CN110256349B - Polysubstituted pyrazoles and process for their preparation - Google Patents
Polysubstituted pyrazoles and process for their preparation Download PDFInfo
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
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- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
Abstract
The invention discloses a method for preparing polysubstituted pyrazole, which develops a novel aryl diazonium salt catalysis system, takes alkyne acid ester and diazo ester derivatives as reaction substrates and toluene as a solvent, and prepares the polysubstituted pyrazole through cyclization/N-H insertion reaction. The method used by the invention has the following characteristics: the method has the advantages of economic reaction, wider substrate universality, mild reaction conditions, capability of being carried out in the air, less catalyst consumption, simple and convenient post-treatment and contribution to the purification and industrial application of products. Meanwhile, the raw materials such as reactants, catalysts and the like used in the invention are cheap and easily available, the reaction composition is reasonable, no ligand is needed, the reaction steps are few, and excellent yield can be obtained by only one-step reaction, thereby meeting the requirements and directions of modern green chemistry and pharmaceutical chemistry.
Description
Technical Field
The invention relates to a polysubstituted pyrazole and a preparation method thereof, belonging to the technical field of organic synthesis.
Background
The polysubstituted pyrazole is a valuable five-membered nitrogen-containing heterocyclic skeleton and has good biological activity, and the derivative of the polysubstituted pyrazole is not only widely applied to insecticides and herbicides, but also has the applications of anti-tumor, anti-inflammation, antibiosis, antipsychotic and the like, thereby playing an important role in the fields of pesticides and medicines. At present, the methods for preparing the polysubstituted pyrazoles are various and have advantages and disadvantages. For example: the most common strategy is to react hydrazine serving as a substrate with a 1, 3-dicarbonyl compound or alkynone to prepare polysubstituted pyrazole, but the substrate has the defects of high toxicity, poor chemical selectivity and the like; the more direct method is that 1, 3-dipole and alkyne generate cycloaddition reaction to prepare polysubstituted pyrazole, both electron-rich diazo compound and electron-poor diazo compound can be used as dipole substrate, the reaction is usually initiated by Lewis acid or heat, and the obtained product is generally simple cyclization product or rearrangement product; the enyne and hydrazine are subjected to C-N bond coupling/hydroammoniation tandem process to prepare pyrazole, but the problem of complicated substrate exists.
Furthermore, it is difficult to synthesize a fully substituted pyrazole derivative in one step by any of the conventional synthetic methods. Therefore, it is very meaningful to develop a novel catalytic system, develop a novel catalyst in order to construct a polysubstituted pyrazole derivative with a rich structure more conveniently and rapidly, and realize the construction of the polysubstituted pyrazole by using the novel catalytic system.
Disclosure of Invention
The invention aims to provide a method for preparing polysubstituted pyrazole, which has rich sources of reaction raw materials, wide universality of reaction substrates, simple and convenient operation and convenient functional synthesis of drug molecules.
In order to achieve the purpose of the invention, the technical scheme adopted by the invention is as follows:
a preparation method of polysubstituted pyrazole comprises the following steps of taking alkyne acid ester and diazo ester derivatives as reaction substrates, taking aryl diazonium salt as a catalyst, and reacting in an organic solvent to prepare the polysubstituted pyrazole.
The invention also discloses application of the aryl diazonium salt as a catalyst in preparation of polysubstituted pyrazole.
When the polysubstituted pyrazole is prepared by the method, the preparation is carried out in an organic solvent by only taking the alkyne acid ester and the diazo ester derivative as reaction substrates and taking the aryl diazonium salt as a catalyst, and other substances are not required to be added.
In the invention, the structural formula of the alkynoic acid ester is one of the following chemical structural formulas:
the structural formula of the diazo ester derivative is one of the following chemical structural formulas:
the chemical structural formula of the polysubstituted pyrazole is as follows:
wherein R is1、R2、R3From a feedstock; in particular, R1The chemical structural formula of (a) is one of the following chemical structural formulas:
R2and R3Independently selected from hydrogen, methoxyA carbonyl group or an ethoxycarbonyl group.
In the technical scheme, the reaction temperature is 40 ℃, and the reaction time is 12 hours; the reaction is carried out in air.
In the above technical scheme, the aryl diazonium salt is selected from 4-bromobenzene tetrafluoroborate diazonium salt, 4-methoxybenzene tetrafluoroborate diazonium salt, 4-tert-butylbenzene tetrafluoroborate diazonium salt, naphthyl tetrafluoroborate diazonium salt, 3-methoxycarbonyl benzenetetrafluoroborate diazonium salt, 4-cyanophenyl tetrafluoroborate diazonium salt or 4-nitrobenzene tetrafluoroborate diazonium salt, preferably the aryl diazonium salt is 4-nitrobenzene tetrafluoroborate diazonium salt; the organic solvent is selected from toluene, benzene, cyclohexane, acetonitrile or tetrahydrofuran, and preferably the organic solvent is toluene.
In the technical scheme, the dosage of the catalyst is 10% of the molar weight of the acetylenic acid ester.
In the technical scheme, the dosage of the diazo ester derivative is 2.4 times of the molar weight of the alkynoic acid ester.
The reaction is carried out in the air, ethyl acetate is firstly used for quenching after the reaction is finished, then a rotary evaporator is used for removing the solvent and silica gel is used for adsorption, and finally the product, namely the polysubstituted pyrazole, is obtained by simple column chromatography with the mixed solvent of ethyl acetate and petroleum ether.
The invention also discloses the polysubstituted pyrazole prepared by the method.
Due to the application of the technical scheme, compared with the prior art, the invention has the following advantages:
1. according to the invention, aryl diazonium salt, preferably 4-nitrophenyl tetrafluoroborate diazonium salt, is adopted as a catalyst to realize cyclization of alkyne acid ester and diazonium ester derivative/N-H insertion domino reaction to prepare the polysubstituted pyrazole, and compared with the prior art, which has the advantages of pre-preparation of raw materials and single reaction mode, the reaction is more economic and the types of products are more abundant.
2. The method disclosed by the invention has the advantages of mild reaction conditions, capability of being carried out in the air, small catalyst consumption, simple and convenient post-treatment, and contribution to purification and large-scale industrial application of products.
3. The method has the advantages of cheap and easily obtained raw materials such as reactants, catalysts and the like, reasonable reaction composition, no need of ligands, few reaction steps, excellent yield by only one-step reaction, accordance with the requirements and directions of modern green chemistry and pharmaceutical chemistry, and suitability for screening high-activity polysubstituted pyrazole medicines.
Detailed Description
The invention is further described below with reference to the following examples:
the raw materials, the catalyst and the additive are all commercial products which can be purchased directly or prepared according to the conventional technology, for example, aryl diazonium fluoroborate can be obtained by the reaction of commercial aromatic amine, sodium nitrite and fluoroboric acid; the diazo ester derivative can be synthesized by simple raw materials such as marketized alcohol, bromoacetyl bromide, p-toluenesulfonyl hydrazide, p-toluenesulfonyl chloride and the like; all reactions of the examples of the invention were carried out in air.
Example one
The reaction flask was charged with 4-nitrophenyltetrafluoroborate diazonium salt (0.03 mmol, 7.2 mg), toluene (2.0mL), compound 1a (0.3 mmol, 52.1 mg), compound 2a (0.72 mmol, 86.5 mg) in that order. Then the system is magnetically stirred and reacts for 12 hours at the temperature of 40 ℃ in the air, and then the reaction product is quenched by ethyl acetate, the solvent is removed by a rotary evaporator, the reaction product is adsorbed by silica gel, and the product 3a is obtained by simple column chromatography, wherein the yield is 89%. The main test data of the prepared product are as follows, and the actual synthesized product is consistent with the theoretical analysis through analysis.
1H NMR (400 MHz, CDCl3) 5.28 (s, 2H), 4.32 (qd, J = 7.1, 3.2 Hz,4H), 4.28 – 4.23 (m, 2H), 4.16 (q, J = 7.1 Hz, 2H), 1.34 – 1.23 (m, 9H), 1.19(t, J = 7.1 Hz, 3H).13C NMR (101 MHz, CDCl3) 13C NMR (101 MHz, CDCl3)166.29, 162.85, 159.98, 157.85, 139.64, 131.67, 121.79, 62.01, 61.87, 61.79,61.50, 54.13, 13.95, 13.85, 13.83, 13.61. HRMS (ESI-TOF): Anal. Calcd. ForC21H21NO4+Na+:393.1268, Found: 393.1277; IR (neat, cm-1): υ 2984.47, 1724.36,1546.60, 1474.80, 1447.41, 1367.89, 1301.61, 1252.55, 1203.30, 1104.26,1070.07, 1019.73。
The reaction flask was charged with 4-nitrophenyltetrafluoroborate diazonium salt (0.03 mmol, 7.2 mg), ethyl acetate (2.0mL), compound 1a (0.3 mmol, 52.1 mg), compound 2a (0.72 mmol, 86.5 mg) in that order. Then the system is magnetically stirred and reacted for 12 hours at the temperature of 40 ℃ in the air, and then the system is quenched by ethyl acetate, and the target product is not detected by thin layer chromatography.
The reaction flask was charged with 4-nitrophenyltetrafluoroboric acid diazonium salt (0.03 mmol, 7.2 mg), N, N-dimethylformamide (2.0mL), compound 1a (0.3 mmol, 52.1 mg), compound 2a (0.72 mmol, 86.5 mg) in that order. Then the system is magnetically stirred and reacted for 12 hours at the temperature of 40 ℃ in the air, and then the system is quenched by ethyl acetate, and the target product is not detected by thin layer chromatography.
Example two
The reaction flask was charged with 4-nitrophenyltetrafluoroborate diazonium salt (0.03 mmol, 7.2 mg), toluene (2.0mL), compound 1b (0.3 mmol, 43.5 mg), and compound 2a (0.72 mmol, 86.5 mg) in that order. Then the system is magnetically stirred and reacts for 12 hours at the temperature of 40 ℃ in the air, and then ethyl acetate is used for quenching, a rotary evaporator is used for removing the solvent, silica gel is used for adsorption, and the product 3b/3 b' can be obtained through simple column chromatography, wherein the yield is 79%. The main test data of the prepared product are as follows, and the actual synthesized product is consistent with the theoretical analysis through analysis.
1H NMR (400 MHz, CDCl3) 5.29 (s, 2H), 4.34 (m, 2H), 4.17 (m, 2H),3.87 (s, 3H), 3.82 (s, 3H), 1.30 (m ,3H), 1.21 (m, 3H).13C NMR (101 MHz,CDCl3) 166.22, 166.20, 163.30, 163.23, 160.44, 159.96, 158.29, 157.75,139.81, 139.43, 131.94, 131.61, 121.55, 121.48, 62.13, 61.97, 61.63, 54.21,54.17, 52.79, 52.77, 52.73, 52.46, 13.97, 13.90, 13.62. HRMS (ESI-TOF): Anal.Calcd. For C21H21NO4+ Na+: 365.0955, Found: 365.0954 ; IR (neat, cm-1): υ2985.23, 1727.12, 1540.37, 1475.40, 1373.25, 1306.15, 1250.45, 1211.32,1176.40, 1106.64, 1073.59, 1020.27, 797.57.
EXAMPLE III
The reaction flask was charged with 4-nitrophenyltetrafluoroborate diazonium salt (0.03 mmol, 7.2 mg), toluene (2.0mL), compound 1c (0.3 mmol, 30.1 mg), compound 2a (0.72 mmol, 86.5 mg) in that order. Then the system is magnetically stirred and reacts for 12 hours at the temperature of 40 ℃ in the air, and then ethyl acetate is used for quenching, a rotary evaporator is used for removing the solvent, silica gel is used for adsorption, and the product 3c/3 c' can be obtained through simple column chromatography, wherein the yield is 71%. The main test data of the prepared product are as follows, and the actual synthesized product is consistent with the theoretical analysis through analysis.
1H NMR (400 MHz, CDCl3) 7.40 (s, 1H), 5.39 (s, 2H), 4.42 (q, J = 7.1Hz, 2H), 4.35 (q, J = 7.1 Hz, 2H), 4.27 – 4.19 (m, 2H), 1.39 (m, 6H), 1.28(m, 3H).13C NMR (101 MHz, CDCl3) 169.61, 166.93, 161.26, 159.03, 142.87,134.32, 113.81, 68.09, 61.84, 61.58, 61.26, 60.94, 54.09, 14.23, 14.08,14.00, 13.98. HRMS (ESI-TOF): Anal. Calcd. For C21H21NO4+ Na+: 321.1057,Found: 321.1068 ; IR (neat, cm-1): υ 2983.14, 1719.25, 1532.64, 1444.89,1375.64, 1266.45, 1206.36, 1109.52, 1084.84, 1022.73, 850.66, 765.57.
Example four
The reaction flask was charged with 4-nitrophenyltetrafluoroborate diazonium salt (0.03 mmol, 7.2 mg), toluene (2.0mL), compound 1d (0.3 mmol, 25.8 mg), compound 2a (0.72 mmol, 86.5 mg) in that order. Then the system is magnetically stirred and reacts for 12 hours at the temperature of 40 ℃ in the air, and then ethyl acetate is used for quenching, a rotary evaporator is used for removing the solvent, silica gel is used for adsorption, and the product 3d/3 d' can be obtained through simple column chromatography, wherein the yield is 63%. The main test data of the prepared product are as follows, and the actual synthesized product is consistent with the theoretical analysis through analysis.
1H NMR (400 MHz, CDCl3) 7.32 (s, 1H), 7.30 (s, 1H), 5.30 (m, 4H),4.33 (q, J = 7.1 Hz, 2H), 4.26 (q, J = 7.1 Hz, 2H), 4.15 (m, 4H), 3.86 (s,3H), 3.81 (s, 3H), 1.30 (m, 6H), 1.18 (m, 6H).13C NMR (101 MHz, CDCl3)166.75, 166.72, 161.49, 161.04, 159.33, 158.81, 142.78, 142.36, 134.28,133.83, 113.67, 113.65, 61.70, 61.47, 61.11, 53.95, 53.91, 52.15, 52.03,14.08, 13.84. HRMS (ESI-TOF): Anal. Calcd. For C21H21NO4+ Na+: 307.0901,Found: 307.0911 ; IR (neat, cm-1): υ 2983.77, 1720.37, 1532.49, 1450.27,1375.87, 1268.40, 1207.17, 1111.23, 1086.45, 1020.48, 845.45, 765.43.
EXAMPLE five
The reaction flask was charged with 4-nitrophenyl tetrafluoroborate diazonium salt (0.03 mmol, 7.2 mg), toluene (2.0mL), compound 1a (0.3 mmol, 52.1 mg), and compound 2b (0.72 mmol, 119.1 mg), in that order. Then the system is magnetically stirred and reacts for 12 hours at the temperature of 40 ℃ in the air, and then ethyl acetate is used for quenching, a rotary evaporator is used for removing the solvent, silica gel is used for adsorption, and the product 3e/3 e' can be obtained through simple column chromatography, wherein the yield is 77%. The main test data of the prepared product are as follows, and the actual synthesized product is consistent with the theoretical analysis through analysis.
1H NMR (400 MHz, CDCl3) 7.25 (m, 20H), 5.65 (m, 4H), 4.47 – 4.34 (m,8H), 1.35 (m, 12H).13C NMR (101 MHz, CDCl3) 165.05, 164.93, 162.62, 159.90,158.45, 157.99, 156.65, 150.00, 149.93, 149.40, 140.24, 139.20, 132.03,131.21, 129.59, 129.43, 129.40, 126.68, 126.28, 126.21, 126.06, 122.66,122.58, 121.37, 121.08, 121.04, 121.01, 62.38, 62.16, 62.12, 61.81, 60.61,54.47, 54.36, 14.02, 13.97, 13.92, 13.69. HRMS (ESI-TOF): Anal. Calcd. ForC21H21NO4+ Na +: 489.1268 , Found: 489.1261; IR (neat, cm-1): υ 2983.93,1732.57, 1482.86, 1244.32, 1187.73, 1167.91, 1093.34, 1064.64, 1021.64,744.38, 687.32.
EXAMPLE six
The reaction flask was charged with 4-nitrophenyl tetrafluoroborate diazonium salt (0.03 mmol, 7.2 mg), toluene (2.0mL), compound 1a (0.3 mmol, 52.1 mg), and compound 2c (0.72 mmol, 129.5 mg) in that order. Then the system is magnetically stirred and reacts for 12 hours at the temperature of 40 ℃ in the air, and then ethyl acetate is used for quenching, a rotary evaporator is used for removing the solvent, silica gel is used for adsorption, and the product 3f/3 f' can be obtained through simple column chromatography, wherein the yield is 85%. The main test data of the prepared product are as follows, and the actual synthesized product is consistent with the theoretical analysis through analysis.
1H NMR (400 MHz, CDCl3) 7.44 – 7.27 (m, 20H), 5.42 – 5.32 (m, 6H),5.19 (m, 6H), 4.37 (m, 2H), 4.24 (m, 2H), 4.17 (m, 2H), 4.07 (m, 2H), 1.34(m, 3H), 1.30 – 1.20 (m, 6H), 1.15 (m, 3H).13C NMR (101 MHz, CDCl3) 13C NMR(101 MHz, CDCl3) 166.24, 162.82, 162.77, 159.96, 159.85, 157.83, 157.76,139.78, 139.41, 134.86, 134.65, 134.04, 131.78, 131.39, 128.68, 128.53,128.50, 128.48, 128.46, 128.43, 128.38, 128.27, 122.15, 121.95, 67.87, 67.54,67.28, 62.10, 61.86, 61.62, 54.26, 54.23, 14.01, 13.75, 13.64. HRMS (ESI-TOF): Anal. Calcd. For C21H21NO4+ Na+: 517.1581, Found: 517.1571; IR (neat,cm-1): υ 2982.90, 1724.63, 1547.55, 1490.24, 1455.67, 1301.35, 1251.67,1186.50, 1104.05, 1069.26, 1017.75, 957.08, 910.21, 795.61, 736.15, 696.78.
EXAMPLE seven
The reaction flask was charged with 4-nitrophenyl tetrafluoroborate diazonium salt (0.03 mmol, 7.2 mg), toluene (2.0mL), compound 1a (0.3 mmol, 52.1 mg), and compound 2d (0.72 mmol, 116.2 mg), in that order. Then the system is magnetically stirred and reacts for 12 hours at the temperature of 40 ℃ in the air, and then the reaction product is quenched by ethyl acetate, the solvent is removed by a rotary evaporator, the reaction product is adsorbed by silica gel, and the product can be obtained by simple column chromatography with the yield of 81 percent, wherein the solvent is removed by the rotary evaporator. The main test data of the prepared product are as follows, and the actual synthesized product is consistent with the theoretical analysis through analysis.
1H NMR (400 MHz, CDCl3) 5.32 (m, 4H), 4.41 – 4.19 (m, 16H), 3.47 –3.33 (m, 8H), 3.28 (m, 12H), 2.01 – 1.79 (m, 8H), 1.37 – 1.26 (m, 12H).13CNMR (101 MHz, CDCl3) 166.34, 162.92, 160.05, 160.02, 157.96, 157.92,139.77, 139.58, 131.73, 131.58, 121.79, 121.78, 68.70, 68.65, 68.54, 68.36,63.29, 63.10, 62.97, 62.83, 62.15, 62.12, 61.93, 61.92, 61.74, 61.62, 58.56,58.53, 54.20, 54.17, 28.78, 28.64, 28.59, 14.05, 13.91, 13.71. HRMS (ESI-TOF): Anal. Calcd. For C21H21NO4+ Na+: 481.1793, Found: 481.1797; IR (neat,cm-1): υ 2981.63, 1724.90, 1546.19, 1464.66, 1300.82, 1252.71, 1202.58,1111.62, 1070.15, 1028.10, 926.34, 796.43, 685.96.
Example eight
The reaction flask was charged with 4-nitrophenyltetrafluoroborate diazonium salt (0.03 mmol, 7.2 mg), toluene (2.0mL), compound 1a (0.3 mmol, 52.1 mg), and compound 2e (0.72 mmol, 103.0 mg) in that order. Then the system is magnetically stirred and reacts for 12 hours at the temperature of 40 ℃ in the air, and then ethyl acetate is used for quenching, a rotary evaporator is used for removing the solvent, silica gel is used for adsorption, and the product can be obtained by simple column chromatography for 3h/3 h', and the yield is 64%. The main test data of the prepared product are as follows, and the actual synthesized product is consistent with the theoretical analysis through analysis.
1H NMR (400 MHz, CDCl3) 5.92 – 5.59 (m, 2H), 5.36 (s, 2H), 5.19 –4.99 (m, 4H), 4.44 – 4.29 (m, 6H), 4.21 (t, J = 6.7 Hz, 2H), 2.55 – 2.41 (m,2H), 2.37 (q, J = 6.7 Hz, 2H), 1.41 – 1.30 (m, 6H).13C NMR (101 MHz, CDCl3)166.43, 166.41, 163.00, 162.95, 160.14, 158.03, 139.92, 139.66, 133.32,133.22, 133.02, 131.87, 131.68, 122.04, 121.94, 117.92, 117.72, 117.71,117.65, 65.32, 64.96, 64.77, 62.21, 62.07, 62.03, 61.74, 54.34, 54.31, 32.89,32.78, 32.60, 14.17, 14.03, 13.84. HRMS (ESI-TOF): Anal. Calcd. For C21H21NO4+Na+: 445.1581, Found: 445.1573; IR (neat, cm-1): υ 2982.62, 1724.62, 1547.07,1473.22, 1250.57, 1197.85, 1105.12, 1070.18, 1018.40, 918.93, 796.02, 685.84.
Example nine
The reaction flask was charged with 4-methoxyphenyltetrafluoroboric acid diazonium salt (0.03 mmol, 6.8 mg), N, N-dimethylformamide (2.0mL), compound 1a (0.3 mmol, 52.1 mg), compound 2a (0.72 mmol, 86.5 mg) in this order. Then the system is magnetically stirred and reacts for 12 hours at the temperature of 40 ℃ in the air, and then the reaction product is quenched by ethyl acetate, the solvent is removed by a rotary evaporator, the reaction product is adsorbed by silica gel, and the product 3a is obtained by simple column chromatography, wherein the yield is 43 percent.
Example ten
The reaction flask was charged with 4-nitrophenyl tetrafluoroborate diazonium salt (0.03 mmol, 7.2 mg), toluene (2.0mL), compound 1a (0.3 mmol, 52.1 mg), and compound 2f (0.72 mmol, 101.5 mg), in that order. Then the system is magnetically stirred and reacts for 12 hours at the temperature of 40 ℃ in the air, and then ethyl acetate is used for quenching, a rotary evaporator is used for removing the solvent, silica gel is used for adsorption, and the product 3i/3 i' can be obtained through simple column chromatography, wherein the yield is 59%. The main test data of the prepared product are as follows, and the actual synthesized product is consistent with the theoretical analysis through analysis.
1H NMR (400 MHz, CDCl3) 5.40 (m, 4H), 4.47 – 4.32 (m, 12H), 4.28 (m,4H), 2.63 (m, 4H), 2.54 (m, 4H), 2.05 (m, 4H), 1.42 – 1.31 (m, 12H).13C NMR(101 MHz, CDCl3) 166.23, 166.21, 162.88, 162.84, 160.08, 159.86, 158.04,157.77, 140.07, 139.38, 131.95, 131.43, 122.30, 122.12, 79.35, 79.26, 79.24,79.12, 70.60, 70.45, 70.40, 63.84, 63.46, 63.26, 62.31, 62.19, 62.13, 61.80,54.37, 54.31, 18.87, 18.82, 18.68, 14.17, 14.04, 13.84. HRMS (ESI-TOF): Anal.Calcd. For C21H21NO4+ Na+: 441.1268, Found: 441.1261; IR (neat, cm-1): υ3286.42, 2981.73, 1724.75, 1547.31, 1471.96, 1303.56, 1250.92, 1186.56,1107.32, 1070.00, 999.53, 862.02, 795.85, 647.95。
Claims (5)
1. The preparation method of the polysubstituted pyrazole is characterized by comprising the following steps of reacting in an organic solvent by taking aryl diazonium salt as a catalyst and alkyne ester and diazo ester derivatives as reaction substrates to prepare the polysubstituted pyrazole;
the structural formula of the alkynoic acid ester is one of the following chemical structural formulas:
the structural formula of the diazo ester derivative is one of the following chemical structural formulas:
the chemical structural formula of the polysubstituted pyrazole is as follows:
R1the chemical structural formula of (a) is one of the following chemical structural formulas:
R2and R3Independently selected from hydrogen, methoxycarbonyl or ethoxycarbonyl;
the aryl diazonium salt is selected from 4-methoxybenzene tetrafluoroborate diazonium salt or 4-nitrobenzene tetrafluoroborate diazonium salt.
2. The process for preparing polysubstituted pyrazoles according to claim 1, wherein: the reaction temperature is 40 ℃, and the reaction time is 12 hours; the reaction is carried out in air.
3. The process for preparing polysubstituted pyrazoles according to claim 1, wherein: the organic solvent is selected from toluene, benzene, cyclohexane, acetonitrile or tetrahydrofuran.
4. The process for preparing polysubstituted pyrazoles according to claim 1, wherein: the dosage of the catalyst is 10 percent of the molar weight of the acetylenic acid ester; the dosage of the diazo ester derivative is 2.4 times of the molar weight of the acetylenic acid ester.
5. The process for preparing polysubstituted pyrazoles according to claim 1, wherein: after the reaction is finished, ethyl acetate is used for quenching the reaction, the solvent is removed, silica gel is used for adsorption, and column chromatography is carried out to obtain the product, namely the polysubstituted pyrazole.
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