Process for the preparation of mesotrione intermediates

Abstract

This invention relates to the field of herbicide technology, specifically to a method for preparing a sulfadiazine intermediate, comprising: (1) reacting 3,4-dichloronitrobenzene, methyl cyanoacetate, and a first base in the presence of a first solvent to obtain a compound of formula (II); (2) reacting the compound of formula (II) with sodium methanethiol in the presence of a second solvent to obtain a compound of formula (III); and (3) reacting the compound of formula (III) with a second base and hydrogen peroxide in the presence of a third solvent to obtain the sulfadiazine intermediate of formula (I). This method has the advantages of mild reaction conditions, high reaction yield and purity, and low cost, making it suitable for industrial production.

Description

Technical Field

[0001] This invention relates to the field of herbicide technology, and specifically to a method for preparing a sulfadiazine intermediate. Background Technology

[0002] Sulfonazole, developed by Jelicon, is a triketone herbicide, specifically an HPPD inhibitor (para-hydroxyphenylpropionate dioxygenase inhibitor). Its mechanism of action involves absorption and translocation through the young roots of weeds. After absorption, sensitive weeds experience inhibition of HPPD synthesis, leading to tyrosine accumulation. This inhibits the biosynthesis of plastoquinones and tocopherols, consequently affecting carotenoid biosynthesis, resulting in weed bleaching and death. Because it acts on carotenoid synthesis, it eliminates cross-resistance with triazine herbicides and can be used alone, in combination, or continuously to control weeds in corn fields, making it widely applicable. Therefore, the synthesis of sulfonazole and its intermediates has attracted considerable attention.

[0003] It is usually prepared from the intermediate 2-chloro-4-methylsulfonylbenzoic acid. Currently, most reported methods for preparing 2-chloro-4-methylsulfonylbenzoic acid both domestically and internationally involve the chlorination of 4-methylsulfonyltoluene, such as CN102627591A, CN113735745A, CN113603626A, and CN104086466A. Among them, CN102627591A first prepares 4-methylsulfonyltoluene to obtain 4-methylsulfonyl-2-chloro-toluene, and then oxidizes the methyl group at high temperature to prepare 2-chloro-4-methylsulfonylbenzoic acid. The reaction mechanism is shown below:

[0004]

[0005] The above method for preparing 2-chloro-4-methylsulfonyltoluene from 4-methylsulfonyltoluene has the following drawbacks: 4-methylsulfonyltoluene is oxidized by oxygen under the action of cobalt salt catalyst, resulting in low reaction efficiency and safety hazards; 4-methylsulfonyltoluene reacts with nitric acid at high temperature of 175-195℃, posing safety hazards and making it prone to accidents, which is not conducive to large-scale industrial production; in addition, 4-methylsulfonyltoluene is expensive and has a long production cycle.

[0006] Therefore, there is an urgent need for a method for preparing sulfadiazine intermediates that is mild, has high yield, high purity, and low cost. Summary of the Invention

[0007] The purpose of this invention is to overcome the problems of high starting material cost, low reaction yield and purity, harsh reaction conditions, safety hazards, and unfavorable conditions for large-scale production in existing methods for preparing sulfadiazine intermediates, and to provide a new method for preparing sulfadiazine intermediates.

[0008] To achieve the above objectives, the present invention provides a method for preparing a sulfadiazine intermediate, the method comprising the following steps:

[0009] (1) In the presence of a first solvent, 3,4-dichloronitrobenzene, methyl cyanoacetate and a first base are reacted to give the compound shown in formula (II).

[0010]

[0011] (2) In the presence of a second solvent, the compound shown in formula (II) is reacted with sodium methanethiol to give the compound shown in formula (III).

[0012]

[0013] (3) In the presence of a third solvent, the compound shown in formula (III) and the second base and hydrogen peroxide are subjected to a third reaction to obtain the sulfadiazine intermediate shown in formula (I).

[0014]

[0015] Compared with existing technologies, this invention provides a novel method for preparing sulfadiazine intermediates. This method uses 3,4-dichloronitrobenzene as a starting material, which is relatively easy to obtain and reduces production costs. By cleverly designing steps (1)-(3), the target product (the compound shown in formula (I)) is finally obtained, avoiding safety hazards and complex process flow defects. It has the advantages of mild reaction conditions, high reaction yield and purity, and low cost, making it convenient for industrial production. At the same time, the sulfadiazine intermediates obtained by the method provided by this invention all have a purity of over 90 wt%, a yield of over 90%, and an overall yield of over 82% for steps (1)-(3). Detailed Implementation

[0016] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0017] In this invention, unless otherwise specified, the terms "first," "second," and "third" do not indicate a sequential order, nor do they limit the specific materials or steps; they are merely used to distinguish between different materials or steps. For example, in "first reaction," "second reaction," and "third reaction," "first," "second," and "third" are simply used to indicate that these are not the same reaction; similarly, in "first alkali" and "second alkali," "first," "second," and "third" are simply used to indicate that these are not the same type of alkali.

[0018] This invention provides a method for preparing a sulfadiazine intermediate, the method comprising the following steps:

[0019] (1) In the presence of a first solvent, 3,4-dichloronitrobenzene, methyl cyanoacetate and a first base are reacted to give the compound shown in formula (II).

[0020]

[0021] (2) In the presence of a second solvent, the compound shown in formula (II) is reacted with sodium methanethiol to give the compound shown in formula (III).

[0022]

[0023] (3) In the presence of a third solvent, the compound shown in formula (III) and the second base and hydrogen peroxide are subjected to a third reaction to obtain the sulfadiazine intermediate shown in formula (I).

[0024]

[0025] In some embodiments of the present invention, preferably, in step (1), the conditions for the first reaction include: a temperature of 40-140°C, preferably 60-120°C; and a time of 4-14 h, preferably 5-10 h. Using these preferred conditions is more conducive to improving the reaction yield and reaction purity of the compound represented by formula (II).

[0026] In some embodiments of the present invention, preferably, in step (1), the molar ratio of 3,4-dichloronitrobenzene, methyl cyanoacetate, and the first base is 1:1.05-1.5:1-1.2, more preferably 1:1.05-1.1:1-1.1. Using these preferred conditions is more conducive to improving the reaction yield and reaction purity of the compound represented by formula (II).

[0027] In one specific embodiment of the present invention, in step (1), the amount of methyl cyanoacetate used relative to 1 mol of 3,4-dichloronitrobenzene is 1.05-1.5 mol, preferably 1.05-1.1 mol; the amount of the first base used is 1-1.2 mol, preferably 1-1.1 mol.

[0028] In some embodiments of the present invention, preferably, in step (1), the first base is selected from inorganic bases and / or organic bases, more preferably from at least one of sodium methoxide, sodium ethoxide, triethylamine, N,N-diisopropylethylamine, pyridine, sodium carbonate, potassium carbonate, sodium formate, sodium acetate, potassium acetate and N,N-dimethylaniline, and more preferably from sodium methoxide and / or potassium carbonate.

[0029] In some embodiments of the present invention, preferably, in step (1), the amount of the first solvent used relative to 1g of 3,4-dichloronitrobenzene is 1-10g, for example, 1g, 2g, 3g, 4g, 5g, 8g, 10g, and any value in any range of any two values, preferably 1-5g.

[0030] In this invention, the type of the first solvent is subject to a wide range of selection, as long as the first reaction is carried out in the presence of the first solvent. Preferably, in step (1), the first solvent is selected from organic solvents, more preferably from at least one of dimethyl sulfoxide, chlorobenzene, N,N-dimethylformamide, N,N-dimethylacetamide, cyclohexane, dichloroethane, ethanol, tetrahydrofuran, propylene oxide, and 1,2-epoxybutane, and more preferably from at least one of N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide.

[0031] In some embodiments of the present invention, preferably, in step (2), the conditions for the second reaction include: a temperature of 15-40°C, preferably 20-25°C; and a time of 0.1-10 h, preferably 1-5 h. Using these preferred conditions is more conducive to improving the reaction yield and reaction purity of the compound represented by formula (III).

[0032] In some embodiments of the present invention, preferably, in step (2), the molar ratio of the compound represented by formula (II) to sodium methanethiol is 1:1.05-1.5, more preferably 1:1.05-1.1. Using these preferred conditions is more conducive to improving the reaction yield and reaction purity of the compound represented by formula (III).

[0033] In a preferred embodiment of the present invention, preferably, the compound represented by formula (II), sodium methanethiol, and a catalyst are subjected to the second reaction to obtain the compound represented by formula (III).

[0034] In some embodiments of the present invention, preferably, the amount of catalyst used is 0.01-0.05 mol relative to 1 mol of the compound represented by formula (II), for example, 0.01 mol, 0.015 mol, 0.02 mol, 0.03 mol, 0.04 mol, 0.05 mol, and any value within the range of any two values, preferably 0.01-0.02 mol.

[0035] In one specific embodiment of the present invention, in step (2), the amount of sodium methanethiol equivalent to 1 mol of the compound shown in formula (II) is 1.05-1.5 mol, preferably 1.05-1.1 mol; the amount of catalyst is 0.01-0.05 mol, preferably 0.01-0.02 mol.

[0036] In this invention, the catalyst used in step (2) can further catalyze the compound of formula (II) and sodium methanethiol to carry out a second reaction; wherein the catalyst includes, but is not limited to, tetrabutylammonium bromide.

[0037] In some embodiments of the present invention, preferably, in step (2), the amount of the second solvent used is 1-10g relative to 1g of the compound represented by formula (II), for example, 1g, 2g, 3g, 4g, 5g, 8g, 10g, and any value in the range of any two values, preferably 1-5g.

[0038] In this invention, the type of the second solvent is widely selectable, as long as the second reaction is carried out in the presence of the second solvent. Preferably, in step (2), the second solvent is selected from organic solvents, more preferably from at least one of toluene, acetonitrile, dichloroethane, tetrahydrofuran, chloroform, and N,N-dimethylformamide; more preferably from toluene and / or dichloroethane.

[0039] In some embodiments of the present invention, in step (3), the conditions for the third reaction include: a temperature of 20-110°C, preferably 40-90°C; and a time of 2-7 h, preferably 3-6 h. Using these preferred conditions is more conducive to improving the reaction yield and reaction purity of the compound represented by formula (I).

[0040] In some embodiments of the present invention, in step (3), the molar ratio of the compound represented by formula (III), the second base, and hydrogen peroxide is 1:0.01-0.5:0.1-1, preferably 1:0.05-0.15:0.7-0.9. Using these preferred conditions is more conducive to improving the reaction yield and reaction purity of the compound represented by formula (I).

[0041] In one specific embodiment of the present invention, in step (3), the amount of the second base relative to 1 mol of the compound shown in formula (III) is 0.01-0.5 mol, preferably 0.05-0.15 mol; the amount of hydrogen peroxide is 0.1-1 mol, preferably 0.7-0.9 mol.

[0042] In some embodiments of the present invention, preferably, the second alkali is selected from inorganic alkalis, more preferably from at least one of sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide, and more preferably from at least one of sodium carbonate, sodium hydroxide and potassium hydroxide.

[0043] In some embodiments of the present invention, preferably, in step (3), the amount of the third solvent used is 1-10g relative to 1g of the compound represented by formula (III), for example, 1g, 2g, 3g, 4g, 5g, 8g, 10g, and any value in the range of any two values, preferably 1-5g.

[0044] In this invention, the type of the third solvent is subject to a wide range of selection, as long as the third reaction is carried out in the presence of the third solvent. Preferably, in step (3), the third solvent is selected from inorganic solvents and / or organic solvents, more preferably from at least one of water, toluene, acetonitrile, cyclohexane, dichloroethane, ethanol, tetrahydrofuran, chloroform, and DMF, and more preferably from toluene and / or dichloroethane.

[0045] The present invention will be described in detail below through embodiments.

[0046] In the following examples, unless otherwise specified, all raw materials used are commercially available products.

[0047] Example 1

[0048] (1) Preparation of the compound shown in formula (II)

[0049] In a 500 mL four-necked flask equipped with a mechanical stirrer, thermometer, and condenser, 57.6 g (0.3 mol) of 3,4-dichloronitrobenzene, 160 g of N,N-dimethylformamide, and 41.4 g (0.3 mol) of potassium carbonate were added sequentially. The mixture was stirred and heated to 60 °C. 32.67 g (0.33 mol) of methyl cyanoacetate was added dropwise over 1 hour. The mixture was kept at 60 °C and reacted for 10 hours. After the reaction was completed, the solvent N,N-dimethylformamide was removed under reduced pressure and reused to obtain the compound shown in formula (II).

[0050] The compound represented by formula (II) has a purity of 98 wt% and a yield of 97% (based on 3,4-dichloronitrobenzene).

[0051] (2) Preparation of the compound shown in formula (III)

[0052] In a 500 mL four-necked flask equipped with a mechanical stirrer, thermometer, and condenser, 0.3 mol of the compound shown in formula (II), 115.5 g of sodium methanethiol aqueous solution (0.33 mol 20 wt%), 0.96 g of tetrabutylammonium bromide (0.003 mol), and 200 g of toluene were added sequentially. The mixture was reacted at 25 °C for 1 h. After the reaction was completed, the mixture was allowed to stand and separate into layers. The toluene layer was desorbed under reduced pressure and the solvent toluene was reused to obtain the compound shown in formula (III).

[0053] The compound represented by formula (III) has a purity of 96 wt% and a yield of 97% (based on the compound represented by formula (II)).

[0054] (3) Preparation of the compound shown in formula (I)

[0055] In a 500mL four-necked flask equipped with a mechanical stirrer, thermometer, and condenser, 0.3mol of the compound shown in formula (III), 3.18g of sodium carbonate (0.03mol), 27.21g of hydrogen peroxide (0.24mol, 30wt%), and 120g of water were added sequentially. The mixture was reacted at 90℃ for 3h. After the reaction was completed, the mixture was acidified and filtered to obtain the compound shown in formula (I).

[0056] The compound represented by formula (I) has a purity of 98 wt% and a yield of 95.8% (based on the compound represented by formula (III)).

[0057] The overall yield of the above steps (1)-(3) was 90.14%.

[0058] Example 2

[0059] (1) Preparation of the compound shown in formula (II)

[0060] In a 500 mL four-necked flask equipped with a mechanical stirrer, thermometer, and condenser, 57.6 g (0.3 mol) of 3,4-dichloronitrobenzene, 160 g of N,N-dimethylformamide, and 41.4 g (0.3 mol) of potassium carbonate were added sequentially. The mixture was stirred and heated to 120 °C. 32.67 g (0.33 mol) of methyl cyanoacetate was added dropwise over 1 hour. The mixture was kept at 120 °C for 5 hours. After the reaction was completed, the solvent N,N-dimethylformamide was removed under reduced pressure and reused to obtain the compound shown in formula (II).

[0061] The compound represented by formula (II) has a purity of 98.5 wt% and a yield of 97.3% (based on 3,4-dichloronitrobenzene).

[0062] (2) Preparation of the compound shown in formula (III)

[0063] In a 500 mL four-necked flask equipped with a mechanical stirrer, thermometer, and condenser, 0.3 mol of the compound shown in formula (II), 115.5 g of sodium methanethiol aqueous solution (0.33 mol 20 wt%), 0.96 g of tetrabutylammonium bromide (0.003 mol), and 200 g of 1,2-dichloroethane were added sequentially. The mixture was reacted at 20 °C for 1.5 h. After the reaction was completed, the mixture was allowed to stand and separate into layers. The 1,2-dichloroethane layer was desorbed under reduced pressure and the solvent 1,2-dichloroethane was reused to obtain the compound shown in formula (III).

[0064] The compound represented by formula (III) has a purity of 97 wt% and a yield of 96.8% (based on the compound represented by formula (II)).

[0065] (3) Preparation of the compound shown in formula (I)

[0066] In a 500mL four-necked flask equipped with a mechanical stirrer, thermometer, and condenser, 0.3mol of the compound shown in formula (III), 1.2g of sodium hydroxide (0.03mol), 27.21g of hydrogen peroxide (0.24mol, 30wt%), and 120g of water were added sequentially. The mixture was reacted at 70℃ for 4h. After the reaction was completed, the mixture was acidified and filtered to obtain the compound shown in formula (I).

[0067] The compound represented by formula (I) has a purity of 98 wt% and a yield of 96% (based on the compound represented by formula (III)).

[0068] The overall yield of the above steps (1)-(3) was 90.42%.

[0069] Example 3

[0070] In a 500 mL four-necked flask equipped with a mechanical stirrer, thermometer, and condenser, 57.6 g (0.3 mol) of 3,4-dichloronitrobenzene, 160 g of N,N-dimethylacetamide, and 16.2 g (0.3 mol) of sodium methoxide were added sequentially. The mixture was stirred and heated to 90 °C. 32.67 g (0.33 mol) of methyl cyanoacetate was added dropwise over 1 hour. The mixture was kept at 90 °C for 7 hours. After the reaction was completed, the solvent N,N-dimethylacetamide was removed under reduced pressure and reused to obtain the compound shown in formula (II).

[0071] The compound represented by formula (II) has a purity of 99 wt% and a yield of 98.3% (based on 3,4-dichloronitrobenzene).

[0072] (2) Preparation of the compound shown in formula (III)

[0073] In a 500 mL four-necked flask equipped with a mechanical stirrer, thermometer, and condenser, 0.3 mol of the compound shown in formula (II), 115.5 g of sodium methanethiol aqueous solution (0.33 mol 20 wt%), 0.96 g of tetrabutylammonium bromide (0.003 mol), and 200 g of 1,2-dichloroethane were added sequentially. The mixture was reacted at 25 °C for 1 h. After the reaction was completed, the mixture was allowed to stand and separate into layers. The 1,2-dichloroethane layer was desorbed under reduced pressure and the solvent 1,2-dichloroethane was reused to obtain the compound shown in formula (III).

[0074] The compound represented by formula (III) has a purity of 97 wt% and a yield of 96.8% (based on the compound represented by formula (II)).

[0075] (3) Preparation of the compound shown in formula (I)

[0076] In a 500 mL four-necked flask equipped with a mechanical stirrer, thermometer, and condenser, 0.3 mol of the compound shown in formula (III), 1.692 g (0.03 mol) of potassium hydroxide, 27.21 g (0.24 mol, 30 wt%) of hydrogen peroxide, and 120 g of water were added sequentially. The mixture was reacted at 70 °C for 4 h. After the reaction was completed, the mixture was acidified and filtered to obtain the compound shown in formula (I).

[0077] The compound represented by formula (I) has a purity of 98 wt% and a yield of 96.5% (based on the compound represented by formula (III)).

[0078] The overall yield of the above steps (1)-(3) was 91.82%.

[0079] Example 4

[0080] The method of Example 1 is followed, except that in step (1), the molar ratio of 3,4-dichloronitrobenzene, methyl cyanoacetate and the first base is replaced with 1:1.15:1.15, while the other conditions are the same, to obtain the compound shown in formula (II);

[0081] The compound represented by formula (II) has a purity of 94 wt% and a yield of 92.4% (based on 3,4-dichloronitrobenzene).

[0082] The remaining steps are the same, yielding the compound shown in formula (I);

[0083] The overall yield of the above steps (1)-(3) was 85.86%.

[0084] Example 5

[0085] The method of Example 1 is followed, except that in step (2), the molar ratio of the compound shown in formula (II) and sodium methanethiol is replaced with 1:1.15, and the other conditions are the same, to obtain the compound shown in formula (III);

[0086] The compound represented by formula (III) has a purity of 92 wt% and a yield of 91.5% (based on the compound represented by formula (II)).

[0087] The remaining steps are the same, yielding the compound shown in formula (I);

[0088] The overall yield of the above steps (1)-(3) was 85.03%.

[0089] Example 6

[0090] The method of Example 1 is followed, except that in step (3), the molar ratio of the compound shown in formula (III), the second base and hydrogen peroxide is replaced with 1:0.2:1, and the other conditions are the same, to obtain the compound shown in formula (I);

[0091] The compound represented by formula (I) has a purity of 91 wt% and a yield of 90% (based on the compound represented by formula (III)).

[0092] The overall yield of the above steps (1)-(3) was 84.68%.

[0093] Comparative Example 1

[0094] The compound shown in formula (I) is produced according to the existing process route:

[0095]

[0096] The method includes: adding 51g (0.3mol) of 4-methylsulfonyltoluene, 150g of dichloroethane, 5g of ferric chloride, and 10g of iodine sequentially to a 500mL four-necked flask equipped with a mechanical stirrer, thermometer, and condenser; heating to 70-80℃ and introducing 46.8g (0.6mol) of chlorine gas to generate 4-methylsulfonyl-2-chloro-toluene; washing with 50mL of 10wt% sodium hydroxide solution after the reaction is complete; and allowing the mixture to stand and separate into layers to obtain a dichloroethane solution of 4-methylsulfonyl-2-chloro-toluene. Next, a dichloroethane solution of 4-methylsulfonyl-2-chloro-toluene was added to an autoclave, along with cobalt acetate, 35g of 10wt% hydrobromic acid, and 20g of glacial acetic acid. The mixture was heated to 150℃-200℃ under 16atm O2, with oxygen continuously added during the reaction process, and the pressure maintained at 16atm. After the reaction was complete, the temperature was lowered to 20℃, and the dichloroethane phase was separated. Desolvation was then performed to obtain the sulfadiazine intermediate, which is the compound shown in formula (I).

[0097] The compound represented by formula (I) has a purity of 90 wt% and a yield of 80%.

[0098] As can be seen from the above embodiments, the method provided by the present invention, that is, using 3,4-dichloronitrobenzene as the starting material, and finally obtaining the target product through steps (1)-(3), avoids defects such as harsh reaction conditions and high cost, and has the advantages of mild conditions, high reaction yield and purity and low cost.

[0099] Compared to Example 4, this application improves the overall yield of the reaction by adopting a preferred molar ratio of 3,4-dichloronitrobenzene, methyl cyanoacetate, and the first base, thereby increasing the yield of the compound shown in Formula (II).

[0100] Compared to Example 5, this application improves the overall yield of the reaction by using a preferred molar ratio of the compound shown in Formula (II) and sodium methanethiol, thereby increasing the yield of the compound shown in Formula (III).

[0101] Compared to Example 6, this application improves the overall yield of the reaction by adopting a preferred molar ratio of the compound shown in Formula (III), the second base, and hydrogen peroxide, thereby increasing the yield of the compound shown in Formula (I).

[0102] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A process for the preparation of a sulfentrazone intermediate characterized in that, The method comprises the following steps: (1) a first reaction of 3,4-dichloronitrobenzene, methyl cyanoacetate and a first base in the presence of a first solvent to obtain a compound represented by formula (II), (II); (2) a second reaction of the compound represented by formula (II) and sodium thiomethoxide in the presence of a second solvent to obtain a compound represented by formula (III), (III); (3) a third reaction of the compound represented by formula (III) and a second base and hydrogen peroxide in the presence of a third solvent to obtain a mesotrione intermediate represented by formula (I), （I）。 2. The method of claim 1, wherein, In step (1), the first reaction has a temperature of 40-140℃ and a time of 4-14h.

3. The method of claim 2, wherein, In step (1), the first reaction has a temperature of 60-120℃ and a time of 5-10h.

4. The method of claim 1, wherein, In step (1), the molar ratio of 3,4-dichloronitrobenzene, methyl cyanoacetate and the first base is 1:1.05-1.5:1-1.

2. And / or, in step (1), the amount of the first solvent is 1-10g per 1g of 3,4-dichloronitrobenzene.

5. The method of claim 4, wherein, In step (1), the molar ratio of 3,4-dichloronitrobenzene, methyl cyanoacetate and the first base is 1:1.05-1.5:1-1.

2. 1.05-1.1：1-1.1； And / or, in step (1), the amount of the first solvent is 1-5g per 1g of 3,4-dichloronitrobenzene.

6. The method of claim 1, wherein, In step (1), the first base is selected from inorganic bases and / or organic bases. And / or, the first solvent is selected from organic solvents.

7. The method of claim 6, wherein, In step (1), the first base is selected from at least one of sodium methoxide, sodium ethoxide, triethylamine, N,N-diisopropylethylamine, pyridine, sodium carbonate, potassium carbonate, sodium formate, sodium acetate, potassium acetate and N,N-dimethylaniline. And / or, the first solvent is selected from at least one of dimethyl sulfoxide, chlorobenzene, N,N-dimethylformamide, N,N-dimethylacetamide, cyclohexane, dichloroethane, ethanol, tetrahydrofuran, propylene oxide and 1,2-butylene oxide.

8. The method of claim 7, wherein, In step (1), the first base is selected from sodium methoxide and / or potassium carbonate. And / or, the first solvent is selected from at least one of N,N-dimethylformamide, N,N-dimethylacetamide and dimethyl sulfoxide.

9. The method of claim 1, wherein, In step (2), the second reaction has a temperature of 15-40℃ and a time of 0.1-10h.

10. The method of claim 9, wherein, In step (2), the second reaction has a temperature of 20-25℃ and a time of 1-5h.

11. The method of claim 1, wherein, In step (2), the molar ratio of the compound represented by formula (II) and sodium thiomethoxide is 1:1.05-1.

5. And / or, the second reaction is carried out in the presence of a catalyst. And / or, the amount of the catalyst is 0.01-0.05mol per 1mol of the compound represented by formula (II).

12. The method of claim 11, wherein, In step (2), the molar ratio of the compound represented by formula (II) and sodium thiomethoxide is 1:1.05-1.

1. And / or, the amount of the catalyst is 0.01-0.02mol per 1mol of the compound represented by formula (II).

13. The method of claim 1, wherein, In step (2), the amount of the second solvent is 1-10g per 1g of the compound represented by formula (II). And / or, the second solvent is selected from organic solvents.

14. The method of claim 13, wherein, In step (2), the amount of the second solvent is 1-5 g relative to 1 g of the compound of formula (II). And / or, the second solvent is selected from at least one of toluene, acetonitrile, dichloroethane, tetrahydrofuran, chloroform and N,N-dimethylformamide.

15. The method of claim 14, wherein, In step (2), the second solvent is selected from toluene and / or dichloroethane.

16. The method of claim 1, wherein, In step (3), the third reaction conditions include: temperature is 20-110°C; time is 2-7 h.

17. The method of claim 16, wherein, In step (3), the third reaction conditions include: temperature is 40-90°C; time is 3-6 h.

18. The method of claim 1, wherein, In step (3), the molar ratio of the compound of formula (III), the second base and hydrogen peroxide is 1:0.01-0.5:0.1-1. And / or, the amount of the third solvent is 1-10 g relative to 1 g of the compound of formula (III).

19. The method of claim 18, wherein, In step (3), the molar ratio of the compound of formula (III), the second base and hydrogen peroxide is 1:0.05-0.15:0.7-0.

9. And / or, the amount of the third solvent is 1-5 g relative to 1 g of the compound of formula (III).

20. The method of claim 1, wherein, In step (3), the second base is selected from inorganic bases. And / or, the third solvent is selected from inorganic solvents and / or organic solvents.

21. The method of claim 20, wherein, In step (3), the second base is selected from at least one of sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide. And / or, the third solvent is selected from at least one of water, toluene, acetonitrile, cyclohexane, dichloroethane, ethanol, tetrahydrofuran, chloroform and DMF.

22. The method of claim 21, wherein, In step (3), the second base is selected from at least one of sodium carbonate, sodium hydroxide and potassium hydroxide. And / or, the third solvent is selected from toluene and / or dichloroethane.

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