Preparation method of N-sulfonyl pyrazole compound

Abstract

The invention belongs to the technical field of green organic synthesis, and particularly relates to a preparation method of an N-sulfonyl pyrazole compound. According to the preparation method, the eutectic solvent which is easy to prepare is used as a reaction solvent and also used as a catalyst to catalyze a sulfonyl hydrazine compound and a beta-dicarbonyl compound to be subjected to a cyclization reaction, and the N-sulfonyl pyrazole compound is prepared. According to the preparation method, the product can be obtained only through one-step reaction, preparation is efficient, and operation is easy and convenient; post-treatment is simple, a solid-state product is directly separated out from a system in the reaction process without extraction of an organic solvent, a liquid-state product can be obtained through extraction, and complex post-treatment such as column chromatography purification is not needed; the product is high in yield, good in universality, cheap and easily available in raw materials, low in cost and suitable for industrial large-scale production; meanwhile, the eutectic solvent used in the invention has good biodegradability and small volatility, can be recycled, and meets the development requirements of green chemistry.

Description

Technical Field

[0001] The invention belongs to the technical field of green organic synthesis, and specifically relates to a method for preparing an N-sulfonylpyrazole compound. Background Art

[0002] Pyrazole is a very important class of N-heterocyclic skeleton compounds, which are widely used in medicine and pesticides. At the same time, due to the importance of sulfonyl compounds in drugs, people have been committed to introducing sulfonyl fragments into the molecular framework specified by pyrazole. Among them, sulfonyl hydrazide and its variant sulfonyl hydrazone, as an important source of sulfonyl fragments, have excellent reactivity and have received extensive attention in the synthesis of N-sulfonyl pyrazole compounds in recent years.

[0003] Although the synthesis methods of N-sulfonyl pyrazole compounds have been reported, such as the cyclization reaction of sulfonyl hydrazide with enaminoketone / dithioacetal ketene, the traditional synthesis methods have complicated preparation steps, which limits their application in the field of 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 high efficiency.

[0005] In order to achieve the above object, the present invention provides the following technical solutions: The present invention provides a method for preparing an N-sulfonylpyrazole compound, comprising the following steps: A sulfonylhydrazide compound, a β-dicarbonyl compound and a deep eutectic solvent (DESs) are mixed for a cyclization reaction to obtain the N-sulfonylpyrazole compound; the deep eutectic solvent includes one or two of choline chloride (ChCl)-oxalic acid (OA) and choline chloride (ChCl)-ethylene glycol (EG).

[0006] Preferably, the sulfonylhydrazide compound has a structure shown in Formula I: Formula I; In Formula I, R 1 is phenyl, substituted phenyl, naphthyl, pyridyl or quinolyl.

[0007] 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.

[0008] Preferably, the β-dicarbonyl compound has a structure shown in Formula II: Formula II; In Formula II, R2 C 1 ~C 4 Alkyl or phenyl; R 3 is H, methyl or halogen.

[0009] Preferably, the C 1 ~C 4 The alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; the halogen group is fluoro, chloro, bromo or iodo.

[0010] Preferably, the molar ratio of the sulfonylhydrazide compound to the β-dicarbonyl compound is 1-1.2:1-1.5; the molar ratio of the sulfonylhydrazide compound to the volume of the low eutectic solvent is not greater than 1.75 mmol:0.43 mL.

[0011] 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.

[0012] Preferably, the temperature of the cyclization reaction is 60-90°C, and the insulation time is more than 1 h; the cyclization reaction is carried out in an oil bath.

[0013] 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 sequentially cooled, water is added, solid-liquid separation and drying; when the N-sulfonylpyrazole compound is a liquid, the post-treatment is method two, and the method two is: the obtained product system is sequentially cooled, water is added, extracted, solvent removed and dried.

[0014] 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.

[0015] The present invention provides a method for preparing N-sulfonylpyrazole compounds. The present invention uses a low eutectic solvent as a reaction solvent and a catalyst to catalyze a sulfonylhydrazine compound and a β-dicarbonyl compound to perform a cyclization reaction to prepare N-sulfonylpyrazole compounds. The preparation method provided by the present invention only requires one-step reaction to obtain a product, and the preparation is efficient and easy to operate; the post-treatment is simple, and the solid product in the reaction process is directly precipitated from the system without organic solvent extraction, and the liquid product can be obtained by extraction without complex post-treatment such as column chromatography purification; the product has a high yield and good versatility, and the raw materials are cheap and easy to obtain, the cost is low, and it is 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

[0016] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. 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 creative work.

[0017] Figure 1 This is the infrared spectrum of the deep eutectic solvent prepared in Example 11; Figure 2 This is a thermogravimetric analysis diagram of the deep eutectic solvent prepared in Example 11; Figure 3 This is the H NMR spectrum of the N-sulfonylpyrazole compound prepared in Example 12; Figure 4 This is the NMR carbon spectrum of the N-sulfonylpyrazole compound prepared in Example 12; Figure 5 This is a high-resolution mass spectrum of the N-sulfonylpyrazole compound prepared in Example 12; Figure 6 is a liquid chromatogram of the N-sulfonylpyrazole compound prepared in Example 12; Figure 7 This is a graph showing the relationship between the number of cycles of the deep eutectic solvent in Test Example 3 and the yield of N-sulfonylpyrazole compounds. DETAILED DESCRIPTION

[0018] The present invention provides a method for preparing an N-sulfonylpyrazole compound, comprising the following steps: A sulfonyl hydrazide compound, a β-dicarbonyl compound and a low eutectic solvent are mixed to carry out a cyclization reaction to obtain the N-sulfonyl pyrazole compound.

[0019] The present invention mixes a sulfonylhydrazide compound, a β-dicarbonyl compound and a low eutectic solvent to obtain a reaction solution. In the present invention, the sulfonylhydrazide compound has a structure shown in Formula I: Formula I; In Formula I, R 1 is phenyl, substituted phenyl, naphthyl, pyridyl or quinolyl.

[0020] 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.

[0021] In the present invention, the sulfonyl hydrazide compound may include one or more of benzenesulfonyl hydrazide, 4-methoxybenzenesulfonyl hydrazide, 4-fluorobenzenesulfonyl hydrazide, 4-nitrobenzenesulfonyl hydrazide, 4-bromobenzenesulfonyl hydrazide, 2,4,6-trimethylbenzenesulfonyl hydrazide, p-toluenesulfonyl hydrazide, m-toluenesulfonyl hydrazide, 2-naphthalenesulfonyl hydrazide, 4,4'-oxybisbenzenesulfonyl hydrazide and 2,4,6-triisopropylbenzenesulfonyl hydrazide.

[0022] In the present invention, the β-dicarbonyl compound has a structure shown in Formula II: Formula II; In Formula II, R 2 C 1 ~C 4 Alkyl or phenyl; R 3 is H, methyl or halogen.

[0023] In the present invention, the C 1 ~C 4 The 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.

[0024] 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.

[0025] In the present invention, the molar ratio of the sulfonyl hydrazide 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.

[0026] 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 amount 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 low eutectic solvent prepared by the present invention is uniform and stable, and the product yield is higher by using choline chloride-ethylene glycol.

[0027] In the present invention, the preparation method of the deep eutectic solvent can be: choline chloride is mixed with oxalic acid or ethylene glycol, and stirred at 70-100 ° C for 0.5-1 h for hydrogen bonding to obtain a colorless, transparent, and stable deep eutectic solvent. The present invention allows choline chloride and oxalic acid or ethylene glycol to form a deep eutectic solvent with a melting point lower than that of any single substance through hydrogen bonding.

[0028] In the present invention, the ratio of the amount of the sulfonylhydrazide compound to the volume of the low 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 mL, 1.6 mmol:2.4 mL, 1.6 mmol:2.5 mL, 1.75 mmol:0.43 mL, 1.75 mmol:0.75 mL, 1.75 mmol:1 mL, 1.75 mmol:1.2 mL, 1.75 mmol:1.4 mL, 1.75 mmol:1.6 mL, 1.75 mmol:1.8 mL, 1.75 mmol:2 mL, 1.75 mmol:2.2 mL, 1.75 mmol:2.4 mL or 1.75 mmol:2.5 mL. The present invention adopts the low eutectic solvent in the above amount to better dissolve the reaction raw materials sulfonyl hydrazide compound and β-dicarbonyl compound.

[0029] After obtaining the reaction solution, the present invention further performs a cyclization reaction on the reaction solution to obtain the N-sulfonylpyrazole compound. In the present invention, the temperature of the cyclization reaction can be 60-90 ° C, specifically 60 ° C, 65 ° C, 70 ° C, 75 ° C, 80 ° C, 85 ° C or 90 ° C, and the insulation time can be more than 1 h, specifically 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 15 h, 18 h, 21 h, 24 h or 36 h; the cyclization reaction can be carried out under oil bath conditions. The preparation method provided by the present invention has mild reaction conditions and is easy to achieve industrialization and scale.

[0030] In the present invention, the chemical reaction of the cyclization reaction is as follows: .

[0031] 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 one, and the method one may be: sequentially cooling, adding water, solid-liquid separation and drying the product system obtained by the cyclization reaction.

[0032] In the present invention, the final temperature of the cooling may be room temperature; the ratio of the volume of the water to the amount of the sulfonylhydrazine compound may be no less than 20 mL:3.5 mmol; the solid-liquid separation may be filtration; and the filtration may be suction filtration. During the cyclization reaction, a solid product will precipitate, and adding water can allow the solid product to precipitate completely, while diluting the low eutectic solvent, facilitating subsequent solid-liquid separation.

[0033] In the present invention, when the N-sulfonylpyrazole compound is a liquid, the post-treatment may be a second method, and the second method may be: cooling, adding water, extracting, removing solvents and drying the product system obtained by the cyclization reaction in sequence; the extractant for extraction may be an organic solvent; the organic solvent may be ethyl acetate; the solvent removal may be rotary evaporation. During the cyclization reaction, the liquid product will not precipitate. In the present invention, by adding water, it is convenient to extract the liquid product with an organic solvent in the subsequent step, and no complicated post-treatment means such as column chromatography purification is required.

[0034] The present invention can obtain N-sulfonylpyrazole compounds by simple post-treatment. Most of the N-sulfonylpyrazole compounds prepared by the present invention are solid, and the product can be obtained by post-treatment according to the first method. Only a small amount of N-sulfonylpyrazole compounds are liquid, and the product can be obtained by post-treatment according to the second method, and no complicated treatment such as column chromatography purification is required.

[0035] In the present invention, the post-treatment may further include dehydrating the liquid obtained by the solid-liquid separation or the raffinate obtained by the extraction, and collecting the low eutectic solvent for recycling; the dehydration method may be distillation; and the distillation may be reduced pressure distillation. The present invention realizes the recycling of the low eutectic solvent by dehydration.

[0036] In the present invention, the structure of the N-sulfonylpyrazole compound is shown in Formula III: Formula III; In Formula III, R 1 is phenyl, substituted phenyl, naphthyl, pyridyl or quinolyl; R 2 C 1 ~C 4 Alkyl or phenyl; R 3 is H, methyl or halogen.

[0037] 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; the C 1 ~C 4 The 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.

[0038] In order to further illustrate the present invention, the scheme of the present invention is described in detail below in conjunction with the accompanying drawings and embodiments, but they should not be understood as limiting the protection scope of the present invention.

[0039] Example 1 Preparation of Choline Chloride-Oxalic Acid Deep Eutectic Solvent: 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 respectively, 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-oxalic acid low eutectic solvent for use.

[0040] Example 2 Preparation of Choline Chloride-Oxalic Acid Deep Eutectic Solvent: 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 respectively, 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-oxalic acid low eutectic solvent for use.

[0041] Example 3 Preparation of Choline Chloride-Oxalic Acid Deep Eutectic Solvent: 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, react by hydrogen bonding for 30 min, cool to room temperature, and dry to obtain a choline chloride-oxalic acid low eutectic solvent for use.

[0042] Example 4 Preparation of Choline Chloride-Oxalic Acid Deep Eutectic Solvent: 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 respectively, 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-oxalic acid low eutectic solvent for use.

[0043] Example 5 Preparation of Choline Chloride-Oxalic Acid Deep Eutectic Solvent: 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 respectively, 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-oxalic acid low eutectic solvent for use.

[0044] Example 6 Preparation of Choline Chloride-Oxalic Acid Deep Eutectic Solvent: 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 respectively, 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-oxalic acid low eutectic solvent for use.

[0045] Example 7 Preparation of Choline Chloride-Ethylene Glycol Deep Eutectic Solvent: 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 respectively, 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 low eutectic solvent for use.

[0046] Example 8 Preparation of Choline Chloride-Ethylene Glycol Deep Eutectic Solvent: 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 respectively, 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 low eutectic solvent for use.

[0047] Example 9 Preparation of Choline Chloride-Ethylene Glycol Deep Eutectic Solvent: 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 respectively, 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 low eutectic solvent for use.

[0048] Example 10 Preparation of Choline Chloride-Ethylene Glycol Deep Eutectic Solvent: 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 respectively, 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 low eutectic solvent for use.

[0049] Example 11 Preparation of Choline Chloride-Ethylene Glycol Deep Eutectic Solvent: 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 respectively, 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 low eutectic solvent for use.

[0050] Example 12 Preparation of N-sulfonylpyrazole compound—N-p-toluenesulfonyl-3,5-dimethylpyrazole: Toluenesulfonyl hydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a low eutectic solvent (the low 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, and thin layer chromatography was continuously used for monitoring during the reaction. After the reaction was completed, the mixture was cooled to room temperature, and an appropriate amount (30 mL) of water was added to precipitate the product, which was filtered to obtain an N-sulfonyl pyrazole compound, N-toluenesulfonyl-3,5-dimethylpyrazole, as a white solid (yield of 98.23%) with a melting point of 92-94 °C. The NMR hydrogen spectrum, NMR carbon spectrum, high-resolution mass spectrum and liquid chromatogram of the N-sulfonyl pyrazole compound prepared in this example are shown as follows: Figures 3 to 6 As shown: 1 H NMR (400 MHz, CDCl 3 ) 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, CDCl 3 ) 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 N 2 O 2 S[M+H] + : 251.0854; found: 251.0856.

[0051] 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.

[0052] Example 13 Preparation of N-sulfonylpyrazole compounds: The preparation method of this example is the same as that of Example 12, except that the low eutectic solvent of Example 11 is replaced by the low eutectic solvent of Example 9, and the amount of the low eutectic solvent is replaced by 3.5 mL to obtain N-sulfonylpyrazole compounds (yield is 94.73%).

[0053] Example 14 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant amounts): The preparation method of this example is the same as that of Example 13, except that the amount of p-toluenesulfonyl hydrazide 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 is 91.71%).

[0054] Example 15 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant amounts): The preparation method of this example is the same as that of Example 13, except that the amount of p-toluenesulfonyl hydrazide 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 is 89.14%).

[0055] Example 16 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant amounts): The preparation method of this example is the same as that of Example 13, except that the amount of p-toluenesulfonyl hydrazide 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 is 82.65%).

[0056] Example 17 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant amounts): The preparation method of this example is the same as that of Example 13, except that the amount of p-toluenesulfonyl hydrazide 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 is 76.21%).

[0057] Example 18 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant amounts): The preparation method of this example is the same as that of Example 13, except that the amount of p-toluenesulfonyl hydrazide 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 is 42.29%).

[0058] Example 19 Preparation of N-sulfonylpyrazole compounds (reaction temperature adjustment): 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 an N-sulfonylpyrazole compound (yield is 74.19%).

[0059] Example 20 Preparation of N-sulfonylpyrazole compounds (reaction temperature adjustment): 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 an N-sulfonylpyrazole compound (the yield is 84.11%).

[0060] Example 21 Preparation of N-sulfonylpyrazole compounds (reaction temperature adjustment): 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 an N-sulfonylpyrazole compound (yield is 46.03%).

[0061] Example 22 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent): The preparation method of this example is the same as that of Example 12, except that the volume of the low eutectic solvent of Example 12 is replaced with 1.5 mL to obtain an N-sulfonylpyrazole compound (yield is 91.23%).

[0062] Example 23 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent): The preparation method of this example is the same as that of Example 12, except that the volume of the low eutectic solvent of Example 12 is replaced with 2 mL to obtain an N-sulfonylpyrazole compound (yield is 93.67%).

[0063] Example 24 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent): The preparation method of this example is the same as that of Example 12, except that the volume of the low eutectic solvent of Example 12 is replaced with 2.5 mL to obtain an N-sulfonylpyrazole compound (yield is 95.06%).

[0064] Example 25 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent): The preparation method of this example is the same as that of Example 12, except that the volume of the low eutectic solvent of Example 12 is replaced with 3.5 mL to obtain an N-sulfonylpyrazole compound (yield is 97.44%).

[0065] Example 26 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent): The preparation method of this example is the same as that of Example 12, except that the volume of the low eutectic solvent of Example 12 is replaced with 4 mL to obtain an N-sulfonylpyrazole compound (yield is 96.46%).

[0066] Example 27 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent): The preparation method of this example is the same as that of Example 12, except that the volume of the low eutectic solvent of Example 12 is replaced with 4.5 mL to obtain an N-sulfonylpyrazole compound (yield is 93.36%).

[0067] Example 28 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent): The preparation method of this example is the same as that of Example 12, except that the volume of the low eutectic solvent of Example 12 is replaced with 5 mL to obtain an N-sulfonylpyrazole compound (yield is 92.84%).

[0068] Example 29 Preparation of N-sulfonylpyrazole compounds (adjustment of the amount of deep eutectic solvent): The preparation method of this example is the same as that of Example 12, except that the volume of the low eutectic solvent of Example 12 is replaced with 8 mL to obtain an N-sulfonylpyrazole compound (yield is 91.35%).

[0069] Example 30 Preparation of N-sulfonylpyrazole compounds (reaction time adjustment): 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%).

[0070] Example 31 Preparation of N-sulfonylpyrazole compounds (reaction time adjustment): 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%).

[0071] Example 32 Preparation of N-sulfonylpyrazole compounds (reaction time adjustment): 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 an N-sulfonylpyrazole compound (yield is 95.18%).

[0072] Example 33 Preparation of N-sulfonylpyrazole compounds (reaction time adjustment): 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 an N-sulfonylpyrazole compound (yield is 95.09%).

[0073] Example 34 Preparation of N-sulfonylpyrazole compounds (adjustment of the type of deep eutectic solvent): 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%.

[0074] Example 35 Preparation of N-sulfonylpyrazole compounds (adjustment of the type of deep eutectic solvent): 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%.

[0075] Example 36 Preparation of N-sulfonylpyrazole compounds (adjustment of the type of deep eutectic solvent): 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 10. The raw material conversion rate of this example is 100%, and the product yield of the N-sulfonylpyrazole compound is 94.95%.

[0076] Example 37 Preparation of N-sulfonylpyrazole compounds (adjustment of the type of deep eutectic solvent): 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 11. The raw material conversion rate of this example is 100%, and the product yield of the N-sulfonylpyrazole compound is 97.44%.

[0077] Example 38 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types): In a 50 mL dry round-bottom flask, benzenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a low eutectic solvent (the low eutectic solvent prepared in Example 11) were added in sequence, and 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, and an appropriate amount (30 mL) of water was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a white solid (yield of 84.71%) with a melting point of 80-82 °C.

[0078] 1 H NMR (400 MHz, CDCl 3 ) 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, CDCl 3 ) 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 N 2 O 2 S [M+H] + : 237.0698; found:237.0699.

[0079] Example 39 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types): In a 50 mL dry round-bottom flask, 4-methoxybenzenesulfonyl hydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a low eutectic solvent (the low eutectic solvent prepared in Example 11) were added in sequence, and 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, and an appropriate amount (30 mL) of water was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a white solid (yield of 97.69%) with a melting point of 126-128 °C.

[0080] 1 H NMR (400 MHz, CDCl 3 ) 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, CDCl 3 ) 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 N 2 O 3 S [M+H] + : 267.0803;found: 267.0806.

[0081] Example 40 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types): In a 50 mL dry round-bottom flask, 4-fluorobenzenesulfonyl hydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a low eutectic solvent (the low eutectic solvent prepared in Example 11) were added in sequence, and 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, and an appropriate amount (30 mL) of water was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a white solid (yield of 87.28%) with a melting point of 87-89 °C.

[0082] 1 H NMR (400 MHz, CDCl 3) 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, CDCl 3 ) 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 N 2 O 2 SF [M+H] + : 255.0604; found:255.0607.

[0083] Example 41 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types): In a 50 mL dry round-bottom flask, 4-nitrobenzenesulfonyl hydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a low eutectic solvent (the low eutectic solvent prepared in Example 11) were added in sequence, and 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, and an appropriate amount (30 mL) of water was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a white solid (yield of 91.08%) with a melting point of 177-179 °C.

[0084] 1 H NMR (400 MHz, CDCl 3 ) 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, CDCl 3 ) 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 N3 O 4 S[M+H] + : 282.0548; found:282.0542.

[0085] Example 42 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types): In a 50 mL dry round-bottom flask, 4-bromobenzenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a low eutectic solvent (the low eutectic solvent prepared in Example 11) were added in sequence, and 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, and an appropriate amount (30 mL) of water was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a white solid (yield of 91.56%) with a melting point of 94-96 °C.

[0086] 1 H NMR (400 MHz, CDCl 3 ) 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, CDCl 3 ) 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 N 2 O 2 SBr[M+H] + : 314.9803.0548; found:314.9804.

[0087] Example 43 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types): In a 50 mL dry round-bottom flask, 2,4,6-trimethylbenzenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a low eutectic solvent (the low eutectic solvent prepared in Example 11) were added in sequence, and the mixed system was reacted at 70 °C for 5 h, during which it was continuously monitored by thin layer chromatography. After the reaction was completed, it was cooled to room temperature, and an appropriate amount (30 mL) of water was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a white solid (yield of 92.18%) with a melting point of 106-108 °C.

[0088] 1 H NMR (400 MHz, CDCl 3 ) 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 C NMR (100 MHz, CDCl 3 ) δ: 151.85,144.05, 143.64, 140.67, 132.63, 132.00, 109.40, 22.42, 21.07, 13.78, 12.90;HRMS calcd for C 14 H 19 N 2 O 2 S [M+H] + : 279.1167; found: 279.1170.

[0089] Example 44 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types): In a 50 mL dry round-bottom flask, p-toluenesulfonyl hydrazide (3.5 mmol), 3-methylacetylacetone (3.5 mmol) and 3 mL of a low eutectic solvent (the low eutectic solvent prepared in Example 11) were added in sequence, and 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, and an appropriate amount (30 mL) of water was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a white solid (yield of 95.63%) with a melting point of 139-141 °C.

[0090] 1 H NMR (400 MHz, CDCl 3 ) 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, CDCl 3 ) δ:153.60, 144.81, 139.49, 135.42, 129.73, 127.33, 117.15, 21.52, 12.30, 11.20,7.89; HRMS calcd for C13 H 17 N 2 O 2 S [M+H] + : 265.1011; found:265.1008.

[0091] Example 45 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types): In a 50 mL dry round-bottom flask, p-toluenesulfonyl hydrazide (3.5 mmol), 3,5-diheptanone (3.5 mmol) and 3 mL of a low eutectic solvent (the low eutectic solvent prepared in Example 11) were added in sequence, and the mixed system was reacted at 70 °C for 5 h, during which it was continuously monitored by thin layer chromatography. After the reaction was completed, it was cooled to room temperature, and an appropriate amount (30 mL) of water was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a colorless liquid (the yield was 89.42%).

[0092] 1 H NMR (400 MHz, CDCl 3 ) 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 C NMR (100 MHz, CDCl 3 ) δ158.91, 150.46, 144.93, 135.30, 129.67, 127.38, 107.14, 21.52, 21.47, 20.29,12.98, 12.75; HRMS calcd for C 14 H 19 N 2 O 2 S [M+H] + : 279.1167; found: 279.1167.

[0093] Example 46 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types): In a 50 mL dry round-bottom flask, p-toluenesulfonyl hydrazide (3.5 mmol), 2,6-dimethyl-3,5-diheptanone (3.5 mmol) and 3 mL of a low eutectic solvent (the low eutectic solvent prepared in Example 11) were added in sequence, and the mixed system was reacted at 70 °C for 5 h, during which it was continuously monitored by thin layer chromatography. After the reaction was completed, it was cooled to room temperature, and an appropriate amount (30 mL) of water was added to precipitate the product, which was filtered to obtain an N-sulfonylpyrazole compound as a light yellow liquid (the yield was 86.79%).

[0094] 1 H NMR (400 MHz, CDCl 3 ) 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); 13 C NMR (100 MHz, CDCl 3 ) δ: 163.30,156.20, 144.80, 135.57, 129.58, 127.50, 104.17, 27.99, 26.27, 23.36, 22.04,21.57; HRMS calcd for C 16 H 23 N 2 O 2 S [M+H] + : 307.1480; found: 307.1481.

[0095] Example 47 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types): In a 50 mL dry round-bottom flask, m-toluenesulfonyl hydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a low eutectic solvent (the low eutectic solvent prepared in Example 11) were added in sequence, and the mixed system was reacted at 70 °C for 24 h, during which it was continuously monitored by thin layer chromatography. After the reaction was completed, it was cooled to room temperature, an appropriate amount of water (30 mL) was added, and the product 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 (the yield was 76.35%).

[0096] 1 H NMR (400 MHz, CDCl 3 ) 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 C NMR (100 MHz, CDCl 3 ) δ:153.51, 143.99, 139.62, 138.13, 134.72, 129.09, 127.82, 124.64, 110.77,21.32, 13.83, 13.13; HRMS calcd for C 12 H 14 N 2 O 2 SNa [M+Na] + : 273.0677; found:273.0674.

[0097] Example 48 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types): 2-Naphthalenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of low eutectic solvent (the low eutectic solvent prepared in Example 11) were added in sequence to a 50 mL dry round-bottom flask, and the mixed system was reacted at 70 °C for 24 h, during which it was continuously monitored by thin layer chromatography. After the reaction was completed, it was cooled to room temperature, an appropriate amount of water (30 mL) was added, and the product was extracted with ethyl acetate. The organic solvent in the product was removed by rotary evaporation and dried to obtain N-sulfonylpyrazole compounds as a light yellow liquid (the yield was 80.78%).

[0098] 1 H NMR (400 MHz, CDCl 3 ) 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, CDCl 3 ) 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 C15 H 14 N 2 O 2 SNa [M+Na] + : 309.0675; found:309.0674.

[0099] Example 49 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types): In a 50 mL dry round-bottom flask, 4,4'-oxybisbenzenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a low eutectic solvent (the low eutectic solvent prepared in Example 11) were added in sequence, and the mixed system was reacted at 70 °C for 24 h, during which it was continuously monitored by thin layer chromatography. After the reaction was completed, it 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 of 93.90%) with a melting point of 169-171 °C.

[0100] 1 H NMR (400 MHz, CDCl 3 ) 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, CDCl 3 ) 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 N 4 O 5 S 2 Na [M+Na] + : 509.0931; found: 509.0929.

[0101] Example 50 Preparation of N-sulfonylpyrazole compounds (adjustment of reactant types): In a 50 mL dry round-bottom flask, 2,4,6-triisopropylbenzenesulfonylhydrazide (3.5 mmol), acetylacetone (3.5 mmol) and 3 mL of a low eutectic solvent (the low eutectic solvent prepared in Example 11) were added in sequence, and the mixed system was reacted at 70 °C for 24 h, during which it was continuously monitored by thin layer chromatography. After the reaction was completed, it was cooled to room temperature, and an appropriate amount (30 mL) of water was added to precipitate the product, which was filtered and dried to obtain an N-sulfonylpyrazole compound as a light yellow liquid (the yield was 80.86%).

[0102] 1 H NMR (400 MHz, CDCl 3 ) 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, CDCl 3 ) 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 N 2 O 2 SNa [M+Na] + : 385.1928; found: 385.1926.

[0103] Test Example 1 The deep eutectic solvent prepared in Example 11 was tested by infrared spectroscopy. The results are as follows: Figure 1 As shown. Figure 1 It can be seen that the low eutectic solvent of Example 11 is between 3600 and 3100 cm -1 The absorption peak is broader than that of single components of choline chloride and ethylene glycol, and the peak intensity is reduced, indicating that a large number of hydrogen bonds are formed in the choline chloride and ethylene glycol eutectic solvent system, including HO...H, NH...N and NH...O hydrogen bonds.

[0104] Test Example 2 Thermogravimetric analysis of the low eutectic solvent prepared in Example 11 showed the following results: Figure 2 As shown, TG is the thermogravimetric curve and DTG is the thermogravimetric differential curve. Figure 2 It can be seen that the low 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 low eutectic solvent of Example 11 has thermal stability below 115 °C; and choline chloride decomposes in the temperature range of 275-350 °C.

[0105] Test Example 3 The effect of recycling the low 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 low eutectic solvent (Example 11) were added to a 50 mL dry round-bottom flask in sequence, and the mixed system was reacted at 70 ° C for 5 h, during which 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 low eutectic solvent was added to 3 mL for the second reaction, and so on, the third reaction, the fourth reaction and the fifth reaction were carried out in sequence. The results are as follows Figure 7 shown.

[0106] 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 did not decrease significantly, proving that the preparation method provided by the present invention can recycle the low eutectic solvent.

[0107] The test results of Examples 1 to 10 are similar to those of Example 11 and are not described in detail here.

[0108] It can be seen from the above examples that the preparation method provided by the present invention has simple steps, high preparation efficiency, the low eutectic solvent can be recycled, the product yield is high, and the preparation cost is reduced.

[0109] Although the above embodiment describes the present invention in detail, 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 protection scope 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 for a cyclization reaction to obtain the N-sulfonylpyrazole compound; The deep eutectic solvent includes one or both of choline chloride-oxalic acid and choline chloride-ethylene glycol.

2. The preparation method according to claim 1, characterized in that: The sulfonylhydrazide compound has a structure shown in Formula I: Formula I; In Formula I, R 1 is phenyl, substituted phenyl, naphthyl, pyridyl or quinolyl.

3. The preparation method according to claim 2, characterized in that: The substituted phenyl group is a halogen phenyl group, a nitrophenyl group, a tolyl group or a methoxyphenyl group; The halophenyl group is a fluorophenyl group, a chlorophenyl group, a bromophenyl group or an iodophenyl group.

4. The preparation method according to claim 1, characterized in that: The β-dicarbonyl compound has a structure shown in Formula II: Formula II; In Formula II, R 2 is C1~C4 alkyl or phenyl; R 3 is H, methyl or halogen.

5. The preparation method according to claim 4, characterized in that: The C1~C4 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; The halogen is a fluoro group, a chloro group, a bromo group or an iodo group.

6. The preparation method according to claim 1 or 2, characterized in that: The molar ratio of the sulfonyl hydrazide compound to the β-dicarbonyl compound is 1-1.2:1-1.5; The ratio of the amount of the sulfonylhydrazide compound to the volume of the low eutectic solvent is no more than 1.75 mmol:0.43 mL.

7. The preparation method according to claim 1, characterized in that: 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.

8. The preparation method according to claim 1 or 7, characterized in that: The temperature of the cyclization reaction is 60-90°C, the insulation time is more than 1 h, and the cyclization reaction is carried out in an oil bath.

9. 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: sequentially 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, adding water, extracting, removing solvents and drying the obtained product system.

10. The preparation method according to claim 9, characterized in that: The post-treatment further includes removing water from the liquid obtained by the solid-liquid separation or the raffinate obtained by the extraction, and collecting the low eutectic solvent for recycling.

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