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CN-117623947-B - Synthesis method of bifenazate intermediate

CN117623947BCN 117623947 BCN117623947 BCN 117623947BCN-117623947-B

Abstract

The application discloses a synthesis method of a bifenazate intermediate, and relates to the technical field of organic synthesis. The synthesis method comprises the steps of taking 4-methoxyaniline as a starting material, performing diazotization reaction to obtain 4-methoxybenzene diazonium salt, decomposing the 4-methoxybenzene diazonium salt to form aryl free radicals, adding a certain amount of benzene for coupling reaction to obtain 4-methoxybiphenyl, performing halogenation reaction by using a halogenating reagent to obtain 4-methoxy-3-halobiphenyl, and finally adding metal amide for nucleophilic substitution to obtain 4-methoxy-3-aminobiphenyl. The synthesis method of 4-methoxy-3-aminobiphenyl provided by the application avoids relatively dangerous and harsh reactions such as nitration, grignard reaction and the like, the reaction process is relatively safe, the raw materials of the reaction are cheap and easy to obtain, the reaction yield is high, the reaction condition is mild, the synthesis route is short, the equipment investment is small, and the industrialization is easy.

Inventors

  • GONG QIANG
  • LIU SHENGXUE
  • REN JIAMIN
  • WANG GUANGYAO
  • ZHAO ZHENDONG
  • Ge Ankang
  • LU XIAOYAN
  • SHI BINBIN
  • ZHU XIAOYU

Assignees

  • 绍兴上虞新银邦生化有限公司

Dates

Publication Date
20260512
Application Date
20231130

Claims (8)

  1. 1. A synthesis method of a bifenazate intermediate is characterized by comprising the following steps: s1, adding 4-methoxyaniline into hydrochloric acid, dissolving and clearing, cooling the system to 0 ℃, slowly adding sodium nitrite, and carrying out heat preservation for reaction to obtain a reaction solution containing 4-methoxybenzene; S2, adding benzene and sodium carbonate into the reaction liquid obtained in the step S1, controlling the reaction temperature, and preserving heat for reaction, after the reaction is finished, adding water, uniformly stirring, standing for layering, removing an organic layer, and removing a solvent after reduced pressure distillation to obtain 4-methoxybiphenyl; s3, adding the 4-methoxyl biphenyl obtained in the S2 into the solvent A, adding a halogenating reagent, reducing the temperature, and preserving heat for halogenating reaction; S4, adding 4-methoxy-3-halobiphenyl into the solvent B, uniformly stirring, cooling to 0 ℃, controlling the temperature to be constant, adding metal amide, uniformly stirring after the addition, slowly heating, preserving heat for amination reaction, dripping the reaction liquid into ice water after the reaction is finished, carrying out layering and liquid separation through extraction, drying an organic phase, and removing the solvent after reduced pressure distillation to obtain 4-methoxy-3-aminobiphenyl; The synthetic route is as follows: wherein, X is one of F, cl, br, I; The halogenating reagent is one of X2, hypohalite MXO, N-halogenated succinimide NXS, dihaloamine DXDMH and sulfuryl halide SO2X2, wherein X is one of F, cl, br, I; The metal amide is one of NaNH 2 、KNH 2 、LiNH 2 、Ca(NH 2 ) 2 .
  2. 2. The method for synthesizing the bifenazate intermediate according to claim 1, wherein the molar ratio of reactants 4-methoxyaniline, hydrochloric acid, sodium nitrite, benzene and sodium carbonate is 1 (2-8): 1-1.5): 4-6): 2-4.
  3. 3. The method for synthesizing the bifenazate intermediate according to claim 1, wherein the time of the heat preservation reaction in S1 is 1-3h.
  4. 4. The method for synthesizing the intermediate of bifenazate according to claim 1, wherein the reaction temperature in S2 is 0-10 ℃ and the reaction time is 1-5h.
  5. 5. The method for synthesizing the intermediate of bifenazate according to claim 1, wherein the molar ratio of the reactant 4-methoxybiphenyl, the solvent A and the halogenated reagent in S3 is 1 (15-17): 1-1.5.
  6. 6. The method for synthesizing a bifenazate intermediate according to claim 1, wherein the halogenation reaction temperature in S3 is 0-20 ℃ and the reaction time is 2-5h.
  7. 7. The method for synthesizing the intermediate of bifenazate according to claim 1, wherein the molar ratio of the reactant 4-methoxy-3-halobiphenyl, the solvent B and the metal amide in S4 is 1 (15-19): 1-3.
  8. 8. The method for synthesizing a bifenazate intermediate according to claim 1, wherein the amination reaction temperature in S4 is 70-95 ℃ and the reaction time is 2-6h.

Description

Synthesis method of bifenazate intermediate Technical Field The application relates to the field of organic synthesis technology, in particular to a synthesis method of a bifenazate intermediate. Background The bifenazate is a novel selective foliar spray acaricide, is chemically named as 3- (4-methoxyl biphenyl-3-yl) isopropyl carbazate, is effective for all life stages of mites, has knockdown activity and ovicidal activity on mites, has long effective period, can be used for preventing and controlling two-point spider mites, apple panonychus ulmi, etc. on crops such as apples, grapes, peaches, strawberries, drupes, etc., is harmless to beneficial mites and beneficial insects, is environment-friendly, is very suitable for comprehensive treatment of insects, and can powerfully promote development of agricultural industry. 4-Methoxy-3-aminobiphenyl is an important intermediate in the synthetic line of biphenylhydrazine ester, and the following preparation methods of 4-methoxy-3-aminobiphenyl are mainly available in the prior art: route one: The process takes biphenyl as a raw material, is sulfonated to produce 4-sulfonyl biphenyl, is subjected to high-temperature alkali fusion to produce 4-hydroxy biphenyl, is subjected to nitration reaction and methylation reaction, and is finally subjected to palladium-carbon catalytic hydrogenation to reduce nitro to obtain 4-methoxy-3-amino biphenyl, but the process requires high-temperature alkali fusion, has high requirements on production equipment, has huge potential safety hazards in production of nitration reaction and high-pressure catalytic hydrogenation reduction reaction, generates a large amount of strong alkali and strong acid waste liquid, and has the problems of high energy consumption, harsh reaction conditions and the like. Route two: The route takes 3-bromo-5-methoxyaniline as a raw material, phenylboronic acid and inorganic base are added with a catalyst palladium ligand under the protection of nitrogen to generate 4-methoxy-3-aminobiphenyl by coupling, but the route reaction is SUZUKI coupling reaction, and catalyst metal palladium is used, so that the cost is high, and in addition, the raw materials are expensive and are not easy to obtain. Route three: The method is characterized in that 4-methoxyl bromobenzene is used as a solvent under the protection of inert gas, dry tetrahydrofuran is used as a solvent, a substrate reacts with magnesium powder to obtain a Grignard reagent, then the Grignard reagent reacts with bromobenzene under the catalysis of a catalyst to obtain 4-methoxyl biphenyl, and then 4-methoxy-3-aminobiphenyl is obtained through nitration and palladium-carbon catalytic hydrogenation reduction reaction under high pressure. In the prior art, the preparation method of 4-methoxy-3-aminobiphenyl has the technical problems of high requirements on production equipment, high energy consumption, high production price, difficult separation of byproducts and the like. Therefore, a novel method with environmental protection, high yield and low production cost is required to be found so as to meet the urgent demands of the market on the product. Disclosure of Invention Aiming at the defects of the prior art, the invention aims to provide a synthesis method of 4-methoxy-3-aminobiphenyl, which is used for solving the problems of expensive raw materials, unstable raw material sources, high production cost, large equipment investment, high production equipment requirement, high production energy consumption and the like in the prior art. The application provides a synthesis method of a bifenazate intermediate, which adopts the following technical scheme: A synthesis method of a bifenazate intermediate comprises the following steps: s1, adding 4-methoxyaniline into hydrochloric acid, dissolving and clearing, cooling the system to 0 ℃, slowly adding sodium nitrite, and carrying out heat preservation for reaction to obtain a reaction solution containing 4-methoxybenzene; S2, adding benzene and sodium carbonate into the reaction liquid obtained in the step S1, controlling the reaction temperature, and preserving heat for reaction, after the reaction is finished, adding water, uniformly stirring, standing for layering, removing an organic layer, and removing a solvent after reduced pressure distillation to obtain 4-methoxybiphenyl; s3, adding the 4-methoxyl biphenyl obtained in the S2 into the solvent A, adding a halogenating reagent, reducing the temperature, and preserving heat for halogenating reaction; S4, adding 4-methoxy-3-halobiphenyl into the solvent B, uniformly stirring, cooling to 0 ℃, controlling the temperature to be constant, adding metal amide, uniformly stirring after the addition, slowly heating, preserving heat for amination reaction, dripping the reaction liquid into ice water after the reaction is finished, carrying out layering and liquid separation through extraction, drying an organic phase, and removing the solvent after reduced pre