Type I Chiral Porous Liquid Materials and Applications

Abstract

The present invention relates to the technical field of chiral stationary phases for gas chromatography columns, and specifically relates to type I chiral porous liquid materials and their applications. The type I chiral porous liquid materials of the present invention combine the characteristics of chiral porous solid materials and liquid materials. The synthesis raw materials are easily available, the synthesis method is relatively simple, and the column preparation cost is low. The chromatographic column of the present invention is applied to gas chromatography analysis, has strong chiral separation ability, has good resolution performance for racemic compounds including esters, aldehydes, amines, alcohols, ketones, epoxides and amino acid derivatives, and has the characteristics of fast separation speed, good resolution effect, good stability and recyclability.

Description

Technical Field

[0001] The present invention relates to the technical field of chiral stationary phases for gas chromatography columns, and specifically relates to type I chiral porous liquid materials and their applications. Background Art

[0002] Before the application of porous solid materials such as zeolites, MOFs, and POCs, the solid powders need to be processed or integrated. During this process, the material structure may be changed, thereby reducing its performance. In addition, problems such as mechanical fatigue and physical aging of solid materials will limit their applications in industrial production. Therefore, by designing and synthesizing porous solid materials to prepare new materials with permanent porosity and fluidity characteristics, and applying them in the fields of gas storage and separation can effectively overcome the above-mentioned disadvantages, thereby promoting the application and development of porous solid materials. Porous liquids are a new type of porous material that has rapidly developed in recent years, combining the permanent porosity of porous solids and the fluidity of liquids. The concept of porous liquids was first proposed by James in an article in 2007, and is divided into three types according to different host systems, including type I: composed of pure rigid hosts with cavities; type II: porous molecular cage types dissolved in sterically hindered solvents; type III: porous framework materials dispersed in sterically hindered solvents.

[0003] Porous organic cages are a new type of porous crystal material with internal cavities of a three-dimensional cage-like structure orderly stacked through weak interactions. This structure has characteristics such as high stability, excellent solubility, adjustable internal cavities, and easy processing and functionalization in solutions, and has attracted much attention in the synthesis of porous liquids. In 2012, James et al. synthesized the first type I porous liquid by combining iminophosphine and a cage system. The outer surface of the cage has covalently bonded alkyl groups, and when it reaches the melting point, it will form a viscous fluid, and up to 30% of the pores are empty in the molten state. Using organic cages as porous hosts can prepare type I and type II porous liquids according to different synthesis strategies, providing feasibility for designing porous liquids based on porous cages. Summary of the Invention

[0004] The purpose of the present invention is to provide, in view of the deficiencies of the prior art, a type I chiral porous liquid material and its application as a gas chromatography stationary phase. Using the type I chiral porous liquid material based on chiral organic molecular cages as the chiral stationary phase of the chromatographic column shows excellent chiral separation performance and can separate many chiral compounds including esters, aldehydes, amines, alcohols, ketones, epoxides, and amino acid derivatives.

[0005] To achieve the above-mentioned invention purpose, on the one hand, the present invention provides a type I chiral porous liquid material, and its structure is shown in the following formula:

[0006]

[0007] On the other hand, the present invention provides a method for preparing a type I chiral porous liquid material, comprising the following steps:

[0008] S1. Preparation of 3,3',5,5'-tetraformyl-4,4'-biphenyldiol: After mixing hexamethylenetetramine and 4,4'-biphenyldiol at a molar ratio of (10 - 12):1, trifluoroacetic acid is added, and the reaction is carried out at 100 - 110 °C. After the reaction ends,

[0009] hydrochloric acid solution is added, and the mixture is stirred and refluxed for 3 - 5 h to obtain 3,3',5,5'-tetraformyl-4,4'-biphenyldiol;

[0010] S2. Preparation of prismatic molecular cage NC1-R: 3,3',5,5'-tetraformyl-4,4'-biphenyldiol, (1R,2R)-1,2-cyclohexanediamine and KOH at a molar ratio of 1:(21 - 23):(4 - 6) are dissolved in an ethanol aqueous solution, and the reaction is carried out at 85 - 95 °C. After the reaction ends, recrystallization is carried out to obtain NC1-R;

[0011] S3. Preparation of type I chiral porous liquid material NC1-R-PL: NC1-R and 1,4-dibromobutane at a mass-volume ratio of 1 g:(1.5 - 1.8) ml are stirred and reacted at 65 °C to prepare intermediate M, and then intermediate M and 1-allylimidazole at a mass-volume ratio of 1 g:(1.2 - 1.4) ml are stirred and reacted at 65 °C to obtain NC1-R-PL.

[0012] On the other hand, the present invention provides the application of the type I chiral porous liquid material as a gas chromatography stationary phase.

[0013] Furthermore, the type I chiral porous liquid material is used as a gas chromatography stationary phase for separating enantiomers.

[0014] Furthermore, the enantiomers are chiral compounds from esters, aldehydes, amines, alcohols, ketones, epoxides and amino acid derivatives.

[0015] On the other hand, the present invention provides a chromatographic column comprising the above-mentioned type I chiral porous liquid material as a stationary phase.

[0016] Fifthly, the present invention provides a method for preparing the above-mentioned chromatographic column, comprising the following steps:

[0017] S1. NC1-R-PL is dissolved in dichloromethane to prepare a solution of 1 - 5 mg / mL, and then it is mixed with a 2 - 6 mg / mL solution of polysiloxane OV-1701 in an equal volume as the stationary liquid;

[0018] S2. Etch the inner wall of the capillary column with an aqueous solution of an alkali, rinse the inner wall with water and then wash the inner wall with an aqueous solution of an acid to neutralize the residual alkali, and then rinse the inner wall of the capillary column with water until the pH value of the effluent is 7 to roughen the inner wall of the capillary column;

[0019] S2. Fill the roughened capillary column with the stationary liquid and prepare it by the static coating method.

[0020] It has been found that the type I chiral porous liquid material of the present invention can preferentially bind one enantiomer relative to the other enantiomer when contacting a mixture of enantiomers. Therefore, the chiral porous material of the present invention can be used in the resolution method.

[0021] On the other hand, a method for separating a mixture of enantiomers, the method comprising passing a composition containing the mixture of enantiomers through the above chromatographic column.

[0022] Further, the method for separating a mixture of enantiomers includes contacting a composition containing the mixture of enantiomers with the above material. After the mixture of enantiomers has been allowed to stand for a time sufficient to achieve equilibrium, the porous chiral material can be suitably separated by removing the solid material from the composition containing the mixture of enantiomers. One enantiomer can be carried within the type I chiral porous liquid material, and the other remains in the composition in the reaction vessel.

[0023] Further, the method for separating a mixture of enantiomers includes the following steps:

[0024] S1. Pass a composition containing the mixture of enantiomers through a chromatographic column containing the type I chiral porous liquid material according to claim 1 as the stationary phase;

[0025] S2. Contact a composition containing the mixture of enantiomers with the type I chiral porous liquid material according to claim 1 for a time sufficient to equilibrate the composition; and

[0026] S3. Obtain the crystal structure of the material obtained in S2.

[0027] From the crystal structure of the material obtained in step S1, the enantiomer with the longest retention time can be identified.

[0028] The type I chiral porous liquid material can be used to separate enantiomers of a wide range of materials with different structures. They can be used to separate racemic mixtures or compositions in which one enantiomer is present in excess. They can be particularly used to separate enantiomers of chiral compounds from esters, aldehydes, amines, alcohols, ketones, epoxides and amino acid derivatives.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] (1) The type-I chiral porous liquid material of the present invention combines the characteristics of chiral porous solid materials and liquid materials. The synthetic raw materials used in the invention are easily available, the synthesis method is relatively simple, and the column manufacturing cost is low.

[0031] (2) The triangular prism molecular cage porous liquid NC1-R-PL chromatographic column of the present invention is applied to gas chromatography analysis, has strong chiral separation ability, and has good resolution performance for racemic compounds including esters, aldehydes, amines, alcohols, ketones, epoxides and amino acid derivatives.

[0032] (3) The chromatographic column of the present invention has the characteristics of fast separation speed, good resolution effect, good stability, and can be reused repeatedly. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 is a schematic diagram of the synthesis of the type-I chiral porous liquid material used in the present invention;

[0034] Figure 2 is a scanning electron microscope image of the inner wall and cross-section of the chromatographic column prepared in the present invention;

[0035] Figure 3 is a chromatogram of the repeatability and stability test of the chromatographic column of the present invention;

[0036] Figure 4 is a chromatogram of the resolution of some chiral compounds using the chromatographic column of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0037] To enable those skilled in the art to better understand the technical solution of the present invention, the present invention will be described in detail below in conjunction with specific embodiments. The experimental methods without specific conditions noted in the following examples are usually carried out according to conventional conditions or according to the conditions recommended by the manufacturer. The test materials used in the following examples are, unless otherwise specified, obtained from regular biochemical reagent stores. Unless otherwise stated, percentages and parts are calculated by weight. Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to the described content can be applied to the present invention. The preferred implementation methods and materials described herein are for illustrative purposes only.

[0038] The technical solution of the present invention will be further described in detail below in conjunction with specific examples and drawings. It should be understood that the following examples are only used to explain the present invention and are not used to limit the present invention.

[0039] The inventor constructed a triangular prism molecular cage NC1-R, and then reacted NC1-R with 1,4-dibromobutane to synthesize an intermediate M. Finally, type I chiral porous material NC1-R-PL was obtained by reacting M with 1-allylimidazole (the synthesis route is shown in Figure 1 ). Using it as a gas chromatography stationary phase, an NC1-R-PL capillary column was prepared. This column has good resolution performance and enantioselectivity for various types of chiral compounds.

[0040] Example 1 Preparation of type I chiral porous liquid material

[0041] 84 g of hexamethylenetetramine and 9.66 g of 4,4'-biphenyldiol were placed in a 1000 mL round-bottom flask, and 294 mL of trifluoroacetic acid was added to the round-bottom flask. The reaction was carried out at 105 °C for 7 days. After the reaction was completed, 100 mL of a pre-prepared 4 mol L-1 hydrochloric acid solution was added to the flask, and then the mixture was continuously stirred and refluxed in an oil bath at 100 °C for 4 h. After the temperature dropped to room temperature, a solid powder was obtained by centrifugation. The product was washed successively with deionized water, methanol, and cyclohexane, and vacuum dried in an oven at 70 °C. Finally, the product was dissolved in dimethyl sulfoxide, stirred and refluxed at 90 °C for 3 h, and then filtered while it was hot to obtain a filtrate. After the filtrate was left standing for 4 days, the recrystallized product was washed repeatedly with water and methanol and then dried to obtain 3,3',5,5'-tetraformyl-4,4'-biphenyldiol;

[0042] 0.15 g of 3,3',5,5'-tetraformyl-4,4'-biphenyldiol and 0.15 g of potassium hydroxide were weighed and placed in a 500 mL three-necked round-bottom flask. Then, 150 mL of a water / ethanol (60 mL / 90 mL) mixed solution was added to the flask, and the mixture was stirred at 90 °C for half an hour to fully dissolve the solute. Secondly, 1.26 g of (1R,2R)-1,2-cyclohexanediamine was dissolved in a beaker containing 50 mL of ethanol, sonicated, and then transferred to a dropping funnel and slowly dropped into the three-necked round-bottom flask. The mixed solution was stirred and refluxed at 90 °C for 24 h. After the reaction was completed and the temperature dropped to room temperature, suction filtration was carried out. After the filtrate was left standing for 5 days, a product precipitated at the bottom. The product was centrifuged and washed with deionized water, and vacuum dried at 70 °C. Finally, the product was recrystallized with dichloromethane to obtain a prismatic molecular cage NC1-R;

[0043] Weigh 0.26 g of NC1-R and 0.16 g of potassium carbonate and dissolve them in 43 mL of chloroform. Under a nitrogen atmosphere, add 0.43 mL of 1,4-dibromobutane, and stir and reflux the mixed solution at 65 °C for 2 days. After the reaction is cooled to room temperature, perform suction filtration. Treat the filtrate on a rotary evaporator to obtain a yellow product. Wash the product with n-hexane multiple times and then dry it under vacuum at 50 °C to finally obtain intermediate M. Secondly, weigh 0.26 g of intermediate M and place it in a 100 mL round-bottom flask. Then add 32 mL of chloroform and dissolve it by ultrasonic treatment. Subsequently, under a nitrogen atmosphere, add 0.32 mL of 1-allylimidazole to the round-bottom flask, and then transfer the flask to an oil bath pre-set at 65 °C and stir and reflux for 2 days. After the reaction is cooled to room temperature, wash the product with n-hexane repeatedly multiple times and then dry it under vacuum in an oven to finally obtain the type I chiral porous liquid material NC1-R-PL.

[0044] Example 2 Preparation of chromatographic column

[0045] Take a quartz capillary column with a length of 15 m and an inner diameter of 0.25 mm. First, continuously rinse the capillary column with NaOH (1.0 mol / L) solution for 2 hours. Secondly, rinse the capillary column with ultrapure water until it is neutral. Then, rinse the capillary column with HCl (0.1 mol / L) solution for 2 hours. Again, rinse it with ultrapure water until it is neutral. Finally, connect one end of the capillary column to the injection port of the gas chromatograph and pass nitrogen to dry it at 120 °C for 6 hours to obtain a capillary column with a roughened inner wall;

[0046] Weigh 30 mg of the chiral porous liquid NC1-R-PL prepared in Example 1 and 45 mg of OV-1701 and dissolve them in 10 mL of dichloromethane respectively to prepare a 3.0 mg / mL NC1-R-PL solution and a 4.5 mg / mL OV-1701 solution. Take 1 mL of each and mix them evenly to obtain a stationary phase solution, and perform ultrasonic treatment. Charge the prepared stationary phase solution into the capillary column with roughened inner wall in step (4), and use the static coating method to prepare the column. Seal one end of the capillary column, connect the other end to a vacuum system, and place the capillary column in a water bath at 39 °C to evaporate the dichloromethane in the capillary. The stationary phase is evenly coated on the inner wall of the capillary column, and the required chromatographic column is thus prepared.

[0047] Example 3 Chromatographic resolution effect test

[0048] Investigate the chromatographic resolution effect of the chromatographic column on different types of racemic compounds. The chromatographic conditions are as follows: High-purity nitrogen is used as the carrier gas, the injection port temperature is 250 °C, and the detector temperature is 250 °C;

[0049] (a) Methyl 2-bromobutyrate, column temperature 170 °C, nitrogen linear velocity 12.0 cm s -1 ;

[0050] (b) DL-2-Phenylpropionaldehyde, column temperature 155 °C, nitrogen linear velocity 13.3 cm s -1 ;

[0051] (c) 1-(Naphthalen-2-yl)ethanamine, column temperature 180 °C, nitrogen linear velocity 12.8 cm s -1 ;

[0052] (d) 2,3-Butanediol, column temperature 175 °C, nitrogen linear velocity 12.9 cm s -1 ;

[0053] (e) 2-Methylpentanal, column temperature 170 °C, nitrogen linear velocity 13.0 cm s -1 ;

[0054] (f) 2-Methyltetrahydrofuran-3-one, column temperature 140 °C, nitrogen linear velocity 13.2 cm s -1 ;

[0055] (g) 3-Chloro-2-butanone, column temperature 140 °C, nitrogen linear velocity 13.4 cm s -1 ;

[0056] (h) n-Butyl glycidyl ether, column temperature 130 °C, nitrogen linear velocity 13.9 cm s -1 ;

[0057] (i) Methyl 2-bromopropionate, column temperature 110 °C, nitrogen linear velocity 14.3 cm s -1 ;

[0058] (j) β-Butyrolactone, column temperature 140 °C, nitrogen linear velocity 17.7 cm s -1 ;

[0059] (k) Citronellal, column temperature 190 °C, nitrogen linear velocity 13.8 cm s -1 ;

[0060] (l) Epichlorohydrin, column temperature 150 °C, nitrogen linear velocity 14.0 cm s -1 ;

[0061] (m) α-Pinene, column temperature 150 °C, nitrogen linear velocity 12.7 cm s -1 ;

[0062] (n) Carvone, column temperature 170 °C, nitrogen linear velocity 12.8 cm s -1 ;

[0063] (o) Glutamine, column temperature 200 °C, nitrogen linear velocity 12.5 cm s -1 ;

[0064] (p) Lysine, column temperature 170 °C, nitrogen linear velocity 12.6 cm s -1 ;

[0065] (q) Isoleucine, column temperature 155 °C, nitrogen linear velocity 12.6 cm s -1 ;

[0066] (r) Tryptophan, column temperature 145 °C, nitrogen linear velocity 12.4 m s -1 .

[0067] From Figure 4 it can be seen that the NC1-R-PL gas chromatography chiral separation column of the present invention exhibits good enantioselectivity for many different types of chiral compounds including esters, aldehydes, amines, alcohols, ketones, epoxides, and amino acid derivatives, etc.

[0068] Example 4

[0069] To study the stability and repeatability of the NC1-R-PL capillary chiral column prepared in Example 1, methyl 2-bromobutyrate (column temperature 170 °C) was selected as the analyte for testing. First, the repeatability of the NC1-R-PL coated column was explored, and the selected analyte was tested when the column was just used, after 100 injections, and after 300 injections; then, the stability of the NC1-R-PL column was studied, and methyl 2-bromobutyrate was separated and analyzed on the NC1-R-PL column after being held at 200 °C for 3 h and 8 h. The separation chromatograms are as attached Figure 3 . Chromatographic conditions: High-purity nitrogen was used as the carrier gas, the injection port temperature was 250 °C, and the detector temperature was 250 °C.

[0070] From Figure 3 it can be known that there is no obvious change in the resolution and retention time of the NC1-R-PL coated column for methyl 2-bromobutyrate when it is just used, after 100 injections, and after 300 injections, and after repeated injections after high-temperature treatment, there is also no significant change in its separation chromatogram, and the baseline has no obvious drift, indicating that the chromatographic column of the present invention has good stability and repeatability and has good practical application prospects.

[0071] Finally, it should be noted that the above description is only the preferred embodiment of the present invention. Those skilled in the art can make various similar representations under the inspiration of the present invention without violating the purpose and claims of the present invention. Such transformations all fall within the protection scope of the present invention.

Claims

1. Type I chiral porous liquid material, characterized in that, Its structure is shown in the following formula:

2. The preparation method of the type I chiral porous liquid material according to claim 1, characterized in that, It includes the following steps: S1. Preparation of 3,3',5,5'-tetraformyl-4,4'-biphenyldiol: Mix hexamethylenetetramine and 4,4'-biphenyldiol with a molar ratio of (10 - 12):1, add trifluoroacetic acid, react at 100 - 110 °C. After the reaction, add hydrochloric acid solution and stir and reflux for 3 - 5 h to obtain 3,3',5,5'-tetraformyl-4,4'-biphenyldiol; S2. Preparation of prismatic molecular cage NC1-R: Dissolve 3,3',5,5'-tetraformyl-4,4'-biphenyldiol, (1R,2R)-1,2-cyclohexanediamine and KOH with a molar ratio of 1:(21 - 23):(4 - 6) in an ethanol aqueous solution, react at 85 - 95 °C. After the reaction, perform recrystallization to obtain NC1-R; S3. Preparation of type I chiral porous liquid material NC1-R-PL: Stir and react NC1-R and 1,4-dibromobutane with a mass-to-volume ratio of 1 g:(1.5 - 1.8) ml at 65 °C to obtain intermediate M. Then stir and react intermediate M and 1-allylimidazole with a mass-to-volume ratio of 1 g:(1.2 - 1.4) ml at 65 °C to obtain NC1-R-PL; The synthetic route is as follows:

3. Application of the type I chiral porous liquid material described in claim 1 as a gas chromatography stationary phase.

4. The application according to claim 3, characterized in that: For separating enantiomers.

5. The application according to claim 4, wherein: The enantiomers are from chiral compounds of esters, aldehydes, amines, alcohols, ketones, epoxides and amino acid derivatives.

6. Chromatographic column, characterized in that: Comprising the type I chiral porous liquid material described in claim 1 as the stationary phase.

7. The preparation method of the chromatographic column according to claim 6, characterized in that, It includes the following steps: S1. Dissolve NC1-R-PL in dichloromethane to prepare a solution of 1 - 5 mg / mL, and then mix it with a poly(dimethylsiloxane) OV-1701 solution of 2 - 6 mg / mL in equal volume as the stationary liquid; S2. Etch the inner wall of the capillary column with an aqueous solution of a base, wash the inner wall with water and then wash the inner wall with an aqueous solution of an acid to neutralize the residual base, and then wash the inner wall of the capillary column with water until the pH value of the effluent is 7 to roughen the inner wall of the capillary column; S2. Fill the stationary liquid into the roughened capillary column and prepare it by the static coating method.

8. A method for separating an enantiomer mixture, the method comprising passing a composition containing the enantiomer mixture through the chromatographic column described in claim 6 or through the chromatographic column prepared by the method described in claim 7.

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