A method for preparing a sulfonylurea

Abstract

The present application relates to a preparation method of cyprosulfamide, and the cyprosulfamide is prepared by using a one-pot method, and the method specifically comprises the following steps: adding an organic base, a reaction solvent, 2-chloro-3-(2,2,2-trifluoroethoxy)methyl-4-methylsulfonylbenzoic acid and a Curtius condensing agent into a reaction container, heating and refluxing for 3-5 h to generate an active ester intermediate; after the reaction solution containing the active ester intermediate is cooled, 1,3-cyclohexanedione and acetone cyanohydrin are added to perform a condensation rearrangement reaction, and cyprosulfamide is generated. The one-pot synthesis process is adopted, the use of dimethyl sulfoxide is avoided, compared with a traditional process, the method is green, environmentally friendly, has low safety risks, has high yield and good purity, and is more suitable for industrialized production.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of organic compound preparation, and particularly relates to a preparation method of tembotrione. BACKGROUND

[0002] Tembotrione is a triketone HPPD inhibitor herbicide. HPPD inhibitor herbicides have the characteristics of high activity, low residue, safety to mammals and environmental friendliness, and have become a hot product in the corn herbicide market.

[0003] At present, the preparation of tembotrione mainly has the following methods: 1. As shown in the Chinese patent with the publication number CN1323292A, first, 2-chloro-3-cyclohexyloxy methyl-4-methylsulfonylbenzoic acid is treated with oxalyl chloride, and finally, tembotrione is prepared with acetone cyanohydrin; the oxalyl chloride used in the preparation process has high toxicity and strong corrosion, which is harmful to human health, is easy to cause safety hazards, and the by-product hydrogen chloride of the process pollutes the environment more. 2. As shown in the Chinese patent with the publication number CN109678767A, first, 2-chloro-3-(2,2,2-trifluoroethoxy) methyl-4-methylsulfonylbenzoic acid is reacted with thionyl chloride as an acylating agent to generate 2-chloro-3-(2,2,2-trifluoroethoxy) methyl-4-methylsulfonylbenzoyl chloride, and then 1,3 cyclohexanedione and acetone cyanohydrin are subjected to condensation rearrangement reaction to obtain the target product tembotrione; this method is a more common industrialized method at present, but it still has the following problems: 1) thionyl chloride causes great disturbance to the environment and human health; 2) the acylation reaction and the condensation rearrangement reaction are carried out separately, the acylation kettle and the condensation rearrangement kettle need to be designed separately, the equipment cost is high, and the yield of the two-step reaction is low. SUMMARY

[0004] The purpose of the present application is to overcome the defects in the prior art, and provide a preparation method of tembotrione, which adopts a one-pot synthesis process, avoids the use of dimethyl sulfoxide, is green, environmentally friendly, safe, has high yield and good purity, and is more suitable for industrial production.

[0005] To achieve the above-mentioned purpose, the technical solutions adopted by the present application are as follows:

[0006] A preparation method of tembotrione, which adopts a one-pot synthesis process, and specifically includes the following steps:

[0007] An organic base, a reaction solvent, 2-chloro-3-(2,2,2-trifluoroethoxy) methyl-4-methylsulfonylbenzoic acid and a Curtius condensing agent are added into a reaction container, heated to reflux for 3-5 h to generate an active ester intermediate; after the reaction solution containing the active ester intermediate is cooled, 1,3 cyclohexanedione and acetone cyanohydrin are added to carry out condensation rearrangement reaction to generate tembotrione.

[0008] As a further technical solution, in the heating reflux process, 2-chloro-3-(2,2,2-trifluoroethoxy) methyl-4-methylsulfonyl benzoic acid is first reacted with the Curtius condensing agent to form the corresponding acyloxy phosphonium positive ion, and then the active ester intermediate is formed by the attack of benzotriazole oxy.

[0009] As a further technical solution, the organic base is triethylamine or triethylene diamine.

[0010] The reaction solvent uses one or more of 1,2 dichloroethane, sec-butyl acetate, and xylene.

[0011] As a further technical solution, the molar ratio of 2-chloro-3-(2,2,2-trifluoroethoxy) methyl-4-methylsulfonyl benzoic acid, organic base, and Curtius condensing agent is 1:(1.5-2.5):(1.1-2.0).

[0012] As a further technical solution, the temperature of the heating reflux reaction is 75-85℃.

[0013] As a further technical solution, the molar ratio of 2-chloro-3-(2,2,2-trifluoroethoxy) methyl-4-methylsulfonyl benzoic acid, 1,3-cyclohexanedione, and acetone cyanohydrin is 1:(1.0-1.1):(0.01-0.03).

[0014] As a further technical solution, the temperature of the condensation rearrangement reaction is 30-40℃, and the time is 1-5 hours, preferably 2h, 3h, or 4h.

[0015] As a further technical solution, the molar ratio of 2-chloro-3-(2,2,2-trifluoroethoxy) methyl-4-methylsulfonyl benzoic acid, organic base, Curtius condensing agent, 1,3-cyclohexanedione, and acetone cyanohydrin is 1:(1.5-2.5):(1.1-2.0):(1.0-1.1):(0.01-0.03), first add 2-chloro-3-(2,2,2-trifluoroethoxy) methyl-4-methylsulfonyl benzoic acid, 1,2 dichloroethane, Curtius condensing agent, and triethylamine to a 50L four-necked flask, heat to 80℃ in a water bath (about 30min), then reflux at 80℃ for 5h to form the active ester intermediate; after the active ester intermediate is cooled to room temperature, add (drop) 1,3-cyclohexanedione and acetone cyanohydrin; heat to 35℃ in a water bath (about 10min), and keep the temperature for 4h; after the reaction is completed, the reaction liquid is cooled to 20℃, and is ready for use.

[0016] As a further technical solution, after the condensation rearrangement reaction is completed, a post-treatment step is included,

[0017] The post-treatment comprises: after the reaction solution containing the metamifop is cooled, sequentially performing acidification, water washing, desolventizing, crystallization, suction filtration, and drying treatment to obtain the metamifop product.

[0018] As a further technical solution, the post-treatment comprises: after the reaction solution containing the metamifop is cooled, adding a dilute acid solution dropwise to pH 1, standing and separating into layers, retaining the organic phase, extracting the aqueous phase with a reaction solvent, then washing the combined organic phase with water, and then distilling at 70 DEG C under reduced pressure to 85 DEG C to obtain a concentrated solution; then adding a preheated crystallization solvent, stirring until uniform, naturally cooling to induce crystallization, continuing to cool to 10-15 DEG C after crystallization, then suction filtering the product, and drying the filtered product to obtain the metamifop product.

[0019] As a further technical solution, the crystallization solvent is one or more of methanol, ethanol, and isopropanol.

[0020] As a further technical solution, the amount of the crystallization solvent added is 2-4 times (preferably 3 times) the weight of the concentrated solution.

[0021] As a further technical solution, the dilute acid solution is a hydrochloric acid solution with a mass concentration of 10%.

[0022] As a further technical solution, during the reduced pressure distillation, when the solution volume is reduced to 25-35% (preferably 30%) of the original volume, an equal weight of water is added, and the distillation under reduced pressure is continued at 70 DEG C to 85 DEG C; the pressure during the distillation under reduced pressure before the addition of water is 0.08 MPa, and the pressure during the distillation under reduced pressure after the addition of water is 0.09 MPa.

[0023] As a further technical solution, the crystallization solvent is added in two steps: first, an amount of crystallization solvent equal to the volume of the concentrated solution is added after the completion of the reduced pressure distillation but before the breaking of the vacuum, and second, the remaining crystallization solvent is added while hot after the breaking of the vacuum.

[0024] As a further technical solution, the post-treatment comprises: after the reaction solution containing the metamifop is cooled, adding a dilute acid solution dropwise to pH 1, standing and separating into layers, retaining the organic phase, extracting the aqueous phase with a reaction solvent, then washing the combined organic phase with water, and then distilling at 70 DEG C under reduced pressure to 85 DEG C to obtain a concentrated solution; then adding a preheated crystallization solvent, stirring until uniform, naturally cooling to induce crystallization, continuing to cool to 10-15 DEG C after crystallization, then suction filtering the product, and drying the filtered product to obtain the metamifop product.

[0025] As a further technical solution, in the process of vacuum distillation, the pressure of vacuum distillation before adding water is 0.08 MPa, and the pressure of vacuum distillation after adding water is 0.09 MPa.

[0026] The synthetic route of the present application is:

[0027]

[0028] Compared with the prior art, the present application has the beneficial effects that:

[0029] 1. The present application first directly acts the Carter condensing agent on 2-chloro-3-(2,2,2-trifluoroethoxy) methyl-4-methylsulfonyl benzoic acid to form an active ester, and then condenses and rearranges the active ester with 1,3-cyclohexanedione to generate cyprosulfamide. Compared with the traditional process, it does not need to use dimethyl sulfoxide and other acylating reagents, which is friendly to equipment, personnel and environment on the one hand, and avoids the solvent removal operation in the intermediate process, so that the synthesis of cyprosulfamide can be completed in one reactor, simplifying the process steps and saving equipment cost.

[0030] 2. The present application strictly limits the type of condensing agent, the type of base, the reaction temperature and the reaction form, ensures that the chemical reaction with active ester as the intermediate state can proceed normally, greatly improves the reaction yield and reduces the probability of side reactions.

[0031] 3. In the post-treatment step, water is added in the process of vacuum distillation to reduce the viscosity of the concentrated liquid, which can prevent the material from solidifying during the desolventization process and cause the problem of subsequent resolubilization difficulty; and after vacuum distillation, the methanol is divided into two parts and added before and after the vacuum is broken, which can reduce the loss of solvent, thereby achieving the purpose of saving materials and reducing cost.

[0032] The present application adopts one-pot synthesis process, avoids the use of dimethyl sulfoxide, and compared with the traditional process, it is green, environmentally friendly, low in safety risk, high in yield and good in purity, and more suitable for industrial production. DETAILED DESCRIPTION

[0033] The technical solutions of the present application will be described below in conjunction with specific embodiments. Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0034] The raw materials used in the present application are commercially available.

[0035] Example 1

[0036] A preparation method of CS, which is carried out by one-pot method, specifically comprising the following steps:

[0037] Step 1, synthesis:

[0038] A 50L four-necked flask is added with 2-chloro-3-(2,2,2-trifluoroethoxy) methyl-4-methylsulfonyl benzoic acid 6.7kg, 1,2 dichloroethane 30kg, Cart condensing agent 12.82kg, triethylamine 4.9kg, and heated to 80℃ in water bath (about 30min for heating), then refluxed at 80℃ for 5h to generate active ester intermediate; after the active ester intermediate is cooled to room temperature, 1,3 cyclohexanedione 2.28kg and acetone cyanohydrin 0.08kg are added (dropwise); heated to 35℃ in water bath (about 10min for heating), and kept for 4h for reaction; after the reaction is completed, the reaction solution is cooled to 20℃;

[0039] Step 2, post-treatment:

[0040] To the reaction solution cooled to 20℃, 10% hydrochloric acid solution is added dropwise until pH = 1 (1.54eq), and then separated into layers after standing; the aqueous phase is extracted with 1,2 dichloroethane, and the combined organic phase is washed with water once, and then distilled at 70℃ under reduced pressure; when the volume of the solution is reduced to 30% of the original volume by distillation under reduced pressure, a sticky substance can be observed by naked eye; at this time, an equal weight of water is added, and a dropping funnel containing 6.7kg of methanol is installed on the four-necked flask, and then the distillation under reduced pressure is continued at 70℃ until 85℃ to obtain a concentrated solution; during the distillation under reduced pressure, the pressure is 0.08MPa before adding water, and the pressure is 0.09MPa after adding water; after the distillation under reduced pressure is completed, there is no wall sticking phenomenon; before breaking the vacuum, the methanol in the dropping funnel is added to the concentrated solution, and then after breaking the vacuum, 13.4kg of preheated methanol at 50℃ is added, and stirred for 1h until uniform, and then naturally cooled to precipitate crystals; after the precipitation, the temperature is continuously lowered to 10-15℃, and the material is filtered out by suction filtration, and dried at 70℃ to obtain white solid, which is CS product 8.01kg with content of 98.7% and yield of 92.8%.

[0041] Example 2

[0042] A preparation method of CS, which is carried out by one-pot method, specifically comprising the following steps:

[0043] Step 1, synthesis:

[0044] To 50L four-port flask, add 2-chloro-3-(2,2,2-trifluoroethoxy) methyl-4-methylsulfonylbenzoic acid 6.7 kg, 1,2 dichloroethane 30 kg, carter condensing agent 14.1 kg (31.88 mol), triethylamine 4.9 kg, heat to 80 °C in water bath (about 30 min for heating), then reflux at 80 °C for 5 h to generate active ester intermediate; after the active ester intermediate is cooled to room temperature, add (drop) 1,3 cyclohexanedione 2.28 kg and acetone cyanohydrin 0.08 kg; heat to 35 °C in water bath (about 10 min for heating), and keep the temperature for 4 h; after the reaction is completed, cool the reaction solution to 20 °C;

[0045] Step 2, post-treatment:

[0046] To the reaction solution cooled to 20 °C, drop 10% hydrochloric acid solution to pH = 1 (1.54 eq), stand and separate, extract the aqueous phase with 1,2 dichloroethane, combine the organic phases, wash with water once, then distill under reduced pressure at 70 °C, when the volume of the solution is 30% of the original volume, a sticky mass can be seen with the naked eye, at this time, add an equal weight of water, and install a drop funnel containing 6.7 kg of methanol on the four-port flask, then continue to distill under reduced pressure at 70 °C, to 85 °C, to obtain a concentrated solution; during the distillation under reduced pressure, the pressure is 0.08 MPa before adding water, and the pressure is 0.09 MPa after adding water, when the distillation under reduced pressure is completed, there is no wall sticking phenomenon, before breaking the vacuum, add the methanol in the drop funnel to the concentrated solution, then break the vacuum, and then add 13.4 kg of preheated 50 °C methanol, stir for 1 h until uniform, then naturally cool to precipitate crystals, continue to cool to 10-15 °C after precipitation, filter out the material, and dry at 70 °C to obtain white solid, which is the finished product of metrafenone 8.15 kg, with a content of 98.3% and a yield of 94.1%.

[0047] Example 3

[0048] A method for preparing metrafenone, which is carried out by one-pot method, specifically comprising the following steps:

[0049] Step 1, synthesis:

[0050] To 50L four-port flask, add 2-chloro-3-(2,2,2-trifluoroethoxy) methyl-4-methylsulfonylbenzoic acid 6.7 kg, 1,2 dichloroethane 30 kg, carter condensing agent 14.1 kg (31.88 mol), triethylamine 4.9 kg, heat to 80 °C in water bath (about 30 min for heating), then reflux at 80 °C for 5 h to generate active ester intermediate; after the active ester intermediate is cooled to room temperature, add (drop) 1,3 cyclohexanedione 2.28 kg and acetone cyanohydrin 0.08 kg; heat to 35 °C in water bath (about 10 min for heating), and keep the temperature for 4 h; after the reaction is completed, cool the reaction solution to 20 °C;

[0051] Step 2, post-treatment:

[0052] To the reaction solution cooled to 20°C, add dropwise a 10% hydrochloric acid solution to pH = 1 (1.54 eq), stand and separate, extract the aqueous phase with sec-butyl acetate, combine the organic phases, wash with water once, then distill under reduced pressure at 70°C, when the volume of the solution is reduced to 30% of the original volume, a sticky mass is visible to the naked eye, at this time, add an equal weight of water, and install a dropping funnel containing 6.7 kg of methanol on the four-necked flask, then continue to distill under reduced pressure at 70°C to 85°C to obtain a concentrated solution; during the distillation under reduced pressure, the pressure is 0.08 MPa before adding water, and the pressure is 0.09 MPa after adding water, when the distillation under reduced pressure is complete, there is no wall sticking phenomenon, before breaking the vacuum, add the methanol in the dropping funnel to the concentrated solution, then break the vacuum, and then add 13.4 kg of L preheated to 50°C, stir for 1 h until uniform, then naturally cool to 10-15°C, filter the material, and dry at 70°C to obtain a white solid, which is the finished product of metrafenone 7.88 kg, content 97.5%, yield 90.16%.

[0053] Example 4

[0054] A method for preparing metrafenone, which is carried out by one-pot method, specifically comprising the following steps:

[0055] Step 1, synthesis:

[0056] Into a 50 L four-necked flask, add 2-chloro-3-(2,2,2-trifluoroethoxy)methyl-4- methylsulfonylbenzoic acid 6.7 kg, 1,2 dichloroethane 30 kg, Cat condensing agent 14.1 kg (31.88 mol), and triethylenediamine 7.4 kg (65.9 mol), heat to 80°C in a water bath (about 30 min for heating), then reflux at 80°C for 5 h to generate an active ester intermediate; after cooling the active ester intermediate to room temperature, add (dropwise) 1,3 cyclohexanedione 2.28 kg and acetone cyanohydrin 0.08 kg; heat to 35°C in a water bath (about 10 min for heating), and keep the temperature for 4 h; after the reaction is completed, cool the reaction solution to 20°C;

[0057] Step 2, post-treatment:

[0058] To the reaction solution cooled to 20℃, add 10% hydrochloric acid solution dropwise to pH = 1 (1.54 eq), stand and separate, extract the aqueous phase with 1,2 dichloroethane, combine the organic phases, wash with water once, then distill under reduced pressure at 70℃, when the volume of the solution is reduced to 30% of the original volume, a sticky mass is visible to the naked eye, at this point, add an equal weight of water, and install a dropping funnel containing 6.7 kg of methanol on the four-necked flask, then continue to distill under reduced pressure at 70℃, to 85℃, to obtain a concentrated solution; during the distillation under reduced pressure, the pressure is 0.08 MPa before adding water, and the pressure is 0.09 MPa after adding water, when the distillation under reduced pressure is complete, there is no wall sticking phenomenon at this point, before breaking the vacuum, add the methanol in the dropping funnel to the concentrated solution, then break the vacuum, and then add 13.4 kg of preheated 50℃ methanol, stir for 1 h until uniform, then naturally cool to 10-15℃, filter the material, and dry at 70℃ to obtain a white solid, which is the finished product of metrafenone 8.2 kg, content 97.6%, yield 93.9%.

[0059] Comparative Example 1

[0060] A method for preparing metrafenone, which is carried out by one-pot method, specifically comprising the following steps:

[0061] Step 1, synthesis:

[0062] Into a 50 L four-necked flask, add 2-chloro-3-(2,2,2-trifluoroethoxy)methyl-4- methylsulfonylbenzoic acid 6.7 kg, 1,2 dichloroethane 30 kg, Cat condensing agent 12.85 kg (29 mol), sodium carbonate 3.59 kg (26 mol), heat to 80℃ in water bath (about 30 min for heating), then reflux at 80℃ for 5 h to generate an active ester intermediate; after the active ester intermediate is cooled to room temperature, add (drop) 1,3 cyclohexanedione 2.31 kg and acetone cyanohydrin 0.08 kg; heat to 35℃ in water bath (about 10 min for heating), and keep the temperature for 4 h to generate metrafenone, after the reaction is completed, cool the reaction solution to 20℃;

[0063] Step 2, post-treatment: same as Example 1;

[0064] The finished product of metrafenone prepared in this comparative example is 7.2 kg, content 96.2%, yield 81.3%.

[0065] Comparative Example 2

[0066] A method for preparing metrafenone, which is carried out by one-pot method, specifically comprising the following steps:

[0067] Step 1, synthesis:

[0068] Into a 50L four-necked flask, add 2-chloro-3-(2, 2, 2-trifluoroethoxy) methyl-4- methylsulfonylbenzoic acid 6.7kg, 1, 2 dichloroethane 30kg, HBTU condensing agent 10.9kg, triethylamine 4.9kg, heat to 80℃ (heat for about 30min) in water bath, then reflux at 80℃ for 5h, then cool to room temperature, add (dropwise) 1, 3 cyclohexanedione 2.29kg and acetone cyanohydrin 0.08kg; after dropwise addition, the reaction solution is dark yellow turbid liquid, heat to 35℃ (heat for about 10min) in water bath, then keep at this temperature for 4h, the color of the reaction solution turns to bright yellow at the later stage, after reaction, cool the reaction solution to 20℃;

[0069] Step 2, post-treatment: same as example 1;

[0070] The comparative example 1 obtains 7.1kg of final product of mesotrione, with a content of 96.3% and a yield of 80.3%.

[0071] Comparative example 3

[0072] A method for preparing mesotrione, which is carried out by one-pot method, specifically comprising the following steps:

[0073] Step 1, synthesis:

[0074] Into a 50L four-necked flask, add 2-chloro-3-(2, 2, 2-trifluoroethoxy) methyl-4- methylsulfonylbenzoic acid 6.7kg, 1, 2 dichloroethane 30kg, CDI condensing agent 4.7kg, triethylamine 4.9kg, heat to 80℃ (heat for about 30min) in water bath, then reflux at 80℃ for 5h, then control the quality of the reaction solution, no active ester intermediate is generated, cool to room temperature, add (dropwise) 1, 3 cyclohexanedione 2.29kg and acetone cyanohydrin 0.08kg, after dropwise addition, heat to 35℃ (heat for about 10min) in water bath, then keep at this temperature for 6h, after reaction, mesotrione is generated, then cool the reaction solution to 20℃;

[0075] Step 2, post-treatment: same as example 1;

[0076] The comparative example 1 obtains 7.1kg of final product of mesotrione, with a content of 96.3% and a yield of 80.3%.

[0077] Comparative example 4

[0078] A method for preparing mesotrione, which is carried out by one-pot method, specifically comprising the following steps:

[0079] Step 1, synthesis:

[0080] Into a 50L four-necked flask was added 2-chloro-3-(2,2,2-trifluoroethoxy)methyl-4- methanesulfonylbenzoic acid 6.7 kg, 1,2 dichloroethane 30 kg, at 12 ℃ added cat's condensing agent 12.85 kg, triethylamine 4.9 kg, stirred for 15 h, after cooling to room temperature, added (dropwise) 1,3 cyclohexanedione 2.31 kg and acetone cyanohydrin 0.08 kg; water bath heating to 35 ℃ (heating for about 10 min), incubated for 4 h, the reaction was completed, the product cyclosulfamide was generated, the reaction solution was cooled to 20 ℃;

[0081] Step 2, post-processing: the same as example 1;

[0082] The cyclosulfamide product prepared in this comparative example was 7.7 kg, with a content of 85.2% and a yield of 77.0%.

[0083] Comparative example 5

[0084] A method for preparing cyclosulfamide, which is carried out by one-pot method, specifically comprising the following steps:

[0085] Step 1, synthesis: into a 50L four-necked flask was added 2-chloro-3-(2,2,2-trifluoroethoxy)methyl-4- methanesulfonylbenzoic acid 6.7 kg, 1,2 dichloroethane 30 kg, then at 12 ℃ added cat's condensing agent 12.85 kg, triethylamine 4.9 kg, 1,3 cyclohexanedione 2.31 kg and acetone cyanohydrin 0.08 kg, stirred for 15 h, to generate cyclosulfamide, after the reaction was completed, the reaction solution was ready for use;

[0086] Step 2, post-processing: the same as example 1;

[0087] The cyclosulfamide product prepared in this comparative example was 5.1 kg, with a content of 80.3% and a yield of 48.1%.

[0088] Comparative example 6

[0089] A method for preparing cyclosulfamide, specifically comprising the following steps:

[0090] Step 1, synthesis: into a 50L reaction flask was added 2-chloro-3-(2,2,2-trifluoroethoxy)methyl-4- methanesulfonylbenzoic acid 6.7 kg, 0.1 kg of DMF, 4.09 kg of thionyl chloride, and 25 kg of 1,2 dichloroethane was heated to reflux, after the reaction was completed, the solvent was removed by transferring to another reaction flask, then 2.32 kg of 1,3-cyclohexanedione, 30 kg of dichloroethane, 4.9 kg of triethylamine was added dropwise at 25-30 ℃, stirred for 8 h, after the reaction was completed, 0.08 kg of acetone cyanohydrin was added, and the stirring reaction was continued for 6 h, after the reaction was completed, the reaction solution was cooled to 20 ℃, and was ready for use;

[0091] Step 2, post-processing: the same as example 1;

[0092] The comparative example prepared 7.1 kg of final product of tembotrione, with a content of 97.1%, and a yield of 81%.

[0093] The above-described embodiments are merely preferred examples of the present application and are not intended to exhaustively enumerate all possible implementations of the present application. Any obvious modifications made by those skilled in the art without departing from the principles and spirit of the present application should be considered to be within the scope of the claims of the present application.

Claims

1. A method for preparing cyclic sulfonone, characterized in that, The one-pot method for preparing cyclic sulfonones includes the following steps: An organic base, a reaction solvent, 2-chloro-3-(2,2,2-trifluoroethoxy)methyl-4-methanesulfonylbenzoic acid and Carter's condensing agent are added to a reaction vessel and heated under reflux for 3-5 hours to generate an active ester intermediate. After the reaction solution containing the active ester intermediate is cooled, 1,3-cyclohexanedione and acetone cyanohydrin are added to carry out a condensation rearrangement reaction to generate a cyclosulfonone. The organic base is triethylamine or triethylenediamine; The temperature of the heating reflux reaction is 75~85℃; The condensation rearrangement reaction is carried out at a temperature of 30-40°C for 1-5 hours.

2. The method for preparing a cyclic sulfonone according to claim 1, characterized in that, The reaction solvent is one or more of 1,2-dichloroethane, sec-butyl acetate, and xylene.

3. The method for preparing a cyclic sulfonone according to claim 2, characterized in that, The molar ratio of 2-chloro-3-(2,2,2-trifluoroethoxy)methyl-4-methanesulfonylbenzoic acid, organic base, and Carter condensing agent is 1:(1.5~2.5):(1.1~2.0).

4. The method for preparing a cyclic sulfonone according to claim 1, characterized in that, The molar ratio of 2-chloro-3-(2,2,2-trifluoroethoxy)methyl-4-methanesulfonylbenzoic acid, 1,3-cyclohexanedione, and acetone cyanohydrin is 1:(1~1.1):(0.01~0.03).

5. The method for preparing a cyclic sulfonone according to claim 1, characterized in that, After the condensation rearrangement reaction is completed, post-processing steps are also included. The post-processing includes: cooling the reaction solution containing cyclosulfonone, followed by acidification, water washing, solvent removal, crystallization, filtration, and drying to obtain the cyclosulfonone product.

6. The method for preparing a cyclic sulfonone according to claim 5, characterized in that, The post-processing includes: cooling the reaction solution containing cyclosulfonone, adding dilute acid solution dropwise until the pH is 1, allowing it to stand and separate into layers, retaining the organic phase, extracting the aqueous phase with the reaction solvent, combining the organic phases and washing with water, then distilling under reduced pressure at 70°C to 85°C to obtain a concentrated solution, then adding a preheated crystallization solvent, stirring until uniform, allowing it to cool naturally to crystallize, continuing to cool to 10-15°C after crystallization, then filtering out the material, drying the filter material to obtain the cyclosulfonone product.

7. The method for preparing a cyclic sulfonone according to claim 6, characterized in that, The crystallization solvent is one or more of methanol, ethanol, and isopropanol; The amount of crystallization solvent added is 2-4 times the weight of the concentrate; The dilute acid solution used is a 10% hydrochloric acid solution.

8. The method for preparing a cyclic sulfonone according to claim 6, characterized in that, During vacuum distillation, when the solution volume is reduced to 25-35% of its original volume, an equal weight of water is added, and vacuum distillation continues at 70℃ to 85℃. The pressure of vacuum distillation before adding water is 0.08 MPa, and the pressure of vacuum distillation after adding water is 0.09 MPa.

9. The method for preparing a cyclic sulfonone according to claim 6, characterized in that, The crystallization solvent is added in two stages. The first stage is before the vacuum distillation is completed and the cavitation is broken, adding an amount of crystallization solvent equal to the volume of the concentrate. The second stage is after the cavitation is broken, while the remaining crystallization solvent, which has been preheated, is added while the solvent is still hot.

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