阅读说明：本技术 一种氟唑菌酰胺中间体的合成方法 (Synthetic method of fluxapyroxad intermediate ) 是由 刘玉超 安静 王恩来 徐武双 于 2021-10-22 设计创作，主要内容包括：本发明涉及一种氟唑菌酰胺中间体的合成方法。为了解决现有合成工艺条件苛刻、复杂、成本高、不安全等问题,本发明将3,4,5-三氟苯硼酸和结构式为的化合物在催化剂、碱和溶剂存在的条件下反应,得到结构式为的氟唑菌酰胺中间体,R～(1)为硝基或胺基,R～(2)为氯或溴,催化剂为胺类催化剂和相转移催化剂。本发明简化了制备工艺,降低了生产成本,提高了安全性,同时提高了产物的收率,具有很高的实用价值,有利于工业化生产,应用前景广阔。(The invention relates to a synthesis method of a fluxapyroxad intermediate. In order to solve the problems of harsh, complex, high cost, unsafe and the like of the existing synthesis process, the invention uses 3,4, 5-trifluoro-phenylboronic acid and the structural formula as In the presence of a catalyst, a base and a solvent to obtain a compound of the formula Fluxapyroxad intermediate of (A), R 1 Is nitro or amino, R 2 Is chlorine or bromine, and the catalyst is amine catalyst and phase transfer catalyst. The invention simplifies the preparation process, reduces the production cost, improves the safety, improves the yield of the product, has very high practical value, is beneficial to industrial production and has wide application prospect.)

1. The synthesis method of the fluxapyroxad intermediate is characterized in that 3,4, 5-trifluorobenzene boric acid and the structural formula shown in the specification are usedIn the presence of a catalyst, a base and a solvent to obtain a compound of the formulaFluxapyroxad intermediate of (A), R¹Is nitro or amino, R²Is the chlorine or the bromine,

the catalyst is amine catalyst and phase transfer catalyst, and the amine catalyst is selected from、、OrThe phase transfer catalyst is selected from polyether compounds, cyclic crown ether compounds and quaternary ammonium saltsOne or more of a compound, a quaternary ammonium base compound, or a quaternary phosphonium salt compound.

2. The synthesis method according to claim 1, wherein the amount of the phase transfer catalyst is 1 to 100% by mass of the 3,4, 5-trifluorophenylboronic acid.

3. The synthesis method of claim 1, wherein the phase transfer catalyst is one or more of tetrabutylammonium bromide, 1,4,7,10,13, 16-hexaoxacyclooctadecane, or polyethylene glycol.

4. The method of claim 1, wherein the base is one or more of sodium hydroxide, potassium carbonate, sodium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, or sodium hydride.

5. The method of claim 1, wherein the solvent is one or more of toluene, o-xylene, m-xylene, methylene chloride, tetrahydrofuran, dichloroethane, N-dimethylformamide, N-methylpyrrolidone, methylcyclohexane, or cyclohexane.

6. The synthesis method according to claim 1, wherein the molar ratio of the 3,4, 5-trifluorophenylboronic acid to the amine catalyst is 1: 0.05-10.

7. The synthesis method according to claim 1, wherein the molar ratio of the 3,4, 5-trifluorophenylboronic acid to the base is 1: 0.1-5.

8. The method of claim 1 wherein said 3,4, 5-trifluorophenylboronic acid and said compound of formulaThe molar ratio of the compound (1) to the compound (2) is 1: 0.8-2.

9. The synthesis method according to claim 1, wherein the mass ratio of the 3,4, 5-trifluorophenylboronic acid to the solvent is 1: 1-10.

10. The synthesis method according to claim 1, wherein the reaction temperature is 25-150 ℃.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of a fluxapyroxad intermediate.

Background

Fluxapyroxad belongs to carboxamide chemicals, and has a structural formula as follows:in such a way that succinate dehydrogenase in complex II of the mitochondrial respiratory chain is inhibited, thereby inhibiting spore germination, germ tube and mycelium growth of the target fungus. The fluxapyroxad can prevent and treat at least 26 fungal diseases, and can be used for nearly hundreds of crops, such as grain crops, bean vegetables, oil crops, pome and stone fruit trees, root and tuber vegetables and fruit vegetables. Fluxapyroxad has no carcinogenicity, no teratogenicity, no side effect on reproduction, no genetic toxicity, no neurotoxicity and no immunotoxicity.

3,4, 5-trifluoro-2-aminobiphenyl (b)) And 3,4, 5-trifluoro-2-nitrobiphenyl (b)) The intermediate is a key intermediate for synthesizing pesticide fluxapyroxad, and the traditional synthesis method mainly takes halogenated aromatic hydrocarbon and aryl boric acid as initial raw materials and is prepared by transition metal catalytic Suzuki coupling, but because the reaction uses transition metal, the requirements on no water and no oxygen in a reaction system are high, the toxicity is high, the cost is high, the catalyst is difficult to recover, the yield is low, and the operation is complicated. Therefore, a more efficient, simple and safer synthesis method of an environment-friendly fluxapyroxad intermediate is needed.

Disclosure of Invention

The invention aims to provide a method for synthesizing fluxapyroxad intermediate with higher yield without using transition metal catalyst.

In order to achieve the purpose, the invention adopts the technical scheme that:

the invention provides a synthesis method of fluxapyroxad intermediate, which comprises the following steps of3,4, 5-trifluoro-phenylboronic acid and the structural formulaIn the presence of a catalyst, a base and a solvent to obtain a compound of the formulaFluxapyroxad intermediate of (A), R¹Is nitro or amino, R²Is halogen, the catalyst is amine catalyst and phase transfer catalyst, the amine catalyst is selected from、、OrOne or more of (a).

According to the invention, R²Is chlorine or bromine.

According to the invention, the phase transfer catalyst is selected from one or more of polyether compounds, cyclic crown ether compounds, quaternary ammonium salt compounds, quaternary ammonium base compounds or quaternary phosphonium salt compounds.

Preferably, the dosage of the phase transfer catalyst is 1-100% of the mass of the 3,4, 5-trifluorobenzene boric acid.

Further, the amount of the phase transfer catalyst is not more than 50% by mass, still more preferably not more than 30% by mass, still more preferably not more than 20% by mass, and particularly preferably not more than 10% by mass, of the 3,4, 5-trifluorobenzene boronic acid, and the amount of the phase transfer catalyst is not less than 4% by mass, still more preferably not less than 6% by mass, and still more preferably not less than 8% by mass, of the 3,4, 5-trifluorobenzene boronic acid.

Preferably, the phase transfer catalyst is one or more of tetrabutylammonium bromide, 1,4,7,10,13, 16-hexaoxacyclooctadecane, or polyethylene glycol.

More preferably, the number average molecular weight of the polyethylene glycol is 200-800, still more preferably 200-600, and still more preferably 300-500.

According to the invention, the alkali is one or more of sodium hydroxide, potassium carbonate, sodium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate or sodium hydride.

According to the invention, the solvent is one or more of toluene, o-xylene, m-xylene, tetrahydrofuran, dichloromethane, dichloroethane, N-dimethylformamide, N-methylpyrrolidone, methylcyclohexane, or cyclohexane.

According to the invention, the molar ratio of the 3,4, 5-trifluoro-phenylboronic acid to the amine catalyst is 1: 0.1-10.

Further, the molar ratio of the 3,4, 5-trifluoro-phenylboronic acid to the amine catalyst is 1: 0.1-5.

Still further, the molar ratio of the 3,4, 5-trifluoro-phenylboronic acid to the amine catalyst is 1: 0.1-1.5.

Furthermore, the molar ratio of the 3,4, 5-trifluoro-phenylboronic acid to the amine catalyst is 1: 0.1-0.5.

According to the invention, the molar ratio of the 3,4, 5-trifluoro-phenylboronic acid to the base is 1: 0.1-5.

Further, the molar ratio of the 3,4, 5-trifluorophenylboronic acid to the base is not more than 1:0.2, still more preferably not more than 1:0.4, still more preferably not more than 1:0.6, and the molar ratio of the 3,4, 5-trifluorophenylboronic acid to the base is not less than 1:3.5, still more preferably not less than 1: 2.

According to the invention, the 3,4, 5-trifluoro-phenylboronic acid and the structural formula are shown in the specificationThe molar ratio of the compound (1) to the compound (2) is 1: 0.8-2.

Further, the 3,4, 5-trifluoro-phenylboronic acid and the structural formula are shown in the specificationThe molar ratio of the compound (a) is not more than 1:0.9, still more preferably not more than 1:1, and the 3,4, 5-trifluorophenylboronic acid and the structural formula areThe molar ratio of the compound (b) is not less than 1:1.8, more preferably not less than 1:1.5, still more preferably not less than 1: 1.2.

According to the invention, the mass ratio of the 3,4, 5-trifluoro-phenylboronic acid to the solvent is 1: 1-10.

Further, the mass ratio of the 3,4, 5-trifluorobenzene boric acid to the solvent is less than or equal to 1:2, and more preferably less than or equal to 1:4, and the mass ratio of the 3,4, 5-trifluorobenzene boric acid to the solvent is greater than or equal to 1:8, and more preferably greater than or equal to 1: 6.

According to the invention, the reaction temperature is 25-150 ℃.

Further, the reaction temperature is 130 ℃ or lower, more preferably 120 ℃ or lower, still more preferably 110 ℃ or lower, and the reaction temperature is 45 ℃ or higher, still more preferably 60 ℃ or higher.

Specifically, the reaction time can be properly adjusted according to the reaction temperature, preferably, the reaction time is 4-10 hours, and more preferably, the reaction time is 5-8 hours.

The reaction equation of the invention is as follows:

。

the invention uses some cheap and little toxic catalysts on the premise of not using transition metal catalysts, obtains higher yield which can reach more than 90 percent and is more suitable for industrial production.

Due to the application of the technical scheme, compared with the prior art, the invention has the following advantages:

the synthesis method of the fluxapyroxad intermediate uses a few cheap and low-toxicity amine catalysts to replace transition metal catalysts, and deeply researches reaction solvents, material ratios and the like, thereby simplifying the preparation process, reducing the production cost, improving the safety and simultaneously improving the yield of the product. Furthermore, a phase transfer catalyst is used in the reaction process, so that the yield is further improved, the reaction time is shortened, and the production efficiency is improved.

Detailed Description

All of the features disclosed in this specification, or all of the steps in any method or process so disclosed, may be combined in any combination, except combinations where mutually exclusive features or steps are expressly stated.

In the traditional process for synthesizing 3,4, 5-trifluoro-2-aminobiphenyl or 3,4, 5-trifluoro-2-nitrobiphenyl by Suzuki coupling, a transition metal catalyst such as a Pd-type or Ni-type catalyst is required, the cost is high, the reaction condition is harsh, the requirement on water and oxygen absence is high, and the yield can reach 96% in reports, but the traditional process uses 2, 2-dimethyl-1, 3-bis (diphenylphosphine) propane which is a ligand difficult to obtain commercially, the ligand is required to be prepared by self, the preparation process condition is harsh, so that the yield is poor, the preparation cost is high, the difficulty is high, and the safety is low in the prior art.

At present, with respect to Suzuki coupling reaction, recent research reports that an amine catalyst can catalyze some Suzuki coupling reactions, in patent CN112538052A, it is mentioned that an amine catalyst can substitute for a transition metal catalyst to catalyze Suzuki coupling reactions, and the inventors use the amine catalyst in coupling reactions of 3,4, 5-trifluoro-2-aminobiphenyl or 3,4, 5-trifluoro-2-nitrobiphenyl, and found that although the catalytic reaction can be performed, the yield is significantly reduced, the inventors have performed a large amount of optimization of reaction conditions, and neither can improve the yield, which shows that the amine catalyst has selectivity to raw materials, and the catalyst mentioned in patent CN112538052A has a poor catalytic effect on coupling reactions of 3,4, 5-trifluoro-2-aminobiphenyl or 3,4, 5-trifluoro-2-nitrobiphenyl, in addition, the amine catalyst used in patent CN112538052A is relatively expensive, and is not suitable for industrial production.

Therefore, the inventor carries out a large number of experiments and finally finds that the Suzuki coupling reaction of 3,4, 5-trifluoro-phenylboronic acid and halogenated aromatic hydrocarbon serving as raw materials,、、orThe catalyst can be used as a catalyst to successfully catalyze the reaction, and the catalyst has lower cost, and further, the yield of the 3,4, 5-trifluoro-2-aminobiphenyl or the 3,4, 5-trifluoro-2-nitrobiphenyl is obviously improved by optimizing the synthesis process and far exceeds the yield of the transition metal catalyst, so that the difficulty and the production cost of the preparation process are reduced.

The invention will now be further described with reference to specific examples, but the invention should not be limited to these examples, but may be substituted by other equivalent or similarly purposed alternative features unless specifically stated. Unless expressly stated otherwise, each feature is only an example of a generic series of equivalent or similar features. Terms used in the present invention generally have meanings commonly understood by those of ordinary skill in the art, unless otherwise specified. In the following examples, the amount of the phase transfer catalyst used was calculated to be 10% by mass of 3,4, 5-trifluorophenylboronic acid.

Example 1

568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-chloroaniline are added into a reaction vessel, and then the catalyst is added(56.8 mmol) and potassium carbonate 568.5 mmol, adding tetrabutylammonium bromide (10%), adding solvent toluene 500 g under the protection of nitrogen, heating to 110 ℃, keeping the temperature and stirring for 5 hours, reacting completely, stopping the reaction, washing with 200 g of water, repeating the washing operation for three times, drying with anhydrous sodium sulfate, filtering and desolventizing to obtain a crude product, and purifying by column chromatography to obtain the product 3,4, 5-trifluoro-2-aminobiphenyl 540.1 mmol with the yield of 95%.

Example 2

568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-chloroaniline are added into a reaction vessel, and then the catalyst is added(56.8 mmol) and potassium carbonate 568.5 mmol, adding tetrabutylammonium bromide (10%), adding solvent toluene 500 g under the protection of nitrogen, heating to 110 ℃, keeping the temperature and stirring for 5 hours, reacting completely, stopping the reaction, washing with 200 g of water, repeating the washing operation for three times, drying with anhydrous sodium sulfate, filtering and desolventizing to obtain a crude product, and purifying by column chromatography to obtain the product 3,4, 5-trifluoro-2-aminobiphenyl 545.8 mmol with the yield of 96%.

Example 3

568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-chloroaniline are added into a reaction vessel, and then the catalyst is added(56.8 mmol) and potassium carbonate 568.5 mmol, adding tetrabutylammonium bromide (10%), adding solvent toluene 500 g under the protection of nitrogen, heating to 110 ℃, keeping the temperature and stirring for 5 hours, reacting completely, stopping the reaction, washing with 200 g of water, repeating the washing operation for three times, drying with anhydrous sodium sulfate, performing suction filtration and desolventizing to obtain a crude product, and purifying by column chromatography to obtain the product 3,4, 5-trifluoro-2-aminobiphenyl 557.1 mmol with the yield of 98%.

Example 4

568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-chloroaniline are added into a reaction vessel, and then the catalyst is added(56.8 mmol) and potassium carbonate 568.5 mmol, adding tetrabutylammonium bromide (10%), adding solvent toluene 500 g under the protection of nitrogen, heating to 110 ℃, keeping the temperature and stirring for 5 hours, reacting completely, stopping the reaction, washing with 200 g of water, repeating the washing operation for three times, drying with anhydrous sodium sulfate, performing suction filtration and desolventizing to obtain a crude product, and purifying by column chromatography to obtain the product 3,4, 5-trifluoro-2-aminobiphenyl 557.1 mmol with the yield of 98%.

Example 5

568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-bromoaniline are added into a reaction vessel, and then the catalyst is added(56.8 mmol) and potassium carbonate 568.5 mmol, adding tetrabutylammonium bromide (10%), adding solvent toluene 500 g under the protection of nitrogen, heating to 110 ℃, keeping the temperature and stirring for 5 hours, reacting completely, stopping the reaction, washing with 200 g of water, repeating the washing operation for three times, drying with anhydrous sodium sulfate, filtering and desolventizing to obtain a crude product, and purifying by column chromatography to obtain the product 3,4, 5-trifluoro-2-aminobiphenyl 551.4 mmol with the yield of 97%.

Example 6

568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-chloronitrobenzene are added into a reaction vessel, and then the catalyst is added(56.8 mmol) and potassium carbonate 568.5 mmol, adding 18 crown 6 (10%), adding 500 g of solvent toluene under the protection of nitrogen, heating to 110 ℃, keeping the temperature and stirring for 5 hours, reacting completely, stopping the reaction, washing with 200 g of water, repeating the washing operation for three times, drying with anhydrous sodium sulfate, filtering and desolventizing to obtain a crude product, and purifying by column chromatography to obtain 523.0 mmol of the product of 3,4, 5-trifluoro-2-nitrobiphenyl, wherein the yield is 92%.

Example 7

568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-chloronitrobenzene are added into a reaction vessel, and then the catalyst is added(56.8 mmol) and potassium carbonate 568.5 mmol, adding 18 crown 6 (10%), adding 500 g of solvent toluene under the protection of nitrogen, heating to 110 ℃, keeping the temperature and stirring for 5 hours, reacting completely, stopping the reaction, washing with 200 g of water, repeating the washing operation for three times, drying with anhydrous sodium sulfate, filtering and desolventizing to obtain a crude product, and purifying by column chromatography to obtain the product 3,4, 5-trifluoro-2-nitrobiphenyl 511.6 mmol with the yield of 90%.

Example 8

568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-chloronitrobenzene are added into a reaction vessel, and then the catalyst is added(56.8 mmol) and potassium carbonate 568.5 mmol, adding 18 crown 6 (10%), adding 500 g of solvent toluene under the protection of nitrogen, heating to 110 ℃, keeping the temperature and stirring for 5 hours, reacting completely, stopping the reaction, washing with 200 g of water, repeating the washing operation for three times, washing with 200 g of water for three times, drying with anhydrous sodium sulfate, performing suction filtration and desolventizing to obtain a crude product, and purifying by column chromatography to obtain 528.7 mmol of the product 3,4, 5-trifluoro-2-nitrobiphenyl, wherein the yield is 93%.

Example 9

568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-chloronitrobenzene are added into a reaction vessel, and then the catalyst is added(56.8 mmol) and potassium carbonate 568.5 mmol, adding 18 crown 6 (10%), adding 500 g of solvent toluene under the protection of nitrogen, heating to 110 ℃, keeping the temperature and stirring for 5 hours, reacting completely, stopping the reaction, washing with 200 g of water, repeating the washing operation for three times, drying with anhydrous sodium sulfate, filtering and desolventizing to obtain a crude product, and purifying by column chromatography to obtain 528.7 mmol of the product of 3,4, 5-trifluoro-2-nitrobiphenyl, wherein the yield is 93%.

Example 10

568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-bromonitrobenzene are added into a reaction vessel, and then the catalyst is added(56.8 mmol) and potassium carbonate 568.5 mmol, adding tetrabutylammonium bromide (10%), adding solvent toluene 500 g under the protection of nitrogen, heating to 110 ℃, keeping the temperature and stirring for 5 hours, reacting completely, stopping the reaction, washing with 200 g of water, repeating the washing operation for three times, drying with anhydrous sodium sulfate, filtering and desolventizing to obtain a crude product, and purifying by column chromatography to obtain the product 3,4, 5-trifluoro-2-nitraminobiphenyl 517.3 mmol with the yield of 91%.

Comparative example 1

Adding 568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-bromoaniline into a reaction container, adding catalysts of palladium chloride (170.5 mmol) and 568.5 mmol of potassium carbonate, adding 500 g of tetrahydrofuran solvent under the protection of nitrogen, heating to 70 ℃, stirring for 5 hours, reacting completely, using the catalysts of palladium chloride to catalyze the reaction, ensuring no water and no oxygen in the reaction system, stopping the reaction, washing with 200 g of water, repeating the washing operation for three times, drying with anhydrous sodium sulfate, performing suction filtration and desolventization to obtain a crude product, and purifying by column chromatography to obtain 545.8 mmol of the product of 3,4, 5-trifluoro-2-aminobiphenyl with the yield of 80%.

Comparative example 2

568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-bromonitrobenzene are added into a reaction container, catalysts of palladium chloride (170.5 mmol) and potassium carbonate 568.5 mmol are added, 500 g of solvent toluene is added under the protection of nitrogen, the temperature is raised to 70 ℃, the mixture is stirred for 5 hours, the reaction is complete, no water and no oxygen exist in a reaction system when the catalyst of palladium chloride is used for catalytic reaction, 200 g of water is used for washing after the reaction is stopped, the washing operation is repeated for three times, anhydrous sodium sulfate is dried, suction filtration and desolventization are carried out to obtain a crude product, and the product of 3,4, 5-trifluoro-2-nitrobiphenyl 397.9 mmol is obtained after column chromatography purification, and the yield is 70%.

Comparative example 3

568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-bromoaniline are added into a reaction container, catalysts of tetratriphenylphosphine palladium (170.5 mmol) and 568.5 mmol of potassium carbonate are added, 500 g of solvent tetrahydrofuran is added under the protection of nitrogen, the mixture is heated to 70 ℃ and stirred for 5 hours to react completely, no water and no oxygen exist in a reaction system when the catalyst of tetratriphenylphosphine palladium is used for catalytic reaction, after the reaction is stopped, 200 g of water is used for washing, the water washing operation is repeated for three times, anhydrous sodium sulfate is dried, a crude product is obtained by suction filtration and desolventization, and the product of 3,4, 5-trifluoro-2-aminobiphenyl 426.3 mmol is obtained after column chromatography purification, and the yield is 75%.

Comparative example 4

Adding 568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-bromoaniline into a reaction container, adding catalysts of palladium chloride (170.5 mmol) and 568.5 mmol of potassium carbonate, adding 500 g of solvent dioxane under the protection of nitrogen, heating to 70 ℃, stirring for 5 hours, reacting completely, stopping the reaction when no water or oxygen exists in a reaction system during catalytic reaction of the catalyst of palladium chloride, washing with 200 g of water, repeating the washing operation for three times, drying with anhydrous sodium sulfate, performing suction filtration and desolventization to obtain a crude product, and purifying by column chromatography to obtain 432.1mmol of the product of 3,4, 5-trifluoro-2-aminobiphenyl with the yield of 76%.

Comparative example 5: using the amine catalysts mentioned in the patent CN112538052A

568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-bromoaniline are added into a reaction vessel, and then the catalyst is added(284.3 mmol) and potassium carbonate 568.5 mmol, adding 500 g of solvent xylene under the protection of nitrogen, heating to 70 ℃, stirring for 8 hours, reacting completely, stopping reaction, washing with 200 g of water, repeating the washing operation for three times, drying with anhydrous sodium sulfate, performing suction filtration and desolventizing to obtain a crude product, and purifying by column chromatography to obtain 220 mmol of the product 3,4, 5-trifluoro-2-aminobiphenyl with the yield of 38%.

Comparative example 6: using the amine catalysts mentioned in the patent CN112538052A

568.5 mmol of 3,4, 5-trifluoro-phenylboronic acid and 596.93 mmol of o-bromonitrobenzene are added into a reaction vessel, and then the catalyst is added(284.3 mmol) and potassium carbonate 568.5 mmol, adding 500 g of solvent xylene under the protection of nitrogen, heating to 70 DEG CStirring for 8 hours, completely reacting, stopping reaction, washing with 200 g of water, repeating the washing operation for three times, drying with anhydrous sodium sulfate, carrying out suction filtration and desolventizing to obtain a crude product, and purifying by column chromatography to obtain 85.3mmol of the product 3,4, 5-trifluoro-2-nitrobiphenyl with the yield of 15%.

The above embodiments are merely illustrative of the technical ideas and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the contents of the present invention and implement the present invention, and not to limit the protection scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.