Continuous flow microreactor device with replaceable filler and application of continuous flow microreactor device in amide preparation reaction

Abstract

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

Description

Technical Field

[0001] The invention relates to a replaceable filler type continuous flow microreactor device and application thereof in amide preparation reaction, belonging to the technical field of fine chemical technology. Background Art

[0002] As one of the most important structural units in organic chemistry, biochemistry and materials chemistry, amide structure has a wide range of uses in the fields of medicine, pesticides and materials. Common amide synthesis strategies are to react carboxylic acid derivatives (such as acyl chlorides, anhydrides or esters) with amines, or to prepare them by direct dehydration condensation reaction of carboxylic acids and amines under the action of equivalent condensing agents (such as carbonyl imidazoles). Although these synthesis methods are very efficient, they require the use of expensive and toxic raw materials, or produce a large amount of by-products during the synthesis process, have poor atom economy, and are not environmentally friendly, which does not meet the requirements of green and sustainable chemical development. Therefore, establishing a new green and sustainable synthesis strategy to construct amide modules is an urgent need in the field of organic synthesis today.

[0003] Chinese patent CN115594603A invented a method for preparing N-tert-butyl-4-aminobenzamide by a microchannel reactor. This invention reduces three waste pollution, is green and environmentally friendly, has a high synthesis yield, and strongly mixes N-tert-butyl-4-nitrobenzamide solution and hydrogen in a microchannel reactor, which is safe, reliable and efficient. Chinese patent CN118221543A invented a method for preparing 4-aminobenzamide compounds by a microchannel reactor. This invention uses p-nitrobenzoic acid ester and amine compounds as raw materials, and synthesizes 4-aminobenzamide compounds in a step through a microchannel reactor in the presence of a catalyst and hydrogen. It is not only easy to operate, safe, and environmentally friendly, but also the amount of amine compounds is greatly reduced, thereby saving raw material costs and reducing the difficulty of recovery, which is suitable for large-scale industrial production. However, the above-mentioned microreactor has a complex structure, has the problem of frequent replacement of the reactor, difficulty in replacement, and easy to cause blockage.

[0004] Therefore, it is necessary to optimize the design of a microreactor whose interior is easy to regulate and replace, so as to achieve more stable and durable microreactor operation and enable it to be better applied to amide preparation reactions. Summary of the invention

[0005] In order to solve the shortcomings of the prior art, the purpose of the present invention is to provide a simple continuous flow microreactor device with replaceable fillers and its application in the preparation of amide reactions, which is used to solve the problems of frequent replacement, easy clogging and high production cost of ordinary microreactors in the preparation of amide reactions, and can improve the efficiency and selectivity of the reaction.

[0006] In order to achieve the above object, the present invention adopts the following technical solution:

[0007] In a first aspect, the present invention provides a replaceable filler 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, the interior of which is filled with replaceable porous fillers, and the porous fillers have both microporous and mesoporous structures; the upper and lower ends of the tube body are respectively provided with filter screens for intercepting porous fillers of different sizes, and the filter screens at both ends are respectively connected to the material inlet and outlet joints through fixings to stabilize the fillers; a blade ring and a sealing ring are sequentially arranged between the fixing and the tube body from top to bottom.

[0009] Furthermore, the hole size of 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 body may 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 of the porous filler ranges from 0.1 to 1000 microns.

[0013] Furthermore, the fixing member is a connecting screw.

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

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

[0016] In a second aspect, the present invention provides a method for preparing an amide compound, wherein the preparation method uses the replaceable filler continuous flow microreactor device described in the first aspect, and the preparation method comprises the following steps:

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

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

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

[0020] Preferably, the ketoxime compound is benzophenone oxime, cyclohexanone oxime, 4-phenylbutyl-3-ene-2-ketone oxime, acetophenone oxime, cyclohexane-1-ketone oxime, and 1-(4-aminophenyl)ethane-1-ketone 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 of the porous filler is in the range of 0.1-1000 microns.

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

[0024] Preferably, the post-treatment comprises the following steps: after the reaction solution is concentrated, 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 an amide compound.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

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

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

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

[0029] (4) The particle fillers of different sizes in the replaceable filler-type continuous flow microreactor of the present invention can be used in combination.

[0030] (5) The replaceable filler continuous flow microreactor of the present invention has low cost.

[0031] (6) The replaceable filler-type continuous flow microreactor device of the present invention is applied to the preparation of amide compounds and can obtain a higher product yield compared to conventional microreactors. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0033] Figure 1 Schematic diagram of the packed micro-reaction tube of the present invention Figure 1 ;

[0034] Figure 2 Schematic diagram of the packed micro-reaction tube of the present invention Figure 2 ;

[0035] Figure 3 It is an enlarged schematic diagram of the connection screws and filter discs in the micro-reaction tube structure;

[0036] Figure 4 It is an overall schematic diagram of the replaceable filler type continuous flow microreactor device of the present invention.

[0037] The reference numerals are as follows:

[0038] 1-liquid pipeline system; 2-gas pipeline system; 3-microreactor; 4-cooling and product collection system; 11-raw material tank; 12-feed pump; 21-gas cylinder; 22-gas flow meter; 31-tube body; 32-porous filler; 33-filter sieve plate; 34-material inlet and outlet joint; 35-fixing part; 36-blade ring; 37-sealing ring.

[0039] Figure 5-Figure 10 The nitrogen adsorption-desorption curves of porous Al2O3, porous SiO2, porous ZrO2, TS-1, HTS-1, and COF used in the examples are shown in order. DETAILED DESCRIPTION

[0040] In order to make the purpose, technical solutions and advantages of the present invention more clear, the present invention is further described in detail below in conjunction with embodiments.

[0041] refer to Figures 1 to 4The present invention provides a replaceable filler continuous flow microreactor device, comprising 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 interior of which is filled with a replaceable porous filler 32, and the porous filler 32 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 intercepting porous fillers of different sizes, and the filter screen plates 33 at both ends are respectively connected to the material inlet and outlet joints 34 through fixings 35 to stabilize the filler; a blade ring 36 and a sealing ring 37 are sequentially arranged between the fixing 35 and the tube body 31 from top to bottom.

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

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

[0045] More specifically, the inner diameter of the tube body 31 may 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 of the porous filler 32 ranges from 0.1 to 1000 microns.

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

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

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

[0050] The above-mentioned microreactor device is used to prepare amide compounds, and the specific examples are as follows:

[0051] Embodiment 1:

[0052] Benzophenone oxime (19.7g, 0.1mol, 1.0 equivalent), triethylamine (27.75mL, 0.2mmol, 2.0 equivalent) are dissolved in CH3CN (500mL, 0.2M) to configure the reaction solution, and the reaction solution is added to the raw material tank. The reaction solution and SO2F2 gas enter the packed microreactor (microreactor inner diameter 2.1mm, length 30cm) through the liquid phase feed pump and the gas pipeline system respectively, and react under the reaction temperature of 20-30℃. The reaction solution flow rate is controlled to be 0.5ml / min by adjusting the feed pump, the gas flow rate is controlled to be 0.5ml / min by the gas flow meter, and the back pressure valve controls the microreactor pressure to be 0.1MPa to control the reaction solution residence time to be 10 minutes. After the reaction is completed, the reaction solution flows out from the reactor outlet and is collected by the collection tank, and the reaction tail gas is collected by the tail gas collection device. After the reaction solution was concentrated, it 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 a crude product. The crude product was recrystallized from ethyl acetate / petroleum ether to obtain 18.7 g of the product benzanilide, with a yield of 95%.

[0053] Table 1. Effect of different porous fillers on the yield of the reaction of benzophenone oxime to prepare benzanilide

[0054]

[0055] Comparative Example 1:

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

[0057] Table 2. Corning Comparison of the yield of the reaction of benzophenone oxime to benzanilide between G1SiC reactor and replaceable filler microreactor

[0058]

[0059]

[0060] Embodiment 2:

[0061] Cyclohexanone oxime (11.3g, 0.1mol, 1.0 equivalent) and triethylamine (27.75mL, 0.2mmol, 2.0 equivalent) were dissolved in CH3CN (500mL, 0.2M) to prepare the reaction solution, and the reaction solution was added to the raw material tank. The reaction solution and SO2F2 gas were respectively introduced into the packed microreactor (microreactor inner diameter 3mm, length 30cm) through the liquid phase feed pump and the gas pipeline system, 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 control the reaction solution flow rate to 1ml / min, the gas flow meter to control the gas flow rate to 1ml / min, and the back pressure valve to control the microreactor pressure to 0.2MPa. After the reaction was completed, the reaction solution was collected from the reactor outlet and collected by the collection tank, and the reaction tail gas was collected by the tail gas collection device. After the reaction solution was concentrated, it was extracted with 500mL ethyl acetate / water (1:1 volume ratio), and the organic phase was concentrated to obtain 10.1g 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 fillers on the yield of cyclohexanone oxime to caprolactam

[0063]

[0064] Comparative Example 2:

[0065] The microchannel reactor used in the comparative example is Corning G1SiC reactor. Dissolve cyclohexanone oxime (11.3g, 0.1mol, 1.0 equivalent) and triethylamine (27.75mL, 0.2mmol, 2.0 equivalent) in CH3CN (500mL, 0.2M) to prepare the reaction solution, and add the reaction solution to the raw material tank. The reaction solution and SO2F2 gas enter the microchannel reactor through the liquid phase feed pump and the gas pipeline system respectively, and react at a reaction temperature of 20-30℃. The reaction solution residence time is controlled to be 10 minutes by adjusting the feed pump to control the reaction solution flow rate to 15ml / min, the gas flow meter to control the gas flow rate to 15ml / min, and the back pressure valve to control the microreactor pressure to 0.2MPa. After the reaction is completed, the reaction solution flows out from the reactor outlet and is collected by the collection tank, and the reaction tail gas is collected by the tail gas collection device. After the reaction solution is concentrated, it is extracted with 500mL ethyl acetate / water (1:1 volume ratio), and the organic phase is concentrated to obtain 8.6g 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 the yield of cyclohexanone oxime to caprolactam reaction between G1SiC microreactor and replaceable filler microreactor

[0067]

[0068] Embodiment three:

[0069] 4-phenylbutyl-3-ene-2-one oxime (16.1g, 0.1mol, 1.0 equivalent) and triethylamine (27.75mL, 0.2mmol, 2.0 equivalent) were dissolved in CH3CN (500mL, 0.2M) to prepare the reaction solution, and the reaction solution was added to the raw material tank. The reaction solution and SO2F2 gas were respectively introduced into the packed microreactor (microreactor inner diameter 4.6mm, length 30cm) through the liquid phase feed pump and the gas pipeline system, and the reaction was carried out under the reaction temperature of 20-30℃. The reaction solution flow rate was controlled to be 2.5ml / min by adjusting the feed pump and the gas flow rate was controlled to be 2.5ml / min by the gas flowmeter. And the back pressure valve controlled the microreactor pressure to be 0.3MPa to control the reaction solution residence time to be 10 minutes. After the reaction was completed, the reaction solution was collected by the collection tank after flowing out from the reactor outlet, and the reaction tail gas was collected by the tail gas collection device. After the reaction solution was concentrated, it 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 a crude product. The crude product was recrystallized from ethyl acetate / petroleum ether to obtain 15.6 g of N-phenylvinyl acetamide, with a yield of 97%.

[0070] Table 5 Effect of different porous fillers on the yield of the reaction of 4-phenylbutyl-3-ene-2-one oxime to prepare N-phenylacetamide

[0071]

[0072] Comparative Example 3:

[0073] The microchannel reactor used in the comparative example is Corning G1SiC reactor. 4-phenylbutyl-3-ene-2-one oxime (16.1g, 0.1mol, 1.0 equivalent) and triethylamine (27.75mL, 0.2mmol, 2.0 equivalent) were dissolved in CH3CN (500mL, 0.2M) to prepare the reaction solution, and the reaction solution was added to the raw material tank. The reaction solution and SO2F2 gas entered the microchannel reactor through the liquid phase feed pump and the gas pipeline system respectively, and reacted at a reaction temperature of 20-30°C. The reaction solution flow rate was controlled to be 15ml / min by adjusting the feed pump and the gas flow rate was controlled to be 15ml / min by the gas flowmeter. And the back pressure valve controlled the microreactor pressure to be 0.3MPa to control the reaction solution residence time to be 10 minutes. After the reaction is completed, the reaction solution flows out from the reactor outlet and is collected by the collection tank, and the reaction tail gas is collected by the tail gas collection device. After the reaction solution was concentrated, it 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 a crude product. The crude product was recrystallized from ethyl acetate / petroleum ether to obtain 13.7 g of N-phenylvinyl acetamide, with a yield of 85%.

[0074] Table 6. Corning Comparison of the yield of cyclohexanone oxime to caprolactam reaction between G1SiC microreactor and replaceable filler microreactor

[0075]

[0076] Embodiment 4:

[0077] 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, and the reaction solution was added to the raw material tank. The reaction solution and SO2F2 gas were respectively introduced into the packed microreactor (microreactor inner diameter 0.53 mm, length 30 cm) through the liquid phase feed pump and the gas pipeline system, and the reaction was carried out at a reaction temperature of 20-30 ° C. The reaction solution residence time was controlled to be 10 minutes by adjusting the feed pump to control the reaction solution flow rate to 0.03 ml / min, the gas flow meter to control the gas flow rate to 0.03 ml / min, and the back pressure valve to control the microreactor pressure to 0.1 MPa. After the reaction was completed, the reaction solution was collected from the reactor outlet and collected by the collection tank, and the reaction tail gas was collected by the tail gas collection device. After the reaction solution was concentrated, it 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 obtain 13.2 g of N-phenylacetamide with a yield of 98%.

[0078] Table 7. Effect of different porous fillers on the yield of the reaction of acetophenone oxime to prepare phenylacetamide

[0079]

[0080]

[0081] Comparative Example 4:

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

[0083] Table 8. Corning Comparison of the yield of the reaction of acetophenone oxime to N-phenylacetamide between G1SiC microreactor and replaceable filler microreactor

[0084]

[0085] Comparative experiment:

[0086] For the reaction steps in Example 1, the packed microreactor uses porous ZrO2 filler to compensate for the effect of different filler mesh sizes on the reaction yield.

[0087] The preparation method of the porous ZrO2 filler is as follows:

[0088] (1) Weigh 2.0g of zirconium oxychloride into a three-necked flask, add 5ml of ionized water and 10ml of anhydrous ethanol. Shake the three-necked flask to mix evenly, then fix the flask in a 55℃ water bath. Measure 1.2ml of ammonia water (25wt%) into a dropping funnel, add 22.8ml of deionized water to dilute (dilute 20 times), fix the dropping funnel on the three-necked flask, start to drip slowly, and keep the temperature constant for 1h after the dripping is completed. After heating, filter the obtained product and rinse with a small amount of deionized water.

[0089] (2) Measure 10 ml of concentrated ammonia water (25 wt%) into a round-bottom flask, add 200 ml of deionized water to dilute, take 8.0 g of the above-mentioned product after filtration (without drying), add it into the round-bottom flask, and control the overall pH of the solution to be about 10. Place the round-bottom flask in an 80°C water bath, set up a condensation reflux device and start to keep warm. Keep warm at 80°C for 12 hours, then soak for 12 hours (overnight), keep warm at 80°C for 12 hours again, then soak for 12 hours, take out and filter the obtained product, rinse with a small amount of deionized water, and then place it in an oven at 80°C to dry for 5 hours. After drying, place it in a 350°C muffle furnace and roast it for 2 hours to obtain a porous ZrO2 filler.

[0090] Table 9. Comparison of the yields of the reaction of preparing benzanilide from benzophenone oxime using porous ZrO2 fillers with different mesh sizes

[0091]

[0092] In addition, the preparation method of the porous filler COF is the following steps:

[0093] (1) 1,3,5-tris(4-aminophenyl)benzene (TPB, 0.04 mmol) and 2,5-divinylbenzaldehyde (DVA, 0.06 mmol) were placed in a centrifuge tube. 5 mL of acetonitrile was then added to the centrifuge tube and ultrasonicated for 1 min to completely dissolve.

[0094] (2) After that, 0.3-0.7 mL of 12 M acetic acid was added to the centrifuge tube. The mixture was then vigorously shaken on a vortex mixer for 10 seconds and allowed to stand at room temperature for 72 hours.

[0095] (3) The yellow precipitate 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 a porous COF filler.

[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 packings

[0098] Porous filler factory model <![CDATA[Al2O3]]> CNOOC Tianjin Chemical Research and Design Institute Co., Ltd. TC-101-1 <![CDATA[SiO2]]> Beijing Dekedaojin 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 replaceable filler 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; characterized in that: The microreactor is a packed microreactor tube, which includes a tube body, the interior of which is filled with replaceable porous fillers, and the porous fillers have both microporous and mesoporous structures; the upper and lower ends of the tube body are respectively provided with filter screens for intercepting porous fillers of different sizes, and the filter screens at both ends are respectively connected to the material inlet and outlet joints through fixings to stabilize the fillers; a blade ring and a sealing ring are sequentially arranged between the fixing and the tube body from top to bottom.

2. The replaceable filler continuous flow microreactor device according to claim 1, characterized in that: The hole size of the filter screen is adjustable.

3. The replaceable filler continuous flow microreactor device according to claim 1, characterized in that: The inner diameter of the tube is 0.1-10 mm.

4. The replaceable filler continuous flow microreactor device according to claim 1, characterized in that: The particle size of the porous filler is in the range of 0.1-1000 microns.

5. The replaceable filler continuous flow microreactor device according to claim 1, characterized in that: The fixing member is a connecting screw.

6. The replaceable filler continuous flow microreactor device according to claim 1, characterized in that: The liquid pipeline system includes a raw material tank and a feed pump, the raw material tank and the feed pump are connected through a liquid pipeline, and the feed pump is connected to the top of the microreactor through the liquid pipeline.

7. The replaceable filler continuous flow microreactor device according to claim 1, characterized in that: The gas pipeline system comprises a gas cylinder and a gas flow meter, the gas cylinder and the gas flow meter are connected through a gas pipeline, and the gas flow meter is connected to the top of the microreactor through the gas pipeline.

8. A method for preparing an amide compound, characterized in that: The preparation method uses the replaceable filler continuous flow microreactor device according to any one of claims 1 to 7, and the preparation method comprises the following steps: (1) dissolving a ketoxime compound and triethylamine in acetonitrile to prepare a reaction solution; (2) The reaction liquid prepared in step (1) and SO2F2 gas enter the microreactor through the liquid pipeline system and the gas pipeline system respectively, and the Beckmann rearrangement reaction is carried out at 20-30° C.; wherein the reaction liquid flow rate is controlled to be 0.01-2.5 ml / min, the gas flow rate is controlled to be 0.01-2.5 ml / min, and the microreactor pressure is controlled to be 0.1-0.5 MPa to control the reaction liquid residence time to be 10-60 minutes, that is, the reaction time is 10-60 minutes; (3) After the reaction is completed, the reaction liquid flows out from the outlet of the microreactor and is collected by a cooling and product collection system. The collected reaction liquid is post-treated to obtain an amide compound.

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

10. The preparation method according to claim 8, characterized in that: The porous filler is selected from porous Al2O3, porous SiO2, porous ZrO2, TS-1, HTS-1, ETS-10, and COF.

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