CN109369498A - A kind of method that microreactor continuously synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4- - Google Patents
A kind of method that microreactor continuously synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4- Download PDFInfo
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- CN109369498A CN109369498A CN201811518245.8A CN201811518245A CN109369498A CN 109369498 A CN109369498 A CN 109369498A CN 201811518245 A CN201811518245 A CN 201811518245A CN 109369498 A CN109369498 A CN 109369498A
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- nitrile
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- bromine
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- 238000000034 method Methods 0.000 title claims abstract description 44
- 239000000243 solution Substances 0.000 claims abstract description 75
- 238000006243 chemical reaction Methods 0.000 claims abstract description 68
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 66
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 65
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 62
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 62
- 239000011259 mixed solution Substances 0.000 claims abstract description 17
- 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
- 235000019441 ethanol Nutrition 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 11
- ZOAISSYFNQZAAW-UHFFFAOYSA-N 2-methyl-1h-pyrrole-3-carbonitrile Chemical compound CC=1NC=CC=1C#N ZOAISSYFNQZAAW-UHFFFAOYSA-N 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 150000003233 pyrroles Chemical class 0.000 claims 2
- 230000008569 process Effects 0.000 abstract description 6
- 238000002360 preparation method Methods 0.000 abstract description 5
- 238000005516 engineering process Methods 0.000 abstract description 4
- 230000001681 protective effect Effects 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000004821 distillation Methods 0.000 abstract description 2
- 238000005265 energy consumption Methods 0.000 abstract description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 18
- 239000012043 crude product Substances 0.000 description 14
- 238000005893 bromination reaction Methods 0.000 description 7
- -1 chlorphenyl Chemical group 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000031709 bromination Effects 0.000 description 4
- 238000005457 optimization Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000036632 reaction speed Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 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 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
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- NHOWDZOIZKMVAI-UHFFFAOYSA-N (2-chlorophenyl)(4-chlorophenyl)pyrimidin-5-ylmethanol Chemical compound C=1N=CN=CC=1C(C=1C(=CC=CC=1)Cl)(O)C1=CC=C(Cl)C=C1 NHOWDZOIZKMVAI-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 230000000895 acaricidal effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
-
- 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 kind of methods that microreactor continuously synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-, this method is reacted by the way that 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution to be continuously passed into microreactor simultaneously with bromine solution, gained mixed solution is reacted after flowing through more than two reaction modules in microreactor with the hydrogen peroxide solution being passed into microreactor, distillation, to realize the continuous preparation of 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile bromo- to 4-.The method of the present invention, entire process flow is simple, process is continuous, has the characteristics that high-efficient, low energy consumption, pollution-free, is a kind of efficient, environmentally protective continuous synthesis technology of the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-, it is suitable for extensive continuous preparation, is convenient for industrialized utilization.
Description
Technical field
The present invention relates to the sides that a kind of microreactor continuously synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-
Method.
Background technique
The bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4- be aryl-pyrrolidine nitrile Insecticidal and acaricidal agent chlorfenapyr and
The important intermediate of chlorine chlorfenapyr, primary synthetic methods are to be passed through with 2- rubigan -5- trifluoromethyl-pyrroles -3- nitrile with bromine
Bromination reaction synthesizes to obtain.Industrial generally to use interval synthetic method, which has the advantages that easy to operate, cost is relatively low,
But existing simultaneously reaction speed needs the disadvantages of excessive, generation spent acid is more, security risk is bigger than normal compared with slow, raw material bromine.
Microreactor, i.e. micro passage reaction refer generally to answer by the small size back that micro Process and precision processing technology manufacture
System, micro-indicate that the channel of process fluid is small, and the outer dimension without referring to micro-reactor apparatus is small or the yield of product is small.It is micro-
Reaction technology is a kind of newcooperative medical system of microchannel formula reactor substitution traditional batch reactor established on the basis of continuous flowing
Work technology has many advantages, such as good mixing property, highly-safe, but common microreactor is used for 2- rubigan -5- trifluoro
The bromination synthesis of methylpyrrole -3- nitrile is not fully solved disadvantage present in above-mentioned general batch bromination method.Therefore, it obtains
A kind of reaction speed is fast, bromine dosage is few, generate substantially without spent acid, environmentally protective microreactor continuously synthesizes bromo- 2- pairs of 4-
The method of chlorphenyl -5- trifluoromethyl pyrpole -3- nitrile, for improving the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-
Application range have a very important significance.
Summary of the invention
The technical problem to be solved by the present invention is to overcome the deficiencies of the prior art and provide, a kind of reaction speed is fast, bromine
Dosage is few, generate substantially without spent acid, environmentally protective microreactor continuously synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrrole of 4-
The method for coughing up -3- nitrile.
In order to solve the above technical problems, the technical solution adopted by the present invention are as follows:
A kind of method that microreactor continuously synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-, including with
Lower step: 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution and bromine solution are continuously passed into microreactor simultaneously
Reacted, gained mixed solution flowed through in microreactor after more than two reaction modules be passed into it is double in microreactor
Oxygen aqueous solution is reacted, and distillation obtains the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-.
Above-mentioned method, it is further improved, the microreactor by with microfluidic circuit reaction module series connection and
At；The quantity of reaction module is 5~20 in the microreactor；The liquid holdup of the single reaction module is 5mL.
Above-mentioned method, further improved, the 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution and bromine
Solution is passed into microreactor from the 1st reaction module；Hydrogen peroxide solution reaction module from the 3rd to the 12nd is passed through
Into microreactor.
Above-mentioned method, further improved, the 2- in the 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution
The molar ratio of bromine in rubigan -5- trifluoromethyl pyrpole -3- nitrile and the bromine solution is 1: 0.5~0.6；The dioxygen
H in aqueous solution2O2Molar ratio with the bromine in the bromine solution is 1.0~1.3: 1.
Above-mentioned method, further improved, the 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution is by 2- pairs
Chlorphenyl -5- trifluoromethyl pyrpole -3- nitrile is prepared after mixing with solvent；2- rubigan -5- the trifluoromethyl pyrpole -
The mass content of 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile is 5%~20% in 3- nitrile solution；The solvent is methanol
Or ethyl alcohol.
Above-mentioned method, further improved, the bromine solution is prepared after being mixed by bromine with solvent；The bromine
The mass content of bromine is 2%~10% in plain solution；The solvent is methanol or ethyl alcohol.
Above-mentioned method, further improved, the hydrogen peroxide solution is prepared after being mixed by hydrogen peroxide with solvent；Institute
State the H in hydrogen peroxide solution2O2Mass content be 0.5%~5%；The solvent is methanol or ethyl alcohol；The matter of the hydrogen peroxide
Measuring score is 30%.
Above-mentioned method, further improved, the 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution is passed through
Rate is 1.37g/min~5.46g/min；The rate that is passed through of the bromine solution is 0.8g/min~4.0g/min；It is described double
The rate that is passed through of oxygen aqueous solution is 0.34g/min~3.4g/min.
Above-mentioned method, further improved, the temperature of reaction module is controlled at 50 DEG C~78 DEG C in the microreactor.
Compared with the prior art, the advantages of the present invention are as follows:
(1) the present invention provides a kind of microreactors continuously to synthesize the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- of 4-
The method of nitrile, it is micro- anti-by the way that 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution and bromine solution to be continuously passed into simultaneously
Answer in device and reacted, gained mixed solution flowed through in microreactor after more than two reaction modules be passed into microreactor
In hydrogen peroxide solution reacted, distill, to realize the company of bromo- to 4- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile
Continuous preparation.In the present invention, 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution is first passed into micro- react with bromine solution
It reacting in device, the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4- is made in part material bromination in this reaction process,
Hydrobromic acid is also produced in the reaction process simultaneously；Further, by gained mixed solution (containing hydrobromic acid) in microreactor
In flow through more than two reaction modules after continue to react with the hydrogen peroxide solution being passed into microreactor, the reaction process
In, since bromine source concentration gradually decreases in microreactor system, before being aoxidized at this time by the hydrogen peroxide solution being added after utilizing
Hydrobromic acid is oxidized to bromine, and gained bromine is continued and the complete 2- rubigan -5- three of unreacted by the hydrobromic acid generated in system
Methyl fluoride pyrroles's -3- nitrile carries out bromination reaction, further synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-, together
The hydrogen bromide that Shi Zaici is generated continues to continue on for the bromination reaction synthesis bromo- 2- rubigan-of 4- at bromine by hydrogen peroxide oxidation again
5- trifluoromethyl pyrpole -3- nitrile, thus by constantly carrying out bromination, oxidation cycle, it is continuous to synthesize the bromo- 2- rubigan -5- of 4-
Trifluoromethyl pyrpole -3- nitrile can not only realize making full use of for bromine atom, reduce bromine inventory, reduce production cost, and
And the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of more high-purity 4- can also be synthesized, while microreactor system
In substantially without spent acid generate.The method of the present invention, entire process flow is simple, process is continuous, with high-efficient, low energy consumption, without dirt
The features such as dye is that efficient, the environmentally protective bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4- of one kind continuously synthesizes work
Skill.
(2) in the present invention, microreactor is the reactor being connected in series by the reaction module with microfluidic circuit, is passed
Matter, heat transfer efficiency are good, can quickly mix 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution with bromine, hydrogen peroxide, and
Strict control flow velocity and reaction ratio have many advantages, such as that fast reaction speed, high conversion rate, safety are good, are suitable for connecting on a large scale
Continuous preparation, is convenient for industrialized utilization.
It (3) is 1 by the molar ratio of optimization 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile and bromine in the method for the present invention
: 0.5~0.6, H2O2Molar ratio with bromine is 1.0~1.3: 1, now enables each reaction mass uniform with accurate ratio moment
Mixing, can significantly improve the utilization rate of bromine atom, to realize the efficient utilization to bromine atom；By optimization 2- to chlorobenzene
In base -5- trifluoromethyl pyrpole -3- nitrile solution the mass content of 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile be 5%~
20%, the mass content of bromine is 2%~10% in bromine solution, the H in hydrogen peroxide solution2O2Mass content be 0.5%~
5%, raw material is had preferable mobility, is conducive to feed pump and turns material, while ensure that production efficiency；By optimization 2- to chlorobenzene
The rate that is passed through of base -5- trifluoromethyl pyrpole -3- nitrile solution is 1.37g/min~5.46g/min, and bromine solution is passed through rate
The rate that is passed through for 0.8g/min~4.0g/min, hydrogen peroxide solution is 0.34g/min~3.4g/min, makes each reaction mass
It is passed through rate to be mutually matched, guarantees that reaction obtains optimum response proportion, thus react each reaction mass sufficiently, raw material availability
It is obviously improved；By controlling the temperature of reaction module in microreactor at 50 DEG C~78 DEG C, make reaction in suitable temperature strip
It is carried out under part, to obtain preferable reaction effect, and no coupling product generates.As it can be seen that preparation method of the invention, former by optimization
Material amount ratio, the mass content of raw material, raw material are passed through rate and reaction temperature, can greatly reduce the dosage of raw material, especially
It is the dosage of bromine, and product content can be significantly improved, wherein product content is up to 98.5%.
Specific embodiment
Below in conjunction with specific preferred embodiment, the invention will be further described, but not thereby limiting the invention
Protection scope.
Unless otherwise instructed, agents useful for same of the present invention is commercially available, and instrument equipment of the present invention is that conventional instrument is set
Standby, operating method of the present invention is conventional practices.
Embodiment 1
A kind of method that microreactor continuously synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-, including with
Lower step:
(1) it prepares solution: 27.3g 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile is mixed with 518.7g methanol
To 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution.8g bromine and 392g methanol are mixed to get bromine solution.It will
The hydrogen peroxide and 334.3g methanol that 5.7g mass fraction is 30% are mixed to get hydrogen peroxide solution.
(2) obtained 2- will be prepared in step (1) to chlorobenzene to be passed through rate as 5.46g/min, 4.0g/min respectively
Base -5- trifluoromethyl pyrpole -3- nitrile solution is continuously pumped into the 1st reaction module of microreactor simultaneously with bromine solution and carries out
Reaction, control each reaction module temperature be 50 DEG C, gained mixed solution flow through microreactor the 3rd reaction module it
Afterwards, it is that 3.4g/min is pumped into the hydrogen peroxide solution prepared and obtained in step (1) into microreactor to be passed through rate, makes to mix molten
Liquid is reacted with hydrogen peroxide solution, is flowed out after flowing through 10 reaction modules in total from microreactor outlet, is obtained bromo- 2- pairs of 4-
Chlorphenyl -5- trifluoromethyl pyrpole -3- nitrile crude product.Crude product is distilled, the bromo- 2- rubigan -5- three of 33.8g 4- is obtained
Methyl fluoride pyrroles's -3- nitrile, content 98.1%.
Embodiment 2
A kind of method that microreactor continuously synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-, including with
Lower step:
(1) it prepares solution: 27.3g 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile is mixed with 245.7g methanol
To 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution.8g bromine and 152g methanol are mixed to get bromine solution.It will
The hydrogen peroxide and 164.3g methanol that 5.7g mass fraction is 30% are mixed to get hydrogen peroxide solution.
(2) obtained 2- will be prepared in step (1) to chlorobenzene to be passed through rate as 2.73g/min, 1.6g/min respectively
Base -5- trifluoromethyl pyrpole -3- nitrile solution is continuously pumped into the 1st reaction module of microreactor simultaneously with bromine solution and carries out
Reaction, control each reaction module temperature be 64 DEG C, gained mixed solution flow through microreactor the 5th reaction module it
Afterwards, it is that 1.7g/min is pumped into the hydrogen peroxide solution prepared and obtained in step (1) into microreactor to be passed through rate, makes to mix molten
Liquid is reacted with hydrogen peroxide solution, is flowed out after flowing through 15 reaction modules in total from microreactor outlet, is obtained bromo- 2- pairs of 4-
Chlorphenyl -5- trifluoromethyl pyrpole -3- nitrile crude product.Crude product is distilled, the bromo- 2- rubigan -5- three of 34.9g 4- is obtained
Methyl fluoride pyrroles's -3- nitrile, content 98.4%.
Embodiment 3
A kind of method that microreactor continuously synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-, including with
Lower step:
(1) it prepares solution: 27.3g 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile is mixed with 109.2g methanol
To 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile.8g bromine and 72g methanol are mixed to get bromine solution.By 5.7g mass
The hydrogen peroxide and 28.3g methanol that score is 30% are mixed to get hydrogen peroxide solution.
(2) obtained 2- will be prepared in step (1) to chlorobenzene to be passed through rate as 1.37g/min, 0.8g/min respectively
Base -5- trifluoromethyl pyrpole -3- nitrile solution is continuously pumped into the 1st reaction module of microreactor simultaneously with bromine solution and carries out
Reaction, controls 64 DEG C of temperature of each reaction module, after gained mixed solution flows through the 5th reaction module of microreactor,
It is that 0.34g/min is pumped into the hydrogen peroxide solution prepared and obtained in step (1) into microreactor to be passed through rate, makes mixed solution
It is reacted with hydrogen peroxide solution, is flowed out after flowing through 15 reaction modules in total from microreactor outlet, obtain the bromo- 2- of 4- to chlorine
Phenyl -5- trifluoromethyl pyrpole -3- nitrile crude product.Crude product is distilled, the bromo- 2- rubigan -5- trifluoro of 34.2g 4- is obtained
Methylpyrrole -3- nitrile, content 98.3%.
Embodiment 4
A kind of method that microreactor continuously synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-, including with
Lower step:
(1) it prepares solution: 27.3g 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile is mixed with 245.7g methanol
To 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution.8.8g bromine and 167.2g methanol are mixed to get bromine solution.
The hydrogen peroxide that 7.17g mass fraction is 30% is mixed to get hydrogen peroxide solution with 207.88g methanol.
(2) obtained 2- will be prepared in step (1) to chlorobenzene to be passed through rate as 2.73g/min, 1.76g/min respectively
Base -5- trifluoromethyl pyrpole -3- nitrile solution is continuously pumped into the 1st reaction module of microreactor simultaneously with bromine solution and carries out
Reaction, controls 64 DEG C of temperature of each reaction module, after gained mixed solution flows through the 5th reaction module of microreactor,
It is that 2.15g/min is pumped into the hydrogen peroxide solution prepared and obtained in step (1) into microreactor to be passed through rate, makes mixed solution
It is reacted with hydrogen peroxide solution, is flowed out after flowing through 15 reaction modules in total from microreactor outlet, obtain the bromo- 2- of 4- to chlorine
Phenyl -5- trifluoromethyl pyrpole -3- nitrile crude product.Crude product is distilled, the bromo- 2- rubigan -5- trifluoro of 34.8g 4- is obtained
Methylpyrrole -3- nitrile, content 98.1%.
Embodiment 5
A kind of method that microreactor continuously synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-, including with
Lower step:
(1) it prepares solution: 27.3g 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile is mixed with 245.7g methanol
To 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution.9.6g bromine and 182.4g methanol are mixed to get bromine solution.
The hydrogen peroxide that 8.84g mass fraction is 30% is mixed to get hydrogen peroxide solution with 164.3g methanol.
(2) obtained 2- will be prepared in step (1) to chlorobenzene to be passed through rate as 2.73g/min, 1.92g/min respectively
Base -5- trifluoromethyl pyrpole -3- nitrile solution is continuously pumped into the 1st reaction module of microreactor simultaneously with bromine solution and carries out
Reaction, controls 64 DEG C of temperature of each reaction module, after gained mixed solution flows through the 5th reaction module of microreactor,
It is that 2.65g/min is pumped into the hydrogen peroxide solution prepared and obtained in step (1) into microreactor to be passed through rate, makes mixed solution
It is reacted with hydrogen peroxide solution, is flowed out after flowing through 15 reaction modules in total from microreactor outlet, obtain the bromo- 2- of 4- to chlorine
Phenyl -5- trifluoromethyl pyrpole -3- nitrile crude product.Crude product is distilled, the bromo- 2- rubigan -5- trifluoro of 34.6g 4- is obtained
Methylpyrrole -3- nitrile, content 98.3%.
Embodiment 6
A kind of method that microreactor continuously synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-, including with
Lower step:
(1) it prepares solution: 27.3g 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile is mixed with 245.7g ethyl alcohol
To 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution.8.8g bromine and 167.2g ethyl alcohol are mixed to get bromine solution.
The hydrogen peroxide that 7.17g mass fraction is 30% is mixed to get hydrogen peroxide solution with 207.88g ethyl alcohol.
(2) obtained 2- will be prepared in step (1) to chlorobenzene to be passed through rate as 2.73g/min, 1.76g/min respectively
Base -5- trifluoromethyl pyrpole -3- nitrile solution is continuously pumped into the 1st reaction module of microreactor simultaneously with bromine solution and carries out
Reaction, controls the temperature 70 C of each reaction module, after gained mixed solution flows through the 8th reaction module of microreactor,
It is that 2.15g/min is pumped into the hydrogen peroxide solution prepared and obtained in step (1) into microreactor to be passed through rate, makes mixed solution
It is reacted with hydrogen peroxide solution, is flowed out after flowing through 16 reaction modules in total from microreactor outlet, obtain the bromo- 2- of 4- to chlorine
Phenyl -5- trifluoromethyl pyrpole -3- nitrile crude product.Crude product is distilled, the bromo- 2- rubigan -5- trifluoro of 35.8g 4- is obtained
Methylpyrrole -3- nitrile, content 98.5%.
Embodiment 7
A kind of method that microreactor continuously synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-, including with
Lower step:
(1) it prepares solution: 27.3g 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile is mixed with 245.7g ethyl alcohol
To 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution.8.8g bromine and 167.2g ethyl alcohol are mixed to get bromine solution.
The hydrogen peroxide that 7.17g mass fraction is 30% is mixed to get hydrogen peroxide solution with 207.88g ethyl alcohol.
(2) obtained 2- will be prepared in step (1) to chlorobenzene to be passed through rate as 2.73g/min, 1.76g/min respectively
Base -5- trifluoromethyl pyrpole -3- nitrile solution is continuously pumped into the 1st reaction module of microreactor simultaneously with bromine solution and carries out
Reaction, controls 78 DEG C of temperature of each reaction module, after gained mixed solution flows through the 12nd reaction module of microreactor,
It is that 2.15g/min is pumped into the hydrogen peroxide solution prepared and obtained in step (1) into microreactor to be passed through rate, makes mixed solution
It is reacted with hydrogen peroxide solution, is flowed out after flowing through 20 reaction modules in total from microreactor outlet, obtain the bromo- 2- of 4- to chlorine
Phenyl -5- trifluoromethyl pyrpole -3- nitrile crude product.Crude product is distilled, the bromo- 2- rubigan -5- trifluoro of 34.3g 4- is obtained
Methylpyrrole -3- nitrile, content 98.4%.
The above is only a preferred embodiment of the present invention, protection scope of the present invention is not limited merely to above-mentioned implementation
Example.All technical solutions belonged under thinking of the present invention all belong to the scope of protection of the present invention.It is noted that for the art
Those of ordinary skill for, improvements and modifications without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (9)
1. a kind of method that microreactor continuously synthesizes the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-, feature exist
In, comprising the following steps: 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile solution is continuously passed into simultaneously with bromine solution
Reacted in microreactor, gained mixed solution flowed through in microreactor after more than two reaction modules be passed into it is micro- anti-
It answers the hydrogen peroxide solution in device to be reacted, distills, obtain the bromo- 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile of 4-.
2. the method according to claim 1, wherein the microreactor is by the reaction mould with microfluidic circuit
Block is connected in series；The quantity of reaction module is 5~20 in the microreactor；Individually the liquid holdup of the reaction module is
5mL。
3. according to the method described in claim 2, it is characterized in that, the 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile is molten
Liquid and bromine solution are passed into microreactor from the 1st reaction module；Hydrogen peroxide solution reaction from the 3rd to the 12nd
Module is passed into microreactor.
4. method described in any one of claim 1 to 3, which is characterized in that the 2- rubigan -5- trifluoromethyl
2- rubigan -5- trifluoromethyl pyrpole -3- nitrile and the molar ratio of the bromine in the bromine solution in pyrroles's -3- nitrile solution are
1: 0.5~0.6；H in the hydrogen peroxide solution2O2Molar ratio with the bromine in the bromine solution is 1.0~1.3: 1.
5. according to the method described in claim 4, it is characterized in that, the 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile is molten
Liquid is prepared after being mixed by 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile with solvent；2- rubigan -5- the trifluoro
The mass content of 2- rubigan -5- trifluoromethyl pyrpole -3- nitrile is 5%~20% in methylpyrrole -3- nitrile solution；It is described molten
Agent is methanol or ethyl alcohol.
6. according to the method described in claim 4, it is characterized in that, the bromine solution is prepared into after being mixed by bromine with solvent
It arrives；The mass content of bromine is 2%~10% in the bromine solution；The solvent is methanol or ethyl alcohol.
7. according to the method described in claim 4, it is characterized in that, the hydrogen peroxide solution is made after being mixed by hydrogen peroxide with solvent
It is standby to obtain；H in the hydrogen peroxide solution2O2Mass content be 0.5%~5%；The solvent is methanol or ethyl alcohol；It is described
The mass fraction of hydrogen peroxide is 30%.
8. method described in any one of claim 1 to 3, which is characterized in that the 2- rubigan -5- trifluoromethyl
The rate that is passed through of pyrroles's -3- nitrile solution is 1.37g/min~5.46g/min；The rate that is passed through of the bromine solution is 0.8g/
Min~4.0g/min；The rate that is passed through of the hydrogen peroxide solution is 0.34g/min~3.4g/min.
9. method described in any one of claim 1 to 3, which is characterized in that reaction module in the microreactor
Temperature is controlled at 50 DEG C~78 DEG C.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109776376A (en) * | 2019-03-15 | 2019-05-21 | 湘潭大学 | Apparatus and synthetic method for continuous synthesis of 4-bromo-2-p-chloro-5-trifluoromethylpyrrole-3-carbonitrile |
| CN117586167A (en) * | 2024-01-18 | 2024-02-23 | 山东潍坊双星农药有限公司 | A new synthesis process of fenfonitrile |
| CN118851973A (en) * | 2024-09-28 | 2024-10-29 | 山东潍坊双星农药有限公司 | A preparation method and device of chlorfenapyr |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06279402A (en) * | 1993-03-30 | 1994-10-04 | Ube Ind Ltd | Production of 3-cyano-4-halo-2-aryl-5-trifluoromethylpyrroles |
| CN102746208A (en) * | 2011-04-21 | 2012-10-24 | 新沂永隆化工有限公司 | Economic preparation method of 4-bromine-2-aryl-5-trifluoromethyl-1H-pyrrole-3-nitrile |
-
2018
- 2018-12-12 CN CN201811518245.8A patent/CN109369498B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06279402A (en) * | 1993-03-30 | 1994-10-04 | Ube Ind Ltd | Production of 3-cyano-4-halo-2-aryl-5-trifluoromethylpyrroles |
| CN102746208A (en) * | 2011-04-21 | 2012-10-24 | 新沂永隆化工有限公司 | Economic preparation method of 4-bromine-2-aryl-5-trifluoromethyl-1H-pyrrole-3-nitrile |
Non-Patent Citations (1)
| Title |
|---|
| 刘熠 等: "微通道反应器的研究进展", 《辽宁化工》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109776376A (en) * | 2019-03-15 | 2019-05-21 | 湘潭大学 | Apparatus and synthetic method for continuous synthesis of 4-bromo-2-p-chloro-5-trifluoromethylpyrrole-3-carbonitrile |
| CN109776376B (en) * | 2019-03-15 | 2024-12-06 | 湘潭大学 | Device and method for continuously synthesizing 4-bromo-2-p-chloro-5-trifluoromethylpyrrole-3-carbonitrile |
| CN117586167A (en) * | 2024-01-18 | 2024-02-23 | 山东潍坊双星农药有限公司 | A new synthesis process of fenfonitrile |
| CN118851973A (en) * | 2024-09-28 | 2024-10-29 | 山东潍坊双星农药有限公司 | A preparation method and device of chlorfenapyr |
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