A metal copper complex of pyridine-pyrazolecarboxylic acid with catalytic performance and a preparation method thereof

Abstract

A copper(II) metal complex of pyridine-pyrazolecarboxylic acid with catalytic performance and a preparation method thereof. The copper(II) metal complex of pyridine-pyrazolecarboxylic acid with catalytic performance is a six-coordinate mononuclear metal complex. The structural unit consists of a central metal copper(II), 2 pyrazole-4-carboxylic acid-2-methylenepyridines, and 2 water molecules coordinated to form an octahedral configuration. The preparation steps are simple, providing an experimental basis and synthesis experience for the synthesis of transition metal complexes based on pyridine-pyrazole ligands. The metal copper complex can activate terminal alkynes under mild conditions and catalyze their addition reactions to indigo compounds with high reaction yields and excellent catalytic performance, providing an experimental basis for subsequent addition / substitution reactions of activated alkynes to other electrophilic reagents and having certain potential economic benefits.

Description

Technical Field

[0001] The present invention relates to the field of organic compounds, and particularly to the synthesis of a nitrogen-containing carboxylic acid compound 2-methylenepyridine-1-pyrazole-4-carboxylic acid (hereinafter simply referred to as pyridine-pyrazole carboxylic acid), the preparation method of a complex catalyst formed by this compound and transition metals, and the testing of its catalytic performance. Background Art

[0002] Due to the presence of coordination atoms such as N and O in nitrogen-containing carboxylic acid substances, coupled with the spatial structure effect, if a stable five / six-membered ring structure is formed with metal atoms, they have very excellent coordination properties. Therefore, many nitrogen-containing carboxylic acid compounds, especially pyridine or pyrazole compounds, are widely used organic ligands. Since pyridine-pyrazole carboxylic acid compounds contain abundant nitrogen and oxygen atoms, they can efficiently form multidentate stable coordination with some transition metals to form various novel-structured and excellent catalytic-performance new transition metal complex catalysts. At the same time, the surplus nitrogen atoms in pyrazole and the carboxyl oxygen atoms can also recognize and form hydrogen bonds with other groups containing active hydrogen. In addition, the pyridine and pyrazole rings also have aromaticity, so that a supramolecular system capable of forming large Pi bonds and various hydrogen bond interactions can be formed, laying a good foundation for self-assembly and self-repair. Summary of the Invention

[0003] The first object of the present invention is to provide a copper metal complex of pyridine-pyrazole carboxylic acid with catalytic performance and its preparation method.

[0004] The second object of the present invention is to provide the catalytic application of the above-mentioned copper metal complex of pyridine-pyrazole carboxylic acid.

[0005] The structural formula of the copper metal complex of pyridine-pyrazole carboxylic acid with catalytic performance is [CoL 2 (H 2 O) 2 , the crystal belongs to the C2 / c space group, is monoclinic, and its unit cell parameters are: α = 90°, β = 112.642(2)°, γ = 90°.

[0006] The copper metal complex of pyridine-pyrazole carboxylic acid with catalytic performance is a six-coordinate mononuclear metal complex, and its structural unit is composed of a central metal copper (II), 2 pyrazole-4-carboxylic acid-2-methylenepyridines and 2 water molecules coordinated. The central element copper is coordinated with the oxygen atoms (O2, O2’) in two coordinated water molecules, a nitrogen atom (N1) on the pyrazole ring in one ligand, a nitrogen atom (N2) on the pyridine ring, and a nitrogen atom (N1’) on the pyrazole ring and a nitrogen atom (N2’) on the pyridine ring in another ligand, forming an octahedral configuration.

[0007] The preparation method of the pyridine-pyrazolecarboxylic acid metal copper complex with catalytic performance comprises the following steps:

[0008] 1) Synthesis of the pyrimidine-pyrazole ligand;

[0009] In step 1), the specific method for the synthesis of the pyrimidine-pyrazole ligand may be as follows: In a container equipped with a magnetic stirrer, 4-pyrazolecarboxylic acid, 2-chloromethylpyridine hydrochloride and a phase transfer catalyst are respectively added and added to the above flask. 100 mL of THF is added and stirred. Another beaker is taken, a strong base is weighed and dissolved in 100 mL of water; then the aqueous solution of the strong base is slowly added to the reaction solution in the flask under stirring. After adding, the reaction is stirred at room temperature for a certain time; then the temperature is raised to the reflux state and heated under reflux for a certain time; after the reaction is completed, THF is removed by concentration under reduced pressure, and then the pH of the reaction solution is adjusted with 1 mol / L hydrochloric acid, and a white solid gradually precipitates. The white solid-containing product is placed in a refrigerator at 4 °C for a period of time. After most of the solid has precipitated, filtration is carried out, and the filter residue is washed with petroleum ether to obtain a white powder solid, which is the crude product of the pyridine-pyrazolecarboxylic acid ligand. The crude product is recrystallized with an alcohol organic solvent to obtain the pyrimidine-pyrazolecarboxylic acid ligand. The obtained pyrimidine-pyrazole ligand is a white crystal with a yield of 84% - 93%.

[0010] The base is one of sodium hydroxide and potassium hydroxide; the molar concentration of the base in the solvent may be 0.05 - 2.0 mol / L; the molar ratio of the 4-pyrazolecarboxylic acid to the base may be 1:(3 - 5); the molar ratio of the 4-pyrazolecarboxylic acid to the 2-chloromethylpyridine hydrochloride may be 1:(1 - 2); the alcohol organic solvent may be selected from one of methanol, ethanol, isopropanol, etc.; the stirring time may be 0.5 - 2 h, the reflux reaction time may be 6 - 36 h, the pH = 3 - 6; the time for placing in the refrigerator is 3 - 8 hours.

[0011] 2) Preparation of the pyridine-pyrazolecarboxylic acid metal copper complex;

[0012] In step 2), the specific method for the preparation of the pyridine-pyrazolecarboxylic acid metal copper complex may be as follows: The pyridine-pyrazole ligand is dissolved in a mixed solvent of ethylene glycol / water, and copper dichloride solid (CuCl 2 , this is a commercial reagent) is added, and then 10 uL of NaOH solution is added, and the mixture is stirred evenly. The reaction is carried out by heating and stirring at a certain temperature. After the reaction is completed, it is cooled to room temperature, and blue needle-like crystals precipitate. The crystals are filtered, and the filter residue is washed with water to obtain the pyridine-pyrazolecarboxylic acid metal copper complex with catalytic performance;

[0013] The volume ratio of ethylene glycol / water can be (3:1) to (1:2); the molar concentration of the pyridine-pyrazole ligand in the mixed solvent can be 0.01 to 0.5 mol / L; the molar ratio of copper dichloride to the pyridine-pyrazole ligand can be 1:(1.5 to 3); the temperature of the heating and stirring reaction can be 50 to 120 °C, and the heating reaction time can be 10 to 48 h.

[0014] The metal copper complex of pyridine-pyrazolecarboxylic acid with catalytic performance can be used as a catalyst in organic reactions and can efficiently catalyze the addition reaction of terminal alkynes and indigo compounds.

[0015] The conditions for the addition reaction can be: dissolving the metal copper complex of pyridine-pyrazolecarboxylic acid with catalytic performance in an amide solvent, then adding terminal alkyne, organic base and N-benzylindigo, mixing evenly and reacting at room temperature for 12 to 48 h. After the reaction is completed, saturated ammonium chloride is added for quenching, then extracted with an organic solvent, dried over anhydrous sodium sulfate, the solvent is removed under reduced pressure, and the addition product is obtained after column chromatography.

[0016] The amide solvent can be selected from one of DMF, DMAc, etc.; the R 1 group of the terminal alkyne can be an alkyl group or an aryl group; the molar ratio of the terminal alkyne to the metal copper complex of pyridine-pyrazolecarboxylic acid with catalytic performance can be 1:(0.001 to 0.05); the molar concentration of the terminal alkyne in the solvent can be 0.2 to 1.0 mol / L; the molar ratio of the terminal alkyne to N-benzylindigo can be 1:(0.5 to 1.5); the organic base can be selected from one of triethylamine, diisopropylethylamine, DBU, etc., and the molar ratio of the terminal alkyne to the organic base can be 1:(0.5 to 1.5); the volume of the saturated ammonium chloride solution is 5 to 8 times the volume of the reaction solvent; the organic solvent can be selected from one of ethyl acetate, methyl acetate, butyl acetate, etc.

[0017] Compared with the prior art, the beneficial effects achieved by the technical solution of the present invention are:

[0018] The pyridine-pyrazolecarboxylic acid ligand with catalytic performance of the present invention and the synthesis method of its metal copper complex are simple and easy to operate, without complicated purification steps, and only need to adjust the pH or perform suction filtration / recrystallization to obtain a pure product, providing an experimental basis and synthesis experience for the synthesis of transition metal complexes based on pyridine-pyrazole ligands; the metal copper complex can activate terminal alkynes under mild conditions and catalyze their addition reaction to indigo compounds, with high reaction yields and excellent catalytic performance, providing an experimental basis for subsequent addition / substitution reactions of activated alkynes to other electrophilic reagents, and having certain potential economic benefits. Brief Description of the Drawings

[0019] Figure 1 1H NMR spectrum of the pyridine-pyrazolecarboxylic acid ligand of the present invention.

[0020] Figure 2 13C NMR spectrum of the pyridine-pyrazolecarboxylic acid ligand of the present invention.

[0021] Figure 3 GC-MS spectrum of the pyridine-pyrazolecarboxylic acid ligand of the present invention.

[0022] Figure 4 Single crystal structure diagram of the copper pyridine-pyrazolecarboxylate metal complex with catalytic performance in the present invention.

[0023] Figure 5 Single crystal two-dimensional space network diagram of the copper pyridine-pyrazolecarboxylate metal complex with catalytic performance in the present invention.

[0024] Figure 6 IR spectrum of the copper pyridine-pyrazolecarboxylate metal complex with catalytic performance in the present invention.

[0025] Figure 7 1H NMR spectrum of the addition product I in Example 2.

[0026] Figure 8 13C NMR spectrum of the addition product I in Example 2.

[0027] Figure 9 1H NMR spectrum of the addition product II in Example 3.

[0028] Figure 10 13C NMR spectrum of the addition product II in Example 3. Detailed implementation manners

[0029] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present invention clearer and more understandable, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments.

[0030] Example 1: Synthesis of copper pyridine-pyrazolecarboxylate

[0031] 1) The synthesis of the pyrimidine-pyrazole ligand is as follows:

[0032]

[0033] In a 500 mL flask equipped with a magnetic stirrer and a reflux condenser, accurately weigh 2.24 g (20 mmol) of 4-pyrazolecarboxylic acid, 3.94 g (24 mmol) of 2-chloromethylpyridine hydrochloride, and 1.48 g (4 mmol) of tetrabutylammonium iodide, add them to the above flask, add 100 mL of THF and stir. Take another beaker, weigh 4.58 g (70 mmol) of potassium hydroxide, and dissolve it in 100 mL of water; then slowly add the above 100 mL aqueous solution of KOH to the reaction solution in the flask under stirring. After adding, stir the reaction at room temperature for 1 h; then heat it to the reflux state and reflux for 24 h; after the reaction is completed, concentrate under reduced pressure to remove tetrahydrofuran, and then adjust the reaction solution to about pH = 4 with 1 mol / L hydrochloric acid. A white solid gradually precipitates. Place the white solid-containing solution in a refrigerator at 4 °C for 4 hours. After most of the solid has precipitated, perform suction filtration, and wash the filter residue with petroleum ether to obtain a white powder solid, which is the crude product of the pyridine-pyrazolecarboxylic acid ligand. The crude product is recrystallized with ethanol to obtain 3.73 g of white crystals, with a yield of 92%.

[0034] The proton nuclear magnetic resonance spectrum of the pyridine-pyrazolecarboxylic acid ligand ( Figure 1 ) data are as follows: 1 H NMR (DMSO-d 6 , 400 MHz): δ 12.37 (s, 1H), 8.54 - 8.38 (m, 2H), 7.86 - 7.74 (m, 2H), 7.37 - 7.11 (m, 2H), 5.48 (s, 2H).

[0035] The carbon nuclear magnetic resonance spectrum of the pyridine-pyrazolecarboxylic acid ligand ( Figure 2 ) data are as follows: 13 C NMR (DMSO-d 6 , 100 MHz): δ 163.9, 156.0, 149.4, 141.1, 137.3, 134.8, 123.1, 122.0, 115.2, 56.8.

[0036] See Figure 3 , for the gas chromatography-mass spectrometry diagram of the pyridine-pyrazolecarboxylic acid ligand.

[0037] 2) The synthesis of the pyridine-pyrazolecarboxylic acid copper metal complex is as follows:

[0038]

[0039] In a 250 mL container with a magnetic stir bar, add 2.24 g (10 mmol) of 2-methylenepyridine-1-pyrazole-4-carboxylic acid, then add it to 100 mL of a mixed solvent of ethylene glycol / water (v / v = 1 / 1), and then add 0.81 g (6 mmol) of copper dichloride (CuCl2 ) and 10 μL of NaOH solution (1 mol / L) were mixed evenly, and then the reaction system was heated to 100 °C and stirred for 13 h. After the reaction ended, it was cooled to room temperature, and blue rectangular crystals were precipitated. The crystals were filtered by suction, and the filter residue was washed with water and dried to obtain 2.08 g of the metal copper complex of pyridine-pyrazolecarboxylic acid, with a yield of 83%. The main crystallographic data of the metal copper complex of pyridine-pyrazolecarboxylic acid are shown in Table 1.

[0040] See Figures 4 to 6 , Figure 4 is the single crystal structure diagram of the metal copper complex of pyridine-pyrazolecarboxylic acid with catalytic performance; Figure 5 is the two-dimensional space network diagram of the single crystal of the metal copper complex of pyridine-pyrazolecarboxylic acid with catalytic performance; Figure 6 is the infrared spectrum diagram of the metal copper complex of pyridine-pyrazolecarboxylic acid with catalytic performance.

[0041] Table 1

[0042]

[0043] The following gives application examples of catalytic performance.

[0044] Example 2: The addition reaction of 1-hexyne catalyzed by the metal copper complex of pyridine-pyrazolecarboxylic acid with catalytic performance is as follows:

[0045]

[0046] 106 mg (0.2 mmol) of the metal copper complex of pyridine-pyrazolecarboxylic acid was added to a flask with a magnetic stir bar, and 20 mL of dimethylformamide (DMF) was added to dissolve it. Then, 820 mg of 1-hexyne (10 mmol), 2.0 mmol of triethylamine, and 2.37 g (10 mmol) of N-benzylindigo were added. After mixing evenly, the reaction was stirred at room temperature for 24 h, and the reaction was monitored by thin-layer chromatography. After the reaction ended, the solvent was removed under reduced pressure, and 3.10 g of the addition product I was obtained after purification by column chromatography, with a yield of 93%.

[0047] The nuclear magnetic resonance hydrogen spectrum ( Figure 7 ) data of the addition product I are: 1 H NMR (300 MHz, CDCl 3 ) δ 7.58 - 7.50 (m, 1H), 7.41 - 7.17 (m, 6H), 7.14 - 7.06 (m, 1H), 4.94 (d, J = 15.6 Hz, 1H), 4.86 (d, J = 15.6 Hz, 1H), 3.58 (br s, 1H), 2.24 (t, J = 7.2 Hz, 2H), 1.55 - 1.29 (m, 4H), 0.89 (t, J = 7.2 Hz, 3H).

[0048] 13C NMR of the addition product I( Figure 8 ) is as follows: 13 C NMR(75MHz,CDCl 3 ) δ 174.4, 142.1, 135.1, 130.8, 129.4, 128.8, 127.7, 127.1, 124.5, 123.6, 109.7, 88.2, 69.3, 43.9, 30.3, 21.9, 18.2, 13.5.

[0049] Example 3: The addition reaction of 4-bromoacetylene catalyzed by the pyridine-pyrazolecarboxylic acid metal copper complex with catalytic performance is as follows:

[0050]

[0051] 106 mg (0.05 mmol) of the pyridine-pyrazolecarboxylic acid metal copper complex was added to a flask equipped with a magnetic stir bar, and 20 mL of dimethylformamide (DMF) was added to dissolve it. Then, 1.8 g of 4-bromoacetylene (10 mmol), 2.0 mmol of triethylamine, and 2.37 g (10 mmol) of N-benzylindigo were added. After mixing evenly, the reaction was stirred at room temperature for 24 h. The reaction was monitored by thin-layer chromatography. After the reaction was completed, the solvent was removed under reduced pressure. The crude product was purified by column chromatography to obtain 4.05 g of the addition product II, with a yield of 97%.

[0052] 1H NMR of the addition product II( Figure 9 ) is as follows: 1 H NMR(300MHz,CDCl 3 ) δ 7.65 - 7.57(m, 1H), 7.44 - 7.38(m, 2H), 7.36 - 7.22(m, 8H), 7.18 - 7.10(m, 1H), 6.76 - 6.58(m, 1H), 4.93(s, 2H), 4.14(s, 1H).

[0053] 13C NMR of the addition product II( Figure 10 ) is as follows: 13 C NMR(75MHz,CDCl 3 ) δ 174.1, 142.1, 134.9, 133.5, 131.5, 130.5, 128.9, 128.7, 127.8, 127.2, 124.8, 123.8, 123.4, 120.6, 110.0, 86.7, 85.4, 69.6, 44.1.

Claims

1. A copper pyridine-pyrazolecarboxylate complex with catalytic performance, Characterized in that: The copper pyridine-pyrazolecarboxylate complex with catalytic performance is a six-coordinated mononuclear metal complex, and the structural unit consists of a central metal copper(II), 2 pyrazole-4-carboxylic acid-2-methylpyridine and 2 water molecules coordinated to form an octahedral configuration. The structural formula is as follows:

2. A copper pyridine-pyrazolecarboxylate complex with catalytic performance according to claim 1, Characterized in that: The crystal belongs to the C2 / c space group and is monoclinic. Its unit cell parameters are as follows: α = 90°, β = 112.642(2)°, γ = 90°.

3. A preparation method of the copper pyridine-pyrazolecarboxylate complex with catalytic performance according to any one of claims 1 and 2, Characterized in that, Comprising the following steps: 1) Synthesis of pyrimidine-pyrazole ligand: Add 4-pyrazolecarboxylic acid, 2-chloromethylpyridine hydrochloride and a phase transfer catalyst into a container, add tetrahydrofuran and stir, add an alkali solution under stirring, stir at room temperature for reaction, and then heat up to reflux for reaction; 2) Preparation of copper pyridine-pyrazolecarboxylate complex: Dissolve the pyridine-pyrazole ligand obtained in step 1) in a mixed solvent of ethylene glycol / water, add copper dichloride, and then add a NaOH solution, and heat and stir for reaction.

4. The preparation method according to claim 3, Characterized in that: In step 1), after the reaction is completed, concentrate under reduced pressure to remove tetrahydrofuran, then adjust the pH, cool, and after most of the solid precipitates, carry out suction filtration, washing, and recrystallization to obtain the pyrimidine-pyrazolecarboxylic acid ligand.

5. The preparation method according to claim 3, Characterized in that: In step 1), the molar ratio of 4-pyrazolecarboxylic acid to the alkali is 1:(3-5); the molar ratio of 4-pyrazolecarboxylic acid to 2-chloromethylpyridine hydrochloride is 1:(1-2).

6. The preparation method according to claim 3, Characterized in that: In step 2), after the reaction is completed, cool to room temperature, precipitate blue needle-like crystals, filter and wash to obtain the copper pyridine-pyrazolecarboxylate complex.

7. The preparation method according to claim 3, Characterized in that: In step 2), the molar concentration of the pyridine-pyrazole ligand in the mixed solvent is 0.01-0.5 mol / L; the molar ratio of copper dichloride to the pyridine-pyrazole ligand is 1:(1.5-3); the heating temperature is 50-120 °C.

8. The application of the copper pyridine-pyrazolecarboxylate complex with catalytic performance according to any one of claims 1-2 and the copper pyridine-pyrazolecarboxylate complex with catalytic performance prepared by the preparation method according to any one of claims 3-7, Characterized in that: Catalyze the addition reaction of terminal alkynes and indigo compounds.

9. The application according to claim 8, Characterized in that: Dissolve the copper pyridine-pyrazolecarboxylate complex with catalytic performance in an amide solvent, then add terminal alkyne, organic base and N-benzylindigo, mix evenly and react at room temperature.

10. The application according to claim 9, Characterized in that: The molar ratio of the terminal alkyne to the metal copper complex of pyridine-pyrazolecarboxylic acid with catalytic performance is 1:(0.001 - 0.05); the molar ratio of the terminal alkyne to N-benzylindigo is 1:(0.5 - 1.5); the molar ratio of the terminal alkyne to the organic base is 1:(0.5 - 1.5).

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