CN113441122B - Chiral stationary phase of spiral polymer functionalized silica gel microsphere, preparation and application - Google Patents
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Abstract
The invention relates to a preparation method of a spiral polymer functionalized silica gel microsphere Chiral Stationary Phase (CSP) and an application thereof in Chiral Separation. The preparation method comprises the steps of firstly introducing alkynyl on the surface of a silica gel microsphere, then adding a functional monomer (Fmoc-L-phenylalanine derivative) and a catalyst, wherein the monomer can perform alkynyl-alkynyl addition polymerization reaction under the action of the catalyst to form a spiral structure, so that the silica gel microsphere material of the surface modified spiral polymer is prepared. The chiral stationary phase has simple preparation process and mild reaction condition, and can be used for large-scale preparation.
Description
Technical Field
The invention relates to separation of enantiomers, in particular to a separation method of chiral enantiomers, which comprises the steps of modifying the surface of a silicon dioxide microsphere with 3-mercaptopropyl alkynyl, adding a functional monomer with click chemistry reaction chirality and an initiating catalyst, grafting a polymer functional monomer with a spiral structure to the surface of a silicon sphere under the induction of the initiating catalyst to form the silicon dioxide microsphere grafted with a monomolecular functional monomer hybrid spiral polymer, and using the silicon dioxide microsphere for fixing relative chirality through capillary liquid chromatography to realize the resolution of the chiral enantiomers.
Background
Chirality is considered as one of the key structural factors in nature that perform a series of complex functions, widely existing in biological processes. Wherein a helix is one of its simplest and most important states, for example, a polypeptide chain constituting a protein and a deoxynucleotide constituting a DNA chain each have a helical structure. The discovery of the helical structure draws the attention of scientists on the synthesis of helical molecules and helical oligomers, so that the importance of chiral materials is widely recognized. As The research proceeds, a number of phenomena and rules have been discovered, including "chiral magnification effect" (document 1: Green et al "The macromolecular analysis" Angew. chem., int. Ed., 1999, 38 (21): 3138-. The single-handed helical polymer simulates a helical structure in a biological macromolecule, is a unique chiral polymer which is artificially synthesized and can show a chiral amplification effect. In particular, the substituted polyacetylene compound with the helical structure can show excellent optical rotation property under specific preparation conditions, so that the substituted polyacetylene compound has wide application prospects in the fields of chiral resolution, display materials, molecular recognition and the like.
At present, more than 25 percent of the drugs used clinically have optical activity and are chiral drugs. Although chiral isomers have similar physicochemical properties therebetween, they show a large difference in distribution, metabolism, and the like in an organism. For example, the well-known "reaction stop (thalidomide)" event, the inability to isolate and identify chiral compounds has led to a huge tragedy due to the lagging technological level at that time, where people have poorly understood the differences between chiral enantiomers. It follows that the development of chiral resolution technology is of great importance in human life and scientific research. In addition, the hybrid material is formed by combining organic and inorganic parts through chemical bonds, combines the advantages of organic and inorganic components, and is widely applied to the fields of adsorption, catalysis, storage, separation, medicine carrying and the like. By combining the hybrid material with a chiral structure, a hybrid chiral material with more functions and novel is generated, and the hybrid chiral material has great application value in the fields of chiral resolution, enantioselective catalysis, optical devices and the like.
The side chain of the chiral Fmoc-L-phenylalanine is modified to have alkynyl, and the chiral Fmoc-L-phenylalanine is polymerized by chemical reaction to show single helical conformation; and introducing alkynyl on the surface of the silicon sphere by using a silanization reagent, so that the alkynyl on the surface of the silicon sphere and the prepared substituted polyacetylene monomer generate copolymerization reaction to prepare the silica gel microsphere chiral stationary phase with a chiral resolution function.
Disclosure of Invention
The invention aims to provide a spiral polymer functionalized silica gel microsphere Chiral Stationary Phase (CSP) and application thereof, which can be used as a stationary Phase of capillary liquid chromatography to efficiently and quickly separate enantiomers.
The structure thereof is schematically shown in the formula (23< n <29) as follows,
the particle size of the spiral polymer functionalized silica gel microsphere chiral stationary phase is 2.9-3.2 mu m.
The preparation can be carried out as follows,
1) activating the silicon dioxide microspheres;
dispersing 0.8-1.2 g of silicon dioxide microspheres in 30-40 mL of hydrochloric acid solution (2.8-3.2 mol L) under the action of ultrasound -1 ) Placing the mixture in an oil bath at 105-115 ℃ for reflux reaction for 8-12 h. Filtering with sand core funnel to obtain silica microsphere, and sequentially using ultrapure waterWashing the silicon balls with methanol, and then drying the silicon balls in a vacuum drying oven at the temperature of 40-80 ℃ for 12-24 hours;
2) introducing alkynyl on the surface of the silicon dioxide microsphere;
dispersing 0.8-1.2 g of activated silica microspheres obtained in the step 1) in 30-40 mL of dry toluene under the ultrasonic action, adding 0.6-0.7 g of silylation reagent O- (propargyloxy) -N- (triethoxysilylpropyl) carbamate and 100-105 mu L of anhydrous triethylamine, and carrying out reflux reaction for 12-24 h under the protection of nitrogen in 110-120 ℃ oil bath. After the reaction is finished, stirring and cooling to room temperature, then washing the silicon spheres by sequentially using toluene and methanol, and drying in a vacuum drying oven at 100-110 ℃ for 12-24 h; (ii) a
3) Preparing Fmoc-L-phenylalanine functional monomers (spiral polymer monomers);
weighing 0.7-0.8 g of Fmoc-L-phenylalanine (also known as fluorenylmethoxycarbonyl-L-phenylalanine) and dissolving in 50-60 mL of dry Tetrahydrofuran (THF), sequentially adding 0.2-0.3 mL of isobutyl chloroformate and 0.2-0.3 mL of N-methylmorpholine, and stirring at 29-31 ℃ for reaction for 15-20 min. And then 0.12-0.14 mL of propargylamine is dropwise added into the reaction solution, and the mixture is continuously stirred and reacted for 4-5h at the temperature of 29-31 ℃. After the reaction is finished, filtering and discarding the white solid, taking 20-23 mL ethyl acetate to dissolve filtrate, and sequentially using 20-23 mL 2mol L -1 Washing the organic phase with hydrochloric acid and 20-23 mL of saturated sodium bicarbonate solution for three times, and drying the organic phase with 3-5 g of anhydrous magnesium sulfate for 12-18 h. Finally, filtering out anhydrous magnesium sulfate, carrying out rotary evaporation on the reaction liquid to remove the solvent, dissolving the product by using a small amount of tetrahydrofuran, and pouring the product into a large amount of n-hexane for recrystallization to obtain a product;
4) preparing a spiral polymer functionalized silica gel microsphere chiral stationary phase;
dispersing 50-100 mg of the alkynyl functionalized silicon dioxide microspheres prepared in the step 2) in 500-800 mu L of dry tetrahydrofuran; dissolving the Fmoc-L-phenylalanine functional monomer prepared in the step 3) in 500-800 mu L of dry tetrahydrofuran; ultrasonically mixing the two solutions, adding 1.0-2.5 mg of catalyst rhodium dichloride and 0-100 mu L of anhydrous triethylamine, putting a reaction container (ampoule bottle) into liquid nitrogen for freezing, vacuumizing the reaction system, sealing the ampoule bottle by butane flame, then putting the ampoule bottle into a shaking table for oscillation reaction at 30 ℃ for 24-48 h, washing a product by tetrahydrofuran, and putting the product into a vacuum drying oven at 60-80 ℃ for drying for 12-24 h for later use;
the preparation method comprises the steps of firstly introducing alkynyl on the surface of a silica gel microsphere, then adding a functional monomer (Fmoc-L-phenylalanine derivative) and a catalyst, wherein the monomer can perform alkynyl-alkynyl addition polymerization reaction under the action of the catalyst to form a spiral structure, so that the silica gel microsphere material of the surface modified spiral polymer is prepared. The chiral stationary phase has simple preparation process and mild reaction condition, and can be used for large-scale preparation.
Drawings
FIG. 1 is a schematic diagram of the preparation of Fmoc-L-phenylalanine functional monomers.
FIG. 2 is a MALDI-TOF mass spectrum of Fmoc-L-phenylalanine functional monomer.
FIG. 3 is a schematic diagram of the preparation of a spiral polymer functionalized silica gel microsphere stationary phase.
FIG. 4 is a scanning electron microscope image (a is bare silicon sphere, b is surface alkynylated silicon sphere, and c is spiral polymer functionalized silica gel microsphere).
FIG. 5 shows the structure of the enantiomeric compound (a is (+/-) brompheniramine maleate structure, b is DL-beta-phenyllactic acid structure, "+" represents chiral site).
FIG. 6 is a chromatogram for enantiomeric separation. Separating (1) (+/-) bromopheniramine maleate, wherein the chromatographic condition is a capillary column (20.0cm multiplied by 200 mu m i.d.), the mobile phase is acetonitrile/water (95/5, v/v), and the flow rate is 200 mu L/min (before shunting); isolation (2) chromatographic conditions for DL-beta-phenyllactic acid were capillary column (19.8 cm. times.200. mu. m i.d.), mobile phase acetonitrile/water (80/20, v/v) and flow rate 200. mu.L/min (before splitting).
Detailed Description
Examples
Preparation of chiral stationary phase:
1) dioxygenActivating the silicon dioxide microspheres: dispersing 1.0g of silicon dioxide microspheres (2.9-3.2 μm) in 30mL of hydrochloric acid solution (3mol L) under the action of ultrasound -1 ) Placing the mixture in an oil bath at 110 ℃ for reflux reaction for 12 hours. Filtering with a sand core funnel to obtain silicon dioxide microspheres, washing the silicon microspheres with ultrapure water and methanol in sequence, and then drying in a vacuum drying oven at 80 ℃ for 24 hours;
2) connecting alkynyl on the surface of the silicon dioxide microsphere: 1.0g of the activated silica microspheres in the step 1) are dispersed in 30mL of dry toluene under the action of ultrasound, 0.6g of silylation reagent O- (propargyloxy) -N- (triethoxysilylpropyl) carbamate and 100 mu L of anhydrous triethylamine are added, and reflux reaction is carried out for 24h at 120 ℃ under the protection of nitrogen. After the reaction is finished, stirring and cooling to room temperature, then washing the silicon spheres by using toluene and methanol in sequence, and drying for 24 hours in a vacuum drying oven at 100 ℃; (ii) a
3) Preparation of Fmoc-L-phenylalanine functional monomer (helical polymer monomer): 0.775g Fmoc-L-phenylalanine was weighed out and dissolved in 50mL dry Tetrahydrofuran (THF), 0.26mL isobutyl chloroformate and 0.22mL N-methylmorpholine were added in this order, and the reaction was stirred at 30 ℃ for 15 min. Then, 0.13mL of propargylamine was added dropwise to the reaction mixture, and the reaction was continued at 30 ℃ with stirring for 4 hours. After the reaction, the white solid was filtered and discarded, and 20mL of ethyl acetate was taken to dissolve the filtrate, and 2mol L of each was used in order -1 The organic phase is washed three times with hydrochloric acid and with 20mL of saturated sodium bicarbonate solution and dried for 12h using 4g of anhydrous magnesium sulfate. Finally, filtering out anhydrous magnesium sulfate, carrying out rotary evaporation on the reaction liquid to remove the solvent, dissolving the product with 2mL of tetrahydrofuran, and pouring the product into 150mL of n-hexane for recrystallization to obtain a product;
4) preparing a chiral stationary phase of the spiral polymer functionalized silica gel microsphere: 80mg of alkynyl functionalized silica microspheres prepared in the step 2) are dispersed in 800 mu L of dry tetrahydrofuran, and Fmoc-L-phenylalanine functional monomers prepared in the step 3) are dissolved in 800 mu L of dry tetrahydrofuran; ultrasonically mixing the two solutions, adding 2.0mg of catalyst rhodium dichloride and 100 mu L of anhydrous triethylamine, placing a reaction container (ampoule bottle) into liquid nitrogen for freezing, vacuumizing the reaction system, sealing the ampoule bottle by butane flame, placing the ampoule bottle in a shaking table for oscillation reaction at 30 ℃ for 48 hours, washing a product by tetrahydrofuran, and placing the product in a vacuum drying oven at 80 ℃ for drying for 24 hours for later use (document 3: Zhangtongye, synthesis and application research [ D ] of optically active substituted acetylene spiral polymer particles, Beijing chemical university);
filling a chiral capillary liquid chromatographic column: and (3) adding 20mg of the chiral stationary phase prepared in the step 4) into a centrifugal tube filled with 700 mu L of methanol, performing ultrasonic dispersion for 3min, filling the obtained chiral stationary phase homogenate into a homogenate tank, adding magnetons, and pressing the homogenate into a capillary tube through a pneumatic pump under the condition that methanol is used as a displacement liquid and magnetic stirring is performed. The specification of the capillary chromatographic column is 26.0cm multiplied by 200 μm i.d., and the packing pressure is 50 MPa.
Chromatographic characterization
FIG. 2 is a MALDI-TOF mass spectrum of Fmoc-L-phenylalanine functional monomer. The relative molecular mass of the Fmoc-L-phenylalanine functional monomer is 423, the mass-to-charge ratio 447.11 in the mass-to-charge spectrum is the sodium addition peak of the functional monomer, and the mass-to-charge ratio 463.08 is the potassium addition peak of the functional monomer, which indicates that the Fmoc-L-phenylalanine functional monomer is successfully synthesized.
FIG. 4 is a scanning electron microscope image (a is bare silicon sphere, b is surface alkynylated silicon sphere, and c is spiral polymer functionalized silica gel microsphere). By comparing the surface topography of fig. 4a and b, it can be seen that the alkynyl group was successfully introduced to the surface of the silicon sphere; by comparing the surface morphologies of fig. 4b and c, it can be found that the helical polymer was successfully grafted on the surface of the alkynyl functionalized silica gel microsphere.
FIG. 5 shows the structure of the enantiomeric compound (a is (+/-) bromophenylanilide maleate structure; b is DL-. beta. -phenyllactic acid structure; and ". dot." represents a chiral site).
FIG. 6 is a chromatogram for enantiomeric separation. Separating (1) (+/-) bromopheniramine maleate, wherein the chromatographic condition is a capillary column (20.0cm multiplied by 200 mu m i.d.), the mobile phase is acetonitrile/water (95/5, v/v), and the flow rate is 200 mu L/min (before shunting); isolation (2) chromatographic conditions for DL-beta-phenyllactic acid were capillary column (19.8 cm. times.200. mu. m i.d.), mobile phase acetonitrile/water (80/20, v/v) and flow rate 200. mu.L/min (before splitting).
As can be seen from the figure, the enantiomers of two groups of chiral compounds can be well separated, the separation degree of the two enantiomers of (+/-) brompheniramine maleate is 5.6, and the separation degree of the two enantiomers of (+/-) DL-beta-phenyllactic acid is 3.1, which shows that the silica gel microsphere material with the helical structure shows the chiral separation capability on the chiral enantiomers.
The preparation method adopted by the invention has the advantages of simple process, mild reaction conditions, high reaction efficiency and the like, and the prepared silica gel microsphere material with a spiral structure shows high resolution capability on the separation of the (+/-) brompheniramine maleate and the DL-beta-phenyllactic acid chiral enantiomer.
Claims (7)
1. A preparation method of a spiral polymer functionalized silica gel microsphere chiral stationary phase is characterized by comprising the following steps: the stationary phase is characterized in that alkynyl is introduced on the surface of a silicon dioxide microsphere through a silanization reaction, and then a spiral polymer is further grafted through an alkynyl-alkynyl addition reaction, wherein the spiral polymer is formed by self polymerization of Fmoc-L-phenylalanine functional monomers;
after modifying alkynyl on the surface of the silicon dioxide microsphere, adding a functional monomer and a catalyst, and grafting a polymer with a spiral structure to the surface of the silicon sphere under the induction of the catalyst to form the silicon dioxide microsphere grafted with the spiral polymer;
the method can be operated according to the following steps,
1) activation of silica microspheres: dispersing 0.8-1.2 g of silicon dioxide microspheres in 30-40 mL of 2.8-3.2 mol L under the action of ultrasound -1 Carrying out reflux reaction in a hydrochloric acid solution at 105-115 ℃ for 8-12 h; after the reaction is finished, filtering, washing the silicon spheres by ultrapure water and methanol in sequence, and then drying to obtain acidified silicon dioxide microspheres;
2) introducing alkynyl on the surface of the silicon dioxide microsphere: taking 0.8-1.2 g of the silicon dioxide microspheres acidified in the step 1), dispersing the silicon dioxide microspheres in 30-40 mL of dry toluene under the action of ultrasound, adding 0.6-0.7 g of silylation reagent O- (propargyloxy) -N- (triethoxysilylpropyl) carbamate and 100-105 mu L of anhydrous triethylamine, and carrying out reflux reaction for 12-24 h at 110-120 ℃ under the protection of nitrogen; after the reaction is finished, stirring and cooling to room temperature, then washing the silicon spheres by using toluene and methanol in sequence, and drying;
3) preparation of Fmoc-L-phenylalanine functional monomer, namely, helical polymer monomer: weighing 0.7-0.8 g of Fmoc-L-phenylalanine, dissolving in 50-60 mL of tetrahydrofuran, sequentially adding 0.2-0.3 mL of isobutyl chloroformate and 0.2-0.3 mL of N-methylmorpholine, and stirring at 29-31 ℃ for reaction for 15-20 min; then 0.12-0.14 mL of propargylamine is dropwise added into the reaction solution, and stirring and reacting are continued at 29-31 ℃ for 4-5 h; after the reaction is finished, filtering and discarding the white solid, taking 20-23 mL of ethyl acetate to dissolve filtrate, and sequentially using 20-23 mL of 1.9-2 mol L -1 Washing the organic phase with hydrochloric acid and 20-23 mL of saturated sodium bicarbonate solution for three times, and drying the organic phase with 3-5 g of anhydrous magnesium sulfate for 12-18 h; after drying, filtering to remove anhydrous magnesium sulfate, performing rotary evaporation on the reaction liquid to remove the solvent, dissolving the product with 2-5 mL of tetrahydrofuran, and pouring into 100-300mL of n-hexane for recrystallization to obtain a product;
4) preparing a spiral polymer functionalized silica gel microsphere chiral stationary phase: dispersing 50-100 mg of alkynyl functionalized silicon dioxide microspheres prepared in the step 2) in 500-800 mu L of tetrahydrofuran; 40-60mg of Fmoc-L-phenylalanine functional monomer prepared in the step 3) is dissolved in 500-800 mu L of dry tetrahydrofuran; ultrasonically mixing the two solutions, transferring the two solutions into an ampoule bottle, adding 1.0-2.5 mg of catalyst rhodium dichloride and 0-100 mu L of anhydrous triethylamine, freezing the ampoule bottle in liquid nitrogen until the reaction solution becomes solid, vacuumizing a reaction system, sealing the ampoule bottle by using butane flame, then placing the ampoule bottle in a shaking table for oscillation reaction at 29-31 ℃ for 24-48 h, washing a product by using tetrahydrofuran, and then placing the product in a vacuum drying oven at 60-80 ℃ for drying for 12-24 h to obtain the spiral polymer functionalized silica gel microsphere chiral stationary phase.
2. The method of claim 1, wherein:
the preparation process and the structural schematic formula are as follows:
where 23< n < 29.
3. The method of claim 1, wherein:
filling a chiral capillary liquid chromatographic column: adding 15-30 mg of the chiral stationary phase prepared in the step 4) into a centrifuge tube filled with 500-700 mu L of methanol, performing ultrasonic dispersion for 2-3 min to form homogenate, transferring the homogenate into a homogenate tank, adding magnetons, using methanol as a displacement liquid, and pressing the displacement liquid into a capillary tube through a pneumatic pump under magnetic stirring; the specification of the capillary liquid chromatographic column is as follows: the length of the filler is 26.0cm, the inner diameter of the filler is 75 mu m, and the filling pressure is 35-60 MPa.
4. The method of claim 1, wherein:
the particle size of the silicon dioxide microsphere raw material in the step 1) is 2.9-3.2 microns, and the drying process in the step 1) is drying in a vacuum drying oven at 40-80 ℃ for 12-24 hours;
the drying process in the step 2) is drying for 12-24 hours in a vacuum drying oven at 100-110 ℃;
the drying process in the step 4) is drying in a vacuum drying oven at the temperature of 60-80 ℃ for 12-24 hours.
5. A chiral stationary phase of spiral polymer functionalized silica gel microspheres prepared by the preparation method of any one of claims 1 to 4.
6. The application of the spiral polymer functionalized silica gel microsphere chiral stationary phase as claimed in claim 5, is characterized in that: it can be used as the stationary phase of capillary liquid chromatography for chiral separation of enantiomer.
7. Use according to claim 6, characterized in that:
the enantiomers are (+/-) brompheniramine maleate and DL-beta-phenyllactic acid.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104324707A (en) * | 2014-09-16 | 2015-02-04 | 华东理工大学 | Amino diacid hydrophilic chromatographic stationary phase and preparation method thereof |
| CN104910046A (en) * | 2015-04-14 | 2015-09-16 | 哈尔滨工程大学 | Phenylacetylene derivative with double chiral carbon atoms on pendant group and preparation method and application thereof |
| CN105312039A (en) * | 2014-07-17 | 2016-02-10 | 中国科学院大连化学物理研究所 | Beta-cyclodextrin functionalized chiral stationary phase, preparation and application thereof |
| CN105504159A (en) * | 2016-02-02 | 2016-04-20 | 中南大学 | Bonded chiral amino alcohol polymer and preparation method and application thereof |
| CN105642260A (en) * | 2014-12-02 | 2016-06-08 | 中国科学院大连化学物理研究所 | Dendritic C18 silica microsphere stationary phase, preparation and application thereof |
-
2020
- 2020-03-24 CN CN202010213013.2A patent/CN113441122B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105312039A (en) * | 2014-07-17 | 2016-02-10 | 中国科学院大连化学物理研究所 | Beta-cyclodextrin functionalized chiral stationary phase, preparation and application thereof |
| CN104324707A (en) * | 2014-09-16 | 2015-02-04 | 华东理工大学 | Amino diacid hydrophilic chromatographic stationary phase and preparation method thereof |
| CN105642260A (en) * | 2014-12-02 | 2016-06-08 | 中国科学院大连化学物理研究所 | Dendritic C18 silica microsphere stationary phase, preparation and application thereof |
| CN104910046A (en) * | 2015-04-14 | 2015-09-16 | 哈尔滨工程大学 | Phenylacetylene derivative with double chiral carbon atoms on pendant group and preparation method and application thereof |
| CN105504159A (en) * | 2016-02-02 | 2016-04-20 | 中南大学 | Bonded chiral amino alcohol polymer and preparation method and application thereof |
Non-Patent Citations (5)
| Title |
|---|
| "Immobilization of helical poly(phenylacetylene)s having";Yanli Zhou等;《Polymer》;20171010;第17-24页 * |
| "有机倍半硅氧烷的制备及其在手性固定相和单手螺旋碳质纳米纤维中的应用";王庆锋;《中国优秀硕士学位论文全文数据库 工程科技I辑》;20140915;第13-30页 * |
| D-苯丙氨酸为原料合成螺旋结构聚乙炔高聚物;张艳等;《辽宁化工》;20150930(第09期);第1075-1077页 * |
| 张艳等.D-苯丙氨酸为原料合成螺旋结构聚乙炔高聚物.《辽宁化工》.2015,(第09期),第1075-1077页. * |
| 王庆锋."有机倍半硅氧烷的制备及其在手性固定相和单手螺旋碳质纳米纤维中的应用".《中国优秀硕士学位论文全文数据库 工程科技I辑》.2014,第13-30页. * |
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