Preparation method of pyroxasulfone

Abstract

The invention relates to the field of organic synthesis, and particularly provides a preparation method of pyroxasulfone, which is characterized in that the reaction can be carried out at normal temperature by using quaternary ammonium hydrogen peroxysulfate as a catalyst and an oxidant, the yield is high, no transition metal is needed, the reaction time is short, the content of the reaction intermediate sulfoxide is controlled, and the reaction cost is reduced.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and in particular to a method for preparing sulfonylpyrazole. Background Technology

[0002] Sulfonazole is a pre-emergence soil-applied herbicide developed by Japanese combinatorial chemistry and Anbara Chemical Co., Ltd., applicable to most crop fields. Its mechanism of action involves absorption by weed rootlets and shoots, disrupting seedling meristems and coleoptiles. It is a potential inhibitor of VLCFA (very long-chain fatty acid) biosynthesis in plants, thus suppressing early seedling growth. Its broad-spectrum, high-efficiency, and environmentally friendly characteristics have garnered widespread attention.

[0003] Currently, in the existing disclosed preparation methods, the final preparation of the target product always requires the oxidation of the thioether intermediate (Formula II) to obtain sulfonylpyrazol (Formula I), as shown in the following reaction formula: .

[0004] The m-chloroperoxybenzoic acid (m-CPBA) described in patent WO2004 / 013106A1 is relatively expensive for industrial use and has problems with handling and waste disposal. Furthermore, in the method for preparing formula I from formula II, a sulfoxide derivative (SO derivative) of formula III, which is an intermediate of the oxidation reaction, may occur, and this compound may stop the reaction.

[0005] .

[0006] The preparation methods in patents CN111393427A and CN113831333A have improved upon the above problems by using sodium tungstate and ammonium molybdate as catalysts and hydrogen peroxide to directly oxidize sulfide into sulfone. However, the above methods have long reaction times (8-10 hours), and post-treatment requires quenching with sodium thiosulfate. The operation is cumbersome, the production cycle is long, and the cost is high.

[0007] Patent CN111574511A reports a manufacturing method that does not use transition metals, but uses concentrated sulfuric acid as a catalyst. However, the described yield is low.

[0008] Therefore, whether a method for preparing sulfonylpyrazole with a higher yield can be provided has become an urgent problem to be solved in this field. Summary of the Invention

[0009] To address the problems of high cost, low yield, requirement for transition metals, long reaction time, and easy generation of sulfoxide byproduct in the preparation of sulfonium pyrazine in existing technologies, this invention proposes a method for preparing sulfonium pyrazine. This method uses quaternary ammonium peroxymonosulfate (Bu4NHSO5) as a catalyst and oxidant, allowing the reaction to proceed at room temperature with high yield, no need for transition metals, short reaction time, and control over the content of the reaction intermediate sulfoxide, thus reducing the cost of the reaction.

[0010] The method for preparing sulfonylpyrazole provided by this invention specifically involves reacting compound II with an oxidizing agent in a solvent to obtain sulfonylpyrazole as shown in compound I. The oxidizing agent is a quaternary ammonium salt of peroxythiocyanate. The reaction process is as follows: .

[0011] Furthermore, the peroxythiocyanate quaternary ammonium salt is Bu4NHSO5.

[0012] Furthermore, the preparation method of Bu4NHSO5 is as follows: water and potassium peroxymonosulfate complex salt (Oxone) are added to a reactor, quaternary ammonium salt is added under stirring, the mixture is stirred at room temperature for 0.2-3 hours, the reaction solution is extracted with an organic solvent, and the organic phase is dried and desolventized to obtain white solid Bu4NHSO5; The potassium peroxymonosulfate complex salt (Oxone) is 2KHSO5•KHSO4•K2SO4; the quaternary ammonium salt is tetrabutylammonium bromide; the molar ratio of the potassium peroxymonosulfate complex salt (Oxone) to the quaternary ammonium salt is 1:(4-6), more preferably 1:4.5-5, and most preferably 1:4.9.

[0013] The organic solvent used for extraction is selected from dichloromethane and ethyl acetate; more specifically, the organic solvent used for extraction is dichloromethane.

[0014] Preferably, the specific steps for the oxidation reaction of compound II to obtain compound I are as follows: After adding an organic solvent to the reactor, compound II was added and stirred to dissolve. Then, the oxidant peroxysulfuric acid quaternary ammonium salt was added, and the reaction was carried out at room temperature for 1-5 hours. After the reaction was completed, water was added to the system, and the mixture was filtered and dried to obtain compound I, namely sulfonylpyrazol, as a white solid.

[0015] The organic solvent used is selected from at least one of C1-C8 alcohols, dichloromethane, 1,2-dichloroethane, chlorobenzene, dichlorobenzene, ethyl acetate, butyl acetate, and acetonitrile; the amount of organic solvent used is 5-6 ml per gram of compound II.

[0016] The preferred organic solvent is a C1-C8 alcohol; more preferably, the C1-C8 alcohol is selected from at least one of methanol, ethanol, tert-butanol, butanediol, propylene glycol, isobutanol, isoamyl alcohol, isopropanol, ethylene glycol, and glycerol; even more preferably, it is at least one of methanol and ethanol; and most preferably, it is methanol.

[0017] The main reason for choosing the above-mentioned organic solvent is that it is miscible with water, so there is no need to perform a negative pressure desolvation operation after the reaction is completed, which is more suitable for industrial production.

[0018] As a further improvement, the molar ratio of compound II to the oxidant is 1:2-6; Furthermore, the molar ratio of compound II to the oxidant is 1:3.

[0019] The preparation of sulfonylpyrazole using the above method has the following beneficial effects: 1) The method of the present invention is used to prepare sulfopyrazole under mild reaction conditions, which can be carried out at room temperature, and does not require the use of transition metal salts as catalysts; 2) The reaction time is short, and the reaction time can be shortened by 3-5 hours based on the existing technology. Moreover, the prepared product, sulfopyrazole, has ideal yield and purity, and is suitable for industrial preparation processes. 3) When preparing sulfonylpyrazine by this method, the intermediate can be completely oxidized. Even if the oxidant is in excess, no other impurities will be generated. Therefore, the content of the reaction intermediate sulfoxide is well controllable and can be controlled to be close to zero. Attached Figure Description

[0020] Figure 1 This is the liquid phase spectrum of the product prepared in Example 2. Figure 2 This is the MS spectrum of the product prepared in Example 2. Figure 3 This is the liquid phase tracking spectrum of the reaction in Example 10. Figure 4 This is the liquid phase tracking spectrum of the reaction in Comparative Example 1. Detailed Implementation

[0021] To enable those skilled in the art to better understand the technical solutions of this invention, the technical solutions of the embodiments of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this invention, and not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of this invention.

[0022] Example 1-1 Preparation method of oxidant Bu4NHSO5: Water (45 mL) was added to the reaction flask, followed by Oxone (2 KHSO5•KHSO4•K2SO4, 10.86 g, 18 mmol). Tetrabutylammonium bromide (28.4 g, 88 mmol) was then added with stirring. The reaction was allowed to proceed at room temperature for 0.5 h. The reaction mixture was extracted with dichloromethane (3 × 70 mL), and the organic phases were combined, dried over anhydrous magnesium sulfate, and dissolved under reduced pressure to obtain a white solid (Bu4NHSO5, 30.26 g).

[0023] Examples 1-2 Preparation method of oxidant Bu4NHSO5: The same method as in Example 1-1 was used for preparation, except that the molar ratio of Oxone to tetrabutylammonium bromide was 1:4, and the final amount of Bu4NHSO5 obtained was 26.15g.

[0024] Examples 1-3 Preparation method of oxidant Bu4NHSO5: The same method as in Example 1-1 was used for preparation, except that the molar ratio of Oxone to tetrabutylammonium bromide was 1:6, and the final amount of Bu4NHSO5 obtained was 30.28g.

[0025] Example 2 A method for preparing sulfonylpyrazole, comprising the following steps: 20 mL of methanol was added to a 100 mL three-necked flask, followed by compound II (3.59 g, 0.01 mol, 1 eq). After stirring to dissolve, the oxidant Bu4NHSO5 (10.7 g, 0.03 mol, 3 eq) prepared in Example 1-1 was added. The mixture was stirred at room temperature (25 °C) for 2 h. After the reaction was complete, 10 mL of water was added to the system, and the mixture was stirred thoroughly, filtered, and dried to obtain 3.76 g of white solid sulfonylpyrazine I, with a yield of 96%. The purity of sulfonylpyrazine was determined to be 99.2% by liquid chromatography (LC). The LC and MS spectra of the product are shown below. Figure 1 and 2 As shown, the main peak has a good shape and no extraneous peaks.

[0026] Examples 3-6 Sulfonazole was prepared using the same method as in Example 2, except that the amount of oxidant Bu4NHSO5 was different. The corresponding amounts of oxidant and the yield and content of the reaction products are shown in Table 1.

[0027] Table 1. Yields and purity of sulfonylpyrazole prepared using different amounts of oxidant in Examples 3-6. Serial Number Oxidizing agent (dosage) Yield (%) purity(%) Example 3 0.01mol 58.6 88.1 Example 4 0.02mol 78.3 92.2 Example 5 0.04mol 95.7 99.0 Example 6 0.06mol 95.8 98.9 The results in Table 1 show that when the amount of oxidant is too small, the product yield is low and the product purity is not high, possibly due to the formation of a large amount of sulfoxide byproduct. It is evident that when the amount of oxidant exceeds 0.03 mol, the yield and purity do not differ significantly.

[0028] Example 7

[0029] Sulfonazole was prepared using the same method as in Example 2, except that ethanol was used instead of methanol as the solvent. All other conditions and procedures were the same as in Example 2. 3.77 g of white solid sulfonazole I was obtained, with a yield of 95.5%. The sulfonazole content was determined to be 99.1% by liquid chromatography (LC).

[0030] Example 8

[0031] Sulfonazole was prepared using the same method as in Example 2, except that acetonitrile was used instead of methanol as the solvent. All other conditions and procedures were the same as in Example 2. 3.78 g of white solid sulfonazole I was obtained, with a yield of 95.6%. The sulfonazole content was determined to be 99% by liquid chromatography (LC).

[0032] A comparison of the product content and yield shows that there is little difference between using ethanol and acetonitrile as solvents. Considering both production cost and final yield, methanol is the best solvent.

[0033] Example 9

[0034] A method for preparing sulfonylpyrazole includes the following steps: 20 mL of dichloromethane was added to a 100 mL three-necked reaction flask, followed by compound II (3.59 g, 0.01 mol, 1 eq). After stirring to dissolve, oxidant Bu4NHSO5 (10.7 g, 0.03 mol, 3 eq) was added. The mixture was stirred at room temperature (25 °C) for 2 h. The reaction was monitored, and the intermediate sulfoxide product remained. After continuing the reaction for another h, the intermediate conversion was complete. After the reaction was completed, dichloromethane was removed under negative pressure. Then, methanol (5 mL) and water (10 mL) were added to the residue at the bottom of the flask, stirred thoroughly, filtered, and dried to obtain 3.67 g of white solid sulfonylpyrazine I, with a yield of 93.9%. The sulfonylpyrazine content was determined to be 98% by liquid chromatography (LC).

[0035] Compared to methanol as a solvent, using dichloromethane increases the reaction time by 1 hour, adds an extra solvent removal step, which is more cumbersome, and raises the temperature to 35-40℃ during the solvent removal process, affecting both the yield and content. Therefore, methanol is the preferred solvent.

[0036] Example 10

[0037] A method for preparing sulfonylpyrazole includes the following steps: 1) Preparation of oxidant (PhCH2(CH2CH3)3NHSO5) Water (45 mL) was added to the reaction flask, followed by Oxone (2 KHSO5•KHSO4•K2SO4, 10.86 g, 18 mmol). Benzyltriethylammonium chloride (20.04 g, 88 mmol) was added with stirring. The reaction was allowed to proceed at room temperature for 0.5 h. The reaction mixture was extracted with dichloromethane (3 × 70 mL), and the organic phases were combined, dried over anhydrous magnesium sulfate, and dissolved under reduced pressure to obtain a white solid (PhCH2(CH2CH3)3NHSO5 26.54 g).

[0038] 2) Preparation of sulfonylpyrazole 20 mL of methanol was added to a 100 mL three-necked flask, followed by compound II (3.59 g, 0.01 mol, 1 eq). After stirring to dissolve, the oxidant PhCH2(CH2CH3)3NHSO5 (10.67 g, 0.03 mol, 3 eq) prepared above was added. The mixture was stirred at room temperature (25 °C) for 2 h. Liquid chromatography analysis showed that the sulfide reaction was complete, and the oxidation intermediate sulfoxide accounted for approximately 0.7%. 10 mL of water was added to the system, and the mixture was stirred thoroughly, filtered, and dried to obtain 3.90 g of white solid sulfonylpyrazine I, with a yield of 89.92%. The purity of sulfonylpyrazine was determined to be 90.3% by liquid chromatography (LC).

[0039] like Figure 3 The reaction tracking graph of sulfonylpyrazole shown indicates that the sulfoxide peak is at 1.315 min, with a content of approximately 0.708%. The peak of sulfonylpyrazole is at 1.771 min. PhCH2(CH2CH3)3NHSO5, as an oxidant, showed slightly weaker oxidation performance compared to Bu4NHSO5, indicating incomplete conversion of sulfoxide.

[0040] Comparative Example 1 A method for preparing sulfonylpyrazole: oxidation using potassium persulfate complex salt (Oxone): Add 20 mL of methanol to a 100 mL three-necked reaction flask, then add compound II (3.59 g, 0.01 mol, 1 eq). After stirring to dissolve, add potassium persulfate complex salt Oxone (9.21 g, 0.015 mol, 1.5 eq). Stir at room temperature (25 °C) for 2 h. Liquid chromatography analysis showed that approximately 25% of compound II was converted. Continue the reaction for another 2 h; no further conversion of the sulfide occurred.

[0041] Depend on Figure 4 As shown in the reaction tracking graph of sulfonylpyrazole, the peak position of the raw material sulfide is at 2.630 min, with a content of 75.938%. Using potassium persulfate composite salt as the oxidant resulted in poor reaction performance.

[0042] Comparative Example 2 A method for preparing sulfonylpyrazole, referring to patent CN111574511A, specifically includes the following steps: Compound (II) (0.2 mol) and 300 mL of methanol were added to a 500 mL four-necked flask, followed by 1 mL of concentrated sulfuric acid (98%) and 64.6 g of hydrogen peroxide (0.57 mol, 30%). After stirring for 6 hours, water was added and stirred. The mixture was then filtered and dried to obtain the final product. The actual yield was 70%, lower than the 81% recorded in CN111574511A. Furthermore, this comparative example, using concentrated sulfuric acid as a catalyst, still suffers from low yield and excessively long reaction time.

[0043] Based on the comparison of the above embodiments and comparative examples, it can be seen that the technical solution provided by the present invention has mild reaction conditions, short reaction time, easy operation, high yield, and high product purity.

[0044] The above embodiments are only used to illustrate the technical solutions of the present invention, but the present invention is not limited thereto. Although the present invention has been described in detail with reference to the accompanying drawings and preferred embodiments, those skilled in the art can make various equivalent modifications or substitutions to the embodiments of the present invention without departing from the spirit and essence of the present invention, and such modifications or substitutions should all be within the scope of the present invention. Any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should also be covered within the protection scope of the present invention.

Claims

1. A method for preparing sulfonylpyrazole, specifically comprising the steps of reacting compound II with an oxidizing agent in a solvent to obtain sulfonylpyrazole as shown in compound I, the reaction process being as follows: ； Its features are, The oxidant is peroxythiocyanate quaternary ammonium salt.

2. The method for preparing sulfonylpyrazole according to claim 1, characterized in that, The peroxythiocyanate quaternary ammonium salt is Bu4NHSO5.

3. The method for preparing sulfonylpyrazole according to claim 2, characterized in that, The preparation method of Bu4NHSO5 is as follows: Water and potassium peroxyhydrogen sulfate complex salt were added to the reactor, and quaternary ammonium salt was added under stirring. The mixture was stirred at room temperature for 0.2-3 hours. The reaction solution was extracted with an organic solvent, and the organic phase was dried and desolventized to obtain a white solid, Bu4NHSO5. The potassium peroxymonosulfate complex salt is 2KHSO5•KHSO4•K2SO4; the quaternary ammonium salt is tetrabutylammonium bromide; and the molar ratio of the potassium peroxymonosulfate complex salt to the quaternary ammonium salt is 1:(4-6).

4. The method for preparing sulfonylpyrazole according to claim 3, characterized in that; The organic solvent used for extraction is selected from dichloromethane and ethyl acetate.

5. The method for preparing sulfonylpyrazole according to claim 1, characterized in that, The specific steps are as follows: After adding an organic solvent to the reactor, compound II was added and stirred to dissolve. Then, the oxidant peroxysulfuric acid quaternary ammonium salt was added, and the reaction was carried out at room temperature for 1-5 hours. After the reaction was completed, water was added to the system, and the mixture was filtered and dried to obtain compound I, namely sulfonylpyrazol, as a white solid.

6. The method for preparing sulfonylpyrazole according to claim 5, characterized in that, The molar ratio of compound II to the oxidant is 1:(2-6).

7. The method for preparing sulfonylpyrazole according to claim 5 or 6, characterized in that, The molar ratio of compound II to the oxidant is 1:

3.

8. The method for preparing sulfonylpyrazole according to claim 5, characterized in that, The organic solvent used is selected from at least one of C1-C8 alcohols, dichloromethane, 1,2-dichloroethane, chlorobenzene, dichlorobenzene, ethyl acetate, butyl acetate, and acetonitrile; the amount of organic solvent used is 5-6 ml per gram of compound II.

9. The method for preparing sulfonylpyrazole according to claim 5 or 8, characterized in that, The C1-C8 alcohols are selected from at least one of methanol, ethanol, tert-butanol, butanediol, propylene glycol, isobutanol, isoamyl alcohol, isopropanol, ethylene glycol, and glycerol.

10. The method for preparing sulfonylpyrazole according to claim 9, characterized in that, The C1-C8 small molecule alcohols are at least one of methanol and ethanol.

Images