A replaceable packing type continuous flow microreactor device and its application in the preparation of amide reaction

Abstract

The application discloses a replaceable filler type continuous flow micro-reactor device and application thereof in amide reaction preparation. The replaceable filler type continuous flow micro-reactor device comprises a micro-reactor; the top of the micro-reactor is communicated with a liquid pipeline system and a gas pipeline system respectively, and the bottom of the micro-reactor is connected with a cooling and product collecting system; the micro-reactor is a filler type micro-reaction tube, the filler type micro-reaction tube comprises a tube body, the tube body is internally filled with replaceable porous fillers; the upper and lower ends of the tube body are respectively provided with filter screen plates for intercepting porous fillers with different sizes, and the filter screen plates at the two ends are respectively connected with material inlet and outlet joints through fixing members. The application provides the application of the replaceable filler type continuous flow micro-reactor device in amide reaction preparation, solves the problems of frequent replacement, easy blockage and high production cost of ordinary micro-reactors in amide reaction preparation, and can improve the reaction efficiency and selectivity.

Description

Technical Field

[0001] This invention relates to a replaceable packing type continuous flow microreactor device and its application in the preparation of amides, belonging to the field of fine chemical technology. Background Technology

[0002] Amide structures, as one of the most important structural units in organic chemistry, biochemistry, and materials chemistry, have wide applications in pharmaceuticals, pesticides, and materials. Common synthetic strategies for amides involve reacting carboxylic acid derivatives (such as acyl chlorides, anhydrides, or esters) with amines, or directly dehydrating and condensing carboxylic acids with amines in the presence of an stoichiometric condensing agent (such as carbonyl imidazole). While these methods are highly efficient, they require expensive and toxic raw materials, generate large amounts of byproducts, have poor atom economy, and are environmentally unfriendly, failing to meet the requirements of green and sustainable chemistry. Therefore, establishing new green and sustainable synthetic strategies for constructing amide modules is an urgent need in the field of organic synthesis.

[0003] Chinese patent CN115594603A discloses a method for preparing N-tert-butyl-4-aminobenzamide using a microchannel reactor. This invention reduces pollution from waste gas, wastewater, and solid waste, is environmentally friendly, and achieves high synthesis yield. It involves powerful mixing of N-tert-butyl-4-nitrobenzamide solution and hydrogen in the microchannel reactor, ensuring safety, reliability, and high efficiency. Chinese patent CN118221543A discloses a method for preparing 4-aminobenzamide compounds using a microchannel reactor. This invention uses p-nitrobenzate and amine compounds as raw materials, synthesizing 4-aminobenzamide compounds in one step via a microchannel reactor in the presence of a catalyst and hydrogen. This method is not only simple to operate, highly safe, and environmentally friendly, but also significantly reduces the amount of amine compounds used, thus saving raw material costs and reducing recycling difficulties, making it suitable for large-scale industrial production. However, the aforementioned microreactors have complex structures, leading to frequent and difficult reactor replacements and a tendency to clog.

[0004] Therefore, it is necessary to optimize the design of a microreactor that is easy to control and replace internally in order to achieve more stable and durable microreactor operation, so that it can be better applied to the reaction for amide preparation. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide a simple continuous flow microreactor device with replaceable packing and its application in the preparation of amides. This device solves the problems of frequent replacement, easy clogging, and high production costs of ordinary microreactors in the preparation of amides, and can improve the efficiency and selectivity of the reaction.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] In a first aspect, the present invention provides a replaceable packing type continuous flow microreactor device, comprising a liquid pipeline system, a gas pipeline system, a microreactor, and a cooling and product collection system; the top of the microreactor is connected to the liquid pipeline system and the gas pipeline system respectively, and the bottom of the microreactor is connected to the cooling and product collection system; wherein:

[0008] The microreactor is a packed microreactor tube, which includes a tube body filled with replaceable porous packing material, which has both microporous and mesoporous structures. Filter screens for trapping porous packing material of different sizes are respectively provided at the upper and lower ends of the tube body. The filter screens at both ends are connected to material inlet / outlet connectors via fixing components to stabilize the packing material. A cutting edge ring and a sealing ring are sequentially arranged between the fixing components and the tube body from top to bottom.

[0009] Furthermore, the size of the holes in the filter screen plate is adjustable.

[0010] Furthermore, the inner diameter of the tube is 0.1-10 mm.

[0011] Furthermore, the inner diameter of the tube can be one of 0.25 mm, 0.32 mm, 0.53 mm, 2.1 mm, 3.0 mm or 4.6 mm.

[0012] Furthermore, the particle size range of the porous filler is 0.1-1000 micrometers.

[0013] Furthermore, the fastener is a connecting screw.

[0014] Furthermore, the liquid piping system includes a raw material tank and a feed pump connected via a liquid pipeline, and the feed pump is connected to the top of the microreactor via the liquid pipeline.

[0015] Furthermore, the gas pipeline system includes a gas cylinder and a gas flow meter, which are connected by a gas pipeline, and the gas flow meter is connected to the top of the microreactor via the gas pipeline.

[0016] Secondly, the present invention provides a method for preparing amide compounds, wherein the preparation method uses the replaceable packing continuous flow microreactor device described in the first aspect, and the preparation method includes the following steps:

[0017] (1) Dissolve the ketoxime compound and triethylamine in acetonitrile to prepare a reaction solution;

[0018] (2) The reaction solution prepared in step (1) and SO2F2 gas are introduced into the microreactor through the liquid pipeline system and the gas pipeline system, respectively, and the Beckmann rearrangement reaction is carried out at 20-30℃. The reaction solution flow rate is controlled at 0.01-2.5 ml / min, the gas flow rate is controlled at 0.01-2.5 ml / min, and the microreactor pressure is controlled at 0.1-0.5 MPa to control the residence time of the reaction solution to 10-60 minutes, that is, the reaction time is 10-60 minutes.

[0019] (3) After the reaction is completed, the reaction liquid flows out of the microreactor outlet and is collected by the cooling and product collection system. The collected reaction liquid is then post-processed to obtain amide compounds.

[0020] Preferably, the ketoxime compounds are benzophenone oxime, cyclohexanone oxime, 4-phenylbutyl-3-ene-2-one oxime, acetophenone oxime, cyclohexane-1-one oxime, and 1-(4-aminophenyl)ethane-1-one oxime.

[0021] Preferably, the porous filler is selected from porous Al2O3, porous SiO2, porous ZrO2, TS-1, HTS-1, ETS-10, and COF.

[0022] Preferably, the particle size range of the porous filler is 0.1-1000 micrometers.

[0023] Preferably, the molar ratio of the ketoxime compound to triethylamine is 1:1 to 1:2.

[0024] Preferably, the post-processing includes the following steps: after concentrating the reaction solution, it is extracted with water and ethyl acetate (1:1 volume ratio), the organic phase is concentrated to obtain a crude product, and the crude product is recrystallized from ethyl acetate / petroleum ether to obtain amide compounds.

[0025] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0026] (1) Ordinary fixed-bed reactors can only be filled with large particle packing, while the replaceable packing simple continuous flow microreactor of the present invention can be filled with small particle powder.

[0027] (2) The replaceable packing continuous flow microreactor of the present invention has low requirements for the mechanical strength of the packing.

[0028] (3) The replaceable packing continuous flow microreactor of the present invention can be updated by replacing the packing.

[0029] (4) Different sizes of particle packing material in the replaceable packing continuous flow microreactor described in this invention can be used in combination.

[0030] (5) The replaceable packing continuous flow microreactor of the present invention is inexpensive.

[0031] (6) The replaceable packing continuous flow microreactor device of the present invention is applied to the preparation of amide compounds and can obtain higher product yields compared with conventional microreactors. Attached Figure Description

[0032] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0033] Figure 1 This is a schematic diagram of the packing-type microreactor described in this invention. Figure 1 ;

[0034] Figure 2 This is a schematic diagram of the packing-type microreactor described in this invention. Figure 2 ;

[0035] Figure 3 This is an enlarged schematic diagram of the connecting screws and filter in the microreactor structure;

[0036] Figure 4 This is an overall schematic diagram of the replaceable packing type continuous flow microreactor device described in this invention.

[0037] The accompanying diagrams are labeled as follows:

[0038] 1-Liquid piping system; 2-Gas piping system; 3-Microreactor; 4-Cooling and product collection system; 11-Raw material tank; 12-Feed pump; 21-Gas cylinder; 22-Gas flow meter; 31-Pipe body; 32-Porous packing; 33-Filter sieve plate; 34-Material inlet / outlet connector; 35-Fixed component; 36-Blade ring; 37-Sealing ring.

[0039] Figures 5-10 The following are, in order, nitrogen adsorption-desorption curves of porous Al2O3, porous SiO2, porous ZrO2, TS-1, HTS-1, and COF used in the examples. Detailed Implementation

[0040] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the embodiments.

[0041] refer to Figures 1 to 4This invention provides a replaceable packing type continuous flow microreactor device, including a liquid pipeline system 1, a gas pipeline system 2, a microreactor 3, and a cooling and product collection system 4; the top of the microreactor 3 is connected to the liquid pipeline system 1 and the gas pipeline system 2 respectively, and the bottom of the microreactor 3 is connected to the cooling and product collection system 4; wherein:

[0042] The microreactor 3 is a packed microreactor tube, which includes a tube body 31. The tube body 31 is filled with replaceable porous packing material 32, which has both microporous and mesoporous structures. The upper and lower ends of the tube body 31 are respectively provided with filter screen plates 33 for retaining porous packing material of different sizes. The filter screen plates 33 at both ends are respectively connected to the material inlet / outlet connector 34 through fixing parts 35 to stabilize the packing material. A blade ring 36 and a sealing ring 37 are arranged between the fixing part 35 and the tube body 31 from top to bottom.

[0043] Specifically, the hole size of the filter screen 33 plate is adjustable.

[0044] Specifically, the inner diameter of the tube 31 is 0.1-10 mm.

[0045] More specifically, the inner diameter of the tube 31 can be one of 0.25 mm, 0.32 mm, 0.53 mm, 2.1 mm, 3.0 mm or 4.6 mm.

[0046] Specifically, the particle size range of the porous filler 32 is 0.1-1000 micrometers.

[0047] Specifically, the fastener 35 is a connecting screw.

[0048] Specifically, the liquid pipeline system 1 includes a raw material tank 11 and a feed pump 12, which are connected by a liquid pipeline and the feed pump 12 is connected to the top of the microreactor 3 via the liquid pipeline.

[0049] Specifically, the gas pipeline system 2 includes a gas cylinder 21 and a gas flow meter 22, which are connected by a gas pipeline and the gas flow meter 22 is connected to the top of the microreactor 3 through the gas pipeline 2.

[0050] The preparation of amide compounds using the above-mentioned microreactor device is illustrated in the following specific examples:

[0051] Example 1:

[0052] Benzophenone oxime (19.7 g, 0.1 mol, 1.0 equivalent) and triethylamine (27.75 mL, 0.2 mmol, 2.0 equivalent) were dissolved in CH3CN (500 mL, 0.2 M) to prepare a reaction solution, which was then added to a raw material tank. The reaction solution and SO2F2 gas were fed into a packed microreactor (microreactor inner diameter 2.1 mm, length 30 cm) via a liquid-phase feed pump and a gas pipeline system, respectively, and the reaction was carried out at a reaction temperature of 20-30℃. The residence time of the reaction solution was controlled to be 10 minutes by adjusting the feed pump to control the reaction solution flow rate at 0.5 ml / min, the gas flow meter to control the gas flow rate at 0.5 ml / min, and the back pressure valve to control the microreactor pressure at 0.1 MPa. After the reaction was completed, the reaction solution flowed out of the reactor outlet and was collected in a collection tank, while the reaction tail gas was collected by a tail gas collection device. After concentration, the reaction solution was extracted with 500 mL of ethyl acetate / water (1:1 volume ratio), and the organic phase was concentrated to obtain 19.0 g of crude product. Recrystallization of the crude product from ethyl acetate / petroleum ether yielded 18.7 g of benzoylaniline, with a yield of 95%.

[0053] Table 1. Effect of different porous packing materials on the yield of benzoylaniline in the reaction of benzophenone oxime.

[0054]

[0055] Comparative Example 1:

[0056] The microchannel reactor used in the comparative example was a Corning microchannel reactor. G1SiC reactor. Benzophenone oxime (19.7 g, 0.1 mol, 1.0 equivalent) and triethylamine (27.75 mL, 0.2 mmol, 2.0 equivalent) were dissolved in CH3CN (500 mL, 0.2 M) to prepare the reaction solution, which was then added to the feed tank. The reaction solution and SO2F2 gas were introduced into the microchannel reactor via a liquid-phase feed pump and a gas pipeline system, respectively, and the reaction was carried out at a reaction temperature of 20-30℃. The residence time of the reaction solution was controlled to be 10 minutes by adjusting the flow rate of the reaction solution (15 mL / min) and the gas flow rate (15 mL / min) using a gas flow meter, and by controlling the microreactor pressure to 0.1 MPa using a back pressure valve. After the reaction was completed, the reaction solution flowed out of the reactor outlet and was collected in a collection tank, while the reaction tail gas was collected using a tail gas collection device. After concentration, the reaction solution was extracted with 500 mL of ethyl acetate / water (1:1 volume ratio), and the organic phase was concentrated to obtain 17.0 g of crude product. The crude product was recrystallized from ethyl acetate / petroleum ether to obtain 16.5 g of benzoylaniline, with a yield of 84%.

[0057] Table 2. Corning Comparison of yields of p-benzophenone oxime to benzoylaniline between G1SiC reactor and replaceable packed microreactor

[0058]

[0059]

[0060] Example 2:

[0061] Cyclohexanone oxime (11.3 g, 0.1 mol, 1.0 equivalent) and triethylamine (27.75 mL, 0.2 mmol, 2.0 equivalent) were dissolved in CH3CN (500 mL, 0.2 M) to prepare a reaction solution, which was then added to a raw material tank. The reaction solution and SO2F2 gas were fed into a packed microreactor (microreactor inner diameter 3 mm, length 30 cm) via a liquid-phase feed pump and a gas pipeline system, respectively, and the reaction was carried out at a reaction temperature of 20-30℃. The residence time of the reaction solution was controlled to be 10 minutes by adjusting the feed pump to maintain a reaction solution flow rate of 1 ml / min, the gas flow meter to maintain a gas flow rate of 1 ml / min, and the back pressure valve to maintain a microreactor pressure of 0.2 MPa. After the reaction was completed, the reaction solution flowed out of the reactor outlet and was collected in a collection tank, while the reaction tail gas was collected using a tail gas collection device. After concentration, the reaction solution was extracted with 500 mL of ethyl acetate / water (1:1 volume ratio), and the organic phase was concentrated to obtain 10.1 g of crude product. The crude product was recrystallized from ethyl acetate / petroleum ether to obtain 9.6 g of caprolactam, with a yield of 85%.

[0062] Table 3. Effect of different porous packing materials on the yield of cyclohexanone oxime to caprolactam

[0063]

[0064] Comparative Example 2:

[0065] The microchannel reactor used in the comparative example was a Corning microchannel reactor. G1SiC reactor. Cyclohexanone oxime (11.3 g, 0.1 mol, 1.0 equivalent) and triethylamine (27.75 mL, 0.2 mmol, 2.0 equivalent) were dissolved in CH3CN (500 mL, 0.2 M) to prepare the reaction solution, which was then added to the feed tank. The reaction solution and SO2F2 gas were introduced into the microchannel reactor via a liquid-phase feed pump and a gas pipeline system, respectively, and the reaction was carried out at a reaction temperature of 20-30℃. The residence time of the reaction solution was controlled to be 10 minutes by adjusting the flow rate of the reaction solution (15 mL / min) and the gas flow rate (15 mL / min) of the gas, and by controlling the pressure of the microreactor (0.2 MPa) of the back pressure valve. After the reaction was completed, the reaction solution flowed out of the reactor outlet and was collected in a collection tank, and the reaction tail gas was collected by a tail gas collection device. After concentration, the reaction solution was extracted with 500 mL of ethyl acetate / water (1:1 volume ratio), and the organic phase was concentrated to obtain 8.6 g of crude product. The crude product was recrystallized from ethyl acetate / petroleum ether to obtain 8.0 g of caprolactam, with a yield of 71%.

[0066] Table 4. Corning Comparison of yields of G1SiC microreactor and replaceable packing microreactor for the preparation of caprolactam from cyclohexanone oxime

[0067]

[0068] Example 3:

[0069] 4-Benzobutyl-3-en-2-one oxime (16.1 g, 0.1 mol, 1.0 equivalent) and triethylamine (27.75 mL, 0.2 mmol, 2.0 equivalent) were dissolved in CH3CN (500 mL, 0.2 M) to prepare a reaction solution, which was then added to a raw material tank. The reaction solution and SO2F2 gas were fed into a packed microreactor (microreactor inner diameter 4.6 mm, length 30 cm) via a liquid-phase feed pump and a gas pipeline system, respectively, and the reaction was carried out at a reaction temperature of 20-30℃. The reaction solution residence time was controlled to be 10 minutes by adjusting the feed pump to maintain a reaction solution flow rate of 2.5 ml / min, the gas flow meter to maintain a gas flow rate of 2.5 ml / min, and the back pressure valve to maintain a microreactor pressure of 0.3 MPa. After the reaction was completed, the reaction solution flowed out of the reactor outlet and was collected in a collection tank, while the reaction tail gas was collected by a tail gas collection device. After concentration, the reaction solution was extracted with 500 mL of ethyl acetate / water (1:1 volume ratio), and the organic phase was concentrated to obtain 15.8 g of crude product. Recrystallization of the crude product from ethyl acetate / petroleum ether yielded 15.6 g of N-styreneacetamide, with a yield of 97%.

[0070] Table 5. Effect of different porous packing materials on the yield of N-styrene acetamide in the reaction of 4-phenylbutyl-3-en-2-one oxime.

[0071]

[0072] Comparative Example 3:

[0073] The microchannel reactor used in the comparative example was a Corning microchannel reactor. G1SiC reactor. 4-Benzobutyl-3-en-2-one oxime (16.1 g, 0.1 mol, 1.0 equivalent) and triethylamine (27.75 mL, 0.2 mmol, 2.0 equivalent) were dissolved in CH3CN (500 mL, 0.2 M) to prepare the reaction solution, which was then added to the feed tank. The reaction solution and SO2F2 gas were introduced into the microchannel reactor via a liquid-phase feed pump and a gas pipeline system, respectively, and the reaction was carried out at a reaction temperature of 20-30℃. The residence time of the reaction solution was controlled to be 10 minutes by adjusting the feed pump flow rate to 15 ml / min, the gas flow rate to 15 ml / min, and the back pressure valve to 0.3 MPa. After the reaction was completed, the reaction solution flowed out of the reactor outlet and was collected in a collection tank, while the reaction tail gas was collected by a tail gas collection device. After concentration, the reaction solution was extracted with 500 mL of ethyl acetate / water (1:1 volume ratio), and the organic phase was concentrated to obtain 14.8 g of crude product. Recrystallization of the crude product from ethyl acetate / petroleum ether yielded 13.7 g of N-styreneacetamide, with a yield of 85%.

[0074] Table 6. Corning Comparison of yields of G1SiC microreactor and replaceable packing microreactor for the preparation of caprolactam from cyclohexanone oxime

[0075]

[0076] Example 4:

[0077] A 0.1 mol acetophenone oxime (13.5 g) and 0.2 mmol triethylamine (27.75 mL, 0.2 mmol) were dissolved in 500 mL of 0.2 M CH3CN to prepare a reaction solution, which was then added to a raw material tank. The reaction solution and SO2F2 gas were fed into a packed microreactor (microreactor inner diameter 0.53 mm, length 30 cm) via a liquid-phase feed pump and a gas pipeline system, respectively, and the reaction was carried out at a reaction temperature of 20-30 °C. The residence time of the reaction solution was controlled to be 10 minutes by adjusting the feed pump to maintain a reaction solution flow rate of 0.03 mL / min, the gas flow meter to maintain a gas flow rate of 0.03 mL / min, and the back pressure valve to maintain a microreactor pressure of 0.1 MPa. After the reaction was completed, the reaction solution flowed out of the reactor outlet and was collected in a collection tank, while the reaction tail gas was collected using a tail gas collection device. After concentration, the reaction solution was extracted with 500 mL of ethyl acetate / water (1:1 volume ratio), and the organic phase was concentrated to obtain 13.4 g of crude product. The crude product was recrystallized from ethyl acetate / petroleum ether to give 13.2 g of N-phenylacetamide, with a yield of 98%.

[0078] Table 7. Effect of different porous packing materials on the yield of acetophenone oxime to phenylacetamide

[0079]

[0080]

[0081] Comparative Example 4:

[0082] The microchannel reactor used in the comparative example was a Corning microchannel reactor. G1SiC reactor. Acetophenone oxime (13.5 g, 0.1 mol) and triethylamine (27.75 mL, 0.2 mmol) were dissolved in CH3CN (500 mL, 0.2 M) to prepare the reaction solution, which was then added to the feed tank. The reaction solution and SO2F2 gas were introduced into the microchannel reactor via a liquid-phase feed pump and a gas pipeline system, respectively, and the reaction was carried out at a reaction temperature of 20-30℃. The residence time of the reaction solution was controlled to be 10 minutes by adjusting the flow rate of the reaction solution (15 mL / min) and the gas flow rate (15 mL / min) using a gas flow meter, and by controlling the pressure of the microreactor to 0.1 MPa using a back pressure valve. After the reaction was completed, the reaction solution flowed out of the reactor outlet and was collected in a collection tank, while the reaction tail gas was collected using a tail gas collection device. After concentration, the reaction solution was extracted with 500 mL of ethyl acetate / water (1:1 volume ratio), and the organic phase was concentrated to obtain 12.4 g of crude product. The crude product was recrystallized from ethyl acetate / petroleum ether to give 11.7 g of N-phenylacetamide, with a yield of 87%.

[0083] Table 8. Corning Comparison of yields of N-phenylacetamide from acetophenone oxime in the reaction of G1SiC microreactor and replaceable packing microreactor

[0084]

[0085] Comparative experiment:

[0086] For the reaction steps in Example 1, porous ZrO2 packing material was selected for the packed microreactor to compensate for the influence of different packing mesh sizes on the reaction yield.

[0087] The preparation method of porous ZrO2 filler includes the following steps:

[0088] (1) Weigh 2.0 g of zirconium oxychloride into a three-necked flask, add 5 ml of deionized water and 10 ml of anhydrous ethanol. Shake the flask to mix thoroughly, then fix the flask in a 55°C water bath. Measure 1.2 ml of ammonia water (25 wt%) into a dropping funnel, add 22.8 ml of deionized water to dilute (20 times dilution), fix the dropping funnel on the three-necked flask, and begin to slowly add the solution dropwise. After the addition is complete, maintain the temperature for 1 hour. After heating is complete, filter the obtained product and rinse with a small amount of deionized water.

[0089] (2) Measure 10 ml of concentrated ammonia (25 wt%) into a round-bottom flask, add 200 ml of deionized water to dilute it, and take 8.0 g of the filtered product (undried) and add it to the round-bottom flask, controlling the overall pH of the solution to approximately 10. Place the round-bottom flask in an 80°C water bath, set up the reflux condenser, and start heat preservation. After heat preservation at 80°C for 12 h, soak for 12 h (overnight), then heat preservation at 80°C for 12 h again, soak for 12 h, take it out and filter the obtained product, rinse with a small amount of deionized water, and then place it in an 80°C oven to dry for 5 h. After drying, place it in a muffle furnace at 350°C and calcine for 2 h to obtain porous ZrO2 packing.

[0090] Table 9. Comparison of yields of benzoylaniline in the reaction of benzophenone oxime to benzoylaniline using porous ZrO2 fillers of different mesh sizes.

[0091]

[0092] In addition, the preparation method of porous packing COF is as follows:

[0093] (1) Place 1,3,5-tris(4-aminophenyl)benzene (TPB, 0.04 mmol) and 2,5-divinylbenzaldehyde (DVA, 0.06 mmol) into centrifuge tubes. Then add 5 mL of acetonitrile to the centrifuge tubes and sonicate for 1 min to dissolve completely.

[0094] (2) Then, add 0.3-0.7 mL of 12M acetic acid to the centrifuge tube. Subsequently, vortex the mixture vigorously for 10 seconds and let it stand at room temperature for 72 hours.

[0095] (3) The yellow precipitate obtained was collected by centrifugation and washed three times with anhydrous tetrahydrofuran (THF) and ethanol, respectively. Finally, the powder was dried at 60°C under high vacuum for 24 hours to obtain the porous COF packing.

[0096] In addition, the sources of the porous fillers Al2O3, SiO2, TS-1, and HTS-1 used in the examples are shown in Table 10:

[0097] Table 10. Manufacturers and Models of Porous Packing Materials

[0098] <![CDATA[Al2O3]]> CNOOC Tianjin Chemical Research and Design Institute Co., Ltd. TC-101-1 <![CDATA[SiO2]]> Beijing Deco Island Gold Technology Co., Ltd. <![CDATA[DK-SiO2-15]]> TS-1 Tianjin Nanhua Catalyst Co., Ltd. NKF-8 HTS-1 Sinopec Hunan Jianchang Petrochemical Co., Ltd.

Claims

1. A method for preparing an amide compound, characterized in that: The preparation method uses a replaceable packing continuous flow microreactor device, which includes a liquid pipeline system, a gas pipeline system, a microreactor, and a cooling and product collection system. The top of the microreactor is connected to both the liquid pipeline system and the gas pipeline system, and the bottom of the microreactor is connected to the cooling and product collection system. The microreactor is a packed microreactor tube, which includes a tube body filled with replaceable porous packing material, which has both microporous and mesoporous structures. Filter sieves for trapping porous packing material of different sizes are respectively provided at the upper and lower ends of the tube body. The filter sieves at both ends are connected to material inlet / outlet joints via fixing components to stabilize the packing material. A cutting ring and a sealing ring are arranged sequentially from top to bottom between the fixing components and the tube body. The porous packing material is selected from one of porous Al2O3, porous SiO2, porous ZrO2, TS-1, HTS-1, ETS-10, and COF. The preparation method includes the following steps: (1) Dissolve the ketoxime compound and triethylamine in acetonitrile to prepare a reaction solution; (2) The reaction solution and SO2F2 gas prepared in step (1) are introduced into the microreactor through the liquid pipeline system and the gas pipeline system, respectively, and the Beckmann rearrangement reaction is carried out at 20-30℃. The reaction solution flow rate is controlled at 0.01-2.5 ml / min, the gas flow rate is controlled at 0.01-2.5 ml / min, and the microreactor pressure is controlled at 0.1-0.5MPa to control the residence time of the reaction solution to 10-60 minutes, that is, the reaction time is 10-60 minutes. (3) After the reaction is completed, the reaction solution flows out of the microreactor outlet and is collected by the cooling and product collection system. The collected reaction solution is then post-processed to obtain amide compounds.

2. The preparation method according to claim 1, characterized in that: The size of the holes in the filter screen plate is adjustable.

3. The preparation method according to claim 1, characterized in that: The inner diameter of the tube is 0.1-10 mm.

4. The preparation method according to claim 1, characterized in that: The particle size range of the porous filler is 0.1-1000 micrometers.

5. The preparation method according to claim 1, characterized in that: The fastener is a connecting screw.

6. The preparation method according to claim 1, characterized in that: The liquid piping system includes a raw material tank and a feed pump, which are connected by a liquid pipeline, and the feed pump is connected to the top of the microreactor via the liquid pipeline.

7. The preparation method according to claim 1, characterized in that: The gas pipeline system includes a gas cylinder and a gas flow meter, which are connected by a gas pipeline, and the gas flow meter is connected to the top of the microreactor via the gas pipeline.

8. The preparation method according to claim 1, characterized in that: The ketoxime compounds mentioned are benzophenone oxime, cyclohexanone oxime, 4-phenylbutyl-3-ene-2-one oxime, acetophenone oxime, cyclohexane-1-one oxime, and 1-(4-aminophenyl)ethane-1-one oxime.

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