxypropionate herbicide developed by Nissan Chemical Industries, Ltd. in Japan. Its chemical name is ethyl (R)-2-[4-(6-chloroquinoxalin-2-yloxy)]propionate, and its specific structure is as follows: .

[0003] At present, the traditional industrial route is as follows: Using 4-chloro-o-nitroaniline and diketene as raw materials, through condensation, cyclization, reduction, chlorination, and two-step etherification with hydroquinone to obtain quizalofop-P-ethyl. In the cyclization and etherification processes of this route, a strong alkaline aqueous solution is required, generating a large amount of waste salts and resulting in high environmental protection costs; both the cyclization and etherification processes are heterogeneous reactions and solid by-products are generated, requiring relatively high requirements for continuous flow equipment and a relatively long reaction time. Summary of the Invention

[0004] In order to overcome the deficiencies of the traditional batch kettle synthesis method, such as long reaction time, large safety hazards, high energy consumption, and low efficiency, the purpose of the present invention is to provide a fully continuous flow preparation method of quizalofop-P-ethyl. The reaction time of this method is greatly shortened, the yield and production efficiency of the product quizalofop-P-ethyl are significantly improved, the degree of automation of the process is significantly increased, the energy consumption is greatly reduced, the safety is greatly enhanced, the environmental protection cost is reduced, and it is easy to be applied industrially.

[0005] The specific technical solution is as follows: A fully continuous flow preparation method of quizalofop-P-ethyl, the specific steps are as follows: (1) The chlorinated o-nitroaniline solution and hydrogen are respectively introduced into the first micro mixer for mixing, and then enter the first fixed bed reactor equipped with a metal catalyst for continuous hydrogenation reaction to obtain 4-chloro-o-phenylenediamine material, and the material enters the first receiving tank; (2) The 4-chloro-o-phenylenediamine material flowing out from the first receiving tank in step (1) and the ethyl glyoxylate solution are respectively introduced into the second micro mixer for mixing, and then enter the first micro reactor for continuous cyclization reaction. The product suspension flowing out is mixed with toluene through an on-line filtering device to obtain a toluene suspension of 2-hydroxy-6-chloroquinoxaline; (3) The 2-hydroxy-6-chloroquinoxaline toluene suspension and the phosphorus oxychloride solution flowing out from the online filtration device in step (2) enter the third micro-mixer for mixing respectively, and then enter the second micro-reactor for continuous chlorination reaction; after the product is neutralized with alkali in the third micro-reactor, it is extracted and separated by a continuous extraction separator to obtain a 2,6-dichloroquinoxaline toluene solution; (4) The 2,6-dichloroquinoxaline toluene solution is fed into a solvent switching device for solvent switching to obtain a N,N-dimethylformamide solution of 2,6-dichloroquinoxaline; (5) The N,N-dimethylformamide solution of 2,6-dichloroquinoxaline flowing out from the solvent switching device in step (4) and hydroquinone / catalyst are respectively transported to the fifth micro-mixer for mixing, and then enter the second fixed-bed reactor filled with potassium carbonate for continuous etherification reaction to obtain a material of 4-(6-chloro-2-quinoxalinoxy)phenol; (6) The material of 4-(6-chloro-2-quinoxalinoxy)phenol flowing out from the second fixed-bed reactor in step (5) and the catalyst / (S)-ethyl 2-chloropropionate reaction solution enter the sixth micro-mixer for mixing respectively, and then enter the third fixed-bed reactor for continuous etherification reaction to obtain a solution of the target product quizalofop-p-ethyl.

[0006] Further, the chloro-o-nitroaniline in step (1) is 4-chloro-2-nitroaniline or 5-chloro-2-nitroaniline; the solvent in the chloro-o-nitroaniline solution is any one of methanol, ethanol, and isopropanol; the metal catalyst is a Raney Nickel catalyst.

[0007] Further, in step (1), the flow rate of the chloro-o-nitroaniline solution fed into the first fixed-bed reactor is controlled so that the liquid flow rate is in the range of 1.5 - 2.5 mL / min; the hydrogen flow rate fed into the first micro-mixer is controlled so that the hydrogen flow rate is in the range of 35 - 50 sccm; the temperature in the first fixed-bed reactor is controlled at 15 - 35 °C; the residence time of the mixed reaction material in the first fixed-bed reactor is 30 - 60 s; the back pressure during the reaction is 0.5 - 2.0 MPa.

[0008] 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-o-phenylenediamine solution obtained in step (1) and the ethyl glyoxylate solution fed into the first micro-reactor is controlled so that the molar ratio of 4-chloro-o-phenylenediamine to ethyl glyoxylate is in the range of 1:1.05 - 1.2; the temperature in the first micro-reactor is controlled at 60 - 100 °C; the residence time of the mixed reaction material in the first micro-reactor is 10 - 20 min; the back pressure during the reaction is 0.2 - 1 MPa.

[0009] Further, in step (3), control the flow rate ratio of the 2-hydroxy-6-chloroquinoxaline toluene suspension obtained in step (2) and the phosphorus oxychloride solution fed into the second microreactor, so that the molar ratio of 2-hydroxy-6-chloroquinoxaline to phosphorus oxychloride is in the range of 1:0.8 to 1.5; control the temperature in the third micromixer and the second microreactor within the range of 80 to 105 °C; the residence time of the mixed reaction materials in the second microreactor is 5 to 10 min; the residence time of the crude product mixture in the continuous extraction separator is 0.1 to 20 min; control the temperature in the continuous extraction separator to be 30 to 50 °C.

[0010] Further, in step (4), control the temperature in the solvent switching device to be 110 to 115 °C, and at the same time, purge with nitrogen. The toluene vapor is recovered by the reflux device, and the solvent N,N-dimethylformamide is introduced to obtain the N,N-dimethylformamide solution of 2,6-dichloroquinoxaline. Further, in step (5), control the flow rate ratio of the 2,6-dichloroquinoxaline solution obtained in step (4) and the mixed solution of the catalyst / hydroquinone fed into the second fixed-bed reactor, so that the molar ratio of 2,6-dichloroquinoxaline to hydroquinone is in the range of 1:1.1 to 1.5; control the temperature in the second fixed-bed reactor to be 100 to 130 °C; the residence time of the mixed materials in the second fixed-bed reactor is 2.5 to 6.7 min.

[0011] Further, in step (6), control the flow rate ratio of the solution of 4-(6-chloro-2-quinoxalinoxy)phenol obtained in step (4) and the mixed solution of the catalyst / (S)-ethyl 2-chloropropionate fed into the third fixed-bed reactor, so that the molar ratio of 4-(6-chloro-2-quinoxalinoxy)phenol to (S)-ethyl 2-chloropropionate is in the range of 1:1.2 to 1.8; control the temperature in the third fixed-bed reactor to be 75 to 120 °C; the residence time of the mixed materials in the third fixed-bed reactor is 3.0 to 13.0 min.

[0012] Further, the filler in the second fixed-bed reactor and the third fixed-bed reactor is any one of potassium carbonate, sodium hydroxide, and potassium hydroxide, and the catalyst described in steps (5) and (6) is tetrabutylammonium chloride or tetrabutylammonium bromide.

[0013] Further, the first micromixer, the second micromixer, the third micromixer, the fourth micromixer, the fifth micromixer, and the sixth micromixer are any one of a T-shaped micromixer, a Y-shaped micromixer, and a cross-shaped micromixer.

[0014] Advantages of the present invention (1) Abandon the traditional industrial route and choose a new process with a shorter synthetic route, making the reaction more environmentally friendly, the solvent recyclable, with higher economic benefits and greater industrialization potential.

[0015] (2) The fully continuous flow microchannel reaction system has excellent mass transfer, heat transfer and material molecule mixing performance, greatly shortening the reaction time and significantly improving the reaction efficiency. The total synthesis of quizalofop-p-ethyl can be completed in about 2 hours, shortened from several days of the traditional batch kettle reaction. (3) The continuous liquid-liquid quenching, continuous liquid-liquid extraction and continuous liquid-liquid separation of the reaction liquid are easy to operate in the continuous flow process, with a fast quenching speed, a safe process, good separation effect, high extraction efficiency, and the separation yield close to the reaction yield. The continuous progress of the reaction process and the liquid-liquid extraction and separation process greatly improves the total process efficiency, and the obtained product has high purity. (4) Realize the continuous synthesis from raw materials to products. The process is continuously carried out without interruption, with a high degree of automation, no need for external intervention in the middle, high space-time efficiency, greatly reducing the number of operators and labor intensity, and significantly reducing production costs. (5) Adopting the fully continuous flow microchannel chemical process can realize the multiphase mixing, mass transfer and reaction process in the micro mixer and microchannel reactor. The conditions are mild, the operation is simple, no stirring device is needed, the energy consumption of the process is greatly reduced, and industrial production can be quickly realized. Brief Description of the Drawings

[0016] Figure 1 It is a schematic flow chart of the present invention In the figure: 1. The first micro mixer; 2. The first fixed bed reactor; 3. The gas-liquid separator; 4. The first receiving tank; 5. The second micro mixer; 6. The first micro reactor; 7. The online filtering device; 8. The third micro mixer; 9. The second micro reactor; 10. The fourth micro mixer; 11. The third micro reactor; 12. The continuous extraction device; 13. The solvent switching device; 14. The second receiving tank; 15. The fifth micro mixer; 16. The second fixed bed reactor; 17. The sixth micro mixer; 18. The third fixed bed reactor. Specific Embodiments

[0017] To describe in detail the technical content, structural features, achieved objectives and effects of the technical solution, the following further explains with specific embodiments in conjunction with the drawings. This embodiment is implemented on the premise of the technical solution of the present invention, and gives detailed implementation manners and specific operation processes, but the protection scope of the present invention is not limited to the following embodiments.

[0018] The reaction equation of the present invention is as follows:

[0019] The reaction process is asFigure 1 As shown in the figure, it includes the following steps: Chlorinated o-nitroaniline and a hydrogen source are mixed by a first micro-mixer 1 and then enter a first fixed-bed reactor 2 filled with a metal catalyst Raney Nickel for reaction. Then, they are separated by a gas-liquid separator 3. The separated 4-chloro-o-phenylenediamine flows into a first receiving tank 4. Then, it is mixed with ethyl glyoxylate by a second micro-mixer 5 and enters a first micro-reactor 6 for reaction. The resulting reaction solution enters an online filtering device 7 and is mixed with toluene to obtain a 2-hydroxy-6-chloroquinoxaline toluene suspension. The 2-hydroxy-6-chloroquinoxaline toluene suspension and phosphorus oxychloride solution are mixed by a third micro-mixer 8 and enter a second micro-reactor 9 for reaction. The resulting reaction solution and sodium hydroxide are mixed by a fourth micro-mixer 10 and enter a third micro-reactor 11 for neutralization. The mixed solution is transported to a continuous extraction separator 12. The aqueous phase flows out from the heavy-phase outlet of the continuous extraction device 12. The organic phase containing the product 2,6-dichloroquinoxaline flows out from the light-phase outlet of the continuous extraction device 12 to a solvent switching device 13. Nitrogen is introduced for purging. The toluene vapor is recovered by a reflux device. Solvent N,N-dimethylformamide is introduced to obtain an N,N-dimethylformamide solution of 2,6-dichloroquinoxaline, which is received by a second receiving tank 14. Then, it is mixed with a mixed solution of a catalyst (5 mol%) / hydroquinone in N,N-dimethylformamide in a fifth micro-mixer 15 and enters a second fixed-bed reactor 16 for reaction to obtain an N,N-dimethylformamide solution of 4-(6-chloro-2-quinoxalinoxy)phenol. It is mixed with a mixed solution of a catalyst / (S)-ethyl 2-chloropropionate in N,N-dimethylformamide in a sixth micro-mixer 17 and enters a third fixed-bed reactor 18 for reaction to obtain quizalofop-p-ethyl.

[0020] Example 1: Total continuous flow synthesis of quizalofop-p-ethyl The micro-mixer in this example is a T-shaped micro-mixer A methanol solution of 4-chloro-2-nitroaniline (0.2 M) and hydrogen (50 sccm) are respectively and simultaneously transported into a first micro-mixer 1 at a flow rate of 2.5 mL / min for mixing and then input into a first fixed-bed reactor 2 (the reaction volume is 10.0 ml, filled with 15 g of Raney Nickel catalyst). The back pressure value of the back pressure valve is set to 1.0 Mpa. The temperature of the first fixed-bed reactor 2 is controlled at 25°C. After reacting for 60 s (i.e., the residence time of the mixed reaction materials in the first fixed-bed reactor 2 is 60 s), the mixed reaction materials flow out from the outlet of the first fixed-bed reactor 2. After separating the gas components by a gas-liquid separator 3, they are collected by a first receiving tank 4. Sampling and detection show that the conversion rate of 4-chloro-2-nitroaniline is 100%. At this time, a methanol solution of 4-chloro-o-phenylenediamine (0.2 M) is obtained.

[0021] The methanol solution of 4-chloro-o-phenylenediamine (0.2 M) obtained in the previous step and the methanol solution of ethyl glyoxylate (1.2 equivalents, 0.24 M) are respectively fed into the second micromixer 5 for mixing and then input into the first microreactor for cyclization reaction. The back pressure valve is set at 0.5 MPa, the temperature of the microreactor is controlled at 90 °C. After reacting for 15 min (i.e., the residence time of the mixed reaction materials in the first microreactor 6 is 15 min), the mixed reaction materials flow out through the outlet and are mixed with toluene through the online filter device 7 to obtain a toluene suspension of 2-hydroxy-6-chloroquinoxaline.

[0022] The toluene suspension of 2-hydroxy-6-chloroquinoxaline obtained in the previous step is transported to the third micromixer 8 by a peristaltic pump. At the same time, a toluene solution of phosphorus oxychloride is transported to the third micromixer 8 by a polytetrafluoroethylene plunger pump. After the two streams of materials are mixed, they enter the second microreactor 9. By calibrating the flow rate of the peristaltic pump, the molar ratio of 2-hydroxy-6-chloroquinoxaline to phosphorus oxychloride is controlled at 1:1.2. The temperatures of the third micromixer 8 and the second microreactor 9 are controlled at 95 °C. After reacting for 10 min (i.e., the residence time of the mixed reaction materials in the second microreactor 9 is 10 min), the mixed materials flow out of the second microreactor 9 and are transported to the fourth micromixer 10 together with a 5 M sodium hydroxide solution for mixing and then enter the third microreactor 11 for neutralization. The mixed solution is transported to a continuous extraction separator 12. The temperature in the continuous extraction separator is controlled at 30 °C, and the liquid stays in the continuous extraction separator for 10 min. The aqueous phase flows out from the heavy phase outlet of the continuous extraction device 12, and the organic phase containing the product 2,6-dichloroquinoxaline flows out from the light phase outlet of the continuous extraction device 12.

[0023] The organic phase of 2,6-dichloroquinoxaline from the previous step is transported to the solvent switching device 13. The temperature in the solvent switching device 13 is controlled at 110 - 115 °C, and nitrogen is simultaneously introduced for purging. The toluene vapor is recovered through the reflux device, and the solvent N,N-dimethylformamide is introduced to obtain an N,N-dimethylformamide solution (0.2 M) of 2,6-dichloroquinoxaline. The N,N-dimethylformamide solution of 2,6-dichloroquinoxaline (1.0 equivalent, 0.2 M) obtained in the previous step and the N,N-dimethylformamide mixed solution of tetrabutylammonium chloride (5 mol%) / hydroquinone (1.2 equivalents, 0.24 M) are respectively transported to the fifth micromixer 15 for mixing, and then enter the second fixed bed reactor 16 (filled with potassium carbonate). The temperature in the second fixed bed reactor 16 is controlled at 120 °C. After reacting for 6 min (i.e., the residence time of the mixed reaction materials in the second fixed bed reactor 16 is 6 min), the mixed materials flow out of the second fixed bed reactor 16 to obtain an N,N-dimethylformamide solution (0.2 M) of 4-(6-chloro-2-quinoxalinoxy)phenol. The N,N-dimethylformamide solution of 4-(6-chloro-2-quinoxalinoxy)phenol (1.0 equivalent, 0.2 M) obtained in the previous step and the mixed solution of tetrabutylammonium chloride (5 mol%) / (S)-ethyl 2-chloropropionate in N,N-dimethylformamide (1.5 equivalents, 0.3 M) were respectively fed into the sixth micromixer 17 for mixing, and then entered 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 reacting for 12 min (i.e., the residence time of the mixed reaction materials in the third fixed-bed reactor 18 was 12 min), it flowed out from the third fixed-bed reactor 18. The N,N-dimethylformamide solution of 4-(6-chloro-2-quinoxalinoxy)phenol was collected in the product storage buffer tank. The collected reaction solution was purified to obtain quizalofop-p-ethyl. The overall yield of the multi-step microreaction continuous flow was 45%, and the optical purity of the product was 91% ee 。

[0024] Example 2 The operation of this example was the same as that of Example 1, except that the micromixer used in the reaction in this example was a Y-type micromixer and the starting material was 5-chloro-2-nitroaniline. The overall yield of the obtained product quizalofop-p-ethyl in this example was 45%, and the optical purity of the product was 91% ee 。

[0025] Example 3 The operation of this example was the same as that of Example 1, except that the solutions of 4-chloro-2-nitroaniline and ethyl glyoxylate in this example were ethanol solutions. The overall yield of the obtained product quizalofop-p-ethyl in this example was 42%, and the optical purity of the product was 92% ee 。

[0026] Example 4 The operation of this example was the same as that of Example 1, except that the catalyst tetrabutylammonium chloride was replaced by tetrabutylammonium bromide in this example. The overall yield of the obtained product quizalofop-p-ethyl in this example was 47%, and the optical purity of the product was 88% ee 。

[0027] Example 5 The operation of this example was 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 were sodium hydroxide. The overall yield of the obtained product quizalofop-p-ethyl in this example was 40%, and the optical purity of the product was 82% ee 。

[0028] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit the protection scope of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A fully continuous flow preparation method of Quizalofop-P-ethyl, characterized in that: The specific steps are: (1) introducing the chloro-o-nitroaniline solution and hydrogen into a first micro-mixer (1) for mixing, and then entering a first fixed bed reactor (2) containing a metal catalyst for continuous hydrogenation reaction to obtain 4-chloro-o-phenylenediamine material, which enters a first receiving tank (4); (2) the 4-chloro-o-phenylenediamine material and the ethyl glyoxylate solution flowing out of the first receiving tank (4) in step (1) are respectively introduced into a second micro mixer (5) for mixing, and then enter into a first micro reactor (6) for continuous cyclization reaction, and the product suspension flowing out is mixed with toluene through an online filter device (7) to obtain a toluene suspension of 2-hydroxy-6-chloroquinoxaline; (3) the 2-hydroxy-6-chloroquinoxaline toluene suspension and the phosphorus oxychloride solution flowing out of the online filtration device (7) in step (2) are respectively mixed in a third micro mixer (8), and then enter the second micro reactor (9) to perform a continuous chlorination reaction; the product and the base are neutralized in the third micro reactor (11), and then extracted and separated in a continuous extraction separator (12) to obtain a 2,6-dichloroquinoxaline toluene solution; (4) the 2,6-dichloroquinoxaline toluene solution is flowed into a solvent switching device (13) to perform solvent switching to obtain an N,N-dimethylformamide solution of 2,6-dichloroquinoxaline; (5) The N,N-dimethylformamide solution of 2,6-dichloroquinoxaline and the hydroquinone / catalyst discharged from the solvent switching device (13) in step (4) are respectively transported to a fifth micro mixer (15) for mixing, and then enter a second fixed bed reactor (16) filled with potassium carbonate to perform a continuous etherification reaction to obtain a material of 4-(6-chloro-2-quinoxalineoxy)phenol; (6) The 4-(6-chloro-2-quinoxalineoxy)phenol material and the catalyst / (S)-ethyl 2-chloropropionate reaction solution flowing out of the second fixed bed reactor (16) in step (5) are respectively introduced into a sixth micro-mixer (17) for mixing, and then introduced into a third fixed bed reactor (18) for continuous etherification reaction to obtain a target product, quizalofop-p-ethyl solution.

2. The fully continuous flow preparation method of Quizalofop-P-ethyl according to claim 1, characterized in that: The chloro-o-nitroaniline in step (1) is 4-chloro-2-nitroaniline or 5-chloro-2-nitroaniline; the solvent in the chloro-o-nitroaniline solution is any one of methanol, ethanol and isopropanol; and the metal catalyst is a Raney Nickel catalyst.

3. A fully continuous flow preparation method of Quizalofop-ethyl according to claim 1, characterized in that, In step (1), the flow rate of the chloro-o-nitroaniline solution delivered to 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 the hydrogen delivered to the first micro-mixer (1) is controlled so that the flow rate of the hydrogen is in the range of 35-50 sccm; the temperature in the first fixed bed reactor (2) is controlled at 15-35° C.; the residence time of the mixed reaction materials in the first fixed bed reactor (2) is 30-60 s; and the back pressure during the reaction is 0.5-2.0 MPa.

4. The fully continuous flow preparation method of Quizalofop-Ph-ethyl according to claim 1, characterized in that: The ethyl glyoxylate solution in step (2) is ethyl glyoxylate dissolved in methanol or ethanol, and the flow ratio of the 4-chloro-o-phenylenediamine solution obtained in step (1) and the ethyl glyoxylate solution transported into the first microreactor (6) is controlled so that the molar ratio of 4-chloro-o-phenylenediamine to ethyl glyoxylate is in the range of 1:1.05-1.2; the temperature in the first microreactor (6) is controlled at 60-100° C.; the residence time of the mixed reaction materials in the first microreactor (6) is 10-20 min; and the back pressure during the reaction is 0.2-1 MPa.

5. The fully continuous flow preparation method of Quizalofop-P-ethyl according to claim 1, characterized in that: In step (3), the flow ratio of the 2-hydroxy-6-chloroquinoxaline toluene suspension obtained in step (2) and the phosphorus oxychloride solution transported to the second microreactor (9) is controlled so that the molar ratio of 2-hydroxy-6-chloroquinoxaline to phosphorus oxychloride is in the range of 1:0.8-1.5; the temperature in the third micromixer (8) and the second microreactor (9) is controlled in the range of 80-105° C.; the residence time of the mixed reaction material in the second microreactor (9) is 5-10 min; the residence time of the crude product mixture in the continuous extraction separator (12) is 0.1-20 min; and the temperature in the continuous extraction separator (12) is controlled in the range of 30-50° C.

6. The fully continuous flow preparation method of Quizalofop-Ph-ethyl according to claim 1, characterized in that: In step (4), the temperature in the solvent switching device (13) is controlled at 110-115°C, nitrogen is introduced for purging, toluene vapor is recovered through a reflux device, and solvent N,N-dimethylformamide is introduced to obtain an N,N-dimethylformamide solution of 2,6-dichloroquinoxaline.

7. The fully continuous flow preparation method of Quizalofop-Ph-ethyl according to claim 1, characterized in that: In step (5), the flow ratio of the 2,6-dichloroquinoxaline solution obtained in step (4) and the mixed solution of catalyst / hydroquinone transported to the second fixed bed reactor (16) is controlled so that the molar ratio of 2,6-dichloroquinoxaline to hydroquinone is in the range of 1:1.1 to 1.5; the temperature in the second fixed bed reactor (16) is controlled at 100 to 130° C.; and the residence time of the mixed material in the second fixed bed reactor (16) is 2.5 to 6.7 min.

8. The fully continuous flow preparation method of Quizalofop-Ph-ethyl according to claim 1, characterized in that: In step (6), the flow ratio of the solution of 4-(6-chloro-2-quinoxalineoxy)phenol obtained in step (4) to the mixed solution of catalyst / (S)-ethyl 2-chloropropionate transported to the third fixed bed reactor (18) is controlled so that the molar ratio of 4-(6-chloro-2-quinoxalineoxy)phenol to (S)-ethyl 2-chloropropionate is in the range of 1:1.2 to 1.8; the temperature in the third fixed bed reactor (18) is controlled at 75 to 120° C.; and the residence time of the mixed material in the third fixed bed reactor (18) is 3.0 to 13.0 min.

9. The fully continuous flow preparation method of Quizalofop-Ph-ethyl according to claim 1, characterized in that: The filling material in the second fixed bed reactor (16) and the third fixed bed reactor (18) is any one of potassium carbonate, sodium hydroxide and potassium hydroxide, and the catalyst in step (5) and step (6) is tetrabutylammonium chloride or tetrabutylammonium bromide.

10. The fully continuous flow preparation method of Quizalofop-Ph-ethyl 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-type micromixer, a Y-type micromixer and a cross-type micromixer.

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