CN110404520A - A kind of preparation and application of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase - Google Patents
A kind of preparation and application of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase Download PDFInfo
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- CN110404520A CN110404520A CN201910648878.9A CN201910648878A CN110404520A CN 110404520 A CN110404520 A CN 110404520A CN 201910648878 A CN201910648878 A CN 201910648878A CN 110404520 A CN110404520 A CN 110404520A
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- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/30—Partition chromatography
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Abstract
The invention discloses a kind of preparation methods of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase, silane coupling agent and silica matrix are reacted in alkyl benzene solvent first, mercapto propyl silica gel is made, react mercapto propyl silica gel in organic solvent with quinine, azodiisobutyronitrile, by surface free radical chain transfer reaction, quinine is polymerize and obtains poly- quinine silica gel in mercapto propyl silica gel surface；Then bridging molecules are made with halogenated isocyanates, alkyl imidazole type ionic liquid is modified by nucleophilic substitution in poly- quinine Silica Surface in organic solvent, is prepared into alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase.Chromatographic isolation select performance the result shows that, alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase prepared by the present invention can not only realize the baseline separation of sulfa drugs and base nucleosides under hydrophilic interaction mode, can also be in the separation of rp mode realization non-polar compound and chipal compounds.
Description
Technical field
The present invention relates to a kind of preparation methods of Stationary Phase for HPLC, and in particular to a kind of Bonded Phase is alkyl imidazole type
The silica gel chromatograph stationary phase of ion liquid functionalization quinine, belongs to chromatographic stationary phases technical field.
Background technique
High performance liquid chromatography (HPLC) plays key player in separation analysis field, and stationary phase is as chromatographic isolation skill
The heart of art, the development of chromatographic technique and the innovation of chromatographic stationary phases are closely related, therefore Development of Novel chromatograph packing material is for pushing away
The development of dynamic chromatographic isolation analytical technology has a very important significance.
For quinine as a kind of natural plant biological alkali, raw material is cheap and easy to get；Its contain benzo pyridine, tertiary amine positive center,
Multiple chirality sites and hydroxyl and terminal olefin functional group convenient for modification are suitble to be bonded to silica gel table as modification small molecule
Face is used to separate analysis as chromatographic stationary phases as the integral material of monomer polymerization.Currently based on the filling of quinine derivative
Column and integral post to analyte selectivity, chromatogram column efficiency, in terms of show certain advantage.
Ionic liquid (Ionic liquids, ILs) is a kind of non-molecule object being made of organic cation and anion
Matter, generally liquid under normal temperature and pressure, the replaceability and modifiability of zwitterion part so that its be successfully applied to it is all
It is multi-field.Dinitrogen atom and C in imidazole type ion liquid2 Position has strong electronegativity, provides multiple reaction active sites
Point is modified after being used for, so that imidazole type ion liquid is the highest ionic liquid of the frequency of occurrences so far.Qiu et al. (Zhang M,
Mallik A K, Takafuji M, et al. Anal Chim Acta, 2015, 887: 1-16; Zhang M,
Liang X, Jiang S, et al. Trends Analyt Chem, 2014,53:60-72) review imidazole type ion
The application of liquid bonded silica gel stationary phase, this kind of stationary phase show in ion exchange, hydrophilic interaction, reverse phase/positive isotype
Excellent separating property out.
However, still about the document of the quinine bonded silica gel chromatographic stationary phases of alkyl imidazole type ionic liquid functionalization at present
It has not been reported.Therefore, the excellent properties that the present invention shows quinine and alkyl imidazole type ionic liquid in chromatographic stationary phases
It combines, is prepared for a kind of quinine bonded silica gel chromatographic stationary phases of novel alkyl imidazole type ionic liquid functionalization.
Summary of the invention
The object of the present invention is to provide a kind of systems of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase
Preparation Method.
It is another object of the present invention to the quinine silica gel chromatograph stationary phases to abovementioned alkyl imidazole type ion liquid functionalization
Chromatographic separation performance studied.
One, the preparation of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase
The method that the present invention prepares quinine silica gel chromatograph stationary phase, is first by silane coupling agent and silica matrix in alkyl benzene solvent
Mercapto propyl silica gel is made in middle react, then reacts mercapto propyl silica gel in organic solvent with quinine, azodiisobutyronitrile, passes through table
Quinine polymerize and obtains poly- quinine silica gel in mercapto propyl silica gel surface by face radical chain transfer reaction；Then with halogenated isocyanates
Make bridging molecules, modifies alkyl imidazole type ionic liquid in poly- quinine silica gel table by nucleophilic substitution in organic solvent
Face is prepared into alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase.Specifically includes the following steps:
(1) preparation of mercapto propyl silica gel: by silane coupling agent and silica gel microball with the quality of 1:0.8 ~ 1:1.2 than ultrasonic disperse in
In alkyl benzene solvent, in 80 ~ 100 DEG C of 20 ~ 48 h of mechanic whirl-nett reaction under nitrogen or argon atmosphere protection, it is cooled to room temperature,
Centrifuge washing, vacuum drying, obtains mercapto propyl silica gel；
The structural formula of silane coupling agent is as follows:
Wherein, R3For methoxy or ethoxy；
The alkyl benzene solvent is one of benzene, toluene, dimethyl benzene.
(2) preparation of poly- quinine silica gel: by mercapto propyl silica gel and quinine, azodiisobutyronitrile ultrasonic disperse in organic solvent
In, it is warming up to 65 ~ 100 DEG C of 20 ~ 30 h of mechanic whirl-nett reaction；It is cooled to room temperature, centrifuge washing, is dried in vacuo after reaction,
Obtain poly- quinine silica gel；
Organic solvent is one of anhydrous methylene chloride, chloroform, carbon tetrachloride.
Mercapto propyl silica gel and the mass ratio of quinine are 1:0.7 ~ 1:1.0；The quality of mercapto propyl silica gel and azodiisobutyronitrile
Than for 1:0.01 ~ 1:0.02.
(3) by poly- quinine colloidal silica dispersion in organic solvent, halogen the preparation of poly- chloro-quinine silica gel: is added into dispersion liquid
For isocyanates, 20 ~ 24 h of mechanic whirl-nett reaction, centrifuge washing, vacuum drying obtain poly- chloro-quinine silica gel at room temperature；
The structural formula of the halogenated isocyanates is as follows:
Wherein X is Cl or Br；M=2 or 3.
The mass ratio of poly- quinine silica gel and halogenated isocyanates is 1:0.5 ~ 1:1.0.
Organic solvent is one of anhydrous methylene chloride, chloroform, carbon tetrachloride.
(4) halogenated quinine silica gel, N- alkyl imidazo ion liquid ultrasound point the preparation of quinine silica gel chromatograph stationary phase: will be gathered
It dissipates in organic solvent, is warming up to 80 ~ 100 DEG C of 2 ~ 3d of mechanic whirl-nett reaction under nitrogen atmosphere protection；It is cooled to after reaction
Room temperature, centrifuge washing, vacuum drying obtain target product --- and alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph is solid
Determine phase.
The structural formula of N- alkyl imidazo ion liquid is as follows:
The wherein integer that k is 0 ~ 17.
Organic solvent is one of ethyl alcohol, isopropanol, acetonitrile, DMF, tetrahydrofuran.
The mass ratio for gathering halogenated quinine silica gel and N- alkyl imidazole is 1:1.5 ~ 1:2.0.
The structural formula of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase prepared by the present invention is as follows:
Two, the structural characterization of the quinine silica gel chromatograph stationary phase of alkyl imidazole type ionic liquid functionalization
1, elemental analysis
Table 1 is the elemental analysis of corresponding product in the quinine silica gel chromatograph stationary phase of alkyl imidazole type ionic liquid functionalization.Packet
Include naked silica gel, mercapto propyl silica gel, poly- quinine silica gel, the poly- quinine silica gel of halogenated isocyanates and alkyl imidazole-five kinds of quinine silica gel
Material.Elemental analysis the result shows that, the quinine silica gel chromatograph that alkyl imidazole type ionic liquid functionalization has successfully been prepared is solid
Determine phase.
2, infrared spectrum analysis (FT-IR)
Fig. 1 is the infrared spectroscopy of the quinine silica gel chromatograph stationary phase of alkyl imidazole type ionic liquid functionalization prepared by the present invention
(FT-IR) figure.In the infrared spectrogram of poly- quinine silica gel, in 1515 cm-1With 650 cm-1Two absorption peaks at place are Kui
The stretching vibration and flexural vibrations peak of C=C and C=N in peaceful molecule, it was confirmed that the successful preparation of poly- quinine silica gel；And in alkyl miaow
In azoles-quinine silica gel infrared spectrogram, 1360 cm-1With 1715 cm-1The emerging absorption peak in two, place is imidazole functionalities
Characteristic absorption peak, to confirm that alkyl imidazole is successfully bonded to poly- quinine silica gel.
Three, the chromatographic separation performance of the quinine silica gel chromatograph stationary phase of alkyl imidazole type ionic liquid functionalization
1, stationary phase chiral selectivity is evaluated
Fig. 2 and Fig. 3 is that the quinine silica gel chromatograph stationary phase of alkyl imidazole type ionic liquid functionalization is right under rp mode respectively
Chiral mixture I(R/S)-dibromo bis-naphthol (chromatographic condition are as follows: mobile phase: -50 mM ammonium acetate solution of methanol (60/40,
V/v)；Wavelength: 254 nm；Column temperature: 35 DEG C；Flow velocity: 1.0 mL/min) and chiral mixture II (R/S)-bis-naphthol (chromatography behaviour
Make condition are as follows: mobile phase: -50 mM ammonium acetate solution (35/65, v/v) of methanol；Wavelength: 254 nm；Column temperature: 35 DEG C；Stream
Speed: 0.8 mL/min) chromatographic isolation effect picture, it can be seen from the figure that the stationary phase has well bis-naphthol class isomers
Chiral separation selectivity.
2, the chromatographic separation performance evaluation of hydrophilic interaction mode
Fig. 4 be alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase under hydrophilic interaction mode to 8 kinds of sulphurs
The chromatographic isolation effect picture of amine drug.Chromatographic condition are as follows: mobile phase: -100 mM ammonium acetate solution (95/5, v/ of acetonitrile
V)；Wavelength: 254 nm；Column temperature: 30 DEG C；Flow velocity: 1.0 mL/min.The result shows that the stationary phase can realize sulphur in 7 min
Amine, sulfapryidine, sulfamethazine, sulfamethyldiazine, sulphadiazine, sulfadimethoxine, sulphathiazole and sulphur
The Selective Separation of 8 kinds of sulfa drugs of amine isoxazole.
Fig. 5 be alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase under hydrophilic interaction mode to 7
The chromatographic isolation effect picture of kind base nucleosides.Chromatographic condition are as follows: mobile phase: -100 mM ammonium acetate solution (95/5, v/ of acetonitrile
V)；Wavelength: 254 nm；Column temperature: 30 DEG C；Flow velocity: 1.0 mL/min.The result shows that the stationary phase realizes chest in 11 min
The selection of gland pyrimidine, thymidine, chest pyrimidine, adenosine, 7 kinds of adenine, cytidine and uridine base nucleosides
Property separation.
3, the chromatographic separation performance evaluation of rp mode
Fig. 6 be alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase under rp mode to 7 kinds of Tanaka
The chromatographic isolation effect picture of tester.Chromatographic condition are as follows: mobile phase: methanol-water solution (50/50, v/v)；Wavelength: 254 nm；
Column temperature: 40 DEG C；Flow velocity: 1.0 mL/min.The result shows that the stationary phase can successfully realize uracil, phenol, caffeine, butyl
The Selective Separation of benzene, 7 kinds of amylbenzene, ortho-terphenyl and triphenylene Tanaka testers.
Fig. 7 be alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase under rp mode to 6 kinds of alkane
The chromatographic isolation effect picture of base benzene.Chromatographic condition are as follows: mobile phase: methanol-water solution (50/50, v/v)；Wavelength: 254 nm；Column
Temperature: 40 DEG C；Flow velocity: 1.0 mL/min.The result shows that the stationary phase can successfully be realized under rp mode benzene, toluene, ethylbenzene,
The Selective Separation of 6 kinds of propylbenzene, butyl benzene and amylbenzene alkylbenzenes.
Fig. 8 be alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase under rp mode to more than 8 kinds
The chromatographic isolation effect picture of cycloaromatics.Chromatographic condition are as follows: mobile phase: methanol-water solution (50/50, v/v)；Wavelength: 254 nm；
Column temperature: 40 DEG C；Flow velocity: 1.0 mL/min.The result shows that the stationary phase can successfully be realized under rp mode benzene, naphthalene, acenaphthene, fluorenes,
The Selective Separation of Di, 8 kinds of phenanthrene, fluoranthene and triphenylene polycyclic aromatic hydrocarbons.
In conclusion the chromatographic stationary phases that the present invention is prepared have the advantages that
1, stationary phase structure novel obtained, preparation process raw material are easy to get, and are advantageously implemented commercial production；
2, the stationary phase can combine the separation advantage of quinine and imidazole type ion liquid modified silica-gel stationary phase, can be more
The Selective Separation that plurality of target analyte is realized under mode, has good market application prospect.
Detailed description of the invention
Fig. 1 is the red of poly- quinine silica gel (a) and alkyl imidazole type ionic liquid functionalization quinine silica gel (b) chromatographic stationary phases
External spectrum (FT-IR) figure.
Fig. 2 is the chiral mixture I(R/S of quinine silica gel chromatograph stationary phase of alkyl imidazole type ionic liquid functionalization)-
The separation chromatogram of dibromo bis-naphthol.
Fig. 3 is the chiral mixture of quinine silica gel chromatograph stationary phase of alkyl imidazole type ionic liquid functionalization(R/S)-
The separation chromatogram of bis-naphthol.
Fig. 4 is separation of the alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase to 8 kinds of sulfa drugs
Chromatogram.
Fig. 5 is separation color of the alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase to 7 kinds of base nucleosides
Spectrogram.
Fig. 6 is that alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase divides 7 kinds of Tanaka testers
From chromatogram.
Fig. 7 is separation chromatography of the alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase to 6 kinds of alkylbenzenes
Figure.
Fig. 8 is separation color of the alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase to 8 kinds of polycyclic aromatic hydrocarbons
Spectrogram.
Specific embodiment
Below by specific embodiment to alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase of the present invention
Preparation method be described further.
Embodiment 1
(1) by 3.0 g 3- mercaptopropyltriethoxysilane coupling agents and 3.0 g silica gel ultrasonic disperses in 30.0 ml dimethyl benzenes
In solvent, after being warming up to 90 DEG C of 48 h of mechanic whirl-nett reaction under nitrogen or argon atmosphere protection, it is cooled to room temperature, centrifugation is washed
It washs, is dried in vacuo, obtains mercapto propyl silica gel；
(2) 2.8 g mercapto propyl silica gels, 2.0 g quinines and 28.0 mg azodiisobutyronitrile ultrasonic disperses are anhydrous in 20.0 ml
In chloroform (bonus point screens out water), 65 DEG C of mechanical stirring back flow reaction 30h are warming up to, after object to be mixed is cooled to room temperature,
Centrifuge washing after vacuum drying, obtains poly- quinine silica gel；
(3) 2.1 ml 2- chloroethyl isocyanates are added dropwise to the anhydrous dichloro of 31.0ml containing the poly- quinine silica gel of 2.6 g
In methane uniform dispersion, at room temperature after 20 h of mechanic whirl-nett reaction, centrifuge washing, vacuum drying obtains poly- chloro-quinine silicon
Glue；
(4) 2.4 g are gathered into halogenated quinine silica gel, 3.6 ml N- methylimidazole ultrasonic disperses in 25.0 ml isopropanols, in nitrogen
Atmosphere is enclosed under protection, after being warming up to 85 DEG C of 2 d of mechanic whirl-nett reaction, is cooled to room temperature, centrifuge washing, and vacuum drying obtains institute
State chromatographic stationary phases.
Elemental analysis the result shows that, each step reaction product bonded amount of the stationary phase preparation process is moderate, and separating effect is good
It is good.
Embodiment 2
(1) by 2.5 g 3- mercaptopropyl trimethoxysilane coupling agents and 3.0 g silica gel ultrasonic disperses in 42.0 ml benzene solvents
In, after being warming up to 100 DEG C of 20 h of mechanic whirl-nett reaction under nitrogen or argon atmosphere protection, it is cooled to room temperature, centrifuge washing, very
Sky is dry, obtains mercapto propyl silica gel；
(2) 2.8 g mercapto propyl silica gels, 2.8 g quinines and 50.0 mg azodiisobutyronitrile ultrasonic disperses are anhydrous in 22.0 ml
In chloroform (bonus point screens out water), 100 DEG C of 22 h of mechanical stirring back flow reaction are warming up to, object to be mixed is cooled to room temperature
Afterwards, centrifuge washing after vacuum drying, obtains poly- quinine silica gel；
(3) 1.5 ml chloroethyl isocyanates are added dropwise to anhydrous three chloromethane of 20.0 ml containing the poly- quinine silica gel of 2.6 g
In alkane uniform dispersion, at room temperature after 24 h of mechanic whirl-nett reaction, centrifuge washing, vacuum drying obtains poly- chloro-quinine silica gel；
(4) 2.4 g are gathered into halogenated quinine silica gel, 4.5 ml N- methylimidazole ultrasonic disperses in 35.0 ml ethyl alcohol, in nitrogen
It under atmosphere protection, after being warming up to 90 DEG C of 3 d of mechanic whirl-nett reaction, is cooled to room temperature, centrifuge washing, is dried in vacuo, obtain described
Chromatographic stationary phases.
Elemental analysis the result shows that, the reality stationary phase each element bonded amount is moderate, good separation, but compared with embodiment 1
It is relatively weaker.
Embodiment 3
(1) by 3.5 g 3- mercaptopropyltriethoxysilane coupling agents and 3.0 g silica gel ultrasonic disperses in 28.0 ml toluene solvants
In, it after being warming up to 90 DEG C of 36 h of mechanic whirl-nett reaction under nitrogen atmosphere protection, is cooled to room temperature, centrifuge washing, is dried in vacuo,
Obtain mercapto propyl silica gel；
(2) by 2.8 g mercapto propyl silica gels, 2.5 g quinines and 30.0mg azodiisobutyronitrile ultrasonic disperse in 15.0 ml anhydrous three
In chloromethanes, 70 DEG C of mechanical stirring back flow reaction 30h are warming up to, after object to be mixed is cooled to room temperature, centrifuge washing, vacuum drying
Afterwards, poly- quinine silica gel is obtained；
(3) 1.8 ml3- chloropropyl isocyanates are added dropwise to the anhydrous trichlorine of 25.0 ml containing the poly- quinine silica gel of 2.6 g
In methane uniform dispersion, at room temperature after 22 h of mechanic whirl-nett reaction, centrifuge washing, vacuum drying obtains poly- chloro-quinine silicon
Glue；
(4) 2.4 g are gathered into halogenated quinine silica gel, 4.0 ml N- octylimidazole ultrasonic disperses in 30.0 ml tetrahydrofurans, In
It under nitrogen atmosphere protection, after being warming up to 100 DEG C of 2.5 d of mechanic whirl-nett reaction, is cooled to room temperature, centrifuge washing, is dried in vacuo,
Obtain the chromatographic stationary phases.
Elemental analysis the result shows that, the stationary phase each element bonded amount is relatively low, and separating effect is with respect to Examples 1 and 2
Difference.
Embodiment 4
(1) by 3.0 g 3- mercaptopropyltriethoxysilane coupling agents and 3.0 g silica gel ultrasonic disperses in 35.0 ml toluene solvants
In, it after being warming up to 85 DEG C of 35 h of mechanic whirl-nett reaction under nitrogen atmosphere protection, is cooled to room temperature, centrifuge washing, is dried in vacuo,
Obtain mercapto propyl silica gel；
(2) 2.8 g mercapto propyl silica gels, 2.3 g quinines and 40.0 mg azodiisobutyronitrile ultrasonic disperses are anhydrous in 25.0 ml
In methylene chloride (bonus point screens out water), 65 DEG C of 20 h of mechanical stirring back flow reaction are warming up to, object to be mixed is cooled to room temperature
Afterwards, centrifuge washing after vacuum drying, obtains poly- quinine silica gel；
(3) 2.3 ml3- bromopropyl isocyanates are added dropwise to the anhydrous tetrachloro of 23.0 ml containing the poly- quinine silica gel of 2.6 g
Change in carbon uniform dispersion, at room temperature after 20 h of mechanic whirl-nett reaction, centrifuge washing, vacuum drying obtains poly- chloro-quinine silicon
Glue；
(4) 2.4 g are gathered into halogenated quinine silica gel, 4.5 ml N- methylimidazole ultrasonic disperses in 28.0 ml DMF, in nitrogen
It under atmosphere protection, after being warming up to 95 DEG C of 2 d of mechanic whirl-nett reaction, is cooled to room temperature, centrifuge washing, is dried in vacuo, obtain described
Chromatographic stationary phases.
Elemental analysis the result shows that, the stationary phase each element bonded amount highest, separating effect is optimal in all embodiments
's.
Embodiment 5
(1) 2.5 g 3- mercaptopropyl trimethoxysilane coupling agents and 3.0 g silica gel ultrasonic disperses are molten in 40.0 ml dimethylbenzene
In agent, after being warming up to 80 DEG C of 48 h of mechanic whirl-nett reaction under nitrogen atmosphere protection, it is cooled to room temperature, centrifuge washing, vacuum is dry
It is dry, obtain mercapto propyl silica gel；
(2) 2.8 g mercapto propyl silica gels, 2.4 g quinines and 45.0 mg azodiisobutyronitrile ultrasonic disperses are anhydrous in 18.0 ml
In carbon tetrachloride (bonus point screens out water), 65 DEG C of 24 h of mechanical stirring back flow reaction are warming up to, object to be mixed is cooled to room temperature
Afterwards, centrifuge washing after vacuum drying, obtains poly- quinine silica gel；
(3) 1.4 ml 2- bromoethyl isocyanates are added dropwise to 25.0 ml anhydrous three containing the poly- quinine silica gel of 2.6 g
In chloromethanes uniform dispersion, at room temperature after 22 h of mechanic whirl-nett reaction, centrifuge washing, vacuum drying obtains poly- chloro-quinine
Silica gel；
(4) 2.4 g are gathered into halogenated quinine silica gel, 4.2 ml N- butyl imidazole ultrasonic disperses in 30.0 ml acetonitriles, in nitrogen
It under atmosphere protection, after being warming up to 100 DEG C of 3 d of mechanic whirl-nett reaction, is cooled to room temperature, centrifuge washing, is dried in vacuo, obtains institute
State chromatographic stationary phases.
Elemental analysis the result shows that, the stationary phase each element bonded amount is good, good separation, but compared with 4 phase of embodiment
To weaker, especially under the conditions of hydrophilic pattern.
Embodiment 6
(1) by 5.0 g 3- mercaptopropyltriethoxysilane coupling agents and 5.0 g silica gel ultrasonic disperses in 55.0 ml toluene solvants
In, it after being warming up to 100 DEG C of 36 h of mechanic whirl-nett reaction under nitrogen atmosphere protection, is cooled to room temperature, centrifuge washing, vacuum is dry
It is dry, obtain mercapto propyl silica gel；
(2) by 4.0g mercapto propyl silica gel, 3.5 g quinines and 65.0 mg azodiisobutyronitrile ultrasonic disperses in 45.0 ml anhydrous three
In chloromethanes (bonus point screens out water), 70 DEG C of 25 h of mechanical stirring back flow reaction are warming up to, after object to be mixed is cooled to room temperature, from
Heart washing, after vacuum drying, obtains poly- quinine silica gel；
(3) 2.8 ml 3- chloropropyl isocyanates are added dropwise to 45.0 ml anhydrous three containing the poly- quinine silica gel of 3.5 g
In chloromethanes uniform dispersion, at room temperature after 24 h of mechanic whirl-nett reaction, centrifuge washing, vacuum drying obtains poly- chloro-quinine
Silica gel；
(4) 3.3 g are gathered into halogenated quinine silica gel, 5.5 ml N- octadecyl imidazoles ultrasonic disperses in 45.0 ml isopropanols,
It under nitrogen atmosphere protection, after being warming up to 100 DEG C of 2.5 d of mechanic whirl-nett reaction, is cooled to room temperature, centrifuge washing, is dried in vacuo,
Obtain the chromatographic stationary phases.
Elemental analysis the result shows that, the stationary phase each element bonded amount rather moderate, separating effect is under hydrophilic pattern
Worst, but separation selectivity is optimal under rp mode.
Claims (13)
1. a kind of preparation method of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase, comprising the following steps:
(1) preparation of mercapto propyl silica gel: by silane coupling agent and silica gel microball ultrasonic disperse in alkyl benzene solvent, in nitrogen or
It in 80 ~ 100 DEG C of 20 ~ 48 h of mechanic whirl-nett reaction under argon atmosphere protection, is cooled to room temperature, centrifuge washing, is dried in vacuo, obtains mercapto
Propyl silica gel；
(2) preparation of poly- quinine silica gel: in organic solvent by mercapto propyl silica gel and quinine, azodiisobutyronitrile ultrasonic disperse,
It is warming up to 65 ~ 100 DEG C of 20 ~ 30 h of mechanic whirl-nett reaction；It is cooled to room temperature after reaction, centrifuge washing, is dried in vacuo, obtains poly-
Quinine silica gel；
(3) it the preparation of poly- chloro-quinine silica gel: by poly- quinine colloidal silica dispersion in organic solvent, is added into dispersion liquid halogenated different
Cyanate, 20 ~ 24 h of mechanic whirl-nett reaction, centrifuge washing, vacuum drying obtain poly- chloro-quinine silica gel at room temperature；
(4) preparation of quinine silica gel chromatograph stationary phase: will gather halogenated quinine silica gel, N- alkyl imidazo ion liquid ultrasonic disperse in
Organic solvent is warming up to 80 ~ 100 DEG C of 2 ~ 3d of mechanic whirl-nett reaction under nitrogen atmosphere protection；It is cooled to room temperature after reaction,
Centrifuge washing, vacuum drying, obtains target product --- alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase.
2. a kind of preparation side of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase as described in claim 1
Method, it is characterised in that: in step (1), the structural formula of silane coupling agent is as follows:
Wherein, R3For methoxy or ethoxy.
3. a kind of preparation side of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase as described in claim 1
Method, it is characterised in that: in step (1), the mass ratio of silica gel microball and silane coupling agent is 1:0.8 ~ 1:1.2.
4. a kind of preparation side of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase as described in claim 1
Method, it is characterised in that: in step (1), alkyl benzene solvent is one of benzene, toluene, dimethyl benzene.
5. a kind of preparation side of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase as described in claim 1
Method, it is characterised in that: in step (2), the mass ratio of mercapto propyl silica gel and quinine is 1:0.7 ~ 1:1.0；Mercapto propyl silica gel and idol
The mass ratio of nitrogen bis-isobutyronitrile is 1:0.01 ~ 1:0.02.
6. a kind of preparation side of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase as described in claim 1
Method, it is characterised in that: in step (3), the structural formula of the halogenated isocyanates is as follows:
Wherein X is Cl or Br；M=2 or 3.
7. a kind of preparation side of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase as described in claim 1
Method, it is characterised in that: in step (2), (3), organic solvent is one of anhydrous methylene chloride, chloroform, carbon tetrachloride.
8. a kind of preparation side of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase as described in claim 1
Method, it is characterised in that: in step (4), the structural formula of N- alkyl imidazo ion liquid is as follows:
The wherein integer that k is 0 ~ 17.
9. a kind of preparation side of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase as described in claim 1
Method, it is characterised in that: in step (4), organic solvent is one of ethyl alcohol, isopropanol, acetonitrile, DMF, tetrahydrofuran.
10. a kind of preparation side of alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase as described in claim 1
Method, it is characterised in that: in step (4), the mass ratio for gathering halogenated quinine silica gel and N- alkyl imidazole is 1:1.5 ~ 1:2.0.
11. the alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase of method preparation as described in claim 1 is used
In the separation of chiral bis-naphthol substance.
12. the alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase of method preparation as described in claim 1 is used
In the separation of sulfa drugs.
13. the alkyl imidazole type ionic liquid functionalization quinine silica gel chromatograph stationary phase of method preparation as described in claim 1 is used
In the separation of multiring aromatic hydrocarbon substance.
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