Search

CN-117362284-B - Flumioxazin and its preparation method Process for the preparation of amines

CN117362284BCN 117362284 BCN117362284 BCN 117362284BCN-117362284-B

Abstract

The invention provides a synthesis method of flumioxazin, and belongs to the technical field of pesticide synthesis. The invention takes 2, 4-difluoro nitrobenzene as an initial raw material, and obtains the product flumioxazin through hydrolysis, bromination, etherification, ring closure, propiolation and acylation. The method solves the problems of complicated process, large environmental pollution, low yield and the like of the existing flumioxazin synthesis process.

Inventors

  • GAO YUXING
  • CHEN XINGJIE
  • XU PENGXIANG
  • YE ZIYI

Assignees

  • 厦门大学

Dates

Publication Date
20260512
Application Date
20231013

Claims (6)

  1. 1. The preparation method of flumioxazin is characterized by comprising the following steps: Step 1,2, 4-difluoro nitrobenzene is subjected to hydrolysis reaction in inorganic alkaline aqueous solution to obtain 5-fluoro-2-nitrophenol; Step 2, reacting 5-fluoro-2-nitrophenol with a brominating reagent in a solvent to obtain 4-bromo-5-fluoro-2-nitrophenol; In the step 2, the brominating reagent is one of N-bromosuccinimide and pyridine tribromide salt, and the selected solvent is one of acetonitrile and chloroform; Step 3, 4-bromo-5-fluoro-2-nitrophenol reacts with ethyl 2-bromoacetate in an inert atmosphere in the presence of a solvent after alcohol is removed in an alcohol solution of inorganic base to obtain 4-bromo-5-fluoro-2-nitrophenoxyacetic acid ethyl ester; Step 4, 4-bromo-5-fluoro-2-nitrophenoxyacetic acid ethyl ester reacts with hydrogen in a solvent under a certain pressure in an inert atmosphere in the presence of a catalyst to obtain ; In the step4, the catalyst is Raney nickel; step 5, under the existence of inorganic alkali and solvent, Reacting with 3-bromopropyne to obtain 7-fluoro-6-bromo-4-propargyl-2H-1, 4-benzoxazine-3-one; Step 6, 7-fluoro-6-bromo-4-propargyl-2H-1, 4-benzoxazine-3-one reacts with 3,4,5, 6-tetrahydrophthalimide in the presence of a catalyst in a solvent to obtain flumioxazin; the catalyst in the step 6 is selected from palladium acetate; Wherein, the inorganic base in the step 1, the step 3 and the step 5 is respectively and independently selected from one of sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate; and 3, the inert atmosphere in the step 4 is independently selected from one of nitrogen atmosphere and argon atmosphere.
  2. 2. The method for synthesizing flumioxazin according to claim 1, wherein the temperature is raised to 75-95 ℃ by stirring in the reaction in the step 2, and the reaction is kept for 8-12 hours.
  3. 3. The method of claim 1, wherein in step 4, the solvent is selected from the group consisting of N, N-dimethylformamide, dimethylsulfoxide, N-dimethylacetamide and N-methylpyrrolidone.
  4. 4. The method for synthesizing flumioxazin as claimed in claim 1, wherein in the step 4, the selected certain pressure is 0.6 MPa-1.2 MPa, and the selected reaction temperature is 70-150 ℃.
  5. 5. The method for synthesizing flumioxazin as claimed in claim 1, wherein the molar ratio of the catalyst to 7-fluoro-6-bromo-4-propargyl-2H-1, 4-benzoxazin-3-one in the step 6 is 0.01:1 to 0.03:1.
  6. 6. The method for synthesizing flumioxazin according to claim 1, wherein the temperature is raised to 100-120 ℃ in the reaction in the step 6, and the reaction lasts for 8-12 hours.

Description

Flumioxazin and its preparation method Process for the preparation of amines Technical Field The invention relates to the technical field of pesticide synthesis, in particular to a preparation method of flumioxazin. Background The flumioxazin ((Flumioxazin) also known as Sumisoya is also known as a quick-harvest, is a cyclic imide herbicide in chemical structure and is a protoporphyrinogen oxidase inhibitor herbicide in action mode, is a collar species in other PPO inhibitor herbicides, is a herbicide developed by Sumitomo chemical industry Co., ltd. In 1993, can effectively prevent and remove weeds which cannot be removed by other herbicides (such as glyphosate), and can also be used for preventing and removing gramineous weeds and broadleaf weeds on soybeans, cotton, grapes and many other crops, the following synthetic methods of flumioxazin are available at present: (1) The preparation method adopts m-fluorophenol as a raw material and comprises 5 steps of reaction such as etherification, nitration, reduction cyclization, propynylation and acylation. The raw material m-fluorophenol adopted in the synthetic route is high in price, ether bonds are generated after hydrolysis and then nitrified, the nitrifying reaction condition is severe, the ether bonds are easy to break, the iron powder is adopted for hydrogenation reduction, the yield is low, and a large amount of iron sludge which is difficult to treat is produced. (2) The method adopts 2, 4-difluoronitrobenzene as a raw material and is obtained through 7 steps of reactions such as hydrolysis, etherification, reduction, cyclization, nitration, propynylation, nitroreduction, acylation and the like. In the synthetic route, two hydrogenation reduction steps are needed, so that the cost is greatly increased, the project development is not facilitated, the intermediate is firstly connected with propynyl and then subjected to nitration reduction, the nitro is difficult to selectively reduce, and impurities which are difficult to remove are easy to generate. (3) The preparation method adopts 2, 4-difluoronitrobenzene as a raw material and is obtained through 7 steps of reactions such as hydrolysis, etherification, cyclization, nitration, nitro reduction, phthalic anhydride acylation, propynylation and the like. The synthesis route is similar to the route (2), sodium hydride is needed for the final step of propynyl, the yield is low, and impurities are difficult to remove. Therefore, the existing method for synthesizing flumioxazin has a great room for improvement. Therefore, in order to solve the problems of the above synthetic methods, it is necessary to study a new preparation method of flumioxazin. Disclosure of Invention Aiming at the technical problems of more process steps, large environmental pollution and low yield of the preparation method of the flumioxazin, the invention provides a synthesis method of the flumioxazin. The synthesis route of flumioxazin provided by the invention is as follows: in order to achieve the above purpose, the present invention adopts the following technical scheme: the invention provides a preparation method of flumioxazin, which comprises the following steps: step 1, carrying out hydrolysis reaction on 2, 4-difluoronitrobenzene in an inorganic alkaline water solution to obtain 5-fluoro-2-nitrophenol; Step 2, reacting 5-fluoro-2-nitrophenol with a brominating reagent in a solvent to obtain 4-bromo-5-fluoro-2-nitrophenol; step 3, reacting 4-bromo-5-fluoro-2-nitrophenol with ethyl 2-bromoacetate in an inert atmosphere in the presence of a solvent after removing alcohol in an alcohol solution of inorganic base to obtain ethyl 4-bromo-5-fluoro-2-nitrophenoxyacetate; Step 4, 4-bromo-5-fluoro-2-nitrophenoxy ethyl acetate reacts with hydrogen in a solvent under a certain pressure in an inert atmosphere in the presence of a catalyst to obtain 7-fluoro-6-bromo-4-benzoxazine-3 (4H) -one; step 5, 7-fluoro-6-bromo-2H-1, 4-benzoxazine-3 (4H) -ketone reacts with 3-bromopropylene in the presence of inorganic base and solvent to obtain 7-fluoro-6-bromo-4-propargyl-2H-1, 4-benzoxazine-3-ketone; step 6, 7-fluoro-6-bromo-4-propargyl-2H-1, 4-benzoxazine-3-one reacts with 3,4,5, 6-tetrahydrophthalimide in the presence of a catalyst in a solvent to obtain flumioxazin; Wherein, the inorganic base in the step 2, the step 3 and the step 5 is respectively and independently selected from one of sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate; and 3, the inert atmosphere in the step 4 is independently selected from one of nitrogen atmosphere and argon atmosphere. According to one embodiment of the application, in step 1, the selected aqueous inorganic base is sodium hydroxide, potassium hydroxide, sodium carbonate, or an aqueous potassium carbonate solution, preferably an aqueous sodium hydroxide solution. More preferably 30% aqueous sodium hydroxide. According to one embodiment of the application, in step 1, the solven