阅读说明：本技术 一种苯唑草酮制备方法及其应用 (Preparation method and application of topramezone ) 是由 赵明鑫 蒋玉山 周德伟 王伟胜 于 2020-04-26 设计创作，主要内容包括：本发明公开了一种苯唑草酮制备方法及其应用,包括如下步骤：以2-甲基苯甲醛、溴化试剂、催化剂、盐酸羟胺、碱、乙烯气体、磺酰化试剂和预设溶剂作为反应原料经第一反应过程制得3-[3-溴-甲基-6-(甲基磺酰基)苯基]-4,5-二氢化异噁唑；以丙二酸二乙酯、元甲酸三乙酯、硫酸镍、一元饱和羧酸、甲基肼、烃类溶剂、乙醇溶液和盐酸作为反应原料经第二反应过程制得1-甲基-5-羟基吡唑；以3-[3-溴-甲基-6-(甲基磺酰基)苯基]-4,5-二氢化异噁唑、1-甲基-5-羟基吡唑、三乙胺、碳酸钾、氯化钯、三苯基磷、1,4-二氧六环、水、饱和NaHCO<Sub>3</Sub>溶液和盐酸溶液作为反应原料经第三反应过程制得苯唑草酮,解决了现有流程中含硫中间体会散发臭味的问题和原料比较难以获得的问题。(The invention discloses a preparation method and application of topramezone, which comprises the following steps: the 3- [ 3-bromo-methyl-6- (methylsulfonyl) phenyl is prepared by a first reaction process by using 2-methylbenzaldehyde, a bromination reagent, a catalyst, hydroxylamine hydrochloride, alkali, ethylene gas, a sulfonylation reagent and a preset solvent as reaction raw materials]-4, 5-dihydroisoxazole; taking diethyl malonate, triethyl formate, nickel sulfate, monobasic saturated carboxylic acid, methyl hydrazine, hydrocarbon solvent, ethanol solution and hydrochloric acid as reaction raw materials to prepare 1-methyl-5-hydroxypyrazole through a second reaction process; with 3- [ 3-bromo-methyl-6- (methylsulfonyl) phenyl]-4, 5-dihydroisoxazole, 1-methyl-5-hydroxypyrazole, triethylamine, potassium carbonate, palladium chloride, triphenylphosphine, 1, 4-dioxane, water, saturated NaHCO 3 Solutions andthe topramezone is prepared by taking the hydrochloric acid solution as a reaction raw material through a third reaction process, so that the problem that the sulfur-containing intermediate can disperse odor and the raw material is difficult to obtain in the existing process is solved.)

1. A preparation method of topramezone is characterized by comprising the following steps:

preparing 3- [ 3-bromo-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro isoxazole by using 2-methylbenzaldehyde, a bromination reagent, a catalyst, hydroxylamine hydrochloride, alkali, ethylene gas, a sulfonylation reagent and a preset solvent as reaction raw materials through a first reaction process;

taking diethyl malonate, triethyl formate, nickel sulfate, monobasic saturated carboxylic acid, methyl hydrazine, hydrocarbon solvent, ethanol solution and hydrochloric acid as reaction raw materials to prepare 1-methyl-5-hydroxypyrazole through a second reaction process;

with 3- [ 3-bromo-methyl-6- (methylsulfonyl) phenyl]-4, 5-dihydroisoxazole, 1-methyl-5-hydroxypyrazole, triethylamine, potassium carbonate, palladium chloride, triphenylphosphine, 1, 4-dioxane, water, saturated NaHCO₃The solution and the hydrochloric acid solution are used as reaction raw materials to prepare the topramezone through a third reaction process.

2. The process for preparing topramezone according to claim 1, wherein the first reaction process is:

mixing the 2-methyl benzaldehyde and a bromination reagent in the preset solvent, and adding the catalyst under the condition of a preset constant temperature to perform bromination reaction to prepare 2-bromo-6-methyl benzaldehyde;

carrying out condensation reaction on 2-bromo-6-methylbenzaldehyde, a preset solvent, hydroxylamine hydrochloride and alkali, then introducing ethylene gas and the catalyst, and chloridizing to finally cyclize to obtain 3- [ 2-methyl-6-bromo-phenyl ] -4, 5-dihydro-isoxazole;

adding the sulfonylation reagent, the preset solvent and the catalyst into 3- [ 2-methyl-6-bromo-phenyl ] -4, 5-dihydro isoxazole to prepare 3- [ 2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro isoxazole at a preset constant temperature;

adding the catalyst, the brominating reagent and the predetermined solvent to 3- [ 2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole to produce 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole.

3. The process for preparing topramezone according to claim 2, wherein the brominating reagent is Br₂At least one of BrCl, NBS and HBr, wherein the catalyst is acetic acid, acetic anhydride, iodobenzene, aluminum trichloride, FeCl₃The base is at least one of butyl lithium, L DA, sodium hydroxide, potassium hydroxide, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, potassium carbonate, cesium carbonate, lithium hydroxide, triethylamine, diisopropylamine, DBU, sodium methoxide and sodium ethoxide, the sulfonylation reagent is at least one of methanesulfonyl chloride, methanesulfonic acid and methanesulfonic anhydride, the preset solvent is at least one of dichloromethane, dichloroethane, chloroform, chlorobenzene, toluene, xylene, tetrahydrofuran, methyl acetate, ethyl acetate, methanol, ethanol and isopropanol, and the preset constant temperature range is 30-60 ℃.

4. The process for preparing topramezone according to claim 1, wherein the second reaction process is:

mixing diethyl malonate and triethyl orthoformate with the hydrocarbon solvent in a reaction vessel, and preparing diethyl ethoxymethylidynemalonate under the action of nickel sulfate and the monobasic saturated carboxylic acid;

condensing and cyclizing diethyl ethoxymethylidynemalonate and methylhydrazine in an ethanol solution under the condition of preset low temperature to prepare 1-methyl-5-hydroxypyrazole-4-ethyl carboxylate reaction liquid;

hydrochloric acid is added into the prepared 1-methyl-5-hydroxypyrazole-4-ethyl carboxylate reaction liquid for reflux reaction to prepare 1-methyl-5-hydroxypyrazole.

5. The process for preparing topramezone according to claim 4, wherein the hydrocarbon solvent is at least one of xylene and toluene.

6. The process for preparing topramezone according to claim 4, wherein the saturated monocarboxylic acid is a saturated monocarboxylic acid having 1 to 5 carbon atoms.

7. The process for preparing topramezone according to claim 5, wherein the weight ratio of triethyl orthoformate: diethyl malonate: saturated monocarboxylic acids: nickel sulfate: hydrochloric acid: the mass ratio of methylhydrazine equal to 3: 1: 0.1: 0.0001: 0.24: 0.55.

8. the process for preparing topramezone according to claim 1, wherein the third reaction is:

mixing 3- [ 3-bromo-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole, 1-methyl-5-hydroxypyrazole, triethylamine, potassium carbonate, palladium chloride and triphenylphosphine according to a preset proportion, adding the mixture into an autoclave, and adding 1, 4-dioxane serving as a solvent to prepare a mixed solution;

after the mixed solution is purged by nitrogen and carbon monoxide, waiting for the reaction to be finished under the pressure and heating condition;

after the reaction is finished, carrying out reduced pressure distillation, adding water, and carrying out suction filtration to remove insoluble substances to obtain water-phase filtrate;

extracting the water phase filtrate, adjusting the pH value, extracting again and separating liquid to obtain an organic phase;

and carrying out reduced pressure distillation and solid methanol recrystallization on the organic phase to obtain the topramezone product.

9. The process for preparing topramezone according to claim 8, wherein the ratio of 3- [ 3-bromo-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole: 1-methyl-5-hydroxypyrazole: triethylamine: potassium carbonate: palladium chloride: the mass ratio of triphenylphosphine was 1: 1: 2: 2: 0.05: 0.1.

10. an application of topramezone, which comprises the preparation method of topramezone according to any one of claims 1 to 9, and is characterized by further comprising the application of topramezone in preventing and removing grassy weeds and part of broadleaf weeds in corn fields.

Technical Field

The invention relates to the technical field of chemical synthesis, and particularly relates to a preparation method and application of topramezone.

Background

The trade names of topramezone are Convey, Impact, Clio, bracter and the like, and the topramezone is a novel efficient herbicide developed by Passifer Germany. Topramezone is the first effective component in pyrazolone compounds, can be absorbed by roots, young stems and leaves, conducts apical and basal conduction to meristems in plants, indirectly influences the synthesis of carotenoids by inhibiting 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) in plastoquinone biosynthesis, interferes with the synthesis and function of chloroplasts, and finally causes severe albinism (due to degradation of chlorophyll). Among post-emergence stem and leaf treatment herbicides for corn fields sold in the current market, topramezone is the safest herbicide for corn fields, is safe for all growth periods of corn, and can be used for all corn types except for seed production corn; the herbicide is also the most complete herbicide for corn fields, has a common effect on few broadleaf weeds by using the bract and the fend, but has almost no weeds which can not be prevented by adding atrazine such as tiger plus leaves; the herbicide is also the most expensive herbicide for corn fields, but the problems that the sulfur-containing intermediate is smelly and raw materials are difficult to obtain exist in the existing production process flow, so that an industrial production method suitable for the topramezone is urgently needed to be provided for the industrial production of the topramezone.

Disclosure of Invention

The invention provides a preparation method and application of topramezone, which aim to solve the problems that a sulfur-containing intermediate can cause odor in the production process of topramezone and raw materials are difficult to obtain in the prior art.

A preparation method of topramezone comprises the following steps:

preparing 3- [ 3-bromo-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro isoxazole by using 2-methylbenzaldehyde, a bromination reagent, a catalyst, hydroxylamine hydrochloride, alkali, ethylene gas, a sulfonylation reagent and a preset solvent as reaction raw materials through a first reaction process;

taking diethyl malonate, triethyl formate, nickel sulfate, monobasic saturated carboxylic acid, methyl hydrazine, hydrocarbon solvent, ethanol solution and hydrochloric acid as reaction raw materials to prepare 1-methyl-5-hydroxypyrazole through a second reaction process;

with 3- [ 3-bromo-methyl-6- (methylsulfonyl) phenyl]-4, 5-dihydroisoxazole, 1-methyl-5-hydroxypyrazole, triethylamine, potassium carbonate, palladium chloride, triphenylphosphine, 1, 4-dioxane, water, saturated NaHCO₃The solution and the hydrochloric acid solution are used as reaction raw materials to prepare the topramezone through a third reaction process.

Wherein the first reaction process is as follows:

mixing the 2-methyl benzaldehyde and a bromination reagent in the preset solvent, and adding the catalyst under the condition of a preset constant temperature to perform bromination reaction to prepare 2-bromo-6-methyl benzaldehyde;

carrying out condensation reaction on 2-bromo-6-methylbenzaldehyde, a preset solvent, hydroxylamine hydrochloride and alkali, then introducing ethylene gas and the catalyst, and chloridizing to finally cyclize to obtain 3- [ 2-methyl-6-bromo-phenyl ] -4, 5-dihydro-isoxazole;

adding the sulfonylation reagent, the preset solvent and the catalyst into 3- [ 2-methyl-6-bromo-phenyl ] -4, 5-dihydro isoxazole to prepare 3- [ 2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro isoxazole at a preset constant temperature;

adding the catalyst, the brominating reagent and the predetermined solvent to 3- [ 2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole to produce 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole.

Wherein the brominating reagent is Br₂At least one of BrCl, NBS and HBr, wherein the catalyst is acetic acid, acetic anhydride, iodobenzene, aluminum trichloride, FeCl₃The base is at least one of butyl lithium, L DA, sodium hydroxide, potassium hydroxide, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, potassium carbonate, cesium carbonate, lithium hydroxide, triethylamine, diisopropylamine, DBU, sodium methoxide and sodium ethoxide, the sulfonylation reagent is at least one of methanesulfonyl chloride, methanesulfonic acid and methanesulfonic anhydride, and the preset solvent is dichlorochlorin, methanesulfonic acid and methanesulfonic anhydrideAt least one of methane, dichloroethane, chloroform, chlorobenzene, toluene, xylene, tetrahydrofuran, methyl acetate, ethyl acetate, methanol, ethanol and isopropanol, wherein the preset constant temperature range is 30-60 ℃.

Wherein the second reaction process is as follows:

mixing diethyl malonate and triethyl orthoformate with the hydrocarbon solvent in a reaction vessel, and preparing diethyl ethoxymethylidynemalonate under the action of nickel sulfate and the monobasic saturated carboxylic acid;

condensing and cyclizing diethyl ethoxymethylidynemalonate and methylhydrazine in an ethanol solution under the condition of preset low temperature to prepare 1-methyl-5-hydroxypyrazole-4-ethyl carboxylate reaction liquid;

hydrochloric acid is added into the prepared 1-methyl-5-hydroxypyrazole-4-ethyl carboxylate reaction liquid for reflux reaction to prepare 1-methyl-5-hydroxypyrazole.

Wherein the hydrocarbon solvent is at least one of xylene and toluene.

Wherein the saturated monocarboxylic acid is a saturated monocarboxylic acid having 1 to 5 carbon atoms, and is preferably acetic acid.

Wherein triethyl orthoformate: diethyl malonate: saturated monocarboxylic acids: nickel sulfate: hydrochloric acid: the mass ratio of methylhydrazine equal to 3: 1: 0.1: 0.0001: 0.24: 0.55.

wherein the third reaction is:

mixing 3- [ 3-bromo-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole, 1-methyl-5-hydroxypyrazole, triethylamine, potassium carbonate, palladium chloride and triphenylphosphine according to a preset proportion, adding the mixture into an autoclave, and adding 1, 4-dioxane serving as a solvent to prepare a mixed solution;

after the mixed solution is purged by nitrogen and carbon monoxide, waiting for the reaction to be finished under the pressure and heating condition;

after the reaction is finished, carrying out reduced pressure distillation, adding water, and carrying out suction filtration to remove insoluble substances to obtain water-phase filtrate;

extracting the water phase filtrate, adjusting the pH value, extracting again and separating liquid to obtain an organic phase;

and carrying out reduced pressure distillation and solid methanol recrystallization on the organic phase to obtain the topramezone product.

Wherein 3- [ 3-bromo-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole: 1-methyl-5-hydroxypyrazole: triethylamine: potassium carbonate: palladium chloride: the mass ratio of triphenylphosphine was 1: 1: 2: 2: 0.05: 0.1.

the invention also provides application of topramezone, which comprises the preparation method of topramezone and application of topramezone in preventing and removing gramineous weeds and part of broadleaf weeds in corn fields.

The invention provides a new synthetic route of 3- [ 3-bromo-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro isoxazole in the prior art, avoids the problem that the sulfur-containing intermediate in the prior art can disperse odor, improves the yield of 1-methyl-5-hydroxypyrazole by improving the synthetic route of the 1-methyl-5-hydroxypyrazole process to solve the problem that raw materials are not easy to prepare, and obtains the aim of reducing the production process difficulty by catalytically carbonylating the 3- [ 3-bromo-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydro isoxazole and the 1-methyl-5-hydroxypyrazole to prepare the topramezone, wherein the topramezone has a very good control effect on gramineous weeds and part of broad-leaved weeds in a corn field, has good application prospect.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.

Fig. 1 is a schematic structural diagram of a synthetic process flow for a preparation method of topramezone and an application thereof.

FIG. 2 is a schematic diagram of the synthetic process flow of the preparation of 3- [ 3-bromo-2-methyl-6- (methylsulfonyl) phenyl ] -4, 5-dihydroisoxazole using the topramezone preparation method of the present invention.

FIG. 3 is a schematic diagram of a synthetic process flow for preparing 1-methyl-5-hydroxypyrazole by using the topramezone preparation method and the application thereof.

Fig. 4 is a schematic structural diagram of a synthetic process flow for preparing topramezone by using the topramezone preparation method and the application thereof.

Figure 5 is a chemical equation for topramezone preparation according to the present invention and the use thereof.

Detailed Description

Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar elements or elements having the same or similar function throughout. The embodiments described below with reference to the drawings are illustrative and intended to be illustrative of the invention and are not to be construed as limiting the invention.

In the description of the present invention, it is to be understood that the terms "length", "width", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", and the like, indicate orientations or positional relationships based on the orientations or positional relationships illustrated in the drawings, and are used merely for convenience in describing the present invention and for simplicity in description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed in a particular orientation, and be operated, and thus, are not to be construed as limiting the present invention. Further, in the description of the present invention, "a plurality" means two or more unless specifically defined otherwise.

Referring to fig. 1 to 5, the present invention provides a technical solution: