A method for preparing pyroxasulfone
By avoiding the use of traditional oxidants, sulfonylpyrazine is prepared by reacting 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride with sulfite, which solves the problem of high safety risks in existing methods and achieves safe production with high yield.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- JIANGSU SEVENCONTINENT GREEN TECH RES INST CO LTD
- Filing Date
- 2024-12-20
- Publication Date
- 2026-06-23
AI Technical Summary
The oxidants used in existing sulfonylpyrazine synthesis methods, such as hydrogen peroxide, m-chloroperoxybenzoic acid, and ozone, pose safety risks. A new preparation route that avoids the use of these oxidants needs to be developed.
5,5-Dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride is reacted with sulfite to generate 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate, which is then reacted with pyrazole intermediate to prepare sulfopyrazazole, thus avoiding the use of traditional oxidants.
It reduces production risks, improves process safety, is suitable for large-scale industrial production, and has a high yield in the reaction route.
Smart Images
Figure CN122255124A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of organic synthesis technology, and specifically to a method for preparing sulfonylpyrazine. Background Technology
[0002] Pyroxasulfone, with the structural formula shown below, is a novel, broad-spectrum, and highly effective pre-emergence soil-applied herbicide developed by Japan's Combinatorial Chemicals Co., Ltd. It belongs to the isoxazole class of herbicides. It can be used to control annual broadleaf weeds and grass weeds on crops such as wheat, corn, soybeans, cotton, sunflowers, potatoes, and peanuts. It boasts advantages such as a broad spectrum of weed control, wide applicability to various crops, high activity, safety for both current and subsequent crops, low dosage, and good compatibility. Therefore, it may replace chloroacetamide herbicides in the future, becoming a benchmark for long-chain fatty acid inhibitors and possessing broad market prospects.
[0003]
[0004] Currently reported methods for synthesizing sulfonylpyrazine are basically divided into two types: one involves substitution docking of a halogenated pyrazole intermediate with a dihydroisoxazole thioether compound, followed by oxidation of the resulting thioether intermediate to obtain sulfonylpyrazine; the other route involves a substitution reaction between a pyrazole thiol intermediate and a halodihydroisoxazole, followed by oxidation of the resulting thioether intermediate to obtain the product. Both routes, as shown below, require a final oxidation reaction. Currently, oxidation is mainly achieved using methods such as hydrogen peroxide / sodium tungstate, hydrogen peroxide / acetic acid, ozone, and m-chloroperoxybenzoic acid, but these reagents are not environmentally friendly and pose significant safety risks.
[0005]
[0006] Therefore, a new route for preparing sulfopyrazole needs to be developed to avoid the use of oxidants such as hydrogen peroxide, m-chloroperoxybenzoic acid, and ozone, thereby reducing production risks and improving process safety. Summary of the Invention
[0007] The technical problem to be solved by the present invention is to provide a new method for preparing sulfopyrazole that avoids the use of oxidants.
[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows:
[0009] This invention provides a method for preparing sulfonylpyrazole, which includes the following steps:
[0010] (1) 5,5-Dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride was reacted with sulfite to obtain 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate.
[0011] (2) The 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate was reacted with pyrazole intermediate 3 to obtain sulfopyrazine;
[0012] The general structural formula of the pyrazole intermediate 3 is as follows: Y represents halogen, or
[0013] According to some specific embodiments, the halogen is fluorine, chlorine, bromine or iodine.
[0014] According to some specific embodiments, the sulfite is sodium sulfite or potassium sulfite, and correspondingly, the 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate is sodium 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate or potassium 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate.
[0015] According to some specific embodiments, the molar ratio of 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride to the sulfite is 1:1 to 3, for example, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, and 1:3.
[0016] According to some specific embodiments, step (1) is also carried out in the presence of a solvent, which is one or more of water, C1-C4 alcohols, acetonitrile, and DMF.
[0017] According to some specific implementations, step (1) is also carried out in the presence of an alkali, which is one or more of sodium bicarbonate, potassium bicarbonate, sodium carbonate, and potassium carbonate.
[0018] Further, the molar ratio of the 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride to the base is 1:1 to 3, for example, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, or 1:3.
[0019] According to some specific implementation methods, the reaction temperature of step (1) is controlled to be 25 to 100°C, for example, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, 100°C.
[0020] According to some specific implementation methods, the reaction time of control step (1) is 5 to 10 hours, for example, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, or 10 hours.
[0021] According to some specific embodiments, the molar ratio of the 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate to the pyrazole intermediate 3 is 1:1 to 1.5, for example, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5.
[0022] According to some specific embodiments, step (2) is also carried out in the presence of a solvent, which is one or more of acetonitrile, dichloroethane, DMF, DMAc, DMSO, and NMP.
[0023] According to some specific implementation methods, the reaction temperature of step (2) is controlled to be 0 to 80°C, for example, 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, 80°C.
[0024] According to some specific implementation methods, the reaction time of control step (2) is 2 to 5 hours, for example, 2 hours, 3 hours, 4 hours, 5 hours.
[0025] According to some specific embodiments, the specific reaction steps of the preparation method are as follows:
[0026] (1) Under nitrogen protection, 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride, sulfite, solvent and base are added to the reactor and reacted at 25-100℃. After the reaction is completed, the mixture is extracted with ethanol or water and the ethanol phase is evaporated to dryness to obtain 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfite.
[0027] (2) Under nitrogen protection, 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinic acid, solvent and pyrazole intermediate 3 are added to the reactor and reacted at 0-80°C. After the reaction is completed, the reaction system is poured into water, filtered and dried to obtain the sulfonylpyrazole.
[0028] By adopting the above technical solution, the present invention has the following advantages compared with other processes:
[0029] This application provides a new route for the synthesis of sulfonylpyrazole, which avoids the traditional route that uses oxidants such as hydrogen peroxide, m-chloroperoxybenzoic acid, and ozone to prepare sulfonylpyrazole, greatly reducing the danger of production, improving process safety, and making it suitable for large-scale industrial production. Detailed Implementation
[0030] Because existing routes for preparing sulfonylpyrazole cannot avoid the final oxidation step, which requires highly hazardous oxidants such as hydrogen peroxide, m-chloroperoxybenzoic acid, and ozone, the safety of existing preparation routes is relatively low. Therefore, the applicant proposes a new route for the synthesis of sulfonylpyrazole, the reaction equation of which is as follows:
[0031]
[0032] The novel route for synthesizing sulfopyrazine presented in this application eliminates the need for oxidants such as hydrogen peroxide, m-chloroperoxybenzoic acid, and ozone, significantly reducing the risks of production, improving process safety, and making it suitable for large-scale industrial production. Furthermore, the reaction route presented in this application yields high results.
[0033] All features disclosed in this invention, or steps in all methods or processes disclosed, may be combined in any way, except for mutually exclusive features or steps.
[0034] The technical solutions of the present invention will be further described below with reference to specific embodiments. However, the present invention should not be limited to these embodiments. Unless specifically stated otherwise, all features can be replaced by other equivalent or similar alternative features. Unless specifically stated otherwise, each feature is only one example of a series of equivalent or similar features. The terminology used in the present invention, unless otherwise stated, generally has the meaning commonly understood by those skilled in the art. The implementation conditions adopted in the embodiments can be further adjusted according to different requirements of specific use. Implementation conditions not specified are conventional conditions in the industry. The technical features involved in the various embodiments of the present invention can be combined with each other as long as they do not conflict with each other.
[0035] In this invention, operations without specific instructions are performed at room temperature. The raw materials used in this application are commercially available or can be prepared using conventional methods in the prior art. In this invention, unless otherwise specified, all contents are mass contents, and "%" represents a mass percentage.
[0036] The endpoints and any values of the ranges disclosed herein are not limited to the precise ranges or values, and should be understood to include values close to these ranges or values. For numerical ranges, the endpoint values of the ranges, the endpoint values of the ranges and individual point values, and individual point values can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein. The terms "optional" and "discretionary" mean that they may or may not be included (or may or may not be present).
[0037] In the following embodiments, the intermediate 3 uses Y as Cl.
[0038] Example 1: Preparation of Intermediate 2
[0039] Under nitrogen protection, 19.76 g (0.1 mol, 1.0 eq) of 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride, 100 mL of water, 25.21 g (0.2 mol, 2.0 eq) of sodium sulfite, and 16.8 g (0.2 mol, 2.0 eq) of sodium bicarbonate were added sequentially to a 250 mL four-necked flask. The mixture was heated to 80 °C and reacted for 5 h. After the reaction was completed, the water was removed by vacuum distillation. The obtained solid was extracted with ethanol, the ethanol was combined, and the mixture was evaporated to dryness to give 14.81 g of sodium 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate, with a yield of 80%.
[0040] Example 2: Preparation of Intermediate 2
[0041] Under nitrogen protection, 19.76 g (0.1 mol, 1.0 eq) of 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride, 100 mL of water, 18.91 g (0.15 mol, 1.5 eq) of sodium sulfite, and 16.8 g (0.2 mol, 2.0 eq) of sodium bicarbonate were added sequentially to a 250 mL four-necked flask. The mixture was heated to 80 °C and reacted for 5 h. After the reaction was completed, the water was removed by vacuum distillation. The obtained solid was extracted with ethanol, the ethanol was combined, and the mixture was evaporated to dryness to give 13.14 g of sodium 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate, with a yield of 71%.
[0042] Example 3: Preparation of Intermediate 2
[0043] Under nitrogen protection, 19.76 g (0.1 mol, 1.0 eq) of 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride, 100 mL of water, 25.21 g (0.2 mol, 2.0 eq) of sodium sulfite, and 12.6 g (0.15 mol, 1.5 eq) of sodium bicarbonate were added sequentially to a 250 mL four-necked flask. The mixture was heated to 80 °C and reacted for 5 h. After the reaction was completed, the water was removed by vacuum distillation. The obtained solid was extracted with ethanol, the ethanol was combined, and the mixture was evaporated to dryness to give 13.52 g of sodium 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate, with a yield of 73%.
[0044] Example 4: Preparation of Intermediate 2
[0045] Under nitrogen protection, 19.76 g (0.1 mol, 1.0 eq) of 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride, 100 mL of ethanol, 25.21 g (0.2 mol, 2.0 eq) of sodium sulfite, and 16.8 g (0.2 mol, 2.0 eq) of sodium bicarbonate were added sequentially to a 250 mL four-necked flask. The mixture was heated to 80 °C and reacted for 5 h. After the reaction was complete, 10 g of water was added to the system, the aqueous phase was separated, and the ethanol phase was evaporated to dryness to obtain 14.26 g of sodium 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate, with a yield of 77%.
[0046] Example 5: Preparation of Intermediate 2
[0047] Under nitrogen protection, 19.76 g (0.1 mol, 1.0 eq) of 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride, 100 mL of water, 25.21 g (0.2 mol, 2.0 eq) of sodium sulfite, and 20.02 g (0.2 mol, 2.0 eq) of potassium bicarbonate were added sequentially to a 250 mL four-necked flask. The mixture was heated to 80 °C and reacted for 5 h. After the reaction was completed, the water was removed by vacuum distillation. The obtained solid was extracted with ethanol, the ethanol was combined, and the mixture was evaporated to dryness to give 13.70 g of sodium 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate, with a yield of 74%.
[0048] Example 6: Preparation of sulfonylpyrazole
[0049] Under nitrogen protection, 18.52 g (0.1 mol, 1.0 eq) of sodium 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate, 150 mL of DMSO, and 29.1 g (0.11 mol, 1.1 eq) of intermediate 3 were added sequentially to a 250 mL four-necked flask. The reaction was carried out at room temperature (25 °C) for 2 h. After the reaction was completed, the system was poured into 300 mL of water, filtered, and dried to obtain 36.78 g of sulfonylpyrazol, with a yield of 94%.
[0050] Example 7: Preparation of sulfonylpyrazole
[0051] Under nitrogen protection, 18.52 g (0.1 mol, 1.0 eq) of sodium 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate, 150 mL of DMSO, and 39.68 g (0.15 mol, 1.5 eq) of intermediate 3 were added sequentially to a 250 mL four-necked flask. The reaction was carried out at room temperature (25 °C) for 2 h. After the reaction was completed, the system was poured into 300 mL of water, filtered, and dried to obtain 36.78 g of sulfonylpyrazol, with a yield of 94%.
[0052] Example 8: Preparation of sulfonylpyrazole
[0053] Under nitrogen protection, 18.52 g (0.1 mol, 1.0 eq) of sodium 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate, 150 mL of acetonitrile, and 29.1 g (0.11 mol, 1.1 eq) of intermediate 3 were added sequentially to a 250 mL four-necked flask. The mixture was heated to 60 °C and reacted for 2 h. After the reaction was complete, the system was poured into 300 mL of water, filtered, and dried to obtain 34.82 g of sulfonylpyrazol, with a yield of 89%.
[0054] Example 9: Preparation of sulfonylpyrazole
[0055] Under nitrogen protection, 18.52 g (0.1 mol, 1.0 eq) of sodium 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate, 150 mL of DMF, and 29.1 g (0.11 mol, 1.1 eq) of intermediate 3 were added sequentially to a 250 mL four-necked flask. The reaction was carried out at room temperature (25 °C) for 2 h. After the reaction was completed, the system was poured into 300 mL of water, filtered, and dried to obtain 35.61 g of sulfonylpyrazol, with a yield of 91%.
[0056] Example 10: Preparation of sulfonylpyrazole
[0057] Under nitrogen protection, 18.52 g (0.1 mol, 1.0 eq) of sodium 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate, 150 mL of DMAc, and 29.1 g (0.11 mol, 1.1 eq) of intermediate 3 were added sequentially to a 250 mL four-necked flask. The reaction was carried out at room temperature (25 °C) for 2 h. After the reaction was completed, the system was poured into 300 mL of water, filtered, and dried to obtain 35.22 g of sulfonylpyrazol, with a yield of 90%.
[0058] The present invention has been described in detail above, with the aim of enabling those skilled in the art to understand and implement the invention. However, this description should not be construed as limiting the scope of protection of the invention. All equivalent changes or modifications made in accordance with the spirit and essence of the invention should be included within the scope of protection of the invention.
Claims
1. A method for preparing sulfonylpyrazole, characterized in that: It includes the following steps: (1) 5,5-Dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride was reacted with sulfite to obtain 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate. (2) The 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate was reacted with pyrazole intermediate 3 to obtain sulfopyrazine; The general structural formula of the pyrazole intermediate 3 is as follows: Y represents halogen, or 2. The method for preparing sulfonylpyrazole according to claim 1, characterized in that: The sulfite is sodium sulfite or potassium sulfite, and correspondingly, the 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate is sodium 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate or potassium 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate.
3. The method for preparing sulfonylpyrazole according to claim 1, characterized in that: The molar ratio of 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride to the sulfite is 1:1 to 3.
4. The method for preparing sulfonylpyrazole according to claim 1, characterized in that: Step (1) is also carried out in the presence of a solvent, which is one or more of water, C1-C4 alcohols, acetonitrile, and DMF.
5. The method for preparing sulfonylpyrazole according to claim 1, characterized in that: Step (1) is also carried out in the presence of an alkali, wherein the alkali is one or more of sodium bicarbonate, potassium bicarbonate, sodium carbonate, and potassium carbonate; and the molar ratio of 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride to the alkali is 1:1 to 3.
6. The method for preparing sulfonylpyrazole according to claim 1, characterized in that: The reaction temperature in step (1) is controlled at 25–100°C and the reaction time is controlled at 5–10 h.
7. The method for preparing sulfonylpyrazole according to claim 1, characterized in that: The molar ratio of the 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinate to the pyrazole intermediate 3 is 1:1 to 1.
5.
8. The method for preparing sulfonylpyrazole according to claim 1, characterized in that: Step (2) is also carried out in the presence of a solvent, which is one or more of acetonitrile, dichloroethane, DMF, DMAc, DMSO, and NMP.
9. The method for preparing sulfonylpyrazole according to claim 1, characterized in that: The reaction temperature in step (2) is controlled to be 0–80°C and the reaction time is controlled to be 2–5 h.
10. The method for preparing sulfonylpyrazol according to any one of claims 1 to 9, characterized in that: The specific reaction steps of the preparation method are as follows: (1) Under nitrogen protection, 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfonyl chloride, sulfite, solvent and base are added to the reactor and reacted at 25-100℃. After the reaction is completed, the mixture is extracted with ethanol or water and the ethanol phase is evaporated to dryness to obtain 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfite. (2) Under nitrogen protection, 5,5-dimethyl-4,5-dihydroisoxazole-3-sulfinic acid, solvent and pyrazole intermediate 3 are added to the reactor and reacted at 0-80°C. After the reaction is completed, the reaction system is poured into water, filtered and dried to obtain the sulfonylpyrazole.