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

Abstract

The invention belongs to the technical field of separation materials, and particularly relates to a double-chiral covalent organic framework material as well as a preparation method and application thereof. Two sulfydryl-containing chiral molecules including a sulfydryl-containing saccharide-derived thioether chiral group and a sulfydryl-containing amino acid or peptide-derived thioether chiral group are introduced into the double-chiral covalent organic framework material, so that the number of chiral recognition sites is increased; the two chiral molecules have various recognition effects such as hydrogen-bond interaction and / or subject-object recognition effect and / or pi-pi interaction between the two chiral molecules and a chiral substance, are beneficial to separation of polar chiral compounds, have the advantages of stable chemical properties, controllable size, good mechanical stability and the like, and can be directly used as a chromatographic column stationary phase for separating the chiral substance.

Description

Technical Field

[0001] The present invention belongs to the technical field of separation materials, and particularly relates to a dual-chiral covalent organic framework material, a preparation method thereof, and an application thereof. Background Art

[0002] Chiral enantiomers often have significant differences in pharmacological effects and physiological activities. Therefore, chiral separation is extremely important in the fields of medicinal chemistry, clinical medicine, agricultural science, etc. In chiral separation technology, chiral stationary phase chromatography is the most applicable method for separating chiral substances. Among them, the chiral stationary phase, as the core of the chiral chromatographic column, has a great influence on chiral separation. Therefore, the preparation of highly efficient chiral materials is the key to improving the efficiency of chiral separation.

[0003] "Post-modification", as a common method for preparing chiral materials, is to introduce various chiral molecules into achiral materials to endow the materials with the ability of chiral separation. Currently, a variety of chiral molecules have been developed for constructing chiral materials, including supramolecules such as cyclodextrin, chiral biomolecules, and chiral organic small molecules, etc. Currently, the widely used separation materials are silica-based chiral composite materials, but their preparation processes are relatively complex, the use conditions are limited, and it is difficult to control the size. Therefore, it is necessary to develop a new type of easily prepared and controllable chiral material as the chiral chromatographic stationary phase to meet more chiral separation requirements. Covalent organic frameworks are porous materials with characteristics such as high stability, high specific surface area, and easy regulation and modification, and are suitable as chromatographic stationary phases. However, currently, the preparation of most chiral covalent organic frameworks used as chromatographic stationary phases is often relatively complex and time-consuming, most chiral modifications also require relatively harsh conditions, and the size is uncontrollable.

[0004] Therefore, it is of great significance to provide a covalent organic framework material with controllable size, which is beneficial to the separation of polar chiral compounds; and has a mild preparation process, is simple and fast to prepare. Summary of the Invention

[0005] The present invention aims to solve one or more of the above-mentioned technical problems existing in the prior art, and at least provides a beneficial choice. Specifically, the present invention provides a dual-chiral covalent organic framework material, which has controllable size and is beneficial to the separation of polar chiral compounds; and has a mild preparation process, is simple and fast to prepare.

[0006] Inventive concept of the present invention: In the present invention, two kinds of mercapto-containing chiral molecules, namely mercapto-containing sugar-derived thioether chiral groups and mercapto-containing amino acid or peptide-derived thioether chiral groups, are introduced into the covalent organic framework material. The number of chiral recognition sites increases, and there are multiple recognition effects such as hydrogen bonding and / or host-guest recognition and / or π-π interaction between the two chiral molecules and chiral substances, which is beneficial to the separation of polar chiral compounds. Moreover, it has the advantages of stable chemical properties, controllable size, and good mechanical stability, and can be directly used as a stationary phase of a chromatographic column for separating chiral substances.

[0007] Therefore, in the first aspect of the present invention, a dual-chiral covalent organic framework material is provided.

[0008] Specifically, the chemical structural formula of the dual-chiral covalent organic framework material is:

[0009]

[0010] The SR 1 includes a mercapto-containing sugar-derived thioether chiral group;

[0011] The SR 2 includes a mercapto-containing amino acid or peptide-derived thioether chiral group.

[0012] In the second aspect of the present invention, a preparation method of the dual-chiral covalent organic framework material described in the first aspect of the present invention is provided.

[0013] Specifically, the preparation method of the dual-chiral covalent organic framework material includes the following steps:

[0014] (1) Mix a covalent organic framework building block containing an amino group and a covalent organic framework building block containing an aldehyde group, and react to obtain intermediate product 1;

[0015] (2) Mix the intermediate product 1 obtained in step (1), an initiator, and a substance containing a first chiral group, and react to obtain intermediate product 2;

[0016] (3) Mix the intermediate product 2 obtained in step (2) and a substance containing a second chiral group, and react to prepare the dual-chiral covalent organic framework material;

[0017] The first chiral group in the substance containing the first chiral group includes a mercapto-containing sugar-derived thioether chiral group; the second chiral group in the substance containing the second chiral group includes a mercapto-containing amino acid or peptide-derived thioether chiral group.

[0018] Preferably, the covalent organic framework building block containing an amino group includes 1,3,5-tris(4-aminophenyl)benzene.

[0019] Preferably, the aldehyde group-containing covalent organic framework building unit includes tetrafluoroterephthalaldehyde and 1,4-dialdehyde-2,5-divinylbenzene.

[0020] Preferably, the molar ratio of the amino group-containing covalent organic framework building unit to the aldehyde group-containing covalent organic framework building unit is 1:(1-2); more preferably, the molar ratio of the amino group-containing covalent organic framework building unit to the aldehyde group-containing covalent organic framework building unit is 1:(1.3-1.6). For example, the molar ratio of the amino group-containing covalent organic framework building unit to the aldehyde group-containing covalent organic framework building unit includes but is not limited to 1:1.3, 1:1.4, 1:1.5 or 1:1.6.

[0021] Preferably, in the aldehyde group-containing covalent organic framework building unit, the molar ratio of 1,4-dialdehyde-2,5-divinylbenzene to tetrafluoroterephthalaldehyde is 1:(0.5-3); more preferably, the molar ratio of 1,4-dialdehyde-2,5-divinylbenzene to tetrafluoroterephthalaldehyde is 1:(0.8-2.5); for example, the molar ratio of 1,4-dialdehyde-2,5-divinylbenzene to tetrafluoroterephthalaldehyde includes but is not limited to 1:1, 1:1.5, 1:2 or 1:2.5.

[0022] Preferably, in step (1), the mixing further includes adding a catalyst and an organic solvent, and the volume ratio of the catalyst to the organic solvent is 1:(10-50); for example, the volume ratio includes but is not limited to 1:10, 1:20, 1:30, 1:40 or 1:50.

[0023] Preferably, the catalyst includes acetic acid.

[0024] Preferably, the concentration of the catalyst is 3-15 mol / L. For example, the concentration of the catalyst includes but is not limited to 3 mol / L, 6 mol / L, 9 mol / L, 12 mol / L or 15 mol / L.

[0025] Preferably, the organic solvent includes acetonitrile.

[0026] Preferably, in step (1), the temperature of the reaction is 10-40 °C; more preferably, the temperature of the reaction is 15-35 °C; for example, the temperature of the reaction includes but is not limited to 15 °C, 20 °C, 25 °C, 30 °C or 35 °C;

[0027] Preferably, in step (1), the reaction time is 12-72 h; more preferably, the reaction time is 18-30 h; for example, the reaction time includes but is not limited to 18 h, 19 h, 20 h, 21 h, 22 h, 23 h, 24 h, 25 h, 26 h, 27 h, 28 h, 29 h or 30 h.

[0028] Specifically, in step (1), the reaction is a Schiff base reaction.

[0029] Preferably, in step (1), after the reaction, washing and drying are further carried out, and preferably but not limited to washing with an ether solvent and a ketone solvent.

[0030] Preferably, in step (2), the substance containing the first chiral group includes at least one of perthiols-β-cyclodextrin, monothiol-β-cyclodextrin, and 5-thio-D-glucose.

[0031] Preferably, in step (2), the initiator includes a photoinitiator; more preferably, the photoinitiator includes benzoin dimethyl ether.

[0032] Preferably, in step (2), the molar ratio of the intermediate 1 to the substance containing the first chiral group is 1:(2-6); for example, the molar ratio includes but is not limited to 1:2, 1:3, 1:4, 1:5, or 1:6.

[0033] Preferably, in step (2), the mixing includes adding a solvent; more preferably, the solvent includes at least one of ethanol, N,N-dimethylformamide, acetone, ethyl acetate, toluene, tetrahydrofuran, and water.

[0034] Preferably, in step (2), the temperature of the reaction is 10-80°C; more preferably, the temperature of the reaction is 20-40°C; for example, the temperature of the reaction includes but is not limited to 20°C, 25°C, 30°C, 35°C, or 40°C.

[0035] Preferably, in step (2), the reaction time is 0.1-2 h; more preferably, the reaction time is 0.5-1.5 h, and for example, the reaction time includes but is not limited to 0.5 h, 1.0 h, or 1.5 h.

[0036] Preferably, in step (2), the reaction is carried out under light assistance.

[0037] Preferably, in step (2), after the reaction, washing and drying are further carried out, and preferably but not limited to washing with an amide solvent and an alcohol solvent.

[0038] Preferably, in step (3), the substance containing the second chiral group includes a thiol-containing chiral amino acid or peptide.

[0039] Preferably, in step (3), the molar ratio of the intermediate 2 to the substance containing the second chiral group is 1:(3-6); for example, the molar ratio of the intermediate 2 to the substance containing the second chiral group includes but is not limited to 1:3, 1:4, 1:5, or 1:6.

[0040] Preferably, in step (3), the temperature of the reaction is 0 - 40°C; more preferably, the temperature of the reaction is 5 - 30°C.

[0041] Preferably, in step (3), the reaction time is 7 - 16 h; more preferably, the reaction time is 8 - 12 h.

[0042] Preferably, in step (3), the mixing further includes adding a buffer solution.

[0043] Preferably, the buffer solution includes a phosphate buffer solution.

[0044] Preferably, in step (3), the reaction is carried out under an inert gas atmosphere, and the inert gas includes nitrogen.

[0045] Preferably, after the reaction in step (3), washing and drying are carried out, and preferably but not limited to washing with water and alcohol solvents.

[0046] The third aspect of the present invention provides an application of the chiral covalent organic framework material described in the first aspect of the present invention in separating chiral substances.

[0047] Compared with the prior art, the beneficial effects of the technical solution provided by the present invention are as follows:

[0048] (1) In the present invention, two mercapto - containing chiral molecules, namely mercapto - containing sugar - derived thioether chiral groups and mercapto - containing amino acid or peptide - derived thioether chiral groups, are introduced into the covalent organic framework material. The number of chiral recognition sites increases, and there are multiple recognition interactions such as hydrogen bonding and / or host - guest recognition and / or π - π interaction between the two chiral molecules and chiral substances, which is beneficial to the separation of polar chiral compounds. Moreover, it has the advantages of stable chemical properties, controllable size, and good mechanical stability, and can be directly used as the stationary phase of a chiral chromatographic column for separating chiral substances, showing good application prospects.

[0049] (2) In the present invention, a chiral covalent organic framework material with dual chirality is prepared by gradually modifying chiral groups through mild "post - modification" methods such as photo - assisted methods. The preparation method is simple, fast, has mild reaction conditions, and low cost. By controlling the dosage of the catalyst and / or the covalent organic framework building unit, the size of the covalent organic framework material can be controlled.

[0050] (3) By using a small amount of the chiral covalent organic framework material prepared in the present invention, effective separation of chiral compounds can be achieved, which can reduce costs. Description of the Drawings

[0051] Figure 1Schematic diagram of the preparation process flow of the dual-chiral covalent organic framework material in Example 1 of the present invention;

[0052] Figure 2 Infrared spectrum test chart of the products of steps (1), (2), and (3) in Example 1 of the present invention;

[0053] Figure 3 Scanning electron microscope image of the products of steps (1), (2), and (3) in Example 1 of the present invention;

[0054] Figure 4 Scanning electron microscope image of the covalent organic framework material microspheres in Examples 2-5 of the present invention;

[0055] Figure 5 Scanning electron microscope image of the product in Comparative Example 1 of the present invention;

[0056] Figure 6 X-ray diffraction pattern of the dual-chiral covalent organic framework material in Example 1 of the present invention before and after soaking in chemical reagents;

[0057] Figure 7 Separation chromatogram of the dual-chiral covalent organic framework material in Example 1 of the present invention for phenylalkanolic chiral compounds;

[0058] Figure 8 Separation chromatogram of the dual-chiral covalent organic framework material in Example 1 of the present invention for the drug intermediate (R) / (S)-ethyl mandelate;

[0059] Figure 9 Separation chromatogram of the dual-chiral covalent organic framework material in Example 1 of the present invention for the heterocyclic chiral compound (R) / (S)-indanol. Detailed implementation manners

[0060] In order to make those skilled in the art more clearly understand the technical solutions described in the present invention, the following examples are listed for illustration. It should be noted that the following examples do not limit the scope of protection required by the present invention.

[0061] Unless otherwise specified, the raw materials, reagents, or devices used in the following examples can be obtained from conventional commercial channels or can be obtained by existing known methods.

[0062] Example 1

[0063] A dual-chiral covalent organic framework material, whose structural formula is:

[0064]

[0065] SR 1 Is a thioether chiral group derived from fully mercapto-β-cyclodextrin;

[0066] SR 2 A glutathione-derived thioether chiral group.

[0067] A method for preparing a two-chiral covalent organic framework material, comprising the following steps:

[0068] (1) Disperse 1,3,5-tris(4-aminophenyl)benzene (TAPB, 28.1 mg) in 2.5 mL of acetonitrile, and add 0.15 mL of acetic acid (HAc, 12 mol / L); disperse 1,4-dialdehyde-2,5-divinylbenzene (DEB, 7.5 mg) and 2,3,5,6-tetrafluorobenzaldehyde (TFPA, 16.5 mg) in 2.5 mL of acetonitrile, and add 0.15 mL of acetic acid (12 mol / L); ultrasonically dissolve until completely dissolved, then quickly mix and homogenize for 20 seconds, and let stand at room temperature for reaction for 24 h; wash the reaction product with tetrahydrofuran and acetone three times, and finally vacuum dry at room temperature for 12 h to obtain covalent organic framework material microspheres (COF-1);

[0069] (2) Disperse 10 mg of COF-1 in 38.0 mL of absolute ethanol and 2.0 mL of anhydrous N,N-dimethylformamide, add perthioglycol-β-cyclodextrin (SH-CD, 28.7 mg) and photoinitiator benzoin dimethyl ether (8.3 mg, 0.2 eq / thiol), and react at room temperature for 1 h under 365 nm ultraviolet light assistance; wash the reaction product with anhydrous N,N-dimethylformamide and ethanol three times, and finally vacuum dry at room temperature for 12 h to obtain perthioglycol-β-cyclodextrin modified single-chiral COF-1 (SHCD-COF-1);

[0070] (3) Add SHCD-COF-1 (10 mg), reduced glutathione (GSH, 18.9 mg) and 6 mL of phosphate buffer solution (pH = 7.2 - 7.4) to a pressure-resistant three-necked flask, and pass nitrogen for 2 min, and react in an ice-water bath for 10 h; wash the reaction product with water and ethanol twice, and vacuum dry at room temperature for 12 h to obtain a two-chiral covalent organic framework material (GSH-SHCD-COF-1).

[0071] The schematic process flow diagram for the preparation of the two-chiral covalent organic framework material in Example 1 is as Figure 1 shown.

[0072] Example 2

[0073] The difference between Example 2 and Example 1 is only that the total amount of acetic acid with a concentration of 12 mol / L in the reaction of step (1) in Example 2 is 0.1 mL, and the others are the same as in Example 1.

[0074] That is, step (1) of Example 2 is specifically as follows: Disperse 1,3,5-tris(4-aminophenyl)benzene (28.1 mg) in 2.5 mL of acetonitrile, and add half of the amount of acetic acid (i.e., 0.05 mL); Disperse 1,4-diformyl-2,5-divinylbenzene (7.5 mg) and 2,3,5,6-tetrafluorobenzene-1,4-dicarbaldehyde (16.5 mg) in 2.5 mL of acetonitrile, and add the remaining half of the amount of acetic acid (i.e., 0.05 mL); Ultrasonic until completely dissolved, then quickly mix and homogenize for 20 seconds, and let stand at room temperature for reaction for 24 h; Wash the reaction product with tetrahydrofuran and acetone three times, and finally vacuum dry at room temperature for 12 h to obtain covalent organic framework material microspheres.

[0075] Example 3

[0076] The difference between Example 3 and Example 2 is only that the total amount of acetic acid with a concentration of 12 mol / L in the reaction of step (1) of Example 3 is 0.2 mL, and the others are the same as Example 2.

[0077] Example 4

[0078] The difference between Example 4 and Example 2 is only that the total amount of acetic acid with a concentration of 12 mol / L in the reaction of step (1) of Example 4 is 0.4 mL, and the others are the same as Example 2.

[0079] Example 5

[0080] The difference between Example 5 and Example 2 is only that the total amount of acetic acid with a concentration of 12 mol / L in the reaction of step (1) of Example 5 is 0.5 mL, and the others are the same as Example 2.

[0081] Comparative Example 1

[0082] The difference between Comparative Example 1 and Example 1 is that Comparative Example 1 only performs step (1), does not perform step (2) and step (3), and the amino-containing covalent organic framework building unit used is 2,4,6-tris(4-aminophenyl)-1,3,5-triazine.

[0083] The specific preparation process of step (1) of Comparative Example 1 is as follows:

[0084] 2,4,6-Tris(4-aminophenyl)-1,3,5-triazine (28.3 mg) was dispersed in 2.5 mL of acetonitrile, and 0.15 mL of acetic acid (12 mol / L) was added; 1,4-diformyl-2,5-divinylbenzene (7.5 mg) and 2,3,5,6-tetrafluorobenzaldehyde (16.5 mg) were dispersed in 2.5 mL of acetonitrile and 0.15 mL of acetic acid (12 mol / L) was added, and ultrasonicated until completely dissolved, then quickly mixed and homogenized for 20 s, and allowed to react at room temperature for 24 h; the reaction product was washed 3 times with tetrahydrofuran and acetone, and finally vacuum dried at room temperature for 12 h to obtain the product.

[0085] Performance Test

[0086] 1. Infrared Spectroscopy Test

[0087] The products of steps (1), (2), and (3) of Example 1 were respectively subjected to infrared spectroscopy test, and the infrared spectrogram is as Figure 2 shown.

[0088] It can be seen from Figure 2 that the characteristic peak of the imine bond (-C=N-) in the covalent organic framework appears at 1701 cm -1 , indicating that the Schiff base reaction has occurred for the building blocks and the covalent organic framework microspheres have been successfully synthesized. The characteristic peaks after the modification of perthiomalic-β-cyclodextrin and glutathione appear at 2880 cm -1 , 1077 cm -1 and 1039 cm -1 . It can be known from Figure 2 that the chiral covalent organic framework material of the present invention has been successfully prepared.

[0089] 2. Scanning Electron Microscopy Observation

[0090] The products of steps (1), (2), and (3) of Example 1 were respectively subjected to scanning electron microscopy observation, and the scanning electron micrograph is as Figure 3 shown. Among them, Figure 3 Figure (A) in it is the scanning electron micrograph of the product COF-1 in step (1) of Example 1; Figure 3 Figure (B) in it is the scanning electron micrograph of the product SHCD-COF-1 in step (2) of Example 1; Figure 3 Figure (C) in it is the scanning electron micrograph of the product GSH-SHCD-COF-1 in step (3) of Example 1.

[0091] From Figure 3It can be clearly seen that the above three products obtained in steps (1)-(3) are all spherical, with uniform particle sizes and a size of 1.5±0.2 μm. In addition, the particle size of the covalent organic framework microspheres obtained in step (1) remains basically unchanged before and after modification with perthioglycol-β-cyclodextrin and glutathione.

[0092] Scanning electron microscopy observations were carried out on the covalent organic framework material microspheres obtained in step (1) of Examples 2-5. The scanning electron micrographs are as Figure 4 shown. Among them, Figure 4 Figures (A), (B), (C), and (D) in

[0093] are the scanning electron micrographs of the covalent organic framework material microspheres of Examples 2-5, respectively. Figure 4 It can be seen that when the total amount of catalyst acetic acid is 0.1 mL, 0.2 mL, 0.4 mL, and 0.5 mL respectively, covalent organic framework material microspheres with uniform particle sizes can be obtained, and the sizes are approximately 2.8 μm, 2.1 μm, 1.0 μm, and 0.5 μm respectively. Since the particle size of the covalent organic framework material microspheres remains basically unchanged before and after modification with chiral groups, the dual-chiral covalent organic framework material can be prepared with controllable size at room temperature by controlling the amount of acetic acid.

[0094] Scanning electron microscopy analysis was carried out on the product of Comparative Example 1, and the results are as Figure 5 shown.

[0095] From Figure 5 it can be seen that when the amino-containing covalent organic framework building unit is replaced from 1,3,5-tris(4-aminophenyl)benzene to 2,4,6-tris(4-aminophenyl)-1,3,5-triazine, the product material is particles with uneven particle sizes. And the preparation of spherical materials is a prerequisite for the covalent organic framework material microspheres to be directly used as the stationary phase for liquid chromatography. Therefore, the product of Comparative Example 1 cannot be directly used as the stationary phase for liquid chromatography. In the present invention, the amino-containing covalent organic framework building unit needs to use 1,3,5-tris(4-aminophenyl)benzene to obtain covalent organic framework material microspheres with uniform particle sizes, which can then be directly used as the stationary phase for liquid chromatography.

[0096] 3. X-ray diffraction analysis

[0097] The dual-chiral covalent organic framework materials prepared in Example 1 were respectively placed in solvents of 0.1 mol / L NaOH, methanol (MeOH), isopropanol (IPA), N,N-dimethylformamide (DMF), and n-hexane, and soaked for 48 h. X-ray diffraction analysis was carried out on the dual-chiral covalent organic framework materials without soaking chemical reagents and the dual-chiral covalent organic framework materials after soaking in each group of chemical reagents. The X-ray diffraction patterns are as Figure 6 shown.

[0098] FromFigure 6 It can be seen that there are basically no differences in the X-ray diffraction patterns of the materials in each group before soaking and after soaking in different solvents, indicating that the covalent organic framework material prepared by the present invention has good stability in common chromatographic mobile phases or other solvents and has the potential to be used as a chromatographic stationary phase.

[0099] 4. Chiral separation test

[0100] The spherical double-chiral covalent organic framework material prepared in Example 1 was used as the chiral chromatographic stationary phase. Before packing the column, 100 mg of GSH-SHCD-COF-1 in Example 1 was dispersed in 20 mL of an isopropanol / acetonitrile mixed solution to obtain a dispersion. Acetonitrile was selected as the replacement liquid, and under the condition of 25 MPa, the dispersion was packed into a stainless steel column with a length of 3 cm and a diameter of 2.1 mm. The chromatographic column was rinsed with acetonitrile at 0.1 mL / min on a liquid chromatograph for 24 h.

[0101] Using phenylalkanols chiral compounds (R) / (S)-1-(4-F-phenyl)ethanol, (R) / (S)-1-(4-Cl-phenyl)ethanol, (R) / (S)-1-(4-Br-phenyl)ethanol, (R) / (S)-1-phenyl-1-propanol, the drug intermediate (R) / (S)-ethyl mandelate and the heterocyclic chiral compound (R) / (S)-indanol as chiral target probe molecules, chiral separation was carried out using high performance liquid chromatography.

[0102] The specific chromatographic method is as follows:

[0103] The chromatographic conditions for the phenylalkanols chiral compounds (R) / (S)-1-(4-F-phenyl)ethanol, (R) / (S)-1-(4-Cl-phenyl)ethanol, (R) / (S)-1-phenyl-1-propanol and (R) / (S)-1-phenylethanol are respectively: the mobile phase is isopropanol, the flow rate is 0.15 mL / min, the column temperature is 30 °C, and the detection wavelength is 254 nm.

[0104] The chromatographic conditions for the drug intermediate (R) / (S)-ethyl mandelate are: the mobile phase is isopropanol, the flow rate is 0.15 mL / min, the column temperature is 30 °C, and the detection wavelength is 254 nm.

[0105] The chromatographic conditions for the heterocyclic chiral compound (R) / (S)-indanol are: the mobile phase is n-hexane / ethanol (v:v = 95:5), the flow rate is 0.20 mL / min, the column temperature is 30 °C, and the detection wavelength is 254 nm.

[0106] The double-chiral covalent organic framework material of Example 1 was directly used as the liquid chromatographic stationary phase, and the separation chromatogram of the phenylalkanols chiral compounds is as Figure 7 shown. Among them, Figure 7Figure (A) therein is the separation chromatogram of R / S-1-(4-F-phenyl)ethanol, Figure 7 Figure (B) therein is the separation chromatogram of R / S-1-(4-Cl-phenyl)ethanol, Figure 7 Figure (C) therein is the separation chromatogram of R / S-1-phenyl-1-propanol, Figure 7 Figure (D) therein is the separation chromatogram of (R) / (S)-1-phenylethanol.

[0107] In Example 1, the dual-chiral covalent organic framework material is directly used as the liquid chromatography stationary phase, and the separation chromatogram of the drug intermediate (R) / (S)-ethyl mandelate is as Figure 8 shown.

[0108] In Example 1, the dual-chiral covalent organic framework material is directly used as the liquid chromatography stationary phase, and the separation chromatogram of the heterocyclic chiral compound (R) / (S)-indanol is as Figure 9 shown.

[0109] It can be seen from Figures 7 - 9 that when the dual-chiral covalent organic framework material of the present invention is used as the stationary phase, only 100 g is required to achieve the effective separation of multiple types of chiral compounds, and the resolution of (R) / (S)-1-(4-F-phenyl)ethanol, (R) / (S)-1-(4-Cl-phenyl)ethanol, (R) / (S)-1-phenyl-1-propanol and (R) / (S)-1-phenylethanol are 1.56, 1.68, 1.47 and 1.60 respectively; the resolution of (R) / (S)-ethyl mandelate is 1.16, and the resolution of (R) / (S)-indanol is 1.44. In addition, under a high pressure of 25 MPa, the dual-chiral covalent organic framework material can be directly loaded into the chromatographic column and applied, proving its good mechanical stability.

[0110] In summary, the specific amino group-containing covalent organic framework building unit and aldehyde group-containing covalent organic framework building unit of the present invention react through a Schiff base reaction to form a three-component covalent organic framework microsphere, and then by adopting a step-by-step modification method, a dual-chiral covalent organic framework material with uniform particle size, controllable size, good chemical stability and good mechanical properties can be prepared, which can be directly used as the liquid chromatography stationary phase to achieve the effective separation of multiple types of chiral compounds. At the same time, its process conditions are mild, the process is simple, the preparation is rapid, and the cost is low.

[0111] The above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit the protection scope of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A covalent organic framework material, characterized in that: Its chemical structure is: The SR1 includes a saccharide-derived thioether chiral group containing a thiol group; The SR2 comprises a thiol-containing amino acid or a peptide-derived thioether chiral group.

2. The method for preparing a covalent organic framework material according to claim 1, characterized in that: The following steps are involved: (1) mixing an amino group-containing covalent organic backbone building unit and an aldehyde group-containing covalent organic backbone building unit, reacting the mixture, and obtaining an intermediate product 1; (2) mixing the intermediate product 1 obtained in step (1), an initiator, and a substance containing a first chiral group, and reacting them to obtain an intermediate product 2; (3) mixing the intermediate product 2 obtained in step (2) and the substance containing the second chiral group, and reacting them to obtain the covalent organic framework material; The first chiral group in the substance containing the first chiral group comprises a sulfhydryl-containing sugar-derived thioether chiral group; The second chiral group in the substance containing a second chiral group comprises a thioether chiral group derived from an amino acid or a peptide containing a thiol group.

3. The preparation method according to claim 2, characterized in that: The amino-containing covalent organic backbone building motif includes 1,3,5-tris(4-aminophenyl)benzene; and / or, the aldehyde-containing covalent organic backbone building motif includes tetrafluoroterephthalaldehyde and 1,4-dialdehyde-2,5-divinylbenzene.

4. The preparation method according to claim 3, characterized in that: The molar ratio of the amino-containing covalent organic backbone building unit to the aldehyde-containing covalent organic backbone building unit is 1:(1-2); and / or, in the aldehyde-containing covalent organic backbone building unit, the molar ratio of the 1,4-dialdehyde-2,5-divinylbenzene to tetrafluoroterephthalaldehyde is 1:(0.5-3).

5. The preparation method according to claim 2, characterized in that: In step (1), the mixing further comprises adding a catalyst and an organic solvent, and the volume ratio of the catalyst to the organic solvent is 1:(10-50).

6. The preparation method according to claim 2, characterized in that: In step (1), the reaction temperature is 10-40°C; and / or the reaction time is 12-72h.

7. The preparation method according to claim 2, characterized in that: In step (2), the substance containing the first chiral group includes at least one of perthio-β-cyclodextrin, monothio-β-cyclodextrin, and 5-thio-D-glucose; and / or the initiator includes a photoinitiator.

8. The preparation method according to claim 2, characterized in that: In step (2), the molar ratio of the intermediate product 1 to the substance containing the first chiral group is 1:(2-6); and / or the mixing further comprises adding a solvent; and / or the reaction temperature is 10-80°C; and / or the reaction time is 0.1-2h; and / or the reaction is carried out under light assistance.

9. The preparation method according to claim 2, characterized in that: In step (3), the substance containing a second chiral group includes a chiral amino acid or peptide containing a thiol group; and / or the molar ratio of the intermediate 2 to the substance containing a second chiral group is 1:(3-6); and / or the reaction temperature is 0-40°C; and / or the reaction time is 7-16h; and / or the mixing further includes adding a buffer solution.

10. Use of the covalent organic framework material according to claim 1 in separating chiral substances.

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