Squaric acid skeleton covalent organic framework supported palladium catalyst as well as preparation method and application thereof

Abstract

The invention discloses a squaric acid skeleton covalent organic framework supported palladium catalyst as well as a preparation method and application thereof, and belongs to the technical field of heterogeneous catalyst preparation. The preparation method of the squaric acid skeleton covalent organic framework supported palladium catalyst comprises the following steps: putting melem and squaric acid into a pressure-resistant pipe, adding a mixed solvent of water and methanol, reacting, cooling to room temperature, carrying out suction filtration, collecting a solid, and drying to obtain COF-SME; mixing a palladium acetate solution with COF-SME, reacting at room temperature, performing suction filtration after the reaction, and washing and drying a filter cake to obtain the catalyst Pd-coated COF-SME. When the catalyst Pd-coated COF-SME is used for catalyzing a Suzuki-Miyaura coupling reaction, nitrogen protection is not needed, the catalytic efficiency is high, the temperature is low, the dosage is low, the yield of a target product is high, and the catalyst Pd-coated COF-SME is convenient to recycle.

Description

Technical Field

[0001] The present invention relates to a squaric acid framework covalently organic framework supported palladium catalyst, a preparation method thereof and an application thereof, and belongs to the technical field of heterogeneous catalyst preparation. Background Art

[0002] Covalent Organic Framework (abbreviated as COF) materials have triggered a wide and in-depth research boom in the scientific research field due to their excellent properties such as low density, high specific surface area, precisely designable pore size and good crystallinity. Compared with traditional porous materials, the internal pore size of COF shows high uniformity, and the framework has excellent designability, which makes it show unique advantages in the catalytic field. Moreover, COF has good stability, and its high specific surface area and reasonably designed heteroatom-rich framework can firmly anchor metal ions, which opens up broad prospects for the recovery and reuse of COF-based metal catalysts. Based on this, carefully designing and successfully preparing a COF material with a suitable framework structure and capable of loading a large amount of metal is undoubtedly a research direction with great scientific value and application potential.

[0003] The Suzuki reaction (Suzuki coupling reaction) was first reported by Akira Suzuki in 1979. Due to its wide applicability to substrates and high tolerance to various functional groups, this reaction has become the first choice for constructing C-C couplings and has been widely used in many fields such as drug synthesis, preparation of natural compounds, material research and development, and pesticide production. In the Suzuki reaction, the precise selection of palladium catalysts and ligands is one of the key factors for the success of the reaction. For different reaction substrates, matching appropriate catalysts and ligands can significantly accelerate the reaction process and improve the reaction efficiency.

[0004] After decades of continuous development, a rich variety of palladium catalysts and ligands have emerged, such as classical systems like palladium acetate, tetrakis(triphenylphosphine)palladium, and bis(triphenylphosphine)palladium dichloride. However, it cannot be ignored that these traditional catalysts expose a series of problems that need to be solved urgently. For example, the catalyst is extremely easy to quickly deactivate during the reaction, resulting in a sharp decline in catalytic activity; after the reaction, toxic metal ions remain in the product, bringing great challenges to the subsequent purification work of the product; the palladium catalyst itself is costly and difficult to achieve effective recycling, which to a certain extent limits the popularization and application of this type of reaction in large-scale industrial production. Summary of the Invention

[0005] Aiming at the deficiencies of the existing technologies, the purpose of the present invention is to provide a squaric acid framework covalent organic framework supported palladium catalyst, its preparation method and application. The squaric acid framework covalent organic framework supported palladium catalyst is a heterogeneous catalyst Pd@COF-SME formed by supporting palladium on an ionic covalent organic framework rich in a large number of heteroatoms. In the catalytic Suzuki-Miyaura coupling reaction, this catalyst has mild, fast reaction conditions, does not require nitrogen, has a low catalyst dosage and can be recycled. For example, in the application of catalyzing the synthesis of the intermediate of the drug adapalene, compared with the reported catalysts such as bis(triphenylphosphine)palladium dichloride or tris(dibenzylideneacetone)dipalladium, the catalyst Pd@COF-SME provided by the present invention can complete the reaction quickly, and the obtained product has high purity, is white in color and easy to purify, and the catalyst can be removed only by suction filtration. While the product catalyzed by bis(triphenylphosphine)palladium dichloride has a black color and low purity due to the difficulty in removing the catalyst.

[0006] In order to achieve the above purpose, the following technical solutions are provided:

[0007] The present invention provides a preparation method of a squaric acid framework covalent organic framework supported palladium catalyst, comprising the following steps:

[0008] (1) Put melamine and squaric acid in a pressure-resistant tube, add a mixed solvent of water and methanol, degas, heat and react, cool to room temperature, filter by suction, and subject the collected solid to Soxhlet extraction with an organic solvent, and dry the solid to obtain COF-SME;

[0009] (2) In a reaction vessel, add a palladium acetate solution dissolved in an organic solvent and the COF-SME prepared in step (1), react at room temperature, filter by suction after the reaction, wash the filter cake, and dry to obtain the catalyst Pd@COF-SME.

[0010] In one embodiment, the molar ratio of the squaric acid to melamine in step (1) is 2-4:3-5; preferably 3:4.5.

[0011] In one embodiment, the volume ratio of water to methanol in the mixed solvent in step (1) is 1-50:1-50; preferably 6:1.

[0012] In one embodiment, the solid-liquid ratio of the squaric acid and melamine to the mixed solvent in step (1) is 100-200:1-5, mg / mL; preferably 100-150:1-5.

[0013] In one embodiment, the degassing in step (1) is to freeze in a liquid nitrogen bath and pump to vacuum to remove the residual air.

[0014] In one embodiment, the heating reaction in step (1) is carried out under an inert gas seal, the reaction temperature is 60 - 90 °C, and the time is 5 - 60 hours.

[0015] In one embodiment, the organic solvent in step (1) is one or a mixture of methanol, ethanol, dichloromethane, and o-dichlorobenzene.

[0016] In one embodiment, the time for Soxhlet extraction in step (1) is 1 - 48 h.

[0017] In one embodiment, the mass ratio of palladium acetate to COF-SME in step (2) is 1 - 6:10 - 30.

[0018] In one embodiment, the organic solvent in step (2) is one or a mixture of methanol, ethanol, dichloromethane, and o-dichlorobenzene.

[0019] The present invention also provides the catalyst Pd@COF-SME prepared by the method described above.

[0020] The present invention also provides the application of the catalyst Pd@COF-SME described above in the catalytic Suzuki-Miyaura reaction.

[0021] In one embodiment, the application is specifically: mixing the haloarene, phenylboronic acid, potassium carbonate, and the catalyst Pd@COF-SME evenly, adding an appropriate amount of solvent, and heating and reacting at 25 - 60 °C to obtain the coupling product.

[0022] In one embodiment, the molar ratio of the haloarene, phenylboronic acid, potassium carbonate, and the catalyst Pd@COF-SME is 1 - 2:1 - 3:2.0:0.0001 - 0.002; preferably 1:1.2:2.0:0.001.

[0023] In one embodiment, the haloarene includes any one of bromobenzene, p-bromoacetophenone, p-nitrobromobenzene, p-bromoacetonitrile, and p-hydroxybromobenzene.

[0024] In one embodiment, the solvent is water.

[0025] In one embodiment, the specific reaction formula of the Suzuki-Miyaura reaction is:

[0026]

[0027] Among them, R is any substituent at a position other than the halogen on the benzene ring; R is any one of a hydroxyl group, a nitro group, an aldehyde group, a carboxyl group, a carbonyl group, a cyano group, a methoxy group, an acyl group, and an isocyano group, and X is a halogen (X = F, Cl, Br, I).

[0028] The present invention also provides a method for catalytically preparing the intermediate of the drug adapalene, adapalene ester, based on the catalyst Pd@COF-SME. The method includes: uniformly mixing 3-(1-adamantyl)-4-methoxyphenylboronic acid, methyl 7-bromo-2-naphthoate, potassium carbonate, and the catalyst Pd@COF-SME, adding a solvent, and heating for reaction to obtain adapalene ester.

[0029] In one embodiment, the heating reaction temperature is 25-60°C and the time is 20-40 min.

[0030] In one embodiment, the molar ratio of 3-(1-adamantyl)-4-methoxyphenylboronic acid, methyl 7-bromo-2-naphthoate, potassium carbonate, and the catalyst Pd@COF-SME is 1-2:1-3:1-10:0.0001-0.002; preferably 1:1.2:2.0:0.001.

[0031] In one embodiment, the solvent is water.

[0032] In one embodiment, the reaction scheme is as follows:

[0033]

[0034] Beneficial effects:

[0035] The present invention provides a squaric acid framework covalently organic framework supported palladium catalyst, its preparation method and application. This catalyst uses the highly crystalline ionic covalently organic framework COF-SME rich in heteroatoms in the framework as a carrier to support palladium. Due to its characteristics of high heteroatoms, high crystallinity, and ionization, compared with other porous materials, this covalently organic framework material can well support the palladium catalyst;

[0036] (1) The synthesis raw materials of the covalently organic framework COF-SME used in the present invention, squaric acid and melamine, are cheaper and easier to obtain compared with other covalently organic framework materials, and the large-scale production cost is lower;

[0037] (2) The palladium catalyst Pd@COF-SME provided by the present invention does not require nitrogen protection during the catalytic Suzuki-Miyaura coupling reaction, has high catalytic efficiency and low temperature; for the reaction of haloarene and phenylboronic acid, the reaction can be completed under the conditions of 6 min and 45°C, and the yield of the reaction product can reach more than 95%; for the complex drug intermediate adapalene ester, the reaction can be completed under the conditions of 30 min and 45°C, and the yield reaches more than 95%;

[0038] (3) The palladium catalyst Pd@COF-SME provided by the present invention can complete the reaction without adding any ligands, and the catalytic equivalent of the required palladium catalyst Pd@COF-SME is extremely low. Only 0.1 mmol% is required to complete the reaction. For example, only 0.8 mg of the palladium catalyst is required to catalyze 1 mmol of phenylboronic acid reaction, and it is convenient for recycling. Description of the Drawings

[0039] Figure 1 Infrared spectra of covalent organic framework COF-SME, squaric acid (SA), and melem in Example 1;

[0040] Figure 2 Solid-state NMR carbon spectrum of covalent organic framework COF-SME in Example 1;

[0041] Figure 3 PXRD patterns of covalent organic framework COF-SME in Example 1 and palladium catalyst Pd@COF-SME in Example 1;

[0042] Figure 4 XPS full spectra of covalent organic framework COF-SME in Example 1 and palladium catalyst Pd@COF-SME in Example 1. Detailed Description of the Invention

[0043] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the scope of protection of the present invention. The following specific embodiments further describe the present invention.

[0044] Example 1

[0045] Preparation of COF-SME and catalyst Pd@COF-SME, including the following steps:

[0046]

[0047] (1) 98.18 mg (0.45 mmol) of melem and 34.22 mg (0.3 mmol) of squaric acid were placed in a pressure-resistant tube, 5 mL of a mixed solvent of water and methanol (volume ratio 6:1) was added, degassed under a liquid nitrogen bath, and sealed in an argon atmosphere. Then, it was heated to room temperature and reacted at 80 °C for 36 hours, cooled to room temperature, filtered by suction, the collected solid was extracted by Soxhlet extraction with methanol for 1 day, and the solid was dried to obtain COF-SME;

[0048] (2) In a 100 mL round-bottom flask, palladium acetate (6 mg) was dissolved in 10 mL of methanol, and then 20 mg of COF-SME was added. The reaction was carried out at room temperature for 12 hours. After the reaction, filtration was performed. The filter cake was washed three times with methanol and dichloromethane, and then dried at 80 °C to obtain the catalyst Pd@COF-SME.

[0049] The catalyst Pd@COF-SME was characterized by infrared spectroscopy, solid-state nuclear magnetic resonance, powder X-ray diffraction, and X-ray photoelectron spectroscopy. The results are shown in the appendix Figures 1 to 4 .

[0050] Figure 1 The infrared spectra of squaric acid (SA), melem, and COF-SME are shown. COF-SME exhibits a C=O stretching vibration band at 1655 cm -1 . This band shows a blue shift compared to squaric acid (1640 cm -1 ), which is caused by the extended π-conjugation of COF-SME. The peaks at 1481 cm -1 and 1340 cm -1 belong to the characteristic stretching vibrations of the triazine ring. The shaped peak at 1733 cm -1 is attributed to the C=N stretching vibration, and the shaped peak at 1265 cm -1 is attributed to the C-N stretching vibration. The above results all demonstrate the successful synthesis of COF-SME.

[0051] Figure 2 The solid-state nuclear magnetic resonance of COF-SME is shown. The peaks at 204 ppm, 192 ppm, and 154 ppm are attributed to the carbons of the squaric acid tetracyclic ring, and the peaks at 162 and 165 ppm are attributed to the carbons of the heptazine ring. The solid-state nuclear magnetic resonance carbon spectrum indicates the successful condensation of the two monomers and the successful preparation of COF-SME.

[0052] Figure 3 The XRD patterns of COF-SME and Pd@COF-SME are shown. There is a sharp peak at 6°, which is consistent with the simulated XRD data by software. The surface COF-SME is a highly crystalline covalent organic framework material, rather than a non-covalent organic polymer. The XRD image of Pd@COF-SME also shows a sharp peak at 6°, indicating that the loading of palladium acetate on COF-SME does not destroy its original crystal form, and the crystal form of Pd@COF-SME is also beneficial to the catalytic reaction.

[0053] Figure 4 The survey XPS spectra of COF-SME and Pd@COF-SME are shown. It can be observed that there are peaks in the Pd 3d region of Pd@COF-SME, indicating that COF-SME has successfully loaded palladium acetate.

[0054] Comparative Example 1

[0055] The difference from Example 1 is only that melem is replaced by melamine, and other parameters and conditions are the same as those in Example 1, obtaining Pd@COF-SMA.

[0056] Comparative Example 2

[0057] The difference from Example 1 is only that melem is replaced by benzene-1,3,5-tricarbohydrazide, and other parameters and conditions are the same as those in Example 1, obtaining Pd@COF-SB.

[0058] Example 2

[0059] The Suzuki-Miyaura coupling reaction catalyzed by Pd@COF-SME is as follows:

[0060] 121.93 mg (1.0 mmol) of phenylboronic acid, 188.41 mg (1.2 mmol) of bromobenzene, 276.41 mg (2.0 mmol) of potassium carbonate, and 0.8 mg (0.001 mmol) of Pd@COF-SME were respectively added into a 25 mL single-necked flask, 10 mL of water was added, and the mixture was stirred at a constant temperature of 45 °C for 6 min. After the reaction was completed, the filter cake was collected by suction filtration. The filter cake was rinsed with dichloromethane, and the yield of the organic phase was determined by gas chromatography. The remaining filter cake was convenient for recycling the catalyst Pd@COF-SME.

[0061] Example 3

[0062] The difference from Example 2 is only that the reaction substrate bromobenzene is respectively replaced by p-bromoacetophenone, p-nitrobromobenzene, p-bromoacetonitrile, and p-hydroxybromobenzene, and other parameters and conditions are the same as those in Example 2.

[0063] Comparative Example 3

[0064] The difference from Example 2 is only that the catalyst is replaced by Pd@COF-SMA, and other parameters and conditions are the same as those in Example 2.

[0065] Comparative Example 4

[0066] The difference from Example 2 is only that the catalyst is replaced by Pd@COF-SB, and other parameters and conditions are the same as those in Example 2.

[0067] Result analysis

[0068] Table 1. Yields obtained with different substrates

[0069]

[0070] Table 2. Yields obtained with different catalysts

[0071]

[0072] Example 4

[0073] Preparation of adapalene ester, an intermediate of the drug adapalene, catalyzed by Pd@COF-SME is as follows:

[0074] 3-(1-Adamantyl)-4-methoxyphenylboronic acid (362.29 mg, 1.0 mmol), methyl 7-bromo-2-naphthoate (318.13, 1.2 mmol), potassium carbonate (276.41 mg, 2.0 mmol), and Pd@COF-SME (0.8 mg, 0.001 mmol) were separately added into a 25 mL single-neck flask. 10 mL of water was added, and the mixture was stirred at a constant temperature of 45 °C for 30 min. After the reaction was completed, the filter cake and the filtrate were collected by suction filtration. The filter cake was rinsed with dichloromethane and dried to obtain the recycled palladium catalyst Pd@COF-SMA, which could be recycled. After the filtrate was concentrated by rotary evaporation, it was separated by column chromatography to obtain the product adapalene ester with a yield of 95%.

[0075] The examples provided above are not intended to limit the scope covered by the present invention, nor are the described steps intended to limit the order of their execution. Obvious improvements made by those skilled in the art in combination with the existing common general knowledge also fall within the protection scope defined by the claims of the present invention.

Claims

1. A preparation method of a squaric acid framework covalently organic framework supported palladium catalyst, characterized in that, The preparation method comprises the following steps: (1) Melamine and squaric acid are placed in a pressure-resistant tube, a mixed solvent of water and methanol is added, degassed, heated for reaction, cooled to room temperature, filtered by suction, the collected solid is extracted by Soxhlet extraction with an organic solvent, and the solid is dried to obtain COF-SME; (2) In a reaction vessel, a palladium acetate solution dissolved in an organic solvent and the COF-SME prepared in step (1) are added, reacted at room temperature, filtered by suction after the reaction, the filter cake is washed and dried to obtain the catalyst Pd@COF-SME.

2. The preparation method according to claim 1, characterized in that, In step (1), the molar ratio of squaric acid to melamine is 2-4:3-5.

3. The preparation method according to claim 1, characterized in that, In step (2), the mass ratio of palladium acetate to COF-SME is 1-6:10-30.

4. The catalyst Pd@COF-SME obtained by the preparation method according to any one of claims 1 to 3.

5. Use of the catalyst Pd@COF-SME according to claim 4 in the Suzuki-Miyaura reaction.

6. The application according to claim 5, characterized in that, The use is to uniformly mix a haloarene, phenylboronic acid, potassium carbonate and the catalyst Pd@COF-SME according to claim 4, add a solvent, and heat the reaction at 25-60 °C to obtain a coupling product.

7. The application according to claim 6, wherein The molar ratio of the haloarene, phenylboronic acid, potassium carbonate, and catalyst Pd@COF-SME is 1-2:1-3:2.0:0.0001-0.

002.

8. The application according to claim 7, wherein The haloarene includes any one of bromobenzene, p-bromoacetophenone, p-nitrobromobenzene, p-bromoacetonitrile, and p-hydroxybromobenzene.

9. The application according to claim 6, wherein The solvent is water.

10. A method for catalytically preparing the intermediate adapalene ester of the drug adapalene based on the catalyst Pd@COF-SME, characterized in that, The method includes: uniformly mixing 3-(1-adamantyl)-4-methoxyphenylboronic acid, methyl 7-bromo-2-naphthoate, potassium carbonate, and the catalyst Pd@COF-SME according to claim 4, adding a solvent, and heating the reaction to obtain adapalene ester.

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