阅读说明：本技术 一种手性共轭微孔聚合物/二氧化硅复合膜的制备方法 (Preparation method of chiral conjugated microporous polymer/silicon dioxide composite membrane ) 是由 藏雨 徐亮 黄媛 贾宏葛 吴云峰 谢禹杰 崔嘉 荆博宇 于 2020-05-11 设计创作，主要内容包括：本发明属于手性共轭微孔聚合物制备技术领域,公开了一种手性共轭微孔聚合物/二氧化硅复合膜的制备方法,包括：制备带有初始聚合位点的多孔二氧化硅薄片A；向三颈瓶中加入2,5-二溴对苯二甲酰氯和D-薄荷醇,抽真空,氮气保护后注入甲苯,加热并搅拌反应,得到淡黄色油状液体,旋蒸获得粗产物,通过硅胶层析柱纯化得到单体B；向三颈瓶中加入多孔二氧化硅薄片A、1,3,5-三(4-炔基苯基)苯、三苯基膦、碘化亚铜和双三苯基膦氯化钯,然后注入三乙胺作为溶剂,加热并搅拌反应,向三颈瓶中加入单体B,加热并搅拌反应,制得粗产物,粗产物取出后分别使用甲苯、氯仿、碘化钾饱和溶液冲洗,干燥得到手性共轭微孔聚合物/二氧化硅复合膜。(The invention belongs to the technical field of preparation of chiral conjugated microporous polymers, and discloses a preparation method of a chiral conjugated microporous polymer/silicon dioxide composite membrane, which comprises the following steps: preparing a porous silica sheet A with initial polymerization sites; adding 2, 5-dibromo-p-phthaloyl chloride and D-menthol into a three-necked bottle, vacuumizing, injecting toluene after nitrogen protection, heating and stirring for reaction to obtain a light yellow oily liquid, performing rotary evaporation to obtain a crude product, and purifying by using a silica gel chromatographic column to obtain a monomer B; adding a porous silicon dioxide sheet A, 1,3, 5-tri (4-alkynyl phenyl) benzene, triphenylphosphine, cuprous iodide and bis (triphenylphosphine) palladium chloride into a three-necked bottle, then injecting triethylamine as a solvent, heating and stirring for reaction, adding a monomer B into the three-necked bottle, heating and stirring for reaction to obtain a crude product, taking out the crude product, washing with toluene, chloroform and potassium iodide saturated solutions respectively, and drying to obtain the chiral conjugated microporous polymer/silicon dioxide composite membrane.)

1. A preparation method of a chiral conjugated microporous polymer/silicon dioxide composite membrane is characterized in that the chiral conjugated microporous polymer/silicon dioxide composite membrane is prepared by an in-situ polymerization method by taking porous silicon dioxide as a substrate and a chiral conjugated microporous polymer as a skin layer, and the preparation method comprises the following steps:

s1, preparing a porous silicon dioxide sheet A with an initial polymerization site;

s2, adding 2, 5-dibromo terephthaloyl chloride and D-menthol into a three-necked bottle, vacuumizing, injecting toluene after nitrogen protection, heating to 70-90 ℃, continuously stirring at 70-90 ℃ for reaction for 12-15 hours to obtain light yellow oily liquid, performing rotary evaporation on the light yellow oily liquid to obtain a crude product, and purifying the crude product through a silica gel chromatographic column to obtain a monomer B;

s3, adding the porous silicon dioxide sheet A with the initial polymerization site, 1,3, 5-tri (4-alkynyl phenyl) benzene, triphenylphosphine, cuprous iodide and bis-triphenylphosphine palladium chloride, which are prepared in the step S1, into a three-necked bottle, then injecting triethylamine as a solvent, stirring and reacting at the temperature of 90-110 ℃ for 1 hour, adding the monomer B, which is prepared in the step S2, into the three-necked bottle after stirring, stirring and reacting at the temperature of 115-125 ℃ for 24 hours to prepare a crude product, taking out the crude product, washing the crude product with toluene, chloroform and potassium iodide saturated solutions respectively, and drying the washed product to obtain the chiral conjugated microporous polymer/silicon dioxide composite membrane.

2. The method of claim 1, wherein the step S1 of preparing the porous silica sheet a with initial polymerization sites comprises:

s11, polishing to prepare a porous silicon dioxide sheet a with the thickness of less than 2.00mm, the diameter of less than 15.0mm and a smooth surface;

s12, placing the porous silicon dioxide sheet a into absolute ethyl alcohol, performing ultrasonic treatment at least three times, then placing the porous silicon dioxide sheet a into hydrochloric acid, performing ultrasonic treatment at least three times, and drying after the ultrasonic treatment is completed to obtain a hydroxylated porous silicon dioxide sheet b;

s13, filling the hydroxylated porous silica sheet b into a single-mouth bottle, injecting a toluene solution c containing (4-bromophenoxy) trimethylsilane, and then oscillating in a vibrating water bath for reaction for 30 minutes to obtain the porous silica sheet A with the initial polymerization site.

3. The method of claim 2, wherein in step S11, the polishing manner for preparing the porous silica sheet a comprises:

I) polishing the porous silicon dioxide sheet by using 500-mesh sand paper, wherein the thickness of the polished porous silicon dioxide sheet is not more than 2.00mm, and the diameter of the polished porous silicon dioxide sheet is not more than 15.0 mm;

II) polishing the porous silica sheet polished in the step I) with 1200-mesh type sandpaper until a porous silica sheet a having a smooth surface is obtained.

4. The method of claim 2, wherein in step S12:

when the ultrasonic treatment is carried out in the absolute ethyl alcohol, the treatment time of each ultrasonic treatment is 20 minutes;

when the ultrasonic treatment is carried out in the hydrochloric acid, the concentration of the hydrochloric acid is 8.0mol/L, and the treatment time of each ultrasonic treatment is 50 minutes.

5. The method for preparing a chiral conjugated microporous polymer/silica composite membrane according to claim 2, wherein in step S13, the mixing mass ratio of toluene to (4-bromophenoxy) trimethylsilane in solution c is 15: 1.

6. the method of any one of claims 2 to 5, further comprising, before performing step S2, preparing 2, 5-dibromoterephthaloyl chloride:

the 2, 5-dibromo-p-benzoic acid is filled into a three-necked bottle with a spherical reflux condenser tube, the three-necked bottle is sealed, vacuumized and protected by nitrogen, thionyl chloride is injected into the three-necked bottle, the three-necked bottle is heated to 75-85 ℃ in an oil bath, the three-necked bottle is continuously stirred and reacts for 3-5 hours to obtain brown liquid, and the brown liquid is subjected to rotary evaporation to obtain the 2, 5-dibromo-p-phthaloyl chloride.

7. The method for preparing the chiral conjugated microporous polymer/silica composite membrane according to claim 6, wherein in the preparation of the 2, 5-dibromo-p-phthaloyl chloride, the mixing mass ratio of the 2, 5-dibromo-p-benzoic acid to the thionyl chloride is 1: 2-3.

8.7, in the step S2, the mixing mass ratio of 2, 5-dibromoterephthaloyl chloride, D-menthol and toluene is 4-5: 1: 5.

9. the method for preparing a chiral conjugated microporous polymer/silica composite membrane according to claim 8, wherein in the step S2, when the crude product is purified by a silica gel chromatography column, the eluent used is a mixed solvent of n-hexane and ethyl acetate, and the mixed mass ratio of n-hexane to ethyl acetate in the mixed solvent is 20: 1, R_fThe value was 0.31.

10. The method for preparing a chiral conjugated microporous polymer/silica composite membrane according to claim 9, wherein in step S3:

adding at least one porous silica sheet A with an initial polymerization site to a three-necked flask;

the mixing mass ratio of the porous silicon dioxide sheet A with the initial polymerization site to the 1,3, 5-tri (4-alkynyl phenyl) benzene, the triphenylphosphine, the cuprous iodide, the bis-triphenylphosphine palladium chloride, the triethylamine and the monomer B is 1: 20: 24: 12: 12-14: 10: 400-420.

Technical Field

The invention belongs to the technical field of preparation of chiral conjugated microporous polymers, and particularly relates to a preparation method of a chiral conjugated microporous polymer/silicon dioxide composite membrane.

Background

In the prior art, because the nature pure chiral substances are limited in types and quantity, how to artificially prepare and obtain a single enantiomer with a use effect becomes the focus and focus of research in the field of biomedicine nowadays. To date, there are roughly 3 methods for obtaining single enantiomer drugs: chiral source synthesis, asymmetric synthesis and resolution of racemates.

The chiral source synthesis method and the asymmetric synthesis method have the disadvantages of complicated preparation process, complicated purification process, high production cost and extremely low yield.

The membrane separation technology in the racemate separation method has the advantages of high yield, low energy consumption, no pollution, high separation purity and the like, and is considered to be one of the methods with great potential for large-scale chiral separation. The membrane separation technology comprises a chiral separation liquid membrane and a chiral separation solid membrane, wherein the chiral separation liquid membrane has high transmission speed but poor stability; the chiral separation solid membrane with good stability is difficult to realize high selectivity and high flux at the same time so far.

In conclusion, it is of great significance to further develop a chiral separation solid membrane with good stability, high precision and large flux.

Disclosure of Invention

The invention aims to provide a preparation method of a chiral conjugated microporous polymer/silicon dioxide composite membrane; specifically, the method comprises the following steps: the chiral conjugated microporous polymer/silicon dioxide composite membrane with a plurality of chiral recognition sites and a stable porous structure is prepared by taking the porous silicon dioxide as a substrate and the chiral conjugated microporous polymer as a skin layer, so that the selectivity and the flux of a racemate are effectively improved in the process of enantiomer resolution.

In order to achieve the purpose, the invention provides the following technical scheme: a preparation method of a chiral conjugated microporous polymer/silicon dioxide composite membrane, which takes porous silicon dioxide as a substrate and a chiral conjugated microporous polymer as a skin layer, prepares the chiral conjugated microporous polymer/silicon dioxide composite membrane by an in-situ polymerization method, and comprises the following steps:

s1, preparing a porous silicon dioxide sheet A with an initial polymerization site;

s2, adding 2, 5-dibromo terephthaloyl chloride and D-menthol into a three-necked bottle, vacuumizing, injecting toluene after nitrogen protection, heating to 70-90 ℃, continuously stirring at 70-90 ℃ for reaction for 12-15 hours to obtain light yellow oily liquid, performing rotary evaporation on the light yellow oily liquid to obtain a crude product, and purifying the crude product through a silica gel chromatographic column to obtain a monomer B;

s3, adding the porous silicon dioxide sheet A with the initial polymerization site, 1,3, 5-tri (4-alkynyl phenyl) benzene, triphenylphosphine, cuprous iodide and bis-triphenylphosphine palladium chloride, which are prepared in the step S1, into a three-necked bottle, then injecting triethylamine as a solvent, stirring and reacting at the temperature of 90-110 ℃ for 1 hour, adding the monomer B, which is prepared in the step S2, into the three-necked bottle after stirring, stirring and reacting at the temperature of 115-125 ℃ for 24 hours to prepare a crude product, taking out the crude product, washing the crude product with toluene, chloroform and potassium iodide saturated solutions respectively, and drying the washed product to obtain the chiral conjugated microporous polymer/silicon dioxide composite membrane.

Further, the step S1, when preparing the porous silica sheet a having initial polymerization sites, includes:

s11, polishing to prepare a porous silicon dioxide sheet a with the thickness of less than 2.00mm, the diameter of less than 15.0mm and a smooth surface;

s12, placing the porous silicon dioxide sheet a into absolute ethyl alcohol, performing ultrasonic treatment at least three times, then placing the porous silicon dioxide sheet a into hydrochloric acid, performing ultrasonic treatment at least three times, and drying after the ultrasonic treatment is completed to obtain a hydroxylated porous silicon dioxide sheet b;

s13, filling the hydroxylated porous silica sheet b into a single-mouth bottle, injecting a toluene solution c containing (4-bromophenoxy) trimethylsilane, and then oscillating in a vibrating water bath for reaction for 30 minutes to obtain the porous silica sheet A with the initial polymerization site.

Preferably, in step S11, the polishing method for preparing the porous silica sheet a includes:

I) polishing the porous silicon dioxide sheet by using 500-mesh sand paper, wherein the thickness of the polished porous silicon dioxide sheet is not more than 2.00mm, and the diameter of the polished porous silicon dioxide sheet is not more than 15.0 mm;

II) polishing the porous silica sheet polished in the step I) with 1200-mesh type sandpaper until a porous silica sheet a having a smooth surface is obtained.

Preferably, in step S12: when the ultrasonic treatment is carried out in the absolute ethyl alcohol, the treatment time of each ultrasonic treatment is 20 minutes; when the ultrasonic treatment is carried out in the hydrochloric acid, the concentration of the hydrochloric acid is 8.0mol/L, and the treatment time of each ultrasonic treatment is 50 minutes.

Preferably, in the step S13, the mixing mass ratio of toluene to (4-bromophenoxy) trimethylsilane in the solution c is 15: 1.

further, before performing step S2, the method further comprises the following steps: the 2, 5-dibromo-p-benzoic acid is filled into a three-necked bottle with a spherical reflux condenser tube, the three-necked bottle is sealed, vacuumized and protected by nitrogen, thionyl chloride is injected into the three-necked bottle, the three-necked bottle is heated to 75-85 ℃ in an oil bath, the three-necked bottle is continuously stirred and reacts for 3-5 hours to obtain brown liquid, and the brown liquid is subjected to rotary evaporation to obtain the 2, 5-dibromo-p-phthaloyl chloride.

Preferably, the heating temperature may be preferably 80 ℃ with respect to the oil bath, and the reaction time may be preferably 4 hours with respect to the continuous stirring.

Furthermore, when the 2, 5-dibromo-p-phthaloyl chloride is prepared, the mixing mass ratio of the 2, 5-dibromo-p-benzoic acid to the thionyl chloride is 1: 2-3.

Further, in the step S2, the mixing mass ratio of the 2, 5-dibromoterephthaloyl chloride, the D-menthol and the toluene is 4-5: 1: 5.

preferably, in the step S2, the heating temperature may be preferably 80 ℃, and the reaction may be preferably continued to be stirred for 14 hours.

Preferably, in step S2, when the silica gel chromatography column is performed on the crude product, the eluent used is a mixed solvent of n-hexane and ethyl acetate, and the mixing mass ratio of n-hexane to ethyl acetate in the mixed solvent is 20: 1, R_fThe value was 0.31.

Further, in step S3: adding at least one porous silica sheet A with an initial polymerization site to a three-necked flask; the mixing mass ratio of the porous silicon dioxide sheet A with the initial polymerization site to the 1,3, 5-tri (4-alkynyl phenyl) benzene, the triphenylphosphine, the cuprous iodide, the bis-triphenylphosphine palladium chloride, the triethylamine and the monomer B is 1: 20: 24: 12: 12-14: 10: 400-420.

Compared with the prior art, the invention has the following beneficial effects:

in the invention, the porous silicon dioxide is used as a substrate, the chiral conjugated microporous polymer is used as a skin layer, and the chiral conjugated microporous polymer/silicon dioxide composite membrane with a plurality of chiral recognition sites and a stable porous structure is prepared, so that the selectivity and the flux of a raceme can be effectively improved in the process of splitting an enantiomer, and the actual use requirements of high stability, high precision and large flux in the process of membrane separation are further met.

Detailed Description

The technical solutions in the embodiments of the present invention will be described clearly and completely with reference to the following embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The invention provides a preparation method of a chiral conjugated microporous polymer/silicon dioxide composite membrane; specifically, the method comprises the following steps: preparing a chiral conjugated microporous polymer/silicon dioxide composite membrane by using porous silicon dioxide as a substrate and a chiral conjugated microporous polymer as a surface through an in-situ polymerization method;

the preparation method of the chiral conjugated microporous polymer/silicon dioxide composite membrane can provide the following specific examples:

s1, preparing a porous silicon dioxide sheet A with an initial polymerization site;

specifically, the method includes the following steps:

(1) the porous silica piece was polished with 500-mesh type sandpaper, and the polished porous silica piece had a thickness of 2.00mm and a diameter of 15.0 mm.

(2) The porous silica sheet polished in S1 was polished with 1200-mesh type sandpaper until a porous silica sheet a having a smooth surface was obtained.

(3) Putting the porous silicon dioxide sheet a into 100mL of absolute ethyl alcohol, carrying out ultrasonic treatment for three times, wherein the treatment time is 20 minutes each time, then putting the treated porous silicon dioxide sheet a into 50.0mL of 8.0mol/L hydrochloric acid, carrying out ultrasonic treatment for three times, wherein the treatment time is 50 minutes each time, putting the treated porous silicon dioxide sheet a into a vacuum drying oven after completing the ultrasonic treatment, and drying to obtain a hydroxylated porous silicon dioxide sheet b.

(4) The hydroxylated porous silica flakes b were charged into a single-neck flask, and a toluene (15.0 ml) solution c containing (4-bromophenoxy) trimethylsilane (1.00 g, 4.08 mmol) was injected, followed by shaking reaction in a shaking water bath for 30 minutes to obtain porous silica flakes A with initial polymerization sites.

S2, preparing 2, 5-dibromo terephthaloyl chloride;

specifically, in the step, 2, 5-dibromo-p-benzoic acid and thionyl chloride are used as preparation raw materials, and the mixing mass ratio of the 2, 5-dibromo-p-benzoic acid to the thionyl chloride is 1: 2-3;

in the present embodiment, it is more preferable that 1: 2.6;

(5) 2, 5-dibromo-p-benzoic acid (5.00 g, 17.8 mmol) is filled into a 50mL three-necked bottle with a spherical reflux condenser tube, vacuum pumping is carried out after sealing, nitrogen protection is carried out, thionyl chloride (13.0 mL, 180 mmol) is injected into the three-necked bottle, the three-necked bottle is heated to 80 ℃ in an oil bath and stirred for reaction for 4 hours to obtain brown liquid, and the brown liquid is subjected to rotary evaporation to obtain the 2, 5-dibromo-p-phthaloyl chloride.

S3, preparing a monomer B by using 2, 5-dibromo terephthaloyl chloride, D-menthol and toluene as raw materials;

specifically, in the step, the mixing mass ratio of the 2, 5-dibromo-p-phthaloyl chloride, the D-menthol and the toluene is 4-5: 1: 5;

in the present embodiment, it may be more preferably 4.5: 1: 5;

(6) adding D-menthol (4.00g, 25.6mmol) into a 50mL three-necked bottle filled with 2, 5-dibromo-p-phthaloyl chloride in the step (5), vacuumizing, injecting 20mL of toluene after nitrogen protection, heating to 80 ℃, continuously stirring at 80 ℃ for reaction for 14 hours to obtain light yellow oily liquid, performing rotary evaporation on the light yellow oily liquid to obtain a crude product, and purifying the crude product by a silica gel chromatographic column to obtain a monomer B;

specifically, when the crude product is purified by a silica gel chromatographic column, the eluent is a mixed solvent of n-hexane and ethyl acetate, and the mixed mass ratio of n-hexane to ethyl acetate in the mixed solvent is 20: 1, R_fThe value was 0.31.

S4, preparing a chiral conjugated microporous polymer/silicon dioxide composite membrane by using a porous silicon dioxide sheet A with an initial polymerization site, 1,3, 5-tri (4-alkynyl phenyl) benzene, triphenylphosphine, cuprous iodide, bis (triphenylphosphine) palladium chloride, triethylamine and a monomer B as raw materials;

specifically, in the step, the mixing mass ratio of the porous silica sheet a with the initial polymerization site to 1,3, 5-tris (4-alkynyl phenyl) benzene, triphenylphosphine, cuprous iodide, bis-triphenylphosphine palladium chloride, triethylamine, and the monomer B is 1: 20: 24: 12: 12-14: 10: 400-420;

in the present embodiment, it is more preferable that 1: 20: 24: 12: 13: 10: 418;

in this example, the above-mentioned starting materials are added in exactly the following reaction sequence: adding a porous silica sheet A with an initial polymerization site prepared in the step (4), 1,3, 5-tri (4-alkynyl phenyl) benzene (20.0mg, 0.133mmol), triphenylphosphine (24mg, 0.092mmol), cuprous iodide (12.0mg, 0.064mmol) and bis-triphenylphosphine palladium chloride (12.94mg, 0.0184mmol) into a 100mL three-necked flask, then injecting 10mL triethylamine as a solvent, stirring at 100 ℃ for 1 hour, adding a monomer B (418mg, 1.00mmol) prepared in the step (6) into the three-necked flask after stirring, stirring at 120 ℃ for 24 hours to prepare a crude product, taking out the crude product, washing with toluene, chloroform and potassium iodide saturated solutions respectively, washing, and drying to obtain the chiral conjugated microporous polymer/silica composite membrane.

In summary, the chiral conjugated microporous polymer/silica composite membrane is a composite structure with porous silica as a substrate and a chiral conjugated microporous polymer as a skin layer, wherein the porous silica has a stable porous structure, and the chiral conjugated microporous polymer has a plurality of chiral recognition sites, so that the stability of the whole composite membrane can be ensured, and the selectivity and the flux of the composite membrane can be improved.

It is noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.

Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.