Novel chiral covalent organic framework material as well as preparation method and application thereof

Abstract

The invention discloses a novel chiral covalent organic framework material as well as a preparation method and application thereof. The chiral covalent organic framework compound is prepared by the following steps: carrying out Mitsunobo or SN2 reaction, Ullmann coupling and reduction reaction on chiral diol and iodohydroxy ethyl nicotinate to obtain an axial chiral bipyridine aldehyde group monomer, and carrying out Schiff base reaction on the axial chiral bipyridine aldehyde group monomer and a polyamino substituted monomer under a solvothermal condition. The chiral covalent organic framework compound disclosed by the invention can be complexed with various metals such as palladium, copper, nickel and the like to form a heterogeneous catalyst for asymmetric reaction, shows good catalytic effect and chiral selectivity, and also has good chemical stability; after the reaction, separation and recovery of the catalyst can be realized through simple centrifugation or filtration, so that the environmental pollution is effectively reduced, the cost is reduced, and the application prospect is good.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of covalent organic framework materials, and particularly relates to a novel chiral covalent organic framework material and a preparation method and application thereof. BACKGROUND

[0002] Chirality is one of the basic properties of nature, and is closely related to life, so the study of chirality is of great significance to the origin of life and human life. Enantiomers of chiral substances have the same physical properties, but there are differences in physiological and pharmacological activities, and some even have opposite effects, so it is crucial to obtain chiral pure compounds. Chiral separation, chiral resolution and chiral catalysis are the main ways to obtain chiral compounds. These methods all need chirality as an inducer to effectively obtain chiral compounds. The uniform chiral compound inducer system has the disadvantages of large amount of use and difficulty in separation from the product, so the wide application of small molecule chiral compounds in industry is limited. In order to solve these problems, chiral porous materials have emerged as the times require.

[0003] Chiral porous materials are a kind of very important chiral materials. Because of the porous characteristics, chiral porous materials have very wide applications in the fields of chiral separation, chiral resolution and chiral catalysis. In recent years, the developed chiral porous materials mainly include chiral polymer materials, chiral molecular sieve materials, chiral metal organic framework (MOFs) materials and chiral covalent organic framework (COFs) materials. Compared with polymer materials, COFs materials have regular pore structure; compared with molecular sieve materials, COFs materials are easy to adjust the structure; compared with MOFs materials, COFs materials have better stability. However, the characteristics of few types and difficult to synthesize of chiral COFs materials hinder the development and industrial application of chiral COFs materials. SUMMARY

[0004] The purpose of the present application is to solve the above technical problems, and provide a novel chiral covalent organic framework material and a preparation method and application thereof. The prepared chiral covalent organic framework material has good stability, and can be used as a heterogeneous catalyst in asymmetric C-H activation reaction, arylization reaction and 1,4 addition reaction.

[0005] In order to achieve the above object, the present application provides a preparation method of a novel chiral covalent organic framework material, including a preparation method of a series of axially chiral bipyridine aldehyde-based monomers and a synthesis method of the covalent organic framework material.

[0006] The first aspect of the present application provides a preparation method of an axially chiral bipyridine aldehyde-based monomer, specifically including the following steps:

[0007] The structure of the axially chiral bipyridine aldehyde-based monomer a4 is as follows: The reaction process is as follows:

[0008]

[0009] The preparation steps of the monomer include:

[0010] The ethyl 5-hydroxy nicotinate reacts with iodine under the action of a base to generate a substitution reaction, after the reaction is completed, an acid is added to adjust the pH to be acidic, and yellow solids are precipitated, and after being extracted, washed and dried, the compound a1 is obtained in the form of light yellow powder.

[0011] Preferably, the base is sodium carbonate, and the acid is dilute hydrochloric acid.

[0012] Preferably, the molar amount of the iodine is 1 to 1.5 times that of the ethyl 5-hydroxy nicotinate, and the molar amount of the base is 2 to 2.5 times that of the ethyl 5-hydroxy nicotinate.

[0013] Preferably, the substitution reaction is carried out in deionized water, the reaction temperature is 15-40℃, the reaction time is 4-24 hours, and the pH value is adjusted to 2-3.

[0014] Preferably, deionized water is used for washing.

[0015] Under an inert atmosphere, the (2R, 4R)-pentanediol and the ethyl 5-iodohydroxy nicotinate undergo Mitsunobu reaction under the action of triphenylphosphine and an azo compound, after the reaction is completed, the solvent is spin-dried, and the compound a2 is obtained in the form of white crystals after the crude product is purified.

[0016] Preferably, the inert atmosphere is a nitrogen atmosphere, and the azo compound is diisopropyl azodicarboxylate.

[0017] Preferably, the molar amount ratio of the (2R, 4R)-pentanediol, the ethyl 5-iodohydroxy nicotinate, the triphenylphosphine and the azo compound is 1:2-2.5:2.2-3:2.2-3.

[0018] Preferably, the Mitsunobu reaction is carried out in anhydrous solvent, more preferably in anhydrous tetrahydrofuran.

[0019] Preferably, the feeding order of the reaction is that the alcohol, iodo-hydroxynicotinic acid ethyl ester and triphenylphosphine are dissolved in the solvent, and then the azo compound is added dropwise into the mixture.

[0020] Preferably, the reaction mixture is stirred at low temperature for 10-60 minutes, then the azo compound is added dropwise, followed by warming to room temperature for reaction, and the reaction time is 12-30 hours.

[0021] Preferably, the purification is carried out by silica gel column chromatography, more preferably, the eluent used is ethyl acetate and petroleum ether system (ethyl acetate: petroleum ether = 1:3-1:5, V / V).

[0022] Under an inert atmosphere, the Ullmann coupling reaction of a2 with copper catalyst is carried out, and after the reaction is completed, the compound is obtained as white crystals a3 through post-treatment.

[0023] Preferably, the inert atmosphere is nitrogen atmosphere, and the copper catalyst is copper powder.

[0024] Preferably, the molar ratio of a2 to copper catalyst is 1:5.

[0025] Preferably, the Ullmann coupling reaction is carried out in dimethyl sulfoxide solvent, the reaction temperature is 80°C, and the reaction time is 12-24 hours.

[0026] Preferably, the post-treatment method is filtration with diatomite, extraction with brine and ethyl acetate, and purification by silica gel column chromatography; more preferably, the eluent used is ethyl acetate and petroleum ether system (ethyl acetate: petroleum ether = 1:2-1:4, V / V).

[0027] Finally, a3 is reduced to the corresponding aldehyde under the action of morpholine and a reducing agent under an inert atmosphere. After quenching after the reaction is completed, the compound is obtained as white crystals a4 through post-treatment.

[0028] Preferably, the inert atmosphere is nitrogen atmosphere, and the reducing agent is diisobutylaluminum hydride.

[0029] Preferably, the molar ratio of a3, the reducing agent and morpholine is 1:7-9:7.2-9.2, more preferably, the molar ratio is 1:8:8.2.

[0030] Preferably, the reduction reaction is carried out in anhydrous solvent, more preferably in anhydrous tetrahydrofuran.

[0031] Preferably, the feeding order of the reaction is that morpholine is dissolved in the solvent, then the reducing agent is added, and finally a3 is added.

[0032] Preferably, the reaction mixture is reacted at low temperature, more preferably, the reaction temperature is 0°C.

[0033] Preferably, the quenching method is stirring after adding acid and solvent, more preferably, the acid is dilute hydrochloric acid and the solvent is diethyl ether.

[0034] Preferably, the post-treatment method is purification by silica gel column chromatography after extraction with ethyl acetate; more preferably, the eluent used is an ethyl acetate and petroleum ether system (ethyl acetate: petroleum ether = 1:1-2:1, V / V).

[0035] The structures of the axially chiral bipyridine monomers b4 and c4 are as follows: The reaction processes are as follows:

[0036]

[0037] The preparation steps of the monomers include:

[0038] Under an inert atmosphere, nucleophilic substitution reaction of (2R, 3R)-butanediol with acyl chloride is carried out, and after post-treatment, b1 is obtained. Nucleophilic substitution reaction of (2R, 5R)-hexane-2, 5-diol with acyl chloride is carried out, and after post-treatment, c1 is obtained.

[0039] Preferably, the inert atmosphere is a nitrogen atmosphere, and the acyl chlorides are p-toluenesulfonyl chloride and methanesulfonyl chloride, respectively.

[0040] Preferably, the molar ratio of the diol to acyl chloride is 1:2-3, more preferably, the molar ratio is 1:2.5.

[0041] Preferably, the solvents for the nucleophilic substitution reactions are pyridine and dichloromethane, respectively.

[0042] Preferably, the reaction temperature is feeding at -20-0°C and warming to room temperature.

[0043] Preferably, the post-treatment method of the monomer b1 is removing pyridine under reduced pressure, dissolving the residue in dichloromethane, washing with ammonia water, dilute hydrochloric acid, and brine, drying with anhydrous sodium sulfate, evaporating the solvent, and purifying the residue by silica gel column chromatography. More preferably, the eluent used is an ethyl acetate and petroleum ether system (ethyl acetate: petroleum ether = 1:3-1:5, V / V). The post-treatment method of the monomer c1 is extracting with dichloromethane after adding dilute hydrochloric acid. The organic layer is washed with saturated sodium bicarbonate aqueous solution and dried with anhydrous sodium sulfate. After filtration and evaporation of the solvent, the crude product (2R, 5R)-hexane-2, 5-dimethyl methanesulfonate is obtained. More preferably, the concentration of the dilute hydrochloric acid is 1-2M.

[0044] b1 or c1 undergoes SN2 substitution reaction with a1 under inert atmosphere in the presence of NaH in a solvent, and after washing, extraction, drying, and evaporation of the solvent, white solid b2 or c2 is obtained by silica gel column purification.

[0045] Preferably, the inert atmosphere is a nitrogen atmosphere, and the reaction solvent is DMF.

[0046] Preferably, the washing agent is a sodium hydroxide aqueous solution, and the extraction solvent is dichloromethane; more preferably, the concentration of the sodium hydroxide aqueous solution is 1-2 M.

[0047] Preferably, the eluent for the silica gel column purification is an ethyl acetate and petroleum ether system (ethyl acetate: petroleum ether = 1:3-1:5, V / V).

[0048] b2 or c2 undergoes Ullmann coupling reaction under the action of a copper catalyst under inert atmosphere, and after the reaction is completed, the compound is obtained as white crystals b3 or c3 after post-treatment.

[0049] Preferably, the inert atmosphere is a nitrogen atmosphere, and the copper catalyst is thiophene-2-carboxylic acid cuprous.

[0050] Preferably, the molar amount ratio of b2 or c2 to the copper catalyst is 1:3.

[0051] Preferably, the Ullmann coupling reaction is carried out in N-methylpyrrolidone solvent, the reaction temperature is room temperature, and the reaction time is 24-72 hours.

[0052] Preferably, the post-treatment method is washing with brine followed by purification by silica gel column chromatography; more preferably, the eluent used is an ethyl acetate and petroleum ether system (ethyl acetate: petroleum ether = 1:2-1:4, V / V).

[0053] Finally, b3 or c3 is reduced to the corresponding aldehyde under the action of morpholine and a reducing agent under inert atmosphere. After quenching after the reaction is completed, the compound is obtained as white crystals b4 or c4 after post-treatment.

[0054] Preferably, the inert atmosphere is a nitrogen atmosphere, and the reducing agent is diisobutylaluminum hydride.

[0055] Preferably, the molar amount ratio of b3, c3, the reducing agent, and morpholine is 1:7-9:7.2-9.2, and more preferably, the molar amount ratio is 1:8:8.2.

[0056] Preferably, the reduction reaction is carried out in anhydrous solvent, and more preferably, in anhydrous tetrahydrofuran.

[0057] Preferably, the order of feeding the reaction is to dissolve morpholine in the solvent, then add the reducing agent, and finally add b3 or c3.

[0058] Preferably, the reaction mixture is reacted at low temperature, more preferably, the reaction temperature is 0℃.

[0059] Preferably, the quenching method is stirring after adding acid and solvent, more preferably, the acid is dilute hydrochloric acid and the solvent is diethyl ether.

[0060] Preferably, the post-treatment method is purification by silica gel column chromatography after extraction with ethyl acetate; more preferably, the eluent used is an ethyl acetate and petroleum ether system (ethyl acetate: petroleum ether = 1:1-2:1, V / V).

[0061] The second aspect of the application provides a method for synthesizing a covalent organic framework material, which specifically comprises the following steps:

[0062] The axially chiral bipyridine aldehyde-based monomer a4, b4 or c4, the polyamino-substituted functional monomer, the solvent and the catalyst are mixed and placed in a reaction device, and the reaction device is subjected to liquid nitrogen degassing and sealing treatment.

[0063] The structure of the polyamino-substituted monomer is as follows:

[0064]

[0065] Preferably, the solvent is a mixed solvent of solvent A and solvent B, the solvent A is o-dichlorobenzene or n-butanol, the solvent B is at least one of mesitylene and dioxane, the volume ratio of the solvent A to the solvent B is 1:(1-5); the catalyst is an aqueous acetic acid solution with a concentration of 3-9 mol / L, and the heating reaction time is 3-7 days.

[0066] Preferably, the reaction device is a thick-walled pressure-resistant glass tube; the liquid nitrogen degassing and sealing treatment comprises: sequentially subjecting the thick-walled pressure-resistant glass tube to liquid nitrogen freezing, vacuumizing and thawing, and after 3 cycles, sealing the tube by tightly screwing a cock under vacuum.

[0067] The reaction device obtained in the above step is placed in a constant-temperature heating device, and the substances in the mixed system are subjected to a Schiff base reaction to obtain a reaction system; the reaction system is unsealed from the reaction device and sequentially subjected to filtration and washing to obtain the chiral covalent organic framework material.

[0068] Preferably, the temperature of the Schiff base reaction is 90-130℃; the time of the Schiff base reaction is 72-120 hours.

[0069] Preferably, the number of washing times is 2-5 times, and the washing liquid is dichloromethane, tetrahydrofuran, methanol or ethanol, acetone, etc.

[0070] The third aspect of the present application provides a preparation method of a metal heterogeneous catalyst based on a chiral covalent organic framework material.

[0071] A metal palladium heterogeneous catalyst based on a chiral covalent organic framework material is prepared by complexing reaction of palladium acetate and the chiral covalent organic framework material in a solvent, and then filtering and washing.

[0072] Preferably, the molar ratio of the palladium acetate to the chiral covalent organic framework compound is 1:(0.5-1).

[0073] Preferably, the temperature of the complexing reaction is 15-50℃, and the time of the complexing reaction is 12-24 hours.

[0074] Preferably, the solvent is dichloromethane.

[0075] A metal copper heterogeneous catalyst based on a chiral covalent organic framework material is prepared by complexing reaction of cuprous iodide and the chiral covalent organic framework material in a solvent, and then filtering and washing.

[0076] Preferably, the molar ratio of the cuprous iodide to the chiral covalent organic framework compound is 1:(0.5-1).

[0077] Preferably, the temperature of the complexing reaction is 15-50℃, and the time of the complexing reaction is 12-24 hours.

[0078] Preferably, the solvent is acetonitrile.

[0079] The fourth aspect of the present application provides the application of the metal heterogeneous catalyst based on a chiral covalent organic framework material as a catalyst for C-H activation reaction, arylization reaction and 1,4 addition reaction.

[0080] Preferably, the C-H activation reaction is carried out by reacting a substrate and the chiral heterogeneous catalyst containing metal palladium or metal copper in a mixed solvent.

[0081] Preferably, the substrate of the C-H activation reaction has the following structural formula:

[0082] Preferably, the solution of the C-H activation reaction is a well-soluble organic solvent. More preferably, the organic solvent is dichloromethane, chloroform, tetrahydrofuran or toluene.

[0083] Preferably, the temperature of the C-H activation reaction is 0-100℃, preferably 20-50℃, and further preferably 30℃.

[0084] Preferably, the arylization reaction is carried out by reacting the substrate and the chiral heterogeneous catalyst containing metal palladium or metal copper in a mixed solvent.

[0085] Preferably, the substrate of the arylization reaction has the structural formula

[0086] Preferably, the solution of the arylization reaction is a well-soluble organic solvent. More preferably, the organic solvent is dichloromethane, trifluoroethanol.

[0087] Preferably, the temperature of the arylization reaction is 0-100℃, preferably 0-30℃, and further preferably 0℃.

[0088] Preferably, the 1,4-addition reaction is carried out by reacting the substrate and the chiral heterogeneous catalyst containing metal palladium in a mixed solvent.

[0089] Preferably, the substrate of the 1,4-addition reaction has the structural formula

[0090] Preferably, the solution of the 1,4-addition reaction is a well-soluble organic solvent. More preferably, the organic solvent is a mixed solvent of acetic acid, tetrahydrofuran and water.

[0091] Preferably, the temperature of the 1,4-addition reaction is 0-100℃, preferably 30-80℃, and further preferably 50℃.

[0092] The beneficial effects of the technical solution of the present application are as follows: the present application successfully synthesizes a series of axially chiral bipyridine aldehyde monomers: these monomers have a unique axially chiral structure, providing key precursor support for subsequent preparation of chiral covalent organic framework materials (COFs). At the same time, the present application develops a new type of chiral covalent organic framework material: the material exhibits excellent physical and chemical stability, can maintain the integrity of its structure and function under a variety of environmental conditions, and has wide application potential. Through direct synthesis, chiral sites can be uniformly loaded on the covalent organic framework, ensuring the consistency and efficiency of the chiral function of the material, and providing high-quality material basis for the field of chiral catalysis, separation, etc.

[0093] Specifically:

[0094] (1) The preparation raw material of the chiral covalent organic framework material of the present application is cheap, the preparation condition is simple, has the advantages of low preparation cost and large amount of preparation.

[0095] (2) The chiral covalent organic framework material can complex metal to form a heterogeneous catalyst. In C-H activation reaction, arylization reaction and 1,4 addition reaction, the metal heterogeneous catalyst based on the chiral covalent organic framework in the application can effectively asymmetrically catalyze intramolecular addition of the substrate, the recyclable characteristics can reduce the production cost, and has good industrial application prospect, instead of expensive and difficult to recycle homogeneous catalyst, and reduces the loss of metal. BRIEF DESCRIPTION OF DRAWINGS

[0096] Figure 1 is the nuclear magnetic hydrogen spectrum of the axially chiral aldehyde monomer a4 prepared in Example 1;

[0097] Figure 2 is the circular dichroism spectrum of the axially chiral aldehyde monomer a4 prepared in Example 1;

[0098] Figure 3 is the X-ray powder diffraction pattern of the chiral organic covalent framework material prepared in Example 1;

[0099] Figure 4 is the infrared spectrum of the chiral organic covalent framework material prepared in Example 1;

[0100] Figure 5 is the circular dichroism spectrum of the chiral organic covalent framework material prepared in Example 1;

[0101] Figure 6 is the nuclear magnetic hydrogen spectrum of the axially chiral aldehyde monomer b4;

[0102] Figure 7 is the nuclear magnetic hydrogen spectrum of the axially chiral aldehyde monomer c4;

[0103] Figure 8 is the nuclear magnetic hydrogen spectrum of the product of Example 4;

[0104] Figure 9 is the liquid chromatography separation diagram of the enantiomeric product obtained by using the chiral organic covalent framework material prepared in the application to load palladium or copper metal for asymmetric catalytic C-H activation reaction;

[0105] Figure 10 is the nuclear magnetic hydrogen spectrum of the product of Example 5;

[0106] Figure 11 is the liquid chromatography separation diagram of the enantiomeric product obtained by using the chiral organic covalent framework material prepared in the application to load palladium metal for asymmetric arylization reaction;

[0107] Figure 12 is the yield and ee value of the product after the catalyst in the embodiment of the application is recycled for 5 times

[0108] Figure 13 is the product of Example 6 nuclear magnetic hydrogen spectrum;

[0109] Figure 14 is the liquid chromatogram of the enantiomeric product obtained by asymmetric catalytic 1,4 addition reaction of the chiral organic covalent framework material loaded with palladium metal prepared by the present application. DETAILED DESCRIPTION

[0110] The technical solutions in the embodiments of the present application will be described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all the other embodiments obtained by those skilled in the art without creative work fall within the scope of protection of the present application.

[0111] Herein, the special word "embodiment" as "exemplary" explained any embodiment does not have to be interpreted as superior or better than other embodiments. In the performance index test of the embodiments of the present application, unless otherwise specified, the conventional test method in the art is adopted. It should be understood that the terms described in the present application are only for describing the specific embodiments, and are not used to limit the disclosure of the present application.

[0112] Unless otherwise specified, the technical and scientific terms used herein have the same meanings as generally understood by those skilled in the art to which the present application belongs; as the test methods and technical means not specially noted in the present application are the experimental methods and technical means generally used by those skilled in the art.

[0113] In order to better illustrate the content of the present application, a large number of specific details are given in the specific embodiments below. Those skilled in the art should understand that the present application can also be implemented without some specific details. In the embodiments, some methods, means, instruments, equipment and the like which are well known to those skilled in the art are not described in detail, in order to highlight the main idea of the present application. The technical features disclosed in the embodiments of the present application can be combined arbitrarily, provided that they do not conflict, and the technical solutions obtained belong to the disclosure of the embodiments of the present application.

[0114] In order to better understand the present application, the present application will be further specifically described by the following embodiments, but it should not be understood as limiting the present application. Some non-essential improvements and adjustments made by those skilled in the art according to the above disclosure of the present application are also regarded as falling within the scope of protection of the present application.

[0115] Example 1: A new preparation method of chiral covalent organic framework material, the specific implementation steps are as follows: Step one, preparation of axially chiral bipyridine aldehyde monomer

[0116]

[0117] Ethyl 5-hydroxy nicotinate (1.67 g, 10 mmol), iodine (2.79 g, 11 mmol) and sodium carbonate (2.65 g, 25 mmol) were dispersed in 50 mL of deionized water. After 5 hours of reaction at 25 °C, the solution was acidified with dilute hydrochloric acid, and the pH was adjusted to 2. Yellow solids were precipitated from the solution, which were collected by suction filtration, washed with deionized water, dried and 1.52 g (5.2 mmol) was used in the next step. The above product and (2R,4R)-pentanediol (260 mg, 2.5 mmol), triphenylphosphine (1.57 g, 6 mmol) were dissolved in anhydrous tetrahydrofuran (10 mL) under nitrogen atmosphere and stirred at 0 °C for 10 minutes. Diisopropyl azodicarboxylate (1.21 g, 6 mmol) was added dropwise to the above solution within 30 minutes. After the addition, the reaction temperature was slowly increased to room temperature and continued to stir for 28 hours. The solvent was removed and further purified by silica gel column chromatography using ethyl acetate and petroleum ether system (ethyl acetate: petroleum ether = 1:3, V / V) as eluent to obtain compound a2. a2 (654 mg, 1 mmol), copper powder (318 mg, 5 mmol) were added to 5 mL of dimethyl sulfoxide and heated to 80 °C and continued to react for 20 hours under nitrogen atmosphere. After filtration through celite, extraction with ethyl acetate and brine, further purification by silica gel column chromatography using ethyl acetate and petroleum ether system (ethyl acetate: petroleum ether = 1:3, V / V) as eluent to obtain compound a3. Morpholine (428 mg, 4.92 mmol) was dissolved in 4 mL of anhydrous tetrahydrofuran and stirred at 0 °C for 10 minutes under nitrogen atmosphere, and 4.8 mL of diisobutylaluminum hydride (1.0 M solution) was added dropwise to the solution, and a3 (240 mg, 0.6 mmol) was added. After stirring at 0 °C for 10 minutes, the reaction was quenched with 10 mL of 1 M dilute hydrochloric acid and 20 mL of ether, and the aqueous phase was extracted with ethyl acetate and then purified by silica gel column chromatography using ethyl acetate and petroleum ether system (ethyl acetate: petroleum ether = 2:1, V / V) as eluent to obtain compound a4.

[0118] Figure 1 is the nuclear magnetic resonance spectrum of the axially chiral aldehyde-based framework monomer a4 in Example 1. Figure 2 is the circular dichroism spectrum of the axially chiral aldehyde-based framework monomer a4 in Example 1. As shown in Figure 1 , the two hydrogen atoms of the aldehyde group, the hydrogen atoms on the pyridine ring, the methylene hydrogen on the alkyl chain, and the methyl hydrogen atoms are shown in the nuclear magnetic resonance spectrum, proving the successful synthesis of the compound. As shown in Figure 2 , the circular dichroism spectrum shows that the axially chiral aldehyde-based monomer a4 has obvious optical properties.

[0119] Step two, preparation of chiral covalent organic framework material

[0120] In the thick-walled pressure tube, add tetra(4-aminophenyl)methane (19 mg, 0.05 mmol) or tetra(4-aminophenyl)porphyrin (34 mg, 0.05 mmol), chiral aldehyde-based monomer a4 (31 mg, 0.1 mmol), n-butanol 0.4 mL, mesitylene 1.6 mL, ultrasonic for 10 minutes, then add 0.2 mL of 3M acetic acid aqueous solution and ultrasonic for another 10 minutes, and after three cycles of liquid nitrogen freezing, vacuumizing, thawing and vacuumizing, seal the tube by tightening the stopcock under vacuum, and after warming to room temperature, heat at 120°C for 5 days, unseal, vacuum filter, and then wash with acetone, acetonitrile, and methanol successively, and vacuum dry to obtain a 3D chiral covalent organic framework material or a 2D chiral covalent organic framework material, and the structural formulas are as follows:

[0121]

[0122] Figure 3 is the powder X-ray diffraction pattern of the 3D chiral covalent organic framework in Example 1. Figure 4 is the infrared spectrum of the 3D chiral covalent organic framework in Example 1. Figure 5 is the circular dichroism spectrum of the 3D chiral covalent organic framework in Example 1. As shown in Figure 3 , the powder X-ray diffraction pattern shows that the chiral covalent organic framework in the example has good crystallinity, and the diffraction peaks are not substantially changed after loading metal. As shown in Figure 4 , the infrared spectrum shows the N-H peak of the amino monomer and the C=O vibration peak of the aldehyde-based monomer, and an obvious C=N bond stretching vibration peak is generated, indicating the successful preparation of the chiral covalent organic framework. As shown in Figure 5 , the circular dichroism spectrum shows that the chiral covalent organic framework has optical activity in the ultraviolet band.

[0123] Step three, loading metal palladium or metal copper on the chiral covalent organic framework to obtain a single-atom metal catalyst with chiral catalytic sites

[0124] Dissolve palladium acetate (11 mg, 0.048 mmol) in dichloromethane, and add the 3D chiral covalent organic framework (25 mg, 0.026 mmol) or 2D chiral covalent organic framework (32 mg, 0.026 mmol) prepared in step two to the above solution and stir at 25°C for 24 hours. After the reaction is completed, vacuum filter and wash with dichloromethane several times, and dry to obtain a chiral single-atom metal catalyst loaded with metal palladium, and the structural formulas are as follows:

[0125]

[0126] Cuprous iodide (9 mg, 0.047 mmol) was dissolved in acetonitrile, and the 3D chiral covalent organic framework (25 mg, 0.026 mmol) or 2D chiral covalent organic framework (32 mg, 0.026 mmol) prepared in step two was added to the above solution and stirred at 25°C for 24 hours. After the reaction was completed, it was suction filtered and washed with solvents such as acetonitrile and methanol several times, and after drying, the chiral single-atom metal catalyst loaded with copper metal was obtained, and the structural formulae are as follows:

[0127]

[0128] Example 2: A preparation method of a new type of chiral covalent organic framework material, and the specific implementation steps are as follows: step one, preparing an axially chiral aldehyde-based framework monomer

[0129]

[0130] To a solution of 5-hydroxy nicotinic acid ethyl ester (1.67 g, 10 mmol), iodine (2.79 g, 11 mmol) and sodium carbonate (2.65 g, 25 mmol) in 50 mL of deionized water was stirred at 25 °C for 5 hours. The reaction mixture was acidified with dilute hydrochloric acid and the pH was adjusted to 2. A yellow solid was precipitated from the solution. The yellow solid was filtered, washed with deionized water and dried. 1.17 g (4 mmol) of the yellow solid was used in the next step. To a solution of p-toluenesulfonyl chloride (4.78 g, 25 mmol) in 15 mL of pyridine was stirred at 0 °C. (2R, 4R)-butanediol (901 mg, 10 mmol) was added to the solution. The reaction mixture was stirred at room temperature overnight. The pyridine was removed under reduced pressure. The residue was dissolved in dichloromethane and washed with 15 mL of aqueous ammonia, 20 mL of 1 M hydrochloric acid and 20 mL of brine successively. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated and the residue was purified by silica gel column chromatography using a mixture of ethyl acetate and petroleum ether (ethyl acetate: petroleum ether = 1:3, V / V) as eluent to give (2R, 3R)-butane-2,3-diyl (4-methylbenzenesulfonate) b1. To a solution of a1 (1.17 g, 4 mmol) in 10 mL of DMF was stirred at 0 °C for 15 min. Sodium hydride (60% dispersion in mineral oil, 0.38 g, 9.6 mmol) was added to the solution. The reaction mixture was stirred at 0 °C for another 15 min. b1 (3.59 g, 9 mmol) was added to the solution. The reaction mixture was heated to 80 °C until the reaction was completed (24 hours). The solvent was removed under reduced pressure. The residue was dissolved in dichloromethane and washed with aqueous sodium hydroxide (1 M, 10 mL x 3). The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated and the residue was purified by silica gel column chromatography using a mixture of ethyl acetate and petroleum ether (ethyl acetate: petroleum ether = 1:3, V / V) as eluent to give compound b2. To a solution of b2 (640 mg, 1 mmol) and cuprous thiophene-2-carboxylate (570 mg, 3 mmol) in 5 mL of NMP was stirred at room temperature for 24 hours. The reaction mixture was dissolved in ethyl acetate and washed with brine three times. The organic layer was further purified by silica gel column chromatography using a mixture of ethyl acetate and petroleum ether (ethyl acetate: petroleum ether = 1:3, V / V) as eluent to give compound b3. To a solution of morpholine (428 mg, 4.92 mmol) in 4 mL of anhydrous tetrahydrofuran was stirred at 0 °C for 10 min. Diisobutylaluminum hydride (4.8 mL) was added to the solution. b3 (232 mg, 0.6 mmol) was added to the solution. The reaction mixture was stirred at 0 °C for another 10 min. The reaction was quenched with 10 mL of 1 M dilute hydrochloric acid and 20 mL of diethyl ether. The aqueous layer was extracted with ethyl acetate and purified by silica gel column chromatography using a mixture of ethyl acetate and petroleum ether (ethyl acetate: petroleum ether = 2:1, V / V) as eluent to give compound b4.

[0131] Figure 6 NMR spectrum of the axially chiral aldehyde-based framework monomer b4 in Example 2.

[0132] Step two, preparation of chiral covalent organic framework material

[0133] In a thick-walled pressure tube, add tetra(4-aminophenyl)methane (19 mg, 0.05 mmol) or tetra(4-aminophenyl)porphyrin (34 mg, 0.05 mmol), chiral aldehyde-based monomer b4 (29.8 mg, 0.1 mmol), n-butanol 0.4 mL, mesitylene 1.6 mL, after ultrasonic for 10 minutes, add 0.2 mL of 3M acetic acid aqueous solution and ultrasonic for another 10 minutes, and after three cycles of liquid nitrogen freezing, vacuumizing, thawing, and sealing the tube by tightening the stopcock under vacuum, heat to room temperature and heat at 120°C for 5 days, unseal, vacuum filter, and then wash successively with acetone, acetonitrile, and methanol solvents and vacuum dry to obtain a 3D chiral covalent organic framework material or a 2D chiral covalent organic framework material.

[0134] Step three, loading of chiral covalent organic framework with metal palladium or metal copper to obtain single-atom metal catalyst with chiral catalytic site

[0135] Dissolve palladium acetate (11 mg, 0.048 mmol) in dichloromethane, take the 3D chiral covalent organic framework (24 mg, 0.026 mmol) or 2D chiral covalent organic framework (31 mg, 0.026 mmol) prepared in step two and add to the above solution and stir at 25°C for 24 hours. After the reaction is completed, vacuum filter and wash with dichloromethane several times, and dry to obtain a chiral single-atom metal catalyst loaded with metal palladium.

[0136] Dissolve cuprous iodide (9 mg, 0.047 mmol) in acetonitrile, take the 3D chiral covalent organic framework (24 mg, 0.026 mmol) or 2D chiral covalent organic framework (31 mg, 0.026 mmol) prepared in step two and add to the above solution and stir at 25°C for 24 hours. After the reaction is completed, vacuum filter and wash with acetonitrile and methanol solvents several times, and dry to obtain a chiral single-atom metal catalyst loaded with metal copper, and the structural formulae are as follows:

[0137]

[0138] Example 3: A method for preparing a new type of chiral covalent organic framework material, and the specific implementation steps are as follows: Step one, preparation of axially chiral aldehyde-based framework monomer

[0139]

[0140] Ethyl 5-hydroxybenzoate (1.67 g, 10 mmol), iodine (2.79 g, 11 mmol) and sodium carbonate (2.65 g, 25 mmol) were dispersed in 50 mL of deionized water, and after 5 hours of reaction at 25 °C, acidified with dilute hydrochloric acid, adjusting the pH to 2, a yellow solid precipitated from the solution, which was filtered, washed with deionized water and dried. 1.52 g (5.2 mmol) was used in the next step. A solution of (2R,5R)-hexane-2,5-diol (0.808 g, 6.8 mmol) and triethylamine (3.80 mL, 27.3 mmol) in dichloromethane (10 mL) was cooled to -20 °C. Methanesulfonyl chloride (2.349 g, 20.5 mmol) was added dropwise, maintaining the temperature between -20 and -15 °C. After completing the addition, the reaction mixture was allowed to warm to room temperature and stirred overnight. 30 mL of 2.0 M hydrochloric acid solution were added and extracted with dichloromethane (15 mL x 3 times). After separating the organic layer, it was washed with saturated aqueous sodium bicarbonate solution (20 mL) and dried over anhydrous sodium sulfate. After filtering and evaporating the solvent, a red oil was obtained (2R,5R)-hexane-2,5-diyl bis methanesulfonate cl. This crude product was used without further purification. Next, al (1.52 g, 5.2 mmol) was dispersed in 10 mL of DMF and stirred at 0 °C for 15 min, after which sodium hydride (60% dispersion in mineral oil, 0.38 g, 9.6 mmol) was added. After continuing to stir at 0 °C for 15 minutes, the crude product cl was added through a dropping funnel. Subsequently, the reaction mixture was heated to 80 °C until the reaction was complete (24 hours). After evaporating the solvent under reduced pressure, the residue was dissolved in dichloromethane, washed with aqueous sodium hydroxide solution (1 M, 10 mL x 3) and dried over anhydrous sodium sulfate. After evaporating the solvent, the compound c2 was purified by column chromatography on silica gel using a system of ethyl acetate and petroleum ether (ethyl acetate: petroleum ether = 1:3, V / V) as eluent. In a nitrogen atmosphere, b2 (640 mg, 1 mmol) and cuprous thiophene-2-carboxylate (570 mg, 3 mmol) were added to 5 mL of NMP and stirred at room temperature for 24 hours. After dissolving in ethyl acetate and washing with brine three times, the compound c3 was further purified by column chromatography on silica gel using a system of ethyl acetate and petroleum ether (ethyl acetate: petroleum ether = 1:3, V / V) as eluent. In a nitrogen atmosphere, morpholine (428 mg, 4.92 mmol) was dissolved in 4 mL of anhydrous tetrahydrofuran and stirred at 0 °C for 10 minutes. 4.8 mL of diisobutylaluminum hydride was added to the solution and c3 (232 mg, 0.6 mmol) was added.After stirring for 10 minutes at 0°C, the reaction was quenched with 10 mL of 1 M dilute hydrochloric acid and 20 mL of diethyl ether, the aqueous phase was extracted with ethyl acetate and then purified by silica gel column chromatography using a system of ethyl acetate and petroleum ether (ethyl acetate: petroleum ether = 2:1, V / V) as the eluent to obtain compound c4.

[0141] Figure 7 The nuclear magnetic resonance spectrum of the chiral aldehyde-based framework monomer c4 in Example 3.

[0142] Step two, preparation of a chiral covalent organic framework material

[0143] In a thick-walled pressure tube, add tetra(4-aminophenyl)methane (19 mg, 0.05 mmol) or tetra(4-aminophenyl)porphyrin (34 mg, 0.05 mmol), chiral aldehyde-based monomer c4 (32.6 mg, 0.1 mmol), n-butanol 0.4 mL, mesitylene 1.6 mL, and after ultrasonic treatment for 10 minutes, add 0.2 mL of 3 M aqueous acetic acid and ultrasonic treatment for another 10 minutes. After three cycles of freezing in liquid nitrogen, vacuumizing, thawing, and sealing the tube by tightening the stopcock under vacuum, the temperature is raised to room temperature and heated at 120°C for 5 days. After unsealing, vacuum filtration, and washing with acetone, acetonitrile, and methanol in sequence, the 3D chiral covalent organic framework material or 2D chiral covalent organic framework material is obtained after vacuum drying.

[0144] Step three, loading of the chiral covalent organic framework with metal palladium or metal copper to obtain a single-atom metal catalyst with a chiral catalytic site

[0145] Dissolve palladium acetate (11 mg, 0.048 mmol) in dichloromethane, and add the 3D chiral covalent organic framework (26 mg, 0.026 mmol) or 2D chiral covalent organic framework (33 mg, 0.026 mmol) prepared in step two to the above solution and stir at 25°C for 24 hours. After the reaction is completed, vacuum filtration and multiple washings with dichloromethane are performed, and the chiral single-atom metal catalyst loaded with metal palladium is obtained after drying.

[0146] Dissolve cuprous iodide (9 mg, 0.047 mmol) in acetonitrile, and add the 3D chiral covalent organic framework (26 mg, 0.026 mmol) or 2D chiral covalent organic framework (33 mg, 0.026 mmol) prepared in step two to the above solution and stir at 25°C for 24 hours. After the reaction is completed, vacuum filtration and multiple washings with solvents such as acetonitrile and methanol are performed, and the chiral single-atom metal catalyst loaded with metal copper is obtained after drying. The structural formulas are as follows:

[0147]

[0148] Example 4: Application of chiral covalent organic framework catalysts supported with palladium or copper in C-H activation asymmetric catalytic reaction, the reaction formula is as follows:

[0149] The specific implementation steps are as follows:

[0150] The 3DCCOF-Pd / 3DCCOF-Cu (10 mg, 0.015 mmol) of Example 1 and NaBArF (31.9 mg, 0.036 mmol, 12.0 mol%) were added to an oven-dried Schlenk tube under nitrogen protection. After adding dichloromethane (3.0 mL) into the Schlenk tube, the mixture was stirred at 30°C for 2 hours under nitrogen protection. Then, compound 2 (0.45 mmol, 1.5 equivalents) and compound 1 (0.30 mmol, 1.0 equivalent) were added at one time. The resulting mixture was continuously stirred at 30°C until compound 1 was completely consumed. After filtration and removal of the solvent under reduced pressure, the product was separated by flash silica gel column chromatography (petroleum ether / ethyl acetate = 30:1, v / v).

[0151] Figure 8 is the nuclear magnetic resonance spectrum of the product in Example 4. Figure 9 is the liquid chromatography separation diagram of the enantiomeric product obtained by using the chiral covalent organic framework material supported with palladium metal prepared in this example in the asymmetric catalytic C-H activation reaction. As shown in Figure 8 , the nuclear magnetic hydrogen spectrum shows that the indole-3-acetate derivative product of the C-H activation reaction is successfully prepared in this example. As shown in Figure 9 , the enantioselectivity of the product is characterized by high performance liquid chromatography, and the ee value of the enantiomeric product obtained in this example reaches 53%.

[0152] Example 5: Application of chiral covalent organic framework catalysts supported with palladium in enantioselective arylation reaction, the reaction formula is as follows:

[0153]

[0154] The specific implementation steps are as follows:

[0155] In a Schlenk tube, 3DCCOF-Pd (10 mg, 0.015 mmol) of Example 1, compound 1 (58.8 mg, 0.2 mmol) and compound 2 (36.5 mg, 0.3 mmol) were added, trifluoroethanol was added to stir and dissolve and react at room temperature until the N-tosyl imine was completely consumed. After filtration and removal of the solvent under reduced pressure, the product was separated by flash column chromatography on silica gel (petroleum ether / ethyl acetate = 6:1, v / v). The resulting powder was washed with dichloromethane and dried in an oven to recover the catalyst 3DCCOF-Pd efficiently. The recovered 3DCCOF-Pd can still catalyze the enantioselective arylation reaction as described above.

[0156] Figure 10 is the nuclear magnetic resonance spectrum of the product in Example 5.

[0157] Figure 11 is the liquid chromatogram of the enantiomeric product obtained after the enantioselective reaction catalyzed by the chiral organic covalent framework material loaded with palladium metal.

[0158] Figure 12 is the yield and ee value of the product after 5 cycles of recycling experiments of the catalyst in Example 5.

[0159] As shown in Figure 10 , the nuclear magnetic hydrogen spectrum shows that the product of the arylation reaction is successfully prepared in this example. As shown in Figure 11 , the enantioselectivity of the product is characterized by high performance liquid chromatography, and the ee value of the enantiomeric product obtained in this example reaches 81%.

[0160] As shown in Figure 12 , the activity of the catalyst remains good after 5 cycles of recycling experiments.

[0161] Example 6: Application of chiral covalent organic framework catalyst loaded with palladium in 1,4 asymmetric addition reaction, the reaction formula is as follows:

[0162]

[0163] The specific implementation steps are as follows:

[0164] In a Schlenk tube, 3DCCOF-Pd (10 mg, 0.015 mmol) of Example 1, compound 1 (19.23 mg, 0.2 mmol) and compound 2 (48.8 mg, 0.4 mmol) were added under nitrogen atmosphere, acetic acid, tetrahydrofuran and water (volume ratio of 0.5:0.25:0.15) were added to stir and dissolve and react at 50-60 °C until 2-cyclohexen-1-one was completely consumed. After filtration and removal of the solvent under reduced pressure, the product was separated by flash silica gel column chromatography (petroleum ether / ethyl acetate = 10:1, v / v).

[0165] Figure 13 is the nuclear magnetic resonance spectrogram of the product in Example 6. Figure 14 is the liquid chromatogram of the enantiomeric product obtained after the chiral organic covalent framework material loaded with palladium metal was used for enantioselective separation. As shown in Figure 13 , the nuclear magnetic hydrogen spectrum shows that the product of the arylation reaction is successfully prepared in this example. As shown in Figure 14 , the enantioselectivity of the product is characterized by high performance liquid chromatography, and the ee value of the enantiomeric product obtained is 23%.

Claims

1. A method for preparing a novel chiral covalent organic framework material, characterized in that, The process includes the following steps: a chiral diol undergoes a Mitsunobo or SN2 reaction with ethyl iodohydroxynicotinate, followed by Ullmann coupling and reduction to obtain an axially chiral bipyridine aldehyde monomer, which is then reacted with a polyamino-substituted monomer under solvothermal conditions via a Schiff base reaction to prepare a chiral covalent organic framework material.

2. The method for preparing a novel chiral covalent organic framework material according to claim 1, characterized in that, The structural formula of the chiral diol is as follows: The structural formula of ethyl iodohydroxynicotinic acid is as follows: The structural formula of the axially chiral bipyridine aldehyde monomer is as follows: The structural formulas of polyamino-substituted monomers are as follows:

3. The method for preparing a novel chiral covalent organic framework material according to claim 2, characterized in that, The solvothermal conditions are as follows: the reaction is carried out under heating in the presence of a first solvent and a catalyst. The first solvent is a mixture of solvent A and solvent B. Solvent A is o-dichlorobenzene or n-butanol, and solvent B is at least one of mesitylene or dioxane. The volume ratio of solvent A to solvent B is 1:1-5. The catalyst is an aqueous solution of acetic acid with a concentration of 3-9 mol / L. The heating reaction time is 3-7 days.

4. The method for preparing a novel chiral covalent organic framework material according to claim 3, characterized in that, Specifically, the steps include the following: S1: Chiral diols are reacted with ethyl iodohydroxynicotinate via Mitsunobo or SN2 reaction, Ullmann coupling and reduction to obtain axially chiral bipyridine aldehyde monomers. S2: The axially chiral bipyridine aldehyde monomer, the polyamino-substituted monomer, the first solvent and the catalyst are mixed and placed in the reaction equipment, and the reaction equipment is degassed and sealed with liquid nitrogen. S3: Place the reaction equipment obtained in step S2 into a constant temperature heating device, and carry out the Schiff base reaction of the substances in the mixed system to obtain the reaction system. Unseal the reaction system from the reaction equipment and filter and wash it in sequence to obtain the chiral covalent organic framework material.

5. The method for preparing a novel chiral covalent organic framework material according to claim 4, characterized in that, In step S1, When the chiral diol is The preparation process of axially chiral bipyridine aldehyde monomers is shown below: When the chiral diol is The preparation process of the axially chiral bipyridine aldehyde monomer is as follows: When the chiral diol is The preparation process of the axially chiral bipyridine aldehyde monomer is as follows: In step S2, the reaction equipment is a thick-walled pressure-resistant glass tube. The liquid nitrogen degassing and sealing process involves sequentially freezing the thick-walled pressure-resistant glass tube with liquid nitrogen, evacuating it, and thawing it. After three cycles, the stopcock is tightened under vacuum to seal the tube. In step S3, the Schiff base reaction temperature is 90-130℃, and the Schiff base reaction time is 72-120 hours; the washing is performed 2-5 times, and the washing solution is at least one of dichloromethane, tetrahydrofuran, methanol, ethanol, and acetone.

6. A novel chiral covalent organic framework material prepared by any one of the preparation methods described in claims 1-5.

7. An application of the novel chiral covalent organic framework material as described in claim 6, characterized in that, The process includes the following steps: a metal compound undergoes a complexation reaction with a chiral covalent organic framework material in a second solvent, and the metal-containing chiral covalent organic framework material is prepared by filtration and washing. This material is then used as a catalyst for CH activation, arylation, or 1,4 addition reactions.

8. The application as described in claim 7, characterized in that, The molar ratio of the metal compound to the chiral covalent organic framework compound is 1:0.5-1; the complexation reaction temperature is 15-50℃, and the complexation reaction time is 12-24 hours; the second solvent is a well-soluble organic reagent.

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