CN116836060A - Preparation method of 2,3, 4-trifluoro nitrobenzene - Google Patents

Preparation method of 2,3, 4-trifluoro nitrobenzene Download PDF

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CN116836060A
CN116836060A CN202310617767.8A CN202310617767A CN116836060A CN 116836060 A CN116836060 A CN 116836060A CN 202310617767 A CN202310617767 A CN 202310617767A CN 116836060 A CN116836060 A CN 116836060A
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reaction
microchannel reactor
trichloronitrobenzene
trichlorobenzene
reactor
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贾永林
成道泉
王祥传
李珂
张力伟
刘玲玲
马淼
张帆
潘澳启
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Shandong Jingbo Agrochemical Technology Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/08—Preparation of nitro compounds by substitution of hydrogen atoms by nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/07—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms
    • C07C205/11—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms having nitro groups bound to carbon atoms of six-membered aromatic rings
    • C07C205/12—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by halogen atoms having nitro groups bound to carbon atoms of six-membered aromatic rings the six-membered aromatic ring or a condensed ring system containing that ring being substituted by halogen atoms

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Abstract

The application belongs to the field of organic synthesis, and particularly relates to a preparation method of 2,3, 4-trifluoro nitrobenzene, in particular to a continuous nitration method by taking 1,2, 3-trichlorobenzene as a starting material and a continuous production of 2,3, 4-trifluoro nitrobenzene by a fluorination microchannel.

Description

Preparation method of 2,3, 4-trifluoro nitrobenzene
Technical Field
The application belongs to the field of organic synthesis, and particularly relates to a preparation method of 2,3, 4-trifluoro nitrobenzene.
Background
2,3, 4-trifluoro nitrobenzene (CAS number: 771-69-7) is pale yellow oily liquid, and is mainly used for synthesizing first-generation fluoroquinolone medicines such as ofloxacin (ofloxacin, trade name Tarivid), levofloxacin, lomefloxacin (lamfloxadim) and the like in the pharmaceutical industry. Meanwhile, the 2,3, 4-trifluoro nitrobenzene is well applied in the pesticide field, the N-acyl-N- (2, 3, 4-trifluoro anilino) propionate compound which is derived and synthesized by the 2,3, 4-trifluoro nitrobenzene is subjected to indoor sterilization biological activity screening test, the control effect on the wheat sheath blight and melon gray mold is more than 70%, and the drug effect of the individual compound is equivalent to that of carbendazim. The 3,4, 5-trifluoro-bromobenzene is prepared by reducing, brominating and diazotizing 2,3, 4-trifluoro-bromobenzene, and the 3,4, 5-trifluoro-bromobenzene is an important pesticide intermediate, is mainly used for synthesizing succinic acid dehydrogenase inhibitor (SDHI) bactericide fluxapyroxad, and is also an important liquid crystal intermediate for producing 4 th-generation TFT color liquid crystal materials. 2,3, 4-trifluoro nitrobenzene is widely used as an important chemical intermediate in the fields of medicine, pesticide, liquid crystal and the like.
At present, 2, 6-dichloroaniline is used as a starting material, and 2,3, 4-trifluoronitrobenzene is prepared through diazo fluorination reaction, nitration reaction and chlorofluoro exchange reaction, and the total yield of the three steps of reaction is about 62 percent (calculated by 2, 6-dichloroaniline). The key in the synthesis of the process is two-step reaction, namely, the decomposition of the diazonium fluoborate is very severe, the heat release is obvious, tar-like substances are easy to form, the dimethyl sulfoxide and sulfolane are used as solvents in the prior art in the fluorination reaction, the use amount is large, and the recovery is difficult. The reaction route is as follows:
in Chinese patent CN01127025, it is reported that o-chloronitrobenzene is used as a starting material, and 2, 3-dichloronitrobenzene is prepared by chlorination; then the 2,3, 4-trifluoro-nitrobenzene is prepared through four steps of fluorination, high-temperature chlorination, nitration and secondary fluorination, and the total yield is about 30 percent (calculated by 2, 3-dichloro-nitrobenzene). The process uses o-chloronitrobenzene with lower cost than 2, 6-dichloroaniline as a raw material, so that diazotization reaction is avoided, explosion risk in the production process is avoided, but the secondary chlorination denitration reaction condition after 2, 3-dichloronitrobenzene fluorination is harsh, the reaction temperature is high, dangerous chlorine is used for chlorination under the condition of high reaction temperature, the safety risk is high, the equipment investment cost is high, the fluorination reaction with troublesome primary wastewater treatment is increased, and the environmental protection investment is large and is not suitable for industrial production. The reaction route is as follows:
gu Jiansong and Zhang Haibin report that 2,3, 4-trifluoronitrobenzene is prepared from 1,2, 3-trichlorobenzene by nitration and fluorination, and the content is 99% but the yield is only 60%. In chinese patent CN201710446278.5, it is also reported that 1,2, 3-trichlorobenzene is used as a raw material, and is subjected to nitration substitution to obtain 2,3, 4-trichloronitrobenzene, KF is added, stirred and dehydrated under the catalysis of TBAB, then reacted at 180 ℃, filtered after the reaction is finished, the filtrate is distilled under reduced pressure and then put into an anhydrous reactor, KF is added, after the dehydration under reduced pressure and under the catalysis of TBAF, the reaction is performed under the condition of ultrasonic power of 120 ℃ and 30KHZ, and finally the 2,3, 4-trifluoronitrobenzene is obtained by rectification. The reaction route is as follows:
in chinese patent CN201910974492.7, it is reported that 2,3, 4-trichloronitrobenzene is obtained by using antimony pentafluoride/hydrogen fluoride fluorination reaction as a raw material, in this process, antimony pentafluoride and hydrogen fluoride react to generate super acid fluoroantimonic acid HSbF6, and because the fluoroantimonic acid is relatively dangerous and is easy to occur a risk accident, and the container for holding the fluoroantimonic acid must be filled with teflon (i.e. polytetrafluoroethylene) material, the requirement for a micro-channel reaction device using the fluoroantimonic acid is relatively high, and the micro-channel fluorination reaction device using the teflon as the material is difficult to process, produce and manufacture, and is not suitable for industrialization.
WO01/81274 reports the fluorination of { tetrakis [ tris (dimethylamino) phosphoranylideneamino ] with phosphazenium compounds]Scale } [ (Me) 2 N 3 ),P＝N] 4 P + F - Although the fluorination reaction yield of the fluorination reagent is high and the fluorination effect is good for the fluorination of the chlorobenzene, the use of the fluorination reagent generates a large amount of wastewater due to poor atom economy, and the price is high, so that the fluorination reagent is not suitable for industrialization.
2, 6-dichloroaniline and o-chloronitrobenzene are taken as raw materials to produce 2, 6-dichlorofluorobenzene through dangerous reactions such as diazotization and chlorination, 3-fluoro-2, 4-dichloronitrobenzene is produced through nitration, diazotization, chlorination and nitration are important dangerous processes which are concerned by China, 3-fluoro-2, 4-dichloronitrobenzene is produced through a fluorination process with potassium fluoride as a fluorine source, the fluorination process must use spray-dried anhydrous potassium fluoride to improve the reactivity, and the conventional kettle type fluorination process also has the problems of high reaction temperature, long reaction time, large reactor equipment size, low production efficiency and unstable product quality because the solubility of the potassium fluoride in a conventional organic solvent is often required to be added with a phase transfer catalyst to improve the yield.
1,2, 3-trichlorobenzene is used as raw material, while dangerous processes such as diazotization and chlorination are avoided, 1,2, 3-trichlorobenzene is used for nitration reaction to generate intermediate product 2,3, 4-trichloronitrobenzene, and concentrated nitric acid, mixed acid and the like are used as nitrating agents for nitration reaction, so that the method has the characteristics of large reaction heat release, heterogeneous mass transfer, heat transfer and the like. Most of traditional processes adopt batch or semi-batch kettle type and other forms, the kettle type process is batch production, the technology is behind, the single kettle material quantity is large, the mass transfer and heat transfer efficiency is poor, the material dispersibility is relatively slow, and the accumulation of raw materials is easy to cause; the temperature rise and reduction is conducted through the jacket, the distance between the jacket wall and the center of the material is far, the heat conduction speed is slow, the temperature rise and reduction time is long, the reaction heat cannot be removed in time, and the like, the local overtemperature and the like are generated in the reaction process, the detection point of the thermometer is a certain distance away from the jacket wall and the center of the material, the temperature measurement has a certain hysteresis property, the actual temperature value cannot be timely and accurately displayed for dangerous processes such as fast reaction speed, large heat release and the like, and thermal runaway is easy to occur, so that explosion accidents occur. In the kettle type intermittent process, the material quantity in the reactor is large, the potential energy scale is large, once thermal runaway occurs, the heat released by the nitration reaction can lead to the temperature rise of a large amount of materials, the side reactions such as multi-nitration, oxidation and the like are initiated, the pyrolysis of the materials is initiated, the explosion result is not considered, and the development requirements of green chemistry and intrinsic safety are not met.
The fluorination process of 2,3, 4-trichloronitrobenzene by using potassium fluoride as fluorine source still has kettle type fluorinated pain points, such as: the recovery of high boiling point polar solvents (DMSO, DMF, sulfolane) is difficult, the reaction temperature is high, the reaction time is long, a phase transfer catalyst and the like are needed to be added, the reaction yield is low, the ultrasonic assisted catalysis is adopted, the yield can be improved, but industrialization is still difficult and heavy, the industrial safety risk of adopting antimony pentafluoride/hydrogen fluoride as a fluorine source is high, and the method does not accord with the current green development trend of the fine chemical industry. Meanwhile, the method for preparing fluoride by using 2,3, 4-trifluoro nitrobenzene as a raw material through fluorine-chlorine exchange is characterized in that fluorine sources commonly used in industry are two main types of hydrogen fluoride and fluoride salt. The fluorination process using hydrogen fluoride as fluorine source has the problems of serious equipment corrosion and high safety risk. While the fluoride salt represented by potassium fluoride generally needs to be added with a large amount of strong polar solvent and a phase transfer catalyst for dissolution assistance, and the advanced production concept of producing aryl fluoride by taking traditional hydrogen fluoride and potassium fluoride as fluorine sources is more and more unsuitable in environmental protection, safety, green and economy.
Therefore, there is still a real urgent need to develop new 2,3, 4-trifluoronitrobenzene synthesis processes.
Disclosure of Invention
Aiming at the defects existing in the prior art, the application provides a preparation method of 2,3, 4-trifluoro nitrobenzene, in particular to a continuous nitration method by taking 1,2, 3-trichlorobenzene as a starting material and a continuous production of 2,3, 4-trifluoro nitrobenzene by using a fluorination microchannel.
Compared with the prior art, the method has the advantages that 1,2, 3-trichlorobenzene, nitric acid and sulfuric acid are used as raw materials, the raw materials are reacted by the micro-channel reactor, the mass transfer and heat transfer efficiency is high, the liquid holdup is small, the safety performance is good, the generated acid wastewater is less, the process is environment-friendly, the period is short, continuous operation can be realized, no amplification effect is generated, the raw materials of 2,3, 4-trichloronitrobenzene, 2,3, 4-trichloronitrobenzene and tetraethylammonium fluoride trichromate are safely produced, and the 2,3, 4-trifluoro nitrobenzene product is obtained by the high yield of the reaction of the micro-channel reactor, the phase transfer catalyst is not required to be added, the polar organic solvent is not used in the reaction, the operation is simple, the reaction yield is high, the continuous production can be realized, the three wastes are fewer, and the cost is low.
The application adopts the specific technical scheme that:
a preparation method of 2,3, 4-trifluoro nitrobenzene comprises the following steps:
step one: the method is characterized in that 1,2, 3-trichlorobenzene, sulfuric acid and nitric acid mixed acid are used as raw materials, and are continuously reacted in a micro-channel reactor to obtain 2,3, 4-trichloronitrobenzene, wherein the reaction equation is as follows:
further comprising the steps of:
sulfuric acid and nitric acid are prepared into a mixed acid solution, and 1,2, 3-trichlorobenzene and chlorinated hydrocarbon solvent are prepared into a mixed solution; and respectively conveying the mixed solution prepared from the 1,2, 3-trichlorobenzene and the chlorinated hydrocarbon solvent and the mixed acid solution into a micro-channel reactor for continuous nitration reaction, and quenching, washing, desolventizing and crystallizing to obtain the 2,3, 4-trichloronitrobenzene product.
The temperature of the nitration reaction in the microchannel reactor is 50-75 ℃; further the temperature of the nitration reaction is 55-85 ℃.
The residence time of the nitration reaction in the microchannel reactor is 30-150s; still further the nitration residence time is from 90 to 120s.
The pressure of the nitration reaction in the microchannel reactor is regulated to be 0.3-2.0MPa through a back pressure valve.
The nitration pressure is 0.4-0.6MPa.
The chlorinated ethylene solvent is one of 1, 2-dichloroethane, 1-dichloroethane, 1, 3-dichloropropane, 1, 2-dichloropropane and n-chlorobutane; the mass ratio of the dosage to the raw material 1,2, 3-trichlorobenzene is (1:1) - (1:3).
The mass concentration of sulfuric acid used for preparing the mixed acid solution is 60-98%, and the mass concentration of nitric acid used is 60-98%.
The molar ratio of the 1,2, 3-trichlorobenzene, the nitric acid and the sulfuric acid is 1:1-1.25:1-1.65, and more preferably 1:1.06:1.35.
The internal channel of the microchannel reactor is in the form of one of heart, umbrella, chinese character 'zhong' shape and diamond, and more preferably is heart-shaped or umbrella-shaped.
Step two: using tetraethylammonium fluoride trichlorfluoride as a fluorine source, and continuously reacting with the mixture in a microchannel reactor to obtain 2,3, 4-trifluoro nitrobenzene, wherein the reaction equation is as follows:
further comprising the steps of:
heating 2,3, 4-trichloronitrobenzene to 60-80 ℃ by a heated stock tank to melt the 2,3, 4-trichloronitrobenzene into flowing liquid; simultaneously storing tetraethylammonium fluoride tri-hydrofluoric acid salt in a 120-DEG stock tank, wherein the tetraethylammonium fluoride tri-hydrofluoric acid salt is also flowing liquid;
and respectively conveying the 2,3, 4-trichloronitrobenzene and tetraethylammonium fluoride tricofluoride salt into a microchannel reactor in a liquid form for continuous fluorination reaction, and obtaining a 2,3, 4-trifluoro nitrobenzene product through quenching, water washing, desolventizing and rectifying.
In this step, the temperature of the fluorination reaction in the microchannel reactor is 140 to 200 ℃, and more preferably 160 ℃.
The residence time of the fluorination reaction in the microchannel reactor is from 30 to 150 minutes, more preferably 48 minutes.
The pressure of the fluorination reaction in the microchannel reactor is regulated to be 0.6-3.0MPa through a back pressure valve.
The fluorination reaction pressure is 0.8-1MPa, and the fluorination reaction does not use a solvent or a phase transfer catalyst.
The feeding mole ratio of the 2,3, 4-trichloronitrobenzene and tetraethylammonium fluoride trichalflite is 1:3-8, and is further limited to be 1:4.
The fluorinated microchannel reactor material may be silicon carbide or a hastelloy material, preferably silicon carbide. The nitrifying micro-channel reactor is made of a Hatype alloy material.
The two-step comprehensive yield of the 2,3, 4-trifluoro nitrobenzene prepared from the raw material 1,2, 3-trichlorobenzene by adopting the preparation method can reach about 87 percent, which is superior to the existing process route which takes 2, 6-dichloroaniline or o-chloronitrobenzene as the raw material, and breaks through the problem that 2, 4-difluoro-3-chloro-nitrobenzene intermediate product cannot be further converted into 2,3, 4-trifluoro nitrobenzene in the fluorination micro-channel process which takes potassium fluoride or anhydrous hydrogen fluoride as fluorine source after the raw material 1,2, 3-trichlorobenzene is nitrified in the prior literature. The preparation process has the advantages of low cost, high yield, high intrinsic safety, less three wastes, simple operation, less equipment investment and the like.
Detailed Description
The foregoing summary of the application is described in further detail below in connection with specific embodiments, but it should not be understood that the scope of the subject matter described above is limited to the following examples. All techniques based on the above description of the present application are within the scope of the present application, and the raw materials used in the following examples are all commercially available products, except for the specific descriptions.
Example 1
The production method of 2,3, 4-trichloronitrobenzene takes 1,2, 3-trichlorobenzene, sulfuric acid and nitric acid mixed acid as raw materials, and the raw materials are continuously reacted in a micro-channel reactor to obtain 2,3, 4-trichloronitrobenzene, wherein the reaction equation is as follows:
the method comprises the following specific steps:
the method comprises the steps of adopting a commercially available microchannel reactor I with a certain model, wherein the size of a channel of the reactor is 1mm by 1.5mm, the liquid holdup of a single piece is l.6mL, the total liquid holdup is about 17.2mL, and the channel is of a heart-shaped flow guide structure, and performing nitration reaction:
270g of 1,2, 3-trichlorobenzene (1.48mol, 1.0 eq.) as a starting material was dissolved in 316g of dichloroethane to prepare a 1,2, 3-trichlorobenzene solution;
a mixed acid was prepared by taking 210g (2.10 mol,1.41 eq.) of 98% by mass sulfuric acid and 103.52g (1.577 mol,1.059 eq.) of 96% by mass fuming nitric acid.
Starting a metering pump, setting the feeding flow rate of the 1,2, 3-trichlorobenzene solution to be 7.3mL/min, setting the feeding flow rate of the mixed acid to be 3.6mL/min, setting the temperature of the heat conducting oil of the micro-channel reactor to be 65 ℃, and setting the residence time of the materials in the micro-channel reactor to be 90s; the pressure in the microchannel reactor was regulated to 0.8MPa by a back pressure valve to begin continuous feed nitration.
Post-treatment: the materials at the outlet of the micro-channel reactor are connected into a treatment tank containing ice water for quenching, and are stirred to room temperature, then separated into liquid, and the lower organic phase is separated, and the conversion rate of the materials is 98.8%, the nitrified products are 97.8% and the dinitrate impurities are 0.5% by sampling and detecting. After purification, 330.6g of 2,3, 4-trichloronitrobenzene (purity 98%) was obtained, and the yield was about 98.11%.
Example 2
The production method of 2,3, 4-trichloronitrobenzene adopts a commercial microchannel reactor II with a certain model, the liquid holdup of a single reactor is 8.0mL, 8 pieces are added, the total liquid holdup is about 64mL, and the channel is of an umbrella-shaped structure for nitration reaction:
642.6g of 1,2, 3-trichlorobenzene (3.54 mol,1 eq.) was dissolved in 709g of 1, 3-dichloropropane to prepare a 1,2, 3-trichlorobenzene solution;
a mixed acid was prepared from 562g (5.62 mol,1.587 eq.) of 98% sulfuric acid and 278.9g (4.25 mol,1.20 eq.) of 96% fuming nitric acid.
Starting a metering pump, setting the feeding flow rate of the 1,2, 3-trichlorobenzene solution to be 27.87mL/min, the feeding flow rate of the mixed acid to be 15.13mL/min, setting the temperature of the heat conducting oil of the microchannel reactor to be 65 ℃, and setting the residence time of materials in the microchannel reactor to be 65s; the pressure in the microchannel reactor was regulated to 0.6MPa by a back pressure valve to begin continuous feed nitration.
Post-treatment: the materials at the outlet of the micro-channel reactor are connected into a treatment tank containing ice water for quenching, and are stirred to room temperature, then separated into liquid, separated into lower organic phase, and sampled and detected to have the raw material conversion rate of 99.6%, the nitrified product of 97.1% and the dinitrate impurity of 0.2%. After purification, 774.3g of 2,3, 4-trichloronitrobenzene (purity 98%) was obtained in a yield of 96.5%.
2,3, 4-trifluoro nitrobenzene is obtained by reacting 2,3, 4-trichloronitrobenzene prepared in the example 1 or 2, and tetraethylammonium fluoride tri-hydrofluoric acid salt is used as raw materials, and the raw materials are continuously reacted in a micro-channel reactor to obtain 2,3, 4-trifluoro nitrobenzene, wherein the reaction equation is as follows:
example 3:
the commercial corning G1 silicon carbide micro-channel reactor is adopted, the volume of the liquid held in a single module is about 10 milliliters, and the reaction path is free from metal contact.
The reaction solution A was 787.22g of 2,3, 4-trichloronitrobenzene liquid (3.47 mol,1 eq.) prepared in example 1 and stored in a constant temperature 80℃tank, and the reaction solution B was 2910.11g of tetraethylammonium fluoride trichromatic liquid (13.9 mol,4.0 eq.) stored in a constant temperature 120℃silicon carbide tank.
The reaction solution A was pumped through a metering pump at a flow rate of 1mL/min into a preheating coil at a temperature of 150℃and a residence time of lmin. The reaction solution B was pumped through a metering pump at a flow rate of 6.15mL/min into a preheating coil at a temperature of 150℃for a residence time of 1min.
The preheated reaction liquid A and reaction liquid B flow into a continuous flow micro-channel reactor, the temperature of the micro-channel reactor is 150 ℃, the pressure in the micro-channel reactor is regulated to 0.9MPa through a back pressure valve, the residence time is 48min, materials at the outlet of the micro-channel reactor are connected into a treatment tank made of a Haalloy material containing ice water, dichloromethane is added for extraction, a water layer is separated to obtain an organic phase, sampling and monitoring are carried out on 95.6% of 2,3, 4-trifluoro-nitrobenzene and 1.6% of 2, 4-difluoro-3-chloro-nitrobenzene, and 557.55g of 2,3, 4-trifluoro-nitrobenzene (purity: 97.2%) is obtained through desolventizing and rectification, and the yield is about 90.7%.
Example 4:
the silicon carbide micro-channel continuous flow reactor customized from Kaileying is adopted, the volume of the liquid held in a single module is about 15 milliliters, 15 groups of modules are arranged, and the reaction path is free from metal contact.
Reaction liquid a was 1349.52g of 2,3, 4-trichloronitrobenzene liquid (5.96 mol,1 eq.) prepared in example 1 and stored in a constant temperature 80 ℃ tank, and reaction liquid B was 4988.7g of tetraethylammonium fluoride trichromatic liquid (23.84 mol,4.0 eq.) stored in a constant temperature 120 ℃ silicon carbide material tank.
The reaction solution A was pumped through a metering pump at a flow rate of 1mL/min into a preheating coil at a temperature of 160℃and a residence time of l min. The reaction solution B was pumped through a metering pump at a flow rate of 6.15mL/min into a preheating coil at a temperature of 160℃for a residence time of 1min. The preheated reaction liquid A and reaction liquid B flow into a continuous flow micro-channel reactor, the temperature of the micro-channel reactor is 160 ℃, the pressure in the micro-channel reactor is regulated to 0.9MPa through a back pressure valve, the residence time is 55min, materials at the outlet of the micro-channel reactor are connected into a treatment tank made of a Haalloy material containing ice water, dichloromethane is added for extraction, a water layer is separated to obtain an organic phase, sampling and monitoring are carried out on 96.2% of 2,3, 4-trifluoro nitrobenzene and 1.98% of 2, 4-difluoro-3-chloro-nitrobenzene, and the 913.32g of 2,3, 4-trifluoro nitrobenzene (purity: 97.0%) is obtained through desolventizing and rectification, and the yield is about 86.5%.
Comparative example 1:
600g of 98% concentrated sulfuric acid (6.0 mol), 500g of 1,2, 3-trichlorobenzene (2.75 mol,1.0 eq.) and 750g of dichloroethane are added into a reaction bottle, the temperature is raised under stirring, 227.09g of 96% fuming nitric acid (3.46 mol,1.25 eq.) is slowly added dropwise under stirring, after the dropwise addition is finished, the temperature is kept at 80-85 ℃ for 3 hours, the conversion rate of the sample detection raw material is 97%, the nitrified product is 92%, the dinitration impurity is 3.8%, the reaction is finished, the mixture is kept still under heat preservation for layering, and 556.2g of 2,3, 4-trichloronitrobenzene (purity: 95%) is obtained by purifying, and the yield is 89.1%.
Comparative example 2:
49.96g of 2,3, 4-trichloronitrobenzene (0.22 mol,1.0 eq.) and 230.8g of tetraethylammonium fluoride (1.10 mol,5.0 eq.) were added to a 500mL Ha-type alloy reaction vessel, the temperature was slowly raised with stirring, the temperature was controlled at 180℃and maintained for 20 hours, the temperature was lowered, sampling was performed to detect the conversion of the raw material of 93.1%, and sampling was performed to detect 72.0% of 2,3, 4-trifluoronitrobenzene and 19.4% of 2, 4-difluoro-3-chloro-nitrobenzene. Dichloromethane was added for extraction, and the aqueous layer was separated to obtain an organic phase, which was desolventized and distilled to obtain 23.76g of 2,3, 4-trifluoronitrobenzene (purity: 95.0%) in 61% yield.
Comparative examples 1 and 2 employed a kettle reaction, and compared with the technical scheme of the present application, had the disadvantages of lower yield than examples and longer reaction time than examples.
Comparative example 3:
the commercial corning G1 silicon carbide micro-channel reactor is adopted, the volume of the liquid held in a single module is about 10 milliliters, and the reaction path is free from metal contact.
The reaction solution A was a solution prepared by stirring and mixing 472.33g of 2,3, 4-trichloronitrobenzene liquid (2.08 mol,1 eq.) stored in a constant temperature 80℃tank, 604.2g of potassium fluoride (10.4 mol,5.0 eq.) and tetraphenylphosphine bromide (26.16 g,0.062mol,0.03 eq.) as a phase transfer catalyst in 2.43kg of sulfolane.
The reaction solution A was pumped through a metering pump at a flow rate of 1mL/min into a preheating coil at a temperature of 150℃for a residence time of l min. The reaction solution B was pumped through a metering pump at a flow rate of 10.28mL/min into a preheating coil at a temperature of 150℃for a residence time of 1min. The preheated reaction liquid A and reaction liquid B flow into a continuous flow micro-channel reactor, the temperature of the micro-channel reactor is 150 ℃, the pressure in the micro-channel reactor is regulated to 0.9MPa through a back pressure valve, the residence time is 130min, the outlet materials of the micro-channel reactor are connected into a treatment tank containing ice water, methylene dichloride is added for extraction, the water layer is separated to obtain an organic phase, sampling and monitoring are carried out on 40.6% of 2,3, 4-trifluoronitrobenzene, 20.8% of 2, 4-difluoro-3-chloro-nitrobenzene and 35.2% of raw material residual 2,3, 4-trichloronitrobenzene.
Comparative example 4:
the commercial corning G1 silicon carbide micro-channel reactor is adopted, the volume of the liquid held in a single module is about 10 milliliters, and the reaction path is free from metal contact.
The reaction solution A was prepared from 188.93g of 2,3, 4-trichloronitrobenzene liquid (0.91 mol,1 eq.) stored in a constant temperature 80℃tank, and the reaction solution B was prepared from 84g of anhydrous hydrogen fluoride (4.55 mol,5.0 eq.) stored in a constant temperature 0℃tank.
Pumping the reaction liquid A into a preheating coil pipe with the temperature of 150 ℃ through a metering pump at the flow rate of 1mL/min, keeping the residence time of l min, pumping the preheated reaction liquid A and the reaction liquid B into a continuous flow micro-channel reactor at the flow rate of 10.28mL/min through the metering pump, regulating the temperature of the micro-channel reactor to 150 ℃, regulating the pressure in the micro-channel reactor to 1MPa through a back pressure valve, keeping the residence time of 140min, introducing the materials at the outlet of the micro-channel reactor into a treatment tank made of a Ha-type alloy material containing ice water, adding methylene dichloride for extraction, separating a water layer to obtain an organic phase, sampling and monitoring 50% of 2,3, 4-trifluoro-nitrobenzene, 18.6% of 2, 4-difluoro-3 chloro-nitrobenzene and 28.2% of raw materials.
Comparative examples 3 and 4, although using the microchannel fluorination reactors, have the disadvantages that the fluorine sources are potassium fluoride and anhydrous hydrogen fluoride, respectively, and the microchannel fluorination reaction using potassium fluoride and anhydrous hydrogen fluoride as the fluorine sources is poor in effect, the raw material reaction is incomplete, the intermediate product of 2, 4-difluoro-3-chloro-nitrobenzene cannot be converted into the product, and the content of the target product is low, as can be seen by comparison with examples. The technical proposal of the application has obviously better effect than the prior art.
It will be apparent to those skilled in the art that the present application has been described in detail by way of illustration only, and it is not intended to be limited by the above-described embodiments, as long as various insubstantial modifications of the method concepts and aspects of the application are employed or the inventive concepts and aspects of the application are directly applied to other applications without modification, all within the scope of the application.

Claims (10)

1. A preparation method of 2,3, 4-trifluoro nitrobenzene is characterized in that: the method comprises the following steps:
step one: taking mixed acid of 1,2, 3-trichlorobenzene, sulfuric acid and nitric acid as raw materials, and continuously reacting in a micro-channel reactor to obtain 2,3, 4-trichloronitrobenzene;
step two: tetraethylammonium fluoride trichlorfluoride is used as a fluorine source to react with 2,3, 4-trichloronitrobenzene continuously in a microchannel reactor to obtain 2,3, 4-trifluoro nitrobenzene.
2. The method for producing 2,3, 4-trifluoronitrobenzene according to claim 1, wherein: the first step is as follows: sulfuric acid and nitric acid are prepared into a mixed acid solution, and 1,2, 3-trichlorobenzene and chlorinated hydrocarbon solvent are prepared into a mixed solution; and respectively conveying the mixed solution prepared from the 1,2, 3-trichlorobenzene and the chlorinated hydrocarbon solvent and the mixed acid solution into a micro-channel reactor for continuous nitration reaction, and quenching, washing, desolventizing and crystallizing to obtain the 2,3, 4-trichloronitrobenzene.
3. The method for producing 2,3, 4-trifluoronitrobenzene according to claim 1, wherein: the second step is as follows: 2,3, 4-trichloronitrobenzene and tetraethylammonium fluoride tricofluoride are respectively conveyed into a microchannel reactor in a liquid form for continuous fluorination reaction, and 2,3, 4-trifluoro nitrobenzene is obtained through quenching, water washing, desolventizing and rectifying.
4. The method for producing 2,3, 4-trifluoronitrobenzene according to claim 2, wherein: the feeding mole ratio of the 1,2, 3-trichlorobenzene, the nitric acid and the sulfuric acid is 1 to 1.25:1 to 1.65; the temperature of the nitration reaction in the microchannel reactor is 50-75 ℃, and the pressure of the nitration reaction is 0.4-0.6MPa; the residence time of the nitration reaction in the microchannel reactor is 30-150s; the chlorinated ethylene solvent is one of 1, 2-dichloroethane, 1-dichloroethane, 1, 3-dichloropropane, 1, 2-dichloropropane and n-chlorobutane; the mass ratio of the dosage to the raw material 1,2, 3-trichlorobenzene is (1:1) - (1:3).
5. The process for producing 2,3, 4-trifluoronitrobenzene according to claim 4, wherein: the feeding mole ratio of the 1,2, 3-trichlorobenzene, the nitric acid and the sulfuric acid is 1:1.06:1.35; the temperature of the nitration reaction is 55-85 ℃; the residence time of the nitration reaction is 90-120s.
6. The method for producing 2,3, 4-trifluoronitrobenzene according to claim 2, wherein: the pressure of the nitration reaction in the microchannel reactor is regulated to be 0.3-2.0MPa through a back pressure valve; the mass concentration of sulfuric acid used for preparing the mixed acid solution is 60-98%, and the mass concentration of nitric acid used is 60-98%.
7. The method for producing 2,3, 4-trifluoronitrobenzene according to claim 1, wherein: the internal channel of the microchannel reactor is in the form of one of heart, umbrella, chinese character 'zhong' shape and diamond.
8. A process for the preparation of 2,3, 4-trifluoronitrobenzene as claimed in claim 3, wherein: the feeding mole ratio of the 2,3, 4-trichloronitrobenzene and tetraethylammonium fluoride trichromate is 1:3-8; the temperature of the fluorination reaction in the microchannel reactor is 140-200 ℃, the pressure of the fluorination reaction is 0.8-1MPa, and the residence time of the fluorination reaction in the microchannel reactor is 30-150min.
9. The method for producing 2,3, 4-trifluoronitrobenzene according to claim 8, wherein: the feeding mole ratio of 2,3, 4-trichloronitrobenzene and tetraethylammonium fluoride tricofluoride is 1:4, the temperature of the fluorination reaction in the microchannel reactor is 160 ℃, and the residence time of the fluorination reaction in the microchannel reactor is 48min.
10. A process for the preparation of 2,3, 4-trifluoronitrobenzene as claimed in claim 3, wherein: the pressure of the fluorination reaction in the microchannel reactor is regulated to be 0.6-3.0Mpa through a back pressure valve; the fluorinated microchannel reactor is made of silicon carbide or a Ha-type alloy.
CN202310617767.8A 2023-05-26 2023-05-26 Preparation method of 2,3, 4-trifluoro nitrobenzene Pending CN116836060A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117486728A (en) * 2023-12-28 2024-02-02 山东国邦药业有限公司 Efficient circulating fluorination reagent and preparation method and application thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117486728A (en) * 2023-12-28 2024-02-02 山东国邦药业有限公司 Efficient circulating fluorination reagent and preparation method and application thereof
CN117486728B (en) * 2023-12-28 2024-05-17 山东国邦药业有限公司 Efficient circulating fluorination reagent and preparation method and application thereof

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