A method for synthesizing mesotrione and its homologues

Abstract

The present invention belongs to the field of organic synthesis. The present invention provides a method for synthesizing mesotrione and its homologues, wherein enol esters of mesotrione and its analogues are subjected to rearrangement reaction in an organic solvent by using an alkali metal salt to obtain target mesotrione and its analogues. The preparation method provided by the present invention can be widely used for the synthesis of mesotrione and its homologues, simplifies the preparation process, shortens the reaction time, and effectively improves the yield and reduces the production cost.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to a synthesis method of mesotrione and its analogs, in particular to a synthesis method of sulcotrione, mesotrione and dichloroquinolinetrione. Background Art

[0002] Triketone herbicides are another type of HPPD (parahydroxyphenylpyruvate dioxidase) inhibitor developed after pyrazole herbicides. They are characterized by broad-spectrum herbicidal activity and can be used both before and after emergence. There are currently 12 varieties on the market or under development. They are fenquinotrione, ketospiradox, lancotrione, mesotrione, quintrione, sulcotrione, bicyclopyrone, tefuryltrione, tembotrione, benzobicyclon, quinotrione or methylquinotrione. The advantages of this type of herbicide: ① The storage stability of the aqueous solution is good, and it is not easy to volatilize and photolyze; ② It has good physical compatibility with other herbicides, which is conducive to the development of mixed preparations; ③ It is a weak acid herbicide and is easy for plants to absorb. Due to its good performance and broad market, its synthesis method has also attracted widespread attention, but the rearrangement process is complicated and the yield is low. Summary of the invention

[0003] The object of the present invention is to provide a method for synthesizing mesotrione and its analogs with simple process and high conversion rate.

[0004] To achieve the above purpose, the present invention adopts the following technical solution:

[0005] A method for preparing mesotrione and its analogs, comprising: subjecting enol esters of mesotrione and its analogs to rearrangement reaction in an organic solvent using an alkali metal salt to obtain target mesotrione and its analogs;

[0006] The mesotrione and its analogs include fenquinotrione, ketospiradox, lancotrione, mesotrione, quintrione, sulcotrione, bicyclopyrone, tefuryltrione, tembotrione, benzobicyclon or quinoline or methylquinoline.

[0007] 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 carbonate, potassium bicarbonate, sodium sulfide, potassium sulfide, sodium hydrogensulfate, potassium hydrogensulfate, 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 carbonate, potassium bicarbonate, sodium sulfide, potassium sulfide, sodium nitrite, and cesium chloride.

[0008] The molar ratio of the alkali metal salt to the enol ester of mesotrione and its analogs is 0.05-2.0.

[0009] The organic solvent is selected from a polar organic solvent or a non-polar organic solvent;

[0010] The polar organic solvent is acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, hexamethylphosphoric triamide (HMPA), tetrahydrofuran, methyl isobutyl ketone, ethyl acetate, and 1,3-dimethyl-2-imidazolidinone.

[0011] The non-polar organic solvent is: toluene, xylene, chlorobenzene, dichloromethane, dichloroethane, chloroform, and carbon tetrachloride.

[0012] The rearrangement reaction is carried out at a temperature of 20-80°C and a reaction time of 0.5-5 hours.

[0013] When the rearrangement reaction is carried out in a non-polar organic solvent, a phase transfer catalyst may be added to accelerate the reaction; wherein the amount of the phase transfer catalyst added is 1-10% (molar ratio).

[0014] The phase transfer catalyst can be selected from conventional phase transfer catalysts 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-diazabicycloundec-7-ene (DBU) or one or two of triethylenediamine.

[0015] The advantages of the present invention are:

[0016] The method of the present invention uses inorganic salts of alkali metals, especially nitrite, sodium (potassium) hydroxide, sodium carbonate (potassium or cesium), sodium (potassium) bicarbonate, sodium (potassium) sulfide, sodium nitrite, cesium chloride, etc., in an organic solvent to complete the rearrangement reaction of enol ester to triketone target compound, further simplifying the operation, improving the yield, and reducing the production cost. The method is easy to industrialize. DETAILED DESCRIPTION

[0017] The following specific examples are used to further illustrate the present invention, but the present invention is by no means limited to these examples; and the percentages involved in the following examples are all mass percentages, such as content, purity, etc.

[0018] In the above preparation process, the content of the product is determined by high performance liquid chromatography using an external standard method.

[0019] In addition, the enol ester raw material (compound of formula II) and metal salt and / or phase transfer catalyst used in the present invention can be obtained from the market or prepared according to the prior art.

[0020] Mesotrione Preparation Example 1

[0021] 10.16 g (0.03 mol) of enol ester, 2.08 g (0.03 mol) of sodium nitrite and 150 mL of N,N-dimethylformamide were added to a reaction bottle, and then stirred at room temperature for reaction. After 1 hour, HPLC detected that the reaction was complete. The reaction solution was poured into ice water, and the pH was adjusted to 1.5 with dilute hydrochloric acid. A yellow solid precipitated, which was washed with water and dried. The weight was 8.73 g, and the yield was 86%.

[0022] Preparation Example 2 of Mesotrione

[0023] 5.08 g (0.015 mol) of enol ester, 1.20 g (0.03 mol) of sodium hydroxide, 50 mL of dichloromethane and 0.25 g of phase transfer catalyst 15-crown-5 were added to a reaction flask, and then stirred at room temperature. After 1 hour, HPLC detected that the reaction was complete. The reaction solution was decompressed and desolventized, and the residue was added with water and stirred. Dilute hydrochloric acid was used to adjust the pH to 1, and a yellow solid precipitated. It was washed with water and dried, weighing 4.47 g, with a yield of 88%.

[0024] In addition, by changing the different substituents of the raw materials in the reaction formula and following the above-mentioned preparation process, compounds of formula I represented by different substituents can also be obtained, which also shows the wide application of the method of the present invention.

Claims

1. A method for synthesizing mesotrione and its homologues, characterized in that : The enol ester of mesotrione and its analogs is subjected to rearrangement reaction in an organic solvent by using an alkali metal salt to obtain the target mesotrione and its analogs; The mesotrione and its analogs include fenquinone, cyclohexanedione, 2-[2-chloro-3-[2-(1,3-dioxolan-2-yl)ethoxy]-4-methylsulfonylbenzoyl]-3-hydroxy-2-cyclohexene-1-one, mesotrione, dichloroquinolinetrione, sulcotrione, flupyralidone, furfuryl ester ketone, cyclosulfone, bicyclosulfone, quinolinetrione or methylquinolinetrione; The alkali metal salt is sodium hydroxide or sodium nitrite; The organic solvent is one or both of N,N-dimethylformamide and dichloromethane.

2. The method for synthesizing mesotrione and its homologues according to claim 1, characterized in that: The molar ratio of the alkali metal salt to the enol ester of mesotrione and its analogs is 0.05-2.

0.

3. The method for synthesizing mesotrione and its homologues according to claim 1, characterized in that: The rearrangement reaction is carried out at a temperature of 20-80°C and a reaction time of 0.5-5 hours.

4. The method for synthesizing mesotrione and its homologues according to any one of claims 1 to 3, characterized in that: When the rearrangement reaction is carried out in dichloromethane, a phase transfer catalyst is added to accelerate the reaction; wherein the molar ratio of the phase transfer catalyst added is 1-10%.