A functionalized magnetic nanoparticle and its application as a chiral extractant in the liquid-liquid extraction resolution of chiral compounds

Abstract

The present invention discloses a functionalized magnetic nanoparticle and its application as a chiral extractant in the liquid-liquid extraction for resolving chiral compounds. In the present invention, SBE-β-CD is used as a functional molecule, and it is coated onto the surface of magnetic nanoparticles by a one-pot method to prepare the functionalized magnetic nanoparticles, which simplifies the operation and shortens the preparation time. The functionalized magnetic nanoparticles are used as chiral extractants in the liquid-liquid extraction for resolving chiral compounds. By replacing the enantioselective adsorption with a simple and rapid liquid-liquid extraction, the recognition and resolution rate of chiral compounds are effectively improved. Depending on the superparamagnetism of the magnetic nanomaterials, the problem of difficult recovery is effectively solved.

Description

(1) Technical Field

[0001] The present invention relates to a functionalized magnetic nanoparticle and its application as a chiral extractant in the liquid-liquid extraction for the resolution of chiral compounds. (2) Background Art

[0002] Chirality is the basic symmetry of elements, molecules and even macroscopic objects (such as human hands), and is also the basic property of the molecular structure in nature. The physical and chemical properties of the two enantiomers of a chiral molecule are basically the same, but each enantiomer shows different physiological and pharmacological effects in the chiral life system, especially for chiral drugs. The enantioselective liquid-liquid extraction technology combines enantiomeric recognition with solvent extraction, and has the advantages of simple equipment, easy operation, easy scale-up, good separation effect, etc., and has broad application prospects. The chiral recognition process in enantioselective liquid-liquid extraction is closely related to host-guest chemistry, and its chiral recognition principle is achieved by the formation of diastereomers through the intermolecular force between the chiral extractant and the enantiomer. However, the high-value chiral reagents currently used in chiral liquid-liquid extraction are difficult to recover after extraction, are not convenient for repeated use, and do not conform to the sustainable development concept of green environmental protection.

[0003] Magnetic nanomaterials have broad application prospects in high-efficiency separation, sensitive measurement and selective catalysis due to their physical lengths different from those of conventional magnetic materials. Magnetic nanomaterials have significant advantages in the field of chiral recognition and separation due to their superparamagnetism, modifiability and recyclability. The rich groups on the surface of magnetic nanomaterials can be modified by a variety of chiral reagents, so they have chiral recognition ability, and are also relatively easy to be separated from the experimental solution under the action of an external magnetic field and can be reused. However, currently functionalized magnetic nanomaterials are mainly used in the research of enantioselective adsorption, and the research objects are mainly limited to aromatic amino acids. The process of enantioselective adsorption takes a long time, which is not conducive to the rapid separation and analysis of enantiomers, and the relatively single research object also limits the further use of functionalized magnetic nanoparticles.

[0004] Chinese Patent CN202111657351.6 reported by Wang Xiujuan et al. discloses a preparation method of magnetic nanoparticles for adsorbing aflatoxin; Chinese Patent CN201611254959.3 reported by Miao Lei et al. discloses the preparation of a chiral resolution additive for simply modifying magnetic nanoparticles and used as a polymer additive for chiral separation. There has been no patent on the method of bonding sulfobutyl ether-β-cyclodextrin (SBE-β-CD) to magnetic nanoparticles and using them for chiral liquid-liquid extraction resolution. (III) Summary of the Invention

[0005] The object of the present invention is to provide a functionalized magnetic nanoparticle and its application as a chiral extractant in the liquid-liquid extraction for the resolution of chiral compounds. Using SBE-β-CD as the functional molecule, it is coated on the surface of magnetic nanoparticles by a one-pot method, which simplifies the operation and shortens the preparation time. The functionalized magnetic nanoparticle is used as a chiral extractant in the chiral liquid-liquid extraction for the resolution of chiral compounds. By replacing the enantioselective adsorption with a simple and rapid chiral liquid-liquid extraction, the recognition and resolution rate of chiral compounds are effectively improved. Depending on the superparamagnetism of magnetic nanomaterials, the problem of difficult recovery is effectively solved.

[0006] The technical solution adopted by the present invention is as follows:

[0007] The present invention provides a functionalized magnetic nanoparticle, and the functionalized magnetic nanoparticle is prepared according to the following steps:

[0008] (1) Dissolve FeCl2 and FeCl3 in distilled water, heat the solution to 70 - 90 °C, quickly add ammonia water (preferably with a mass concentration of 25%), and continue the reaction for 20 - 60 min; after the reaction is completed, cool to room temperature, and wash the obtained suspension with distilled water until the pH is close to neutral; separate the bare Fe3O4 magnetic nanoparticles from the suspension by magnetic adsorption, and freeze-dry to remove the residual moisture in the magnetic nanoparticles to obtain magnetic nanoparticles;

[0009] (2) Take the magnetic nanoparticles obtained in step (1), ultrasonically disperse them in an aqueous citric acid solution, and mechanically stir at 20 - 50 °C for 6 - 24 h; after the reaction is completed, separate the magnetic nanoparticles by magnetic adsorption, wash them several times with distilled water, and freeze-dry to remove the residual moisture to obtain citric acid-modified magnetic nanoparticles;

[0010] (3) Take the citric acid-modified magnetic nanoparticles obtained in step (2), ultrasonically disperse them in a mixed solution of isopropanol and distilled water, add ammonia water and tetraethyl orthosilicate (TEOS), and mechanically stir at 20 - 50 °C for 6 - 24 h; after the reaction is completed, separate the magnetic nanoparticles by magnetic adsorption, wash them several times with distilled water, and freeze-dry to remove the residual moisture to obtain silica-coated magnetic nanoparticles;

[0011] (4) Drop [3-(2,3-epoxypropoxy)propyl]trimethoxysilane (GPTES) into an anhydrous N,N-dimethylformamide solution containing sulfobutylether-β-cyclodextrin (SBE-β-CD), and mechanically stir at 40 - 70 °C for 1 - 6 h to obtain a reaction solution;

[0012] (5) Disperse the silica-coated magnetic nanoparticles described in step (3) ultrasonically in the reaction solution described in step (4), and continue mechanical stirring for 6 - 24 h; after the reaction is completed, cool the reaction solution to room temperature, wash it three times with N,N-dimethylformamide, ethanol, and distilled water respectively, and then freeze-dry to remove the residual moisture to obtain functionalized magnetic nanoparticles (Fe3O4 / SiO2 / GP / SBECD MNPs).

[0013] Preferably, in step (1), the molar ratio of the feed of FeCl2 to FeCl3 is 1:2 - 5, preferably 1:2; the total concentration of iron ions of FeCl2 and FeCl3 in distilled water is 0.1 - 1.0 M, preferably 0.30 M. The volume of ammonia water used is 0.5 - 2.0 mL / g based on the total mass of the feed of FeCl2 and FeCl3, preferably 1.0 mL / g.

[0014] Preferably, in step (1), heat the solution to 80 °C, quickly add ammonia water, and continue the reaction for 30 min.

[0015] Preferably, in step (2), the concentration of the citric acid aqueous solution is 0.3 M, and the volume of the citric acid aqueous solution used is 100 - 300 mL / g (preferably 200 mL / g) based on the mass of the magnetic nanoparticles described in step (1); preferably, ultrasonically disperse at 20 Hz and mechanically stir at 25 °C for 12 h.

[0016] Preferably, in step (3), the volume ratio of isopropyl alcohol to distilled water is 3 - 6:1 (preferably 5:1), and the total volume of isopropyl alcohol and distilled water used is 100 - 300 mL / g (preferably 240 mL / g) based on the mass of the citric acid-modified magnetic nanoparticles described in step (2); the volume of ammonia water used is 1 - 10 mL / g (preferably 5 mL / g) based on the mass of the citric acid-modified magnetic nanoparticles described in step (2); the volume of tetraethyl orthosilicate used is 1 - 10 mL / g (preferably 1 mL / g) based on the mass of the citric acid-modified magnetic nanoparticles described in step (2).

[0017] Preferably, in step (3), ultrasonically disperse at 40 Hz and mechanically stir at 25 °C for 6 h.

[0018] Preferably, in step (4), the volume of the anhydrous N,N-dimethylformamide solution used is 10 - 30 mL / g (preferably 19 mL / g) based on the mass of SBE-β-CD; the volume of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane used is 0.1 - 1 mL / g (preferably 0.5 mL / g) based on the mass of SBE-β-CD.

[0019] Preferably, in step (4), mechanically stir at 50 °C for 3 h.

[0020] Preferably, in step (5), the volume of the reaction solution in step (4) is 20 - 60 mL / g (preferably 40 mL / g) based on the mass of the silica-coated magnetic nanoparticles in step (3).

[0021] Preferably, in step (5), ultrasonic dispersion is carried out at 40 Hz and mechanical stirring is carried out at 50 °C for 12 h.

[0022] Preferably, freeze-drying in steps (1), (2), (3), and (5) is carried out at -70 °C.

[0023] The present invention also provides an application of the functionalized magnetic nanoparticles as a chiral extractant in the liquid-liquid extraction for resolving chiral compounds, wherein the chiral compounds are acidic or basic chiral compounds, including trans-paroxetine, acetyltropic acid or N-methyl duloxetine.

[0024] Compared with the prior art, the beneficial effects of the present invention are mainly reflected in that: in the existing method, preparing magnetic nanoparticles requires first reacting a silane coupling agent with the magnetic nanoparticles, and then bonding with other chiral reagents. The synthesis time is long, the bonding rate of the chiral reagents is relatively low, and the separation effect is not clear. The functionalized magnetic nanoparticles prepared by the present invention first react SBE-β-CD with a silane coupling agent in a solvent, and then coat them onto the surface of the magnetic nanoparticles by a one-pot method. The preparation process has mild conditions, simple operation, short preparation time, and high SBE-β-CD coating rate; the functionalized magnetic nanoparticles have high chiral recognition ability, significant separation effect, and a wide range of separation objects, and can be used for the recognition and resolution of basic or acidic chiral compounds, especially the chiral liquid-liquid extraction resolution of various drugs / intermediates, with high economic benefits. (IV) BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 : Schematic diagram of the synthesis of functionalized magnetic nanoparticles.

[0026] Figure 2 : Thermogravimetric curve of the functionalized magnetic nanoparticles prepared in Example 1: Curve a represents the thermogravimetric curve of Fe3O4 magnetic nanoparticles in step (1) of Example 1, curve b represents the thermogravimetric curve of silica-coated magnetic nanoparticles in step (3) of Example 1, and curve c represents the thermogravimetric curve of functionalized magnetic nanoparticles in step (5) of Example 1.

[0027] Figure 3 : Flow chart of chiral liquid-liquid extraction resolution.

[0028] Figure 4 : High performance liquid chromatography (HPLC) diagrams before and after liquid-liquid extraction in Example 2; Curve a represents the HPLC diagram of the aqueous phase before chiral liquid-liquid extraction, and curve b represents the HPLC diagram of the organic phase after chiral liquid-liquid extraction.

[0029] Figure 5 : HPLC (High Performance Liquid Chromatography) diagrams before and after liquid-liquid extraction in Example 3; Curve a represents the HPLC diagram of the aqueous phase before chiral liquid-liquid extraction, and curve b represents the HPLC diagram of the organic phase after chiral liquid-liquid extraction.

[0030] Figure 6 : HPLC (High Performance Liquid Chromatography) diagrams before and after liquid-liquid extraction in Example 4; Curve a represents the HPLC diagram of the aqueous phase before chiral liquid-liquid extraction, and curve b represents the HPLC diagram of the organic phase after chiral liquid-liquid extraction. (V) Specific Embodiments

[0031] The present invention will be further described below in conjunction with specific embodiments, but the protection scope of the present invention is not limited thereto:

[0032] In the embodiments of the present invention, the high performance liquid chromatography used is a Shimadzu analytical LC-20A high performance liquid chromatograph (Shimadzu, Japan), which includes an SPD-20A UV detector, a dual LC-20ATvp liquid phase pump, a CTO-10ASvp column oven, a LabSolutions chromatographic workstation, a 20 μL injection loop, etc.

[0033] The room temperature is 25 - 30 °C. The mass concentration of the ammonia water (NH4OH solution) used is 25%.

[0034] Example 1: Functionalized Magnetic Nanoparticles

[0035] (1) Accurately weigh 2.5 g (0.02 mol) of FeCl2 and 6.5 g (0.04 mol) of FeCl3 (molar ratio 1:2), and dissolve them in 200 mL of distilled water so that the total concentration of iron ions in the solution is 0.30 M. Heat the solution to 80 °C, quickly add 25 mL of ammonia water, and continue the reaction for 30 min. After the reaction, cool to room temperature, and wash the obtained suspension with distilled water until the pH is close to neutral. Separate the bare Fe3O4 magnetic nanoparticles from the suspension by magnetic adsorption, and freeze-dry at -70 °C to remove the residual moisture in the magnetic nanoparticles, obtaining 4.2 g of Fe3O4 magnetic nanoparticles with an average particle size of 12 nm.

[0036] (2) Ultrasonically disperse 1 g of dry Fe3O4 magnetic nanoparticles in 200 mL of a citric acid aqueous solution (0.30 M) at 20 Hz, and mechanically stir at 25 °C for 12 h. After the reaction, separate the magnetic nanoparticles by magnetic adsorption, wash three times with distilled water, and freeze-dry at -70 °C to remove the residual moisture, obtaining 0.91 g of citric acid-modified Fe3O4 magnetic nanoparticles.

[0037] (3) 1 g of dried citric acid-modified Fe3O4 magnetic nanoparticles was ultrasonically dispersed in a mixed solution of 200 mL of isopropanol and 40 mL of distilled water at 40 Hz, and 5 mL of ammonia and 1 mL of tetraethyl orthosilicate (TEOS) were added, and mechanically stirred at 25°C for 6 h. After the reaction, the magnetic nanoparticles were separated by magnetic adsorption, washed three times with distilled water, and freeze-dried at -70°C to remove residual water, obtaining 1.1 g of silica-coated magnetic nanoparticles.

[0038] (4) 1 mL of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane (GPTES) was added dropwise to 40 mL of anhydrous N,N-dimethylformamide solution containing 2.1 g of sulphobutyl ether β-cyclodextrin (SBE-β-CD), and the mixture was mechanically stirred at 50° C. for 3 h to obtain 40 mL of a reaction solution.

[0039] (5) Take 1g of dried silica-coated magnetic nanoparticles and disperse them in 40mL of the reaction solution of step (4) by ultrasonic dispersion at 40Hz, and continue mechanical stirring for 12h. After the reaction is completed, the reaction solution is cooled to room temperature, washed three times with N,N-dimethylformamide, ethanol, and distilled water respectively, and then freeze-dried at -70℃ to remove the residual water, to obtain 1.0g of functionalized magnetic nanoparticles (Fe3O4 / SiO2 / GP / SBECD MNPs) with an average particle size of 20nm. The synthesis schematic diagram is shown in the figure. Figure 1 Its thermogravimetric curve is shown as Figure 2 As shown, the successful bonding of SBE-β-CD can be known from the change of thermal weight loss in the second stage (200-400°C).

[0040] Example 2: Functionalized magnetic nanoparticles as chiral extractants for chiral liquid-liquid extraction and separation of trans-parocalol

[0041] The aqueous phase contained 2 mmol·L -1 Trans-paroxol phosphate buffer (pH 9.0, 0.10 mol·L -1 ) composition, and the peak area of ​​the chromatographic peaks of (R)-trans-parocol and (S)-trans-parocol in the aqueous phase was detected by HPLC. 2 mL of aqueous phase, 2 mL of dichloromethane and 100 mg of the functionalized magnetic nanoparticles described in Example 1 were placed in a 10 mL stoppered centrifuge tube. After sufficient shaking, the tube was placed in a 5°C constant temperature water bath for equilibration for 2 hours, and then the peak area of ​​the chromatographic peaks of (R)-trans-parocol and (S)-trans-parocol in the organic phase was detected by HPLC. The distribution coefficient and separation factor were calculated according to the formula, as shown in FIG. Figure 3 shown.

[0042] HPLC images of trans-parocalol before and after extraction are shown in Figure 4 shown.

[0043] The distribution coefficient (D) and separation factor (α) can be calculated by the following formulas:

[0044]

[0045]

[0046] In the formula: A total represents the peak area of the enantiomer in the aqueous phase before extraction; A org represents the peak area of the enantiomer in the organic phase after extraction. The enantiomers refer to (R)-trans-paroxetine and (S)-trans-paroxetine.

[0047] After calculation, the distribution coefficients of (R)-trans-paroxetine and (S)-trans-paroxetine are 1.601 and 2.921 respectively, and the separation factor is 1.824. The results show that the prepared functionalized magnetic nanoparticles have good chiral recognition ability for trans-paroxetine.

[0048] The detection conditions of high performance liquid chromatography are: H&E SP ODS-AC 18 (150×4.6mm i.d., 5μm) chromatographic column; column temperature 25°C; mobile phase is phosphate buffer solution containing 2 mmol·L -1 SBE-β-CD (pH 3.0, 5 mmol·L -1 ): acetonitrile (85:15, v / v), isocratic elution mode, flow rate: 0.8 mL / min; detection wavelength: 215 nm; injection volume: 20 μL.

[0049] Example 3: Functionalized magnetic nanoparticles as chiral extractants for chiral liquid-liquid extraction of N-methyl duloxetine

[0050] The aqueous phase consists of phosphate buffer solution containing 2 mmol·L -1 N-methyl duloxetine (pH 8.0, 0.10 mol·L -1 ). The peak areas of the chromatographic peaks of (R)-N-methyl duloxetine and (S)-N-methyl duloxetine in the aqueous phase are detected by HPLC. 2 mL of the aqueous phase, 2 mL of n-hexane and 25 mg of the functionalized magnetic nanoparticles described in Example 1 are placed in a 10 mL stoppered centrifuge tube. After shaking well, it is left to stand in a constant temperature water bath at 5°C for 2 h. Then, the peak areas of the chromatographic peaks of (R)-N-methyl duloxetine and (S)-N-methyl duloxetine in the organic phase are detected by HPLC, and the distribution coefficient and separation factor are calculated according to the formula in Example 2.

[0051] The HPLC diagrams of N-methyl duloxetine before and after extraction are shown in Figure 5 as follows.

[0052] After calculation, the distribution coefficients of (S)-N-methyl duloxetine and (R)-N-methyl duloxetine are 2.971 and 4.398 respectively, and the separation factor is 1.480. The results show that the prepared functionalized magnetic nanoparticles have certain chiral recognition ability for N-methyl duloxetine.

[0053] The detection conditions of high performance liquid chromatography are: H&E SP ODS-AC 18 (150×4.6mm i.d., 5μm) chromatographic column; column temperature 35°C; mobile phase is phosphate buffer solution containing 5 mmol·L -1 SBE-β-CD (pH 3.0, 5 mmol·L -1 ): acetonitrile (68:32, v / v), isocratic elution mode, flow rate: 0.8 mL / min; detection wavelength: 230 nm; injection volume: 20 μL.

[0054] Example 4: Functionalized magnetic nanoparticles as chiral extractants for chiral liquid-liquid extraction to resolve acetyltropic acid

[0055] The aqueous phase consists of phosphate buffer solution (pH 3.0, 0.10 mol·L -1 ) containing 2 mmol·L acetyltropic acid. The peak areas of the chromatographic peaks of (R)-acetyltropic acid and (S)-acetyltropic acid in the aqueous phase are detected by HPLC. 2 mL of the aqueous phase, 2 mL of n-butyl acetate and 50 mg of the functionalized magnetic nanoparticles described in Example 1 are placed in a 10 mL stoppered centrifuge tube. After shaking well, it is left to stand in a constant temperature water bath at 5°C for 2 h, and then the peak areas of the chromatographic peaks of (R)-acetyltropic acid and (S)-acetyltropic acid in the organic phase are detected by HPLC. The distribution coefficient and separation factor are calculated using the formula in Example 2. -1

[0056] The HPLC diagrams of acetyltropic acid before and after extraction are shown in Figure 6 the figure.

[0057] After calculation, the distribution coefficients of (R)-acetyltropic acid and (S)-acetyltropic acid are 0.630 and 0.879 respectively, and the separation factor is 1.396. The results show that the prepared functionalized magnetic nanoparticles have certain chiral recognition ability for acetyltropic acid.

[0058] The detection conditions of high performance liquid chromatography are: H&E SP ODS-AC 18 (150×4.6mm i.d., 5μm) chromatographic column; column temperature 25°C; mobile phase is phosphate buffer solution containing 25 mmol·L -1Phosphate buffer solution (pH 3.0, 5 mmol·L -1 ) of hydroxypropyl-β-cyclodextrin (HP-β-CD): acetonitrile (90:10, v / v), isocratic elution mode, flow rate: 0.8 mL / min; detection wavelength: 220 nm; injection volume: 20 μL.

[0059] Comparative Example 1:

[0060] Change 2.1 g of trans-butyl ether β-cyclodextrin in step (4) of Example 1 to 1.1 g, and keep other operations the same to obtain 0.98 g of functionalized magnetic nanoparticles.

[0061] Perform chiral resolution by the method of Example 2. The separation factor obtained for trans-paroxetine is 1.351, and the chiral recognition ability is somewhat reduced.

[0062] Comparative Example 2:

[0063] Change 2.1 g of trans-butyl ether β-cyclodextrin in step (4) of Example 1 to 3.2 g, and keep other operations the same to obtain 1.0 g of functionalized magnetic nanoparticles.

[0064] Perform chiral resolution by the method of Example 2. The separation factor obtained for trans-paroxetine is 1.470, and the chiral recognition ability is somewhat reduced.

[0065] Comparative Example 3:

[0066] Change 2.5 g (0.02 mol) of FeCl2 and 6.5 g (0.04 mol) of FeCl3 (molar ratio 1:2) in step (1) of Example 1 to 1.2 g (0.01 mol) of FeCl2 and 8.2 g (0.05 mol) of FeCl3 (molar ratio 1:5), and keep other operations the same to obtain 2.6 g of Fe3O4 magnetic nanoparticles, with a reduced yield.

[0067] Comparative Example 4:

[0068] Change 100 mg of the functionalized magnetic nanoparticles described in Example 1 in Example 2 to 50 mg of the functionalized magnetic nanoparticles described in Example 1, and keep other operations the same. The separation factor obtained for trans-paroxetine is 1.473, and the chiral resolution effect is reduced.

[0069] Comparative Example 5:

[0070] Change 25 mg of the functionalized magnetic nanoparticles described in Example 1 in Example 3 to 50 mg of the functionalized magnetic nanoparticles described in Example 1, and keep other operations the same. The separation factor obtained for N-methyl duloxetine is 1.412, and the chiral resolution effect is reduced.

[0071] Comparative Example 6:

[0072] In Example 4, 50 mg of the functionalized magnetic nanoparticles described in Example 1 was changed to 100 mg of the functionalized magnetic nanoparticles described in Example 1, and other operations were the same. As a result, the separation factor obtained for tropic acid was 1.150, and the chiral resolution effect decreased.

[0073] The method of the present invention prepared SBE-β-CD-bonded functionalized magnetic nanoparticles, and realized the separation of enantiomers of trans-paroxetine, N-methyl duloxetine and tropic acid in the liquid-liquid extraction resolution of chiral compounds. The functionalized magnetic nanoparticles have good chiral recognition ability, can be used as chiral extractants to recognize enantiomer molecules in the liquid-liquid extraction resolution, and the preparation process is simple, the reaction is mild, and the cost is low.

Claims

1. A functionalized magnetic nanoparticle, characterized in that, The functionalized magnetic nanoparticles are prepared according to the following steps: (1) Dissolve FeCl2 and FeCl3 in distilled water, heat the solution to 70 - 90 °C, quickly add ammonia water, and continue the reaction for 20 - 60 min; after the reaction is completed, cool to room temperature, and wash the obtained suspension with distilled water until the pH is close to neutral; separate the bare Fe3O4 magnetic nanoparticles from the suspension by magnetic adsorption, and freeze-dry to remove the residual water in the magnetic nanoparticles to obtain magnetic nanoparticles; the molar ratio of the feed amount of FeCl2 to FeCl3 is 1:2 - 5; the total concentration of iron ions of FeCl2 and FeCl3 in distilled water is 0.1 - 1.0 M; the volume of ammonia water used is 0.5 - 2.0 mL / g based on the total mass of the feed of FeCl2 and FeCl3; (2) Take the magnetic nanoparticles obtained in step (1), ultrasonically disperse them in an aqueous citric acid solution, and mechanically stir at 20 - 50 °C for 6 - 24 h; after the reaction is completed, separate the magnetic nanoparticles by magnetic adsorption, wash them several times with distilled water, and then freeze-dry to remove the residual water to obtain citric acid-modified magnetic nanoparticles; (3) Take the citric acid-modified magnetic nanoparticles obtained in step (2), ultrasonically disperse them in a mixed solution of isopropanol and distilled water, add ammonia water and tetraethyl orthosilicate, and mechanically stir at 20 - 50 °C for 6 - 24 h; after the reaction is completed, separate the magnetic nanoparticles by magnetic adsorption, wash them several times with distilled water, and then freeze-dry to remove the residual water to obtain silica-coated magnetic nanoparticles; (4) Dropwise add [3-(2,3-epoxypropoxy)propyl]trimethoxysilane to an anhydrous N,N-dimethylformamide solution containing sulfobutyl ether-β-cyclodextrin, and mechanically stir at 40 - 70 °C for 1 - 6 h to obtain a reaction solution; (5) Take the silica-coated magnetic nanoparticles obtained in step (3), ultrasonically disperse them in the reaction solution obtained in step (4), and continue mechanical stirring for 6 - 24 h; after the reaction is completed, cool the reaction solution to room temperature, wash it three times with N,N-dimethylformamide, ethanol, and distilled water respectively, and then freeze-dry to remove the residual water to obtain functionalized magnetic nanoparticles.

2. The functionalized magnetic nanoparticles according to claim 1, wherein, In step (2), the concentration of the aqueous citric acid solution is 0.3 M, and the volume of the aqueous citric acid solution used is 100 - 300 mL / g based on the mass of the magnetic nanoparticles obtained in step (1).

3. The functionalized magnetic nanoparticles according to claim 1, wherein In step (2), ultrasonically disperse at 20 Hz and mechanically stir at 25 °C for 12 h.

4. The functionalized magnetic nanoparticles according to claim 1, wherein In step (3), the volume ratio of isopropanol to distilled water is 3 - 6:1, and the total volume of isopropanol and distilled water used is 100 - 300 mL / g based on the mass of the citric acid-modified magnetic nanoparticles obtained in step (2); the volume of ammonia water used is 1 - 10 mL / g based on the mass of the citric acid-modified magnetic nanoparticles obtained in step (2); the volume of tetraethyl orthosilicate used is 1 - 10 mL / g based on the mass of the citric acid-modified magnetic nanoparticles obtained in step (2).

5. The functionalized magnetic nanoparticles according to claim 1, wherein In step (4), the volume of the anhydrous N,N-dimethylformamide solution is 10 - 30 mL / g based on the mass of sulfobutyl ether-β-cyclodextrin; the volume of [3-(2,3-epoxypropoxy)propyl]trimethoxysilane is 0.1 - 1 mL / g based on the mass of sulfobutyl ether-β-cyclodextrin.

6. The functionalized magnetic nanoparticles according to claim 1, characterized in that, In step (5), the volume of the reaction solution in step (4) is 20 - 60 mL / g based on the mass of the silica-coated magnetic nanoparticles in step (3).

7. The functionalized magnetic nanoparticles according to claim 1, wherein In steps (3) and (5), the ultrasonic dispersion is carried out at 40 Hz.

8. Use of the functionalized magnetic nanoparticles according to claim 1 as a chiral extractant in the liquid-liquid extraction for resolving chiral compounds.

9. The application according to claim 8, wherein The chiral compounds include trans-paroxetine, acetyltropic acid or N-methyl duloxetine.

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