CN109369498B - Method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by using microreactor - Google Patents
Method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by using microreactor Download PDFInfo
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- CN109369498B CN109369498B CN201811518245.8A CN201811518245A CN109369498B CN 109369498 B CN109369498 B CN 109369498B CN 201811518245 A CN201811518245 A CN 201811518245A CN 109369498 B CN109369498 B CN 109369498B
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- 238000000034 method Methods 0.000 title claims abstract description 45
- XNFIRYXKTXAHAC-UHFFFAOYSA-N tralopyril Chemical compound BrC1=C(C(F)(F)F)NC(C=2C=CC(Cl)=CC=2)=C1C#N XNFIRYXKTXAHAC-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 16
- 239000000243 solution Substances 0.000 claims abstract description 73
- 238000006243 chemical reaction Methods 0.000 claims abstract description 72
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 70
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 64
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 64
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 64
- ZXLQPJBQKJYNGN-UHFFFAOYSA-N 2-(4-chlorophenyl)-5-(trifluoromethyl)-1h-pyrrole-3-carbonitrile Chemical compound N1C(C(F)(F)F)=CC(C#N)=C1C1=CC=C(Cl)C=C1 ZXLQPJBQKJYNGN-UHFFFAOYSA-N 0.000 claims abstract description 49
- 239000011259 mixed solution Substances 0.000 claims abstract description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 63
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- 239000002904 solvent Substances 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000010924 continuous production Methods 0.000 abstract description 2
- 238000005265 energy consumption Methods 0.000 abstract description 2
- 239000012043 crude product Substances 0.000 description 14
- 238000005086 pumping Methods 0.000 description 14
- 239000002994 raw material Substances 0.000 description 10
- 238000005893 bromination reaction Methods 0.000 description 6
- 239000002253 acid Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000036632 reaction speed Effects 0.000 description 4
- 239000002699 waste material Substances 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- 230000031709 bromination Effects 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000000895 acaricidal effect Effects 0.000 description 1
- 239000000642 acaricide Substances 0.000 description 1
- -1 aryl pyrrole nitrile Chemical compound 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- CWFOCCVIPCEQCK-UHFFFAOYSA-N chlorfenapyr Chemical compound BrC1=C(C(F)(F)F)N(COCC)C(C=2C=CC(Cl)=CC=2)=C1C#N CWFOCCVIPCEQCK-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 238000003754 machining Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention discloses a method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by a microreactor, which comprises the steps of continuously introducing a 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile solution and a bromine solution into the microreactor for reaction, allowing the obtained mixed solution to flow through more than two reaction modules in the microreactor, reacting with a hydrogen peroxide solution introduced into the microreactor, and distilling to realize continuous preparation of 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile. The method has the characteristics of simple whole process flow, continuous process, high efficiency, low energy consumption, no pollution and the like, is an efficient, green and environment-friendly 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile continuous synthesis process, is suitable for large-scale continuous preparation, and is convenient for industrial utilization.
Description
Technical Field
The invention relates to a method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile by using a microreactor.
Background
The 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile is an important intermediate of aryl pyrrole nitrile as an insecticide, acaricide chlorfenapyr and chlorochlorfenapyr, and is synthesized by bromination reaction of 2-p-chlorophenyl-5-trifluoromethyl-pyrrole-3-nitrile and bromine. The process generally adopts a batch synthesis method in industry, has the advantages of simple operation and low cost, but has the defects of low reaction speed, excessive bromine raw material, more generated waste acid, large safety risk and the like.
Microreactors, i.e., microchannel reactors, generally refer to small reaction systems fabricated by microfabrication and precision machining techniques, and "micro" refers to small channels of process fluids, and does not refer to small physical dimensions of a microreaction device or small product yields. The micro-reaction technology is a novel chemical technology which is established on the basis of continuous flow and replaces a traditional batch reactor with a micro-channel reactor, and has the advantages of good mixing performance, high safety and the like, but the defects of the common batch bromination method are not completely overcome when the common microreactor is used for the bromination synthesis of 2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile. Therefore, the method for continuously synthesizing the 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by using the green and environment-friendly microreactor, which has the advantages of high reaction speed, low bromine consumption, basically no waste acid and great significance for improving the application range of the 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile, is obtained.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by using a micro-reactor, which has the advantages of high reaction speed, low bromine consumption, basically no waste acid and environmental protection.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
a method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by a microreactor comprises the following steps: and continuously introducing the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile solution and a bromine solution into the microreactor simultaneously for reaction, allowing the obtained mixed solution to flow through more than two reaction modules in the microreactor, reacting with a hydrogen peroxide solution introduced into the microreactor, and distilling to obtain the 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile.
The method is further improved, the microreactor is formed by connecting reaction modules with microfluidic circuits in series, the number of the reaction modules in the microreactor is 5-20, and the liquid holdup of a single reaction module is 5m L.
In the method, the solution of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile and the solution of bromine are introduced into the microreactor from the 1 st reaction module; the hydrogen peroxide solution is introduced into the microreactor from the 3 rd to the 12 th reaction modules.
In the method, the molar ratio of the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile in the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile solution to the bromine in the bromine solution is further improved to be 1: 0.5-0.6; the hydrogen peroxide is dissolved in waterH in liquid2O2The molar ratio of the bromine to bromine in the bromine solution is 1.0-1.3: 1.
In the method, the solution of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile is prepared by mixing 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile with a solvent; the mass content of the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile in the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile solution is 5-20%; the solvent is methanol or ethanol.
In the method, the bromine solution is prepared by mixing bromine and a solvent; the mass content of bromine in the bromine solution is 2-10%; the solvent is methanol or ethanol.
In the method, the hydrogen peroxide solution is further improved and prepared by mixing hydrogen peroxide and a solvent; h in the hydrogen peroxide solution2O2The mass content of (A) is 0.5-5%; the solvent is methanol or ethanol; the mass fraction of the hydrogen peroxide is 30%.
In the method, the flow rate of the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile solution is 1.37g/min to 5.46 g/min; the introduction rate of the bromine solution is 0.8g/min to 4.0 g/min; the introduction rate of the hydrogen peroxide solution is 0.34 g/min-3.4 g/min.
In the method, the temperature of the reaction module in the microreactor is controlled to be 50-78 ℃.
Compared with the prior art, the invention has the advantages that:
(1) the invention provides a method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by a microreactor, which comprises the steps of continuously introducing a 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile solution and a bromine solution into the microreactor for reaction, allowing the obtained mixed solution to flow through more than two reaction modules in the microreactor, reacting with a hydrogen peroxide solution introduced into the microreactor, and distilling to realize continuous preparation of 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile. In the invention, a 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile solution and a bromine solution are introduced into a microreactor to react, part of raw materials are brominated in the reaction process to prepare 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile, and hydrobromic acid is also generated in the reaction process; further, the obtained mixed solution (containing hydrobromic acid) flows through more than two reaction modules in the microreactor and then continuously reacts with the hydrogen peroxide solution introduced into the microreactor, in the reaction process, as the concentration of a bromine source in the microreactor system is gradually reduced, the hydrobromic acid is oxidized into bromine by using the added hydrogen peroxide solution generated in the system before oxidation, the obtained bromine is continuously subjected to bromination reaction with the unreacted 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile to further synthesize 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile, and the generated hydrogen bromide is continuously oxidized into bromine by the hydrogen peroxide and continuously used for bromination reaction to synthesize the 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile, therefore, the 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile is continuously synthesized by continuously performing bromination and oxidation cycles, so that not only can the bromine atoms be fully utilized, the bromine feeding amount be reduced, and the production cost be reduced, but also more high-purity 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile can be synthesized, and meanwhile, no waste acid is generated in a microreactor system. The method has the characteristics of simple whole process flow, continuous process, high efficiency, low energy consumption, no pollution and the like, and is a high-efficiency, green and environment-friendly continuous synthesis process of the 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile.
(2) In the invention, the microreactor is a reactor formed by connecting reaction modules with a microfluid loop in series, has good mass transfer and heat transfer efficiency, can quickly mix 2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile solution with bromine and hydrogen peroxide, strictly controls the flow rate and the reaction ratio, has the advantages of high reaction speed, high conversion rate, good safety and the like, is suitable for large-scale continuous preparation, and is convenient for industrial utilization.
(3) In the method, the molar ratio of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile to bromine is optimized to be 1: 0.5-0.6, and H2O2The mole ratio of the bromine to the bromine is 1.0 to1.3: 1, so that all reaction materials can be instantly and uniformly mixed in a precise proportion, and the utilization rate of bromine atoms can be obviously improved, thereby realizing the efficient utilization of the bromine atoms; by optimizing the mass content of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile in the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile solution to be 5-20 percent, the mass content of bromine in the bromine solution to be 2-10 percent and H in the hydrogen peroxide solution2O2The mass content of the raw materials is 0.5-5%, so that the raw materials have better fluidity, the raw materials are beneficial to material transfer of a feeding pump, and the production efficiency is ensured; the introduction rate of the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile solution is optimized to be 1.37 g/min-5.46 g/min, the introduction rate of the bromine solution is 0.8 g/min-4.0 g/min, and the introduction rate of the hydrogen peroxide solution is 0.34 g/min-3.4 g/min, so that the introduction rates of the reaction materials are matched with each other, the optimal reaction ratio is ensured to be obtained through the reaction, the reaction materials are fully reacted, and the utilization rate of the raw materials is obviously improved; the temperature of a reaction module in the microreactor is controlled to be 50-78 ℃, so that the reaction is carried out under a proper temperature condition, a better reaction effect is obtained, and no by-product is generated. Therefore, the preparation method can greatly reduce the consumption of the raw materials, particularly the consumption of the bromine, and can obviously improve the product content by optimizing the consumption ratio of the raw materials, the mass content of the raw materials, the introduction rate of the raw materials and the reaction temperature, wherein the product content is up to 98.5 percent.
Detailed Description
The invention is further described below with reference to specific preferred embodiments, without thereby limiting the scope of protection of the invention.
Unless otherwise specified, the reagents used in the invention are all commercially available, the instruments and equipment used in the invention are all conventional instruments and equipment, and the operation methods adopted in the invention are all conventional operation methods.
Example 1
A method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by a microreactor comprises the following steps:
(1) preparing a solution: 27.3g of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile was mixed with 518.7g of methanol to give a solution of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile. 8g of bromine was mixed with 392g of methanol to give a bromine solution. 5.7g of hydrogen peroxide with the mass fraction of 30 percent and 334.3g of methanol are mixed to obtain hydrogen peroxide solution.
(2) And (2) continuously pumping the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile solution prepared in the step (1) and a bromine solution into a 1 st reaction module of the microreactor for reaction at the introduction rate of 5.46g/min and 4.0g/min respectively, controlling the temperature of each reaction module to be 50 ℃, pumping the hydrogen peroxide solution prepared in the step (1) into the microreactor at the introduction rate of 3.4g/min after the obtained mixed solution flows through the 3 rd reaction module of the microreactor, reacting the mixed solution with the hydrogen peroxide solution, and flowing out from the outlet of the microreactor after flowing through 10 reaction modules in total to obtain a 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile crude product. The crude product was distilled to give 33.8g of 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile having a content of 98.1%.
Example 2
A method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by a microreactor comprises the following steps:
(1) preparing a solution: 27.3g of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile was mixed with 245.7g of methanol to give a solution of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile. 8g of bromine was mixed with 152g of methanol to obtain a bromine solution. 5.7g of hydrogen peroxide with the mass fraction of 30 percent and 164.3g of methanol are mixed to obtain hydrogen peroxide solution.
(2) And (2) continuously pumping the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile solution prepared in the step (1) and a bromine solution into a 1 st reaction module of the microreactor for reaction at the introduction rate of 2.73g/min and 1.6g/min respectively, controlling the temperature of each reaction module to be 64 ℃, pumping the hydrogen peroxide solution prepared in the step (1) into the microreactor at the introduction rate of 1.7g/min after the obtained mixed solution flows through the 5 th reaction module of the microreactor, reacting the mixed solution with the hydrogen peroxide solution, and flowing out from the outlet of the microreactor after flowing through 15 reaction modules in total to obtain the 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile crude product. The crude product was distilled to give 34.9g of 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile having a content of 98.4%.
Example 3
A method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by a microreactor comprises the following steps:
(1) preparing a solution: 27.3g of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile were mixed with 109.2g of methanol to give 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile. 8g of bromine was mixed with 72g of methanol to obtain a bromine solution. 5.7g of hydrogen peroxide with the mass fraction of 30 percent and 28.3g of methanol are mixed to obtain hydrogen peroxide solution.
(2) And (2) continuously pumping the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile solution prepared in the step (1) and a bromine solution into a 1 st reaction module of the microreactor for reaction at the introduction rate of 1.37g/min and 0.8g/min respectively, controlling the temperature of each reaction module to be 64 ℃, pumping the hydrogen peroxide solution prepared in the step (1) into the microreactor at the introduction rate of 0.34g/min after the obtained mixed solution flows through the 5 th reaction module of the microreactor, reacting the mixed solution with the hydrogen peroxide solution, and flowing out from an outlet of the microreactor after flowing through 15 reaction modules in total to obtain a 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile crude product. The crude product was distilled to give 34.2g of 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile having a content of 98.3%.
Example 4
A method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by a microreactor comprises the following steps:
(1) preparing a solution: 27.3g of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile was mixed with 245.7g of methanol to give a solution of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile. 8.8g of bromine was mixed with 167.2g of methanol to give a bromine solution. 7.17g of hydrogen peroxide with the mass fraction of 30 percent and 207.88g of methanol are mixed to obtain hydrogen peroxide solution.
(2) And (2) respectively pumping the 2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile solution prepared in the step (1) and a bromine solution into the 1 st reaction module of the microreactor at the introduction rates of 2.73g/min and 1.76g/min simultaneously and continuously for reaction, controlling the temperature of each reaction module to be 64 ℃, pumping the hydrogen peroxide solution prepared in the step (1) into the microreactor at the introduction rate of 2.15g/min after the obtained mixed solution flows through the 5 th reaction module of the microreactor, enabling the mixed solution to react with the hydrogen peroxide solution, and flowing out from the outlet of the microreactor after flowing through 15 reaction modules in total to obtain the 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile crude product. The crude product was distilled to give 34.8g of 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile having a content of 98.1%.
Example 5
A method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by a microreactor comprises the following steps:
(1) preparing a solution: 27.3g of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile was mixed with 245.7g of methanol to give a solution of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile. 9.6g of bromine was mixed with 182.4g of methanol to obtain a bromine solution. 8.84g of hydrogen peroxide with the mass fraction of 30 percent and 164.3g of methanol are mixed to obtain hydrogen peroxide solution.
(2) And (2) respectively pumping the 2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile solution prepared in the step (1) and a bromine solution into the 1 st reaction module of the microreactor at the introduction rates of 2.73g/min and 1.92g/min simultaneously and continuously for reaction, controlling the temperature of each reaction module to be 64 ℃, pumping the hydrogen peroxide solution prepared in the step (1) into the microreactor at the introduction rate of 2.65g/min after the obtained mixed solution flows through the 5 th reaction module of the microreactor, enabling the mixed solution to react with the hydrogen peroxide solution, and flowing out from the outlet of the microreactor after flowing through 15 reaction modules in total to obtain the 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile crude product. The crude product was distilled to give 34.6g of 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile having a content of 98.3%.
Example 6
A method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by a microreactor comprises the following steps:
(1) preparing a solution: 27.3g of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile was mixed with 245.7g of ethanol to give a solution of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile. 8.8g of bromine was mixed with 167.2g of ethanol to give a bromine solution. 7.17g of hydrogen peroxide with the mass fraction of 30 percent is mixed with 207.88g of ethanol to obtain hydrogen peroxide solution.
(2) And (2) respectively pumping the 2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile solution prepared in the step (1) and a bromine solution into the 1 st reaction module of the microreactor at the introduction rates of 2.73g/min and 1.76g/min simultaneously and continuously for reaction, controlling the temperature of each reaction module to be 70 ℃, pumping the hydrogen peroxide solution prepared in the step (1) into the microreactor at the introduction rate of 2.15g/min after the obtained mixed solution flows through the 8 th reaction module of the microreactor, enabling the mixed solution to react with the hydrogen peroxide solution, and flowing out from the outlet of the microreactor after flowing through 16 reaction modules in total to obtain the 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile crude product. The crude product was distilled to give 35.8g of 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile having a content of 98.5%.
Example 7
A method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by a microreactor comprises the following steps:
(1) preparing a solution: 27.3g of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile was mixed with 245.7g of ethanol to give a solution of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile. 8.8g of bromine was mixed with 167.2g of ethanol to give a bromine solution. 7.17g of hydrogen peroxide with the mass fraction of 30 percent is mixed with 207.88g of ethanol to obtain hydrogen peroxide solution.
(2) And (2) respectively pumping the solution of 2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile prepared in the step (1) and the bromine solution into the 1 st reaction module of the microreactor at the introduction rates of 2.73g/min and 1.76g/min simultaneously and continuously for reaction, controlling the temperature of each reaction module to be 78 ℃, pumping the hydrogen peroxide solution prepared in the step (1) into the microreactor at the introduction rate of 2.15g/min after the obtained mixed solution flows through the 12 th reaction module of the microreactor, enabling the mixed solution to react with the hydrogen peroxide solution, and flowing out from the outlet of the microreactor after flowing through 20 reaction modules in total to obtain the crude product of 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile. The crude product was distilled to give 34.3g of 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile having a content of 98.4%.
The above description is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above-described embodiments. All technical schemes belonging to the idea of the invention belong to the protection scope of the invention. It should be noted that modifications and embellishments within the scope of the invention may be made by those skilled in the art without departing from the principle of the invention, and such modifications and embellishments should also be considered as within the scope of the invention.
Claims (9)
1. A method for continuously synthesizing 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile by a microreactor is characterized by comprising the following steps: continuously introducing a 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile solution and a bromine solution into the microreactor from the 1 st reaction module to react, allowing the obtained mixed solution to flow through more than two reaction modules in the microreactor, reacting with a hydrogen peroxide solution introduced into the microreactor, and distilling to obtain 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile; the microreactor is formed by connecting reaction modules with a microfluid loop in series.
2. The method according to claim 1, wherein the number of the reaction modules in the microreactor is 5-20, and the liquid holdup of a single reaction module is 5m L.
3. The method according to claim 2, wherein the aqueous hydrogen peroxide solution is passed into the microreactor from the 3 rd to the 12 th reaction modules.
4. A process according to any one of claims 1 to 3, wherein the molar ratio of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile in the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile solution to bromine in the bromine solution is 1: 0.5 to 0.6; h in the hydrogen peroxide solution2O2The molar ratio of the bromine to bromine in the bromine solution is 1.0-1.3: 1.
5. The method according to claim 4, wherein the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile solution is prepared by mixing 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile with a solvent; the mass content of the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile in the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-nitrile solution is 5-20%; the solvent is methanol or ethanol.
6. The method according to claim 4, wherein the bromine solution is prepared by mixing bromine with a solvent; the mass content of bromine in the bromine solution is 2-10%; the solvent is methanol or ethanol.
7. The method according to claim 4, wherein the hydrogen peroxide solution is prepared by mixing hydrogen peroxide and a solvent; h in the hydrogen peroxide solution2O2The mass content of (A) is 0.5-5%; the solvent is methanol or ethanol; the mass fraction of the hydrogen peroxide is 30%.
8. The method according to any one of claims 1 to 3, wherein the 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile solution is introduced at a rate of 1.37 to 5.46 g/min; the introduction rate of the bromine solution is 0.8g/min to 4.0 g/min; the introduction rate of the hydrogen peroxide solution is 0.34 g/min-3.4 g/min.
9. The method according to any one of claims 1 to 3, wherein the temperature of the reaction module in the microreactor is controlled to be 50 ℃ to 78 ℃.
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