阅读说明：本技术 一种硝磺草酮及其同系物的合成方法 (Synthesis method of mesotrione and homologs thereof ) 是由 芦志成 刘鹏飞 关爱莹 李慧超 杨萌 叶艳明 刘长令 于 2020-06-28 设计创作，主要内容包括：本发明属于有机合成领域,本发明提供了一种硝磺草酮及其同系物的合成方法,将硝磺草酮及其类似物的烯醇酯在有机溶剂中,利用碱金属盐的作用,进行重排反应,获得目标物硝磺草酮及其类似物。本发明提供的制备方法可以广泛的用于硝磺草酮及其同系物的合成,简化了制备工艺,缩短了反应时间,且有效提高收率、降低生产成本。(The invention belongs to the field of organic synthesis, and provides a method for synthesizing mesotrione and analogues thereof. The preparation method provided by the invention can be widely used for synthesizing mesotrione and homologs thereof, simplifies the preparation process, shortens the reaction time, effectively improves the yield and reduces the production cost.)

1. A method for synthesizing mesotrione and its homologues is characterized in that enol esters of mesotrione and its analogues are subjected to rearrangement reaction in an organic solvent under the action of alkali metal salt to obtain target mesotrione and its analogues;

said mesotrione and analogues thereof include fenquinotrione, ketospiradox, lancotrione, mesotrione, quintrine, sulcotrione, bicyclopyrone, tefuryltrione, tembotrione, benzobicyclon or quintocetone or mequintocetone.

2. The method of synthesizing mesotrione and its homologs as claimed in claim 1, wherein the alkali metal salt is one or more of sodium hydride, lithium hydroxide, sodium borohydride, sodium cyanoborohydride, sodium hydroxide, potassium hydroxide, sodium bisulfite, sodium sulfite, sodium bisulfate, sodium carbonate, sodium bicarbonate, cesium carbonate, potassium bicarbonate, sodium sulfide, potassium sulfide, sodium hydrosulfide, potassium hydrosulfide, sodium thiosulfate, sodium hydrogen phosphate, potassium hydrogen phosphate, sodium phosphate, potassium phosphate, sodium amide, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium nitrite, cesium chloride.

3. The process of synthesizing mesotrione and its homologs according to claim 1, wherein the molar ratio of alkali metal salt to enol ester of mesotrione and its analogs is between 0.05 and 2.0.

4. The process of synthesizing mesotrione and its homologs as claimed in claim 1, wherein the organic solvent is selected from the group consisting of polar organic solvents and non-polar organic solvents.

5. The process for the synthesis of mesotrione and its homologs as claimed in claim 1, wherein said rearrangement reaction is carried out at a temperature of 20-80 ℃ for a period of 0.5-5 hours.

6. The process for the synthesis of mesotrione and its homologues as claimed in any one of claims 1 to 5, wherein when said rearrangement reaction is carried out in a non-polar organic solvent, a phase transfer catalyst is added to accelerate the reaction; wherein, the addition amount of the phase transfer catalyst is 1-10% (mol ratio).

Technical Field

The invention belongs to the field of organic synthesis, in particular relates to a method for synthesizing mesotrione and analogues thereof, and particularly relates to a method for synthesizing mesotrione, mesotrione and quinclorac.

Background

Triketones are another class of HPPD (p-hydroxyphenylpyruvate dioxygenase) inhibitors developed after pyrazoles. Its advantages are broad-spectrum herbicidal activity and high effect both before and after emergence. There are currently 12 varieties on the market or under development. They are fenquinotrione, ketospiradox, lancotrione, mesotrione, quintrine, sulcotrione, bicyclopyrone, tefuryltrione, tembotrione, benzobicyclon, clethodim or mequintocetone. The advantages of the herbicide are as follows: the storage stability of the aqueous solution is good, and the aqueous solution is not easy to volatilize and photolyze; secondly, the herbicide has good physical compatibility with other herbicides, and is beneficial to developing mixed preparations; and the weak acid herbicide is convenient for plants to absorb. Due to good performance and wide market, the synthesis method also draws wide attention, but the rearrangement process has complex process and low yield.

Disclosure of Invention

The invention aims to provide a method for synthesizing mesotrione and analogues thereof, which has the advantages of simple process and high conversion rate.

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

a preparation method of mesotrione and analogues thereof comprises the steps of carrying out rearrangement reaction on enol esters of mesotrione and analogues thereof in an organic solvent under the action of alkali metal salt to obtain target mesotrione and analogues thereof;

said mesotrione and analogues thereof include fenquinotrione, ketospiradox, lancotrione, mesotrione, quintrine, sulcotrione, bicyclopyrone, tefuryltrione, tembotrione, benzobicyclon or quintocetone or mequintocetone.

The alkali metal salt is one or more of sodium hydride, lithium hydroxide, sodium borohydride, sodium cyanoborohydride, sodium hydroxide, potassium hydroxide, sodium bisulfite, sodium sulfite, sodium bisulfate, sodium carbonate, sodium bicarbonate, cesium carbonate, potassium bicarbonate, sodium sulfide, potassium sulfide, sodium hydrosulfate, potassium hydrosulfate, sodium thiosulfate, sodium hydrogen phosphate, potassium hydrogen phosphate, sodium phosphate, potassium phosphate, sodium amide, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium nitrite and cesium chloride. Preferred are sodium hydride, lithium hydroxide, sodium borohydride, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, cesium carbonate, potassium bicarbonate, sodium sulfide, potassium sulfide, sodium nitrite, cesium chloride.

The molar ratio of the alkali metal salt to the enol ester of mesotrione and analogues thereof is between 0.05 and 2.0.

The organic solvent is selected from a polar organic solvent or a non-polar organic solvent;

the polar organic solvent is acetonitrile, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, hexamethylphosphoric triamide (HMPA), tetrahydrofuran, methyl isobutyl ketone, ethyl acetate and 1, 3-dimethyl-2-imidazolidinone.

The non-polar organic solvent is: toluene, xylene, chlorobenzene, dichloromethane, dichloroethane, chloroform, carbon tetrachloride.

The rearrangement reaction is carried out at the temperature of 20-80 ℃ and the reaction time is 0.5-5 hours.

When the rearrangement reaction is carried out in a nonpolar organic solvent, a phase transfer catalyst can be added to accelerate the reaction; wherein, the addition amount of the phase transfer catalyst is 1-10% (mol ratio).

The phase transfer catalyst may be selected from one or two of the phase transfer catalysts conventional in the art, such as PEG-200, PEG-400, PEG-600, 18 crown-6, 15 crown-5, cyclodextrin, benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, tetramethylammonium bromide, tributylmethylammonium chloride, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, pyridine, tributylamine, methyltriphenylphosphonium bromide, tetrabutylphosphonium bromide, 1, 8-diazabicycloundecen-7-ene (DBU), or triethylenediamine.

The invention has the advantages that:

the method uses inorganic salt of alkali metal, especially nitrite, sodium (potassium) hydroxide, sodium (potassium) carbonate, sodium (potassium) bicarbonate, sodium (potassium) sulfide, sodium nitrite, cesium chloride and the like to complete rearrangement reaction of enol ester to triketone target compounds in an organic solvent, further simplifies the operation, improves the yield and reduces the production cost. The method is easy for industrial production.

Detailed Description

The following specific examples are intended to further illustrate the invention, but the invention is by no means limited to these examples; and the percentages referred to in the following examples are all mass percentages, such as content, purity, etc.

The content of the product in the preparation process is determined by adopting an external standard method through high performance liquid chromatography.

In addition, the enol ester starting material (compound of formula II) and the metal salt and/or the phase transfer catalyst employed in the present invention can be obtained commercially or prepared according to the prior art.

Preparation of mesotrione example 1

10.16g (0.03mol) of enol ester, 2.08g (0.03mol) of sodium nitrite and 150mL of N, N-dimethylformamide are added into a reaction bottle, then the mixture is stirred at room temperature for reaction, after 1 hour, HPLC detects that the reaction is complete, the reaction liquid is poured into ice water, dilute hydrochloric acid is used for adjusting the pH value to 1.5, yellow solid is separated out, the mixture is washed with water and dried, 8.73g of the mixture is weighed, and the yield is 86%.

Preparation of mesotrione example 2

5.08g (0.015mol) of enol ester, 1.20g (0.03mol) of sodium hydroxide, 50mL of dichloromethane and 0.25g of phase transfer catalyst 15-crown-5 are added into a reaction bottle, then the mixture is stirred at room temperature for reaction, HPLC (high performance liquid chromatography) detects that the reaction is complete after 1 hour, the reaction solution is decompressed and desolventized, water is added into the residue for stirring, dilute hydrochloric acid is used for adjusting the pH value to 1, yellow solid is separated out, the mixture is washed with water and dried, 4.47g is weighed, and the yield is 88%.

In addition, the compound shown in the formula I with different substituents can be obtained by changing different substituents of raw materials in the reaction formula according to the description of the preparation process, and the application of the method of the invention is also shown.