CN112774636A - Chiral covalent organic framework bonded silicon sphere chromatographic stationary phase, preparation and application thereof - Google Patents
Chiral covalent organic framework bonded silicon sphere chromatographic stationary phase, preparation and application thereof Download PDFInfo
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- 239000013310 covalent-organic framework Substances 0.000 title claims abstract description 45
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- 229910052682 stishovite Inorganic materials 0.000 claims description 13
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- 150000000190 1,4-diols Chemical class 0.000 claims description 12
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- 229940079593 drug Drugs 0.000 claims description 11
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- CBCKQZAAMUWICA-UHFFFAOYSA-N 1,4-phenylenediamine Chemical compound NC1=CC=C(N)C=C1 CBCKQZAAMUWICA-UHFFFAOYSA-N 0.000 claims description 8
- WYTRYIUQUDTGSX-UHFFFAOYSA-N 1-phenylpropan-2-ol Chemical group CC(O)CC1=CC=CC=C1 WYTRYIUQUDTGSX-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 8
- 238000009210 therapy by ultrasound Methods 0.000 claims description 7
- 238000004140 cleaning Methods 0.000 claims description 6
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000007789 gas Substances 0.000 claims description 4
- 238000012986 modification Methods 0.000 claims description 4
- 230000004048 modification Effects 0.000 claims description 4
- OBFQBDOLCADBTP-UHFFFAOYSA-N aminosilicon Chemical compound [Si]N OBFQBDOLCADBTP-UHFFFAOYSA-N 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
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- 230000004913 activation Effects 0.000 claims description 2
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- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims 2
- 229910052786 argon Inorganic materials 0.000 claims 1
- 239000000543 intermediate Substances 0.000 claims 1
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- 238000004587 chromatography analysis Methods 0.000 description 4
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/223—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material containing metals, e.g. organo-metallic compounds, coordination complexes
- B01J20/226—Coordination polymers, e.g. metal-organic frameworks [MOF], zeolitic imidazolate frameworks [ZIF]
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 - B01D15/36
- B01D15/3833—Chiral chromatography
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/29—Chiral phases
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Abstract
The invention relates to a preparation method and application of a chiral covalent organic framework bonded macroporous silicon sphere chromatographic stationary phase. Chiral monomers are polymerized in situ on the surfaces and in the pore channels of the macroporous silicon spheres to form a chiral covalent organic framework, so that the material retains the chiral characteristics of the functional monomers, and the chiral compounds can be effectively separated. The chiral covalent organic framework grows in situ on the bonding site, so that the silicon ball can be completely coated without sealing the tail; the novel stationary phase takes silicon spheres as a matrix, so that the mechanical strength of the material is greatly improved, and the problem that the application of the chiral covalent organic framework material in the field of chromatographic stationary phases is limited due to insufficient rigidity and uneven particle size is solved; meanwhile, the advantages of high thermal stability, large specific surface area and uniform pore size distribution of the covalent organic framework are reserved; in addition, the used silicon spheres are macroporous silicon spheres, the appropriate pore diameter effectively improves the loading capacity of the chiral stationary phase, and the stationary phase is expected to be applied to separation of chiral macromolecules.
Description
The technical field is as follows:
the invention relates to the technical field of chromatographic separation stationary phases, in particular to a preparation method and application of a chiral covalent organic framework bonded silicon sphere chromatographic stationary phase.
Background art:
since the chiral drug enantiomers composed of chiral compounds with pharmacological activity may have significant differences in pharmacological activity, metabolic process, toxicity, and the like in organisms, the research of developing single enantiomer products or converting racemic drugs into chiral drugs has become a hotspot in the field of drug research. Chiral drug enantiomer separation techniques have also attracted general attention. Among chiral resolution methods, chromatography is a powerful chiral resolution tool because of its advantages of rapidness, high efficiency, easy preparation, etc., and among them, the chiral stationary phase method is most widely used.
The Covalent Organic Framework (COF) material is used as a pure organic crystalline porous material, has a definite structure and a regular pore channel structure, is rich and various in construction units, adjustable in structural function, large in specific surface area, and has a plurality of advantages of excellent thermal stability and chemical stability and the like. Thus, COF materials are a good platform to study chirality. Since the first example of the synthesis of Chiral Covalent Organic Frameworks (CCOFs) in 2014 (chem.commun.,2014,50,1292), chromatography workers have been trying to develop CCOF as a method for chromatography chiral stationary phases. In 2016 Sehemy et al CCOF was bonded to a quartz capillary column for gas chromatography, the first separation of chiral compounds was performed using CCOF (nat. Commun.,2016,7,12104), after which Chinese patent CN201910207541.4 also applied CCOF to capillary gas chromatography columns. However, the work in liquid chromatography is slow, and chiral liquid chromatography separation (j.am.chem.soc.,2018,140,892) is not applied to three-dimensional CCOF as a stationary phase until 2018, trerion, etc., but COF as a liquid chromatography stationary phase has a problem of non-uniform particle size of material particles. The problem can be well solved by using the silica spheres as the matrix to prepare the chiral covalent organic framework bonded silica sphere chromatographic stationary phase, but the report on the aspect is rare (Chinese patent CN 201710586820.7).
The invention content is as follows:
the invention aims to overcome the defects of the prior art and provides preparation and application of a chiral covalent organic framework bonded silica sphere chromatographic stationary phase.
The purpose of the invention is realized by the following technical scheme:
the preparation and application of a chiral covalent organic framework bonded silica sphere chromatographic stationary phase comprises the following specific preparation steps:
(1) silica gel particle activation treatment
Dispersing 5g of silica gel particles (Suzhou nano micro-technology, Inc.) in 20-60ml of 0.05-0.2 mol/L diluted alkali solution, carrying out ultrasonic treatment for 20-40 min, washing with water until the solution is neutral, washing with anhydrous methanol for 3-5 times, and then washing with toluene for 1 time.
(2) Amino modification of silica gel particles
Dispersing the activated silica gel particles in 20-60mL of a mixed solution of toluene and 3-Aminopropyltriethoxysilane (APTES), ultrasonically mixing uniformly, and heating and refluxing for reaction for 18-20 h. Washing with methanol and drying to obtain amino silicon ball SiO2@NH2。
(3) In situ polymerization of chiral COF
Dispersing amino silicon spheres in 1, 4-dioxane, adding a chiral 1, 4-diol derived tetra-aldehyde monomer (R, R-TTA) and p-phenylenediamine, finally adding acetic acid as a reaction catalyst, carrying out reflux reaction in an inert atmosphere, cleaning and drying to obtain the chiral covalent organic framework bonded macroporous silicon sphere chromatographic stationary phase.
The pore diameter of the macroporous silica gel is 20-50 nm.
The mass ratio of the chiral 1, 4-diol derived tetra-aldehyde monomer to the amino macroporous silicon spheres is 1: 0.1-1: 5.
The molar ratio of the chiral 1, 4-diol derived tetra-aldehyde monomer to the p-phenylenediamine is 1: 0.5-1: 5.
The molar ratio of the acetic acid to the chiral 1, 4-diol-derived tetra-aldehyde monomer is 1: 0.05-1: 2.
The reaction temperature is 100-120 ℃, and the reaction time is 3-5 days.
The prepared covalent organic framework bonded silica gel stationary phase can be filled into a chromatographic column to complete the analysis and preparation of the chiral drug intermediate.
Chiral monomers are polymerized in situ on the surfaces and in the pore channels of the macroporous silicon spheres to form a chiral covalent organic framework, so that the material retains the chiral characteristics of the functional monomers, and the chiral compounds can be effectively separated. The novel stationary phase takes silicon spheres as a matrix, so that the mechanical strength of the material is greatly improved, and the problem that the application of the chiral covalent organic framework material in the field of chromatographic stationary phases is limited due to insufficient rigidity and uneven particle size is solved; meanwhile, the advantages of high thermal stability, large specific surface area and uniform pore size distribution of the covalent organic framework are reserved; in addition, the used silicon spheres are macroporous silicon spheres, the appropriate pore diameter effectively improves the loading capacity of the chiral stationary phase, and the stationary phase is expected to be applied to separation of chiral macromolecules.
Compared with the prior art, the invention has the following positive effects:
the chiral covalent organic framework bonded silica sphere chromatographic stationary phase prepared by the invention has special separation selectivity provided by the chiral covalent organic framework, has the mechanical properties of silica spheres, has uniform particle size, can be applied to high performance liquid chromatography column packing, and has good application effect on chiral drug separation.
The chiral covalent organic framework bonded silica sphere chromatographic stationary phase prepared by the invention grows in situ on a bonding site, can completely coat a silica sphere without sealing a tail, and simultaneously retains the advantages of high thermal stability, large specific surface area and uniform pore size distribution of the covalent organic framework; in addition, the used silicon spheres are macroporous silicon spheres, the appropriate pore diameter effectively improves the loading capacity of the chiral stationary phase, and the stationary phase is expected to be applied to separation of chiral macromolecules.
Description of the drawings:
FIG. 1 is a flow chart of the preparation of chiral covalent organic framework bonded silica sphere chromatographic stationary phase according to an embodiment of the present invention;
FIG. 2 is a scanning electron microscope image of a chiral covalent organic framework bonded silica sphere chromatographic stationary phase according to an embodiment of the present invention.
FIG. 3 shows SiO in example 1 of the present invention2@ CCOF and aminosilicone Sphere (SiO)2@NH2) The aperture profile of (a).
FIG. 4 is a thermogravimetric analysis curve of chiral covalent organic framework bonded silica sphere chromatographic packing in example 1 of the present invention, wherein FIG. 4a is chiral covalent organic framework bonded silica sphere chromatographic packing; FIG. 4b shows chromatography packing of silica amide spheres.
FIG. 5 is a high performance liquid chromatogram of racemic 1-phenyl-2-propanol isomer on a packing column of chiral covalent organic framework bonded silica sphere chromatographic packing provided in example 1 of the present invention.
FIG. 6 is a high performance liquid chromatogram of racemic 1-phenyl-2-propanol isomer on a silica amide sphere packing column.
The specific implementation mode is as follows:
the following provides a specific embodiment of the preparation of the chiral covalent organic framework bonded macroporous silica sphere chromatographic stationary phase of the invention: example 1:
according to the scheme shown in FIG. 1, 5g of silica gel particles (pore diameter 20nm) were dispersed in 30mL of 0.1mol/L diluted alkali solution, sonicated for 40min, washed with water until the solution became neutral, washed 5 times with anhydrous methanol, and then washed 1 time with toluene. Then, the activated silica gel particles are dispersed in 30mL of mixed solution of toluene and 3-Aminopropyltriethoxysilane (APTES) in a volume ratio of 5:1, uniformly mixed by ultrasound, and heated for reflux reaction for 20 h. Washing with methanol, and drying to obtain amino macroporous silicon ball SiO2@NH2。
On the surface of amino silica gel, taking a tetra-aldehyde monomer (R, R-TTA) derived from p-phenylenediamine and chiral 1, 4-diol as a monomer, and carrying out in-situ polymerization on a chiral covalent organic framework bonded silica gel chromatographic stationary phase, wherein the method comprises the following specific steps:
(1) adding 0.5g of macroporous amino silica gel with the aperture of 20nm into 30mL of 1, 4-dioxane to uniformly disperse the macroporous amino silica gel;
(2) adding 1g R, R-TTA (chiral 1, 4-diol derived tetra-aldehyde monomer) and 100mg p-phenylenediamine, and performing ultrasonic treatment until the monomers are completely dissolved;
(3) adding 1mL of acetic acid as a reaction catalyst, sealing a reaction system, and filling nitrogen as protective gas;
(4) heating the system to 100 ℃ in an oil bath, and carrying out reflux reaction for 3 days;
(5) sequentially and respectively washing the obtained material with 1, 4-dioxane and ethanol for three times, and drying at 50 ℃ to obtain the chiral covalent organic framework bonded silica gel chromatographic stationary phase SiO2@CCOF。
The obtained chromatogram stationary phase scanning electron micrograph of the chiral covalent organic framework bonded silica gel is shown in figure 2, and the stationary phase SiO can be clearly observed2The @ CCOF surface roughness indicates that the chiral co-oiler frame is successfully bonded to the silicon sphere surface. SiO 22@ CCOF and aminosilicone Sphere (SiO)2@NH2) The pore size distribution of (A) is shown in FIG. 3, from which it can be seen that SiO2@NH2The pore size distribution of the particles is about 20nm, and after the chiral covalent organic framework layer is modified, the pore size distribution is about 9 nm. The results show that the CCOF layer grows not only on SiO2The outer surface of the particles is simultaneously grown on SiO2The inner surface of the mesopores of the particles. The results of elemental analysis and fixed phase ratio surface area and mean pore size are shown in table 1. Compared with SiO2@NH2，SiO2The carbon content of @ CCOF increased from 5.22% to 21.87%, while the contents of nitrogen and hydrogen increased from 1.83% and 1.57% to 4.11% and 2.24%, respectively, indicating that the chiral covalent organic framework was successfully bonded to the surface of the silica gel microspheres.
TABLE 1 results of elemental analysis experiments and specific surface area and mean pore diameter of materials
a:The results of specific surface area and average pore size were calculated from the adsorption isotherms by the BJH method
FIG. 4 is a thermogravimetric analysis of the chiral covalent organic framework bonded silica gel chromatographic stationary phase provided in this example and of a silica amide sphere chromatographic packing of comparative example. The thermogravimetric analysis result shows that the macroporous silica gel matrix and the silica gel matrix both show better thermal stability.
Application example 1:
2.2g of the chiral covalent organic framework bonded silica gel chromatographic stationary phase described in example 1 was taken at 150kg/cm3Slurry-wise packed under pressure into a stainless steel column 4.6mm in internal diameter and 150mm in length, and purified by high performance liquid chromatography using n-hexane: 99% isopropyl alcohol: 1(V/V) as a mobile phase, the flow rate is 1mL/min, the column temperature: at 30 ℃, the detection wavelength is: 254nm, high performance liquid chromatography of racemic 1-phenyl-2-propanol isomerAnd (4) performing spectral separation to obtain a chromatogram of the drug intermediate 1-phenyl-2-propanol shown in figure 5. The racemic 1-phenyl-2-propanol isomer is basically separated from the baseline completely, which shows that the chromatographic fixed phase prepared by the invention has good separation effect relative to the chiral compound.
The hand-type covalent organic framework bonded silica gel chromatographic stationary phase prepared by the invention is expected to be widely applied in the field of hand-type drug separation.
Comparative example 1:
the macroporous amino silica gel stationary phase (i.e., amino macroporous silica spheres SiO) described in example 1 was taken2@NH2)2.2g at 150kg/cm3Slurry-wise packed under pressure into a stainless steel column 4.6mm in internal diameter and 150mm in length, and purified by high performance liquid chromatography using n-hexane: 99% isopropyl alcohol: 1(V/V) as a mobile phase, the flow rate is 1mL/min, the column temperature: at 30 ℃, the detection wavelength is: 254nm, when racemic 1-phenyl-2-propanol isomer is subjected to high performance liquid chromatography separation, effective resolution cannot be realized, and as shown in a chromatogram of a drug intermediate 1-phenyl-2-propanol shown in fig. 6, racemate cannot be effectively resolved even if separation conditions are changed.
Preparation example 2:
dispersing 5g silica gel particles (aperture 20nm) in 40mL of 0.2mol/L diluted alkali solution, performing ultrasonic treatment for 40min, washing with water until the solution is neutral, washing with anhydrous methanol for 5 times, and washing with toluene for 1 time. Subsequently, the activated silica gel particles are dispersed in 40mL of mixed solution of toluene and 3-Aminopropyltriethoxysilane (APTES) in a volume ratio of 10:1, uniformly mixed by ultrasound, and heated for reflux reaction for 20 h. Washing with methanol, and drying to obtain amino macroporous silicon ball SiO2@NH2. On the surface of the amino silica gel, 0.5g of macroporous amino silica gel with the pore diameter of 20nm is added into 30mL of 1, 4-dioxane to be uniformly dispersed, and then 2g R, R-TTA (chiral 1, 4-diol derived tetra-aldehyde monomer) and 100mg of p-phenylenediamine are added, and ultrasonic treatment is carried out until the monomers are completely dissolved; adding 1mL of acetic acid as a reaction catalyst, sealing a reaction system, and filling nitrogen as protective gas; heating the system to 100 ℃ in an oil bath, and carrying out reflux reaction for 3 days; finally, the resulting material was washed three times with 1, 4-dioxane and ethanol, respectively, in sequence, 5Drying at 0 ℃ to obtain chiral covalent organic framework bonded silica gel chromatographic stationary phase SiO2@CCOF。
Preparation example 3:
dispersing 5g silica gel particles (aperture 20nm) in 50mL of 0.2mol/L diluted alkali solution, performing ultrasonic treatment for 40min, washing with water until the solution is neutral, washing with anhydrous methanol for 5 times, and washing with toluene for 1 time. Subsequently, the activated silica gel particles were dispersed in 50mL of a mixed solution of toluene and 3-Aminopropyltriethoxysilane (APTES) in a volume ratio of 10:1, and the mixture was subjected to ultrasonic mixing and then heated under reflux for 20 hours. Washing with methanol, and drying to obtain amino macroporous silicon ball SiO2@NH2. On the surface of the amino silica gel, 0.5g of macroporous amino silica gel with the pore diameter of 20nm is added into 50mL of 1, 4-dioxane to be uniformly dispersed, and then 1g R, R-TTA (chiral 1, 4-diol derived tetra-aldehyde monomer) and 50mg of p-phenylenediamine are added, and ultrasonic treatment is carried out until the monomers are completely dissolved; adding 1mL of acetic acid as a reaction catalyst, sealing a reaction system, and filling nitrogen as protective gas; heating the system to 100 ℃ in an oil bath, and carrying out reflux reaction for 3 days; finally, the obtained material is sequentially and respectively washed by 1, 4-dioxane and ethanol for three times, and dried at 50 ℃ to obtain the chiral covalent organic framework bonded silica gel chromatographic stationary phase SiO2@CCOF。
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, several modifications and decorations can be made without departing from the concept of the present invention, and these modifications and decorations should also be regarded as being within the protection scope of the present invention.
Claims (10)
1. A method for preparing a chiral covalent organic framework bonded macroporous silica sphere chromatographic stationary phase is characterized by comprising the following specific preparation steps:
(1) silica gel particle activation treatment
Dispersing the silica gel particles in a dilute alkali solution, carrying out ultrasonic treatment for more than 10min (preferably 20-40 min), and cleaning to obtain activated silica gel particles;
(2) amino modification of silica gel particles
Dispersing the activated silica gel particles in toluene and 3-Uniformly mixing the mixed solution of Aminopropyltriethoxysilane (APTES), and heating and refluxing for reaction for more than 15 hours (preferably 18-20 hours); (ii) a Washing with methanol, and drying to obtain amino macroporous silicon ball SiO2@NH2；
(3) In situ polymerization of chiral COF
Dispersing amino silicon spheres in 1, 4-dioxane, adding a chiral 1, 4-diol derived tetra-aldehyde monomer (R, R-TTA) and p-phenylenediamine, finally adding acetic acid as a reaction catalyst, carrying out reflux reaction in an inert atmosphere, cleaning and drying to obtain the chiral covalent organic framework bonded macroporous silicon sphere chromatographic stationary phase.
2. The preparation method according to claim 1, wherein the silica gel in step 1) has a pore size of 20 to 50 nm;
the diluted alkali solution is 0.05-0.2 mol/L (preferably 0.08-0.15 mol/L), and the alkali is one or more of sodium hydroxide or potassium hydroxide.
3. The method according to claim 1 or 2, wherein the step 1) cleaning process is: and taking out the treated silica gel particles from the alkali solution, washing the silica gel particles with water until the solution is neutral, washing the silica gel particles with anhydrous methanol for 3-5 times, and then washing the silica gel particles with toluene for more than 1 time.
4. The method according to claim 1, wherein the reaction mixture,
the volume ratio of the toluene to the 3-Aminopropyltriethoxysilane (APTES) in the mixed solution in the step 2) is 10: 1-5: 1 (preferably 8: 1-6: 1).
5. The method of claim 1, wherein in step 3):
the mass ratio of the chiral 1, 4-diol derived tetra-aldehyde monomer to the amino macroporous silicon spheres is 1: 0.1-1: 5, preferably 1: 2-1: 3;
the molar concentration ratio of the chiral 1, 4-diol derived tetra-aldehyde monomer to the p-phenylenediamine is 1: 0.5-1: 5, preferably 1: 1-1: 2;
the molar concentration ratio of the acetic acid to the chiral 1, 4-diol derived tetra-aldehyde monomer is 1: 0.05-1: 2, preferably 1: 1-1: 1.5.
6. The method according to claim 1, wherein the reaction temperature is 100 to 120 ℃ and the reaction time is 3 to 5 days.
7. The method of claim 1, wherein in step 3): the cleaning is sequentially and respectively cleaning by using 1, 4-dioxane and ethanol; the inert atmosphere gas is one or more than two of nitrogen or argon.
8. A stationary phase prepared by the method of any one of claims 1 to 7.
9. Use of the stationary phase of claim 8 in the analysis and/or preparation of a chiral pharmaceutical intermediate.
10. The use of claim 9, wherein the chiral drug intermediate is 1-phenyl-2-propanol.
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