A method for the synthesis of a sulfentrazone intermediate

Abstract

The application discloses a synthesis method of a sulfentrazone intermediate. A compound shown in formula II is chlorinated in the presence of a solvent to synthesize a compound shown in formula I by adding a composite catalyst, wherein the composite catalyst comprises catalyst A and catalyst B in a weight ratio of 0.1-20:0.01-10; the catalyst A is one or both of a metal or a metal chloride; and the catalyst B is a compound capable of reacting with water to remove water in a reaction system. The method is simple in operation, easy to industrialize, relatively mild in reaction environment, cheap in catalyst, and high in reaction yield and product content.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to a method for synthesizing a mesotrione intermediate. Background Technology

[0002] Methionyl is a triazoline herbicide characterized by low toxicity, broad spectrum of activity, and high efficacy. Its chemical name is N-(2,4-dichloro-5-(4-(difluoromethyl)-3-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)phenyl)methanesulfonamide. An important intermediate in its preparation is 1-(2,4-dichlorophenyl)-3-methyl-4-R (R being H or difluoromethyl)-1,2,4-triazol-5-one (hereinafter referred to as Compound I), whose chemical structure is as follows:

[0003]

[0004] There are currently many methods for synthesizing compound I:

[0005] Patent US005468868 describes a method for dichlorination using acetic acid and water. This method involves high dichlorination temperatures and dichlorination is carried out in a proton-containing solvent mixed with acetic acid and water, which greatly increases the risk of corrosion and perforation of the reaction vessel, requiring frequent replacement of the chlorination reaction vessel. Patent CN112125859 uses dichloroethane and water as solvents and molecular sieves as catalysts for the chlorination reaction. The introduction of water increases the risk of HF loss during the chlorination reaction, increases the requirements for the reaction vessel, and is not conducive to industrialization. Patent CN102993108A uses a mixture of hydrogen peroxide and hydrochloric acid for dichlorination, but it suffers from high raw material prices and high risk factors, limiting its application in industrial processes.

[0006] Patent CN 106478532 reports a dichlorination method that uses o-chlorophenylhydrazine as a raw material to synthesize 1-(2-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one, followed by dichlorination in dichloroethane using a composite catalyst of ferric chloride, antimony trichloride, and silica. This synthesis method uses a large proportion of antimony trichloride as the composite catalyst, which is prone to deactivation, expensive, and harmful to the aquatic environment, resulting in high catalytic synthesis and post-processing costs, hindering industrialization. Summary of the Invention

[0007] Purpose of the invention

[0008] To overcome the above shortcomings, the present invention aims to provide a method for synthesizing a mesotrione intermediate. This method is simple to operate and easy to industrialize, the reaction environment is relatively mild, the catalyst used is inexpensive and readily available, the reaction yield and product content after solvent removal and filtration are high, no further purification is required, and it can be directly used for subsequent reactions.

[0009] Solution

[0010] To achieve the objectives of this invention, the technical solution adopted is as follows:

[0011] In a first aspect, the present invention provides a method for synthesizing a mesotrione intermediate, wherein the compound shown in Formula II is synthesized by chlorination reaction of the compound in the presence of a solvent with the addition of a composite catalyst, wherein the composite catalyst comprises catalyst A and catalyst B in a weight ratio of 0.1–20:0.01–10; catalyst A is one or more of a metal or a metal chloride; catalyst B is a compound capable of reacting with water to remove water from the reaction system; optionally, catalyst B may be selected from one or more of acid anhydrides, orthoformates, halosilanes, acyl chlorides, and inorganic non-metallic chlorides capable of reacting with water.

[0012]

[0013] In Equation I, X and Y are each independently H or Cl, and X and Y are not simultaneously H or Cl;

[0014] In Formula I and Formula II, R is H or difluoromethyl.

[0015] Optionally, the compound of formula II can be 1-(4-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one, 1-(2-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one, 1-(4-chlorophenyl)-3-methyl-4-hydro-1,2,4-triazol-5-one or 1-(2-chlorophenyl)-3-methyl-4-hydro-1,2,4-triazol-5-one.

[0016] During the research and development process, the inventors discovered that using catalyst B could improve the reaction yield and product purity. Through continuous research, they found that trace amounts of water in the reaction system or environment could lead to side reactions and the loss of F groups, affecting the reaction yield. By using catalyst B, which can react with water, to thoroughly remove water, side reactions and the loss of F groups can be effectively reduced, enabling the reaction yield to reach 98% and the product purity to reach over 97%. This not only benefits subsequent reactions but also greatly increases production capacity.

[0017] Further, the weight ratio of catalyst A to catalyst B is 0.1-10:0.1-10, optionally 0.1-10:0.1-5, optionally 0.1-10:0.1-3, optionally 0.1-10:0.1-2.5, optionally 0.1-5:1-3, optionally 1:1-3, or optionally 1:1-2.5.

[0018] Further, in the catalyst A, the ratio of metal to metal chloride is 1:0 to 1:10 or 0:1 to 10:1; optionally, it is 1:0 to 1:5, optionally, it is 1:0.5 to 1:5, optionally, it is 1:0.5 to 1:2, optionally, it is 1:1 to 1:2, optionally, it is 1:1 or 1:2.

[0019] Further, the catalyst A is selected from one or more of Fe, FeCl2, FeCl3, Zn, ZnCl2, Al, AlCl3, Cu, CuCl2, and CuCl; optionally, the catalyst A is selected from one or more of Fe, FeCl2, and FeCl3.

[0020] Further, the amount of catalyst A added is 0.1%-5% of compound II, optionally 0.1%-4%, optionally 0.1%-2.5%, optionally 0.1%-4%, optionally 0.1%-2.5%, optionally 0.1%-2%, optionally 0.1%-0.75%, optionally 0.5%-2%, optionally 0.5%-1%, optionally 0.5%-0.75%.

[0021] The catalyst B is selected from one or more of the following: acid anhydrides, orthoformates, halosilanes, acyl chlorides, and inorganic non-metallic chlorides that can react with water.

[0022] Optionally, the acid anhydrides that can react with water include one or more of the following: acetic anhydride, trifluoroacetic anhydride, P2O5, P2O3, PO3, propionic anhydride, butyric anhydride, methyl acetic anhydride, methyl propionic anhydride, methyl butyric anhydride, ethyl propionic anhydride, ethyl butyric anhydride, malonic anhydride, succinic anhydride, 2-vinyl succinic anhydride, maleic anhydride, trans-butenedioic anhydride (maleic anhydride), glutaric anhydride, and adipic anhydride.

[0023] Optionally, orthoformates that can react with water include one or more of trimethyl orthoformate, triethyl orthoformate, and tripropyl orthoformate.

[0024] Optionally, the halosilanes that can react with water include one or more of trimethylchlorosilane, trimethylbromosilane, trimethyliodosilane, dimethyldichlorosilane, dimethylvinylchlorosilane, dimethylmonochlorosilane, and dimethyldibromosilane;

[0025] Optionally, the acyl chlorides that can react with water include one or more of the following: oxaloyl chloride, acetyl chloride, propionyl chloride, butyryl chloride, isopropionyl chloride, malonyl chloride, succinyl chloride, maleic anhydride chloride, trans-butenedyl chloride, glutaryl chloride, phosgene, triphosgene, benzoyl chloride, and phenylacetyl chloride.

[0026] Optionally, the inorganic nonmetallic chloride that can react with water is selected from SOCl. 2、 One or more of SO2Cl2, SO3, phosphorus trichloride, phosphorus pentachloride, and phosphorus oxychloride;

[0027] Furthermore, the catalyst B is selected from one or more of phosphorus trichloride, phosphorus pentachloride, acetic anhydride, acetyl chloride, SOCl2, SO2Cl2, and trimethylchlorosilane.

[0028] Further, the amount of catalyst B added is 0.1%-10% of compound II, optionally 0.5%-2%, optionally 0.5%-1.25%, preferably 0.5%-1.25%.

[0029] Furthermore, the chlorinating agent used includes one or more of chlorine, sulfonyl chloride, PCl3, and PCl5, with chlorine being the preferred agent.

[0030] Further, the solvent is one or more of chlorobenzene, dichlorobenzene, 1,2-dichloroethane, 1,2-dibromoethane, 1,1-dibromoethane, 1,1-dichloroethane, chloroform, carbon tetrachloride, acetonitrile, dichloromethane, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and acetic acid; preferably a chloroalkane, and optionally, the chloroalkane includes one or more of chlorobenzene, chloroform, 1,1-dichloroethane, 1,2-dichloroethane, and carbon tetrachloride.

[0031] Furthermore, the temperature of the chlorination reaction is 20℃-150℃, optionally 30℃-90℃, optionally 50℃-75℃, or optionally 50℃-70℃.

[0032] Furthermore, the reaction time of the chlorination reaction is 0.5h-48h; optionally, it is 1h-12h; optionally, it is 3h-12h.

[0033] Beneficial effects

[0034] (1) The present invention uses catalyst A and catalyst B together to carry out dichlorination. The catalyst is inexpensive, the raw materials are readily available, and it has little environmental impact. During the research and development, the inventors found that using catalyst B can improve the reaction yield and product purity. Continuous research revealed that trace amounts of water in the reaction system or environment can lead to side reactions and the loss of F groups, affecting the reaction yield. By using catalyst B, which can react with water, to thoroughly remove water, side reactions and the loss of F groups can be effectively reduced, enabling the reaction yield to reach 98%. After solvent removal and filtration, the product purity can reach over 97%, which can be directly used for subsequent reactions, improving the yield and quality of subsequent reactions and greatly increasing production capacity.

[0035] (2) The catalyst of the present invention is inexpensive, environmentally friendly, does not need to be prepared separately, can be added separately, is simple to operate, and is conducive to industrialization.

[0036] (3) The dichlorination of the present invention uses an aprotic solvent, the reaction conditions are mild, the solvent is easy to recover, the reaction yield is high, and it is easy to industrialize. Detailed Implementation

[0037] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0038] Furthermore, to better illustrate the present invention, numerous specific details are provided in the following detailed embodiments. Those skilled in the art should understand that the present invention can be practiced without certain specific details. In some embodiments, materials, methods, means, etc., well-known to those skilled in the art, are not described in detail in order to highlight the spirit of the present invention.

[0039] Unless otherwise expressly stated, throughout the specification and claims, the term "comprising" or its variations such as "including" or "comprises" shall be understood to include the stated elements or components without excluding other elements or other components.

[0040] The product content in the following examples was confirmed by liquid chromatography or gas chromatography, the reaction process was tracked using the area normalization method, and the purity and yield were calculated using the external standard method.

[0041] The 1-(4-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one, 1-(2-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one, 1-(4-chlorophenyl)-3-methyl-4-hydro-1,2,4-triazol-5-one, and 1-(2-chlorophenyl)-3-methyl-4-hydro-1,2,4-triazol-5-one in the following examples are commercially available.

[0042] The synthetic route for 1-(2,4-dichlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one can be as follows:

[0043]

[0044] Example 1

[0045] 40g of 1-(4-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of 1,1-dichloroethane, 0.2g of Fe powder, and 0.3g of PCl3 were added to the flask. The mixture was heated to 70℃, and 1.2 eq of Cl2 was introduced. After reacting for 5 hours, a sample was taken to test the reaction. After the reaction was completed, water was added to remove the solvent, the mixture was filtered, dried, and tested. The conversion rate was 99.9%, the solid mass of the product was 45.77g, the purity was 97.2%, and the yield was 98.2%.

[0046] Example 2

[0047] 40g of 1-(4-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of 1,2-dichloroethane, 0.2g of Fe powder, and 0.3g of trimethylchlorosilane were added to the flask. The mixture was heated to 70℃, and 1.2 eq of Cl2 was introduced. After 5 hours of reaction, a sample was taken to test the reaction. After the reaction was completed, water was added to remove the solvent, the mixture was filtered, dried, and tested. The conversion rate was 99.9%, the product solid mass was 45.40g, the purity was 97.8%, and the yield was 98.0%.

[0048] Example 3

[0049] 40g of 1-(4-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of 1,2-dichloroethane, 0.25g of FeCl2, and 0.4g of PCl5 were added to the flask. The mixture was heated to 70℃, and 1.2 eq of Cl2 was bubbled through it. After 5 hours of reaction, a sample was taken to test for complete reaction. After desolvation with water, filtration, and drying, the conversion rate was 99.9%, the product solid mass was 45.8g, the purity was 97.0%, and the yield was 98.1%.

[0050] Example 4

[0051] 40g of 1-(4-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of 1,2-dichloroethane, 0.2g of Zn powder, and 0.5g of trimethylchlorosilane were added to the flask. The mixture was heated to 70℃, and 1.2 eq of Cl2 was bubbled through it. After 6 hours of reaction, a sample was taken to test for complete reaction. After desolvation with water, filtration, and drying, the conversion rate was 99.9%, the product solid mass was 45.63g, the purity was 97.4%, and the yield was 98.1%.

[0052] Example 5

[0053] 40g of 1-(4-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of 1,2-dichloroethane, 0.2g of Fe powder, and 0.5g of SOCl2 were added to the flask. The mixture was heated to 70℃, and 1.2 eq of Cl2 was bubbled through it. After reacting for 6 hours, a sample was taken to test if the reaction was complete. After adding water to remove solvent, the mixture was filtered, dried, and tested. The conversion rate was 99.9%, the solid mass of the product was 45.44g, the purity was 97.7%, and the yield was 98.0%.

[0054] Example 6

[0055] 40g of 1-(4-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of 1,2-dichloroethane, a mixed catalyst of 0.1g Fe + 0.1g FeCl2, and 0.5g PCl3 were added to the flask. The mixture was heated to 70℃, and 1.2 eq Cl2 was introduced. After reacting for 5 hours, a sample was taken to test for complete reaction. After desolvation with water, filtration, and drying, the product yield was 99.9%, with a solid mass of 45.73g, a purity of 97.1%, and a yield of 98.0%.

[0056] Example 7

[0057] 40g of 1-(2-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of carbon tetrachloride, 0.5g of FeCl3 powder, and 0.5g of PCl3 were added to the flask. The mixture was heated to 70℃, and 1.2 eq of Cl2 was bubbled through it. After 5 hours of reaction, a sample was taken to test the reaction. After the reaction was complete, water was added to remove the solvent, the mixture was filtered, dried, and tested. The conversion rate was 99.9%, the solid mass of the product was 45.63g, the purity was 96.9%, and the yield was 97.6%.

[0058] Example 8

[0059] 40g of 1-(4-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of 1,2-dichloroethane, 0.2g of Fe powder, and 0.5g of acetic anhydride were added to the flask. The mixture was heated to 60℃, and 1.3 eq of Cl2 was bubbled through it. After 5 hours of reaction, a sample was taken to test the reaction. After the reaction was complete, water was added to remove the solvent, the mixture was filtered, dried, and tested. The conversion rate was 99.9%, the solid mass of the product was 45.73g, the purity was 97.2%, and the yield was 98.1%.

[0060] Example 9

[0061] 40g of 1-(4-chlorophenyl)-3-methyl-4-difluoromethyl-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of chloroform, 0.2g of Fe powder, 0.2g of acetic anhydride, and 0.3g of PCl3 were added to the flask. The mixture was heated to 70℃, and 1.2 eq of Cl2 was introduced. After reacting for 5 hours, a sample was taken to test the reaction. After the reaction was completed, water was added to remove the solvent, the mixture was filtered, dried, and tested. The conversion rate was 99.9%, the product solid mass was 45.87g, the content was 97.0%, and the yield was 98.2%.

[0062] The synthetic route for 1-(2,4-dichlorophenyl)-3-methyl-4-hydro-1,2,4-triazol-5-one can be as follows:

[0063]

[0064] Example 10

[0065] 40g of 1-(4-chlorophenyl)-3-methyl-4-hydro-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of 1,1-dichloroethane, 0.2g of Fe powder, and 0.3g of PCl3 were added to the flask. The mixture was heated to 60℃, and 1.2 eq of Cl2 was introduced. After reacting for 5 hours, a sample was taken to test the reaction. After the reaction was completed, water was added to remove the solvent, the mixture was filtered, dried, and tested. The conversion rate was 99.9%, the solid mass of the product was 46.96g, the purity was 97.2%, and the yield was 98.0%.

[0066] Example 11

[0067] 40g of 1-(2-chlorophenyl)-3-methyl-4-hydro-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of 1,2-dichloroethane, 0.2g of Fe powder, and 0.5g of trimethylchlorosilane were added to the flask. The mixture was heated to 60℃, and 1.2 eq of Cl2 was introduced. After 5 hours of reaction, a sample was taken for testing. After the reaction was complete, water was added to remove solvent, the mixture was filtered, dried, and tested. The conversion rate was 99.9%, the product solid mass was 46.96g, the purity was 97.1%, and the yield was 97.9%.

[0068] Example 12

[0069] 40g of 1-(4-chlorophenyl)-3-methyl-4-hydro-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of 1,2-dichloroethane, a mixed catalyst of 0.1g Fe + 0.2g FeCl2, and 0.5g PCl3 were added to the flask. The mixture was heated to 70℃, and 1.2 eq Cl2 was introduced. After reacting for 5 hours, a sample was taken to test for complete reaction. Water was added to remove solvent, the mixture was filtered, dried, and tested. The conversion rate was 99.9%, the product solid mass was 46.96g, the purity was 97.3%, and the yield was 98.1%.

[0070] Example 13

[0071] 40g of 1-(4-chlorophenyl)-3-methyl-4-hydro-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of 1,2-dichloroethane, 0.2g of Fe powder, and 0.5g of acetic anhydride were added to the flask. The mixture was heated to 70℃, and 1.2 eq of Cl2 was bubbled through it. After 6 hours, a sample was taken to test the reaction. After the reaction was complete, water was added to remove the solvent, the mixture was filtered, dried, and tested. The conversion rate was 99.99%, the solid mass of the product was 46.91g, the purity was 97.5%, and the yield was 98.2%.

[0072] Example 14

[0073] 40g of 1-(4-chlorophenyl)-3-methyl-4-hydro-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of 1,2-dichloroethane, 0.2g of Fe powder, and 0.5g of SOCl2 were added to the flask. The mixture was heated to 70℃, and 1.2 eq of Cl2 was bubbled through it. After reacting for 6 hours, a sample was taken to test if the reaction was complete. After adding water to remove solvent, the mixture was filtered, dried, and tested. The conversion rate was 99.9%, the product solid mass was 47.05g, the purity was 96.9%, and the yield was 97.9%.

[0074] Example 15

[0075] 40g of 1-(4-chlorophenyl)-3-methyl-4-hydro-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of chlorobenzene, 0.2g of FeCl2, 0.2g of acetic anhydride, and 0.3g of PCl3 were added to the flask. The mixture was heated to 70℃, and 1.2 eq of Cl2 was bubbled through it. After reacting for 6 hours, a sample was taken to test if the reaction was complete. After adding water to remove the solvent, the mixture was filtered, dried, and tested. The conversion rate was 99.9%, the product solid mass was 46.91g, the content was 97.3%, and the yield was 98.0%.

[0076] Example 16

[0077] 40g of 1-(4-chlorophenyl)-3-methyl-4-hydro-1,2,4-triazol-5-one was added to a four-necked flask equipped with a stirrer and a thermometer. 200g of carbon tetrachloride, 0.2g of FeCl2, and 0.5g of PCl3 were added to the flask. The mixture was heated to 50℃, and 1.2 eq of Cl2 was bubbled through it. After reacting for 6 hours, a sample was taken to test the reaction. After the reaction was complete, water was added to remove the solvent, the mixture was filtered, dried, and tested. The conversion rate was 99.9%, the solid mass of the product was 46.57g, the purity was 97.8%, and the yield was 97.8%.

[0078] The products from Examples 1-16 above, after solvent removal and filtration, achieve a purity of over 97%, and can be directly used in subsequent reactions to improve the yield and quality of those reactions.

[0079] Comparative Example 1

[0080] The difference from Example 1 is that no catalyst Fe powder and PCl3 were added, the conversion rate was 96%, the product solid mass was 46.60 g, the content was 70%, and the yield was 75%. Although Comparative Example 1 had a higher conversion rate, it produced more side reactions, the product purity was insufficient, the yield was low, and more purification steps were required.

[0081] Comparative Example 2

[0082] The difference from Example 1 is that no catalyst PCl3 was added, resulting in a conversion rate of 99.9%, a product solid mass of 46.62 g, a content of 89.5%, and a yield of 92.1%. In Comparative Example 2, the absence of catalyst B, which effectively removes water, leads to more side reactions, resulting in lower product purity and yield, significantly impacting subsequent reactions.

[0083] Comparative Example 3

[0084] The difference from Example 7 is that PCl3 was replaced with silicon dioxide, resulting in a conversion rate of 99.9%, a product solid mass of 46.50 g, a content of 91.2%, and a yield of 93.6%. While the purity and yield of this comparative example are somewhat improved compared to Comparative Example 2, the yield is still not ideal. The inventors believe that the physical adsorption of water by silicon dioxide, and the existence of an adsorption-desorption equilibrium during the chlorination process, makes it difficult to further improve the purity and yield.

[0085] Comparative Example 4

[0086] The difference from Example 7 is that PCl3 was replaced with antimony trichloride, the conversion rate was 99.9%, the product solid mass was 46.05g, the content was 91.3%, and the yield was 92.8%.

[0087] Comparative Example 5

[0088] The difference from Example 1 is that PCl3 was replaced with anhydrous magnesium sulfate, the conversion rate was 99.9%, the product solid mass was 46.34 g, the content was 92.0%, and the yield was 94.1%.

[0089] Comparative Example 6

[0090] The difference from Example 1 is that PCl3 was replaced with 4A molecular sieve, the conversion rate was 99.9%, the product solid mass was 46.29g, the content was 92.2%, and the yield was 94.2%.

[0091] The purity (content) of the products after distillation and filtration in the above comparative examples 1 to 6 was less than 92.5%. Products with this level of purity are not conducive to subsequent reactions and require further purification before they can be used in subsequent reactions, which greatly reduces production efficiency.

[0092] The inventors discovered that although adding other catalysts to catalyst A, such as silica, antimony trichloride, anhydrous magnesium sulfate, and 4A molecular sieve (component ratios 3-5), could slightly improve the yield and purity, the effect was not significant, and further purification was still required for subsequent reactions. Through continuous research and summarization, it was found that this might be because such catalysts could not effectively remove trace amounts of water in the reaction system, leading to side reactions and the loss of F groups. Further research revealed that by using catalyst B, which can react with water, to thoroughly remove water, side reactions and the loss of F groups could be effectively reduced, enabling the reaction yield to reach 98% and the product purity to reach over 97%. This not only allows for direct subsequent reactions but also facilitates subsequent reactions, greatly improving production capacity.

[0093] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for synthesizing a mesotrione intermediate, comprising chlorinating the compound of formula II in the presence of a solvent by adding a composite catalyst to synthesize the compound of formula I, wherein, The composite catalyst is selected from catalyst A and catalyst B in a weight ratio of 1:1 to 2.5; catalyst B is a compound that can react with water to remove water from the reaction system. ； In Equation I, X and Y are each independently H or Cl, and X and Y are not simultaneously H or Cl; In Formula I and Formula II, R is H or difluoromethyl; The amount of catalyst A added is 0.1%-5% of compound II; The catalyst A is selected from one or more of Fe, FeCl2, FeCl3, Zn, ZnCl2, Al, and AlCl3; The catalyst B is selected from one or more of phosphorus trichloride, phosphorus pentachloride, acetic anhydride, propionic anhydride, acetyl chloride, oxaloyl chloride, propionyl chloride, SOCl2, SO2Cl2, trimethylchlorosilane, trimethylbromosilane, trimethyliodosilane, dimethyldichlorosilane, and dimethylmonochlorosilane.

2. The synthesis method according to claim 1, characterized in that, The catalyst A is selected from metals and metal chlorides in a weight ratio of 1:0 to 1:10; The metal is selected from one or more of Fe, Zn, and Al, and the metal chloride is selected from FeCl2, FeCl3, ZnCl2, and AlCl3.

3. The synthesis method according to claim 1, characterized in that, The catalyst A is selected from metals and metal chlorides in a weight ratio of 0:1 to 10:1; The metal is selected from one or more of Fe, Zn, and Al, and the metal chloride is selected from FeCl2, FeCl3, ZnCl2, and AlCl3.

4. The synthesis method according to claim 2, characterized in that, In catalyst A, the weight ratio of metal to metal chloride is 1:0 to 1:

5.

5. The synthesis method according to claim 2, characterized in that, In catalyst A, the weight ratio of metal to metal chloride is 1:0.5 to 1:

5.

6. The synthesis method according to claim 2, characterized in that, In catalyst A, the weight ratio of metal to metal chloride is 1:0.5 to 1:

2.

7. The synthesis method according to claim 2, characterized in that, In catalyst A, the weight ratio of metal to metal chloride is 1:1 to 1:

2.

8. The synthesis method according to claim 2, characterized in that, In catalyst A, the weight ratio of metal to metal chloride is 1:

1.

9. The synthesis method according to claim 2, characterized in that, In catalyst A, the weight ratio of metal to metal chloride is 1:

2.

10. The synthesis method according to claim 1, characterized in that, The catalyst A is selected from one or more of Fe, Zn, FeCl2 and FeCl3.

11. The synthesis method according to claim 1, characterized in that, The amount of catalyst A added is 0.1% to 4% of compound II.

12. The synthesis method according to claim 1, characterized in that, The amount of catalyst A added is 0.1% to 2.5% of compound II.

13. The synthesis method according to claim 1, characterized in that, The amount of catalyst A added is 0.1% to 2% of compound II.

14. The synthesis method according to claim 1, characterized in that, The amount of catalyst A added is 0.5% to 2% of compound II.

15. The synthesis method according to claim 1, characterized in that, The amount of catalyst A added is 0.5% to 1% of compound II.

16. The synthesis method according to claim 1, characterized in that, The amount of catalyst A added is 0.5% to 0.75% of compound II.

17. The synthesis method according to any one of claims 1 to 16, characterized in that, The catalyst B is selected from one or more of phosphorus trichloride, phosphorus pentachloride, acetic anhydride, acetyl chloride, SOCl2, SO2Cl2, and trimethylchlorosilane.

18. The synthesis method according to any one of claims 1 to 16, characterized in that, The amount of catalyst B added is 0.1%-10% of compound II.

19. The synthesis method according to any one of claims 1 to 16, characterized in that, The amount of catalyst B added is 0.5%-2% of compound II.

20. The synthesis method according to any one of claims 1 to 16, characterized in that, The amount of catalyst B added is 0.5%-1.25% of compound II.

21. The synthesis method according to any one of claims 1 to 16, characterized in that, The amount of catalyst B added is 0.75% to 1.25% of compound II.

22. The synthesis method according to any one of claims 1 to 16, characterized in that, In the chlorination reaction, the chlorinating agents used include one or more of chlorine gas, sulfonyl chloride, PCl3, and PCl5.

23. The synthesis method according to any one of claims 1 to 16, characterized in that, In the chlorination reaction, chlorine gas is used as the chlorinating agent.

24. The synthesis method according to any one of claims 1 to 16, characterized in that, The solvent is one or more of chlorobenzene, dichlorobenzene, 1,2-dichloroethane, 1,2-dibromoethane, 1,1-dibromoethane, 1,1-dichloroethane, chloroform, carbon tetrachloride, acetonitrile, dichloromethane, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and acetic acid.

25. The synthesis method according to any one of claims 1 to 16, characterized in that, The solvent is a chlorinated alkane.

26. The synthesis method according to claim 25, characterized in that, Chlorinated alkanes include one or more of chlorobenzene, chloroform, 1,1-dichloroethane, 1,2-dichloroethane, and carbon tetrachloride.

27. The synthesis method according to any one of claims 1 to 16, characterized in that, The chlorination reaction is carried out at a temperature of 20℃-150℃.

28. The synthesis method according to any one of claims 1 to 16, characterized in that, The chlorination reaction is carried out at a temperature of 30℃-90℃.

29. The synthesis method according to any one of claims 1 to 16, characterized in that, The chlorination reaction is carried out at a temperature of 50℃-75℃.

30. The synthesis method according to any one of claims 1 to 16, characterized in that, The chlorination reaction is carried out at a temperature of 50℃-70℃.

31. The synthesis method according to any one of claims 1 to 16, characterized in that, The chlorination reaction takes 0.5 h to 48 h.

32. The synthesis method according to any one of claims 1 to 16, characterized in that, The chlorination reaction takes 1-12 hours.

33. The synthesis method according to any one of claims 1 to 16, characterized in that, The chlorination reaction takes 3-12 hours.

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