A method for synthesizing N-vinylpyrazole compounds
By carrying out the [3+2] cycloaddition reaction of vinyl sulfonium salt and diazonium compound in an air atmosphere, a five-membered ring is formed and added with vinyl sulfonium salt is solved, and the problems of limited substrate range and severe reaction conditions in the prior art are achieved, and the efficient synthesis of N-vinyl pyrazole compounds at room temperature is achieved, with wide applicability and environmental protection characteristics.
Patent Information
- Application Number
- CN202310477383.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-04-27
- Publication Date
- 2025-07-22
- Estimated Expiration
- 2043-04-27
AI Technical Summary
In the prior art, the synthesis method of N-vinylpyrazole compounds has problems with limited substrate range and severe reaction conditions, especially in the absence of metal catalysts, which makes it difficult to achieve efficient synthesis.
The [3+2] cycloaddition reaction was carried out in an air atmosphere by using vinyl sulfonium salt and diazonium compound to form a five-membered ring, and then the addition was performed with the vinyl sulfonium salt of another molecule to synthesize N-vinylpyrazole compounds. The reaction was carried out at room temperature, and alkali and solvent were used as catalysts.
It has achieved the synthesis of N-vinylpyrazole compounds that are widely applicable under room temperature conditions. The substrate has a wide range of application, rapid reaction, low cost, no metal catalyst and heating, and is green and environmentally friendly.
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Figure CN116496218B_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of compound preparation and relates to a method for synthesizing N-vinylpyrazole compounds. Background Art
[0002] Pyrazole and its reduced forms pyrazoline and pyrazolidine have significant biological activities, and the pyrazole ring is a special scaffold in medicinal chemistry. However, the research on such compounds is still very limited, and there is no report on the synthesis of N-vinylpyrazole compounds using diazo compounds and vinyl sulfonium salts.
[0003] In 2008, Tsuchimoto et al. reported that in the presence of a silver catalyst (AgNO3 or AgOTf), the N–H bond of pyrazole undergoes an addition reaction with phenylacetylene to produce a mixture of regioisomers of 1-substituted pyrazole. Although this method can obtain N-vinylpyrazole compounds, it is not satisfactory in terms of yield and selectivity (Eur. J. Org. Chem. 2008, 4035–4040); in 2017, Garg et al. reported a method for the chemo-, regio- and stereoselective synthesis of (Z)- and (E)-1-styrylpyrazoles without transition metals, that is, adding pyrazole to functionalized terminal alkynes using a superbasic solution of KOH / dimethyl sulfoxide (DMSO). Although this method has a good yield, it requires heating and the use of a super strong base, and the reaction conditions are severe (J. Org. Chem. 2017, 82, 10247–10262).
[0004] In summary, in the current reports on the direct synthesis of N-vinylpyrazole compounds from simple and readily available substrates, there are still problems such as limited substrate scope and severe reaction conditions. Therefore, it is necessary to improve the synthesis method of N-vinylpyrazole compounds. Summary of the Invention
[0005] In view of the above technical problems, the present invention provides a method for synthesizing N-vinylpyrazole compounds, which has a wide substrate scope, does not require the use of a metal catalyst, can react at room temperature, and is green and environmentally friendly.
[0006] To achieve the above object, the present invention adopts the following technical solutions:
[0007] The present invention provides a method for synthesizing N-vinylpyrazole compounds, which comprises the following steps:
[0008] Using the compound shown in Formula I and the compound shown in Formula II as raw materials, under the action of a base and a solvent, in an air atmosphere, reacting at room temperature for 1 h to synthesize the N-vinylpyrazole compound shown in Formula III; the synthesis route is as follows:
[0009]
[0010] Wherein: R1 is selected from hydrogen, alkyl or halogen; R2 is selected from an ester group, trifluoromethyl or cyano.
[0011] In one technical solution, the molar ratio of the compound shown in Formula I to the compound shown in Formula II is 3:1.
[0012] In one technical solution, the addition amount of the base is 600 mol% of the compound shown in Formula II.
[0013] In one technical solution, the addition amount ratio of the solvent to the compound shown in Formula II is 2 mL: 0.2 mmol.
[0014] In one technical solution, the base is selected from one of diazabicyclo, 1,1,3,3-tetramethylguanidine, triethylenediamine, N,N-diisopropylethylamine, triethylamine, cesium carbonate or potassium tert-butoxide.
[0015] In one technical solution, the solvent is selected from one of dichloromethane, acetone, 1,2-dichloroethane, acetonitrile, dimethyl sulfoxide, chloroform, toluene or tetrahydrofuran.
[0016] Compared with the prior art, the beneficial effects of the present invention are as follows:
[0017] The present invention uses vinyl sulfonium salt and diazo compound as raw materials. The diazo compound first forms a five-membered ring through a [3+2] cycloaddition reaction, and then undergoes an addition reaction with another molecule of vinyl sulfonium salt to synthesize N-vinylpyrazole compounds. And at room temperature, the vinyl sulfonium salt can not only react with diazo esters, but also react with carbonyl diazo, trifluoromethyl diazo and cyano diazo, and the substrate scope is wide; the reaction of the present invention is rapid, does not require the use of metal catalysts, has low cost, does not require excessive treatment, does not require heating, and can react at room temperature, which is green and environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Figure 1 1H NMR spectrum of ethyl 4-phenyl-1-(1-phenylethenyl)pyrazole-3-carboxylate in Example 1 of the present invention.
[0019] Figure 2 13C NMR spectrum of ethyl 4-phenyl-1-(1-phenylethenyl)pyrazole-3-carboxylate in Example 1 of the present invention.
[0020] Figure 3 1H NMR spectrum of ethyl 4-(4-methylphenyl)-1-[1-(4-methylphenylethenyl)]pyrazole-3-carboxylate in Example 2 of the present invention.
[0021] Figure 41H-NMR spectrum of ethyl 4-(4-methylphenyl)-1-[1-(4-methylphenyl)vinyl]pyrazole-3-carboxylate in Example 2 of the present invention.
[0022] Figure 5 1H-NMR spectrum of ethyl 4-(4-fluorophenyl)-1-[1-(4-fluorophenyl)vinyl]pyrazole-3-carboxylate in Example 3 of the present invention.
[0023] Figure 6 13C-NMR spectrum of ethyl 4-(4-fluorophenyl)-1-[1-(4-fluorophenyl)vinyl]pyrazole-3-carboxylate in Example 3 of the present invention.
[0024] Figure 7 1H-NMR spectrum of ethyl 4-(4-chlorophenyl)-1-(1-(4-chlorophenyl)vinyl)pyrazole-3-carboxylate in Example 4 of the present invention.
[0025] Figure 8 13C-NMR spectrum of ethyl 4-(4-chlorophenyl)-1-(1-(4-chlorophenyl)vinyl)pyrazole-3-carboxylate in Example 4 of the present invention.
[0026] Figure 9 1H-NMR spectrum of ethyl 4-(4-bromophenyl)-1-(1-(4-bromophenyl)vinyl)-1H-pyrazole-3-carboxylate in Example 5 of the present invention.
[0027] Figure 10 13C-NMR spectrum of ethyl 4-(4-bromophenyl)-1-(1-(4-bromophenyl)vinyl)-1H-pyrazole-3-carboxylate in Example 5 of the present invention.
[0028] Figure 11 1H-NMR spectrum of benzyl 4-phenyl-1-(1-phenylvinyl)pyrazole-3-carboxylate in Example 6 of the present invention.
[0029] Figure 12 13C-NMR spectrum of benzyl 4-phenyl-1-(1-phenylvinyl)pyrazole-3-carboxylate in Example 6 of the present invention. Detailed Description of the Invention
[0030] The following examples are used to illustrate the present invention, but are not intended to limit the scope of protection of the present invention. Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art. The test methods in the following examples are conventional methods unless otherwise specified.
[0031] Example 1 Preparation of Ethyl 4-Phenyl-1-(1-phenylvinyl)pyrazole-3-carboxylate
[0032] Take a glass test tube, first add a magnetic stir bar into it, then add 0.6 mmol of (E)-1-styryl tetrahydro-1H-thiophen-1-ium trifluoromethanesulfonate and 2 mL of dichloromethane, then add 1.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and finally add 0.2 mmol of ethyl diazoacetate. Under magnetic stirring, react at room temperature for 1 h to end the reaction. Detect the final product by TLC, and finally obtain the final product: ethyl 4-phenyl-1-(1-phenylvinyl)-1H-pyrazole-3-carboxylate by column chromatography separation, with a yield of 80%.
[0033] The above reaction equation is as follows:
[0034]
[0035] The 1H NMR spectrum of ethyl 4-phenyl-1-(1-phenylvinyl)-1H-pyrazole-3-carboxylate is characterized as follows (the spectrum is shown in Figure 1 ): 1 1H NMR (400 MHz, CDCl3) δ 7.39 (s, 1H), 7.38–7.19 (m, 10H), 5.76 (d, J = 0.9 Hz, 1H), 5.27 (d, J = 0.9 Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H), 1.23 (t, J = 7.1 Hz, 3H).
[0036] The 13C NMR spectrum of ethyl 4-phenyl-1-(1-phenylvinyl)-1H-pyrazole-3-carboxylate is characterized as follows (the spectrum is shown in Figure 2 ): 13 13C NMR (100 MHz, CDCl3) δ 162.4, 145.1, 141.1, 134.9, 131.3, 130.2, 129.6, 129.2, 128.7, 127.92, 127.89, 127.4, 126.3, 107.8, 61.0, 14.1.
[0037] Example 2 Preparation of ethyl 4-(4-methylphenyl)-1-[1-(4-methylphenyl)vinyl]-1H-pyrazole-3-carboxylate
[0038] Take a glass test tube, first add a magnetic stir bar into it, then add 0.6 mmol of (E)-1-(4-methylstyryl)tetrahydro-1H-thiophen-1-ium trifluoromethanesulfonate and 2 mL of dichloromethane, then add 1.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and finally add 0.2 mmol of ethyl diazoacetate. Under magnetic stirrer stirring, react at room temperature for 1 h to end the reaction. Detect the final product by TLC, and finally obtain the final product: ethyl 4-(4-methylphenyl)-1-[1-(4-methylphenyl)vinyl]-1H-pyrazole-3-carboxylate by column chromatography separation, with a yield of 78%.
[0039] The above reaction equation is as follows:
[0040]
[0041] The 1H NMR spectrum of ethyl 4-(4-methylphenyl)-1-[1-(4-methylphenyl)vinyl]pyrazole-3-carboxylate is characterized as follows (the spectrum is shown in Figure 3 ): 1 H NMR(400MHz,CDCl3)δ7.38(s,1H),7.27(d,J=8.1Hz,2H),7.22(d,J=8.2Hz,2H),7.14(d,J=8.0Hz,2H),7.09(d,J=7.9Hz,2H),5.71(s,1H),5.24(s,1H),4.30(q,J=7.1Hz,2H),2.32(s,3H),2.29(s,3H),1.27(t,J=7.1Hz,3H).
[0042] The 13C NMR spectrum of ethyl 4-(4-methylphenyl)-1-[1-(4-methylphenyl)vinyl]pyrazole-3-carboxylate is characterized as follows (the spectrum is shown in Figure 4 ): 13 C NMR(100MHz,CDCl3)δ162.5,145.1,140.9,139.7,137.2,132.1,130.1,129.3,129.1,128.7,128.4,127.8,126.3,107.1,61.0,21.3,21.2,14.2.
[0043] Example 3 Preparation of ethyl 4-(4-fluorophenyl)-1-[1-(4-fluorophenyl)vinyl]pyrazole-3-carboxylate
[0044] Take a glass test tube, first add a magnetic stir bar into it, then add 0.6 mmol of (E)-1-(4-fluorostyryl)tetrahydro-1H-thiophen-1-ium trifluoromethanesulfonate and 2 mL of dichloromethane, then add 1.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and finally add 0.2 mmol of ethyl diazoacetate. Under magnetic stirring, react at room temperature for 1 h, and the reaction ends. The final product, ethyl 4-(4-fluorophenyl)-1-[1-(4-fluorophenyl)vinyl]pyrazole-3-carboxylate, is detected by TLC, and finally the final product is obtained by column chromatography separation with a yield of 50%.
[0045] The above reaction equation is as follows:
[0046]
[0047] The 1H NMR spectrum of ethyl 4-(4-fluorophenyl)-1-[1-(4-fluorophenyl)vinyl]pyrazole-3-carboxylate is characterized as follows (the spectrum is shown in Figure 5 ): 1 H NMR(400MHz,CDCl3)δ7.47(s,1H),7.45–7.35(m,4H),7.14–7.01(m,4H),5.79(d,J=1.1Hz,1H),5.34(d,J=1.1Hz,1H),4.36(q,J=7.1Hz,2H),1.32(t,J=7.1Hz,3H).
[0048] The 13C NMR spectrum of ethyl 4-(4-fluorophenyl)-1-[1-(4-fluorophenyl)vinyl]pyrazole-3-carboxylate is characterized as follows (the spectrum is shown in Figure 6 ): 13 C NMR(100MHz,CDCl3)δ163.4(d, 1 J C-F =250.0Hz),162.27,162.32(d, 1 J C-F =246.8Hz),144.2,141.1,130.97(d, 4 J C-F =3.4Hz),130.95(d, 3 J C-F =8.1Hz),130.1,129.8(d, 3 J C-F =8.4Hz),127.2(d, 4 J C-F =3.4Hz),125.5,115.8(d, 2 J C-F =21.9Hz),114.9(d, 2 J C-F =21.6Hz),107.9,61.1,14.1.
[0049] Example 4 Preparation of Ethyl 4-(4-chlorophenyl)-1-(1-(4-chlorophenyl)vinyl)pyrazole-3-carboxylate
[0050] Take a glass test tube. First, add a magnetic stir bar into it. Secondly, add 0.6 mmol of (E)-1-(4-chlorostyryl)tetrahydro-1H-thiophen-1-ium trifluoromethanesulfonate and 2 mL of dichloromethane. Then, add 1.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Finally, add 0.2 mmol of ethyl diazoacetate. Under magnetic stirring, react at room temperature for 1 h to end the reaction. Detect the final product by TLC, and finally obtain the final product: ethyl 4-(4-chlorophenyl)-1-(1-(4-chlorophenyl)vinyl)-1H-pyrazole-3-carboxylate through column chromatography, with a yield of 68%.
[0051] The above reaction equation is as follows:
[0052]
[0053] The 1H NMR characterization of ethyl 4-(4-chlorophenyl)-1-(1-(4-chlorophenyl)vinyl)-1H-pyrazole-3-carboxylate is as follows (the spectrum is shown in Figure 7 ): 1 H NMR(400MHz,CDCl3)δ7.49(s,1H),7.43–7.37(m,4H),7.36–7.30(m,4H),5.81(s,1H),5.39(s,1H),4.37(q,J=7.1Hz,2H),1.33(t,J=7.1Hz,3H).
[0054] The 13C NMR characterization of ethyl 4-(4-chlorophenyl)-1-(1-(4-chlorophenyl)vinyl)-1H-pyrazole-3-carboxylate is as follows (the spectrum is shown in Figure 8 ): 13 C NMR(100MHz,CDCl3)δ162.2,144.2,141.2,135.7,133.6,133.2,130.6,130.1,129.6,129.1,129.0,128.2,125.4,108.6,61.2,14.2.
[0055] Example 5 Preparation of ethyl 4-(4-bromophenyl)-1-(1-(4-bromophenyl)vinyl)-1H-pyrazole-3-carboxylate
[0056] Take a glass test tube. First, add a magnetic stir bar into it. Secondly, add 0.6 mmol of (E)-1-(4-bromostyryl)tetrahydro-1H-thiophen-1-ium trifluoromethanesulfonate and 2 mL of dichloromethane. Then, add 1.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Finally, add 0.2 mmol of ethyl diazoacetate. Under magnetic stirring, react at room temperature for 1 h to end the reaction. Detect the final product by TLC, and finally obtain the final product: ethyl 4-(4-bromophenyl)-1-(1-(4-bromophenyl)vinyl)-1H-pyrazole-3-carboxylate through column chromatography, with a yield of 77%.
[0057] The above reaction equation is as follows:
[0058]
[0059] The 1H NMR characterization of ethyl 4-(4-bromophenyl)-1-(1-(4-bromophenyl)vinyl)-1H-pyrazole-3-carboxylate is as follows (the spectrum is shown in Figure 9 ): 1 H NMR(400MHz,CDCl3)δ7.55(d,J=8.6Hz,2H),7.51–7.47(m,3H),7.33(d,J=8.5Hz,2H),7.27(d,J=7.4Hz,2H),5.81(s,1H),5.40(s,1H),4.37(q,J=7.1Hz,2H),1.33(t,J=7.1Hz,3H).
[0060] The 13C NMR characterization of ethyl 4-(4-bromophenyl)-1-(1-(4-bromophenyl)vinyl)-1H-pyrazole-3-carboxylate is as follows (the spectrum is shown in Figure 10 ): 13 C NMR(100MHz,CDCl3)δ162.2,144.2,141.1,133.7,132.0,131.1,130.9,130.09,130.07,129.3,125.4,124.0,121.7,108.6,61.2,14.2.
[0061] Example 6 Preparation of benzyl 4-phenyl-1-(1-phenylvinyl)pyrazole-3-carboxylate
[0062] Take a glass test tube. First, add a magnetic stir bar into it. Secondly, add 0.6 mmol of (E)-1-styryl-1,2,3,4-tetrahydro-1H-thiophen-1-ium trifluoromethanesulfonate and 2 mL of dichloromethane. Then, add 1.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Finally, add 0.2 mmol of benzyl diazoacetate. Under magnetic stirring, react at room temperature for 1 h to complete the reaction. Detect the final product by TLC, and finally separate the final product by column chromatography: benzyl 4-phenyl-1-(1-phenylethenyl)-1H-pyrazole-3-carboxylate, with a yield of 79%.
[0063] The above reaction equation is as follows:
[0064]
[0065] The 1H NMR characterization of benzyl 4-phenyl-1-(1-phenylethenyl)-1H-pyrazole-3-carboxylate is as follows (the spectrum is shown in Figure 11 ): 1 1H NMR (400 MHz, CDCl3) δ 7.47 (s, 1H), 7.43–7.37 (m, 7H), 7.35–7.27 (m, 8H), 5.86 (s, 1H), 5.36 (s, 1H), 5.35 (s, 2H).
[0066] The 13C NMR characterization of benzyl 4-phenyl-1-(1-phenylethenyl)-1H-pyrazole-3-carboxylate is as follows (the spectrum is shown in Figure 12 ): 13 13C NMR (100 MHz, CDCl3) δ 162.3, 145.1, 140.9, 135.6, 134.9, 131.3, 130.2, 129.6, 129.2, 128.7, 128.31, 128.25, 127.98, 127.96, 127.9, 127.4, 126.4, 107.8, 66.5.
[0067] Example 7 Preparation of 2-(Trimethylsilyl)ethyl 4-phenyl-1-(1-phenylethenyl)-1H-pyrazole-3-carboxylate
[0068] Take a glass test tube. First, add a magnetic stir bar into it. Secondly, add 0.6 mmol of (E)-1-styryl-1,2,3,4-tetrahydro-1H-thiophen-1-ium trifluoromethanesulfonate and 2 mL of dichloromethane. Then, add 1.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Finally, add 0.2 mmol of 2-(trimethylsilyl)ethyl diazoacetate. Under magnetic stirring, react at room temperature for 1 h to complete the reaction. Detect the final product by TLC, and finally obtain the final product: 2-(trimethylsilyl)ethyl 4-phenyl-1-(1-phenylvinyl)-1H-pyrazole-3-carboxylate by column chromatography, with a yield of 64%.
[0069] The above reaction equation is as follows:
[0070]
[0071] Example 8 Preparation of cyclohexyl 4-phenyl-1-(1-phenylvinyl)-1H-pyrazole-3-carboxylate
[0072] Take a glass test tube. First, add a magnetic stir bar into it. Secondly, add 0.6 mmol of (E)-1-styryl-1,2,3,4-tetrahydro-1H-thiophen-1-ium trifluoromethanesulfonate and 2 mL of dichloromethane. Then, add 1.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Finally, add 0.2 mmol of cyclohexyl diazoacetate. Under magnetic stirring, react at room temperature for 1 h to complete the reaction. Detect the final product by TLC, and finally obtain the final product: cyclohexyl 4-phenyl-1-(1-phenylvinyl)-1H-pyrazole-3-carboxylate by column chromatography, with a yield of 66%.
[0073] The above reaction equation is as follows:
[0074]
[0075] Example 9 Preparation of 4-phenyl-1-(1-phenylvinyl)-3-(trifluoromethyl)-1H-pyrazole
[0076] Take a glass test tube. First, add a magnetic stir bar into it. Secondly, add 0.6 mmol of (E)-1-styryl-1,2,3,4-tetrahydro-1H-thiophen-1-ium trifluoromethanesulfonate and 2 mL of dichloromethane. Then, add 1.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Finally, add 0.2 mmol of 2-diazo-1,1,1-trifluoroethane. Under magnetic stirring, react at room temperature for 1 h to complete the reaction. Detect the final product by TLC, and finally obtain the final product: 4-phenyl-1-(1-phenylvinyl)-3-(trifluoromethyl)-1H-pyrazole by column chromatography, with a yield of 30%.
[0077] The above reaction equation is as follows:
[0078]
[0079] Example 10 Preparation of 4-Phenyl-1-(1-phenylethenyl)-1H-pyrazole-3-carbonitrile
[0080] Take a glass test tube. First, add a magnetic stir bar into it. Second, add 0.6 mmol of (E)-1-styryltetrahydro-1H-thiophen-1-ium trifluoromethanesulfonate and 2 mL of dichloromethane. Then, add 1.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Finally, add 0.2 mmol of diazoacetonitrile. Under stirring with a magnetic stirrer, react at room temperature for 1 h to end the reaction. Detect the final product by TLC, and finally separate the final product: 4-Phenyl-1-(1-phenylethenyl)-1H-pyrazole-3-carbonitrile by column chromatography with a yield of 35%.
[0081] The above reaction equation is as follows:
[0082]
[0083] Example 11 Preparation of Pent-2-yn-1-yl 1-(1-phenylethenyl)-1H-pyrazole-3-carboxylate
[0084] Take a glass test tube. First, add a magnetic stir bar into it. Second, add 0.6 mmol of (E)-1-styryltetrahydro-1H-thiophen-1-ium trifluoromethanesulfonate and 2 mL of dichloromethane. Then, add 1.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Finally, add 0.2 mmol of pent-2-yn-1-yl diazoacetate. Under stirring with a magnetic stirrer, react at room temperature for 1 h to end the reaction. Detect the final product by TLC, and finally separate the final product: Pent-2-yn-1-yl 1-(1-phenylethenyl)-1H-pyrazole-3-carboxylate by column chromatography with a yield of 80%.
[0085] The above reaction equation is as follows:
[0086]
[0087] Example 12 Preparation of 2-(Thiophen-2-yl)ethyl 4-phenyl-1-(1-phenylethenyl)-1H-pyrazole-3-carboxylate
[0088] Take a glass test tube. First, add a magnetic stir bar into it. Second, add 0.6 mmol of (E)-1-styryl tetrahydro-1H-thiophen-1-ium trifluoromethanesulfonate and 2 mL of dichloromethane. Then, add 1.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Finally, add 0.2 mmol of 2-(thiophen-2-yl)ethyl diazoacetate. Stir the mixture with a magnetic stirrer at room temperature for 1 h to complete the reaction. Detect the final product by TLC, and finally obtain the final product: 2-(thiophen-2-yl)ethyl 4-phenyl-1-(1-phenylethenyl)-1H-pyrazole-3-carboxylate by column chromatography with a yield of 83%.
[0089] The above reaction equation is as follows:
[0090]
[0091] Example 13 Preparation of allyl 4-phenyl-1-(1-phenylethenyl)-1H-pyrazole-3-carboxylate
[0092] Take a glass test tube. First, add a magnetic stir bar into it. Second, add 0.6 mmol of (E)-1-styryl tetrahydro-1H-thiophen-1-ium trifluoromethanesulfonate and 2 mL of dichloromethane. Then, add 1.2 mmol of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Finally, add 0.2 mmol of allyl diazoacetate. Stir the mixture with a magnetic stirrer at room temperature for 1 h to complete the reaction. Detect the final product by TLC, and finally obtain the final product: allyl 4-phenyl-1-(1-phenylethenyl)-1H-pyrazole-3-carboxylate by column chromatography with a yield of 63%.
[0093] The above reaction equation is as follows:
[0094]
[0095] Examples 14 - 19
[0096] Examples 14 - 19 are basically the same as Example 1, except that: the types of bases are different. Under different base conditions, the yields of the product ethyl 4-phenyl-1-(1-phenylethenyl)-1H-pyrazole-3-carboxylate are shown in Table 1.
[0097] Table 1 Yields of the product under different base conditions
[0098] Example Base Solvent Yield Example 1 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) Dichloromethane 80％ Example 14 1,1,3,3-Tetramethylguanidine Dichloromethane 40％ Example 15 1,4-Diazabicyclo[2.2.2]octane (DABCO) Dichloromethane 10％ Example 16 N,N-Diisopropylethylamine (DIPEA) Dichloromethane 35％ Example 17 Triethylamine Dichloromethane 25％ Example 18 Cesium carbonate Dichloromethane 30％ Example 19 Potassium tert-butoxide Dichloromethane 20％
[0099] As can be seen from Table 1, for the substrate vinyl sulfonium salt and ethyl diazoacetate, the product can be obtained under different base conditions, and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is the best base.
[0100] Examples 20 to 28
[0101] Examples 20 to 28 are basically the same as Example 1, except that: the types of solvents are different. The yields of the product ethyl 4-phenyl-1-(1-phenylethenyl)-1H-pyrazole-3-carboxylate under different solvent conditions are shown in Table 2.
[0102] Table 2 Product yields under different solvent conditions
[0103]
[0104]
[0105] The above results show that the product can be obtained under different solvent conditions. For the substrate vinyl sulfonium salt and ethyl diazoacetate, dichloromethane is the best solvent.
[0106] The above-described embodiments are only preferred embodiments of the present invention, which are only used to explain the present invention and do not limit the scope of implementation of the present invention. For those skilled in the art of this technology, of course, other implementation manners can be easily made by means of substitution or change according to the technical content disclosed in this specification. Therefore, all changes and improvements made on the principle of the present invention should be included within the scope of the patent application of the present invention.
Claims
1. A method for synthesizing N-vinylpyrazole compounds, characterized in that, It includes the following steps: Using the compound shown in Formula I and the compound shown in Formula II as raw materials, under the action of a base and a solvent, in an air atmosphere, reacting at room temperature for 1 h to synthesize the N-vinylpyrazole compound shown in Formula III; the base is selected from one of diazabicyclo, 1,1,3,3-tetramethylguanidine, triethylenediamine, N,N-diisopropylethylamine, triethylamine, cesium carbonate or potassium tert-butoxide; the solvent is selected from one of dichloromethane, acetone, 1,2-dichloroethane, acetonitrile, dimethyl sulfoxide, chloroform, toluene or tetrahydrofuran; The synthesis route is as follows: Wherein: R1 is selected from hydrogen or halogen; R2 is selected from trifluoromethyl or cyano.
2. The synthesis method of an N-vinylpyrazole compound according to claim 1, characterized in that, The molar ratio of the compound shown in Formula I to the compound shown in Formula II is 3:
1.
3. The synthesis method of an N-vinyl pyrazole compound according to claim 1, characterized in that, The addition amount of the base is 600 mol% of the compound shown in Formula II.
4. The synthesis method of an N-vinyl pyrazole compound according to claim 1, characterized in that, The addition amount ratio of the solvent to the compound shown in Formula II is 2 mL:0.2 mmol.