1,3,5-trisubstituted pyrazoles and methods for their preparation

Abstract

The application belongs to the technical field of organic synthesis, and particularly relates to a 1,3,5-trisubstituted pyrazole compound and a preparation method thereof. The preparation method of the 1,3,5-trisubstituted pyrazole compound provided by the application comprises the following steps: mixing a hydrazine compound, an alpha-bromoketone compound, a photocatalyst, an alkaline compound, an additive and a polar organic solvent, and performing an addition cyclization reaction under light irradiation to obtain the 1,3,5-trisubstituted pyrazole compound. The preparation method has the advantages of mild conditions, easy control, high reaction efficiency, economical steps, cheap and easily available raw materials, no use of oxidants, good functional group tolerance and the like, and the prepared 1,3,5-trisubstituted pyrazole compound has high purity, the purity is 98.5-99.9%, and has great market promotion value.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a 1,3,5-trisubstituted pyrazole compound and its preparation method. Background Technology

[0002] 1,3,5-Trisubstituted pyrazole compounds frequently serve as the backbones of certain pharmaceuticals and pesticides, playing a vital role in their research and development. For example, celecoxib and loratadine are nonsteroidal anti-inflammatory drugs (NSAIDs) used to treat pain or inflammation; teposarrin is a veterinary analgesic with potent anti-inflammatory activity; SC-560 exhibits good anticancer activity; and cyclopropamide and fipronil are highly effective insecticides. Due to their excellent biological activity and synthetic applications, the construction of 1,3,5-trisubstituted pyrazole backbones has attracted considerable attention in recent years.

[0003] Currently, the main methods for synthesizing 1,3,5-trisubstituted pyrazole derivatives are:

[0004] (a) Florian Pünner et al. (Florian Pünner, Yoshihiro Sohtome, Mikiko Sodeoka. Solvent-dependent copper-catalyzed synthesis of pyrazoles under aerobic conditions.[J]. Chemical Communications, 2016, 52(98):14093-14096.DOI:10.1039 / C6CC06935E) reported the synthesis of 1,3,5-trisubstituted pyrazoles from α,β-unsaturated hydrazones under copper acetate catalysis, such as:

[0005]

[0006] However, the above synthesis method requires the use of pre-synthesized raw materials. Raw material 1 must be synthesized first before proceeding to the next step, making the operation process cumbersome and resulting in high costs in materials, time, and labor. Moreover, it requires the use of high-concentration oxygen as an oxidant, making the reaction conditions harsh.

[0007] (b) Silja Hofmann et al. (Silja Hofmann, Martin Linden, Julian Neuner, Felix N. Weber, S. Iegfried R. Waldvogel. Electrochemically enabled oxidative aromatization of pyrazolines[J]. Organic & Biomolecular Chemistry, 2023, 21(22):4694-4701. DOI:10.1039 / D3OB00671A) reported the electrocatalytic conversion of 1,3,5-trisubstituted pyrazolines to 1,3,5-trisubstituted pyrazols, for example:

[0008]

[0009] This method also requires the use of pre-synthesized raw materials, has a complicated operation process, requires high reaction temperature, and has harsh reaction conditions. Furthermore, an increase in reaction temperature can prevent temperature-sensitive substrates from reacting.

[0010] (c) Liqiang Hao et al. (Liqiang Hao, Zhichao Wang, Yangyang Wang, Zhaoziyuan Yang, Xian Liu, Xiaobo Xua, Yafei Ji. Synthesis of pyrazoles from sulfonylhydrazone and benzyl acrylate under transition-metal-free conditions[J]. Organic & Biomolecular Chemistry, 2023, 21(37):7611-7615. DOI:10.1039 / D3OB01172K.) reported that base-promoted synthesis of 1,3,5-trisubstituted pyrazoles from sulfonylhydrazone and benzyl acrylate, such as:

[0011]

[0012] This method also requires the use of pre-synthesized raw materials, has a complicated operation process, requires high reaction temperature, and has harsh reaction conditions. Furthermore, an increase in reaction temperature can prevent temperature-sensitive substrates from reacting.

[0013] Currently, the preparation methods for 1,3,5-trisubstituted pyrazole compounds suffer from drawbacks such as complex processes, demanding conditions, and limited substrate range. Summary of the Invention

[0014] In view of this, the purpose of this invention is to provide a 1,3,5-trisubstituted pyrazole compound and a method for preparing the same. The preparation method of this invention uses commercially available and inexpensive raw materials, employs a simple process, mild conditions, does not use oxidants, has a broad substrate range, and exhibits good functional group tolerance.

[0015] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0016] This invention provides a method for preparing 1,3,5-trisubstituted pyrazole compounds, comprising the following steps:

[0017] A mixture of hydrazine compounds, α-bromoketone compounds, a photocatalyst, a basic compound, an additive, and a polar organic solvent was carried out under light irradiation to obtain the 1,3,5-trisubstituted pyrazole compounds.

[0018] The hydrazine compound has the structure shown in Formula I:

[0019]

[0020] R1 is aryl, substituted aryl, or heteroaryl;

[0021] The α-bromoketone compounds have the structure shown in Formula II:

[0022]

[0023] R2 is aryl, substituted aryl, heteroaryl, or alkyl;

[0024] The 1,3,5-trisubstituted pyrazole compounds have the structure shown in Formula III:

[0025]

[0026] The additives include one or more of sodium benzenesulfinate, sodium 4-methylbenzenesulfinate, and sodium 4-fluorobenzenesulfinate.

[0027] Preferably, the hydrazine compounds include one or more of phenylhydrazine, 4-fluorophenylhydrazine, 4-chlorophenylhydrazine, 4-bromophenylhydrazine, 4-cyanophenylhydrazine, 4-methoxyphenylhydrazine, 3-chlorophenylhydrazine, 3-bromophenylhydrazine, 3-trifluoromethylphenylhydrazine, 3-methylphenylhydrazine, 2-fluorophenylhydrazine, 2-chlorophenylhydrazine, 2-bromophenylhydrazine, 2-methylphenylhydrazine, 2-hydrazylpyridine, and 2-naphthylhydrazine.

[0028] Preferably, the α-bromoketone compounds include one or more of 2-bromoacetophenone, 2-bromo-4'-(trifluoromethyl)acetophenone, 2-bromo-4'-fluoroacetophenone, 2-bromo-4'-chloroacetophenone, 2,4'-dibromoacetophenone, 2-bromo-4'-iodoacetophenone, 2-bromo-4'-methylacetophenone, 2-bromo-4'-methoxyacetophenone, 2,3'-dibromoacetophenone, 2-bromo-2'-chloroacetophenone, 2-bromo-3',4'-dimethoxyacetophenone, 2-bromo-5'-fluoro-2'-methoxyacetophenone, 2-(2-bromoacetyl)pyridine, 2-(2-bromoacetyl)thiophene, 2-(2-bromoacetyl)naphthalene, and α-bromocyclopropylacetophenone.

[0029] Preferably, the molar ratio of the hydrazine compound to the α-bromoketone compound is 1:2 to 4.

[0030] Preferably, the photocatalyst comprises a metal photocatalyst and / or a non-metal photocatalyst; the metal photocatalyst comprises Ru(pby)3 and / or Ir[dF(CF3)ppy]2(dtbbpy)PF6; the non-metal photocatalyst comprises one or more of Bengal rose red, Rhodamine B and 4CzIPN.

[0031] Preferably, the molar ratio of the hydrazine compound to the additive is 1:2 to 4.

[0032] Preferably, the illumination is a 10W blue LED; the addition cyclization reaction is carried out at room temperature for 12–24 hours.

[0033] Compared with the prior art, the present invention has the following beneficial effects:

[0034] This invention provides a method for preparing 1,3,5-trisubstituted pyrazole compounds, comprising the following steps: mixing a hydrazine compound, an α-bromoketone compound, a photocatalyst, a basic compound, an additive, and a polar organic solvent, and carrying out an addition cyclization reaction under light irradiation to obtain the 1,3,5-trisubstituted pyrazole compound. This invention involves carrying out an addition cyclization reaction of a hydrazine compound and an α-bromoketone compound under light irradiation to obtain 1,3,5-trisubstituted pyrazole compounds. The preparation method of this invention has advantages such as mild conditions, easy control, high reaction efficiency, economical steps, inexpensive and readily available raw materials, no use of oxidants, and good functional group tolerance (hydrazines containing aryl, substituted aryl, and heteroaryl groups can all react with α-bromoketones). This invention uses one or more of sodium benzenesulfinate, sodium 4-methylbenzenesulfinate, and sodium 4-fluorobenzenesulfinate as additives to rapidly convert α-bromoketones into intermediates. These intermediates can be converted into 1,3,5-trisubstituted pyrazole compounds under light irradiation, thus promoting the addition cyclization reaction. Compared with multi-step synthesis reactions, this invention can obtain the target product in one step, with a reaction yield of 43-82%, and has the advantages of high reaction efficiency and economical steps.

[0035] Moreover, the 1,3,5-trisubstituted pyrazole compounds prepared by this invention have high purity, ranging from 98.5% to 99.9%, and have significant market potential. Detailed Implementation

[0036] This invention provides a method for preparing 1,3,5-trisubstituted pyrazole compounds, comprising the following steps:

[0037] A mixture of hydrazine compounds, α-bromoketone compounds, a photocatalyst, a basic compound, an additive, and a polar organic solvent was carried out under light irradiation to obtain the 1,3,5-trisubstituted pyrazole compounds.

[0038] The hydrazine compound has the structure shown in Formula I:

[0039]

[0040] R1 is aryl, substituted aryl, or heteroaryl;

[0041] The α-bromoketone compounds have the structure shown in Formula II:

[0042]

[0043] R2 is aryl, substituted aryl, heteroaryl, or alkyl;

[0044] The 1,3,5-trisubstituted pyrazole compounds have the structure shown in Formula III:

[0045]

[0046] The additives include one or more of sodium benzenesulfinate, sodium 4-methylbenzenesulfinate, and sodium 4-fluorobenzenesulfinate.

[0047] Unless otherwise specified, all materials and equipment used in this invention are commercially available products in the field.

[0048] In this invention, R1 is preferably phenyl, substituted phenyl, pyridyl, or naphthyl, wherein the substituent in the substituted phenyl group preferably includes a halogen group, cyano group, methoxy group, trifluoromethyl group, or methyl group, and the halogen group preferably includes fluorine, chlorine, bromine, or iodine group; the hydrazine compound preferably includes phenylhydrazine, substituted phenylhydrazine, or naphthylhydrazine, more preferably including one or more of phenylhydrazine, 4-fluorophenylhydrazine, 4-chlorophenylhydrazine, 4-bromophenylhydrazine, 4-cyanophenylhydrazine, 4-methoxyphenylhydrazine, 3-chlorophenylhydrazine, 3-bromophenylhydrazine, 3-trifluoromethylphenylhydrazine, 3-methylphenylhydrazine, 2-fluorophenylhydrazine, 2-chlorophenylhydrazine, 2-bromophenylhydrazine, 2-methylphenylhydrazine, 2-hydrazylpyridine, and 2-naphthylhydrazine.

[0049] In this invention, R2 is preferably phenyl, substituted phenyl, pyridyl, thiophenyl, naphthyl, or cycloalkyl, wherein the substituent in the substituted phenyl group preferably includes a halogen group, cyano group, methoxy group, trifluoromethyl group, or methyl group, and the halogen group preferably includes fluorine, chlorine, bromine, or iodine; the cycloalkyl group preferably includes cyclopropane; and the α-bromoketone compound preferably includes 2-bromoacetophenone, 2-bromo-4'-(trifluoromethyl)acetophenone, 2-bromo-4'-fluoroacetophenone, or 2-bromo-4'-chloroacetophenone. One or more of the following: ketones, 2,4'-dibromoacetophenone, 2-bromo-4'-iodoacetophenone, 2-bromo-4'-methylacetophenone, 2-bromo-4'-methoxyacetophenone, 2,3'-dibromoacetophenone, 2-bromo-2'-chloroacetophenone, 2-bromo-3',4'-dimethoxyacetophenone, 2-bromo-5'-fluoro-2'-methoxyacetophenone, 2-(2-bromoacetyl)pyridine, 2-(2-bromoacetyl)thiophene, 2-(2-bromoacetyl)naphthalene, and α-bromocyclopropylacetophenone.

[0050] In this invention, the molar ratio of the hydrazine compound and the α-bromoketone compound is preferably 1:2 to 4, more preferably 1:4.

[0051] In this invention, the photocatalyst preferably includes a metal photocatalyst and / or a non-metal photocatalyst; the metal photocatalyst preferably includes Ru(pby)3 and / or Ir[dF(CF3)ppy]2(dtbbpy)PF6; the non-metal photocatalyst preferably includes one or more of Bengal rose red, Rhodamine B and 4CzIPN.

[0052] In this invention, the molar ratio of the hydrazine compound to the photocatalyst is preferably 1:0.01 to 0.05, more preferably 1:0.01 to 0.02.

[0053] In this invention, the alkaline compound preferably comprises an inorganic alkaline compound and / or an organic alkaline compound; the inorganic alkaline compound preferably comprises one or more of potassium carbonate, potassium hydroxide, potassium phosphate, and dipotassium hydrogen phosphate; the organic alkaline compound preferably comprises one or more of 1,8-diazabicyclo[5.4.0]undec-7-ene, diethylamine, and triethylamine. This invention utilizes the alkaline compound to provide an alkaline environment.

[0054] In this invention, the molar ratio of the hydrazine compound and the basic compound is preferably 1:2 to 4.

[0055] In this invention, the polar organic solvent preferably includes one or more of N,N-dimethylformamide, acetonitrile, tetrahydrofuran, dichloromethane, and ethanol.

[0056] In this invention, the preferred ratio of the polar organic solvent to the hydrazine compound is 1L:0.05-0.2mol, more preferably 1L:0.05-0.1mol.

[0057] In this invention, the molar ratio of the hydrazine compound and the additive is preferably 1:2 to 4. The additive can promote the conversion of α-bromoketone compounds into trans-1,4-enediones, which then undergo dehydration and cyclization with hydrazine compounds to generate 1,3,5-trisubstituted pyrazole compounds. This process can be completed rapidly in one step. Taking Example 1 as an example, the additive sodium benzenesulfinate can react with 2-bromoacetophenone to generate an intermediate of the pyrazole product: 2-benzenesulfonylacetophenone (CAS: 3406-03-9). 2-benzenesulfonylacetophenone (CAS: 3406-03-9) can react with 2-bromoacetophenone to convert into the intermediate trans-1,2-dibenzoylethylene (CAS: 959-28-4). This intermediate can react with hydrazine under light to convert into 1,3,5-trisubstituted pyrazole compounds. The additives described in this invention can improve the yield of 1,3,5-trisubstituted pyrazole compounds. Without the additives, the yield of 1,3,5-trisubstituted pyrazole compounds is only trace amounts.

[0058] The present invention does not impose any special limitations on the mixing process; the materials can be mixed evenly according to a process known in the art.

[0059] In this invention, the illumination is preferably a 10W blue LED, and the light source is preferably a photocatalytic reactor (WP-TEC-1020), provided by Xi'an Huatai Kesi Co., Ltd. The temperature of the addition cyclization reaction is preferably room temperature, and the time is preferably 12–24 hours, more preferably 18–24 hours. The addition cyclization reaction is preferably carried out under stirring conditions. This invention does not have a specific limitation on the stirring rate; any process well-known in the art can be followed to ensure the reaction proceeds smoothly.

[0060] In this invention, the addition cyclization reaction preferably further includes purifying the resulting product system. The purification method is preferably column chromatography, preferably using a silica gel column. The eluent used in the column chromatography is preferably a mixed solvent of petroleum ether and ethyl acetate; the volume ratio of petroleum ether to ethyl acetate in the mixed solvent is preferably 1–20:1, more preferably 5–15:1. This invention does not impose any special limitations on the specific process of the column chromatography; any method well-known to those skilled in the art can be used. This invention utilizes petroleum ether and ethyl acetate as eluents for purification, enabling the acquisition of the target compound with high purity.

[0061] In this invention, the purity of the 1,3,5-trisubstituted pyrazole compound is preferably 98.5-99.9%, and the yield is preferably 43-82%.

[0062] This invention also provides 1,3,5-trisubstituted pyrazole compounds, with the structural formula shown in any of the following structures:

[0063]

[0064]

[0065] The 1,3,5-trisubstituted pyrazole compounds described in this invention can be used as pharmaceutical intermediates or as skeleton materials for pharmaceuticals and pesticides.

[0066] To further illustrate the present invention, the following detailed description of the 1,3,5-trisubstituted pyrazole compounds and their preparation methods provided by the present invention is provided in conjunction with the embodiments, but these should not be construed as limiting the scope of protection of the present invention.

[0067] Example 1

[0068] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0069]

[0070] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2-bromoacetophenone, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 76% and a purity of 99.9%.

[0071] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0072] 1 H NMR (400MHz, CDCl3, ppm) δ7.99(d,J=7.3Hz,2H),7.92(d,J=7.1Hz,2H),7.63(d,J=7.4H z,1H),7.52(t,J=7.8Hz,4H),7.45(t,J=6.3Hz,4H),7.38(t,J=7.3Hz,2H),7.10(s,1H);

[0073] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ185.6,151.5,140.5,140.2,137.3,133.7,132.1,129.9,129.0,128.8,128.7,128.5,128.2,125.9,124.9,110.8;

[0074] MS(EI,70eV)m / z 324,295,247,105,77;

[0075] HRMS(ESI)m / z[M+H] + calcd for C 22 H 17 N2O 325.1335, found 325.1366.

[0076] Example 2

[0077] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0078]

[0079] At room temperature, 0.1 mmol of 4-fluorophenylhydrazine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 69% and a purity of 99.9%.

[0080] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0081] 1 H NMR (400MHz, CDCl3, ppm) δ7.98(d,J=6.8Hz,2H),7.89(d,J=7.1Hz,2H),7.65( t,J=7.5Hz,1H),7.54-7.42(m,6H),7.37(t,J=7.3Hz,1H),7.15-7.08(m,3H);

[0082] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ185.4,163.4,161.0,151.5,140.5,137.3,136.4,136.3, 133.7,132.0,129.8,128.8,128.7,128.6,126.9,126.8,126.0,116.0,115.8,110.9;

[0083] MS(EI,70eV)m / z 342,313,265,105,77;

[0084] HRMS(ESI)m / z[M+H] + calcd for C 22 H 16 N2OF 343.1241, found 343.1271.

[0085] Example 3

[0086] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0087]

[0088] At room temperature, 0.1 mmol of 4-chlorophenylhydrazine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 66% and a purity of 99.9%.

[0089] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0090] 1 H NMR (400MHz, CDCl3, ppm) δ7.99 (d, J = 7.7Hz, 2H), 7.89 (d, J = 7.6Hz, 2H), 7.67 (d, J = 7.5Hz, 1H), 7.53 (t, J = 7.7Hz, 3H), 7.46-7.35 (m, 6H), 7.09 (s, 1H);

[0091] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ185.4,151.7,140.4,138.7,137.2,134.0,133.9,131.9,129.9,129.1,128.9,128.8,128.7,126.2,125.9,111.1;

[0092] MS(EI,70eV)m / z 358,329,246,105,77;

[0093] HRMS(ESI)m / z[M+H] + calcd for C 22 H 16 N2OCl 359.0946, found 359.0977.

[0094] Example 4

[0095] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0096]

[0097] At room temperature, 0.1 mmol of 4-bromophenylhydrazine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube and stirred for 24 h under a 10 W blue LED. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 64% and a purity of 99.9%.

[0098] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0099] 1 H NMR (400MHz, CDCl3, ppm) δ7.99(d,J=7.2Hz,2H),7.89(d,J=7.0Hz,2H),7.66(d,J=7.5 Hz,1H),7.57-7.51(m,4H),7.43(d,J=7.6Hz,2H),7.38(d,J=8.8Hz,3H),7.09(s,1H);

[0100] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ185.4,151.8,140.4,139.2,137.1,133.8,132.1,131.9,129.9,128.9,128.8,128.7,126.4,125.9,122.0,111.2;

[0101] MS(EI,70eV)m / z 402,375,246,105,77;

[0102] HRMS(ESI)m / z[M+H] + calcd for C 22 H 16 N2OBr 403.0441, found 403.0476.

[0103] Example 5

[0104] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0105]

[0106] At room temperature, 0.1 mmol of 4-cyanophenylhydrazine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 5:1. The purified target product was obtained with a yield of 70% and a purity of 99.9%.

[0107] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0108] 1 H NMR (400MHz, CDCl3, ppm) δ8.00(d,J=8.0Hz,2H),7.89(d,J=7.7Hz,2H),7.75- 7.61(m,5H),7.55(t,J=7.6Hz,2H),7.42(dt,J=23.5,7.4Hz,3H),7.13(s,1H);

[0109] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ185.3,152.5,143.3,140.6,136.8,134.2,133.0,131.5,129.9,129.0,128.9,126.0,125.1,118.3,112.2,111.5;

[0110] MS(EI,70eV)m / z 349,320,272,105,77;

[0111] HRMS(ESI)m / z[M+H] + calcd for C 23 H 16 N3O 350.1288, found 350.1319.

[0112] Example 6

[0113] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0114]

[0115] At room temperature, 0.1 mmol of 4-methoxyphenylhydrazine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube and stirred for 24 h under a 10 W blue LED. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 5:1. The purified target product was obtained with a yield of 60% and a purity of 99.9%.

[0116] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0117] 1 H NMR (400MHz, CDCl3, ppm) δ7.98(d,J=7.2Hz,2H),7.90(d,J=7.4Hz,2H),7.63(d,J=7.6Hz,1H),7.52(d,J =7.6Hz,2H),7.45-7.40(m,4H),7.37(d,J=7.3Hz,1H),7.07(s,1H),6.94(d,J=8.9Hz,2H),3.83(s,3H);

[0118] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ185.6,159.4,151.1,140.4,137.4,133.6,13 3.4,132.2,129.8,128.8,128.6,128.4,126.3,125.9,114.2,110.4,55.6;

[0119] MS(EI,70eV)m / z 354,325,146,105,77;

[0120] HRMS(ESI)m / z[M+H] + calcd for C 23 H 19 N2O2 355.1441, found 355.1473.

[0121] Example 7

[0122] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0123]

[0124] At room temperature, 0.1 mmol of 3-chlorophenylhydrazine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 65% and a purity of 99.9%.

[0125] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0126] 1 H NMR (400MHz, CDCl3, ppm) δ7.98(d,J=8.5Hz,2H),7.90(d,J=7.6Hz,2H),7.65(d,J=7.5Hz,1H ),7.58(s,1H),7.53(t,J=7.6Hz,2H),7.45(t,J=7.4Hz,2H),7.40-7.34(m,4H),7.10(s,1H);

[0127] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ185.3,151.8,141.1,140.6,137.1,134.6,133 .8,131.8,129.8,128.9,128.8,128.7,128.3,125.9,125.3,123.1,111.3;

[0128] MS(EI,70eV)m / z 358,329,246,105,77;

[0129] HRMS(ESI)m / z[M+H] + calcd for C 22 H 16 N2OCl 359.0946, found 359.0978.

[0130] Example 8

[0131] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0132]

[0133] At room temperature, 0.1 mmol of 3-bromophenylhydrazine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 64% and a purity of 99.9%.

[0134] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0135] 1 H NMR (400MHz, CDCl3, ppm) δ7.99(d,J=8.0Hz,2H),7.90(d,J=7.2Hz,2H),7.74(s,1H),7.67(t,J=7.5Hz,1 H),7.57-7.50(m,3H),7.45(t,J=7.4Hz,2H),7.39(d,J=7.4Hz,2H),7.29(d,J=8.0Hz,1H),7.10(s,1H);

[0136] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ185.3,151.9,141.2,140.6,137.1,133.8,131.8, 131.2,130.1,129.8,128.9,128.8,128.7,128.1,125.9,123.6,122.4,111.3;

[0137] MS(EI,70eV)m / z 402,375,246,105,77;

[0138] HRMS(ESI)m / z[M+H] + calcd for C 22 H 16 N2OBr 403.0441, found 403.0476.

[0139] Example 9

[0140] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0141]

[0142] At room temperature, 0.1 mmol of 3-trifluoromethylphenylhydrazine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube and stirred for 24 h under a 10 W blue LED. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 67% and a purity of 99.9%.

[0143] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0144] 1 H NMR (400MHz, CDCl3, ppm) δ7.99(d,J=7.7Hz,2H),7.91(d,J=7.6Hz,2H),7.86(s,1H),7.65(d,J =8.2Hz,3H),7.54(t,J=7.5Hz,3H),7.46(t,J=7.5Hz,2H),7.40(d,J=7.2Hz,1H),7.14(s,1H);

[0145] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ185.3,152.1,140.6,140.6,137.1,133.9,131.7,131.4,129.8, 129.4,128.9,128.8,128.8,128.2,126.0,124.9,124.8,122.2,122.1,122.1,122.0,111.6;

[0146] MS(EI,70eV)m / z 392,363,315,105,77;

[0147] HRMS(ESI)m / z[M+H] + calcd for C 23 H 16 N2OF3393.1209, found 393.1244.

[0148] Example 10

[0149] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0150]

[0151] At room temperature, 0.1 mmol of 3-methylphenylhydrazine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 53% and a purity of 99.9%.

[0152] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0153] 1 H NMR (400MHz, CDCl3, ppm) δ7.98(d,J=7.6Hz,2H),7.91(d,J=7.6Hz,2H),7.64(t,J=7.5Hz,1H),7.51(t,J=7.6Hz,2H),7.44(t,J =7.5Hz,2H),7.39-7.34(m,2H),7.29(t,J=7.7Hz,1H),7.23(d,J=7.9Hz,1H),7.19(d,J=7.4Hz,1H),7.08(s,1H),2.39(s,3H);

[0154] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ185.6,151.3,140.5,140.1,139.1,137.3,133.6,13 2.2,129.9,129.1,128.8,128.7,128.7,128.5,125.9,125.6,122.1,110.6,21.4;

[0155] MS(EI,70eV)m / z 338,323,261,105,77;

[0156] HRMS(ESI)m / z[M+H] + calcd for C 23 H 19 N2O 339.1492, found 339.1522.

[0157] Example 11

[0158] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0159]

[0160] At room temperature, 0.1 mmol of 2-fluorophenylhydrazine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 66% and a purity of 99.9%.

[0161] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0162] 1 H NMR (400MHz, CDCl3, ppm) δ8.00(d,J=6.9Hz,2H),7.90(d,J=6.8Hz,2H),7.75-7.70(m,1H),7.65(t,J=7.4Hz,1H),7 .52(d,J=7.7Hz,2H),7.44(t,J=7.4Hz,2H),7.39(d,J=7.1Hz,2H),7.32(t,J=7.0Hz,1H),7.15(s,1H),7.10(s,1H);

[0163] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ185.1,165.4,157.0,154.5,154.0,152.1,141.6,137.1,133.5,132.2,132.0,130.0 ,129.9,129.8,128.9,128.8,128.6,127.7,127.1,125.9,124.8,124.8,121.9,116.4,116.2,115.0114.8,110.4;

[0164] MS(EI,70eV)m / z 342,323,265,105,77;

[0165] HRMS(ESI)m / z[M+H] + calcd for C 22 H 16 N2OF 343.1241, found 343.1272.

[0166] Example 12

[0167] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0168]

[0169] At room temperature, 0.1 mmol of 2-chlorophenylhydrazine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 65% and a purity of 99.9%.

[0170] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0171] 1 H NMR (400MHz, CDCl3, ppm) δ8.00 (d, J = 7.7Hz, 2H), 7.91 (d, J = 7.7Hz, 2H), 7.69-7.62 (m, 2H), 7.54-7.37 (m, 8H), 7.12 (s, 1H);

[0172] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ184.8,151.8,141.8,138.5,137.1,133.4,132 .0,130.9,130.1,130.0,129.8,129.1,128.8,128.6,127.7,126.0,110.0;

[0173] MS(EI,70eV)m / z 358,323,245,105,77;

[0174] HRMS(ESI)m / z[M+H] + calcd for C 22 H 16 N2OCl 359.0946, found 359.0978.

[0175] Example 13

[0176] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0177]

[0178] At room temperature, 0.1 mmol of 2-bromophenylhydrazine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 62% and a purity of 99.9%.

[0179] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0180] 1 H NMR (400MHz, CDCl3, ppm) δ8.00(d,J=7.2Hz,2H),7.90(d,J=7.4Hz,2H),7.65(t,J=7.9 Hz,3H),7.52(t,J=7.5Hz,3H),7.44(t,J=7.4Hz,2H),7.39-7.32(m,2H),7.11(s,1H);

[0181] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ184.7,151.7,141.6,140.1,137.1,133.4,133 .2,132.0,130.4,129.9,129.4,128.8,128.6,128.3,126.0,121.1,110.1;

[0182] MS(EI,70eV)m / z 402,375,246,105,77;

[0183] HRMS(ESI)m / z[M+H] + calcd for C 22 H 16 N2OBr 403.0441, found 403.0476.

[0184] Example 14

[0185] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0186]

[0187] At room temperature, 0.1 mmol of 2-methylphenylhydrazine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 47% and a purity of 99.9%.

[0188] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0189] 1 H NMR (400MHz, CDCl3, ppm) δ7.96(d,J=7.7Hz,2H),7.91(d,J=6.8Hz,2H),7.64(t,J=7.4Hz,1H),7.52( d,J=7.5Hz,2H),7.44(t,J=7.5Hz,2H),7.34(td,J=16.8,15.0,7.3Hz,5H),7.11(s,1H),2.17(s,3H);

[0190] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ184.8,151.1,141.3,139.8,137.5,135.2,133.4,132 .3,130.8,129.7,129.2,128.8,128.6,128.4,127.3,126.5,125.9,109.6,17.65;

[0191] MS(EI,70eV)m / z 338,233,206,105,77;

[0192] HRMS(ESI)m / z[M+H] + calcd for C 23 H 19 N2O 339.1492, found 339.1526.

[0193] Example 15

[0194] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0195]

[0196] At room temperature, 0.1 mmol of 2-hydrazinopyridine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 5:1. The purified target product was obtained with a yield of 43% and a purity of 99.9%.

[0197] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0198] 1 H NMR (400MHz, CDCl3, ppm) δ8.10 (d, J = 4.9Hz, 1H), 7.99-7.89 (m, 5H), 7.80 (t, J = 7.8Hz, 1 H),7.56(d,J=7.3Hz,1H),7.43(dt,J=15.2,7.3Hz,5H),7.12-7.07(m,1H),7.01(s,1H);

[0199] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ187.7,152.7,151.1,147.5,141.4,138.6,137 .4,133.3,132.1,129.4,128.8,128.7,128.5,126.1,122.0,115.0,108.5;

[0200] MS(EI,70eV)m / z 325,296,248,105,77;

[0201] HRMS(ESI)m / z[M+H] + calcd for C 21 H 16 N3O 326.1288, found 326.1302.

[0202] Example 16

[0203] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0204]

[0205] At room temperature, 0.1 mmol of 2-naphthylhydrazine, 0.4 mmol of 2-bromoacetophenone, 0.001 mmol of Bengal rose red as a photocatalyst, 0.4 mmol of potassium carbonate, 0.2 mmol of sodium benzenesulfinate, and 2.0 mL of N,N-dimethylformamide were added to a reaction tube and stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 50% and a purity of 99.9%.

[0206] 1 H NMR (400MHz, CDCl3, ppm) δ7.99-7.92(m,6H),7.56(dd,J=20.4,12.7Hz,5H),7.47(t,J=8.1Hz,5H),7.40(d,J=7.2Hz,1H),7.25(s,1H);

[0207] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ184.8,151.6,142.5,137.4,137.1,134.2,133.4,132.2,130. 4,129.7,129.6,128.9,128.6,128.3,127.4,126.6,126.0,125.03,124.98,122.6,109.8;

[0208] MS(EI,70eV)m / z 374,297,269,105,77;

[0209] HRMS(ESI)m / z[M+H] + calcd for C 26 H 19 N2O 375.1492, found 375.1525.

[0210] Example 17

[0211] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0212]

[0213] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2-bromo-4'-(trifluoromethyl)acetophenone, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube and stirred for 24 h under a 10 W blue LED. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 60% and a purity of 99.9%.

[0214] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0215] 1 H NMR (400MHz, CDCl3, ppm) δ8.07(d,J=8.1Hz,2H),8.01(d,J=8.1Hz,2H),7.78(d,J=8.1Hz,2H),7.70(d,J=8.2Hz,2H),7.47(q,J=7.5Hz,5H),7.15(s,1H);

[0216] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ184.1,150.2,140.2,140.0,139.8,135.3,135 .1,134.8,130.6,130.3,130.0,129.1,128.8,126.1,125.8,125.0,111.2;

[0217] MS(EI,70eV)m / z 460,444,429,165,77;

[0218] HRMS(ESI)m / z[M+H] + calcd for C 24 H 15 N2OF6461.1083, found 461.1126.

[0219] Example 18

[0220] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0221]

[0222] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2-bromo-4'-fluoroacetophenone, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 64% and a purity of 99.9%.

[0223] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0224] 1 H NMR (400MHz, CDCl3, ppm) δ8.05-7.95(m,2H),7.95-7.81(m,2H),7.49-7.35(m,5H),7.15(dt,J=17.5,8.1Hz,4H),7.02(s,1H);

[0225] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ184.1,167.4,164.8,164.3,161.8,150.7,140.4,140.0,133.6,133.5,1 32.5,132.4,129.0,128.3,128.31,128.28,127.7,127.6,124.8,116.0,115.9,115.8,115.7,110.1;

[0226] MS(EI,70eV)m / z 360,331,265,123,77;

[0227] HRMS(ESI)m / z[M+H] + calcd for C 22 H 15 N2OF2361.1147, found 361.1180.

[0228] Example 19

[0229] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0230]

[0231] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2-bromo-4'-chloroacetophenone, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube and stirred for 24 h under a 10 W blue LED. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 68% and a purity of 99.9%.

[0232] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0233] 1 H NMR (400MHz, CDCl3, ppm) δ7.90 (d, J = 8.6Hz, 2H), 7.83 (d, J = 8.5Hz, 2H), 7.51-7.44 (m, 5H), 7.41 (dt, J = 6.5, 4.8Hz, 4H), 7.04 (s, 1H);

[0234] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ184.2,150.5,140.3,139.9,135.5,134.4,131.2,130.5,129.1,129.0,128.5,127.1,124.9,110.4;

[0235] MS(EI,70eV)m / z 392,363,139,111,77;

[0236] HRMS(ESI)m / z[M+H] + calcd for C 22 H 15 N2OCl2393.0556, found 393.0591.

[0237] Example 20

[0238] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0239]

[0240] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2,4'-dibromoacetophenone, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube and stirred for 24 h under a 10 W blue LED. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 70% and a purity of 99.9%.

[0241] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0242] 1 H NMR (400MHz, CDCl3, ppm) δ7.82(d,J=8.4Hz,2H),7.76(d,J=8.3Hz,2H),7.64(d,J=8.4Hz,2H),7.56(d,J=8.5Hz,2H),7.49-7.36(m,5H),7.03(s,1H);

[0243] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ184.4,150.5,140.3,139.9,135.9,132.1,132.0,131.2,131.0,129.1,128.5,127.4,124.9,122.6,119.1,110.4;

[0244] MS(EI,70eV)m / z 479,453,325,183,77;

[0245] HRMS(ESI)m / z[M+H] + calcd for C 22 H 15 N2OBr2480.9546,found 480.9589.

[0246] Example 21

[0247] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0248]

[0249] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2-bromo-4'-iodoacetophenone, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 65% and a purity of 99.9%.

[0250] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0251] 1 H NMR (400MHz, CDCl3, ppm) δ7.97(d,J=7.3Hz,2H),7.76(d,J=8.3Hz,2H),7.65( d,J=8.4Hz,2H),7.50(dd,J=16.0,8.1Hz,4H),7.45-7.39(m,3H),7.06(s,1H);

[0252] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ185.5,150.4,140.7,140.0,137.9,137.2,133.8,131.7,129.9,129.0,128.7,128.4,127.6,124.9,110.5,94.2;

[0253] HRMS(ESI)m / z[M] + calcd for C 22 H 14 N2OI2575.9190, found 575.9188.

[0254] Example 22

[0255] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0256]

[0257] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2-bromo-4'-methylacetophenone, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube and stirred for 24 h under a 10 W blue LED. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 82% and a purity of 99.9%.

[0258] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0259] 1 H NMR (400MHz, CDCl3, ppm) δ7.90 (d, J = 8.1Hz, 2H), 7.80 (d, J = 8.1Hz, 2H), 7.49 (d, J = 7.8Hz, 2H), 7.42 (t, J = 7.5Hz, 2H),7.37(d,J=7.3Hz,1H),7.30(d,J=7.9Hz,2H),7.25(d,J=8.1Hz,2H),7.04(s,1H),2.45(s,3H),2.40(s,3H);

[0260] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ185.5,151.5,144.7,140.6,140.2,138.3,134.8,130.1,129.5,129.4,129.0,128.0,125.8,124.8,110.3,21.8,21.4;

[0261] MS(EI,70eV)m / z 352,323,233,119,77;

[0262] HRMS(ESI)m / z[M+H] + calcd for C 24 H 21 N2O 353.1648, found 353.1683.

[0263] Example 23

[0264] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0265]

[0266] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2-bromo-4'-methoxyacetophenone, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 5:1. The purified target product was obtained with a yield of 73% and a purity of 99.9%.

[0267] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0268] 1 H NMR (400MHz, CDCl3, ppm) δ7.99(d,J=8.9Hz,2H),7.84(d,J=8.8Hz,2H),7.48(d,J=8.1Hz,2H) ,7.40(t,J=7.5Hz,2H),7.34(t,J=7.3Hz,1H),6.97(d,J=7.6Hz,5H),3.87(d,J=15.5Hz,6H);

[0269] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ184.6,164.2,159.9,151.3,140.8,140.2,132.3 ,130.1,129.0,127.9,127.2,125.0,124.6,114.2,114.0,109.5,55.6,55.4;

[0270] MS(EI,70eV)m / z 384,369,135,92,77;

[0271] HRMS(ESI)m / z[M+H] + calcd for C 24 H 21 N2O3 385.1547, found 385.1584.

[0272] Example 24

[0273] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0274]

[0275] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2,3'-dibromoacetophenone, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 67% and a purity of 99.9%.

[0276] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0277] 1 H NMR (400MHz, CDCl3, ppm) δ8.07 (s, 2H), 7.87 (d, J = 7.8Hz, 1H), 7.82 (d, J = 7.8Hz, 1 H),7.75(d,J=8.0Hz,1H),7.51-7.36(m,7H),7.31(t,J=7.8Hz,1H),7.07(s,1H);

[0278] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ183.9,150.1,140.1,139.8,138.9,136.6,134.0,132.6, 131.5,130.4,130.3,129.1,128.9,128.6,128.3,124.9,124.5,123.1,123.0,110.8;

[0279] MS(EI,70eV)m / z 479,453,325,183,77;

[0280] HRMS(ESI)m / z[M+H] + calcd for C 22 H 15 N2OBr2480.9546,found 480.9591.

[0281] Example 25

[0282] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0283]

[0284] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2-bromo-2'-chloroacetophenone, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 62% and a purity of 99.9%.

[0285] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0286] 1 H NMR (400MHz, CDCl3, ppm) δ7.92 (d, J = 9.5Hz, 1H), 7.55 (t, J = 8.6Hz, 3H), 7.48-7.40 (m, 6H), 7.36-7.27 (m, 3H), 7.20 (s, 1H);

[0287] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ184.1,149.3,140.3,140.0,137.8,132.4,132.3,132.1, 130.9,130.7,130.5,130.4,130.0,129.6,128.9,128.6,127.0,126.8,125.5,115.7;

[0288] MS(EI,70eV)m / z 392,357,139,111,77;

[0289] HRMS(ESI)m / z[M+H] + calcd for C 22 H 15 N2OCl2393.0556, found 393.0592.

[0290] Example 26

[0291] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0292]

[0293] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2-bromo-3',4'-dimethoxyacetophenone, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube and stirred for 24 h under a 10 W blue LED. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 5:1. The purified target product was obtained with a yield of 74% and a purity of 99.9%.

[0294] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0295] 1 H NMR (400MHz, CDCl3, ppm) δ7.66 (d, J = 8.4Hz, 1H), 7.53-7.46 (m, 4H), 7.40 (t, J = 7.9Hz, 3H) ,7.35(d,J=6.8Hz,1H),7.00(s,1H),6.92(dd,J=8.4,4.1Hz,2H),3.94(d,J=17.9Hz,12H);

[0296] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ184.7,154.1,151.3,149.5,149.3,140.8,140.1,130.1,129.0 ,128.0,125.5,125.3,124.6,118.6,111.34,111.25,110.0,109.5,108.9,56.2,56.1,56.0;

[0297] MS(EI,70eV)m / z 444,429,165,137,77;

[0298] HRMS(ESI)m / z[M+H] + calcd for C 26 H 25 N2O5 445.1758, found 445.1799.

[0299] Example 27

[0300] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0301]

[0302] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2-bromo-5'-fluoro-2'-methoxyacetophenone, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube and stirred for 24 h under a 10 W blue LED. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 5:1. The purified target product was obtained with a yield of 68% and a purity of 99.9%.

[0303] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0304] 1 H NMR (400MHz, CDCl3, ppm) δ7.85(dd,J=9.5,3.1Hz,1H),7.47(d,J=7.5Hz,2H),7.37(dt,J=13.5,6.7Hz,3H),7.29(s,1H),7.24(dd,J=8. 0,3.3Hz,1H),7.14-7.09(m,1H),7.02-6.97(m,1H),6.90(dd,J=9.1,4.4Hz,1H),6.79(dd,J=9.1,4.0Hz,1H),3.85(s,3H),3.70(s,3H);

[0305] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ184.1,158.4,157.7,156.0,155.3,154.2,153.2,147.5,141.7,140.0,129.1,129.0,128.7,128.2,125.2 ,124.4,122.4,122.3,120.5,119.6,119.4,116.9,116.6,115.5,115.3,115.1,114.8,114.5,112.9,112.8,112.6,112.5,56.3,56.1;

[0306] MS(EI,70eV)m / z 420,267,239,153,77;

[0307] HRMS(ESI)m / z[M+H] + calcd for C 24 H 19 N2O3F2421.1358,found 421.1399.

[0308] Example 28

[0309] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0310]

[0311] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2-(2-bromoacetyl)pyridine, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 5:1. The purified target product was obtained with a yield of 54% and a purity of 99.9%.

[0312] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0313] 1 H NMR (400MHz, CDCl3, ppm) δ8.73(d,J=4.8Hz,1H),8.65(d,J=4.9Hz,1H),8.11(d,J=7.9Hz,1H),8.0 5-7.97(m,2H),7.85(t,J=7.7Hz,1H),7.73(t,J=7.7Hz,1H),7.53-7.41(m,6H),7.25-7.21(m,1H);

[0314] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ183.0,154.1,151.8,151.3,149.5,149.0,140.9, 139.8,137.1,136.7,128.8,128.4,127.0,125.6,124.0,123.0,120.4,114.5;

[0315] MS(EI,70eV)m / z 326,297,222,105,77;

[0316] HRMS(ESI)m / z[M+Na] + calcd for C 20 H 14 N4ONa 349.1060, found 349.1093.

[0317] Example 29

[0318] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0319]

[0320] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2-(2-bromoacetyl)thiophene, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube and stirred for 24 h under a 10 W blue LED. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 49% and a purity of 99.9%.

[0321] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0322] 1 H NMR (400MHz, CDCl3, ppm) δ7.87(d,J=3.9Hz,1H),7.77(d,J=4.9Hz,1H),7.50-7.38(m,6H),7.32(d,J=5.1Hz,1H),7.21-7.17(m,1H),7.15-7.08(m,2H);

[0323] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ177.0,146.9,143.6,140.2,139.8,135.6,135.1,135.0,129.0,128.5,128.3,127.7,125.6,124.9,124.8,109.5;

[0324] MS(EI,70eV)m / z 336,319,253,111,77;

[0325] HRMS(ESI)m / z[M+H] + calcd for C 18 H 13 N2OS2337.0464, found 337.0495.

[0326] Example 30

[0327] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0328]

[0329] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol 2-(2-bromoacetyl)naphthalene, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube and stirred for 24 h under a 10 W blue LED. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 56% and a purity of 99.9%.

[0330] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0331] 1 H NMR (400MHz, CDCl3, ppm) δ8.58 (s, 1H), 8.39 (s, 1H), 8.13-8.05 (m, 2H), 8.00 (d, J = 11.3Hz, 2H), 7.90 (dd, J = 22.7, 11.3Hz, 4H), 7.67(d,J=7.0Hz,1H),7.59(d,J=7.7Hz,3H),7.50(d,J=3.2Hz,2H),7.45(t,J=6.6Hz,2H),7.39(d,J=8.5Hz,1H),7.29(s,1H);

[0332] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ185.7,151.5,140.9,140.2,135.9,134.7,133.6,133.4,132.33,132.28,129.8,129 .6,129.1,129.0,128.8,128.6,128.30,128.26,128.0,127.8,127.1,126.5,126.3,124.9,124.8,124.0,110.9;

[0333] MS(EI,70eV)m / z 424,297,195,127,77;

[0334] HRMS(ESI)m / z[M+H] + calcd for C 30 H 21 N2O 425.1648, found 425.1687.

[0335] Example 31

[0336] The 1,3,5-trisubstituted pyrazole compounds obtained in this embodiment have the following structures:

[0337]

[0338] At room temperature, 0.1 mmol phenylhydrazine, 0.4 mmol α-bromocyclopropaneethyl ketone, 0.001 mmol Bengal rose red as a photocatalyst, 0.4 mmol potassium carbonate, 0.2 mmol sodium benzenesulfinate, and 2.0 mL N,N-dimethylformamide were added to a reaction tube. The reaction was stirred under a 10W blue LED for 24 h. After the reaction was completed, the product was purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 15:1. The purified target product was obtained with a yield of 45% and a purity of 99.9%.

[0339] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0340] 1 H NMR (400MHz, CDCl3, ppm) δ7.44-7.34(m,5H),6.74(s,1H),2.31(ddd,J=12.4,7.8,4.5Hz,1H),2.03(ddd,J=13 .5,8.4,5.0Hz,1H),1.14(p,J=3.9Hz,2H),1.03-0.98(m,2H),0.94(dt,J=7.4,3.8Hz,2H),0.87-0.80(m,2H);

[0341] 13 C{ 1 H}NMR (100MHz, CDCl3, ppm) δ190.9,155.4,141.0,140.7,128.7,128.2,125.8,108.6,19.9,12.0,9.0,8.2;

[0342] MS(EI,70eV)m / z 252,226,183,116,77;

[0343] HRMS(ESI)m / z[M+H] + calcd for C 16 H 17 N2O 253.1335, found 253.1346.

[0344] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, not all embodiments. Other embodiments can be obtained without creative effort based on the embodiments of the present invention, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method for preparing a 1,3,5-trisubstituted pyrazole compound, characterized in that, Includes the following steps: A mixture of hydrazine compounds, α-bromoketone compounds, a photocatalyst, a basic compound, an additive, and a polar organic solvent was carried out under light irradiation to obtain the 1,3,5-trisubstituted pyrazole compounds. The hydrazine compounds have the structure shown in Formula I: Formula I; The compound of Formula I is selected from one or more of phenylhydrazine, 4-fluorophenylhydrazine, 4-chlorophenylhydrazine, 4-bromophenylhydrazine, 4-cyanophenylhydrazine, 4-methoxyphenylhydrazine, 3-chlorophenylhydrazine, 3-bromophenylhydrazine, 3-trifluoromethylphenylhydrazine, 3-methylphenylhydrazine, 2-fluorophenylhydrazine, 2-chlorophenylhydrazine, 2-bromophenylhydrazine, 2-methylphenylhydrazine, 2-hydrazylpyridine, and 2-naphthylhydrazine; The α-bromoketone compounds have the structure shown in Formula II: Formula II; The compound of Formula II is selected from one or more of the following: 2-bromoacetophenone, 2-bromo-4'-(trifluoromethyl)acetophenone, 2-bromo-4'-fluoroacetophenone, 2-bromo-4'-chloroacetophenone, 2,4'-dibromoacetophenone, 2-bromo-4'-iodoacetophenone, 2-bromo-4'-methylacetophenone, 2-bromo-4'-methoxyacetophenone, 2,3'-dibromoacetophenone, 2-bromo-2'-chloroacetophenone, 2-bromo-3',4'-dimethoxyacetophenone, 2-bromo-5'-fluoro-2'-methoxyacetophenone, 2-(2-bromoacetyl)pyridine, 2-(2-bromoacetyl)thiophene, 2-(2-bromoacetyl)naphthalene, and α-bromocyclopropylacetophenone; The 1,3,5-trisubstituted pyrazole compounds have the structure shown in Formula III: Formula III; The additive is selected from one or more of sodium benzenesulfinate, sodium 4-methylbenzenesulfinate, and sodium 4-fluorobenzenesulfinate; the photocatalyst is selected from Bengal rose red; the alkaline compound is selected from potassium carbonate; and the polar organic solvent is selected from... N, N -Dimethylformamide.

2. The preparation method according to claim 1, characterized in that, The molar ratio of the hydrazine compound and the α-bromoketone compound is 1:2~4.

3. The preparation method according to claim 1 or 2, characterized in that, The molar ratio of the hydrazine compound to the additive is 1:2~4.

4. The preparation method according to claim 1, characterized in that, The illumination is a 10 W blue LED; the addition cyclization reaction is carried out at room temperature for 12-24 hours.

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