A method for synthesizing a polysubstituted pyrazole compound

Abstract

The present application relates to the technical field of organic synthesis, in particular to a synthesis method of polysubstituted pyrazole compounds, which comprises adding aryl diazonium salt 0.6 mmol, enone 0.9 mmol, 0.5 ml of acid and 0.3 mmol of electrolyte into a 10 ml three-necked bottle, and then adding 6 ml of solvent to dissolve; using a carbon rod as an anode and a platinum plate as a cathode, stirring the reaction, monitoring the reaction process by using thin layer chromatography, after the reaction is completed, extracting the mixture with ethyl acetate; drying the organic layer of the mixture with anhydrous sodium sulfate, rotary evaporating the solvent under reduced pressure, purifying the residue by column chromatography, and obtaining the target product; the method uses aryl diazonium salt as a double synthetic substrate under mild electrochemical conditions, continuously generates two free radicals by electrochemical reduction of aryl diazonium salt, directly synthesizes a series of polysubstituted pyrazole compounds, directly and orderly constructs polysubstituted pyrazole compounds without transition metal or external redox agent, is environment-friendly, efficient and high in atom economy.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for synthesizing polysubstituted pyrazole compounds. Background Technology

[0002] Polysubstituted pyrazoles are an important structural framework with wide applications in pharmaceuticals, agrochemicals, functional materials, and ligands. Although progress has been made in the synthesis of polysubstituted pyrazole compounds in recent years, efficient synthesis remains a major challenge and difficulty in organic synthesis.

[0003] Polysubstituted pyrazoles are important structural units with wide applications in various fields, including pharmaceuticals, agrochemicals, and functional materials. Traditional synthetic methods for polysubstituted pyrazoles mainly employ two strategies: 1) functionalization of the pyrazole skeleton; and 2) assembly of new pyrazole rings from acyclic precursors. However, these methods typically require transition metal catalysts, equivalent amounts of redox agents, harsh reaction conditions, and numerous steps, making them difficult to apply in practical synthesis.

[0004] Therefore, ensuring the orderly addition of two free radicals generated by aryl diazonium salts to olefins to form a single product is a major challenge. Summary of the Invention

[0005] The purpose of this invention is to provide a method for synthesizing polysubstituted pyrazole compounds, which aims to solve the problems of existing methods for synthesizing polysubstituted pyrazole compounds, which require the use of transition metal catalysts or redox agents, have harsh reaction conditions and numerous steps, and are difficult to apply in practical synthesis.

[0006] To achieve the above objectives, the present invention provides a method for synthesizing polysubstituted pyrazole compounds, comprising the following steps;

[0007] Add 0.6 mmol of aryl diazonium salt, 0.9 mmol of enone, 0.5 mL of acid and 0.3 mmol of electrolyte to a 10 mL three-necked flask, and dissolve them in 6 mL of solvent.

[0008] A carbon rod was used as the anode and a platinum sheet as the cathode. The reaction was stirred and the reaction process was monitored by thin-layer chromatography. After the reaction was completed, the mixture was extracted with ethyl acetate.

[0009] The organic layer of the mixture was dried with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography to obtain the target product.

[0010] The acid includes one or more of acetic acid, trifluoromethanesulfonic acid, and trifluoroacetic acid.

[0011] The electrolyte includes one or more of tetrabutylammonium hexafluorophosphonate, tetraethylammonium hexafluorophosphonate, tetrabutylammonium tetrafluoroborate, and tetrabutylammonium iodide.

[0012] The solvent includes acetonitrile, dimethyl sulfoxide, and a mixture of dimethyl sulfoxide and water.

[0013] The stirring reaction conditions include a constant current of 5-20 mA, a reaction temperature of 10-40 degrees Celsius, and a stirring reaction time of 0.5-3 hours.

[0014] This invention relates to a method for synthesizing polysubstituted pyrazole compounds. Specifically, it relates to a method for synthesizing polysubstituted pyrazole compounds, comprising adding 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of an acid, and 0.3 mmol of an electrolyte to a 10 mL three-necked flask, and adding 6 mL of solvent to dissolve them; using a carbon rod as the anode and a platinum sheet as the cathode, the reaction is stirred, and the reaction progress is monitored by thin-layer chromatography. After the reaction is complete, the mixture is extracted with ethyl acetate; the organic layer of the mixture is dried with anhydrous sodium sulfate and subjected to vacuum evaporation. The target product was obtained by purifying the residue by column chromatography using a dry solvent. This method uses aryl diazonium salt as a disynthetogen under mild electrochemical conditions. A series of polysubstituted pyrazole compounds were directly synthesized by continuously generating two free radicals through the electrochemical reduction of aryl diazonium salt. Polysubstituted pyrazole compounds can be directly and orderly constructed without transition metals or external redox agents. It is environmentally friendly, efficient and atom-economical. It solves the problem that existing methods for synthesizing polysubstituted pyrazole compounds require transition metal catalysts or redox agents, have harsh reaction conditions and many steps, and are difficult to apply to practical synthesis. Attached Figure Description

[0015] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0016] Figure 1 This is a flowchart of a method for synthesizing polysubstituted pyrazole compounds provided by the present invention.

[0017] Figure 2 This is a schematic diagram of the general formula for a method of synthesizing polysubstituted pyrazole compounds provided by the present invention, wherein R 1 R 2 R 3 =Aromatic group, alkyl group, etc.

[0018] Figure 3 This is the structural diagram of 3-ethyl-5-methyl-1,4-diphenyl-1H-pyrazole (3a).

[0019] Figure 4 This is the structural diagram of 3,5-dimethyl-1,4-diphenyl-1H-pyrazole (3b).

[0020] Figure 5 This is the structural diagram of 3-methyl-1,4-diphenyl-5-propyl-1H-pyrazole (3c).

[0021] Figure 6 This is the structural diagram of 5-butyl-4-(cyclohex-1,5-dien-1-yl)-3-methyl-1-phenyl-1H-pyrazole (3d).

[0022] Figure 7 This is the structural diagram of 3-methyl-1,4,5-triphenyl-1H-pyrazole (3e).

[0023] Figure 8 This is the structural diagram of 3-methyl-1,4-diphenyl-5-(p-tolyl)-1H-pyrazole (3f).

[0024] Figure 9 This is the structural diagram of 5-(4-methoxyphenyl)-3-methyl-1,4-diphenyl-1H-pyrazole (3g).

[0025] Figure 10 It is the structural diagram of 5-(4-fluorophenyl)-3-methyl-1,4-diphenyl-1H-pyrazole (3h).

[0026] Figure 11 It is the structural diagram of 5-(4-chlorophenyl)-3-methyl-1,4-diphenyl-1H-pyrazole (3i).

[0027] Figure 12 It is the structural diagram of 5-(3-bromo-4-fluorophenyl)-3-methyl-1,4-diphenyl-1H-pyrazole (3j).

[0028] Figure 13 It is the structural diagram of 5-(5-bromofuran-2-yl)-3-methyl-1,4-diphenyl-1H-pyrazole (3k).

[0029] Figure 14 It is the structural diagram of 5-(4-bromothiophene-2-yl)-3-methyl-1,4-diphenyl-1H-pyrazole (3l).

[0030] Figure 15 It is the structural diagram of 3-methyl-5-(naphth-2-yl)-1,4-diphenyl-1H-pyrazole (3m).

[0031] Figure 16 This is the structural diagram of 3-ethyl-5-methyl-1,4-di-p-tolyl-1H-pyrazole (3n).

[0032] Figure 17 It is the structural diagram of 1,4-bis(4-(tert-butyl)phenyl)-3-ethyl-5-methyl-1H-pyrazole (3o).

[0033] Figure 18 This is the structural diagram of 1,4-bis(4-chlorophenyl)-3-ethyl-5-methyl-1H-pyrazole (3p).

[0034] Figure 19 It is the structural diagram of 3-ethyl-5-methyl-1,4-bis(4-(trifluoromethyl)phenyl)-1H-pyrazole (3q).

[0035] Figure 20 This is the structural diagram of methyl 4-(5-ethyl-1-(4-(2-methoxy-2-oxyethyl)phenyl)-3-methyl-1H-pyrazole-4-yl)benzoate (3r).

[0036] Figure 21 This is the structural diagram of 5-ethyl-3-methyl-1,4-di(naphthyl-2-yl)-1H-pyrazole (3s).

[0037] Figure 22 This is the structural diagram of 1,4-bis(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-5-ethyl-3-methyl-1H-pyrazole(3t). Detailed Implementation

[0038] Embodiments of the present invention are described in detail below, examples of which are illustrated in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention.

[0039] Please see Figures 1 to 22 The present invention provides a method for synthesizing polysubstituted pyrazole compounds, comprising the following steps;

[0040] S1: 0.6 mmol of aryl diazonium salt, 0.9 mmol of enone, 0.5 mL of acid and 0.3 mmol of electrolyte were added to a 10 mL three-necked flask, and 6 mL of solvent was added to dissolve them.

[0041] In this embodiment of the invention, the acid includes one or more of acetic acid, trifluoromethanesulfonic acid and trifluoroacetic acid; the electrolyte includes one or more of tetrabutylammonium hexafluorophosphonate, tetraethylammonium hexafluorophosphonate, tetrabutylammonium tetrafluoroborate and tetrabutylammonium iodide; and the solvent includes acetonitrile, dimethyl sulfoxide, and a mixture of dimethyl sulfoxide and water.

[0042] Specifically, 0.6 mmol of aryl diazonium salt, 0.9 mmol of enone, 0.5 mL of acid (acetic acid, trifluoromethanesulfonic acid, or trifluoroacetic acid, etc.), and 0.3 mmol of electrolyte (tetrabutylammonium hexafluorophosphonate, tetraethylammonium hexafluorophosphonate, tetrabutylammonium tetrafluoroborate, or tetrabutylammonium iodide, etc.) were added to a 10 mL three-necked flask and dissolved in 6 mL of solvent (acetonitrile, dimethyl sulfoxide, a mixture of dimethyl sulfoxide and water, etc.).

[0043] S2 uses a carbon rod as the anode and a platinum sheet as the cathode, and the reaction is stirred. The reaction process is monitored by thin-layer chromatography. After the reaction is completed, the mixture is extracted with ethyl acetate.

[0044] In this embodiment of the invention, the stirring reaction conditions include a constant current of 5-20 mA, a reaction temperature of 10-40 degrees Celsius, and a stirring reaction time of 0.5-3 hours.

[0045] Specifically, a carbon rod is used as the anode and a platinum sheet as the cathode. The reaction is carried out with a constant current of 5-20 mA and a temperature of 10-40 degrees Celsius, with stirring for 0.5-3 hours. The reaction process is monitored by thin-layer chromatography. After the reaction is completed, the mixture is extracted with ethyl acetate (3×5 mL).

[0046] S3 dried the organic layer of the mixture with anhydrous sodium sulfate, evaporated the solvent under reduced pressure, and purified the residue by column chromatography to obtain the target product.

[0047] In this embodiment of the invention, the organic layer of the mixture is dried with anhydrous sodium sulfate, the solvent is evaporated under reduced pressure, and the residue is purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:15-40 elution) to obtain the target product.

[0048] To better understand this technical solution, the following embodiments are provided for further explanation:

[0049] Preparation and characterization of polysubstituted pyrazole compounds:

[0050] Example 1

[0051] Preparation and characterization of 3-ethyl-5-methyl-1,4-diphenyl-1H-pyrazole (3a):

[0052] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of acetic acid, and 0.3 mmol of tetrabutylammonium hexafluorophosphonate were added to a 10 mL three-necked flask, dissolved in 6 mL of acetonitrile. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 15 mA and at 40 °C with stirring for 2 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:30 elution) to obtain the target product 3a.

[0053] Yellow oil (78%, 61.4 mg). 1 H NMR (400MHz, Chloroform-d) δ750-7.48 (m, 4H), 7.46-7.41 (m, 3H), 7.35-7.31 (m, 3H), 2.72 (q, J=7.6Hz, 2H), 2.31 (s, 3H), 0.91 (t, J=7.6Hz, 3H). 13 C NMR (126MHz, Chloroform-d) δ147.20, 142.77, 139.94, 133.86, 129.85, 129.34, 128 .62, 128.18, 126.82, 125.87, 120.43, 18.17, 13.83, 12.52.HRMS(m / z)(ESI):calcd for C 18 H 19 N2[M+H] + 263.1543, found 263.1550.

[0054] Example 2

[0055] Preparation and characterization of 3,5-dimethyl-1,4-diphenyl-1H-pyrazole (3b):

[0056] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of acetic acid, and 0.3 mmol of tetrabutylammonium hexafluorophosphonate were added to a 10 mL three-necked flask, dissolved in 6 mL of acetonitrile. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 15 mA and at 40 °C with stirring for 2 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:30 elution) to obtain the target product 3a.

[0057] Yellow oil (78%, 61.4 mg). 1H NMR (400MHz, Chloroform-d) δ750-7.48 (m, 4H), 7.46-7.41 (m, 3H), 7.35-7.31 (m, 3H), 2.72 (q, J=7.6Hz, 2H), 2.31 (s, 3H), 0.91 (t, J=7.6Hz, 3H). 13 C NMR (126MHz, Chloroform-d) δ147.20, 142.77, 139.94, 133.86, 129.85, 129.34, 128 .62, 128.18, 126.82, 125.87, 120.43, 18.17, 13.83, 12.52.HRMS(m / z)(ESI):calcd for C 18 H 19 N2[M+H] + 263.1543, found 263.1550.

[0058] Example 3

[0059] Preparation and characterization of 3,5-dimethyl-1,4-diphenyl-1H-pyrazole (3b):

[0060] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoromethanesulfonic acid, and 0.3 mmol of tetraethylhexafluorophosphonate ammonium were added to a 10 mL three-necked flask. 6 mL of dimethyl sulfoxide was added to dissolve the salt. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 10 mA and at 35 °C with stirring for 1.5 h. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:25 elution) to obtain the target product 3b.

[0061] Yellow oil (77%, 57.4 mg). 1 H NMR (400MHz, Chloroform-d) δ7.49-7.45 (m, 5H), 7.44-7.38 (m, 2H), 7.34-7.31 (m, 3H), 2.35 (s, 3H), 2.31 (s, 3H). 13 CNMR (126MHz, Chloroform-d) δ147.29, 140.00, 136.54, 133.92, 129.70, 129.22 ,128.61,127.60,126.60,125.12,121.05,12.79,11.96.HRMS(m / z)(ESI):calcd for C17 H 17 N2[M+H] + 249.1386, found 249.1392.

[0062] Example 4

[0063] Preparation and characterization of 3-methyl-1,4-diphenyl-5-propyl-1H-pyrazole (3c):

[0064] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoromethanesulfonic acid, and 0.3 mmol of tetrabutylhexafluorophosphonate ammonium were added to a 10 mL three-necked flask, dissolved in 6 mL of acetonitrile. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 10 mA and stirred at 35 °C for 2 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:30 elution) to obtain the target product 3c.

[0065] Yellow oil (72%, 59.7 mg). 1 H NMR (400MHz, Chloroform-d) δ7.52-7.47(m, 4H), 7.45-7.41(m, 2H), 7.38-7.30( m, 4H), 2.70-2.66 (m, 2H), 2.28 (s, 2H), 1.65-1.60 (m, 3H), 0.91 (t, J=7.2Hz, 3H). 13 C NMR (126MHz, Chloroform-d) δ151.44, 139.99, 136.58, 134.02, 129.87, 129.21, 128.59 ,127.56,126.68,125.14,120.87,29.04,22.91,14.27,11.83.HRMS(m / z)(ESI):calcd for C 19 H 21 N2[M+H] + 277.1699, found 277.1690.

[0066] Example 5

[0067] Preparation and characterization of 5-butyl-4-(cyclohexyl-1,5-dien-1-yl)-3-methyl-1-phenyl-1H-pyrazole (3d):

[0068] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoroacetic acid, and 0.3 mmol of tetrabutylammonium tetrafluoroborate were added to a 10 mL three-necked flask. 6 mL of a dimethyl sulfoxide and water mixture (v:v = 5:1) was added to dissolve the product. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 15 mA and at 40 °C with stirring for 1.5 h. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:30 elution) to obtain the target product 3d.

[0069] Yellow oil (61%, 53.5mg). 1 H NMR (400MHz, Chloroform-d) δ7.52-7.49(m, 4H), 7.47-7.41(m, 2H), 7.37-7.29(m, 4H), 2.72 -2.67 (m, 2H), 2.28 (s, 3H), 1.60-1.55 (m, 2H), 1.33 (d, J=7.5Hz, 2H), 0.85 (t, J=7.2Hz, 3H). 13 CNMR (101MHz, Chloroform-d) δ151.53, 140.00, 136.32, 133.96, 129.74, 129.06, 128.44, 1 27.35, 126.50, 125.00, 120.68, 31.66, 26.63, 22.69, 13.87, 11.70.HRMS(m / z)(ESI):calcd for C 20 H 22 N2[M+H] + 290.1783, found 290.1778.

[0070] Example 6

[0071] Preparation and characterization of 3-methyl-1,4,5-triphenyl-1H-pyrazole (3e):

[0072] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoroacetic acid, and 0.3 mmol of tetrabutylammonium iodide were added to a 10 mL three-necked flask. 6 mL of dimethyl sulfoxide was added to dissolve the product. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 20 mA and at 40 °C with stirring for 3 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:35 elution) to obtain the target product 3e.

[0073] Yellow oil(65%, 60.5mg).1H NMR (400MHz, Chloroform-d) δ7.61-7.58(m, 2H), 7.54-7.49(m, 4H), 7.43-7.36(m, 3H), 7. 34-7.31(m, 1H), 7.30-7.28(m, 1H), 7.27-7.26(m, 2H), 7.26-7.24(m, 2H), 2.32(s, 3H).13C NMR (126MHz, Chloroform-d) δ149.81, 140.05, 137.81, 133.99, 133.39, 130.47, 129.28, 128.61, 128.27, 127.87, 127.61, 126.89, 125.29, 120.25, 11.85.HRMS(m / z)(ESI):calcd for C22H19N2[M+H]+311.1543, found 311.1549.

[0074] Example 7

[0075] Preparation and characterization of 3-methyl-1,4-diphenyl-5-(p-tolyl)-1H-pyrazole (3f):

[0076] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoroacetic acid, and 0.3 mmol of tetrabutylammonium iodide were added to a 10 mL three-necked flask. 6 mL of a dimethyl sulfoxide and water mixture (v:v = 5:1) was added to dissolve the product. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 20 mA and at 35 °C with stirring for 2.5 h. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:35 elution) to obtain the target product 3f.

[0077] Yellow oil(66%, 64.2mg).1H NMR (400MHz, Chloroform-d) δ7.60-7.58(m, 2H), 7.52-7.48(m, 2H), 7.40-7.36(m, 5H), 7.34-7.30(m, 1H), 7.29-2.27(m, 2H), 7.08-7.06(m, 2H), 2.32(s, 3H), 2.31(s, 3H).13C NMR (101MHz, Chloroform-d) δ149.82, 140.09, 137.71, 137.29, 134.14, 130.48, 129.25, 128 .99, 128.58, 128.13, 127.78, 126.83, 125.28, 120.11, 21.39, 11.84.HRMS(m / z)(ESI):calcd for C23H21N2[M+H]+325.1699, found 325.1670.

[0078] Example 8

[0079] Preparation and characterization of 5-(4-methoxyphenyl)-3-methyl-1,4-diphenyl-1H-pyrazole (3g):

[0080] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoromethanesulfonic acid, and 0.3 mmol of tetrabutylammonium iodide were added to a 10 mL three-necked flask. 6 mL of dimethyl sulfoxide was added to dissolve the product. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 20 mA and at 15 °C with stirring for 2.5 h. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:35 elution) to obtain 3 g of the target product.

[0081] Yellow oil(65%, 66.4mg).1H NMR (400MHz, Chloroform-d) δ7.60-7.57(m, 2H), 7.52-7.48(m, 2H), 7.45-7.42(m, 2H), 7.41-7.3 7(m, 3H), 7.33-7.31(m, 1H), 7.29-7.27(m, 2H), 6.81-6.78(m, 2H), 3.78(s, 3H), 2.30(s, 3H).13C NMR (101MHz, Chloroform-d) δ159.23, 149.58, 140.10, 137.69, 134.15, 130.49, 129.48, 129.25, 128.60, 127.76, 126.83, 125.99, 125.25, 119.91, 113.71, 55.31, 11.86.HRMS(m / z)(ESI):calcd for C23H21N2O[M+H]+341.1648, found341.1658.

[0082] Example 9

[0083] Preparation and characterization of 5-(4-fluorophenyl)-3-methyl-1,4-diphenyl-1H-pyrazole (3h):

[0084] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of acetic acid, and 0.3 mmol of tetrabutylammonium hexafluorophosphonate were added to a 10 mL three-necked flask, dissolved in 6 mL of acetonitrile. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 10 mA and at 25 °C with stirring for 3 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:30 elution) to obtain the target product after 3 hours.

[0085] Yellow oil(67%, 66.0mg).1H NMR (400MHz, Chloroform-d) δ7.58-7.56(m, 2H), 7.52-7.45(m, 4H), 7.42-7.35( m, 3H), 7.33-7.30 (m, 1H), 7.26-7.24 (m, 2H), 6.96-6.91 (m, 2H), 2.30 (s, 3H).13C NMR (101MHz, Chloroform-d) δ 162.52 (d, J = 244.8Hz, 1JCF), 148.91, 139.96, 137.88, 133.79, 130.41, 129.92 (d, J = 8.0Hz, 3JCF), 129.53 (d, J = 3.1Hz, 4JCF) ), 129.30, 128.69, 127.93, 127.01, 125.24, 120.09, 115.21 (d, J=21.4Hz, 2JCF), 11.81.19FNMR (376MHz, Chloroform-d) δ-114.64.HRMS (m / z) (ESI):calcd for C22H18FN2[M+H]+329.1449, found 329.1456.

[0086] Example 10

[0087] Preparation and characterization of 5-(4-chlorophenyl)-3-methyl-1,4-diphenyl-1H-pyrazole (3i):

[0088] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of acetic acid, and 0.3 mmol of tetrabutylammonium tetrafluoroborate were added to a 10 mL three-necked flask. 6 mL of dimethyl sulfoxide was added to dissolve the salt. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 12 mA at 20 °C with stirring for 0.5–3 h. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:30 elution) to obtain the target product 3i.

[0089] Yellow oil(69%, 71.4mg).1H NMR (400MHz, Chloroform-d) δ7.60-7.56(m, 2H), 7.54-7.49(m, 2H), 7.46-7.37( m, 5H), 7.37-7.33 (m, 1H), 7.28-7.24 (m, 2H), 7.24-7.21 (m, 2H), 2.30 (s, 3H).13C NMR (101MHz, Chloroform-d) δ148.64, 139.93, 138.02, 133.69, 133.45, 131.94, 130.40, 129. 47, 129.33, 128.74, 128.49, 128.01, 127.10, 125.26, 120.25, 11.79.HRMS(m / z)(ESI):calcd for C22H18ClN2[M+H]+345.1153, found 345.1155.

[0090] Example 11

[0091] Preparation and characterization of 5-(3-bromo-4-fluorophenyl)-3-methyl-1,4-diphenyl-1H-pyrazole (3j):

[0092] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoroacetic acid, and 0.3 mmol of tetrabutylammonium tetrafluoroborate were added to a 10 mL three-necked flask, dissolved in 6 mL of acetonitrile. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 16 mA and at 25 °C with stirring for 3 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:40 elution) to obtain the target product 3j.

[0093] Yellow oil(61%, 74.5mg).1H NMR (400MHz, Chloroform-d) δ7.84-7.81(m, 1H), 7.58-7.49(m, 4H), 7.44-7.34(m, 4H), 7.30-7.27(m, 1H), 7.27-7.23(m, 2H), 6.95(t, J=8.4Hz, 1H), 2.30(s, 3H).13C NMR (101MHz, Chloroform-d) δ158.64 (d, J=246.2Hz, 1JCF), 147.50, 139.82, 138.13, 133.37, 133.03, 131.10 (d, J=3.8Hz, 4JCF), 130.36, 129 .36, 128.82, 128.73 (d, J=7.1Hz, 3JCF), 128.13, 127.28, 125.26, 120.23, 116.11 (d, J=22.3Hz, 2JCF), 108.97 (d, J=20.8Hz, 2JCF), 11.74.19F NMR(376MHz, Chloroform-d)δ-109.16.HRMS(m / z)(ESI):calcd for C22H17BrFN2[M+H]+407.0554, found 407.0550.

[0094] Example 12

[0095] Preparation and characterization of 5-(5-bromofuran-2-yl)-3-methyl-1,4-diphenyl-1H-pyrazole (3k):

[0096] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of acetic acid, and 0.3 mmol of tetrabutylammonium iodide were added to a 10 mL three-necked flask, dissolved in 6 mL of acetonitrile. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 5 mA and at 40 °C with stirring for 3 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:30 elution) to obtain the target product 3K.

[0097] Yellow oil(63%, 71.7mg).1H NMR (400MHz, Chloroform-d) δ7.56-7.48 (m, 4H), 7.44-7.41 (m, 3H), 7.39-7.34 (m, 3H), 6.22 (d, J=3.2Hz, 1H), 6.09 (d, J=3.2Hz, 1H), 2.24 (s, 3H).13C NMR (101MHz, Chloroform-d) δ150.14, 140.92, 139.72, 137.98, 132.98, 130.48, 129.29, 128. 65, 128.21, 127.56, 125.50, 121.68, 119.70, 112.80, 110.54, 11.47.HRMS(m / z)(ESI):calcd for C20H16BrN2O[M+H]+378.0368, found 378.0378.

[0098] Example 13

[0099] Preparation and characterization of 5-(4-bromothiophene-2-yl)-3-methyl-1,4-diphenyl-1H-pyrazole (3l):

[0100] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of acetic acid, and 0.3 mmol of tetrabutylammonium iodide were added to a 10 mL three-necked flask. 6 mL of dimethyl sulfoxide was added to dissolve the product. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 7 mA and at 35 °C with stirring for 2.5 h. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:40 elution) to obtain 3 μL of the target product.

[0101] Yellow oil(55%, 65.2mg).1H NMR (600MHz, Chloroform-d) δ7.56-7.54(m, 2H), 7.52-7.50(m, 2H), 7.47-7.44(m, 2H), 7.43- 7.39 (m, 2H), 7.36-7.34 (m, 2H), 7.06 (d, J=1.2Hz, 1H), 6.83 (d, J=0.8Hz, 1H), 2.24 (s, 3H).13 CNMR (101MHz, Chloroform-d) δ143.51, 139.67, 138.38, 137.38, 132.89, 130.65, 129.34, 128 .84, 128.15, 127.79, 127.41, 125.26, 122.06, 120.05, 109.70, 11.59.HRMS(m / z)(ESI):calcd for C20H15BrN2NaS[M+Na]+417.0032, found417.0040.

[0102] Example 14

[0103] Preparation and characterization of methyl-5-(naphth-2-yl)-1,4-diphenyl-1H-pyrazole (3m):

[0104] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoromethanesulfonic acid, and 0.3 mmol of tetraethylhexafluorophosphonate ammonium were added to a 10 mL three-necked flask. 6 mL of acetonitrile was added to dissolve the contents. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 9 mA and at 35 °C with stirring for 2.5 h. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:30 elution) to obtain the target product 3m.

[0105] Yellow oil(62%, 67.0mg).1H NMR (400MHz, Chloroform-d) δ8.02-8.01(m, 1H), 7.79-7.77(m, 1H), 7.74-7.69(m, 2H), 7.65-7.62( m, 3H), 7.56-7.51 (m, 2H), 7.45-7.40 (m, 3H), 7.40-7.36 (m, 2H), 7.37-7.31 (m, 3H), 2.35 (s, 3H).13C NMR (101MHz, Chloroform-d) δ149.69, 140.06, 137.95, 133.98, 133.47, 132.91, 130.92, 130.51, 129.32, 128.65, 128.42, 127.94, 127.69, 127.10, 126.98, 126.46, 125.94, 125.92, 125.34, 120.49, 11.84.HRMS(m / z)(ESI):calcd for C26H21N2[M+H]+361.1699, found 361.1697.

[0106] Example 15

[0107] Preparation and characterization of 3-ethyl-5-methyl-1,4-di-p-tolyl-1H-pyrazole (3n):

[0108] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoromethanesulfonic acid, and 0.3 mmol of tetraethylhexafluorophosphonate ammonium were added to a 10 mL three-necked flask, dissolved in 6 mL of acetonitrile. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 17 mA and at 10 °C with stirring for 3 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:20 elution) to obtain the target product 3n.

[0109] Yellow oil (75%, 65.3mg).1H NMR (400MHz, Chloroform-d) δ7.36-7.33 (m, 2H), 7.28-7.25 (m 3H), 7.23-7.19 (m, 3H), 2.68 (q, J=7.6Hz, 2H), 2.41 (d, J=4.8Hz, 6H), 2.28 (s, 3H), 0.90 (t, J=7.6Hz, 3H).13C NMR (101MHz, Chloroform-d) δ147.05, 142.51, 137.90, 137.76, 136.27, 131.12, 129.81, 12 9.70, 129.30, 125.67, 119.98, 21.35, 21.30, 18.16, 13.90, 12.58.HRMS(m / z)(ESI):calcd for C20H23N2[M+H]+291.1856, found 291.1857.

[0110] Example 16

[0111] Preparation and characterization of 1,4-bis(4-(tert-butyl)phenyl)-3-ethyl-5-methyl-1H-pyrazole (3o):

[0112] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoroacetic acid, and 0.3 mmol of tetrabutylammonium hexafluorophosphonate were added to a 10 mL three-necked flask. 6 mL of dimethyl sulfoxide was added to dissolve the product. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 20 mA and at 20 °C with stirring for 2.5 h. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:25 elution) to obtain the target product 3o.

[0113] Yellow oil(71%, 79.8mg).1H NMR (500MHz, Chloroform-d) δ7.50-7.47(m, 2H), 7.47-7.43(m, 2H), 7.41-7.38(m, 2H), 7.28-7.2 5 (m, 2H), 2.73 (q, J=7.5Hz, 2H), 2.31 (s, 3H), 1.38 (s, 9H), 1.37 (s, 9H), 0.95 (t, J=7.5Hz, 3H).13C NMR (126MHz, Chloroform-d) δ151.05, 149.31, 147.08, 142.51, 137.69, 131.08, 129.34, 126.12, 1 25.42, 125.37, 119.87, 34.82, 34.66, 31.55, 31.49, 18.18, 14.06, 12.69.HRMS(m / z)(ESI):calcd for C26H34N2Na[M+Na]+397.2614, found 397.2621.

[0114] Example 17

[0115] Preparation and characterization of 1,4-bis(4-chlorophenyl)-3-ethyl-5-methyl-1H-pyrazole (3p):

[0116] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoromethanesulfonic acid, and 0.3 mmol of tetrabutylammonium tetrafluoroborate were added to a 10 mL three-necked flask. 6 mL of a dimethyl sulfoxide and water mixture (v:v = 5:1) was added to dissolve the product. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 20 mA and at 25 °C with stirring for 0.5 h. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:20 elution) to obtain the target product 3p.

[0117] Yellow oil(67%, 66.6mg).1H NMR (500MHz, Chloroform-d) δ7.50-7.47 (m, 2H), 7.45-7.42 (m, 4H), 7.30-7.25 (m, 2H), 2.71 (q, J=7.5Hz, 2H), 2.28 (s, 3H), 0.94 (t, J=7.5Hz, 3H).13C NMR (126MHz, Chloroform-d) δ147.60, 142.62, 138.66, 133.85, 132.85, 132.32, 131 .06, 129.50, 128.88, 126.85, 119.61, 18.14, 13.81, 12.49.HRMS(m / z)(ESI):calcd for C18H17Cl2N2[M+H]+331.0763found 331.0770.

[0118] Example 18

[0119] Preparation and characterization of 3-ethyl-5-methyl-1,4-bis(4-(trifluoromethyl)phenyl)-1H-pyrazole (3q):

[0120] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoromethanesulfonic acid, and 0.3 mmol of tetrabutylammonium iodide were added to a 10 mL three-necked flask. 6 mL of dimethyl sulfoxide was added to dissolve the product. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 15 mA and at 40 °C with stirring for 0.5 h. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:15 elution) to obtain the target product 3q.

[0121] Yellow oil(65%,77.7mg).1H NMR (400MHz, Chloroform-d) δ7.77-7.75(m, 2H), 7.71-7.69(m, 2H), 7.64-7.62(m, 2 H), 7.44-7.42 (m, 2H), 2.76 (q, J=7.6Hz, 2H), 2.29 (s, 3H), 0.93 (t, J=7.6Hz, 3H).13C NMR (126MHz, Chloroform-d) δ148.20, 142.91, 137.55, 130.03, 130.01 (d, J=32.7Hz, 2JCF), 129.18 (d, J=32.2Hz, 2JCF), 126.62 (d, J=3.8Hz, 3JCF), 125.68 (d, J=3.9Hz, 3JCF), 125.49, 123.95 (d, J=271.0Hz, 1JCF), 123.32, 120.19, 18.25, 13.83, 12.55.19F NMR(376MHz, Chloroform-d)δ-62.43,-62.46.HRMS(m / z)(ESI):calcd for C20H17F6N2[M+H]+399.1290found 399.1297.

[0122] Example 19

[0123] Preparation and characterization of methyl 4-(5-ethyl-1-(4-(2-methoxy-2-oxoethyl)phenyl)-3-methyl-1H-pyrazole-4-yl)benzoate (3r):

[0124] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoromethanesulfonic acid, and 0.3 mmol of tetrabutylammonium tetrafluoroborate were added to a 10 mL three-necked flask, dissolved in 6 mL of acetonitrile. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 25 mA and at 40 °C with stirring for 3 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:20 elution) to obtain the target product 3r.

[0125] Yellow oil(62%, 73.0mg).1H NMR (400MHz, Chloroform-d) δ 8.18-7.15 (m, 2H), 8.12-8.09 (m, 2H), 7.58-7.56 (m, 2H), 7.40-7. 37 (m, 2H), 3.95 (d, J=2.8Hz, 6H), 2.78 (q, J=7.2Hz, 2H), 2.29 (s, 3H), 0.91 (t, J=7.6Hz, 3H).13C NMR (101MHz, Chloroform-d) δ167.11, 166.45, 148.13, 143.760, 142.82, 138.71, 130.86, 129.97, 1 29.65, 129.37, 128.61, 124.90, 120.49, 52.48, 52.30, 18.32, 13.70, 12.64.HRMS(m / z)(ESI):calcd forC23H24N2NaO4[M+Na]+415.1628found 415.1619.

[0126] Example 20

[0127] Preparation and characterization of 5-ethyl-3-methyl-1,4-di(naphthyl-2-yl)-1H-pyrazole (3S):

[0128] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoroacetic acid, and 0.3 mmol of tetrabutylammonium hexafluorophosphate were added to a 10 mL three-necked flask. 6 mL of acetonitrile was added to dissolve the salt. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 20 mA and at 35 °C with stirring for 0.5 h. The reaction progress was monitored by thin-layer chromatography. After the reaction was complete, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:35 elution) to obtain the target product 3S.

[0129] Yellow oil(60%, 65.2mg).1H NMR (400MHz, Chloroform-d) δ7.80-7.97(m, 2H), 7.94-7.87(m, 5H), 7.82-7.80(m, 1H), 7.67-7.64(m, 1H), 7 .57-7.49 (m, 5H), 2.85 (q, J=7.6Hz, 2H), 2.38 (s, 3H), 0.94 (t, J=7.2Hz, 3H).13CNMR (101MHz, Chloroform-d )δ147.68, 143.27, 133.69, 133.44, 132.73, 132.37, 129.38, 128.48, 128.24, 128.34, 128.21, 127.99, 127. 87, 127.01, 126.76, 126.37, 126.00, 124.06, 124.00, 120.56, 18.40, 13.94, 12.65.HRMS(m / z)(ESI):calcd for C26H23N2[M+H]+363.1856found 363.1851.

[0130] Example 21

[0131] Preparation and characterization of 1,4-bis(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-5-ethyl-3-methyl-1H-pyrazole (3t):

[0132] 0.6 mmol of an aryl diazonium salt, 0.9 mmol of an enone, 0.5 mL of trifluoroacetic acid, and 0.3 mmol of tetrabutylammonium hexafluorophosphonate were added to a 10 mL three-necked flask. 6 mL of dimethyl sulfoxide was added to dissolve the product. A carbon rod was used as the anode, and a platinum sheet as the cathode. The reaction was carried out at a constant current of 20 mA and at 40 °C with stirring for 3 hours. The reaction progress was monitored by thin-layer chromatography. After the reaction was completed, the mixture was extracted with ethyl acetate (3 × 5 mL). The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (silica gel, ethyl acetate / petroleum ether = 1:15 elution) to obtain 3 t of the target product.

[0133] Yellow oil(52%, 90.4mg).1H NMR (400MHz, Chloroform-d) δ7.52 (d, J=2.4Hz, 1H), 7.41-7.32 (m, 4H), 7.32-7.26 (m, 2H), 7.25-7.20 (m, 4H), 7.13-7. 10 (m, 1H), 7.06-6.99 (m, 5H), 5.20 (s, 2H), 5.19 (s, 2H), 2.64 (q, J=7.6Hz, 2H), 2.25 (s, 3H), 0.93 (t, J=7.2Hz, 3H).13C NMR (101MHz, Chloroform-d) δ163.17 (d, J=245.5Hz, 1JCF), 154.14, 153.13, 147.25, 143.42, 139.22, 139.14, 138.68, 13 8.60, 132.86, 131.59, 130.43 (d, J=8.2Hz, 2JCF), 130.37 (d, J=8.0Hz, 2JCF), 129.10, 128.25, 127.16, 125.40, 123.85, 12 3.43, 122.58, 122.55, 122.51, 118.90, 115.25 (d, J=20.9Hz, 3JCF), 115.10 (d, J=20.9Hz, 3JCF), 114.23, 114.08, 114.01 ,113.86,70.41,70.23,18.02,13.82,12.08.19FNMR(376MHz,Chloroform-d)δ-112.42,-112.55.HRMS(m / z)(ESI):calcd forC32H27Cl2F2N2O2[M+H]+579.1412found 579.1417.

[0134] The above-disclosed method is merely a preferred embodiment of the synthesis method of a polysubstituted pyrazole compound of the present invention, and should not be construed as limiting the scope of the present invention. Those skilled in the art will understand that all or part of the above-described process can be implemented, and equivalent variations made in accordance with the claims of the present invention are still within the scope of the invention.

Claims

1. A method for synthesizing polysubstituted pyrazole compounds, characterized in that, Includes the following steps; Add 0.6 mmol of aryl diazonium salt, 0.9 mmol of enone, 0.5 mL of acid and 0.3 mmol of electrolyte to a 10 mL three-necked flask, and dissolve them in 6 mL of solvent. A carbon rod was used as the anode and a platinum sheet as the cathode. The reaction was stirred and the reaction process was monitored by thin-layer chromatography. After the reaction was completed, the mixture was extracted with ethyl acetate. The organic layer of the mixture was dried with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography to obtain the target product. The acid includes one or more of acetic acid, trifluoromethanesulfonic acid, and trifluoroacetic acid; the electrolyte includes one or more of tetrabutylammonium hexafluorophosphonate, tetraethylammonium hexafluorophosphonate, tetrabutylammonium tetrafluoroborate, and tetrabutylammonium iodide; the solvent includes acetonitrile, dimethyl sulfoxide, and a mixture of dimethyl sulfoxide and water; the stirring reaction conditions include a constant current of 5-20 mA, a reaction temperature of 10-40°C, and a stirring reaction time of 0.5-3 hours; the general formula for the synthesis of polysubstituted pyrazole compounds is shown below: ； Among them, polysubstituted pyrazole compounds include 3-ethyl-5-methyl-1,4-diphenyl-1H-pyrazole, 3-methyl-1,4-diphenyl-5-propyl-1H-pyrazole, 5-butyl-4-(cyclohexyl-1,5-dien-1-yl)-3-methyl-1-phenyl-1H-pyrazole, 3-methyl-1,4,5-triphenyl-1H-pyrazole, and 3-methyl-1,4-diphenyl-5-(p-tolyl)- 1H-pyrazole, 5-(4-methoxyphenyl)-3-methyl-1,4-diphenyl-1H-pyrazole, 5-(4-fluorophenyl)-3-methyl-1,4-diphenyl-1H-pyrazole, 5-(4-chlorophenyl)-3-methyl-1,4-diphenyl-1H-pyrazole, 5-(3-bromo-4-fluorophenyl)-3-methyl-1,4-diphenyl-1H-pyrazole, 5-(5-bromofuran-2-yl)-3- Methyl-1,4-diphenyl-1H-pyrazole, 5-(4-bromothiophen-2-yl)-3-methyl-1,4-diphenyl-1H-pyrazole, 3-methyl-5-(naphthyl-2-yl)-1,4-diphenyl-1H-pyrazole, 3-ethyl-5-methyl-1,4-di-p-tolyl-1H-pyrazole, 1,4-bis(4-(tert-butyl)phenyl)-3-ethyl-5-methyl-1H-pyrazole, 1,4-bis( 4-Chlorophenyl)-3-ethyl-5-methyl-1H-pyrazole, methyl 4-(5-ethyl-1-(4-(2-methoxy-2-oxyethyl)phenyl)-3-methyl-1H-pyrazole-4-yl)benzoate, 5-ethyl-3-methyl-1,4-di(naphthyl-2-yl)-1H-pyrazole and 1,4-bis(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-5-ethyl-3-methyl-1H-pyrazole.

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