CN117510766A - Double-chiral covalent organic framework material, preparation method and application thereof - Google Patents
Double-chiral covalent organic framework material, preparation method and application thereof Download PDFInfo
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- 239000013310 covalent-organic framework Substances 0.000 title claims abstract description 113
- 239000000463 material Substances 0.000 title claims abstract description 104
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 238000000926 separation method Methods 0.000 claims abstract description 33
- 230000005526 G1 to G0 transition Effects 0.000 claims abstract description 19
- 239000002994 raw material Substances 0.000 claims abstract description 16
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- 239000000126 substance Substances 0.000 claims abstract description 13
- 238000005557 chiral recognition Methods 0.000 claims abstract description 5
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 48
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- 229940079593 drug Drugs 0.000 claims description 22
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 claims description 20
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 20
- 239000000178 monomer Substances 0.000 claims description 20
- 238000001035 drying Methods 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 12
- 230000035484 reaction time Effects 0.000 claims description 12
- 229960001639 penicillamine Drugs 0.000 claims description 11
- WHSQATVVMVBGNS-UHFFFAOYSA-N 4-[4,6-bis(4-aminophenyl)-1,3,5-triazin-2-yl]aniline Chemical compound C1=CC(N)=CC=C1C1=NC(C=2C=CC(N)=CC=2)=NC(C=2C=CC(N)=CC=2)=N1 WHSQATVVMVBGNS-UHFFFAOYSA-N 0.000 claims description 10
- VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 claims description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- 239000011230 binding agent Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- 239000005973 Carvone Substances 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 6
- FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical compound O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 claims description 5
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical class OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 4
- 150000002475 indoles Chemical class 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 238000004729 solvothermal method Methods 0.000 claims description 4
- 238000010257 thawing Methods 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- 239000007853 buffer solution Substances 0.000 claims description 2
- 238000004587 chromatography analysis Methods 0.000 claims description 2
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- IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
- USWINTIHFQKJTR-UHFFFAOYSA-N 3-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C2C=C(S(O)(=O)=O)C(O)=CC2=C1 USWINTIHFQKJTR-UHFFFAOYSA-N 0.000 description 6
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- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical group C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- WJHRAPYKYJKACM-UHFFFAOYSA-N 2,3,5,6-tetrafluoroterephthalaldehyde Chemical compound FC1=C(F)C(C=O)=C(F)C(F)=C1C=O WJHRAPYKYJKACM-UHFFFAOYSA-N 0.000 description 1
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- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
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- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G12/00—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen
- C08G12/02—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen of aldehydes
- C08G12/26—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen of aldehydes with heterocyclic compounds
- C08G12/30—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen of aldehydes with heterocyclic compounds with substituted triazines
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 - B01D15/36
- B01D15/3833—Chiral chromatography
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- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
The invention relates to the technical field of chiral substance separation, in particular to a double-chiral covalent organic framework material, a preparation method and application thereof. The double-chiral covalent organic framework material has a porous property, and the double-chiral covalent organic framework provides a plurality of chiral recognition sites, and the framework structural formula is as follows:the double-chiral covalent organic framework material has the advantages of large specific surface area, uniform pore size distribution, large adsorption capacity, cheap preparation raw materials, mild preparation conditions and environment friendliness and can be prepared in a large amount when being used as a double-chiral chromatographic stationary phase of high performance liquid chromatography.
Description
Technical Field
The invention relates to the technical field of chiral substance separation, in particular to a double-chiral covalent organic framework material, a preparation method and application thereof.
Background
Chirality is an essential feature of biological systems, and most endogenous biomolecules, such as enzymes, polysaccharides, plasma proteins, etc., are present in human body in chirally pure form. Drugs exert their pharmacological effects through stereospecific interactions with these biological macromolecules. Chiral enantiomers play a critical role in medical and biochemical systems, and particularly for drugs or drug candidates, chiral enantiomers exhibit significant differences in pharmacodynamic, pharmacokinetic and toxicological properties, so analysis of chiral enantiomers has become an important research focus in the fields of chemistry, medicine, biology, drug synthesis, etc. More than 50% of the drugs on the market are racemates and the availability of single stereoisomer drugs has become a trend, so that the separation of chiral enantiomers and the availability of single enantiomer drugs is of great importance for human health. However, because enantiomers have the same physical and chemical properties, separation of enantiomers is considered a great challenge.
Among the different types of chiral resolution techniques, chromatographic separation techniques based on Chiral Stationary Phases (CSPs) have proven to be the most attractive and most applicable method for separating and obtaining pure enantiomers. High Performance Liquid Chromatography (HPLC) is a multifunctional, sensitive and easy-to-use tool, is one of the most common ways to separate and obtain single chiral substances, and is a core of high performance liquid chromatography, and the development of stationary phase materials is focused by students, so that the HPLC becomes an important research hotspot in the field of separation science. For substances having different properties, chiral Chromatographic Stationary Phases (CSPs) such as polysaccharides, cyclodextrins, etc. have been developed, which exhibit excellent performance in chiral drug separation, but they lack versatility, and it is difficult to achieve simultaneous separation of different kinds of chiral drugs. Therefore, the preparation of chiral chromatography immobilization with high selectivity has great research significance in chiral drug separation.
In view of this, the present invention has been made.
Disclosure of Invention
The invention aims to provide a bimanual covalent organic framework material, a preparation method and application thereof. The embodiment of the invention provides a novel bimanual covalent organic framework material which has the advantages of large specific surface area, uniform pore size distribution, large adsorption capacity and the like, and can be used as a bimanual chromatographic stationary phase of high performance liquid chromatography.
The invention is realized in the following way:
in a first aspect, embodiments of the present invention provide a bimanual covalent organic framework material, the bimanual covalent organic framework material having a porous nature, and the bimanual covalent organic framework providing a plurality of chiral recognition sites, the framework structural formula of which is:
in a second aspect, an embodiment of the present invention provides a method for preparing a bimanual covalent organic framework material, including: the bimanual covalent organic framework material is formed using a solvothermal method.
In a preferred embodiment, it comprises:
1) 2,4, 6-tris (4-aminophenyl) -1,3, 5-triazine and 2,3,5, 6-tetrafluoro-p-dicarboxaldehyde are taken as raw materials, 1,4 dioxane and trimethylbenzene are added, acetic acid is added, liquid nitrogen is frozen, air extraction and thawing are carried out, and covalent organic framework materials are formed through reaction at a certain temperature;
2) Mixing the covalent organic framework material, an acid binding agent, chiral monomer trans-cyclohexanediamine and a solvent for reaction to form a single chiral covalent organic framework material;
3) And mixing the single chiral covalent organic framework material serving as a raw material, chiral monomer D-penicillamine and a buffer solution to react to form the double chiral covalent organic framework material.
In a preferred embodiment, the mass ratio of 2,4, 6-tris (4-aminophenyl) -1,3, 5-triazine to 2,3,5, 6-tetrafluoro-dicarboxaldehyde in step 1) is 1: (0.7 to 0.9);
preferably, the acetic acid is a mixed solution of acetic acid and water; the 1,4 dioxane is anhydrous 1,4 dioxane;
preferably, the concentration of the acetic acid is 2.8-3.2mol/L;
preferably, the volume ratio of the 1,4 dioxane, the trimethylbenzene and the acetic acid is 1: (0.2-0.4): (0.1 to 0.2);
preferably, the reaction time is 68-75 hours, and the reaction temperature is 115-125 ℃;
preferably, step 1) is carried out after the reaction is completed, and the post-treatment comprises washing and drying;
preferably, the washing comprises: alternately washing for multiple times by using ethanol, 1,4 dioxane and water;
preferably, the drying conditions include a temperature of 75-85℃for a period of 10-14 hours.
In a preferred embodiment, the mass ratio of the covalent organic framework material, the chiral monomer trans-cyclohexanediamine and the acid binding agent in step 2) is 1: (0.2-0.3): (0.45-0.6);
preferably, the acid binding agent comprises anhydrous carbonate, more preferably anhydrous potassium carbonate;
the solvent is selected from furan solvents, preferably tetrahydrofuran;
preferably, the reaction conditions include: the reaction time is 40-50 hours, and the reaction temperature is 80-90 ℃;
preferably, step 2) is carried out after the reaction is completed, wherein the post-treatment comprises washing and drying;
preferably, the washing comprises: methanol and water are alternately washed for a plurality of times;
preferably, the drying conditions include a temperature of 75-85℃for a period of 10-14 hours.
In a preferred embodiment, the mass ratio of the single chiral covalent organic framework material to the chiral monomer D-penicillamine in step 3) is 1: (1.8-2);
preferably, the reaction conditions include: the reaction time is 8-12 hours, and the reaction temperature is 20-30 ℃;
preferably, step 3) is carried out after the reaction is completed, wherein the post-treatment comprises washing and drying;
preferably, the washing comprises: methanol and water are alternately washed for a plurality of times;
preferably, the drying conditions include a temperature of 75-85℃for a period of 10-14 hours.
In a third aspect, embodiments of the present invention provide a chiral chromatographic stationary phase, which is prepared by using the chiral covalent organic framework material.
In a fourth aspect, the present invention provides an application of the above-mentioned bimanual covalent organic framework material in high performance liquid chromatography separation of chiral substances.
In a preferred embodiment, the bimorphic covalent organic framework material acts as a stationary phase for a bimorphic chromatograph when separating chiral substances by high performance liquid chromatography.
In a preferred embodiment, the chiral material comprises a chiral intermediate and a chiral drug;
preferably, the chiral intermediate comprises indole compounds, phenylethanoid compounds and aromatic alcohol compounds;
preferably, the chiral drug comprises cyclohexenone drug, preferably R/S-carvone.
The invention has the following beneficial effects: the bimanual covalent organic framework material provided by the embodiment of the invention can be used as a bimanual chromatographic stationary phase of high performance liquid chromatography, and has the advantages of large specific surface area, uniform pore size distribution, large adsorption capacity, cheap preparation raw materials, mild preparation conditions, environmental friendliness and capability of being prepared in a large amount.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the embodiments will be briefly described below, it being understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and other related drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is an infrared spectrum of a two-chiral covalent organic framework material provided by an embodiment of the invention;
FIG. 2 is an X-ray diffraction pattern of a two-chiral covalent organic framework material provided by an embodiment of the present invention;
FIG. 3 is a graph of a separation chromatogram of a chiral covalent organic framework material versus R/S-indoline-carboxylic acid provided by an embodiment of the invention;
FIG. 4 is a chromatogram of a pair of R/S-mandelic acid separation of a chiral covalent organic framework material provided by an embodiment of the invention;
FIG. 5 is a graph of a separation chromatogram of a bimanual covalent organic framework material provided by an embodiment of the present invention against R/S-4-bromophenyl ethanol;
FIG. 6 is a chromatogram of a pair of R/S-carvone separation chromatograms of a two-chiral covalent organic framework material provided by an embodiment of the invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
In recent years, novel porous materials are considered as potential candidates for chiral chromatographic stationary phases, mainly because of the tunable functions with different chiral building blocks, such as covalent organic porous frameworks (COFs), which have great potential as stationary phases for chiral chromatography, have received great attention. Covalent Organic Frameworks (COFs) are used as novel crystalline porous materials, have a highly ordered structure, are constructed by organic light elements (H, B, C, N, si and O) through strong covalent bonds, have a plurality of unique properties such as rigid structures, low density, high thermal stability and large specific surface area and have permanent porosities, so that chiral functionalized COFs materials have wide prospects as stationary phases for enantiomer separation. Therefore, the design and preparation of a novel chiral COF as a chromatographic stationary phase for chiral drug separation has great significance in the fields of medicine and chemical industry.
The embodiment of the invention provides a bimanual covalent organic framework material, which has a porous property, and the bimanual covalent organic framework provides a plurality of chiral recognition sites, and the framework structural formula is as follows:
the functional groups in the skeleton structure of the bimanual covalent organic skeleton material can provide hydrogen bonds as action sites, and can be used as a chiral chromatographic stationary phase of high performance liquid chromatography for chiral drug intermediates and chiral drug separation analysis. In particular, chiral monomers in the chiral covalent organic framework material can provide multiple action recognition effects such as hydrogen bonding effect, pi-pi effect and the like, so that the chiral organic framework material has specific recognition effects on chiral isomer substances such as indoles, phenylethanoid acids, aromatic alcohols, cyclohexenones and the like.
In a second aspect, an embodiment of the present invention provides a method for preparing a bimanual covalent organic framework material, including: the bimanual covalent organic framework material is formed using a solvothermal method. According to the embodiment of the invention, the bi-chiral covalent organic framework material is synthesized by controlling the reaction temperature through a solvothermal method, and is formed by connecting covalent bonds, so that more chiral monomers are possessed in a molecular structure network framework, and the extraordinary chiral recognition capability is provided for the bi-chiral covalent organic framework material.
The specific process is as follows:
s1, forming a covalent organic framework material;
2,4, 6-tris (4-aminophenyl) -1,3, 5-triazine and 2,3,5, 6-tetrafluoro-p-dicarboxaldehyde are taken as raw materials, anhydrous 1, 4-dioxane and trimethylbenzene are added, ultrasonic is carried out, 2.8-3.2mol/L acetic acid aqueous solution is added dropwise, liquid nitrogen is frozen, air suction and thawing are carried out for 1 time, reaction is carried out at a certain temperature, and the reaction product is washed and dried in vacuum, thus obtaining the covalent organic framework material.
Wherein the mass ratio of the 2,4, 6-tri (4-aminophenyl) -1,3, 5-triazine to the 2,3,5, 6-tetrafluoro-dicarboxaldehyde is 1: (0.7 to 0.9); for example, 1:0.7, 1:0.8, and 1:0.9: any value between (0.7 and 0.9) or a range of values between any two values.
The volume ratio of the 1,4 dioxane, the trimethylbenzene and the acetic acid is 1: (0.2-0.4): (0.1 to 0.2); the reaction time is 68-75 hours, and the reaction temperature is 115-125 ℃.
Specifically, the washing includes: alternately washing for multiple times by using ethanol, 1,4 dioxane and water; the drying condition includes 75-85deg.C for 10-14 hr.
S2, forming a single chiral covalent organic framework material;
the covalent organic framework material prepared in the step S1 is used as a raw material, anhydrous potassium carbonate is added as an acid binding agent, a certain amount of chiral monomer trans-cyclohexanediamine is added, tetrahydrofuran is used as a solvent to react at a certain temperature, and the reaction product is washed and dried in vacuum to obtain the single chiral covalent organic framework material.
Wherein the mass ratio of the covalent organic framework material to the chiral monomer trans-cyclohexanediamine to the acid binding agent is 1: (0.2-0.3): (0.45-0.6); the reaction time is 40-50 hours, and the reaction temperature is 80-90 ℃. The washing comprises the following steps: methanol and water are alternately washed for a plurality of times; the drying condition includes 75-85deg.C for 10-14 hr.
S3, forming a bimanual covalent organic framework material;
the single chiral covalent organic framework material prepared by S2 is taken as a raw material, a certain amount of chiral monomer D-penicillamine is added, a phosphate buffer solution with pH of 7-7.5 is taken as a solvent for reaction at room temperature, and finally washing and vacuum drying are carried out, so that the double chiral covalent organic framework material (COF) is obtained.
Wherein the mass ratio of the single chiral covalent organic framework material to the chiral monomer D-penicillamine is 1: (1.8-2); the reaction time is 8-12 hours, and the reaction temperature is room temperature (20-30 ℃); the washing comprises the following steps: methanol and water are alternately washed for a plurality of times; the drying condition includes 75-85deg.C for 10-14 hr.
In a third aspect, embodiments of the present invention provide a chiral chromatographic stationary phase, which is prepared by using the chiral covalent organic framework material.
The specific process is as follows:
s1, modifying covalent organic framework materials on aminated silica gel;
the preparation method comprises the steps of taking aminated silica gel, 2,4, 6-tris (4-aminophenyl) -1,3, 5-triazine and 2,3,5, 6-tetrafluoro-p-dicarboxaldehyde as raw materials, adding anhydrous 1, 4-dioxane and trimethylbenzene, performing ultrasonic treatment, dropwise adding 2.8-3.2mol/L acetic acid aqueous solution, performing liquid nitrogen freezing-air extraction-thawing for 1 time, reacting at a certain temperature, washing and vacuum drying reaction products, and preparing the modified covalent organic framework material on the aminated silica gel.
Wherein the mass ratio of the aminated silica gel to the 2,4, 6-tri (4-aminophenyl) -1,3, 5-triazine to the 2,3,5, 6-tetrafluoro to dicarboxaldehyde is 5:1: (0.7 to 0.9); for example, 5:1:0.7, 5:1:0.8, 5:1:0.9, etc. 5:1: any value between (0.7 and 0.9) or a range of values between any two values.
The volume ratio of the 1,4 dioxane, the trimethylbenzene and the acetic acid is 1: (0.2-0.4): (0.1 to 0.2); the reaction time is 68-75 hours, and the reaction temperature is 115-125 ℃.
Specifically, the washing includes: alternately washing for multiple times by using ethanol, 1,4 dioxane and water; the drying condition includes 75-85deg.C for 10-14 hr.
S2, forming a single chiral covalent organic framework material from the covalent organic framework material on the amino silica gel;
the preparation method comprises the steps of taking the amination silica gel prepared in the step S1 as a raw material, adding anhydrous potassium carbonate as an acid binding agent, adding a certain amount of chiral monomer trans-cyclohexanediamine, reacting at a certain temperature by taking tetrahydrofuran as a solvent, washing and vacuum drying reaction products, and obtaining the single chiral covalent organic framework material modified on the amination silica gel.
Wherein, the mass ratio of the amination silica gel prepared by S1, the chiral monomer trans-cyclohexanediamine and the acid binding agent is 1: (0.2-0.3): (0.45-0.6); the reaction time is 40-50 hours, and the reaction temperature is 80-90 ℃. The washing comprises the following steps: methanol and water are alternately washed for a plurality of times; the drying condition includes 75-85deg.C for 10-14 hr.
S3, forming a single chiral covalent organic framework material on the amino silica gel into a double chiral covalent organic framework material;
the preparation method comprises the steps of taking the amination silica gel prepared by S2 as a raw material, adding a certain amount of chiral monomer D-penicillamine, taking phosphate buffer solution with pH of 7-7.5 as a solvent, reacting at room temperature, and finally washing and vacuum drying to obtain the double-chiral covalent organic framework material (Si-COF) modified on the amination silica gel.
Wherein, the mass ratio of the amination silica gel prepared by S2 to the chiral monomer D-penicillamine is 1: (1.8-2); the reaction time is 8-12 hours, and the reaction temperature is room temperature (20-30 ℃); the washing comprises the following steps: methanol and water are alternately washed for a plurality of times; the drying condition includes 75-85deg.C for 10-14 hr.
In a fourth aspect, the present invention provides an application of the above-mentioned bimanual covalent organic framework material in high performance liquid chromatography separation of chiral substances.
Specifically, the chiral covalent organic framework material is used as a chiral chromatographic stationary phase when chiral substances are separated by high performance liquid chromatography.
Wherein the chiral substance comprises a chiral intermediate and a chiral drug;
preferably, the chiral intermediate comprises indole compounds, phenylethanoid compounds and aromatic alcohol compounds; for example, R/S-indoline-carboxylic acid, R/S-mandelic acid and R/S-4-bromophenyl ethanol.
Preferably, the chiral drug comprises cyclohexenone drug, preferably R/S-carvone.
The chiral covalent organic framework material provided by the embodiment of the invention can realize separation of indole, phenylethanoid acid and aromatic alcohol chiral medical intermediates, for example, the separation degree of R/S-indoline-carboxylic acid is 2.58 respectively; the separation degree of R/S-mandelic acid is 3.39; the separation degree of R/S-4-bromophenyl ethanol is 2.76.
Separation of cyclohexenone chiral drugs can also be achieved, for example, the separation degree of R/S-carvone is 2.55.
The features and capabilities of the present invention are described in further detail below in connection with the examples.
Example 1
The embodiment of the invention provides a preparation method of a bimanual covalent organic framework material, which comprises the following steps:
s1, preparing a covalent organic framework material:
80mg of 2,4, 6-tris (4-aminophenyl) -1,3, 5-triazine and 72mg of 2,3,5, 6-tetrafluoro-terephthalaldehyde are weighed into a pressure-resistant glass tube of 20ml, 4.8ml of 1,4 dioxane and 1.2ml of trimethylbenzene are added, the mixture is ultrasonically treated until solid is dissolved, 0.6ml of 3mol/L acetic acid aqueous solution is added dropwise, the mixture is frozen by liquid nitrogen, pumped down and thawed for 1 time, the mixture is reacted for 72 hours at 120 ℃, the reaction product is alternately washed for 2 times by ethanol, 1,4 dioxane and water, and finally the mixture is dried in vacuum at 80 ℃ for 12 hours, so that the covalent organic framework material can be obtained.
S2, preparing a single chiral covalent organic framework material:
the covalent organic framework material prepared in the above step is used as a raw material. Weighing 525mg of covalent organic framework material and 368mg of trans-cyclohexanediamine in a pressure-resistant glass tube of 20ml, adding 285mg of anhydrous potassium carbonate, then adding 21ml of tetrahydrofuran, reacting for 48 hours at 85 ℃, alternately washing the reaction product with methanol and water for 2 times, and finally drying in vacuum at 80 ℃ for 12 hours to obtain the single chiral covalent organic framework material.
S3, preparing a bimanual covalent organic framework material COF:
the single chiral covalent organic framework material prepared in the above step is used as a raw material. Weighing 7.8mg of single chiral covalent organic framework material and 15mg of D-penicillamine in a conical flask, adding 10ml of phosphate buffer solution with pH of 7, carrying out ultrasonic treatment for 1min, reacting at room temperature for 10h, alternately washing the reaction product with methanol and water for 2 times, and finally carrying out vacuum drying at 40 ℃ for 12 hours to obtain the chiral covalent organic framework material COF.
Characterization of
And carrying out infrared and X-ray detection on the prepared bimanual covalent organic framework material, wherein the result is shown in fig. 1 and 2.
The infrared characterization chart is shown in FIG. 1, and can be seen from the infrared spectrum (FT-IR) absorption peak, 1500cm -1 The position is a vibration adsorption peak in a triazine ring, which is 1700cm -1 No peak of formaldehyde absorption of tetrafluoro-dicarboxaldehyde, 2853cm -1 Is chiral monomer trans-cyclohexanediamine-CH 2 -CH 2 Absorption peak, 3360cm -1 The absorption peak of D-penicillamine carboxyl in chiral monomer is shown, and the polymerization of the infrared-visible material is successful.
The XRD patterns are shown in figure 2, and the covalent organic framework material and the bimanual covalent organic framework material COF both have diffraction peaks at 3 degrees, thus proving that the material is polymerized successfully.
Example 2
This example provides a multi-chiral chromatographic stationary phase (cof@sio) 2 ) The preparation method of (2) comprises the following steps:
s1, modifying a covalent organic framework material on an aminated silica gel:
550mg of aminated silica gel, 120mg of 2,4, 6-tris (4-aminophenyl) -1,3, 5-triazine and 108mg of 2,3,5, 6-tetrafluoro-p-dicarboxaldehyde are weighed into a pressure-resistant glass tube of 20ml, 7.2ml of 1,4 dioxane and 1.8ml of trimethylbenzene are added, the mixture is ultrasonically and solid-dissolved, 0.9ml of 3mol/L acetic acid aqueous solution is dropwise added, liquid nitrogen is frozen, air-extracted and thawed for 1 time, reaction is carried out for 72 hours at 120 ℃, the reaction product is alternately washed for 2 times by ethanol, 1,4 dioxane and water, and finally the covalent organic framework material modified on the aminated silica gel can be obtained under the condition of vacuum drying at 80 ℃ for 12 hours.
S2, forming a single chiral covalent organic framework material by using the covalent organic framework material on the amino silica gel:
the amino silica gel prepared by S1 is used as a raw material. Weighing 300mg of covalent organic framework material and 86mg of trans-cyclohexanediamine in a pressure-resistant glass tube of 20ml, adding 226mg of anhydrous potassium carbonate, then adding 13ml of tetrahydrofuran, reacting at 85 ℃ for 48h, alternately washing the reaction product with methanol and water for 2 times, and finally carrying out vacuum drying at 80 ℃ for 12 hours to obtain the single chiral covalent organic framework material modified on the amino silica gel.
S3, forming a single chiral covalent organic framework material on the amino silica gel into a chiral covalent organic framework material (COF@SiO) 2 )：
Single prepared in one stepChiral covalent organic framework material is used as raw material. Weighing 20mg of single chiral covalent organic framework material and 37mg of D-penicillamine in a conical flask, adding 26ml of phosphate buffer solution with pH of 7, performing ultrasonic treatment for 1min, reacting at room temperature for 10h, alternately washing the reaction product with methanol and water for 2 times, and finally performing vacuum drying at 40 ℃ for 12 hours to obtain the double chiral covalent organic framework material (COF@SiOO) modified on the aminated silica gel 2 )。
COF@SiO 2 The structural formula is as follows:
application example
The chiral column is formed by utilizing the chiral chromatographic stationary phase, and the specific chromatographic method for R/S-indoline-carboxylic acid, R/S-mandelic acid, R/S-4-bromophenethyl alcohol and carvone is as follows:
chromatographic conditions of R/S-indoline-carboxylic acid: mobile phase: methanol/water (v/v=90:10); flow rate: 0.2mL/min; column temperature: 25 ℃, detection wavelength: 293nm.
Chromatographic conditions of R/S-mandelic acid: methanol/water (v/v=90:10); flow rate: 0.15mL/min; column temperature: 25 ℃, detection wavelength: 233nm.
Chromatographic conditions for R/S-4-phenethyl alcohol: mobile phase: methanol/water (v/v=70:30); flow rate: 0.1mL/min; column temperature: 25 ℃, detection wavelength: 254nm.
Chromatographic conditions of R/S-carvone: mobile phase: methanol/water (v/v=70:30); flow rate: 0.1mL/min; column temperature: 25 ℃, detection wavelength: 210nm.
The results are shown in FIGS. 3-6.
Specifically, FIG. 3 shows an R/S-indoline-carboxylic acid separation chromatogram, and as can be seen from FIG. 3, a 10. Mu. l R/S-indoline-carboxylic acid standard (100. Mu.g/mL) was measured at a wavelength of 293nm at a flow rate of about 0.2 mL/min. The degree of separation of R/S-indoline-carboxylic acid was 2.58, respectively.
FIG. 4 shows an R/S-mandelic acid separation chromatogram, and as shown in FIG. 4, a 10. Mu. l R/S-R/S-mandelic acid standard (100. Mu.g/mL) was measured at a flow rate of about 0.15mL/min and a wavelength of 233nm. The separation degree of R/S-indoline-carboxylic acid is 3.39 respectively.
FIG. 5 shows a separation chromatogram of R/S-4-bromophenyl ethanol, and as shown in FIG. 5, a 10. Mu. l R/S-4-bromophenyl ethanol standard (100. Mu.g/mL) was measured at a wavelength of 254nm at a flow rate of about 0.1 mL/min. The degree of separation of R/S-indoline-carboxylic acid was 2.76, respectively.
FIG. 6 shows an R/S-carvone separation chromatogram, and it is understood from FIG. 6 that 10. Mu. l R/S-carvone standard (100. Mu.g/mL) was measured at a wavelength of 210nm at a flow rate of about 0.1 mL/min. The degree of separation of R/S-indoline-carboxylic acid was 2.55, respectively.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. The double-chiral covalent organic framework material is characterized in that the double-chiral covalent organic framework material has a porous property, and the double-chiral covalent organic framework provides a plurality of chiral recognition sites, and the framework structural formula is as follows:
2. a method of preparing the bimodality covalent organic framework material of claim 1, comprising: the bimanual covalent organic framework material is formed using a solvothermal method.
3. The method of manufacturing according to claim 2, comprising:
1) 2,4, 6-tris (4-aminophenyl) -1,3, 5-triazine and 2,3,5, 6-tetrafluoro-p-dicarboxaldehyde are taken as raw materials, 1,4 dioxane and trimethylbenzene are added, acetic acid is added, liquid nitrogen is frozen, air extraction and thawing are carried out, and covalent organic framework materials are formed through reaction at a certain temperature;
2) Mixing the covalent organic framework material, an acid binding agent, chiral monomer trans-cyclohexanediamine and a solvent for reaction to form a single chiral covalent organic framework material;
3) And mixing the single chiral covalent organic framework material serving as a raw material, chiral monomer D-penicillamine and a buffer solution to react to form the double chiral covalent organic framework material.
4. A process according to claim 3, wherein the mass ratio of 2,4, 6-tris (4-aminophenyl) -1,3, 5-triazine to 2,3,5, 6-tetrafluoro-to-dicarboxaldehyde in step 1) is 1: (0.7 to 0.9);
preferably, the acetic acid is a mixed solution of acetic acid and water; the 1,4 dioxane is anhydrous 1,4 dioxane;
preferably, the concentration of the acetic acid is 2.8-3.2mol/L;
preferably, the volume ratio of the 1,4 dioxane, the trimethylbenzene and the acetic acid is 1: (0.2-0.4): (0.1 to 0.2);
preferably, the reaction time is 68-75 hours, and the reaction temperature is 115-125 ℃;
preferably, step 1) is carried out after the reaction is completed, and the post-treatment comprises washing and drying;
preferably, the washing comprises: alternately washing for multiple times by using ethanol, 1,4 dioxane and water;
preferably, the drying conditions include a temperature of 75-85℃for a period of 10-14 hours.
5. The method according to claim 3, wherein the mass ratio of the covalent organic framework material, the chiral monomer trans-cyclohexanediamine and the acid binding agent in step 2) is 1: (0.2-0.3): (0.45-0.6);
preferably, the acid binding agent comprises anhydrous carbonate, more preferably anhydrous potassium carbonate;
the solvent is selected from furan solvents, preferably tetrahydrofuran;
preferably, the reaction conditions include: the reaction time is 40-50 hours, and the reaction temperature is 80-90 ℃;
preferably, step 2) is carried out after the reaction is completed, wherein the post-treatment comprises washing and drying;
preferably, the washing comprises: methanol and water are alternately washed for a plurality of times;
preferably, the drying conditions include a temperature of 75-85℃for a period of 10-14 hours.
6. The preparation method according to claim 3, wherein the mass ratio of the single chiral covalent organic framework material to the chiral monomer D-penicillamine in step 3) is 1: (1.8-2);
preferably, the reaction conditions include: the reaction time is 8-12 hours, and the reaction temperature is 20-30 ℃;
preferably, step 3) is carried out after the reaction is completed, wherein the post-treatment comprises washing and drying;
preferably, the washing comprises: methanol and water are alternately washed for a plurality of times;
preferably, the drying conditions include a temperature of 75-85℃for a period of 10-14 hours.
7. A bimanual chromatographic stationary phase prepared by the bimanual covalent organic framework material of claim 1.
8. Use of the bimodality covalent organic framework material of claim 1 for high performance liquid chromatography separation of chiral species.
9. The use according to claim 8, wherein the bimanual covalent organic framework material acts as a stationary phase for a bimorph chromatography in the separation of chiral substances by high performance liquid chromatography.
10. The use according to claim 8, wherein the chiral material comprises a chiral intermediate and a chiral drug;
preferably, the chiral intermediate comprises indole compounds, phenylethanoid compounds and aromatic alcohol compounds;
preferably, the chiral drug comprises cyclohexenone drug, preferably R/S-carvone.
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