A method for synthesizing a pyroxasulfone intermediate

Abstract

This invention provides a method for synthesizing a sulfonylpyrazole intermediate, belonging to the field of herbicide intermediate preparation technology. The method includes a condensation reaction of glyoxylic acid and hydroxylamine to generate 2-(hydroxyimino)acetic acid, followed by a chlorobromination reaction of the 2-(hydroxyimino)acetic acid to generate a chlorobromination intermediate. The chlorobromination intermediate then reacts with isobutylene to generate a sulfonylpyrazole intermediate. The key feature is that the chlorobromination reaction is carried out in the presence of sodium bromide and chlorine. This invention can maintain a stable reaction environment while improving the yield and purity of the intermediate product.

Description

Technical Field

[0001] This invention relates to the field of herbicide intermediate preparation technology, specifically to a method for synthesizing a sulfopyrazole intermediate. Background Technology

[0002] Sulfonazole, chemically named 3-[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-ylmethylsulfonyl]-4,5-dihydro-5,5-dimethyl-1,2-isooxazole, has the molecular formula C12H14F5N3O4S, a molecular weight of 391.32, and CAS registry number 447399-55-5. Developed by Japan's Combinatorial Chemicals Co., Ltd., sulfonazole is an isoxazole herbicide used as a pre-emergence treatment in many crop fields. After application, it inhibits the growth of weed roots and shoots, thereby suppressing early seedling growth and damaging meristems and coleoptiles. It is an important potential inhibitor of VLCFA (very long side-chain fatty acids) biosynthesis in plants. Compared to acetochlor and metolachlor, sulfonazole has a wider range of applications, higher bioactivity, and its dosage per unit area is approximately nine times lower than that of acetochlor and chloroacetamide herbicides. The structural formula of sulfonylpyrazole is shown below:

[0003] 3-Bromo-5,5-dimethyl-4,5-dihydroisoxazole and 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole are important intermediates in the synthesis of sulfopyrazole.

[0004] The main existing method for preparing 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole is as follows: using glyoxylic acid as the starting material, it reacts with hydroxylamine to generate 2-(hydroxyimino)acetic acid, then obtains dibromoformaldehyde oxime through bromination, and finally reacts with isobutylene to generate 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole.

[0005] Different manufacturers use different reagents and reaction conditions when performing bromination reactions. Initially, pure liquid bromine was used with sodium bicarbonate or sodium bisulfite to produce dibromoformaldehyde oxime. For example, in the patent document with authorization announcement number CN113336716B, the background technology mentions that using liquid bromine and sodium bicarbonate for bromination produces insoluble impurities, resulting in unstable bromination reactions and low product purity. Furthermore, sodium bicarbonate produces carbon dioxide, which, as a gas, carries away a large amount of liquid bromine when it leaves the liquid reaction system, easily polluting the environment. Therefore, the solution in this patent document is to use sodium bisulfite for the reaction, which solves the problems of unstable reaction and gas carrying away liquid bromine. However, sodium bisulfite produces more by-salts after the reaction, reducing the yield and purity, and increasing the workload of waste treatment in the later stage.

[0006] To address the problem of excessive byproducts, relevant technicians have adopted a bromination reaction using sodium bromide and hydrogen peroxide to reduce the amount of byproducts. For example, in the patent application publication number CN114957233A, step 2 involves "adding sodium bromide and hydrogen peroxide to acetaldehyde oxime formic acid to obtain dibromoformaldehyde oxime." The reaction relies on the oxidation of the intermediate product NaBrO by hydrogen peroxide to form Br2, thereby releasing a quantitative amount of bromine and reducing the waste and consumption of liquid bromine. However, an excess of hydrogen peroxide is required for oxidation to reduce the presence of NaBrO in the product aqueous solution. As a result, the large amount of byproducts generated affects the purity of the subsequent separation of dibromoformaldehyde oxime, leading to poor reaction yield and product purity. Summary of the Invention

[0007] In view of this, the present invention provides a method for synthesizing sulfopyrazole intermediates, which can improve the yield and purity of intermediate products while maintaining a stable reaction environment.

[0008] This invention provides a method for synthesizing a sulfonylpyrazole intermediate, comprising a condensation reaction of glyoxylic acid and hydroxylamine to generate 2-(hydroxyimino)acetic acid, wherein the 2-(hydroxyimino)acetic acid undergoes a chlorobromination reaction to generate a chlorobromination intermediate, and the chlorobromination intermediate further reacts with isobutylene to generate a sulfonylpyrazole intermediate. The method is characterized in that the chlorobromination reaction is carried out in the presence of sodium bromide and chlorine.

[0009] The technical solution of this invention lies in the chlorobromination reaction of 2-(hydroxyimino)acetic acid, which involves both bromination and chlorination. The resulting chlorobromination intermediate is a mixture, which subsequently reacts with isobutylene to generate two sulfonylpyrazine intermediates. Existing technologies mostly use 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole, but do not have an intermediate of 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole. Therefore, this invention significantly improves the preparation of sulfonylpyrazine intermediates by gradually replacing liquid bromine or bromine with chlorine. Furthermore, since only sodium chloride, a byproduct salt, is produced after the reaction, it is easily removed, greatly improving the subsequent purification process. Moreover, chlorine is easier to remove than liquid bromine. Due to the gaseous properties of chlorine, excess chlorine can completely react with sodium bromide, further increasing the purity of the obtained product.

[0010] The dibromoformaldehyde oxime and 2-chloro-2-bromoformaldehyde oxime generated in the above steps cyclize with isobutylene to form a mixture of 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole and 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole, the latter of which 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole is a unique intermediate of sulfopyrazole in this application.

[0011] Furthermore, the temperature of the chlorobromination reaction is 0~30℃.

[0012] Furthermore, the temperature of the chlorobromination reaction is 0~5℃.

[0013] Furthermore, the molar ratio of glyoxylic acid to sodium bromide is 1:2 to 1:3, and the molar ratio of glyoxylic acid to chlorine is 1:1.5 to 1:3.

[0014] Furthermore, the molar ratio of glyoxylic acid to sodium bromide is 1:2.0 to 1:2.1, and the molar ratio of glyoxylic acid to chlorine is 1:1.5 to 1:2.

[0015] Furthermore, after the condensation reaction and before the cyclization reaction, the pH of the reaction system is adjusted to 3.44 using sodium carbonate.

[0016] Furthermore, the molar ratio of glyoxylic acid to hydroxylamine is 1:2.9 to 1:4.0, and is optimized to 1:2.9 to 1:3.5.

[0017] Furthermore, the hydroxylamine is hydroxylamine sulfate or hydroxylamine hydrochloride, the molar ratio of glyoxylic acid to hydroxylamine sulfate is 1:0.8 to 1:1.5, and the molar ratio of glyoxylic acid to hydroxylamine hydrochloride is 1:1 to 1:2.

[0018] Furthermore, the molar ratio of glyoxylic acid to hydroxylamine sulfate is 1:0.8 to 1:1.1, and the molar ratio of glyoxylic acid to hydroxylamine hydrochloride is 1:1 to 1:1.5.

[0019] Furthermore, the cyclization reaction is carried out in the presence of an alkaline catalyst, which is sodium carbonate or potassium carbonate, and the molar ratio of glyoxylic acid to the alkaline catalyst is 1:1 to 1:4.

[0020] Furthermore, the condensation reaction is carried out in water, the chlorobromination intermediate is dibromoformaldehyde oxime and 2-chloro-2-bromoformaldehyde oxime, the sulfonylpyrazolium intermediate is 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole and 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole, and the chlorobromination reaction is carried out in an organic solvent, which is one of dichloroethane, chloroform, and methyl isobutyl ketone.

[0021] Furthermore, the molar ratio of the chlorobromination intermediate to isobutylene is 1:1 to 1:3, preferably 1:1 to 1:1.5.

[0022] Furthermore, the sulfonylpyrazol intermediate then reacts with thiourea in the presence of hydrobromic acid to generate 5,5-dimethyl-4,5-dihydroisoxazole-3-ylthiourea bromate.

[0023] Furthermore, the molar ratio of the chlorobromination intermediate to hydrobromic acid is 1:1.2 to 1:1.8, preferably 1:1.2 to 1:1.5.

[0024] Furthermore, the molar ratio of the chlorobromination intermediate to thiourea is 1:1.2 to 1:1.7, preferably 1:1.2 to 1:1.3.

[0025] Furthermore, the cyclization reaction temperature, that is, the temperature at which isobutylene is added, is 0~40℃, preferably 0~10℃.

[0026] In summary, this application has at least one of the following beneficial technical effects compared with the prior art:

[0027] 1. This invention significantly reduces the use of bromine by changing the chlorobromination reaction environment to use chlorine in an organic environment, thus avoiding the waste of liquid bromine and preventing bromine pollution of the environment. Furthermore, in subsequent reactions, the only byproduct salt produced is sodium chloride, which is only slightly soluble in alcohols in organic solvents, making it very easy to separate. This has a good effect on the subsequent separation and purification of intermediates, resulting in a higher yield and a certain improvement in the purity of the final product.

[0028] 2. The improvement of this invention also lies in reducing the use of liquid bromine, which greatly saves costs and promotes the process, enabling large-scale application and industrial production.

[0029] 3. The method of the present invention slowly releases bromine by reacting sodium bromide with chlorine. The reaction is mild and controllable, and the expensive bromine element is utilized at a high rate without the need for secondary recovery. Attached Figure Description

[0030] Figure 1 This is a schematic diagram of the preparation process of the present invention. Detailed Implementation

[0031] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the following will be described in conjunction with the accompanying drawings of the embodiments of the present invention. Figure 1 The technical solutions of the embodiments of the present invention will be clearly and completely described herein. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. All other embodiments obtained by those skilled in the art based on the described embodiments of the present invention are within the scope of protection of the present invention.

[0032] Example 1

[0033] The preparation method of the sulfonylpyrazole intermediate in this experiment is as follows:

[0034] Add 55g of hydroxylamine sulfate (0.34mol) and 300g of water to a 1000ml four-necked flask, turn on the stirrer, stir evenly, cool down to 23℃, add 60g of glyoxylic acid solution (0.41mol, 50%), and keep warm at 25℃ for 2h after the addition is complete.

[0035] After the heat preservation period, cool the mixture to 3°C and slowly add 122.8g of sodium carbonate (1.13mol). Adjust the pH to around 3.5. A large number of bubbles will be generated during the addition process, so pay attention to the addition speed. After stirring for 10 minutes, adjust the pH to between 3.5 and 4 using a 20% sodium carbonate solution.

[0036] Add 120 g of methyl isobutyl ketone (1.2 mol) and 150 g of sodium bromide (1.46 mol) to the reaction system, stir for 0.5 h, then cool to 5 °C, and purge with approximately 43.6 g (0.61 mol) of chlorine gas. The reaction time is 2 h, and the system temperature is controlled between 0 and 5 °C. The system will turn green. Detect the reaction using liquid chromatography (LC) until the reaction is complete.

[0037] After the heat preservation was completed, the mixture was separated into layers. 66g of sodium carbonate was added to the organic phase, and 22.9g of isobutylene was introduced at a controlled temperature of 0-5℃ to carry out the cyclization reaction. The reaction was carried out at 0-5℃ for 1 hour, and then the temperature was raised to 20℃ for 2 hours. After the liquid phase test showed that the reaction was qualified, the mixture was filtered, and the mother liquor was evaporated to dryness to obtain 126g of a mixture of 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole and 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole. The total purity of the two substances was 96.5%, and the yield was 92.7%.

[0038] Take a 1L four-necked flask, add 50g acetonitrile and 401g MIBK at room temperature, then add 46g thiourea and 101g 48% hydrobromic acid. After dissolving completely, stir at 20℃ for 1h, then control the temperature below 35℃ and add dropwise 126g of a mixture of 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole and 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole. After the addition is complete, keep warm at 35℃ for 3h. A white solid precipitates. Raise the temperature to 50-55℃, evaporate half of the solvent under reduced pressure, add 561g of water to dissolve completely, and let stand to separate the layers. The aqueous phase is the target product, yielding approximately 147g of 5,5-dimethyl-4,5-dihydroisoxazole-3-ylthiourea bromate.

[0039] Example 2

[0040] The difference between this embodiment and Example 1 lies in the change in the amount of chlorine used. By increasing the amount of chlorine input, this embodiment investigates the effect of different chlorine input amounts on the purity and yield of the sulfonylpyrazine intermediate. The specific changes are as follows:

[0041] After adding methyl isobutyl ketone and sodium bromide to the reaction system, the system was stirred for 0.5 h, then cooled to 5 °C. Approximately 58.2 g of chlorine gas was introduced, and the reaction time was 2 h, with the system temperature controlled between 0 and 5 °C. The system turned green. Liquid chromatography (LC) was used to monitor the reaction until it was complete.

[0042] After the heat preservation was completed, the mixture was separated into layers. 66g of sodium carbonate was added to the organic phase, and 22.9g of isobutylene was introduced at a controlled temperature of 0-5℃ to carry out the cyclization reaction. The reaction was carried out at 0-5℃ for 1 hour, and then the temperature was raised to 20℃ for 2 hours. After the liquid phase test showed that the reaction was qualified, the mixture was filtered, and the mother liquor was evaporated to dryness to obtain 120g of a mixture of 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole and 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole. The total purity of the two substances was 95.3%, and the yield was 87.6%.

[0043] Example 3

[0044] The difference between this embodiment and Example 1 lies in the change in the amount of chlorine used. By reducing the amount of chlorine input, this embodiment investigates the effect of different chlorine input amounts on the purity and yield of the sulfonylpyrazine intermediate. The specific changes are as follows:

[0045] After adding methyl isobutyl ketone and sodium bromide to the reaction system, the system was stirred for 0.5 h, then cooled to 5 °C. Approximately 75.6 g of chlorine gas was introduced, and the reaction time was 2 h, with the system temperature controlled between 0 and 5 °C. The system turned green. Liquid chromatography (LC) was used to monitor the reaction until it was complete.

[0046] After the heat preservation was completed, the mixture was separated into layers. 66g of sodium carbonate was added to the organic phase, and 22.9g of isobutylene was introduced at a controlled temperature of 0-5℃ to carry out the cyclization reaction. The reaction was carried out at 0-5℃ for 1 hour, and then the temperature was raised to 20℃ for 2 hours. After the liquid phase test showed that the reaction was qualified, the mixture was filtered, and the mother liquor was evaporated to dryness to obtain 118g of a mixture of 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole and 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole. The total purity of the two substances was 94.2%, and the yield was 85.8%.

[0047]

[0048] Example 4

[0049] The difference between this embodiment and Example 1 lies in the change of the chlorobromination reaction temperature. By gradually increasing the chlorobromination reaction temperature, the influence of chlorobromination temperature on yield and purity is investigated. The specific changes are as follows:

[0050] After adding methyl isobutyl ketone and sodium bromide to the reaction system, the system was stirred for 0.5 h, then cooled to 10 °C. Approximately 43.6 g of chlorine gas was introduced, and the reaction time was 2 h, with the system temperature controlled between 5 and 10 °C. The system turned green. Liquid chromatography (LC) was used to monitor the reaction until it was complete.

[0051] Example 5

[0052] The difference between this embodiment and Example 1 lies in the change of the chlorobromination reaction temperature. By gradually increasing the chlorobromination reaction temperature, the influence of chlorobromination temperature on yield and purity is investigated. The specific changes are as follows:

[0053] After adding methyl isobutyl ketone and sodium bromide to the reaction system, the system was stirred for 0.5 h, then cooled to 15 °C. Approximately 43.6 g of chlorine gas was introduced, and the reaction time was 2 h, with the system temperature controlled between 10 and 15 °C. The system turned green. Liquid chromatography (LC) was used to monitor the reaction until it was complete.

[0054] Example 6

[0055] The difference between this embodiment and Example 1 lies in the change of the chlorobromination reaction temperature. By gradually increasing the chlorobromination reaction temperature, the influence of chlorobromination temperature on yield and purity is investigated. The specific changes are as follows:

[0056] After adding methyl isobutyl ketone and sodium bromide to the reaction system, the system was stirred for 0.5 h, then cooled to 20 °C. Approximately 43.6 g of chlorine gas was introduced, and the reaction time was 2 h. The system temperature was controlled between 15 and 20 °C, and the system turned green. The reaction was monitored by liquid chromatography (LC) until the reaction was complete.

[0057] Example 7

[0058] The difference between this embodiment and Example 1 lies in the change of the chlorobromination reaction temperature. By gradually increasing the chlorobromination reaction temperature, the influence of chlorobromination temperature on yield and purity is investigated. The specific changes are as follows:

[0059] After adding methyl isobutyl ketone and sodium bromide to the reaction system, the system was stirred for 0.5 h, then cooled to 25 °C. Approximately 43.6 g of chlorine gas was introduced, and the reaction time was 2 h, with the system temperature controlled between 20 and 25 °C. The system turned green. Liquid chromatography (LC) was used to detect the reaction until it was complete.

[0060] Example 8

[0061] The difference between this embodiment and Example 1 lies in the change of the chlorobromination reaction temperature. By gradually increasing the chlorobromination reaction temperature, the influence of chlorobromination temperature on yield and purity is investigated. The specific changes are as follows:

[0062] After adding methyl isobutyl ketone and sodium bromide to the reaction system, the system was stirred for 0.5 h, then cooled to 30 °C. Approximately 43.6 g of chlorine gas was introduced, and the reaction time was 2 h, with the system temperature controlled between 25 and 30 °C. The system turned green. Liquid chromatography (LC) was used to detect the reaction until it was complete.

[0063] The yield data for different temperatures in Examples 1 and 4 to 8 are as follows:

[0064]

[0065] During the experiment, it was found that the yield and purity were much higher than those in the prior art when the reaction temperature of chlorobromination was within the range of about 5°C. Therefore, further examples are needed to verify the range within which the effect is equivalent to that of the prior art.

[0066] Example 9

[0067] This embodiment precisely modifies the chlorobromination reaction temperature and accurately implements it at around 5°C. The temperature range is set between -5°C and 10°C for verification. The specific preparation method is basically the same as in Example 1, and the specific temperatures and data are as follows:

[0068]

[0069] Comparative Example 1

[0070] The difference between this comparative example and Example 1 is that the molar ratio of glyoxylic acid to chlorine is less than 1:1.5, and this was carried out to investigate the effect on the yield or purity of the sulfonylpyrazine intermediate product. The specific preparation method is basically the same as that in Example 1, and the specific temperature and data are as follows:

[0071]

[0072] Comparative Example 2

[0073] The difference between this comparative example and Example 1 is that the molar ratio of glyoxylic acid to chlorine is greater than 1:3, and this was implemented to investigate the effect on the yield or purity of the sulfonylpyrazine intermediate product. The specific preparation method is basically the same as in Example 1, and the specific chlorine dosage and data are as follows:

[0074]

[0075] Comparative Example 3

[0076] The difference between this comparative example and Example 1 lies in the reaction temperature of chlorobromination. A reaction temperature greater than 30°C was used for the chlorobromination reaction. The specific preparation method is basically the same as in Example 1, and the specific temperatures and data are as follows:

[0077]

[0078] Comparative Example 4

[0079] The difference between this comparative example and Example 1 lies in the reaction temperature of chlorobromination. A reaction temperature below 0°C was used for the chlorobromination reaction. The specific preparation method is basically the same as in Example 1, and the specific temperatures and data are as follows:

[0080]

[0081] analyze

[0082] As can be seen from Examples 1 to 3, the sulfonylpyrazole intermediate prepared in this application has a purity of over 94.2%. Compared with the traditional sulfonylpyrazole bromide intermediate, this demonstrates the feasibility of the sulfonylpyrazole chloride intermediate. Moreover, the purity is extremely similar to that of the prior art, and the yield is greatly improved.

[0083] Data analysis from Examples 1 and 4 to 8 shows that the technical solution of this application has a significant yield improvement at around 5°C. As the temperature gradually increases, the purity does not change much, but the yield decreases significantly. Based on the above findings, in Example 9, it was found that reaction temperatures below 0°C cause a significant decrease in the yield of sulfonylpyrazine intermediate, with a greater decrease than that between 5°C and 7°C.

[0084] Comparative Example 1 revealed that reducing the input of chlorine significantly reduced the yield of sulfonylpyrazine intermediate, but had little impact on the purity of the intermediate. This is because the small amount of chlorine resulted in the most complete reaction in the overall system, and the remaining 2-(hydroxyimino)acetic acid and sodium bromide were not completely converted into sulfonylpyrazine intermediate, thus causing a decrease in yield. Without excess chlorine, there would be no significant generation of impurity salts, so the impact on purity was minimal.

[0085] Comparative Example 2 revealed that increasing the amount of chlorine input significantly reduced the purity of the sulfonylpyrazole intermediate, but had little effect on the yield. This is because the large amount of chlorine ensured that the remaining 2-(hydroxyimino)acetic acid reacted completely with sodium bromide, thus increasing the yield. However, the excess chlorine produced byproducts that resulted in low purity and slightly altered the yield of the sulfonylpyrazole intermediate.

[0086] Comparative Examples 3 and 4 show that excessively high chlorobromination reaction temperatures can cause the reaction to stagnate, preventing it from continuing. Reactions below 0°C within a 2-hour reaction time will also result in incomplete reactions due to excessively slow reaction times, leading to yields lower than normal. At excessively high temperatures, the high energy of chlorine gas results in short contact time with 2-(hydroxyimino)acetic acid and sodium bromide, hindering the effective formation of chlorobromination intermediates. Conversely, excessively low temperatures slow down the intermolecular motion of activated molecules, causing a decrease in reaction rate and consequently, a reduction in yield and purity.

[0087] The above description represents the preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for synthesizing a sulfonylpyrazole intermediate, comprising a condensation reaction of glyoxylic acid and hydroxylamine to generate 2-(hydroxyimino)acetic acid, wherein the 2-(hydroxyimino)acetic acid undergoes a chlorobromination reaction to generate a chlorobromination intermediate, and the chlorobromination intermediate is further cyclized with isobutylene to generate a sulfonylpyrazole intermediate, characterized in that, The chlorobromination reaction is carried out in the presence of sodium bromide and chlorine; the temperature of the chlorobromination reaction is 0 ~ 30℃; the molar ratio of glyoxylic acid to sodium bromide is 1:2 ~ 1:3, and the molar ratio of glyoxylic acid to chlorine is 1:1.5 ~ 1:3; the reaction environment of the condensation reaction is water; the chlorobromination intermediate is dibromoformaldehyde oxime and 2-chloro-2-bromoformaldehyde oxime; the sulfonylpyrazol intermediate is 3-bromo-5,5-dimethyl-4,5-dihydroisoxazole and 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole; the reaction environment of the chlorobromination reaction is an organic solvent, and the organic solvent is one of dichloroethane, chloroform, and methyl isobutyl ketone.

2. The method for synthesizing the sulfonylpyrazol intermediate as described in claim 1, characterized in that: The chlorobromination reaction is carried out at a temperature of 0 to 5°C.

3. The method for synthesizing the sulfonylpyrazol intermediate as described in claim 1, characterized in that: The molar ratio of glyoxylic acid to sodium bromide is 1:2.0 to 1:2.1, and the molar ratio of glyoxylic acid to chlorine is 1:1.5 to 1:

2.

4. The method for synthesizing the sulfonylpyrazol intermediate as described in claim 1, characterized in that: The reaction process, which is followed by condensation and followed by cyclization, includes adjusting the pH of the reaction system to 3.44 with sodium carbonate.

5. The method for synthesizing the sulfonylpyrazol intermediate as described in claim 1, characterized in that: The hydroxylamine is hydroxylamine sulfate or hydroxylamine hydrochloride, and the molar ratio of glyoxylic acid to hydroxylamine sulfate is 1:0.8 to 1:1.

5. The molar ratio is 1:1 to 1:

2.

6. The method for synthesizing the sulfonylpyrazol intermediate as described in claim 5, characterized in that: The molar ratio of glyoxylic acid to hydroxylamine sulfate is 1:0.8 to 1:1.1, and the molar ratio of glyoxylic acid to hydroxylamine hydrochloride is 1:1 to 1:1.

5.

7. The method for synthesizing the sulfonylpyrazol intermediate as described in claim 1, characterized in that: The cyclization reaction is carried out in the presence of a basic catalyst, which is sodium carbonate or potassium carbonate, and the molar ratio of glyoxylic acid to the basic catalyst is 1:1 to 1:4.

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