Method for synthesizing aspirin by using microchannel continuous flow technology

Abstract

The invention relates to the technical field of aspirin synthesis, in particular to a method for synthesizing aspirin by a microchannel continuous flow technology. According to the technical scheme, the method comprises the following steps: 1, dissolving salicylic acid by using an organic solvent according to a certain proportion through a feeding device; 2, micro-reaction equipment, a micro-channel mixer and a polytetrafluoroethylene reactor are adopted for feeding under nitrogen protection, a heating and heat preservation device is arranged on a water-free and oxygen-free reaction pipe section in the process, and the pipeline temperature is always kept at the reaction temperature. And 4, separating and purifying by adopting a continuous post-treatment device. The micro-channel continuous flow technology is applied to synthesis of aspirin, existing equipment in a laboratory is adopted for feeding and heating, continuous reaction is easy to build, the cost is low, the reaction temperature is low, safety and high efficiency are achieved, and the method can be applied to student experiments, practical training and pilot scale production.

Description

Technical Field

[0001] The invention relates to the technical field of devices for synthesizing aspirin, and in particular to a method for synthesizing aspirin using a microchannel continuous flow technology. Background Art

[0002] Aspirin, also known as acetylsalicylic acid, is an organic compound that is mainly used as an antipyretic and analgesic. It has a good effect on relieving mild or moderate pain, such as toothache, headache, neuralgia, muscle aches and dysmenorrhea. It is also used to reduce fever in fever diseases such as colds and influenza, treat rheumatic pain, etc., and can prevent thrombosis. The synthesis of aspirin is one of the classic organic basic experiments. Its reaction raw materials have a special structure and the product composition is relatively complex, which is a good teaching experiment. Microchannel continuous flow synthesis experiments have had a significant impact in academia and industry in recent years and have become increasingly popular, but today most undergraduate chemistry teaching still relies heavily on the use of traditional chemical synthesis methods using reaction bottles, which have low experimental product yields, long reaction times, and high failure rates.

[0003] Aspirin production lines are often used in chemical practice teaching, but they are dangerous in daily production lines, so it is inconvenient for students to practice. The traditional intermittent reactor preparation process is limited by the temperature and pressure that the equipment can withstand, and it is impossible to safely and effectively strengthen the reaction process. The continuous flow reaction device has high pressure resistance, high temperature, high heat exchange capacity, and can control the reaction rate. It can strengthen the traditional intermittent reactor process, and the safety of the process is more reliable. Summary of the invention

[0004] The purpose of the invention is to solve the problems existing in the background technology and to provide a method for synthesizing aspirin using a microchannel continuous flow technology.

[0005] The technical solution of the present invention is a method for synthesizing aspirin using microchannel continuous flow technology, comprising:

[0006] Step 1: dissolving salicylic acid in an organic solvent in a certain proportion through a feeding device, together with acetic anhydride and concentrated sulfuric acid as reaction materials, wherein the mass ratio of salicylic acid, acetic anhydride and concentrated sulfuric acid is 1:1-2:0.1-0.6;

[0007] Step 2: the feeding device used is any one or more of a peristaltic pump, a syringe pump, a vacuum pump and a nitrogen balloon;

[0008] Step 3: using micro-reaction equipment, microchannel mixer and polytetrafluoroethylene reactor to add materials under nitrogen protection, the process is water-free and oxygen-free, connected to a post-treatment device, the reaction conditions are 60-80°C, the residence time is 0.5-5min, the flow rate is 2-20mL / min, and the reaction tube section is equipped with a heating and heat preservation device to keep the pipeline temperature at the reaction temperature;

[0009] Step 4: Separation and purification using a continuous post-processing device.

[0010] Optionally, the organic solvent is any one of dioxane, acetonitrile, ethyl acetate, dichloroethane, dimethylformamide (DMF) or dimethyl sulfoxide (DMSO), and the mass ratio of the organic solvent to the salicylic acid is 0.2-50:1.

[0011] When the organic solvent is dioxane or ethyl acetate, the mass ratio of dioxane to salicylic acid is 2-8:1. At room temperature, such as 25°C, 1g of salicylic acid corresponds to 4-8mL of dioxane; at 75°C, 1g of salicylic acid corresponds to 2-4mL of dioxane.

[0012] When acetonitrile or dichloroethane is used as the organic solvent, the mass ratio of each organic solvent to salicylic acid is 8-50:1.

[0013] When DMF or DMSO is used as the organic solvent, the mass ratio of each organic solvent to salicylic acid is 0.2-1:1. Specifically, at 75°C, 1g of salicylic acid corresponds to 0.2-0.4mL of DMF or DMSO, and at 25°C, 1g of salicylic acid corresponds to 0.5-1mL of DMF or DMSO.

[0014] Optionally, the micro-reaction device uses a polytetrafluoroethylene tube and a microchannel mixer, and the materials include 316L stainless steel, silicon carbide, and Hastelloy, wherein the shape of the mixer is any one of a heart shape, a wave shape, and a tube shape.

[0015] Optionally, the micro-reaction device has an inner diameter of 3-10 mm and an outer diameter of 5-20 mm.

[0016] Optionally, the reaction section tube length of the micro-reactor is 5-50m.

[0017] Optionally, the feeding reaction section and delayed reaction section pipelines of the micro-reactor are provided with a heating and heat preservation device, which is any one of an electric heating jacket, a warm air system or a liquid circulation heating with an external pipeline, so as to reduce the amount of organic solvent used and improve the reaction efficiency.

[0018] Optionally, the liquid circulation heating device provided in the reaction section of the micro-reactor equipment uses silicone oil or water as the heating medium, and the material of the outer pipe is a rubber tube with heat-insulating properties.

[0019] Optionally, the micro-reaction device has a reaction time of 0.5-2 min, a delayed reaction time of 2-20 min, and also includes a device for synthesizing aspirin using microchannel continuous flow technology;

[0020] The device comprises a premixing system for mixing raw materials, a reaction system for providing reaction conditions for the materials, and a continuous post-processing system for separating and purifying the materials after the reaction. The premixing system and the reaction system, as well as the reaction system and the continuous post-processing system are connected through polytetrafluoroethylene pipes, and valves are provided at the connections to control the inflow and outflow of materials.

[0021] Optionally, the premixing system includes an acetic anhydride raw material tank, a salicylic acid raw material tank, a first pump body and a second pump body, the input end of the first pump body is connected to the acetic anhydride raw material tank, the input end of the second pump body is connected to the salicylic acid raw material tank, the reaction system includes a microchannel reactor, hot and cold wells and a heat exchanger, the hot and cold wells are set to a temperature of 70-80°C, the output ends of the first pump body and the second pump body are both connected to the microchannel reactor, the microchannel reactor and the heat exchanger are connected through a crude product discharge port, the heat exchanger is provided with a water inlet, the heat exchanger and the hot and cold wells are connected through a hot oil inlet, and the microchannel reactor and the hot and cold wells are connected through a hot oil outlet.

[0022] Optionally, the continuous post-treatment system includes a scraped film evaporator, a tubular reactor, and a horizontal scraper centrifuge, the scraped film evaporator is connected to the heat exchanger through a crude product discharge port, the scraped film evaporator is provided with a steam inlet, a condensed water outlet and a dioxane outlet, the dioxane outlet is connected to a third pump body, the dioxane outlet is connected to an input end of the third pump body, and the output end of the third pump body is connected to an oxane receiving tank;

[0023] The scraped film evaporator is provided with a concentrated liquid outlet, the other end of the concentrated liquid outlet is connected to a solid-liquid mixture receiving tank, the solid-liquid mixture receiving tank is connected to a fourth pump body, the solid-liquid mixture receiving tank is connected to the input end of the fourth pump body, the output end of the fourth pump body is connected to the tubular reactor, the tubular reactor is connected to a hot water inlet, the hot water inlet is connected to a fifth pump body, the hot water inlet is connected to the input end of the fifth pump body, and the output end of the fifth pump body is connected to a hot water supplier;

[0024] The tubular reactor and the horizontal scraper centrifuge are connected through a solid-liquid mixture inlet. The horizontal scraper centrifuge is provided with an aspirin discharge port and a liquid discharge port. The aspirin discharge port is connected to an aspirin receiving tank, and the liquid discharge port is connected to a post-processing liquid receiving tank.

[0025] In summary, the present application includes at least the following beneficial technical effects:

[0026] The present invention applies microchannel continuous flow technology to the synthesis of aspirin, uses existing laboratory equipment for feeding and heating, is easy to build a continuous reaction, has low cost, low reaction temperature, is safe and efficient, and can be used on a large scale for student teaching experiments.

[0027] Furthermore, a corresponding milder organic solvent is used to fully dissolve the material, thereby reducing the irritation of the material and preventing the pipeline of the microchannel continuous flow reactor from being blocked. A vacuum pump is used to evacuate air and a feeding device is used to feed the material to create a water-free and oxygen-free reaction environment, thereby increasing the product yield and avoiding product oxidation.

[0028] At the same time, the present invention can use automatic control devices in industrial production to achieve safe and efficient continuous intelligent production. The present invention can be used in industrial production after the equipment is replaced. The production part is connected to continuous automatic post-processing equipment, organic solution recovery equipment, and automatic remote control equipment, which can greatly reduce the production and labor costs of enterprises. At the same time, it is safer and more controllable than the reactor.

[0029] Compared with stainless steel pipes, polytetrafluoroethylene pipes are more transparent, and the flow conditions of the liquid can be intuitively felt, which is convenient for students to understand the principles of microchannel continuous flow reactions and troubleshoot experimental equipment failures. At the same time, the material cost is low and it is easy to install.

[0030] The polytetrafluoroethylene pipe heating system using a water bath or a magnetic heating stirrer is low-cost and simple in structure and can be built by students themselves. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 Provide the technical flow chart of the present invention;

[0032] Figure 2 Provide the teaching experiment diagram of the present invention;

[0033] Figure 3 This is a teaching experiment diagram of a water bath circulation system built by the present invention;

[0034] Figure 4 It is a schematic diagram of the liquid circulation heating structure of the external pipeline;

[0035] Figure 5 It is a schematic diagram of industrial production of the present invention.

[0036] Figure symbols: V1, acetic anhydride raw material tank; V2, salicylic acid raw material tank; V3, oxadiazine receiving tank; V4, post-treatment liquid receiving tank; V5, aspirin receiving tank; V6, solid-liquid mixture receiving tank; P1, first pump body; P2, second pump body; P3, third pump body; P4, fourth pump body; P5, fifth pump body; R1, microchannel reactor; R2, tubular reactor; E1, hot and cold wells; E2, heat exchanger; X1, horizontal scraper centrifuge; T1, scraped film evaporator; B1, hot water supplier; H1, crude product discharge port;

[0037] H2, water inlet; H3, hot oil inlet; H4, hot oil outlet; H5, crude product outlet; H6, steam inlet; H7, condensed water outlet; H8, dioxane outlet; H9, concentrate liquid outlet; H10, hot water inlet; H11, solid-liquid mixture inlet; H12, aspirin outlet; H13, liquid outlet; Z1, back pressure valve; A1, stainless steel three-way valve; A2, outer tube; A3, polytetrafluoroethylene inner tube; A4, liquid inlet; A5, material flow inlet; A6, liquid outlet; A7, material flow outlet. DETAILED DESCRIPTION

[0038] The technical solution of the present invention is further described below in conjunction with the accompanying drawings and specific embodiments.

[0039] Embodiment 1, as Figures 1 to 5 As shown, the technical solution of the present invention comprises the following steps:

[0040] Step 1: Mix and dissolve salicylic acid and acetic anhydride in an organic solvent in a certain proportion to obtain the materials required for the reaction. The organic solvent used in this embodiment is dioxane, which has the advantages of low cost, less material, high melting point and boiling point, and the higher the temperature, the less the amount used;

[0041] Step 2: pre-set the continuous flow tubular reactor, set the temperature of the reaction part to 60-80°C, set the temperature of the collection part to 60-80°C, set the pressure of the vacuum pump to 0.01-1MPa, and the feed rate to 2-20mL / min. Assemble the reaction device required for the experiment as shown in the figure and squeeze the nitrogen balloon or turn on the diaphragm pump to remove the air in the device and check the air tightness of the device, and turn on the heating device to preheat the microchannel reaction system;

[0042] Step 3: After the reaction temperature is stabilized, connect the vacuum pump to the experimental device to allow the reaction materials in step 1 to enter the microchannel reactor, with the residence time of the feed reaction part being 0.5-5 min and the residence time of the delayed reaction part being 5-15 min;

[0043] Step 4: Turn off the device, wait for the collected material to cool to room temperature, add a certain amount of hot water, filter, wash with mixed solvent, and dry to obtain a pure product with a yield of 80%-95%, a melting point of 132°C, and a complete reaction on the TLC plate.

[0044] The microchannel reactor is connected to the mixer by a polytetrafluoroethylene pipe with an inner diameter of 3-10 mm and an outer diameter of 5-20 mm. It has good chemical corrosion resistance and heat transfer performance, can react directly in a water bath or a magnetic heating stirrer, and can also be directly connected to the heating and heat preservation device described in the present invention.

[0045] The reaction principle is as follows:

[0046]

[0047] The present invention can be further understood by giving the following examples:

[0048] The present invention can be used for teaching experiment method example Figure 2 The following steps are shown:

[0049] Dissolve 30 g of salicylic acid and 125 mL of dioxane in a three-necked flask, add 45 mL of acetic anhydride and concentrated sulfuric acid at a catalyst dosage to 80 mL of dioxane to prepare an equal amount of solvent, mix well, and add to the three-necked flask. Pre-set a continuous flow tubular reactor: place the mixing head in a magnetic heating stirrer, set the heating temperature to 75°C, set the vacuum distillation temperature of the receiving bottle to 75°C, turn on the vacuum pump to set the pressure to 0.1 MPa, squeeze the nitrogen balloon to make the feed rate 2 mL / min, and wait until all the air in the continuous flow reactor is exhausted and After the pressure and temperature are stable, the reaction bottle is connected, the feed is reacted, the reaction residence time is 5 minutes, and the reduced pressure distillation time is 10 minutes. When the solution in the receiving bottle is reduced to about 15%-30%, hot water at a temperature of 60-80°C is added. After cooling to room temperature, it is filtered and washed 1-2 times with a mixed solvent of dioxane: water = 1:2, and then dried to obtain white crystals, weighing 35.14 g (0.195 mol), with a yield of 90%. TLC control shows that the salicylic acid reaction is complete, and the melting point of the product is 132°C.

[0050] The present invention can be used for teaching experiments using a self-built water bath circulation system. Figure 3 The following steps are shown:

[0051] Dissolve 30g of salicylic acid and 65mL of dioxane in a three-necked flask, add 45mL of acetic anhydride and concentrated sulfuric acid with a catalyst dosage to 20mL of dioxane to prepare an equal amount of solvent, mix well and add to the three-necked flask, and pre-set a continuous flow tubular reactor: place the mixing head in a magnetic heating stirrer, set the heating temperature to 75℃, set the vacuum distillation temperature of the receiving bottle to 75℃, turn on the hot water circulation pump also placed in the magnetic heating stirrer to maintain the hot water temperature in the outer tube at 75℃, turn on the vacuum pump to set the pressure to 0.1MPa, squeeze the nitrogen balloon to make the feed rate 2mL / min After all the air in the continuous flow reaction device is discharged and the pressure and temperature are stable, the reaction bottle is connected, the feed reaction is carried out, the reaction residence time is 5 minutes, and the reduced pressure distillation time is 10 minutes. When the solution in the receiving bottle is reduced to about 15%-30%, hot water with a temperature of 60-80°C is added. After cooling to room temperature, it is filtered, washed 1-2 times with a mixed solvent of dioxane: water = 1:2, and then dried to obtain white crystals, weighing 34.95g (0.193mol), with a yield of 89%. TLC control shows that the salicylic acid reaction is complete, and the melting point of the product is 132°C.

[0052] The present application relates to a device for synthesizing aspirin using microchannel continuous flow technology, which includes a premixing system for mixing raw materials, a reaction system for providing reaction conditions for the materials, and a continuous post-treatment system for separating and purifying the materials after the reaction. The premixing system and the reaction system, as well as the reaction system and the continuous post-treatment system are connected by polytetrafluoroethylene pipes, and valves are provided at the connections to control the entry and exit of materials.

[0053] The premixing system includes an acetic anhydride raw material tank V1, a salicylic acid raw material tank V2, a first pump body P1 and a second pump body P2, the input end of the first pump body P1 is connected to the acetic anhydride raw material tank V1, and the input end of the second pump body P2 is connected to the salicylic acid raw material tank V2. After the acetic anhydride and salicylic acid in the acetic anhydride raw material tank V1 and the salicylic acid raw material tank V2 are fully dissolved with a sufficient amount of dioxane, they are pumped into the reaction system through pipelines by the first pump body P1 and the second pump body P2 respectively.

[0054] Furthermore, the reaction system includes a microchannel reactor R1, a hot and cold well E1 and a heat exchanger E2. The set temperature of the hot and cold well E1 is 70-80°C. The output ends of the first pump body P1 and the second pump body P2 are both connected to the microchannel reactor R1. The microchannel reactor R1 and the heat exchanger E2 are connected through the crude product discharge port H1. The heat exchanger E2 is provided with a water inlet H2. The heat exchanger E2 and the hot and cold well E1 are connected through a hot oil inlet H3. The microchannel reactor R1 and the hot and cold well E1 are connected through a hot oil outlet H4.

[0055] The length of the pipeline in the heat exchanger E2 is 30-50 m. The first pump body P1 and the second pump body P2 are set to have the same flow rate, which is 2 mL / min-20 mL / min, and the pressure is 0-1 bar.

[0056] The material enters the microchannel reactor R1 under the action of the first pump body P1 and the second pump body P2. After passing through the microchannel reactor R1, the material flows into the polytetrafluoroethylene pipe in the heat exchanger E2 for delayed reaction. The micro-reaction part is provided with the temperature required for the reaction by the hot and cold wells E1. The heated hot oil flows out from the hot oil outlet H4, enters the microchannel reactor R1, and then flows into the heat exchanger E2 through the pipeline, and finally flows back to the hot and cold wells E1 from the hot oil inlet H3.

[0057] In this embodiment, the continuous post-treatment system includes a scraped film evaporator T1, a tubular reactor R2, and a horizontal scraper centrifuge X1. The scraped film evaporator T1 is connected to the heat exchanger E2 through a crude product discharge port H5. The scraped film evaporator T1 is provided with a steam inlet H6, a condensed water outlet H7 and a dioxane outlet H8. The dioxane outlet H8 is connected to a third pump body P3. The dioxane outlet H8 is connected to the input end of the third pump body P3, and the output end of the third pump body P3 is connected to an oxadiazole receiving tank V3.

[0058] Furthermore, the scraper film evaporator T1 is provided with a concentrated liquid outlet H9, the other end of the concentrated liquid outlet H9 is connected to a solid-liquid mixture receiving tank V6, the solid-liquid mixture receiving tank V6 is connected to a fourth pump body P4, the solid-liquid mixture receiving tank V6 is connected to the input end of the fourth pump body P4, the output end of the fourth pump body P4 is connected to the tubular reactor R2, the tubular reactor R2 is connected to a hot water inlet H10, the hot water in the hot water inlet H10 is 75 degrees, the hot water inlet H10 is connected to a fifth pump body P5, the hot water inlet H10 is connected to the input end of the fifth pump body P5, and the output end of the fifth pump body P5 is connected to a hot water supplier B1.

[0059] A back pressure valve Z1 is installed on the crude product discharge port H5. The crude product mixed liquid enters the continuous post-processing system through the crude product discharge port H5. The back pressure valve Z1 adjusts the crude product entry rate in the scraped film evaporator T1. Before the material enters the scraped film evaporator T1, the film evaporator is first preheated to the set temperature and the air pressure is negative pressure so that the material starts to evaporate after entering the scraped film evaporator T1.

[0060] After the scraped film evaporator T1 evaporates part of the dioxane in the incoming crude product, a liquid level sensor is provided in the scraped film evaporator T1. After a certain amount of concentrated liquid is collected from the bottom of the scraped film evaporator T1, the pressure is adjusted to discharge the material from the concentrated liquid outlet H9, enter the solid-liquid mixture receiving tank V6, and then enter the tubular reactor R2 through the concentrated liquid outlet H9 by the fourth pump body P4.

[0061] The liquid evaporated from the scraped film evaporator T1 enters the dioxane receiving tank V3 through the third pump body P3 and the dioxane outlet H8 for recycling.

[0062] Furthermore, the tubular reactor R2 and the horizontal scraper centrifuge X1 are connected through the solid-liquid mixture inlet H11, and the horizontal scraper centrifuge X1 is provided with an aspirin discharge port H12 and a liquid outlet H13, the aspirin discharge port H12 is connected to an aspirin receiving tank V5, and the liquid outlet H13 is connected to a post-processing liquid receiving tank V4.

[0063] The hot water in the hot water supplier B1 enters the tubular reactor R2 through the hot water inlet H10 from the fourth pump body P4, and the concentrated liquid is recrystallized to form a solid-liquid mixture. The solid-liquid mixture in the tubular reactor R2 enters the horizontal scraper centrifuge X1 through the solid-liquid mixture inlet H11 for rejection filtration separation. The crystals in the horizontal scraper centrifuge X1 are sent by its own scraper through the aspirin discharge port H12 into the aspirin receiving tank V5, and the mixed liquid enters the post-processing liquid receiving tank V4 through the liquid outlet H13.

[0064] Working principle: After the acetic anhydride and salicylic acid in the acetic anhydride raw material tank V1 and the salicylic acid raw material tank V2 are fully dissolved with a sufficient amount of dioxane, they are pumped into the reaction system through pipelines by the first pump body P1 and the second pump body P2 respectively. The materials enter the microchannel reactor R1 under the action of the first pump body P1 and the second pump body P2. After passing through the microchannel reactor R1, the materials flow into the polytetrafluoroethylene pipeline in the heat exchanger E2 for delayed reaction. The micro-reaction part is provided with the temperature required for the reaction by the hot and cold wells E1. The heated hot oil flows out from the hot oil outlet H4, enters the microchannel reactor R1, then flows into the heat exchanger E2 through the pipeline, and finally flows back to the hot and cold wells E1 from the hot oil inlet H3. A back pressure valve Z1 is installed on the crude product discharge port H5. The crude product mixed liquid enters the continuous post-processing system through the crude product discharge port H5. The back pressure valve Z1 adjusts the crude product entry rate in the scraper film evaporator T1. Before the material enters the scraper film evaporator T1, the film evaporator is first preheated to the set temperature, and the air pressure is negative pressure, so that the material starts to evaporate after entering the scraper film evaporator T1. After the scraper film evaporator T1 evaporates the dioxane part of the crude product entering, the scraper film evaporator T1 is provided with a liquid level sensor. After the concentrated liquid is collected from the bottom of the scraper film evaporator T1 to a certain amount, the pressure is adjusted to discharge the material from the concentrated liquid outlet H9, enter the solid-liquid mixture receiving tank V6, and then enter the tubular reactor R2 through the concentrated liquid outlet H9 from the fourth pump body P4. The liquid evaporated from the scraper film evaporator T1 enters the oxane receiving tank V3 through the dioxane outlet H8 from the third pump body P3 for recycling. The hot water in the hot water supplier B1 enters the tubular reactor R2 through the fourth pump body P4 through the hot water inlet H10, and the concentrated liquid is recrystallized to form a solid-liquid mixture. The solid-liquid mixture in the tubular reactor R2 enters the horizontal scraper centrifuge X1 through the solid-liquid mixture inlet H11 for rejection and separation. The crystals in the horizontal scraper centrifuge X1 enter the aspirin receiving tank V5 through the aspirin discharge port H12 by the scraper provided by the scraper, and the mixed liquid enters the post-treatment liquid receiving tank V4 through the liquid outlet H13. In summary, the product yield is 70%-95%, and the purity is more than 99%.

[0065] Embodiment 2, as Figure 4 As shown, based on the second embodiment, the liquid circulation heating structure of the external pipeline includes a stainless steel three-way valve A1, an outer tube A2 is fixedly installed inside the stainless steel three-way valve A1, a polytetrafluoroethylene inner tube A3 is fixedly installed inside the outer tube A2, a liquid inlet A4 and a liquid outlet A6 are provided on the outer tube A2, and a material flow inlet A5 and a material flow outlet A7 are provided on the polytetrafluoroethylene inner tube A3.

[0066] The specific working principle of this embodiment is: hot water enters the outer tube A2 through the liquid inlet A4, and the material enters the polytetrafluoroethylene inner tube A3 through the material inlet A5, so that the hot water and the material can exchange heat. After the heat exchange is completed, the material and hot water flow out through the material outlet A7 and the liquid outlet A6 respectively.

[0067] The above specific embodiments are only several optional embodiments of the present invention. Based on the technical solutions of the present invention and the relevant inspirations of the above embodiments, those skilled in the art can make various alternative improvements and combinations to the above specific embodiments.

Claims

1. A method for synthesizing aspirin using microchannel continuous flow technology, characterized in that: include: Step 1, dissolving salicylic acid in an organic solvent in a certain proportion through a feeding device, together with acetic anhydride and concentrated sulfuric acid as reaction materials, wherein the mass ratio of salicylic acid, acetic anhydride and concentrated sulfuric acid is 1:1-2:0.1-0.6; Step 2: the feeding device used is any one or more of a peristaltic pump, a syringe pump, a vacuum pump and a nitrogen balloon; Step 3: using a micro-reaction device, a microchannel mixer and a polytetrafluoroethylene connecting tube to add materials under nitrogen protection, the process is anhydrous and oxygen-free, connected to a post-processing device, the reaction conditions are 60-80°C, the residence time is 0.5-5min, the flow rate is 2-20mL / min, and the reaction tube section is equipped with a heating and heat preservation device to keep the pipeline temperature at the reaction temperature; Step 4: separation and purification using a continuous post-processing device.

2. A method for synthesizing aspirin using microchannel continuous flow technology as claimed in claim 1, characterized in that: The organic solvent is any one of dioxane, acetonitrile, ethyl acetate, dichloroethane, dimethylformamide or dimethyl sulfoxide, and the mass ratio of the organic solvent to the salicylic acid is 4-50:

1.

3. A method for synthesizing aspirin using microchannel continuous flow technology as claimed in claim 2, characterized in that: The micro-reaction device adopts a polytetrafluoroethylene tube and a micro-channel mixer, wherein the shape of the micro-channel mixer is any one of a heart shape, a wave shape and a tube shape.

4. A method for synthesizing aspirin using microchannel continuous flow technology as claimed in claim 3, characterized in that: The micro-reaction device has an inner diameter of 3-10 mm and an outer diameter of 5-20 mm.

5. A method for synthesizing aspirin using microchannel continuous flow technology as claimed in claim 4, characterized in that: The reaction section tube length of the micro-reaction device is 5-50m, and the liquid holding capacity of the micro-reaction device is 5-50mL.

6. A method for synthesizing aspirin using a microchannel continuous flow technology as claimed in claim 5, characterized in that: The micro-reactor equipment feeding reaction section and delayed reaction section pipelines are provided with heating and heat preservation devices, and the heating and heat preservation device is any one of an electric heating jacket, a warm air system or a liquid circulation heating with an external pipeline.

7. A method for synthesizing aspirin using a microchannel continuous flow technology as claimed in claim 6, characterized in that: The liquid circulation heating device provided in the reaction section of the micro-reaction equipment uses silicone oil or water as the heating medium, and the material of the outer pipeline is a rubber tube with heat preservation performance.

8. A method for synthesizing aspirin using microchannel continuous flow technology as claimed in claim 7, characterized in that: The micro-reaction device has a reaction time of 0.5-2 minutes and a delayed reaction time of 2-20 minutes, and also includes a device for synthesizing aspirin using a microchannel continuous flow technology; The device comprises a premixing system for mixing raw materials, a reaction system for providing reaction conditions for the materials, and a continuous post-processing system for separating and purifying the materials after the reaction. The premixing system and the reaction system, as well as the reaction system and the continuous post-processing system are connected through polytetrafluoroethylene pipes, and valves are provided at the connections.

9. A method for synthesizing aspirin using microchannel continuous flow technology as claimed in claim 8, characterized in that: The premixing system comprises an acetic anhydride raw material tank (V1), a salicylic acid raw material tank (V2), a first pump body (P1) and a second pump body (P2), wherein the input end of the first pump body (P1) is connected to the acetic anhydride raw material tank (V1), and the input end of the second pump body (P2) is connected to the salicylic acid raw material tank (V2). The reaction system comprises a microchannel reactor (R1), a hot and cold well (E1) and a heat exchanger (E2), wherein the hot and cold well (E1) is set at a temperature of 70-80°C. ℃, the output ends of the first pump body (P1) and the second pump body (P2) are both connected to the microchannel reactor (R1), the microchannel reactor (R1) and the heat exchanger (E2) are connected through a crude product discharge port (H1), the heat exchanger (E2) is provided with a water inlet (H2), the heat exchanger (E2) and the hot and cold wells (E1) are connected through a hot oil inlet (H3), and the microchannel reactor (R1) and the hot and cold wells (E1) are connected through a hot oil outlet (H4).

10. A method for synthesizing aspirin using microchannel continuous flow technology according to claim 9, characterized in that: The continuous post-treatment system comprises a scraper film evaporator (T1), a tubular reactor (R2), and a horizontal scraper centrifuge (X1); the scraper film evaporator (T1) is connected to a heat exchanger (E2) via a crude product discharge port (H5); the scraper film evaporator (T1) is provided with a steam inlet (H6), a condensed water outlet (H7) and a dioxane outlet (H8); the dioxane outlet (H8) is connected to a third pump body (P3); the dioxane outlet (H8) is connected to an input end of the third pump body (P3); and the output end of the third pump body (P3) is connected to a dioxane receiving tank (V3); The scraper film evaporator (T1) is provided with a concentrated liquid outlet (H9), the other end of the concentrated liquid outlet (H9) is connected to a solid-liquid mixture receiving tank (V6), the solid-liquid mixture receiving tank (V6) is connected to a fourth pump body (P4), the solid-liquid mixture receiving tank (V6) is connected to an input end of the fourth pump body (P4), the output end of the fourth pump body (P4) is connected to the tubular reactor (R2), the tubular reactor (R2) is connected to a hot water inlet (H10), the hot water inlet (H10) is connected to a fifth pump body (P5), the hot water inlet (H10) is connected to an input end of the fifth pump body (P5), and the output end of the fifth pump body (P5) is connected to a hot water supplier (B1); The tubular reactor (R2) and the horizontal scraper centrifuge (X1) are connected via a solid-liquid mixture inlet (H11); the horizontal scraper centrifuge (X1) is provided with an aspirin discharge port (H12) and a liquid outlet (H13); the aspirin discharge port (H12) is connected to an aspirin receiving tank (V5); and the liquid outlet (H13) is connected to a post-treatment liquid receiving tank (V4).

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