Pyrazole derivative as well as preparation method and application thereof

Abstract

The invention discloses a pyrazole derivative and a preparation method and application thereof, and the method comprises the following steps: S1, dissolving reactants in a reaction solution according to a ratio, and then carrying out a heating reflux reaction in an N2 atmosphere; s2, performing extraction, drying and chromatography to obtain a solid product a; s3, adding the solid product a in the S2 into a mixed solvent of methanol and dichloromethane, adding HCl into the mixed solvent to remove a protecting group, then adjusting the pH value of the mixed solvent to 7, and filtering to obtain a solid product b; s4, methanol is added into the solid product b obtained in S3 for recrystallization, and the pyrazole derivative is obtained through filtering and vacuum drying. According to the pyrazole derivative and the preparation method and application thereof, the problems that in the prior art, a monodentate ligand is single in coordination site and simple in coordination form, and an obtained complex is single in structure and function are solved, and multifunctional ligands bringing rich coordination sites are provided.

Description

Technical Field

[0001] The present invention relates to the technical field of pyrazole derivatives, in particular to a pyrazole derivative and a preparation method and application thereof. Background Art

[0002] Bimetallic or heterometallic organic supramolecular polymers assembled from pyrazole derivatives have attracted the interest of more chemists due to their tunable chemical and physical properties, which can show excellent selectivity or resistance to inactivation. Studies have further found that this novel homo- and heterometallic organic supramolecular polymer exhibits good synergistic catalytic effect in catalytic nitro reduction reactions, showing good application prospects and academic value. In recent years, the design and synthesis of pyrazole derivative compounds with good and unique properties has been one of the important research directions in the field of chemical research.

[0003] In the prior art, monodentate ligands are usually used, but such ligands have a single coordination site and a simple coordination form, and the structure and function of the resulting complex are single. Therefore, there is an urgent need for a multifunctional ligand that can provide more abundant coordination sites to obtain pyrazole derivative compounds with abundant coordination forms, diversified functions and outstanding performance. Summary of the invention

[0004] The purpose of the present invention is to provide a pyrazole derivative and a preparation method and application thereof, which solves the problems in the prior art that the monodentate ligand has a single coordination site, a simple coordination form, and a single structure and function of the obtained complex.

[0005] To achieve the above object, the present invention provides a method for preparing a pyrazole derivative, comprising the following steps:

[0006] S1. Dissolve the reactants in the reaction solution according to the proportion, and then heat and reflux the reaction under N2 atmosphere;

[0007] S2, after extraction, drying and chromatography, a solid product a is obtained;

[0008] S3, adding the solid product a of S2 into a mixed solvent of methanol and dichloromethane, adding HCl to the mixed solvent to remove the protecting group, then adjusting the pH of the mixed solvent to 7, and filtering to obtain a solid product b;

[0009] S4. Add methanol to the solid product b of S3 for recrystallization, filter and vacuum dry to obtain a pyrazole derivative.

[0010] Preferably, S1 is specifically:

[0011] 1,4-diethynylbenzene, bistriphenylphosphine palladium dichloride and 4-iodo-(1-pyranyl)pyrazole were dissolved in a mixed solution of triethylamine and tetrahydrofuran, and heated under reflux at 70° C. for 24 h under a N 2 atmosphere.

[0012] Preferably, the molar ratio of 1,4-diethynylbenzene, bistriphenylphosphine palladium dichloride and 4-iodo-(1-pyranyl)pyrazole is 4:1:8;

[0013] The molar volume ratio of the 1,4-diethynylbenzene to the mixed solution of triethylamine and tetrahydrofuran is 1 mmol:5 mL.

[0014] Preferably, the volume ratio of triethylamine to tetrahydrofuran is 1:1.

[0015] Preferably, S1 is specifically:

[0016] Methyl 3-bromobenzoate, 1-THP-4-pyrazole borate, K2CO3 and tetrakistriphenylphosphine palladium were dissolved in 1,4-dioxane solution and reacted at 110°C for 24 hours under N2 atmosphere.

[0017] Preferably, the molar ratio of methyl 3-bromobenzoate, 1-THP-4-pyrazole borate, and K2CO3 is 20:40:30:1;

[0018] The molar volume ratio of the methyl 3-bromobenzoate to 1,4-dioxane is 1 mmol:5 mL.

[0019] Preferably, in S3, the volume ratio of the methanol and dichloromethane mixed solvent is 1:1;

[0020] The concentration of the HCl is 2 mol / L.

[0021] Preferably, in S2, the extraction is carried out using CHCl3;

[0022] The chromatography used an eluent of a mixture of ethyl acetate and dichloromethane in a volume ratio of 20:1.

[0023] To achieve the above object, the present invention further provides a pyrazole derivative, including a pyrazole derivative I and a pyrazole derivative II, wherein the structural formula of the pyrazole derivative I is as follows:

[0024]

[0025] The structural formula of pyrazole derivatives II is as follows:

[0026]

[0027] To achieve the above object, the present invention also provides an application of pyrazole derivatives in coordination chemistry and catalysis.

[0028] Therefore, the present invention adopts the above-mentioned pyrazole derivative and its preparation method and application, and the beneficial effects are as follows:

[0029] (1) The pyrazole derivatives prepared by the present invention have different coordination angles at different positions. By design, the pyrazole derivatives can be coordinated with different metal ions to form compounds with different angles, shapes, and coordination numbers. The compounds are applied to the fields of coordination chemistry and catalysis to obtain materials with good fluorescence properties, photoelectric properties, and catalytic properties.

[0030] (2) The pyrazole derivatives prepared by the present invention are a type of multifunctional ligand (organic bridging ligand) that can provide abundant coordination sites. On the one hand, there are complex hydrogen bonds in the ligands, which are formed by nitrogen-hydrogen bonds on the ligand pyrazole, and different conformations are generated at different positions of the hydrogen bonds. On the other hand, the nitrogen-hydrogen bonds are weakly acidic and will dissociate to release protons under certain conditions. The nitrogen atom after releasing the proton can also participate in the coordination, that is, it has a double coordination site.

[0031] (3) The preparation method of the present invention only involves organic synthesis, has simple operation, low production cost, cheap and easily available raw materials, a yield of more than 75%, simple purification, and is suitable for industrial production.

[0032] The technical solution of the present invention is further described in detail below through the accompanying drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 It is the UV-visible spectrum of 4-nitrophenol before and after adding NaBH4 in the present invention;

[0034] Figure 2 The UV-visible spectra of the present invention after adding the assembly of complex I into 4-nitrophenol as a catalyst;

[0035] Figure 3 The present invention is 4-nitrophenol in the presence of the assembly of complex I -ln (C t / C0) curve changing with time;

[0036] Figure 4 It is a cyclic experimental diagram of the catalytic reduction of 4-nitrophenol by the assembly of the present invention. DETAILED DESCRIPTION

[0037] The technical solution of the present invention is further described below through the accompanying drawings and embodiments.

[0038] Unless otherwise defined, technical or scientific terms used in the present invention shall have the common meanings understood by one having ordinary skills in the field to which the present invention belongs.

[0039] Embodiment 1

[0040] The structural formula of pyrazole derivatives I is as follows:

[0041]

[0042] Its synthetic route is as follows:

[0043]

[0044] The preparation method thereof is specifically as follows:

[0045] Dissolve 1,4-diethynylbenzene (4 mmol), bistriphenylphosphine palladium dichloride (1 mmol), and 4-iodo-(1-pyranyl)pyrazole (8 mmol) in a 20 ml triethylamine and tetrahydrofuran mixed solution. Heat at 70°C under N2 atmosphere for 24 hours, extract with CHCl3, dry, and chromatograph to obtain a solid product a (compound of formula I);

[0046] The solid product a was added to a mixed solvent of 20 mL of methanol and 20 mL of dichloromethane, 1 mL of 2 mol / L HCl was added to the mixed solvent to remove the protecting group, NaHCO3 was added to adjust the pH of the mixed solvent to 7, and the solid product b was obtained by filtration. A large amount of methanol was added to the solid product b for recrystallization, and 850 mg (yield: 85%) of pyrazole derivative I was obtained after filtration and vacuum drying.

[0047] Embodiment 2

[0048] The structural formula of pyrazole derivatives II is as follows:

[0049]

[0050] Its synthetic route is as follows:

[0051]

[0052] The preparation method thereof is specifically as follows:

[0053] Dissolve methyl 3-bromobenzoate (4 mmol), 1-THP-4-pyrazole borate (8 mmol), K2CO3 (6 mmol), tetrakistriphenylphosphine palladium (0.4 mmol) in 20 ml of 1,4-dioxane solution. Heat at 110°C under N2 atmosphere for 24 hours, extract with CHCl3, dry, and chromatograph to obtain solid product a (compound of formula II);

[0054] The solid product a was added to a mixed solvent of 20 mL of methanol and 20 mL of dichloromethane, 1 mL of 2 mol / L HCl was added to the mixed solvent to remove the protecting group, NaHCO3 was added to adjust the pH of the mixed solvent to 7, and the solid product b was obtained by filtration. A large amount of methanol was added to the solid product b for recrystallization, and 660 mg (yield: 75%) of pyrazole derivative II was obtained after filtration and vacuum drying.

[0055] Experimental Testing

[0056] The nuclear magnetic resonance analysis results of the pyrazole derivatives prepared in Examples 1 and 2 are as follows:

[0057] Embodiment 1:

[0058] 1H NMR (400MHz, DMSO) δ = 13.33 (s, 1H), 8.58 (s, 1H), 8.02 (s, 1H), 7.44 (s, 1H).

[0059] Embodiment 2:

[0060] 1H NMR (DMSO-d6, 400MHz): δ = 13.02 (s, 2H), 8.13 (d, J = 7.6Hz, 3H), 7.86 (d, J = 7.9Hz, 1H), 7.75 (d, J = 7.8Hz, 1H), 7.47 (t, J = 7.7Hz, 1H).

[0061] This indicates that the compounds were successfully synthesized. The nitrogen on pyrazole and the nitrogen on pyridine in the pyrazole-pyridine ligands have good coordination ability with metals, so a supramolecular structure is obtained by coordination with metals.

[0062] That is, the pyrazole derivative I prepared in Example 1 is combined with [(bpy)2Pd2(NO3)2](NO3)2 for assembly, and the specific operation is as follows:

[0063] Pyrazole derivative Ⅰ (0.04mmol, 6.76mg) and [(bpy)2Pd2(NO3)2](NO3)2 (0.06mmol, 23.20mg) were dissolved in 1mL DMSO-d6, assembled at room temperature to obtain complex I, and the assembly was monitored by hydrogen spectrum nuclear magnetic resonance tracking.

[0064] The results of NMR analysis of complex I are:

[0065] 1 H NMR (600MHz, DMSO) δ = 9.21 (d, J = 6.8Hz, 4H), 8.80 (d, J = 9.4Hz, 2H), 8.76 (d, J = 9.4Hz, 4H), 8.52 (dd, J = 17.2, 9.2Hz, 6H), 8.48 (d, J = 5.0Hz, 4H), 8.29 (d, J = 6.9Hz, 4H), 7.88-7.79 (m, 8H), 7.76 (t, J = 7.2Hz, 2H), 7.56 (d, J = 5.8Hz, 2H).

[0066] Nitro reduction catalytic test on the assembly of complex Ⅰ

[0067] Due to the highly dispersed nature of palladium ions and good catalytic performance, the nitrobenzene reduction reaction was chosen as a model reaction to evaluate the intrinsic relationship between the assembly of complex I and its catalytic activity. Specifically, the reduction process was monitored by ultraviolet-visible absorption spectroscopy (UV-vis) measurements.

[0068] The reduction of 4-nitrophenol (4-NP) was studied using a SHIMADZU UV-2600UV-Vis spectrophotometer. In a cuvette, nitrophenol (30 μl / 10 mM) in deionized water (3 ml) was added to a NaBH4 (0.16 ml / 0.1 M) solution, followed by the water-dispersed assembly of the nano-scale synthetic compound complex I (1 mg). As the reaction time passed, the color of the solution gradually changed from bright yellow to transparent. Spectral measurements were taken over time. The kinetic data were calculated using a pseudo-first-order rate equation.

[0069] The absorbance change of 4-nitrophenol before and after adding NaBH4 is as follows Figure 1 As shown in Figure 2, it can be seen that the wavelength shifts significantly after adding NaBH4.

[0070] The changes in absorbance after adding the assembly of complex I as a catalyst to 4-nitrophenol are shown in Figure 2 As shown, the absorbance at 400 nm gradually weakened, while the absorbance at 200-300 nm gradually increased, indicating that 4-nitrophenol was gradually reduced to 4-aminophenol.

[0071] 4-nitrophenol in the presence of the complex Ⅰ assembly -ln (C t The curve of / C0) changing with time is as follows Figure 3 As shown. t represents the concentration of NPs at time t, and C0 represents the initial concentration of nitrophenol at t = 0. t / C0 is determined by the relative absorption intensity (A t / A0) was measured. The catalytic reaction rate K of the assembly of complex I was found to be 1.4370 min -1 .

[0072] In order to test the cycling stability of the assembly of complex I, cycling experimental conditions were performed. 4-NP (0.1*10 -3 mmol) was added to the assembly (Pd1.05*10 -5 mmol) and 0.2M NaBH4 aqueous solution (2.3mL) in a quartz test tube. Figure 4 As shown in Figure 2, the cycle stability is good.

[0073] Therefore, the present invention adopts the above-mentioned pyrazole derivative and its preparation method and application to solve the problems in the prior art that the monodentate ligand has a single coordination site, a simple coordination form, and a single structure and function of the resulting complex.

[0074] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that they can still modify or replace the technical solution of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solution to deviate from the spirit and scope of the technical solution of the present invention.

Claims

1. A method for preparing a pyrazole derivative, characterized in that: The following steps are involved: S1. Dissolve the reactants in the reaction solution according to the proportion, and then heat and reflux the reaction under N2 atmosphere; S2, after extraction, drying and chromatography, a solid product a is obtained; S3, adding the solid product a of S2 into a mixed solvent of methanol and dichloromethane, adding HCl to the mixed solvent to remove the protecting group, then adjusting the pH of the mixed solvent to 7, and filtering to obtain a solid product b; S4. Add methanol to the solid product b of S3 for recrystallization, filter and vacuum dry to obtain a pyrazole derivative.

2. The method for preparing a pyrazole derivative according to claim 1, characterized in that: S1 is specifically: 1,4-diethynylbenzene, bistriphenylphosphine palladium dichloride and 4-iodo-(1-pyranyl)pyrazole were dissolved in a mixed solution of triethylamine and tetrahydrofuran, and heated under reflux at 70° C. for 24 h under a N 2 atmosphere.

3. The method for preparing a pyrazole derivative according to claim 2, characterized in that: The molar ratio of 1,4-diethynylbenzene, bistriphenylphosphine palladium dichloride and 4-iodo-(1-pyranyl)pyrazole is 4:1:8; The molar volume ratio of the 1,4-diethynylbenzene to the mixed solution of triethylamine and tetrahydrofuran is 1 mmol:5 mL.

4. The method for preparing a pyrazole derivative according to claim 3, characterized in that: The volume ratio of the triethylamine to tetrahydrofuran is 1:

1.

5. The method for preparing a pyrazole derivative according to claim 1, characterized in that: S1 is specifically: Methyl 3-bromobenzoate, 1-THP-4-pyrazole borate, K2CO3 and tetrakistriphenylphosphine palladium were dissolved in 1,4-dioxane solution and reacted at 110°C for 24 hours under N2 atmosphere.

6. The method for preparing a pyrazole derivative according to claim 5, characterized in that: The molar ratio of methyl 3-bromobenzoate, 1-THP-4-pyrazole borate, and K2CO3 is 20:40:30:1; The molar volume ratio of the methyl 3-bromobenzoate to 1,4-dioxane is 1 mmol:5 mL.

7. The method for preparing a pyrazole derivative according to claim 1, characterized in that: In S3, the volume ratio of the methanol and dichloromethane mixed solvent is 1:1; The concentration of the HCl is 2 mol / L.

8. The method for preparing a pyrazole derivative according to claim 1, characterized in that: In S2, the extraction is carried out using CHCl3; The chromatography used an eluent of a mixture of ethyl acetate and dichloromethane in a volume ratio of 20:

1.

9. A pyrazole derivative prepared by the method for preparing a pyrazole derivative according to any one of claims 1 to 8, characterized in that: It includes pyrazole derivatives I and pyrazole derivatives II, wherein the structural formula of pyrazole derivative I is as follows: The structural formula of pyrazole derivatives II is as follows:

10. Use of the pyrazole derivatives according to claim 9 in coordination chemistry and catalysis.

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