Continuous synthesis system and method of 2-methyl-5-nitroimidazole

Abstract

The present invention provides a continuous synthesis system and synthesis method of 2-methyl-5-nitroimidazole. The system includes a raw material premixing unit, a continuous nitration unit, a continuous post-processing unit and a control unit, wherein the continuous nitration unit includes a mixing-reaction module and a gas treatment module, wherein the mixing-reaction module includes 10 to 40 longitudinally cross-arranged pipelines, wherein the angle formed between the upper and lower adjacent pipelines is 10 to 50°; the problem that the synthesis method of 2-methyl-5-nitroimidazole in the prior art is not suitable for industrialized amplification production can be solved, and the system is suitable for the field of 2-methyl-5-nitroimidazole synthesis.

Description

Technical Field

[0001] The invention relates to the field of 2-methyl-5-nitroimidazole synthesis, and in particular to a continuous synthesis system and a synthesis method of 2-methyl-5-nitroimidazole. Background Art

[0002] 2-Methyl-5-nitroimidazole, molecular formula C 4 H 5 N 3 O 2 , white or light yellow crystalline powder, melting point 252~254℃, insoluble in water, slightly soluble in methanol and ethanol, easily soluble in strong acids and bases. 2-Methyl-5-nitroimidazole is usually used as an intermediate for organic synthesis of drugs such as metronidazole and dimethoate.

[0003] 2-Methyl-5-nitroimidazole has a wide range of uses. In the prior art, 2-methylimidazole is mostly used as a raw material, and nitric acid is added dropwise in a sulfuric acid medium under high temperature conditions to carry out a nitration reaction to obtain the product. However, in the prior art, 2-methyl-5-nitroimidazole is mostly produced in an intermittent operation mode, which has low production efficiency and is not suitable for industrialized large-scale production. Summary of the invention

[0004] The main purpose of the present invention is to provide a continuous synthesis system and method of 2-methyl-5-nitroimidazole, so as to solve the problem that the synthesis method of 2-methyl-5-nitroimidazole in the prior art is not suitable for industrial scale-up production.

[0005] In order to achieve the above object, according to a first aspect of the present invention, a continuous synthesis system of 2-methyl-5-nitroimidazole is provided, the continuous synthesis system comprising:

[0006] The invention comprises a raw material continuous feeding module, a fuming sulfuric acid continuous feeding module, a continuous batching module and a fuming nitric acid continuous feeding module, wherein the fuming sulfuric acid continuous feeding module, the raw material continuous feeding module and the continuous batching module are connected in sequence; the continuous nitration unit comprises a mixing-reaction module and a gas treatment module, wherein the mixing-reaction module comprises a reaction raw material inlet, a gas outlet and a liquid outlet, wherein the reaction raw material inlet is respectively connected to the outlet of the fuming nitric acid continuous feeding module and the outlet of the continuous batching module, and the gas outlet is connected to the inlet of the gas treatment module; the mixing-reaction module comprises 10-40 The invention discloses a method for preparing a novel nanostructured carbon nanotube reactor, comprising a plurality of longitudinally cross-arranged pipelines, wherein the angle formed by the upper and lower adjacent pipelines is 10-50 degrees; a continuous post-processing unit, comprising an alkali solution supply module, a continuous quenching-pH adjustment module, a continuous solid-liquid separation module and a continuous drying module connected in sequence, wherein the inlet of the continuous quenching-pH adjustment module is connected to the liquid outlet of the mixing-reaction module; a control unit, which is electrically connected to the raw material continuous feeding module, the fuming sulfuric acid continuous feeding module, the continuous batching module, the fuming nitric acid continuous feeding module, the mixing-reaction module, the continuous batching module and the alkali solution supply module respectively.

[0007] Furthermore, the raw material continuous feeding module includes a raw material storage device, a raw material feeding device and a raw material feed metering device, wherein the raw material storage device, the raw material feeding device and the raw material feed metering device are connected in sequence; the raw material feed metering device is electrically connected to the control unit to feed back the raw material feed amount to the control unit to adjust the raw material feed amount.

[0008] Furthermore, the oleum continuous feeding module includes an oleum storage device, an oleum feeding device and an oleum feeding metering device, wherein the oleum storage device, the oleum feeding device and the oleum feeding metering device are connected in sequence; the oleum feeding device is used for continuous feeding of oleum; and the oleum feeding metering device is used for feeding back the feeding amount of oleum to the control unit to adjust the feeding speed of oleum.

[0009] Furthermore, the fuming nitric acid continuous feeding module includes a fuming nitric acid storage device, a fuming nitric acid feeding device and a fuming nitric acid feeding metering device, wherein the fuming nitric acid storage device, the fuming nitric acid feeding device and the fuming nitric acid feeding metering device are connected in sequence; the fuming nitric acid feeding device is used for continuous feeding of fuming nitric acid; the fuming nitric acid feeding metering device is used for feeding back the feeding amount of fuming nitric acid to the control unit to adjust the feeding speed of the fuming nitric acid.

[0010] Furthermore, the outlet of the fuming nitric acid continuous feeding module and the outlet of the continuous dosing module are both connected to the inlet of the mixing-reaction module, and the inlet of the gas treatment module and the inlet of the continuous quenching-pH adjustment module are both connected to the outlet of the mixing-reaction module.

[0011] Furthermore, the alkali solution supply module includes an alkali solution storage device, an alkali solution feeding device and an alkali solution feeding metering device; wherein the alkali solution storage device, the alkali solution feeding device and the alkali solution feeding metering device are connected in sequence;

[0012] The alkali solution feeding device is used for continuous feeding of the alkali solution; the alkali solution feeding metering device is used for feeding back the alkali solution feeding amount to the control unit to adjust the alkali solution feeding speed.

[0013] Furthermore, the continuous post-treatment unit 3 also includes a pH monitoring module; the pH monitoring module is electrically connected to the continuous quenching-pH adjustment module and the control unit, respectively, to monitor the pH of the system during the quenching process, and to control the feed rate of the alkali solution supply module so that the pH in the continuous quenching-pH adjustment module is 3~6.

[0014] In order to achieve the above object, according to a second aspect of the present invention, a continuous synthesis method of 2-methyl-5-nitroimidazole is provided, the synthesis method comprising: synthesizing 2-methyl-5-nitroimidazole using any of the above-mentioned continuous production systems of 2-methyl-5-nitroimidazole, the synthesis method comprising:

[0015] S1) in a raw material premixing unit, the raw material and oleum are respectively fed into a continuous batching module through a raw material continuous feeding module and an oleum continuous feeding module for first mixing to obtain a first liquid;

[0016] S2) inputting fuming nitric acid into the continuous nitration unit through the fuming nitric acid continuous feeding module, performing a second mixing of the first liquid and the fuming nitric acid in the mixing-reaction module, causing a nitration reaction, obtaining a second liquid, and the gas generated in the nitration reaction entering the gas treatment module;

[0017] S3) in a continuous post-treatment unit, the second liquid is sequentially passed through a continuous quenching-pH adjustment module, a continuous solid-liquid separation module and a continuous drying module, and quenching, solid-liquid separation and drying are performed in sequence to obtain 2-methyl-5-nitroimidazole;

[0018] A control unit is used to control the feed rate of raw materials, fuming sulfuric acid and fuming nitric acid, as well as the batching temperature and the nitration reaction temperature;

[0019] The raw materials include 2-methylimidazole; the temperature of the first mixing is 100-130°C; and the temperature of the nitration reaction is 110-150°C.

[0020] Furthermore, in S1), the residence time of the first liquid in the continuous dosing module is 10 to 50 minutes.

[0021] Furthermore, in S2), during the nitration reaction, the mass ratio of the raw material, fuming sulfuric acid and fuming nitric acid is 1:(1.5~2.5):(1~1.5); and the nitration reaction time is 30~100min.

[0022] Further, in S3), the quenching temperature is 25-65°C, the quenching time is 10-30 min, and the quenching pH is 3-6.

[0023] By applying the technical solution of the present invention, in the raw material premixing unit, the raw material and fuming sulfuric acid can be mixed uniformly, the raw material reaction liquid is input into the continuous nitration unit, and the second mixing is performed with fuming nitric acid, and the nitration reaction occurs in the mixing-reaction module. The mixing-reaction device includes 10 to 40 longitudinally cross-arranged pipes, and the angle formed between the upper and lower adjacent pipes is 10 to 50 degrees, which can shorten the retention time of the gas in the reactor, and use the kinetic energy of the liquid itself to mix uniformly, avoid the generation of by-products, and the gas can be absorbed by the gas treatment module in time. The liquid product (second liquid) produced by the nitration reaction enters the continuous post-processing unit, and after quenching, solid-liquid separation and drying in sequence, high-purity 2-methyl-5-nitroimidazole can be obtained. Using the continuous synthesis system of the present application, the cycle of synthesizing 2-methyl-5-nitroimidazole can be shortened, the cost is low, the reaction conditions are milder than the reaction conditions in the prior art, and it is more suitable for industrialized scale-up production. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The drawings constituting a part of the present application are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the drawings:

[0025] Figure 1 A schematic diagram of a continuous synthesis system of 2-methyl-5-nitroimidazole according to an embodiment of the present invention is shown.

[0026] The above drawings include the following reference numerals:

[0027] 1. Raw material premixing unit; 11. Raw material continuous feeding module; 111. Raw material storage device; 112. Raw material feeding device; 113. Raw material feeding metering device; 12. Oleum continuous feeding module; 121. Oleum storage device; 122. Oleum feeding device; 123. Oleum feeding metering device; 13. Continuous batching module; 14. Fuming nitric acid continuous feeding module; 141. Fuming nitric acid storage device; 142. Fuming nitric acid feeding device; 143. Fuming nitric acid feeding metering device; 2. Continuous nitration unit; 21. Mixing-reaction module; 22. Gas treatment module; 3. Continuous post-treatment unit; 31. Alkali solution supply module; 311. Alkali solution storage device; 312. Alkali solution feeding device; 313. Alkali solution feeding metering device; 32. Continuous quenching-pH adjustment module; 33. Continuous solid-liquid separation module; 34. Continuous drying module; 35. pH monitoring module; 4. Control unit. DETAILED DESCRIPTION

[0028] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present invention will be described in detail below in conjunction with the embodiments.

[0029] Terminology explanation:

[0030] Oleum: A colorless or slightly colored thick liquid, it is a type of sulfuric acid containing an excess of sulfur trioxide with a concentration of 105%.

[0031] Fuming nitric acid: nitric acid with a concentration of 98%.

[0032] As mentioned in the background technology, the method for synthesizing 2-methyl-5-nitroimidazole in the prior art is not suitable for industrial scale-up production. Therefore, in the present application, the inventors attempt to develop a new continuous synthesis system and synthesis method for 2-methyl-5-nitroimidazole, using fuming sulfuric acid and fuming nitric acid as raw materials, which can realize the industrial scale-up production of high-purity 2-methyl-5-nitroimidazole, and on this basis, propose a series of protection schemes of the present application.

[0033] In a first typical embodiment of the present application, a continuous synthesis system of 2-methyl-5-nitroimidazole is provided. The schematic diagram of the continuous synthesis system is as follows: Figure 1 As shown,

[0034] The raw material premixing unit 1 comprises a raw material continuous feeding module 11, a fuming sulfuric acid continuous feeding module 12, a continuous batching module 13 and a fuming nitric acid continuous feeding module 14, wherein the fuming sulfuric acid continuous feeding module 12, the raw material continuous feeding module 11 and the continuous batching module 13 are connected in sequence;

[0035] The continuous nitration unit 2 includes a mixing-reaction module 21 and a gas processing module 22. The mixing-reaction module includes a reaction raw material inlet, a gas outlet and a liquid outlet. The reaction raw material inlet is respectively connected to the outlet of the fuming nitric acid continuous feeding module 14 and the outlet of the continuous batching module 13, and the gas outlet is connected to the inlet of the gas processing module 22.

[0036] The mixing-reaction module 21 includes 10 to 40, including but not limited to 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 or 40 longitudinally cross-arranged pipes, wherein the angle formed between the upper and lower adjacent pipes is 10 to 50°, including but not limited to 10°, 15°, 20°, 25°, 30°, 35°, 40°, 45° or 50°;

[0037] The continuous post-processing unit 3 comprises an alkali solution supply module 31, a continuous quenching-pH adjustment module 32, a continuous solid-liquid separation module 33 and a continuous drying module 34 which are connected in sequence, and the inlet of the continuous quenching-pH adjustment module 32 is connected to the liquid outlet of the mixing-reaction module 21;

[0038] The control unit 4 is electrically connected to the raw material continuous feeding module 11, the fuming sulfuric acid continuous feeding module 12, the continuous batching module 13, the fuming nitric acid continuous feeding module 14, the mixing-reaction module 21, the continuous batching module 13 and the alkali solution supply module 31 respectively;

[0039] The raw materials include 2-methylimidazole; the temperature of the continuous batching module 13 is set to 100-130°C, including but not limited to 100°C, 101°C, 102°C, 103°C, 104°C, 105°C, 106°C, 107°C, 108°C, 109°C, 110°C, 120°C or 130°C; the temperature of the mixing-reaction module 21 is set to 110-150°C, including but not limited to 110°C, 120°C, 130°C, 140°C or 150°C, preferably 120-130°C.

[0040] The nitration reaction of 2-methyl-5-nitroimidazole requires the use of excess concentrated nitric acid and concentrated sulfuric acid, and the reaction can only be carried out under high temperature conditions. However, the nitration reaction releases a large amount of heat, and the high reaction temperature easily leads to the decomposition of the raw material 2-methylimidazole, reducing the reaction yield. Due to this reason, the existing intermittent production has a large potential safety risk and a low reaction yield. The reaction formula is as follows:

[0041] .

[0042] In a specific embodiment of the present application, first in the raw material premixing unit 1, 2-methylimidazole and fuming sulfuric acid are respectively fed into the continuous batching module 13 through the raw material continuous feeding module 11 and the fuming sulfuric acid continuous feeding module 12 for the first mixing, the temperature of the continuous batching module is controlled within the above-mentioned range to obtain the first liquid, and the fuming nitric acid is provided to the continuous nitration unit through the fuming nitric acid continuous feeding module 14.

[0043] Compared with concentrated sulfuric acid, fuming sulfuric acid has a higher activity in catalyzing nitration reactions. However, in the traditional batch process for producing 2-methyl-5-nitroimidazole, the material risk level of fuming sulfuric acid is higher and the batch process is difficult to control. Considering the process safety, concentrated sulfuric acid is generally used to prepare 2-methyl-5-nitroimidazole, and fuming sulfuric acid with higher activity is not considered. For general continuous reaction devices, a large amount of nitrogen oxide gas will be generated during the reverse process of preparing 2-methyl-5-nitroimidazole. Fuming sulfuric acid contains a large amount of SO 3 Gas will deteriorate the working performance of the continuous reaction device over time and reduce the service life of the device. Therefore, concentrated sulfuric acid is generally used in the continuous reaction device to participate in the reaction of preparing 2-methyl-5-nitroimidazole.

[0044] In the continuous synthesis system of 2-methyl-5-nitroimidazole of the present application, fuming sulfuric acid is used instead of concentrated sulfuric acid, and fuming nitric acid is used instead of concentrated nitric acid. In combination with the parameters of each unit in the continuous system of the present application, the low water content of fuming sulfuric acid (water content will inhibit the nitration reaction) is utilized, and the high activity of fuming sulfuric acid is utilized to further reduce the reaction temperature required for the nitration reaction. In addition, the present application avoids the SO 3 The gas and the possible hazards it may bring make the reaction easier to control, the reaction conditions are relatively mild and safe, and the decomposition and deterioration of the raw material 2-methylimidazole are avoided, thereby improving the reaction yield. The concentration of oleum in this application is 105%.

[0045] In the continuous nitration unit 2, the first liquid and the fuming nitric acid are mixed in the mixing-reaction module 21 for a second time, and a nitration reaction occurs at 110-150°C to obtain a second liquid. This reaction process releases heat and produces NO X After the gas-liquid separation at the outlet of the mixing-reaction module 21, the gas enters the gas treatment module 22 and is directly absorbed and treated by the alkali liquid, and the second liquid is continuously input into the continuous post-treatment unit for post-treatment. The concentration of the fuming nitric acid in this application is 98%.

[0046] The nitration synthesis reaction of 2-methyl-5-nitroimidazole has the characteristics of large amount of gas release, concentrated and intense reaction heat release, etc. The use of traditional microchannel reaction devices will lead to low internal space utilization of the device, and a large amount of reaction gas production will have an adverse effect on the reaction yield of the microchannel reactor. The reaction yield of the product synthesized by using a microchannel reactor in the prior art is usually not higher than 70%; and in the prior art, an exhaust device is often provided to absorb this gas. The exhaust capacity of the existing continuous reaction device is limited, and the large amount of by-product nitrogen oxide gas has an adverse effect on the retention time, residence time distribution and material mixing state of the continuous reactor, resulting in the inability to completely convert the material and reducing the reaction yield.

[0047] The tubular reactor in the mixing-reaction module 21 of the present application adopts a longitudinal cross arrangement, bottom feeding, and high-point discharge, which eliminates the interference of a large amount of gas generated during the reaction process on the residence time of the continuous nitration reaction device, improves the volume utilization rate of the equipment, and ensures that the raw material 2-methylimidazole is completely converted. And the present application controls the angle formed between the upper and lower adjacent pipelines within the range of 10 to 50 degrees, ensuring that the gas is quickly discharged into the gas treatment module, while ensuring the fluidity of the liquid material and its own kinetic energy, which can further improve the mixing effect of the material and the final product yield.

[0048] In order to eliminate the influence of NOx gas generated in large quantities during the reaction process on the continuous reaction performance, the present application adopts a tubular reactor in the mixing-reaction module, which adopts a longitudinal cross arrangement, bottom feeding, and high-point discharging mode to eliminate the interference of a large amount of gas generated during the reaction process on the residence time of the continuous reactor, and utilizes the kinetic energy of the fluid itself to improve the mixing effect of the material, thereby improving the volume utilization rate of the equipment, and having a strong heat exchange capacity. Under the condition of using fuming sulfuric acid and fuming nitric acid to react with the raw material, the raw material 2-methylimidazole can be completely converted. And the reactor of the present application can be used without setting an exhaust device, directly using the kinetic energy of the gas itself and controlling the angles of the upper and lower adjacent pipes, and the gas can be quickly discharged into the processing module, and the time staying in the reactor is short, reducing the generation of by-products, further reducing the cost of production, and the yield is improved compared with the batch reaction and continuous reaction of the prior art. The reactor can be arranged in a shell and extend along the length direction of the shell.

[0049] In the continuous post-treatment unit 3, the nitration reaction completed liquid is sequentially passed through the continuous quenching-pH adjustment module 32, the continuous solid-liquid separation module 33 and the continuous drying module 34. The continuous quenching-pH adjustment module can realize online real-time quenching, avoid the large-scale storage of a large number of highly active systems, and reduce the risk level of industrial production. The alkali solution provided by the alkali solution supply module 31 is used to adjust the pH, obtain the system in the quenching process, perform solid-liquid separation, and dry it to obtain 2-methyl-5-nitroimidazole. Among them, the alkali solution of the alkali solution supply module 31 can be ammonia water, NaOH aqueous solution and Na 2 CO 3 One or more aqueous solutions.

[0050] During the reaction process, the control unit 4 accurately controls the feed rate and reaction temperature of each material according to the control logic of negative feedback regulation.

[0051] The present invention adopts the above-mentioned continuous production system of 2-methyl-5-nitroimidazole to realize the continuous preparation of 2-methyl-5-nitroimidazole, and the system can realize automatic control, save labor, reduce production costs, improve production efficiency, shorten production cycle, and improve the safety of the entire nitration process. It is also convenient to accurately control the process conditions, the nitration reaction yield is high, and at the same time, the solution system generated by the reaction can be quenched online in real time, avoiding the danger caused by long-term storage of a large amount of highly reactive materials, and improving the safety of the entire process system.

[0052] In a preferred embodiment, the raw material continuous feeding module 11 includes a raw material storage device 111, a raw material feeding device 112 and a raw material feeding metering device 113, wherein the raw material storage device 111, the raw material feeding device 112 and the raw material feeding metering device 113 are connected in sequence; the raw material feeding metering device 113 is electrically connected to the control unit 4 to feed back the feed amount of the raw material to the control unit 4 to adjust the feed amount of the raw material. The control unit 4 sends an instruction to adjust the flow rate according to the control logic of negative feedback regulation to ensure the accuracy of the feed amount of the raw material 2-methylimidazole.

[0053] In a preferred embodiment, the oleum continuous feeding module 12 includes a oleum storage device 121, a oleum feeding device 122 and a oleum feeding metering device 123, wherein the oleum storage device 121, the oleum feeding device 122 and the oleum feeding metering device 123 are connected in sequence; the oleum feeding device 122 is used for continuous feeding of oleum; the oleum feeding metering device 123 is used for feeding back the feed amount of oleum to the control unit 4 to adjust the feeding speed of oleum.

[0054] In a preferred embodiment, the fuming nitric acid continuous feeding module 14 includes a fuming nitric acid storage device 141, a fuming nitric acid feeding device 142 and a fuming nitric acid feeding metering device 143, wherein the fuming nitric acid storage device 141, the fuming nitric acid feeding device 142 and the fuming nitric acid feeding metering device 143 are connected in sequence; the fuming nitric acid feeding device 142 is used for continuous feeding of fuming nitric acid; the fuming nitric acid feeding metering device 143 is used for feeding back the feeding amount of fuming nitric acid to the control unit 4 to adjust the feeding speed of fuming nitric acid. The control unit 4 sends a flow adjustment instruction according to the control logic of negative feedback regulation to ensure the accuracy of the fuming nitric acid feeding amount.

[0055] In a preferred embodiment, the outlet of the fuming nitric acid continuous feeding module 14 and the outlet of the continuous dosing module 13 are both connected to the inlet of the mixing-reaction module 21, and the inlet of the gas treatment module 22 and the inlet of the continuous quenching-pH adjustment module 32 are both connected to the outlet of the mixing-reaction module 21.

[0056] In a preferred embodiment, the alkali liquid supply module 31 includes an alkali liquid storage device 311, an alkali liquid feeding device 312 and an alkali liquid feeding metering device 313; wherein, the alkali liquid storage device 311, the alkali liquid feeding device 312 and the alkali liquid feeding metering device 313 are connected in sequence; the alkali liquid feeding device 312 is used for continuous feeding of alkali liquid; the alkali liquid feeding metering device 313 is used for feeding back the feeding amount of alkali liquid to the control unit 4 to adjust the feeding speed of the alkali liquid.

[0057] In a preferred embodiment, the continuous post-treatment unit 3 further includes a pH monitoring module 35, which is electrically connected to the continuous quenching-pH adjustment module 32 and the control unit 4, respectively, to monitor the pH of the system during the quenching process, and to control the feed rate of the alkali solution supply module 31 so that the pH in the continuous quenching-pH adjustment module 32 is 3 to 6. If the acid or base is too high, the solubility of the product in water will increase, resulting in a large loss of mother liquor and a reduction in the reaction yield. The present application avoids the loss of mother liquor by controlling the continuous quenching-pH adjustment module in this pH range to improve the final product yield.

[0058] In a second typical embodiment of the present application, a continuous synthesis method of 2-methyl-5-nitroimidazole is provided, and 2-methyl-5-nitroimidazole is synthesized using any of the above-mentioned continuous production systems of 2-methyl-5-nitroimidazole. The synthesis method comprises: S1) in a raw material premixing unit 1, the raw material and fuming sulfuric acid are respectively input into a continuous batching module 13 through a raw material continuous feeding module 11 and a fuming sulfuric acid continuous feeding module 12 for a first mixing to obtain a first liquid; S2) fuming nitric acid is input into a continuous nitration unit 2 through a fuming nitric acid continuous feeding module 14, and the first liquid and the fuming nitric acid are second mixed in a mixing-reaction module 21 to undergo nitration. reaction to obtain a second liquid, and the gas generated in the nitration reaction enters the gas processing module 22; S3) in the continuous post-processing unit 3, the second liquid is sequentially passed through the continuous quenching-pH adjustment module 32, the continuous solid-liquid separation module 33 and the continuous drying module 34, and quenched, solid-liquid separated and dried in sequence to obtain 2-methyl-5-nitroimidazole; the control unit 4 is used to control the feed rate of the raw material, fuming sulfuric acid and fuming nitric acid, as well as the batching temperature and the nitration reaction temperature; the raw material includes 2-methylimidazole; the temperature of the first mixing is 100~130℃, preferably 120~130℃; the temperature of the nitration reaction is 110~150℃, preferably 120~130℃.

[0059] The first mixing is carried out in the raw material premixing unit. In order to mix the raw material with oleum, heat will be continuously released during the mixing process. By controlling the temperature of the first mixing within the above range, the raw material and oleum can be fully mixed, which is conducive to the subsequent nitration reaction. Moreover, the first mixing of oleum with the raw material utilizes the characteristic of low water content of oleum (water content will inhibit nitration reaction) and takes advantage of the high activity of oleum, so that the nitration reaction can proceed positively within the above temperature range and the reaction is sufficient. Compared with the prior art, the temperature required for the nitration reaction is lower, the safety factor of the continuous synthesis process is higher, the reaction efficiency is higher, and it is more conducive to industrialized scale-up production.

[0060] In a preferred embodiment, in S1), the residence time of the first liquid in the continuous dosing module 13 is 10-50 min, including but not limited to 10, 20, 30, 40 and 50 min; preferably 20-30 min.

[0061] In the continuous dosing module, the residence time and temperature of the first liquid in the continuous dosing module 13 are controlled to ensure that the raw material components in the first liquid can be mixed evenly, improve the mixing effect of the raw materials and reverse sulfuric acid, and adapt to the temperature of the nitration reaction to ensure the efficiency of the reaction.

[0062] In a preferred embodiment, in S2), during the nitration reaction, the mass ratio of the raw material, fuming sulfuric acid and fuming nitric acid is 1:(1.5-2.5):(1-1.5); the reaction time is 30-100 min, including but not limited to 30, 40, 50, 60, 70, 80, 90 or 100 min; preferably 40-60 min.

[0063] The present application improves the conversion rate of raw materials and the yield of products by controlling the mass ratio of raw materials, fuming sulfuric acid and fuming nitric acid, and avoids the waste of resources caused by excessive addition of raw materials and reactants, so that the reaction can be carried out under safe conditions.

[0064] In a preferred embodiment, in S3), the quenching temperature is 25-65°C, including but not limited to 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C, 50°C, 51°C, 52°C, 53°C, 54°C, 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C or 65°C, and the quenching time is 10-30 min, including but not limited to 10, 20, 30, 40 and 50 min; preferably 15-20 min.

[0065] In a preferred embodiment, in S3), the pH of the quenching is adjusted to 3-6 by alkaline solution.

[0066] By controlling the temperature of the continuous quenching-pH adjustment module not to exceed 65°C, and the quenching time and the pH value during quenching are within the above range, the inactivation of reactive materials can be more rapid and complete, the system stability of the quenching process can be maintained, the real-time quenching effect can be achieved, and the safety of the entire process system can be further improved.

[0067] The beneficial effects of the present application will be further explained in detail below in conjunction with specific embodiments.

[0068] Example 1

[0069] S1) The raw material and the oleum solution are respectively input into the continuous batching module through the raw material continuous feeding module and the oleum continuous feeding module in a mass ratio of 1:2 for premixing, the reaction residence time is 25 minutes, the reaction temperature is 100-130°C, and the raw material system (first liquid) is obtained after pretreatment, which is continuously transferred to the mixing-reaction module of the continuous nitration unit.

[0070] S2) Fuming nitric acid is input into the continuous nitration unit through the fuming nitric acid continuous feeding module, and the fuming nitric acid is pumped into the mixing-reaction module at a mass ratio of 1.4:1 with the first liquid. The temperature of the nitration reaction is controlled at 120-130°C, and the residence time is 50 minutes to obtain the second liquid, i.e., the reaction system after nitration. The liquid and the gas are separated at the outlet of the continuous nitration unit, the gas enters the gas treatment module through the gas outlet, and the second liquid is input into the continuous post-treatment unit through the liquid outlet.

[0071] S3) The second liquid is input into the continuous quenching-pH adjustment module for continuous quenching, and the pH of the system is adjusted within the range of 3 to 6 using the alkali provided by the alkali supply module, and the temperature in the module is adjusted not to exceed 65°C. Subsequently, the solid-liquid mixture containing the product is transferred to the continuous solid-liquid separation module for solid-liquid separation, and then enters the continuous drying module for drying to obtain 2-methyl-5-nitroimidazole. The content of the final product 2-methyl-5-nitroimidazole is 99.5%, and the reaction yield is 87.5%.

[0072] Example 2

[0073] S1) is different from Example 1 in that the mass ratio of the raw material to the oleum solution is 1:1.5, and the residence time in the raw material premixing unit is 20 min.

[0074] S2) is different from Example 1 in that the mass ratio of fuming nitric acid to the first liquid is 1:1, and the residence time is 40 min.

[0075] The 2-methyl-5-nitroimidazole content of the final product was 99.0%, and the reaction yield was 85.4%.

[0076] Example 3

[0077] S1) is different from Example 1 in that the mass ratio of the raw material to the oleum solution is 1:2.5, and the residence time in the raw material premixing unit is 60 min.

[0078] S2) is different from Example 1 in that the mass ratio of fuming nitric acid to the first liquid is 1.5:1, and the residence time is 60 min.

[0079] The 2-methyl-5-nitroimidazole content of the final product was 99.2%, and the reaction yield was 86.1%.

[0080] Example 4

[0081] S1) is different from Example 1 in that the mass ratio of the raw material to the oleum solution is 1:3, and the residence time in the raw material premixing unit is 15 min.

[0082] S2) is different from Example 1 in that the mass ratio of fuming nitric acid to the first liquid is 1:2.5, and the residence time is 30 min.

[0083] The 2-methyl-5-nitroimidazole content of the final product is 99%, and the reaction yield is 84.3%.

[0084] Example 5

[0085] S1) is different from Example 1 in that the mass ratio of the raw material to the oleum solution is 1:1, and the residence time in the raw material premixing unit is 40 min.

[0086] S2) is different from Example 1 in that the mass ratio of fuming nitric acid to the first liquid is 1:2, and the residence time is 60 min.

[0087] The 2-methyl-5-nitroimidazole content of the final product was 99%, and the reaction yield was 84.1%.

[0088] Example 6

[0089] S3) is different from Example 1 in that the pH of the reaction system is <3.

[0090] The 2-methyl-5-nitroimidazole content of the final product was 99.5%, and the reaction yield was 84.2%.

[0091] Example 7

[0092] S3) is different from Example 1 in that the pH of the reaction system is >6.

[0093] The 2-methyl-5-nitroimidazole content of the final product is 99.4%, and the reaction yield is 84.3%.

[0094] Comparative Example 1

[0095] First, add 15 g of concentrated sulfuric acid solution into a 250 mL four-necked bottle, control the temperature not to exceed 130 ° C, start adding 2-methylimidazole, and keep warm for 20 min after the addition is completed. Then, start adding fuming nitric acid, keep the temperature at 130~170 ° C during the addition, and keep warm for 150 min after the addition is completed. After the reaction is completed, transfer the reaction system to the pre-prepared alkali solution, and then use the alkali solution to adjust the pH of the system to 3~6. After the temperature is cooled to below 65 ° C, centrifuge to separate 2-methyl-5-nitroimidazole from the solid-liquid mixture, and dry the wet product to obtain 2-methyl-5-nitroimidazole. The product purity is 99.0%, and the reaction yield is 82.1%.

[0096] Comparative Example 2

[0097] The product synthesis was carried out using the device and method of patent application 202211353046.2, which was consistent with the reaction conditions and residence time in each module in Example 1, but the mixing-reaction module in the continuous nitration unit in this patent application was a conventional horizontally placed reactor equipped with an exhaust device and an alkali solution absorption device.

[0098] The 2-methyl-5-nitroimidazole content of the final product was 99.2%, and the reaction yield was 84.0%.

[0099] Comparative Example 3

[0100] The difference from Example 1 is that concentrated sulfuric acid (concentration of 98%) is mixed with the raw materials to participate in the nitration reaction.

[0101] The 2-methyl-5-nitroimidazole content of the final product was 99.1%, and the reaction yield was 82.2%.

[0102] Comparative Example 4

[0103] The difference from Example 1 is that the temperature of the continuous batching module in S1) is set to 140°C.

[0104] The temperature of the mixing-reaction module in S2) is set to 55°C.

[0105] The 2-methyl-5-nitroimidazole content of the final product was 98.6%, and the reaction yield was 81.1%.

[0106] Comparative Example 5

[0107] The difference from Example 1 is that the temperature of the continuous batching module in S1) is set to 90°C.

[0108] The temperature of the mixing-reaction module in S2) is set to 105°C.

[0109] The 2-methyl-5-nitroimidazole content of the final product was 98.4%, and the reaction yield was 80.5%.

[0110] From the above description, it can be seen that the above embodiments of the present invention achieve the following technical effects:

[0111] The present invention adopts the continuous production system of the above-mentioned 2-methyl-5-nitroimidazole to realize the continuous preparation and continuous post-processing of 2-methyl-5-nitroimidazole. The system can realize automatic control, save labor, reduce production costs, improve production efficiency, and is convenient for accurately controlling process conditions. Oleum is used instead of concentrated sulfuric acid to reduce the nitration reaction temperature, avoid the decomposition and deterioration of the raw material 2-methylimidazole, and improve the reaction yield. Moreover, the reactor in the mixing-reaction module of the above-mentioned continuous synthesis system where the nitration reaction occurs utilizes a longitudinal cross design to eliminate the interference of a large amount of gas generated in the reaction process to the residence time of the continuous reactor to the maximum extent, improve the volume utilization rate of the equipment, and ensure that the raw material 2-methylimidazole is completely converted. Thus, without the need to add an exhaust device, the time that the gas stays in the reactor can also be reduced, the generation of by-products can be reduced, and the product yield and purity can be further improved. At the same time, the solution system generated by the nitration reaction is continuously circulated to the continuous post-processing unit, which can realize continuous quenching, avoid the danger caused by the long-term storage of a large amount of highly reactive materials, improve the safety of the entire process system, and is more suitable for continuous amplification production.

[0112] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A continuous synthesis method of 2-methyl-5-nitroimidazole, characterized in that: 2-methyl-5-nitroimidazole is synthesized by using a continuous production system of 2-methyl-5-nitroimidazole, wherein the continuous production system of 2-methyl-5-nitroimidazole comprises: A raw material premixing unit (1) comprises a raw material continuous feeding module (11), a fuming sulfuric acid continuous feeding module (12), a continuous batching module (13) and a fuming nitric acid continuous feeding module (14), wherein the fuming sulfuric acid continuous feeding module (12), the raw material continuous feeding module (11) and the continuous batching module (13) are sequentially connected; A continuous nitration unit (2) comprises a mixing-reaction module (21) and a gas processing module (22), wherein the mixing-reaction module comprises a reaction raw material inlet, a gas outlet and a liquid outlet, wherein the reaction raw material inlet is respectively connected to the outlet of the fuming nitric acid continuous feeding module (14) and the outlet of the continuous batching module (13), and the gas outlet is connected to the inlet of the gas processing module (22); The mixing-reaction module (21) comprises 10 to 40 pipes arranged in a longitudinal cross pattern, wherein the angle formed between the pipes adjacent to each other is 10 to 50°; the pipe is a tubular reactor in which a nitration reaction occurs in the mixing-reaction module (21); the reaction raw material inlet is located at the bottom of the tubular reactor, and the gas outlet and the liquid outlet are located at the top of the tubular reactor; A continuous post-treatment unit (3), comprising an alkali solution supply module (31), a continuous quenching-pH adjustment module (32), a continuous solid-liquid separation module (33) and a continuous drying module (34) connected in sequence, wherein the inlet of the continuous quenching-pH adjustment module (32) is connected to the liquid outlet of the mixing-reaction module (21); A control unit (4) is electrically connected to the raw material continuous feeding module (11), the fuming sulfuric acid continuous feeding module (12), the continuous batching module (13), the fuming nitric acid continuous feeding module (14), the mixing-reaction module (21), the continuous batching module (13) and the alkali solution supply module (31), respectively; The synthesis method comprises: S1) in a raw material premixing unit (1), the raw material and oleum are respectively fed into a continuous batching module (13) through a raw material continuous feeding module (11) and a oleum continuous feeding module (12) for first mixing to obtain a first liquid; S2) inputting fuming nitric acid into the continuous nitration unit (2) through the fuming nitric acid continuous feeding module (14), performing a second mixing of the first liquid and the fuming nitric acid in the mixing-reaction module (21), causing a nitration reaction, obtaining a second liquid, and the gas generated in the nitration reaction entering the gas treatment module (22); S3) in the continuous post-treatment unit (3), the second liquid is sequentially passed through the continuous quenching-pH adjustment module (32), the continuous solid-liquid separation module (33) and the continuous drying module (34), and quenching, solid-liquid separation and drying are performed in sequence to obtain the 2-methyl-5-nitroimidazole; A control unit (4) is used to control the feed rates of the raw materials, the fuming sulfuric acid and the fuming nitric acid, as well as the batching temperature and the nitration reaction temperature; the raw materials include 2-methylimidazole; The temperature of the first mixing is 100-130°C; The temperature of the nitration reaction is 110-150°C.

2. The continuous synthesis method according to claim 1, characterized in that In the above S1), the residence time of the first liquid in the continuous dosing module (13) is 10 to 50 minutes.

3. The continuous synthesis method according to claim 1, characterized in that In S2), during the nitration reaction, the mass ratio of the raw material, the fuming sulfuric acid and the fuming nitric acid is 1:1.5-2.5:1-1.5; The nitration reaction time is 30 to 100 minutes.

4. The continuous synthesis method according to claim 1, characterized in that: In the step S3), the quenching temperature is 25-65° C., the quenching time is 10-30 min, and the quenching pH is 3-6.

5. The continuous synthesis method according to claim 1, characterized in that: The raw material continuous feeding module (11) comprises a raw material storage device (111), a raw material feeding device (112) and a raw material feeding metering device (113), wherein: The raw material storage device (111), the raw material feeding device (112) and the raw material feeding metering device (113) are connected in sequence; The control unit (4) feeds back the feed amount of the raw material to adjust the feed speed of the raw material.

6. The continuous synthesis method according to claim 1, characterized in that: The oleum continuous feeding module (12) comprises an oleum storage device (121), an oleum feeding device (122) and an oleum feeding metering device (123), wherein: The oleum storage device (121), the oleum feeding device (122) and the oleum feeding metering device (123) are connected in sequence; The oleum feeding device (122) is used for continuously feeding the oleum; the oleum feeding metering device (123) is used for feeding back the feeding amount of the oleum to the control unit (4) to adjust the feeding speed of the oleum.

7. The continuous synthesis method according to claim 1, characterized in that: The fuming nitric acid continuous feeding module (14) comprises a fuming nitric acid storage device (141), a fuming nitric acid feeding device (142) and a fuming nitric acid feeding metering device (143), wherein: The fuming nitric acid storage device (141), the fuming nitric acid feeding device (142) and the fuming nitric acid feeding metering device (143) are connected in sequence; The fuming nitric acid feeding device (142) is used for continuously feeding the fuming nitric acid; the fuming nitric acid feeding metering device (143) is used for feeding back the feeding amount of the fuming nitric acid to the control unit (4) to adjust the feeding speed of the fuming nitric acid.

8. The continuous synthesis method according to claim 1, characterized in that: The alkali solution supply module (31) comprises an alkali solution storage device (311), an alkali solution feeding device (312) and an alkali solution feeding metering device (313); The alkali solution storage device (311), the alkali solution feeding device (312) and the alkali solution feeding metering device (313) are connected in sequence; The alkali solution feeding device (312) is used for continuously feeding the alkali solution; the alkali solution feeding metering device (313) is used for feeding back the alkali solution feeding amount to the control unit (4) to adjust the alkali solution feeding speed.

9. The continuous synthesis method according to claim 1, characterized in that: The continuous post-processing unit (3) further comprises a pH monitoring module (35); The pH monitoring module (35) is electrically connected to the continuous quenching-pH regulating module (32) and the control unit (4) respectively, so as to monitor the pH of the system during the quenching process, and to control the feed rate of the alkali solution supply module (31) so that the pH in the continuous quenching-pH regulating module (32) is 3-6.

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