A preparation method of N-sulfonylpyrazole compounds
The cyclization reaction of sulfonylhydrazide compounds and β-dicarbonyl compounds by catalyzing the cyclization reaction of sulfonylhydrazide compounds in the prior art was solved, and efficient and simple compound preparation and industrial application were achieved, and green chemical standards were met.
Patent Information
- Application Number
- CN202510592844.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-09
- Publication Date
- 2025-08-08
- Estimated Expiration
- 2045-05-09
AI Technical Summary
The existing N-sulfonylpyrazole compounds have complicated steps and limit their application in drug research and development and industrial production.
The cyclization reaction of sulfonylhydrazide compound and β-dicarbonyl compound is catalyzed by using a low eutectic solvent as the reaction solvent and catalyst to prepare N-sulfonylpyrazole compounds. A high yield product can be obtained by a single step of reaction and simple post-treatment.
It has achieved efficient preparation of N-sulfonylpyrazole compounds, which are easy to operate, high product yield, cheap and easy to obtain raw materials, suitable for industrial production, and low-eutectic solvents have good biodegradability and meet green chemical requirements.
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Figure CN120097913B_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of green organic synthesis, and particularly relates to a method for preparing an N-sulfonylpyrazole compound. Background Art
[0002] Pyrazoles are a very important class of N-heterocyclic compounds, widely used in pharmaceuticals and pesticides. Given the importance of sulfonyl compounds in pharmaceuticals, research has focused on introducing sulfonyl moieties into the pyrazole molecular framework. Sulfonyl hydrazides and their variants, sulfonylhydrazones, are important sources of sulfonyl moieties and possess excellent reactivity. They have garnered significant attention in the synthesis of N-sulfonyl pyrazoles in recent years.
[0003] Although the synthesis of N-sulfonylpyrazole compounds has been reported, such as the cyclization reaction of sulfonylhydrazide with enaminone / dithioketal, the traditional synthesis method has complicated preparation steps, which limits its application in drug development and industrial scale-up production. Summary of the Invention
[0004] The object of the present invention is to provide a method for preparing N-sulfonylpyrazole compounds. The preparation method provided by the present invention has simple steps and is highly efficient.
[0005] In order to achieve the above object, the present invention provides the following technical solutions:
[0006] The present invention provides a method for preparing an N-sulfonylpyrazole compound, comprising the following steps:
[0007] A sulfonylhydrazide compound, a β-dicarbonyl compound and a deep eutectic solvent (DESs) are mixed to perform a cyclization reaction to obtain the N-sulfonylpyrazole compound; the deep eutectic solvent includes one or both of choline chloride (ChCl)-oxalic acid (OA) and choline chloride (ChCl)-ethylene glycol (EG).
[0008] Preferably, the sulfonylhydrazide compound has a structure shown in Formula I:
[0009] Formula I;
[0010] In Formula I, R 1 is phenyl, substituted phenyl, naphthyl, pyridyl or quinolyl.
[0011] Preferably, the substituted phenyl group is a halogenphenyl group, a nitrophenyl group, a tolyl group or a methoxyphenyl group; the halogenphenyl group is a fluorophenyl group, a chlorophenyl group, a bromophenyl group or an iodophenyl group.
[0012] Preferably, the β-dicarbonyl compound has a structure shown in Formula II:
[0013] Formula II;
[0014] In Formula II, R 2 is a C1~C4 alkyl group or a phenyl group; R 3 is H, methyl or halogen.
[0015] Preferably, the C1-C4 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; and the halogen group is fluoro, chloro, bromo or iodo.
[0016] Preferably, the molar ratio of the sulfonylhydrazide compound to the β-dicarbonyl compound is 1-1.2:1-1.5; and the volume ratio of the sulfonylhydrazide compound to the deep eutectic solvent is not greater than 1.75 mmol:0.43 mL.
[0017] Preferably, the molar ratio of choline chloride to oxalic acid in the choline chloride-oxalic acid is 1-2:1-5; the molar ratio of choline chloride to ethylene glycol in the choline chloride-ethylene glycol is 1-2:1-5.
[0018] Preferably, the temperature of the cyclization reaction is 60-90° C., and the holding time is more than 1 h; the cyclization reaction is carried out in an oil bath.
[0019] Preferably, after the cyclization reaction, the obtained product system is further subjected to post-treatment; when the N-sulfonylpyrazole compound is a solid, the post-treatment is method one, and the method one is: the obtained product system is cooled, water is added, solid-liquid separation and drying are carried out in sequence; when the N-sulfonylpyrazole compound is a liquid, the post-treatment is method two, and the method two is: the obtained product system is cooled, water is added, extracted, solvent removed and dried in sequence.
[0020] Preferably, the post-treatment further comprises removing water from the liquid obtained from the solid-liquid separation or the raffinate obtained from the extraction, and collecting the low eutectic solvent for recycling.
[0021] The present invention provides a method for preparing N-sulfonylpyrazole compounds. The present invention uses a low eutectic solvent as a reaction solvent and also as a catalyst to catalyze the cyclization reaction of a sulfonylhydrazine compound and a β-dicarbonyl compound to prepare an N-sulfonylpyrazole compound. The preparation method provided by the present invention only requires one-step reaction to obtain the product, with efficient preparation and simple operation; the post-processing is simple, and the solid product in the reaction process is directly precipitated from the system without the need for organic solvent extraction, and the liquid product can be obtained by extraction without the need for complex post-processing such as column chromatography purification; the product has a high yield and good versatility, and the raw materials are cheap and easily available, with low cost, making it suitable for industrial-scale production; at the same time, the low eutectic solvent used in the present invention has good biodegradability, can be rapidly degraded in the environment, has low volatility, is easy to prepare, can be recycled, reduces the generation of waste and waste of resources, is friendly to the environment and the health of operators, and meets the development requirements of green chemistry. BRIEF DESCRIPTION OF THE DRAWINGS
[0022] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.
[0023] Figure 1 This is the infrared spectrum of the deep eutectic solvent prepared in Example 11;
[0024] Figure 2 This is a thermogravimetric analysis chart of the deep eutectic solvent prepared in Example 11;
[0025] Figure 3 This is the H NMR spectrum of the N-sulfonylpyrazole compound prepared in Example 12;
[0026] Figure 4 This is the C NMR spectrum of the N-sulfonylpyrazole compound prepared in Example 12;
[0027] Figure 5 This is a high-resolution mass spectrum of the N-sulfonylpyrazole compound prepared in Example 12;
[0028] Figure 6 This is a liquid chromatogram of the N-sulfonylpyrazole compound prepared in Example 12;
[0029] Figure 7 This is a graph showing the relationship between the number of deep eutectic solvent cycles and the yield of N-sulfonylpyrazole compounds in Test Example 3. DETAILED DESCRIPTION
[0030] The present invention provides a method for preparing an N-sulfonylpyrazole compound, comprising the following steps:
[0031] A sulfonylhydrazide compound, a β-dicarbonyl compound and a deep eutectic solvent are mixed to carry out a cyclization reaction to obtain the N-sulfonylpyrazole compound.
[0032] The present invention mixes a sulfonylhydrazide compound, a β-dicarbonyl compound, and a deep eutectic solvent to obtain a reaction solution. In the present invention, the sulfonylhydrazide compound has a structure shown in Formula I:
[0033] Formula I;
[0034] In Formula I, R 1 is phenyl, substituted phenyl, naphthyl, pyridyl or quinolyl.
[0035] In the present invention, the substituted phenyl group may be a halogenphenyl group, a nitrophenyl group, a tolyl group or a methoxyphenyl group; the halogenphenyl group may be a fluorophenyl group, a chlorophenyl group, a bromophenyl group or an iodophenyl group.
[0036] In the present invention, the sulfonylhydrazine compound may include one or more of benzenesulfonylhydrazine, 4-methoxybenzenesulfonylhydrazine, 4-fluorobenzenesulfonylhydrazine, 4-nitrobenzenesulfonylhydrazine, 4-bromobenzenesulfonylhydrazine, 2,4,6-trimethylbenzenesulfonylhydrazine, p-toluenesulfonylhydrazine, m-toluenesulfonylhydrazine, 2-naphthalenesulfonylhydrazine, 4,4'-oxybisbenzenesulfonylhydrazine and 2,4,6-triisopropylbenzenesulfonylhydrazine.
[0037] In the present invention, the β-dicarbonyl compound has a structure shown in Formula II:
[0038] Formula II;
[0039] In Formula II, R 2 is a C1~C4 alkyl group or a phenyl group; R 3 is H, methyl or halogen.
[0040] In the present invention, the C1-C4 alkyl group may be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; the halogen group may be fluoro, chloro, bromo or iodo.
[0041] In the present invention, the β-dicarbonyl compound may include one or more of acetylacetone, 3-methylacetylacetone, 3,5-diheptanone and 2,6-dimethyl-3,5-diheptanone.
[0042] In the present invention, the molar ratio of the sulfonylhydrazide compound to the β-dicarbonyl compound may be 1-1.2:1-1.5, specifically 1.2:1, 1.1:1, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4 or 1:1.5.
[0043] In the present invention, the deep eutectic solvent may include one or both of choline chloride-oxalic acid (a hydrogen-bonded mixture of choline chloride and oxalic acid) and choline chloride-ethylene glycol (a hydrogen-bonded mixture of choline chloride and ethylene glycol), preferably choline chloride-ethylene glycol; the molar ratio of choline chloride to oxalic acid in the choline chloride-oxalic acid may be 1-2:1-5, specifically 1:1, 1:2, 1:3, 1:4, 1:5, 1.5:1, 1.5:2, 1.5:4, 1.5:5, 2:1, 2:3 or 2:5, preferably 2:1; the molar ratio of choline chloride and ethylene glycol in the choline chloride-ethylene glycol can be 1-2:1-5, specifically 1:1, 1:2, 1:3, 1:4, 1:5, 1.5:1, 1.5:2, 1.5:4, 1.5:5, 2:1, 2:3 or 2:5, preferably 1:5. The deep eutectic solvent prepared by the present invention is homogeneous and stable, and the use of choline chloride-ethylene glycol has a higher product yield.
[0044] In the present invention, the deep eutectic solvent can be prepared by mixing choline chloride with oxalic acid or ethylene glycol, and stirring at 70-100°C for 0.5-1 hour to allow hydrogen bonding to occur, thereby obtaining a colorless, transparent, and stable deep eutectic solvent. In the present invention, choline chloride and oxalic acid or ethylene glycol form a deep eutectic solvent having a lower melting point than either element through hydrogen bonding.
[0045] In the present invention, the ratio of the amount of the sulfonylhydrazide compound to the volume of the deep eutectic solvent may be no more than 1.75 mmol:0.43 mL, preferably (1-1.75) mmol:(0.43-2.5) mL, specifically 1 mmol:0.43 mL, 1 mmol:0.75 mL, 1 mmol:1 mL, 1 mmol:1.2 mL, 1 mmol:1.4 mL, 1 mmol:1.6 mL, 1mmol:1.8 mL, 1 mmol:2 mL, 1 mmol:2.2 mL, 1 mmol:2.4 mL, 1 mmol:2.5 mL, 1.2 mmol:0.43 mL, 1.2 mmol:0.75 mL, 1.2 mmol:1 mL, 1.2 mmol:1.2 mL, 1.2 mmol:1.4 mL, 1.2 mmol:1.6 mL, 1.2 mmol:1.8 mL, 1.2 mmol:2 mL, 1.2 mmol: 2.2 mL, 1.2 mmol: 2.4 mL, 1.2 mmol: 2.5 mL, 1.4 mmol: 0.43 mL, 1.4 mmol: 0.75 mL, 1.4 mmol: 1 mL, 1.4 mmol: 1.2 mL, 1.4 mmol: 1.4 mL, 1.4 mmol: 1.6 mL, 1.4 mmol: 1.8 mL, 1.4 mmol: 2 mL, 1.4 mmol: 2.2 mL, 1.4 mmol: 2.4 mL, 1.4 mmol: 2.5 mL, 1.6 mmol: 0.43 mL, 1.6 mmol: 0.75 mL, 1.6 mmol: 1 mL, 1.6 mmol: 1.2 mL, 1.6 mmol: 1.4 mL, 1.6 mmol:1.6 mL, 1.6 mmol:1.8 mL, 1.6mmol:2 mL, 1.6 mmol:2.2 The present invention uses the above-mentioned amount of deep eutectic solvent to better dissolve the reaction raw materials sulfonylhydrazide compound and β-dicarbonyl compound.
[0046] After obtaining the reaction solution, the present invention further subjects the reaction solution to a cyclization reaction to obtain the N-sulfonylpyrazole compound. In the present invention, the cyclization reaction temperature can be 60-90°C, specifically 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, or 90°C, and the holding time can be 1 hour or longer, specifically 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 15 hours, 18 hours, 21 hours, 24 hours, or 36 hours. The cyclization reaction can be carried out in an oil bath. The preparation method provided by the present invention has mild reaction conditions and is easily industrialized and scalable.
[0047] In the present invention, the chemical reaction of the cyclization reaction is as follows:
[0048] .
[0049] In the present invention, the cyclization reaction may further include post-processing the obtained product system; when the N-sulfonylpyrazole compound is a solid, the post-processing may be method 1, and the method 1 may be: cooling the product system obtained by the cyclization reaction, adding water, solid-liquid separation and drying in sequence.
[0050] In the present invention, the final cooling temperature can be room temperature; the ratio of the volume of water to the amount of the sulfonylhydrazide compound can be no less than 20 mL:3.5 mmol; the solid-liquid separation can be filtration, which can be suction filtration. During the cyclization reaction, a solid product will precipitate. Adding water can completely precipitate the solid product and dilute the deep eutectic solvent, facilitating subsequent solid-liquid separation.
[0051] In the present invention, when the N-sulfonylpyrazole compound is a liquid, the post-treatment may be method two, which may include sequentially cooling the product system obtained from the cyclization reaction, adding water, extracting, removing solvents, and drying; the extraction agent may be an organic solvent; the organic solvent may be ethyl acetate; and the solvent removal may be rotary evaporation. The liquid product does not precipitate during the cyclization reaction. The addition of water in the present invention facilitates subsequent extraction of the liquid product with an organic solvent, eliminating the need for complex post-treatment methods such as column chromatography purification.
[0052] The present invention can obtain N-sulfonylpyrazole compounds through simple post-treatment. The N-sulfonylpyrazole compounds prepared by the present invention are mostly solid and can be obtained by post-treatment according to the first method. Only a small amount of N-sulfonylpyrazole compounds are liquid and can be obtained by post-treatment according to the second method, without the need for complex treatment such as column chromatography purification.
[0053] In the present invention, the post-treatment may further include removing water from the liquid obtained by the solid-liquid separation or the raffinate obtained by the extraction, and collecting the deep eutectic solvent for recycling. The water removal method may be distillation, and the distillation may be vacuum distillation. The present invention achieves recycling of the deep eutectic solvent by removing water.
[0054] In the present invention, the structure of the N-sulfonylpyrazole compound is shown in Formula III:
[0055] Formula III;
[0056] In formula III, R 1 is phenyl, substituted phenyl, naphthyl, pyridyl or quinolyl; R 2 is a C1~C4 alkyl group or a phenyl group; R 3 is H, methyl or halogen.
[0057] In the present invention, the substituted phenyl group may be a halophenyl group, a nitrophenyl group, a tolyl group or a methoxyphenyl group; the halophenyl group may be a fluorophenyl group, a chlorophenyl group, a bromophenyl group or an iodophenyl group; the C1~C4 alkyl group may be a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group; the halogen group may be a fluoro group, a chloro group, a bromo group or an iodo group.
[0058] In order to further illustrate the present invention, the scheme of the present invention is described in detail below with reference to the accompanying drawings and embodiments, but they should not be understood as limiting the scope of protection of the present invention.
[0059] Example 1 Preparation of Choline Chloride-Oxalic Acid Deep Eutectic Solvent:
[0060] Take choline chloride (6 mmol) and oxalic acid (3 mmol, the molar ratio of choline chloride:oxalic acid is 2:1) in a round-bottom flask, heat and stir in a constant temperature oil bath at 80°C until melted, and react by hydrogen bonding for 30 min. Cool to room temperature, and dry to obtain a choline chloride-oxalic acid deep eutectic solvent for later use.
[0061] Example 2 Preparation of Choline Chloride-Oxalic Acid Deep Eutectic Solvent:
[0062] Take choline chloride (6 mmol) and oxalic acid (6 mmol, the molar ratio of choline chloride:oxalic acid is 1:1) in a round-bottom flask, heat and stir in a constant temperature oil bath at 80°C until melted, and react by hydrogen bonding for 30 min. Cool to room temperature and dry to obtain a choline chloride-oxalic acid deep eutectic solvent for later use.
[0063] Example 3 Preparation of Choline Chloride-Oxalic Acid Deep Eutectic Solvent:
[0064] Take choline chloride (6 mmol) and oxalic acid (12 mmol, the molar ratio of choline chloride:oxalic acid is 1:2) in a round-bottom flask, heat and stir in a constant temperature oil bath at 80°C until melted, and react by hydrogen bonding for 30 min. Cool to room temperature, and dry to obtain a choline chloride-oxalic acid deep eutectic solvent for later use.
[0065] Example 4 Preparation of Choline Chloride-Oxalic Acid Deep Eutectic Solvent:
[0066] Take choline chloride (6 mmol) and oxalic acid (18 mmol, the molar ratio of choline chloride:oxalic acid is 1:3) in a round-bottom flask, heat and stir in a constant temperature oil bath at 80°C until melted, and react by hydrogen bonding for 30 min. Cool to room temperature and dry to obtain a choline chloride-oxalic acid deep eutectic solvent for later use.
[0067] Example 5 Preparation of Choline Chloride-Oxalic Acid Deep Eutectic Solvent:
[0068] Take choline chloride (6 mmol) and oxalic acid (24 mmol, the molar ratio of choline chloride:oxalic acid is 1:4) in a round-bottom flask, heat and stir in a constant temperature oil bath at 80°C until melted, and react by hydrogen bonding for 30 min. Cool to room temperature, and dry to obtain a choline chloride-oxalic acid deep eutectic solvent for later use.
[0069] Example 6 Preparation of Choline Chloride-Oxalic Acid Deep Eutectic Solvent:
[0070] Take choline chloride (6 mmol) and oxalic acid (4 mmol, the molar ratio of choline chloride:ethylene glycol is 1.5:1) in a round-bottom flask, heat and stir in a constant temperature oil bath at 80°C until melted, and react by hydrogen bonding for 30 min. Cool to room temperature, and dry to obtain a choline chloride-oxalic acid deep eutectic solvent for later use.
[0071] Example 7 Preparation of Choline Chloride-Ethylene Glycol Deep Eutectic Solvent:
[0072] Take choline chloride (6 mmol) and ethylene glycol (6 mmol, the molar ratio of choline chloride:ethylene glycol is 1:1) in a round-bottom flask, heat and stir in a constant temperature oil bath at 80°C until melted, react by hydrogen bonding for 30 min, cool to room temperature, and dry to obtain a choline chloride-ethylene glycol deep eutectic solvent for use.
[0073] Example 8 Preparation of Choline Chloride-Ethylene Glycol Deep Eutectic Solvent:
[0074] Take choline chloride (3 mmol) and ethylene glycol (6 mmol, the molar ratio of choline chloride:ethylene glycol is 1:2) in a round-bottom flask, heat and stir in a constant temperature oil bath at 80°C until melted, react by hydrogen bonding for 30 min, cool to room temperature, and dry to obtain a choline chloride-ethylene glycol deep eutectic solvent for later use.
[0075] Example 9 Preparation of Choline Chloride-Ethylene Glycol Deep Eutectic Solvent:
[0076] Take choline chloride (3 mmol) and ethylene glycol (9 mmol, the molar ratio of choline chloride:ethylene glycol is 1:3) in a round-bottom flask, heat and stir in a constant temperature oil bath at 80°C until melted, react by hydrogen bonding for 30 min, cool to room temperature, and dry to obtain a choline chloride-ethylene glycol deep eutectic solvent for later use.
[0077] Example 10 Preparation of Choline Chloride-Ethylene Glycol Deep Eutectic Solvent:
[0078] Take choline chloride (3 mmol) and ethylene glycol (12 mmol, the molar ratio of choline chloride:ethylene glycol is 1:4) in a round-bottom flask, heat and stir in an 80°C constant temperature oil bath until melted, and react by hydrogen bonding for 30 min. Cool to room temperature and dry to obtain a choline chloride-ethylene glycol deep eutectic solvent for later use.
[0079] Example 11 Preparation of Choline Chloride-Ethylene Glycol Deep Eutectic Solvent:
[0080] Take choline chloride (3 mmol) and ethylene glycol (15 mmol, the molar ratio of choline chloride:ethylene glycol is 1:5) in a round-bottom flask, heat and stir in an 80°C constant temperature oil bath until melted, and react by hydrogen bonding for 30 min. Cool to room temperature and dry to obtain a choline chloride-ethylene glycol deep eutectic solvent for later use.
[0081] Example 12 Preparation of N-sulfonylpyrazole compound—N-p-toluenesulfonyl-3,5-dimethylpyrazole:
[0082] Toluenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a deep eutectic solvent (the deep eutectic solvent prepared in Example 11) were added in sequence to a 50 mL dry round-bottom flask. The mixed system was reacted at 70°C for 5 h, during which time it was continuously monitored by thin-layer chromatography. After the reaction was completed, the mixture was cooled to room temperature, and an appropriate amount of water (30 mL) was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound, N-p-toluenesulfonyl-3,5-dimethylpyrazole, as a white solid (yield 98.23%) with a melting point of 92-94°C. The H NMR spectrum, C NMR spectrum, high-resolution mass spectrum and liquid chromatography of the N-sulfonylpyrazole compound prepared in this example are shown below. Figures 3 to 6 As shown:
[0083] 1 H NMR (400 MHz, CDCl3) δ: 7.83 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz,2H), 5.90 (s, 1H), 2.49 (s, 3H), 2.40 (s, 3H), 2.20 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ: 153.28, 145.06, 143.95, 135.22, 129.78, 127.41, 110.65, 21.52,13.70, 12.97; HRMS calcd for C 12 H 15 N2O2S[M+H] + : 251.0854; found: 251.0856.
[0084] according to Figures 3 to 6 It can be seen that the present invention successfully prepared an N-sulfonylpyrazole compound, N-toluenesulfonyl-3,5-dimethylpyrazole, and its purity was 95.48% as characterized by liquid chromatography.
[0085] Example 13 Preparation of N-sulfonylpyrazole compounds:
[0086] The preparation method of this example is the same as that of Example 12, except that the deep eutectic solvent of Example 11 is replaced by the deep eutectic solvent of Example 9, and the amount of the deep eutectic solvent is replaced by 3.5 mL to obtain N-sulfonylpyrazole compounds (yield: 94.73%).
[0087] Example 14 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant amounts):
[0088] The preparation method of this example is the same as that of Example 13, except that the amount of p-toluenesulfonylhydrazine in Example 13 is replaced by 3 mmol, and the amount of acetylacetone is replaced by 3.3 mmol, to obtain N-sulfonylpyrazole compounds (yield: 91.71%).
[0089] Example 15 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant amounts):
[0090] The preparation method of this example is the same as that of Example 13, except that the amount of p-toluenesulfonylhydrazine in Example 13 is replaced by 3 mmol, and the amount of acetylacetone is replaced by 3.5 mmol, to obtain N-sulfonylpyrazole compounds (yield: 89.14%).
[0091] Example 16 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant amounts):
[0092] The preparation method of this example is the same as that of Example 13, except that the amount of p-toluenesulfonylhydrazine in Example 13 is replaced by 3 mmol, and the amount of acetylacetone is replaced by 3.6 mmol, to obtain N-sulfonylpyrazole compounds (yield: 82.65%).
[0093] Example 17 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant amounts):
[0094] The preparation method of this example is the same as that of Example 13, except that the amount of p-toluenesulfonylhydrazine in Example 13 is replaced by 3 mmol, and the amount of acetylacetone is replaced by 4.5 mmol, to obtain N-sulfonylpyrazole compounds (yield: 76.21%).
[0095] Example 18 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant amounts):
[0096] The preparation method of this example is the same as that of Example 13, except that the amount of p-toluenesulfonylhydrazine in Example 13 is replaced by 3.6 mmol, and the amount of acetylacetone is replaced by 3 mmol, to obtain N-sulfonylpyrazole compounds (yield: 42.29%).
[0097] Example 19 Preparation of N-sulfonylpyrazole compounds (reaction temperature adjustment):
[0098] The preparation method of this example is the same as that of Example 13, except that the reaction temperature of Example 13 is replaced with 60° C. to obtain N-sulfonylpyrazole compounds (yield is 74.19%).
[0099] Example 20 Preparation of N-sulfonylpyrazole compounds (reaction temperature adjustment):
[0100] The preparation method of this example is the same as that of Example 13, except that the reaction temperature of Example 13 is replaced with 80° C. to obtain N-sulfonylpyrazole compounds (yield is 84.11%).
[0101] Example 21 Preparation of N-sulfonylpyrazole compounds (reaction temperature adjustment):
[0102] The preparation method of this example is the same as that of Example 13, except that the reaction temperature of Example 13 is replaced with 90° C. to obtain N-sulfonylpyrazole compounds (yield: 46.03%).
[0103] Example 22 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent):
[0104] The preparation method of this example is the same as that of Example 12, except that the volume of the deep eutectic solvent of Example 12 is replaced with 1.5 mL to obtain N-sulfonylpyrazole compounds (yield: 91.23%).
[0105] Example 23 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent):
[0106] The preparation method of this example is the same as that of Example 12, except that the volume of the deep eutectic solvent of Example 12 is replaced with 2 mL to obtain N-sulfonylpyrazole compounds (yield: 93.67%).
[0107] Example 24 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent):
[0108] The preparation method of this example is the same as that of Example 12, except that the volume of the deep eutectic solvent of Example 12 is replaced with 2.5 mL to obtain N-sulfonylpyrazole compounds (yield: 95.06%).
[0109] Example 25 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent):
[0110] The preparation method of this example is the same as that of Example 12, except that the volume of the deep eutectic solvent of Example 12 is replaced with 3.5 mL to obtain N-sulfonylpyrazole compounds (yield: 97.44%).
[0111] Example 26 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent):
[0112] The preparation method of this example is the same as that of Example 12, except that the volume of the deep eutectic solvent of Example 12 is replaced with 4 mL to obtain N-sulfonylpyrazole compounds (yield: 96.46%).
[0113] Example 27 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent):
[0114] The preparation method of this example is the same as that of Example 12, except that the volume of the deep eutectic solvent of Example 12 is replaced with 4.5 mL to obtain N-sulfonylpyrazole compounds (yield: 93.36%).
[0115] Example 28 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent):
[0116] The preparation method of this example is the same as that of Example 12, except that the volume of the deep eutectic solvent of Example 12 is replaced with 5 mL to obtain N-sulfonylpyrazole compounds (yield: 92.84%).
[0117] Example 29 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent):
[0118] The preparation method of this example is the same as that of Example 12, except that the volume of the deep eutectic solvent of Example 12 is replaced with 8 mL to obtain N-sulfonylpyrazole compounds (yield: 91.35%).
[0119] Example 30 Preparation of N-sulfonylpyrazole compounds (reaction time adjustment):
[0120] The preparation method of this example is the same as that of Example 12, except that the reaction time of Example 12 is replaced with 1 h to obtain N-sulfonylpyrazole compounds (yield is 88.44%).
[0121] Example 31 Preparation of N-sulfonylpyrazole compounds (reaction time adjustment):
[0122] The preparation method of this example is the same as that of Example 12, except that the reaction time of Example 12 is replaced with 3 h to obtain N-sulfonylpyrazole compounds (yield is 94.93%).
[0123] Example 32 Preparation of N-sulfonylpyrazole compounds (reaction time adjustment):
[0124] The preparation method of this example is the same as that of Example 12, except that the reaction time of Example 12 is replaced with 4 h to obtain N-sulfonylpyrazole compounds (yield is 95.18%).
[0125] Example 33 Preparation of N-sulfonylpyrazole compounds (reaction time adjustment):
[0126] The preparation method of this example is the same as that of Example 12, except that the reaction time of Example 12 is replaced with 6 h to obtain N-sulfonylpyrazole compounds (yield is 95.09%).
[0127] Example 34 Preparation of N-sulfonylpyrazole compounds (adjustment of deep eutectic solvent type):
[0128] The preparation method of this example is the same as that of Example 13, except that the deep eutectic solvent of Example 9 is replaced by the deep eutectic solvent of Example 1. The raw material conversion rate of this example is 100%, and the product yield of the N-sulfonylpyrazole compound is 39.47%.
[0129] Example 35 Preparation of N-sulfonylpyrazole compounds (adjustment of deep eutectic solvent type):
[0130] The preparation method of this example is the same as that of Example 13, except that the deep eutectic solvent of Example 9 is replaced by the deep eutectic solvent of Example 8. The raw material conversion rate of this example is 100%, and the product yield of the N-sulfonylpyrazole compound is 90.90%.
[0131] Example 36 Preparation of N-sulfonylpyrazole compounds (adjustment of deep eutectic solvent type):
[0132] The preparation method of this example is the same as that of Example 13, except that the deep eutectic solvent of Example 9 is replaced with the deep eutectic solvent of Example 10. The raw material conversion rate of this example is 100%, and the product yield of the N-sulfonylpyrazole compound is 94.95%.
[0133] Example 37 Preparation of N-sulfonylpyrazole compounds (adjustment of deep eutectic solvent type):
[0134] The preparation method of this example is the same as that of Example 13, except that the deep eutectic solvent of Example 9 is replaced with the deep eutectic solvent of Example 11. The raw material conversion rate of this example is 100%, and the product yield of the N-sulfonylpyrazole compound is 97.44%.
[0135] Example 38 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types):
[0136] Benzenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a deep eutectic solvent (prepared in Example 11) were added sequentially to a 50 mL dry round-bottom flask. The mixture was reacted at 70°C for 5 h, continuously monitored by thin-layer chromatography. After the reaction was completed, the mixture was cooled to room temperature and an appropriate amount of water (30 mL) was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a white solid (yield 84.71%) with a melting point of 80-82°C.
[0137] 1 H NMR (400 MHz, CDCl3) δ: 7.97 – 7.93 (m, 2H), 7.62 (dd, J = 8.5, 6.4Hz, 1H), 7.52 (t, J = 7.7 Hz, 2H), 5.91 (s, 1H), 2.50 (s, 3H), 2.20 (s, 3H); 13 CNMR (100 MHz, CDCl3) δ: 153.59, 144.20, 138.28, 133.95, 129.24, 127.49,110.85, 13.81, 13.09; HRMS calcd for C 11 H 13 N2O2S [M+H] + : 237.0698; found:237.0699.
[0138] Example 39 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types):
[0139] In a 50 mL dry round-bottom flask, 4-methoxybenzenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol), and 3 mL of a deep eutectic solvent (the deep eutectic solvent prepared in Example 11) were added in sequence. The mixture was reacted at 70°C for 5 h, during which time it was continuously monitored by thin-layer chromatography. After the reaction was completed, the mixture was cooled to room temperature and an appropriate amount of water (30 mL) was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a white solid (yield 97.69%) with a melting point of 126-128°C.
[0140] 1 H NMR (400 MHz, CDCl3) δ: 7.90 (dd, J = 8.0, 2.0 Hz, 2H), 6.97 (dd, J=8.0, 2.0 Hz, 2H), 5.88 (s, 1H), 3.85 (s, 3H), 2.49 (s, 3H), 2.20 (s, 3H); 13 CNMR (100 MHz, CDCl3) δ: 163.89, 153.19, 143.87, 129.87, 129.72, 114.41,110.56, 55.67, 13.81, 13.09; HRMS calcd for C 12 H 15 N2O3S [M+H] + : 267.0803;found: 267.0806.
[0141] Example 40 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types):
[0142] 4-Fluorobenzenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol), and 3 mL of a deep eutectic solvent (prepared in Example 11) were added sequentially to a 50 mL dry round-bottom flask. The mixture was reacted at 70°C for 5 h, continuously monitored by thin-layer chromatography. After the reaction was completed, the mixture was cooled to room temperature and an appropriate amount of water (30 mL) was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a white solid (yield 87.28%) with a melting point of 87-89°C.
[0143] 1 H NMR (400 MHz, CDCl3) δ: 8.05–7.93 (m, 2H), 7.27–7.17 (m, 2H), 5.94 (s, 1H), 2.53 (s, 3H), 2.23 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ: 165.79 (d, J =257.3 Hz), 153.85, 144.24, 134.27, 130.51(d, J = 9.7 Hz), 116.62 (d, J = 22.8Hz), 110.93, 13.81,13.11; HRMS calcd for C 11 H 12 N2O2SF [M+H] + : 255.0604; found:255.0607.
[0144] Example 41 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types):
[0145] In a 50 mL dry round-bottom flask, 4-nitrobenzenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol), and 3 mL of a deep eutectic solvent (the deep eutectic solvent prepared in Example 11) were added in sequence. The mixture was reacted at 70°C for 5 h, during which time it was continuously monitored by thin-layer chromatography. After the reaction was completed, the mixture was cooled to room temperature and an appropriate amount of water (30 mL) was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a white solid (yield 91.08%) with a melting point of 177-179°C.
[0146] 1 H NMR (400 MHz, CDCl3) δ: 8.34 (d, J = 8.4 Hz, 2H), 8.13 (d, J = 8.4 Hz,2H), 5.94 (s, 1H), 2.50 (s, 3H), 2.17 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ:154.76, 150.60, 144.71, 143.40, 128.90, 124.39, 111.48, 13.70, 13.01; HRMScalcd for C 11 H 12 N3O4S[M+H] + : 282.0548; found:282.0542.
[0147] Example 42 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types):
[0148] 4-Bromobenzenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol), and 3 mL of a deep eutectic solvent (prepared in Example 11) were added sequentially to a 50 mL dry round-bottom flask. The mixture was reacted at 70°C for 5 h, continuously monitored by thin-layer chromatography. After the reaction was completed, the mixture was cooled to room temperature and an appropriate amount of water (30 mL) was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a white solid (yield 91.56%) with a melting point of 94-96°C.
[0149] 1 H NMR (400 MHz, CDCl3) δ: 7.82 (d, J = 8.7 Hz, 2H), 7.66 (d, J= 8.8 Hz,2H), 5.92 (s, 1H), 2.49 (s, 3H), 2.20 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ:153.59, 144.20, 138.30, 133.94, 129.23, 127.49, 110.84, 13.81, 13.08; HRMScalcd for C 11 H 12 N2O2SBr[M+H] + : 314.9803.0548; found:314.9804.
[0150] Example 43 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types):
[0151] In a 50 mL dry round-bottom flask, 2,4,6-trimethylbenzenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a deep eutectic solvent (the deep eutectic solvent prepared in Example 11) were added in sequence. The mixed system was reacted at 70°C for 5 h, during which time it was continuously monitored by thin-layer chromatography. After the reaction was completed, the mixture was cooled to room temperature and an appropriate amount of water (30 mL) was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a white solid (yield 92.18%) with a melting point of 106-108°C.
[0152] 1 H NMR (400 MHz, CDCl3) δ: 6.96 (s, 2H), 5.88 (s, 1H), 2.56 (s, 6H), 2.45 (s, 3H), 2.31 (s, 3H), 2.16 (s, 3H); 13 HRMS calcd for C 14 H 19 N2O2S [M+H] + : 279.1167; found: 279.1170.
[0153] Example 44 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types):
[0154] To a 50 mL dry round-bottom flask, p-toluenesulfonylhydrazide (3.5 mmol), 3-methylacetylacetone (3.5 mmol), and 3 mL of a deep eutectic solvent (the deep eutectic solvent prepared in Example 11) were added in sequence. The mixture was reacted at 70°C for 5 h, during which time it was continuously monitored by thin-layer chromatography. After the reaction was completed, the mixture was cooled to room temperature, and an appropriate amount of water (30 mL) was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a white solid (yield 95.63%) with a melting point of 139-141°C.
[0155] 1 H NMR (400 MHz, CDCl3) δ: 7.80 (d, J = 7.6 Hz, 2H), 7.29 (d, J = 7.7 Hz,2H), 2.40 (s, 6H), 2.15 (s, 3H), 1.83 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ: 153.60, 144.81, 139.49, 135.42, 129.73, 127.33, 117.15, 21.52, 12.30, 11.20,7.89; 13 H 17 N2O2S [M+H] + : 265.1011; found:265.1008.
[0156] Example 45 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types):
[0157] To a 50 mL dry round-bottom flask, p-toluenesulfonylhydrazide (3.5 mmol), 3,5-diheptanone (3.5 mmol), and 3 mL of a deep eutectic solvent (prepared in Example 11) were added in sequence. The mixture was reacted at 70°C for 5 h while continuously monitored by thin-layer chromatography. After the reaction was completed, the mixture was cooled to room temperature and an appropriate amount of water (30 mL) was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a colorless liquid (yield: 89.42%).
[0158] 1 H NMR (400 MHz, CDCl3) δ: 7.82 (d, J = 7.9 Hz, 2H), 7.29 (d, J = 7.8 Hz,2H), 5.97 (s, 1H), 2.92 (q, J= 7.4 Hz, 2H), 2.59 (q, J = 7.6 Hz, 2H), 2.39 (s,3H), 1.25 (t, J = 7.3 Hz, 3H), 1.17 (t, J = 7.6 Hz, 3H); 13 HRMS calcd for C 14 H 19 N2O2S [M+H] + : 279.1167; found: 279.1167.
[0159] Example 46 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types):
[0160] To a 50 mL dry round-bottom flask, p-toluenesulfonylhydrazide (3.5 mmol), 2,6-dimethyl-3,5-diheptanone (3.5 mmol), and 3 mL of a deep eutectic solvent (prepared in Example 11) were added in sequence. The mixture was reacted at 70°C for 5 h, continuously monitored by thin-layer chromatography. After the reaction was completed, the mixture was cooled to room temperature, and an appropriate amount of water (30 mL) was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a light yellow liquid (yield: 86.79%).
[0161] 1 H NMR (400 MHz, CDCl3) δ: 7.81 (d, J = 7.8 Hz, 1H), 7.28 (d, J = 7.6 Hz,1H), 5.98 (s, 1H), 3.68–3.49 (m, 1H), 3.02–2.82 (m, 1H), 2.40 (s, 3H), 1.25(d, J = 6.8 Hz, 6H), 1.18 (d, J = 7.0 Hz, 6H); 13HRMS calcd for C 16 H 23 N2O2S [M+H] + : 307.1480; found: 307.1481.
[0162] Example 47 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types):
[0163] In a 50 mL dry round-bottom flask, m-toluenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol), and 3 mL of a deep eutectic solvent (the deep eutectic solvent prepared in Example 11) were added in sequence. The mixed system was reacted at 70°C for 24 h, continuously monitored by thin-layer chromatography. After the reaction was completed, the mixture was cooled to room temperature, an appropriate amount of water (30 mL) was added, and the mixture was extracted with ethyl acetate. The organic solvent in the product was removed by rotary evaporation and dried to obtain an N-sulfonylpyrazole compound as a colorless liquid (yield 76.35%).
[0164] 1 H NMR (400 MHz, CDCl3) δ: 7.76–7.61 (m, 2H), 7.34 (s, 2H), 5.83 (s,1H), 2.43 (s, 3H), 2.35 (s, 3H), 2.14 (s, 3H); 13 HRMS calcd for C 12 H 14 N2O2SNa [M+Na] + : 273.0677; found:273.0674.
[0165] Example 48 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types):
[0166] 2-Naphthalenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a deep eutectic solvent (prepared in Example 11) were added sequentially to a 50 mL dry round-bottom flask. The mixture was reacted at 70°C for 24 h while continuously monitored by thin-layer chromatography. After the reaction was completed, the mixture was cooled to room temperature, an appropriate amount of water (30 mL) was added, and the mixture was extracted with ethyl acetate. The organic solvent in the product was removed by rotary evaporation and dried to obtain an N-sulfonylpyrazole compound as a light yellow liquid (yield 80.78%).
[0167] 1 H NMR (400 MHz, CDCl3) δ: 8.58 (s, 1H), 8.07 – 7.80 (m, 4H), 7.73-7.55 (m, 2H), 5.90 (s, 1H), 2.55 (s, 3H), 2.20 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 153.60, 144.14, 135.34, 135.18, 131.95, 129.62, 129.58, 129.52,127.94, 127.70, 122.14, 110.83, 13.92, 13.30; HRMS calcd for C 15 H 14 N2O2SNa [M+Na] + : 309.0675; found:309.0674.
[0168] Example 49 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types):
[0169] In a 50 mL dry round-bottom flask, 4,4'-oxybisbenzenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol), and 3 mL of a deep eutectic solvent (the deep eutectic solvent prepared in Example 11) were added in sequence. The mixture was reacted at 70°C for 24 h, during which time it was continuously monitored by thin-layer chromatography. After the reaction was completed, the mixture was cooled to room temperature and an appropriate amount of water (30 mL) was added to precipitate the product, which was filtered and dried to obtain an N-sulfonylpyrazole compound as a white solid (yield 93.90%) with a melting point of 169-171°C.
[0170] 1 H NMR (400 MHz, CDCl3) δ: 7.98 (d, J = 7.3 Hz, 4H), 7.11 (d, J= 7.4 Hz, 4H), 5.93 (s, 1H), 2.51 (s, 6H), 2.21 (s, 6H); 13 C NMR (100 MHz, CDCl3) δ:160.06, 153.76, 144.25, 133.90, 130.30, 119.45, 110.87, 13.86, 13.17; HRMScalcd for C 22 H 22 N4O5S2Na [M+Na] + : 509.0931; found: 509.0929.
[0171] Example 50 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types):
[0172] 2,4,6-Triisopropylbenzenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a deep eutectic solvent (prepared in Example 11) were added sequentially to a 50 mL dry round-bottom flask. The mixture was reacted at 70 °C for 24 h while continuously monitored by thin-layer chromatography. After the reaction was completed, the mixture was cooled to room temperature and an appropriate amount of water (30 mL) was added to precipitate the product, which was filtered and dried to obtain an N-sulfonylpyrazole compound as a light yellow liquid (yield 80.86%).
[0173] 1 H NMR (400 MHz, CDCl3) δ: 7.10 (s, 2H), 5.81 (s, 1H), 4.11 (m, 2H), 2.83 (m, 1H), 2.27 (s, 3H), 2.10 (s, 3H), 1.17 (d, J = 6.8 Hz, 6H), 1.08 (d, J =6.6 Hz, 12H); 13 C NMR (100 MHz, CDCl3) δ: 154.34, 151.64, 151.21, 142.70,131.43, 123.92, 109.49, 34.13, 29.41, 24.35, 23.39, 13.60, 12.53; HRMS calcdfor C 20 H 30 N2O2SNa [M+Na] + : 385.1928; found: 385.1926.
[0174] Test Example 1
[0175] The deep eutectic solvent prepared in Example 11 was tested by infrared spectroscopy, and the results were as follows: Figure 1 As shown. Figure 1 It can be seen that the deep eutectic solvent of Example 11 has a -1 The absorption peak is broader and the peak intensity is lower than that of the single components of choline chloride and ethylene glycol, indicating that a large number of hydrogen bonds are formed in the choline chloride and ethylene glycol deep eutectic solvent system, including HO...H, NH...N and NH...O hydrogen bonds.
[0176] Test Example 2
[0177] Thermogravimetric analysis of the deep eutectic solvent prepared in Example 11 was performed, and the results were as follows: Figure 2 As shown, TG is the thermogravimetric curve and DTG is the thermogravimetric differential curve. Figure 2 It can be seen that the deep eutectic solvent of Example 11 loses about 68% of its weight in the temperature range of 115-275°C, which is basically corresponding to the mass fraction of ethylene glycol therein, indicating that the deep eutectic solvent of Example 11 is thermally stable below 115°C; choline chloride decomposes in the temperature range of 275-350°C.
[0178] Test Example 3
[0179] The effect of recycling the deep eutectic solvent on the product yield was tested. The test method (reference Example 12) was as follows: p-toluenesulfonyl hydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of the deep eutectic solvent (Example 11) were added sequentially to a 50 mL dry round-bottom flask. The mixed system was reacted at 70 ° C for 5 h, during which time it was continuously monitored by thin layer chromatography. After the reaction was completed, it was cooled to room temperature, 30 mL of water was added to precipitate the product, filtered, and dried to obtain an N-sulfonylpyrazole compound; the filtrate was evaporated to remove water, and the deep eutectic solvent was added to 3 mL for the second reaction. Similarly, the third reaction, the fourth reaction and the fifth reaction were carried out in sequence. The results are shown as follows Figure 7 shown.
[0180] according to Figure 7 It can be seen that the product yield of the first reaction is 98.23%, the product yield of the second reaction is 98.13%, the product yields of the third reaction, the fourth reaction, and the fifth reaction are 98.09%, 97.98%, and 97.90%, respectively. After five cycles, the product yield does not decrease significantly, proving that the preparation method provided by the present invention can recycle the low eutectic solvent.
[0181] The test results of Examples 1 to 10 are similar to those of Example 11 and are not described again here.
[0182] It can be seen from the above examples that the preparation method provided by the present invention has simple steps, high preparation efficiency, the deep eutectic solvent can be recycled, the product yield is high, and the preparation cost is reduced.
[0183] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.
Claims
1. A method for preparing an N-sulfonylpyrazole compound, characterized in that: The following steps are involved: mixing a sulfonylhydrazide compound, a β-dicarbonyl compound, and a deep eutectic solvent to carry out a cyclization reaction to obtain the N-sulfonylpyrazole compound; The deep eutectic solvent is choline chloride-ethylene glycol; The sulfonylhydrazine compound has a structure shown in Formula I: Formula I; In Formula I, R 1 is a substituted phenyl group, wherein the substituted phenyl group is tolyl; The β-dicarbonyl compound has a structure shown in Formula II: Formula II; In Formula II, R 2 is a C1~C4 alkyl group, wherein the C1~C4 alkyl group is a methyl group; R 3 is H; The molar ratio of the sulfonylhydrazide compound to the β-dicarbonyl compound is 1-1.1:1-1.4; The ratio of the amount of the sulfonylhydrazide compound to the volume of the deep eutectic solvent is no greater than 1.75 mmol:0.43 mL; The molar ratio of choline chloride to ethylene glycol in the choline chloride-ethylene glycol is 1-2:1-5; The temperature of the cyclization reaction is 65-85°C.
2. The preparation method according to claim 1, characterized in that The holding time of the cyclization reaction is more than 1 h, and the cyclization reaction is carried out in an oil bath.
3. The preparation method according to claim 1, characterized in that After the cyclization reaction, the obtained product system is further subjected to post-treatment; When the N-sulfonylpyrazole compound is solid, the post-treatment is method 1, which is: cooling the obtained product system, adding water, solid-liquid separation and drying; When the N-sulfonylpyrazole compound is a liquid, the post-treatment is method 2, which is: sequentially cooling the obtained product system, adding water, extracting, removing the solvent, and drying.
4. The preparation method according to claim 3, characterized in that After the post-treatment, the liquid obtained by the solid-liquid separation or the raffinate obtained by the extraction is dehydrated, and the low eutectic solvent is collected for recycling.