Continuous synthesis and separation device suitable for dangerous materials
By designing a continuous synthesis and separation device including reactor and multi-stage distillation unit, the problems of high risk and low yield of raw materials in the synthesis process of 2-cyanoacetoacetate are solved, and high purity and high yield are achieved Product production reduces safety risks and pollution.
Patent Information
- Application Number
- CN202421273023.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-06-05
- Publication Date
- 2024-12-10
- Estimated Expiration
- 2034-06-05
AI Technical Summary
In the prior art, the synthesis process of 2-cyanoacetylethyl cyanoacetate has problems such as high risk of raw materials, low yield, low product purity and serious pollution, which hinders the industrial production of this method.
A continuous synthesis and separation device including a first reactor, a second reactor, a continuous extraction device and a multi-stage distillation unit is designed, and the product is separated by quenching the reaction in the second reactor, combining with multi-stage refinement. Distillation improves product purity and yield, and recycles solvents and treats waste through multi-stage distillation units.
It effectively reduces the safety risks of raw materials, improves the purity and yield of products, and is suitable for the continuous synthesis and separation process of a variety of hazardous materials, achieving efficient production.
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Figure CN222131872U_ABST
Abstract
Description
Technical Field
[0001] The utility model relates to a continuous synthesis and separation device suitable for dangerous materials, in particular to a reaction synthesis and separation process including diketene raw materials. Background Art
[0002] In many synthetic reaction processes, the danger of raw materials is often an important factor that hinders their industrial application. For example, ethyl 2-cyanoacetoacetate is an important pharmaceutical intermediate, one of its main applications is the preparation of finerenone (structural formula Figure 1 As shown in Figure 2, it is a novel non-steroidal selective mineralocorticoid receptor antagonist). One of the synthetic processes is as follows: Figure 2 shown.
[0003] 2-cyano ethyl acetoacetate synthesis process, can be synthesized by methyl acetoacetate and 3-hydroxypropionitrile, such as the process disclosed in Chinese patent CN102285901A, although successfully methyl acetoacetate and 3-hydroxypropionitrile are transesterified under the catalysis of Lewis acid to obtain the target product, but the final product yield is only 50%, the product is yellow, low purity, harsh reaction conditions, and the introduced Lewis acid causes post-processing troubles, and produces great pollution simultaneously. In addition, the process disclosed in Chinese patents CN114524812A and CN103739542A is all synthesized by transesterification of methyl acetoacetate and 3-hydroxypropionitrile under the catalysis of Lewis acid, but there is also a problem of low yield and low product purity. Japanese patent JPH05262696A and Zhang Jing et al. (Zhang Jing, Ji Xianyong, Sun Xiang, Wang Jie. Synthesis of Clevidipine [J]. Chinese Journal of Pharmaceutical Industry, 2011, 42(07): 484-486.) disclose a method for directly synthesizing ethyl 2-cyanoacetoacetate using diketene and 3-hydroxypropionitrile. Although the reaction is a quantitative reaction, the raw material diketene is flammable and explosive, has high toxicity and tear-inducing effect, and is easy to self-polymerize and release a large amount of carbon monoxide to cause an explosion. The danger of the raw material diketene is one of the important factors hindering the industrial production of this method. Utility Model Content
[0004] In view of the above-mentioned deficiencies in the prior art, the purpose of the utility model is to provide a continuous synthesis and separation device suitable for hazardous materials. The continuous synthesis and separation device suitable for hazardous materials is reasonably designed, which is conducive to the convenient realization of continuous synthesis production of hazardous materials and has a high yield.
[0005] The utility model is suitable for a continuous synthesis and separation device for dangerous materials, and is characterized in that it comprises a first reactor, a second reactor, a continuous extraction device and a multi-stage distillation unit which are arranged in sequence;
[0006] The two input ends of the first reactor are respectively connected to the first feed pump and the second feed pump, the water phase output end of the continuous extraction device is connected to an input end of the second reactor, the oil phase output end of the continuous extraction device is connected to a multi-stage distillation unit, and the other input end of the second reactor is connected to the solvent.
[0007] Preferably, the output end of the multi-stage distillation unit is connected to the input end of a post-processor for processing waste.
[0008] Preferably, the first reactor and the second reactor both comprise a mixer and a coil, wherein the first reactor is a three-way mixer, the second reactor is a four-way mixer, the coil in the first reactor is a first coil, and the coil in the second reactor is a second coil.
[0009] Preferably, the multi-stage distillation unit comprises a first distillation device for recovering the solvent, a second distillation device and a third distillation device for distilling to obtain the product, which are arranged in sequence.
[0010] Preferably, the first distillation device, the second distillation device and the third distillation device are scraped film distillation devices.
[0011] Preferably, the multi-stage distillation unit comprises a first scraped film distillation device, a second scraped film distillation device, a third scraped film distillation device and a fifth scraped film distillation device which are arranged in sequence, an output end of the first scraped film distillation device is connected to a four-way mixer so that the solvent recovered by the first scraped film distillation device can be passed into the four-way mixer, an output end of the second scraped film distillation device is connected to a fourth scraped film distillation device and a continuous extraction device in sequence so that the first transition section product obtained by the second scraped film distillation device can be passed into the fourth scraped film distillation device, and the high-proportion product separated by the fourth scraped film distillation device can be recovered into the continuous extraction device, and an output end of the fifth scraped film distillation device is connected to an input end of the second scraped film distillation device so that the remaining second transition section product recovered by the fifth scraped film distillation device can be further distilled in the second scraped film distillation device.
[0012] The utility model designs a second reactor to quench the hazardous materials after the reaction before separating the products, which greatly reduces the safety risks brought by the raw materials. Combined with the reasonable design of the separation device, the product purity and yield are improved, and it can be applied to the continuous synthesis production and separation process of various hazardous materials. BRIEF DESCRIPTION OF THE DRAWINGS
[0013] Figure 1 It is the structural formula diagram of phenerenone;
[0014] Figure 2 It is the synthetic route map of phenerenone;
[0015] Figure 3This is the synthetic reaction diagram of ethyl 2-cyanoacetoacetate;
[0016] Figure 4 This is a schematic diagram of the structure of an embodiment of the utility model;
[0017] Figure 5 It is a schematic diagram of the structure of another embodiment of the utility model. DETAILED DESCRIPTION
[0018] In order to allow readers to more intuitively understand certain specific implementation methods of the present application, the present application also provides the following examples for readers' reference.
[0019] The utility model is applicable to a continuous synthesis and separation device for hazardous materials, comprising a first reactor V1, a second reactor V2, a continuous extraction device V3 and a multi-stage distillation unit V4 which are arranged in sequence;
[0020] The two input ends of the first reactor V1 are respectively connected to the first feed pump P1 and the second feed pump P2, the water phase output end of the continuous extraction device V3 is connected to an input end of the second reactor V2, the oil phase output end of the continuous extraction device V3 is connected to the multi-stage distillation unit V4, and the other input end of the second reactor V2 is connected to the solvent.
[0021] Taking the synthesis of ethyl 2-cyanoacetoacetate as an example, the reaction formula is as follows: Figure 3 As shown, the first feed pump P1 feeds the raw material diketene, and the second feed pump P2 feeds the mixed solution of 3-hydroxypropionitrile and the catalyst, and the reaction liquid is obtained after sufficient reaction in the first reactor V1; the reaction liquid, water and solvent are transported to the second reactor V2 for sufficient quenching reaction, and then the reaction liquid passes through the continuous extraction device V3 to separate the oil phase and the water phase, wherein the water phase can be treated by a water recovery device (the water recovery device can be a water distillation device, a membrane filtration device, etc.) and connected to the feed port of the second reactor V2 for application, the oil phase is transported to the multi-stage distillation unit V4 for distillation to obtain the product, and the residual material at the output end of the multi-stage distillation unit V4 is sent to a post-processor V5 (which can be an incinerator) for treating waste materials for post-processing.
[0022] The first reactor V1 and the second reactor V2 both include a mixer and a coil (coil reactor), wherein the first reactor V1 is a three-way mixer, the second reactor V2 is a four-way mixer, the coil in the first reactor V1 is a first coil (or a first coil reactor), and the coil in the second reactor V2 is a second coil (or a second coil reactor), such as Figure 4 , 5 shown.
[0023] In one embodiment, the multi-stage distillation unit V4 comprises a first distillation device for recovering the solvent, a second distillation device and a third distillation device for distilling to obtain the product, which are arranged in sequence.
[0024] The first distillation device, the second distillation device and the third distillation device can be scraped film distillation devices, wherein the third distillation device can also use processes such as vacuum distillation and centrifugal distillation.
[0025] Another embodiment is (such as Figure 5 As shown), the multi-stage distillation unit V4 includes a first scraped film distillation device, a second scraped film distillation device, a third scraped film distillation device and a fifth scraped film distillation device which are arranged in sequence, an output end of the first scraped film distillation device is connected to a four-way mixer so that the solvent recovered by the first scraped film distillation device is passed into the four-way mixer, an output end of the second scraped film distillation device is connected to a fourth scraped film distillation device and a continuous extraction device in sequence so that the first transition section product obtained by the second scraped film distillation device is passed into the fourth scraped film distillation device, and the high-proportion product separated by the fourth scraped film distillation device is recovered into the continuous extraction device, an output end of the fifth scraped film distillation device is connected to an input end of the second scraped film distillation device so that the remaining second transition section product recovered by the fifth scraped film distillation device is passed to the second scraped film distillation device for further distillation.
[0026] The raw material diketene is conveyed to the three-way mixer by the first feeding pump, and the mixed solution of 3-hydroxypropionitrile and the catalyst is conveyed to the three-way mixer by another feeding pump. After the first coil is fully reacted, water and solvent are conveyed to the four-way mixer and the second coil by the other two feeding pumps respectively to fully quench the reaction. Then, the oil phase and the water phase are separated by a continuous extraction device. The oil phase is passed through the first scraping film distillation device to recover the solvent, the second scraping film distillation device obtains the first transition stage product containing 3-hydroxypropionitrile, the third scraping film distillation device obtains an anhydrous transparent oily product with a purity of >98%, and the remaining material is recovered by the fifth scraping film distillation device. The remaining product (second transition stage product) is sent to the second scraping film distillation device for further distillation to obtain the product, and the remaining high-boiling impurities are waste materials, of which the recovered solvent can be directly applied, and the transition stage product containing 3-hydroxypropionitrile is separated by the fourth scraping film distillation device to obtain a high-proportion product and recovered to the continuous extraction device, and the high-proportion 3-hydroxypropionitrile can be directly used for raw material reaction; after the water phase passes through the water recovery device, the high-purity water is directly applied, and the rest is waste liquid.
[0027] The catalyst may be triethylamine, pyridine, imidazole, piperidine, pyrrole, 1,8-diazabicyclo[5.4.0]undec-7-ene, etc.; the feed pump may be a horizontal flow pump, a peristaltic pump, etc.; the amount of the catalyst is 0.1-1% of the amount of 3-hydroxypropionitrile; the molar ratio of diketone to 3-hydroxypropionitrile is 1:1.01-1:1.1; the temperature of the first coil reactor is constant at 20-50°C, and the residence time of the reaction solution is 0.1-4h, preferably 5min-2h;
[0028] The amount of the catalyst is 0.2% of the amount of 3-hydroxypropionitrile, the molar ratio of diketene to 3-hydroxypropionitrile is 1:1.02, the temperature of the first coil reactor is constant at 30° C., and the residence time of the reaction liquid is 2 hours.
[0029] The above solvent may be benzene, toluene, dichloromethane, chloroform, dichloroethane, trichloroethane, or the like.
[0030] The temperature of the second coil reactor is kept constant at 10-30°C, and the residence time of the reaction liquid is 0.1-2h.
[0031] The solvent is dichloromethane, the temperature of the second coil reactor is kept constant at 15° C., and the residence time of the reaction liquid is 1 hour.
[0032] The water recovery device is a water distillation device, a membrane filtration device, etc., wherein the continuous extraction device is a conventional device and will not be described here.
[0033] The conditions of the first scraped film distillation device are 60-80°C, 5-20 kPa; the conditions of the second scraped film distillation device are 130-160°C, 0.5-2 kPa; the conditions of the third scraped film distillation device are 160-190°C, 0.1-1 kPa;
[0034] The conditions of the fourth wiped film distillation device are 150~180°C and 0.2~1 kPa; the conditions of the fifth wiped film distillation device are 170~200°C and 0.1~1 kPa.
[0035] The conditions of the first scraped film distillation device are 70°C and 10kPa; the conditions of the second scraped film distillation device are 150°C and 1kPa; the conditions of the third scraped film distillation device are 180°C and 0.5kPa; the conditions of the fourth scraped film distillation device are 170°C and 0.5kPa; and the conditions of the fifth scraped film distillation device are 190°C and 0.5kPa.
[0036] The following is a specific example of synthesizing ethyl 2-cyanoacetoacetate using the device provided by the utility model.
[0037] Embodiment 1:
[0038] Through two pumps, a mixed solution of diketene, imidazole and 3-hydroxypropionitrile was introduced at a molar ratio of 3-hydroxypropionitrile: diketene: imidazole = 1:1.03:0.001. The mixed reaction solution passed through a three-way mixer and entered the first coil. The temperature of the first coil was 30°C and the residence time was 2h. Water and dichloromethane were introduced into a four-way mixer at a mass ratio of water: reaction solution: dichloromethane = 0.5:1:2 and entered the second coil. The temperature of the second coil was 15°C and the residence time was 1h. After that, the continuous scraping device was used to obtain the oil phase and the water phase respectively. The oil phase was distilled through a multi-stage scraping distillation device. The product was obtained, and 3-hydroxypropionitrile was recovered and directly used as the raw material at a purity of 90%. The solvent was directly used, and the aqueous phase was directly used after passing through a water recovery device. The conditions of the first scraped film distillation device were 70°C, 10kPa, the conditions of the second scraped film distillation device were 150°C, 1kPa, the conditions of the third scraped film distillation device were 180°C, 0.5kPa, the conditions of the fourth scraped film distillation device were 170°C, 0.5kPa, and the conditions of the fifth scraped film distillation device were 190°C, 0.5kPa. After the system ran for 72 hours, the total yield of the product was 92%, and the product was an anhydrous transparent oily liquid with a purity of>98%.
[0039] Embodiment 2:
[0040] The method of Example 1 is adopted, except that the reaction temperature of the first coil is 40 o C, the temperature in the second coil is 10 o C, the first wiped film distillation unit condition is 90 o C, 3kPa, after the system ran for 96h, the total yield of the product was 90%, and the product was an anhydrous transparent oily liquid with a purity of >98%.
[0041] Embodiment 3:
[0042] The method of Example 2 is adopted, except that the catalyst selected in this example is triethylamine, the total yield of the product is 85%, and the product is an anhydrous transparent oily liquid with a purity of> 98%.
[0043] Embodiment 4:
[0044] The method of Example 1 is adopted, except that the catalyst used in this example is pyridine, and the reaction temperature of the first coil is 40 o C, the temperature in the second coil is 20 o C. After the system was running for 48 hours, the total yield of the product was 90%, and the product was an anhydrous transparent oily liquid with a purity of >98%.
[0045] Embodiment 5:
[0046] The method of Example 4 was adopted, except that the catalyst used in this example was 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). After the system was operated for 48 hours, the total yield of the product was 70%, and the product was an anhydrous transparent oily liquid with a purity of >95%.
[0047] Embodiment 6:
[0048] The method of Example 4 was adopted, except that the catalyst used in this example was pyrrole. After the system was operated for 48 hours, the total yield of the product was 50%, and the product was an anhydrous transparent oily liquid with a purity of >95%.
[0049] Embodiment 7:
[0050] The method of Example 2 was adopted, except that the pressure of the first scraped film distillation device in this example was 2 kPa. After the system was operated for 96 h, the total yield of the product was 91%, and the product was an anhydrous transparent oily liquid with a purity of >98%.
[0051] Embodiment 8:
[0052] The method of Example 2 is adopted, except that the conditions of the first scraped film distillation device in this embodiment are 70 o C, 5kPa, after the system ran for 96h, the total yield of the product was 90%, and the product was an anhydrous transparent oily liquid with a purity of >98%.
[0053] Embodiment 9:
[0054] The method of Example 2 was adopted, except that in this example, the feed ratio of 3-hydroxypropionitrile: diketene: imidazole was 1:1.05:0.0005. After the system was operated for 96 hours, the total yield of the product was 60%, and the product was an anhydrous transparent oily liquid with a purity of >95%.
Claims
1. A continuous synthesis and separation device suitable for hazardous materials, characterized in that: It comprises a first reactor (V1), a second reactor (V2), a continuous extraction device (V3) and a multi-stage distillation unit (V4) which are arranged in sequence; The two input ends of the first reactor (V1) are respectively connected to the first feed pump (P1) and the second feed pump (P2), the water phase output end of the continuous extraction device (V3) is connected to an input end of the second reactor (V2), the oil phase output end of the continuous extraction device (V3) is connected to a multi-stage distillation unit (V4), and the other input end of the second reactor (V2) is connected to the solvent.
2. The continuous synthesis and separation device for hazardous materials according to claim 1, characterized in that: The output end of the multi-stage distillation unit (V4) is connected to the input end of a post-processor (V5) for treating waste materials.
3. The continuous synthesis and separation device for hazardous materials according to claim 1, characterized in that: The first reactor (V1) and the second reactor (V2) both comprise a mixer and a coil, wherein the first reactor (V1) is a three-way mixer, the second reactor (V2) is a four-way mixer, the coil in the first reactor (V1) is a first coil, and the coil in the second reactor (V2) is a second coil.
4. The continuous synthesis and separation device for hazardous materials according to claim 1, characterized in that: The multi-stage distillation unit (V4) comprises a first distillation device for recovering a solvent, a second distillation device and a third distillation device for distilling to obtain a product, which are arranged in sequence.
5. The continuous synthesis and separation device for hazardous materials according to claim 4, characterized in that: The first distillation device, the second distillation device and the third distillation device are wiped film distillation devices.
6. The continuous synthesis and separation device for hazardous materials according to claim 3, characterized in that: The multi-stage distillation unit (V4) includes a first scraped film distillation device, a second scraped film distillation device, a third scraped film distillation device and a fifth scraped film distillation device which are arranged in sequence, an output end of the first scraped film distillation device is connected to a four-way mixer so that the solvent recovered by the first scraped film distillation device is passed into the four-way mixer, an output end of the second scraped film distillation device is connected to a fourth scraped film distillation device and a continuous extraction device in sequence so that the first transition section product obtained by the second scraped film distillation device is passed into the fourth scraped film distillation device, and the high-proportion product separated by the fourth scraped film distillation device is recovered into the continuous extraction device, and an output end of the fifth scraped film distillation device is connected to an input end of the second scraped film distillation device so that the remaining second transition section product recovered by the fifth scraped film distillation device is passed to the second scraped film distillation device for further distillation.
Citation Information
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