CN102553550B - Hybridization chirality stationary phase based on cellulose derivative and preparation method thereof - Google Patents
Hybridization chirality stationary phase based on cellulose derivative and preparation method thereof Download PDFInfo
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- 229920002678 cellulose Polymers 0.000 title claims abstract description 93
- 239000001913 cellulose Substances 0.000 title claims abstract description 93
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 230000005526 G1 to G0 transition Effects 0.000 title abstract description 19
- 238000009396 hybridization Methods 0.000 title abstract description 12
- 229910052710 silicon Inorganic materials 0.000 claims abstract description 29
- 239000010703 silicon Substances 0.000 claims abstract description 29
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 18
- 238000001556 precipitation Methods 0.000 claims description 16
- 238000004132 cross linking Methods 0.000 claims description 15
- -1 propyl group isocyanates Chemical class 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 13
- 239000012948 isocyanate Substances 0.000 claims description 13
- 229910000077 silane Inorganic materials 0.000 claims description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- 239000003153 chemical reaction reagent Substances 0.000 claims description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 10
- 238000001291 vacuum drying Methods 0.000 claims description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 238000001212 derivatisation Methods 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- 239000000377 silicon dioxide Substances 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 6
- 239000004094 surface-active agent Substances 0.000 claims description 6
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 150000007984 tetrahydrofuranes Chemical group 0.000 claims description 5
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 4
- 239000013504 Triton X-100 Substances 0.000 claims description 4
- 229920004890 Triton X-100 Polymers 0.000 claims description 4
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims description 4
- 230000001376 precipitating effect Effects 0.000 claims description 4
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 claims description 3
- 239000013049 sediment Substances 0.000 claims description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 abstract description 27
- 239000002904 solvent Substances 0.000 abstract description 5
- 239000006087 Silane Coupling Agent Substances 0.000 abstract 1
- 238000003980 solgel method Methods 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
- 238000003756 stirring Methods 0.000 description 22
- 150000004676 glycans Chemical class 0.000 description 9
- 229920001282 polysaccharide Polymers 0.000 description 9
- 239000005017 polysaccharide Substances 0.000 description 9
- 239000011148 porous material Substances 0.000 description 9
- 150000003222 pyridines Chemical class 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 238000004090 dissolution Methods 0.000 description 7
- 238000000921 elemental analysis Methods 0.000 description 7
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 7
- 239000000178 monomer Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 238000002411 thermogravimetry Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QUNFCCQHRHTDDB-UHFFFAOYSA-N 1-chloro-3-isocyanato-5-methylbenzene Chemical compound CC1=CC(Cl)=CC(N=C=O)=C1 QUNFCCQHRHTDDB-UHFFFAOYSA-N 0.000 description 6
- MGYGFNQQGAQEON-UHFFFAOYSA-N 4-tolyl isocyanate Chemical class CC1=CC=C(N=C=O)C=C1 MGYGFNQQGAQEON-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000003513 alkali Substances 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- JKGITWJSGDFJKO-UHFFFAOYSA-N ethoxy(trihydroxy)silane Chemical class CCO[Si](O)(O)O JKGITWJSGDFJKO-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 229960001866 silicon dioxide Drugs 0.000 description 4
- ADAKRBAJFHTIEW-UHFFFAOYSA-N 1-chloro-4-isocyanatobenzene Chemical class ClC1=CC=C(N=C=O)C=C1 ADAKRBAJFHTIEW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 238000004237 preparative chromatography Methods 0.000 description 3
- XEFUJGURFLOFAN-UHFFFAOYSA-N 1,3-dichloro-5-isocyanatobenzene Chemical compound ClC1=CC(Cl)=CC(N=C=O)=C1 XEFUJGURFLOFAN-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000005557 chiral recognition Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- GVGUFUZHNYFZLC-UHFFFAOYSA-N dodecyl benzenesulfonate;sodium Chemical compound [Na].CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 GVGUFUZHNYFZLC-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 238000011106 process-scale chromatography Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229940080264 sodium dodecylbenzenesulfonate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- QQQSFSZALRVCSZ-UHFFFAOYSA-N triethoxysilane Chemical compound CCO[SiH](OCC)OCC QQQSFSZALRVCSZ-UHFFFAOYSA-N 0.000 description 1
- YUYCVXFAYWRXLS-UHFFFAOYSA-N trimethoxysilane Chemical compound CO[SiH](OC)OC YUYCVXFAYWRXLS-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention discloses a preparation method of a hybridization chirality stationary phase based on cellulose derivative, which cross-links non-replaced or replaced phenyl isocyanate cellulose derivative with silane coupling agents to prepare hybridization chirality silicon ball stationary phase in a sol-gel method and is simple in operation and easy to control. The prepared cellulose derivative of the hybridization chirality stationary phase is high in content, has good chirality resolution capability and mechanical strength, is good in solvent resistant property, has strong loading capability and is suitable for preparing chromatograph chairality stationary phase.
Description
Technical field
The present invention relates to the preparation field of chiral stationary phase, be specifically related to fixedly phase and preparation method thereof of a kind of hybrid chiral based on cellulose derivative.
Background technology
Progress and development along with medical science, the chromatogram of chiral drug splits and the analysis of optical purity becomes more and more important, chiral stationary phase is a kind of chromatographic separation material with Chiral Separation ability, commercial chiral stationary phase has kind more than 100 at present, wherein the cellulose-derived chiral stationary phase has higher fractionation performance and chromatogram and uploads capacity, is widely used in the enantiomer analysis and separates preparation.
Existing Cellulose-Based Chiral Stationary Phases is with after cellulose hydroxyl derivatization, applies or is bonded to the carrier surfaces such as silica gel and make.1986, Japanese Yoshio Okamoto group made a series of application type chiral stationary phases and successively develops application type cellulose derivative commodity post, as Chiralcel OD and OJ post etc.After this, for the problem such as overcome in the coating-type chiral stationary phase that cellulose derivative is easily run off and the solvent scope of application is narrow, the first passage vulcabond such as Yoshio Okamoto are bonded to aminopropyl silica gel with cellulose derivative and make the bonded chiral post, and Chiracel IB and IC be successful commercialization before and after 2004 years.China, Zou Hanfa etc. also disclose a kind of quick method for preparing the bonded polysaccharide chiral stationary phase in Chinese patent ZL200310105270.0, step is: 1) in the reactor that fills organic solvent, polysaccharide and polysaccharide derivatization reagent can react with trimethoxy silane or the triethoxysilane of hydroxyl reaction function base on polysaccharide with containing, centrifugation is collected solids standby; 2) contain trimethoxy or the triethoxy polysaccharide derivatives with above-mentioned preparation is coated on the exposed silica matrix surface that is usually used in chromatograph packing material, then be placed in reactor, add a certain proportion of toluene and pyridine, after reaction, cooling, use respectively oxolane, methanol wash product, vacuum drying can make the bonded polysaccharide chiral stationary phase again.The peaceful grade of Liu Xiao discloses the preparation method of a kind of bonding-affine compound chiral stationary phase in Chinese patent ZL200710191730.4, key step is: 1) with polysaccharide derivates I through being chemically bonded on chiral stationary phase matrix, obtain fixedly phase of bonding type; 2) polysaccharide derivates II is coated to through affinity bonding type is fixing to be gone up mutually, obtains bonding-affinity composite type polysaccharide chiral stationary phase.
Yet, owing to applying or bonding uses the restriction of the pore volume of silica gel own, general only can bonding or apply the approximately cellulose derivative of 20wt%, make that in the preparative chromatography separation process, the upper carrying capacity of sample can't further improve, limited its application in process-scale chromatography.Simultaneously, the application type cellulose is fixing can only adopt the mixture of n-hexane and alcohol organic solvent as mobile phase mutually, therefore may there be the problems such as enantiomer to be separated solubility in mobile phase is low, make the disposal ability of preparative chromatography decline to a great extent, the economy of chromatographic separation process is had a greatly reduced quality; Improve solubility property if add the organic solvents such as acetone, oxolane, chloroform in mobile phase, thereby can cause again cellulose derivative to lose the chiral Recognition ability.Although the bonding type cellulose is difficult for being dissolved or swelling by the oxolane equal solvent, but due to the larger molecular dimension of cellulose derivative and the pore property of silica-gel carrier itself, make the chirality function base density lower than application type, on sample, carrying capacity and separative efficiency are not as good as application type.Therefore, develop and a kind ofly existingly upload capacity than rich shade spectrum, the wide chiral stationary phase of the solvent scope of application has the wide market demand and application prospect simultaneously.
Summary of the invention
The invention provides the fixedly preparation method of phase of a kind of hybrid chiral based on cellulose derivative, prepared hybrid chiral is fixing has good chiral resolution ability and mechanical strength mutually.
A kind of hybrid chiral based on cellulose derivative is the preparation method of phase fixedly, comprises step:
(1) cellulose is dissolved in N, in N-dimethylacetylamide/lithium chloride system, take anhydrous pyridine as medium, the mixture of the phenyl isocyanate derivatization reagent and three that adds not replacement or replace-(ethyoxyl silicon) propyl group isocyanates, carry out derivative reaction, add precipitating reagent to make the product precipitation after derivative reaction finishes, filter and the dry phenyl isocyanate cellulose derivative that is not replaced or replace;
(2) cellulose derivative in step (1) is dissolved in organic solvent, add again silane coupler to carry out cross-linking reaction, cross-linking products is added to burin-in process in aqueous surfactant solution, the gained sediment after filtration, washing and vacuum drying obtain based on the hybrid chiral of cellulose derivative fixing mutually, i.e. organic inorganic hybridization silicon ball.
In order to reach better invention effect, preferably:
The described phenyl isocyanate derivatization reagent that does not replace or replace is selected
The structural formula of described three-(ethyoxyl silicon) propyl group isocyanates is
Described three-(ethyoxyl silicon) propyl group isocyanates are 1 with the mol ratio of the phenyl isocyanate derivatization reagent that does not replace or replace: 9-99.
Described precipitating reagent is selected methyl alcohol or ethanol.
The mass ratio of described cellulose and three-(ethyoxyl silicon) propyl group isocyanates is 3-4: 1, be more conducive to the regulation and control of follow-up fixedly phase porous character.
The ratio of the milliliter number of the grams of described cellulose derivative and silane coupler is 0.02-0.1: 1, be more conducive to the regulation and control of follow-up fixedly phase porous character.
Described silane coupler is selected a kind of in ethyl orthosilicate, two (triethoxy is silica-based) methane, two (triethoxy is silica-based) ethane, further preferred ethyl orthosilicate.
Described organic solvent is selected oxolane, pyridine, dimethyl sulfoxide (DMSO), chloroform or carrene.Described organic solvent preferably is heated to 30 ℃ of-80 ℃ of uses, is more conducive to the dissolving of cellulose derivative.
Described surfactant is selected ionic or nonionic surface active agent, specifically can select a kind of in lauryl sodium sulfate, softex kw, neopelex, OTAC, Triton X-100 (Triton X-100), further preferably sodium dodecyl sulfate and softex kw.Described aqueous surfactant solution preferably is heated to 40 ℃ of-100 ℃ of uses, and during burin-in process, best vigorous stirring is 10 minutes-120 minutes, is more conducive to the formation of fixing mutually good microstructure.
The condition of described derivative reaction is 40 ℃-100 ℃ (further preferred 60 ℃-100 ℃) reactions 24 hours-72 hours.
The condition of described cross-linking reaction is to react 1 hour-20 hours under 20 ℃-100 ℃.
Described cross-linking reaction is carried out under the condition of 2-11 in the pH value, is more preferably to carry out under the condition of 2-7 in the pH value.
The present invention's raw material used all can be selected the commercially available prod.
Fixedly the hybrid chiral based on cellulose derivative of preparation method's preparation of phase is fixing can be used for mutually preparing chiral column for described hybrid chiral based on cellulose derivative.
Compared with prior art, the present invention has following advantage:
The present invention adopts fixedly phase of phenyl isocyanate cellulose derivative that sol-gal process will not replace or replace and the crosslinked preparation hybrid chiral of silane coupler silicon ball, simple to operate, be easy to control, the prepared hybrid chiral fixedly cellulose derivative content of phase is high, have good chiral resolution ability and mechanical strength, solvent resistance is good and stronger upload capabilities is arranged, and is suitable as the chiral stationary phase that preparative chromatography is separated.
Description of drawings
Fig. 1 is Te Luogeer alkali
The fractionation design sketch of the chiral column that employing embodiment 8 makes; Chromatographic condition is: 35 ℃ of column temperatures; Mobile phase be n-hexane/isopropyl alcohol (90: 10, v/v); Flow velocity 0.3mL/min; Detect wavelength 254nm;
Fig. 2 is Te Luogeer alkali
The fractionation design sketch of the chiral column that employing embodiment 8 makes; Chromatographic condition is: 35 ℃ of column temperatures; Mobile phase be n-hexane/chloroform/isopropyl alcohol (90: 10: 1, v/v/v); Flow velocity 0.3mL/min; Detect wavelength 254nm;
In figure, the peak of the left-handed Te Luogeer alkali of (-) expression, the peak of (+) expression dextrorotation Te Luogeer alkali, ordinate is response, abscissa is the time: minute.
The specific embodiment
Embodiment 1:
1) phenyl isocyanate cellulose derivative chiral silane monomer is synthetic
With 0.2 gram cellulose and appropriate N, N-dimethylacetylamide and appropriate lithium chloride are placed in there-necked flask, stirring and refluxing 1 hour, add 2 milliliters of anhydrous pyridines after cellulose dissolution, the mixture that adds again 0.62 gram (0.005mol) phenyl isocyanate and 0.05 gram (0.0002mol) three-(ethyoxyl silicon) propyl group isocyanates, stir under 80 ℃ and carried out derivative reaction 24 hours, then make the product precipitation with 200 ml methanol, filtering also, drying obtains cellulose derivative;
2) organic inorganic hybridization silicon ball is synthetic
After 0.1 gram cellulose derivative is dissolved in 70 ℃ of oxolanes, add successively 2 milliliters of ethyl orthosilicates and 1 ml water, add acid for adjusting pH to 2,60 ℃ of lower cross-linking reactions 2 hours, it is in 5% lauryl sodium sulfate aqueous solution that the mixture that reaction is obtained splashes into 500 milliliters of 60 ℃ of mass percentage concentration, and in 60 ℃ of vigorous stirring 120 minutes, the precipitation that obtains is filtered with sand core funnel and be that 50% ethanol water, n-hexane wash with concentration expressed in percentage by volume successively, vacuum drying 8 hours namely gets fixedly phase of phenyl isocyanate cellulose-derived chiral hybrid.Through thermogravimetric and elemental analysis, this fixing quality percentage composition of middle cellulose derivative mutually accounts for 80%; Fixedly the phase specific area is 190m
2/ g, average pore size is 13nm.
Embodiment 2:
1) 4-chlorphenyl isocyanates cellulose derivative chiral silane monomer is synthetic
0.2 gram cellulose and appropriate DMA and appropriate lithium chloride are placed in there-necked flask, and 70 ℃ of lower stirring and refluxing 1 hour add 2 milliliters of anhydrous pyridines after cellulose dissolution.Add again 1.23 gram 4-chlorphenyl isocyanates (0.008mol) and 0.05 gram (0.0002mol) three-(ethyoxyl silicon) propyl group isocyanate mixture, stir under 80 ℃ and carried out derivative reaction 24 hours, then make the product precipitation with 200 milliliters of ethanol, filtering also, drying obtains cellulose derivative;
2) organic inorganic hybridization silicon ball is synthetic
after 0.11 gram cellulose derivative is dissolved in 70 ℃ of oxolanes, add successively 4 milliliters of ethyl orthosilicates and 1 ml water, regulate pH to 3, 60 ℃ of lower cross-linking reactions 2 hours, it is in 5% lauryl sodium sulfate aqueous solution that the mixture that reaction is obtained splashes into 500 milliliters of 60 ℃ of mass percentage concentration, and in 60 ℃ of vigorous stirring 50 minutes, the precipitation that obtains is filtered with sand core funnel and be 50% ethanol water successively with concentration expressed in percentage by volume, the n-hexane washing, vacuum drying 8 hours, namely get fixedly phase of 4-chlorphenyl isocyanates cellulose-derived chiral hybrid silicon ball.Through thermogravimetric and elemental analysis, this fixing quality percentage composition of middle cellulose derivative mutually accounts for 65%; Fixedly the phase specific area is 197m
2/ g, average pore size is 14.6nm.
Embodiment 3:
1) p-methylphenyl isocyanates cellulose derivative chiral silane monomer is synthetic
0.2 gram cellulose and appropriate DMA and appropriate lithium chloride are placed in there-necked flask, and 70 ℃ of lower stirring and refluxing 1 hour add 2 milliliters of anhydrous pyridines after cellulose dissolution.The mixture that adds again 0.85 gram p-methylphenyl isocyanates (0.0064mol) and 0.05 gram (0.0002mol) three-(ethyoxyl silicon) propyl group isocyanates, stir under 80 ℃ and carried out derivative reaction 24 hours, then make the product precipitation with 200 ml methanol, filtering also, drying obtains cellulose derivative;
2) organic inorganic hybridization silicon ball is synthetic
after 0.09 gram cellulose derivative is dissolved in 70 ℃ of oxolanes, add successively 3 milliliters of ethyl orthosilicates and 1 ml water, regulate pH to 7, 60 ℃ of lower cross-linking reactions 2 hours, it is in 5% lauryl sodium sulfate aqueous solution that the mixture that reaction is obtained splashes into 500 milliliters of 60 ℃ of mass percentage concentration, and in 60 ℃ of vigorous stirring 10 minutes, the precipitation that obtains is filtered with sand core funnel and be 50% ethanol water successively with concentration expressed in percentage by volume, the n-hexane washing, vacuum drying 8 hours, namely get fixedly phase of p-methylphenyl isocyanates cellulose-derived chiral hybrid silicon ball.Through thermogravimetric and elemental analysis, this fixing quality percentage composition of middle cellulose derivative mutually accounts for 72%:; Fixedly the phase specific area is 200m
2/ g, average pore size is 15nm.
Embodiment 4:
1) 3,5-dichlorophenyl isocyanate cellulose derivative chiral silane monomer synthetic
With 0.2 gram cellulose and appropriate N, N-dimethylacetylamide and appropriate lithium chloride are placed in there-necked flask, 70 ℃ of lower stirring and refluxing 1 hour, add 2 milliliters of anhydrous pyridines after cellulose dissolution, add again 1.24 grams 3, the mixture of 5-dichlorophenyl isocyanate (0.0066mol) and 0.05 gram (0.0002mol) three-(ethyoxyl silicon) propyl group isocyanates, stir under 80 ℃ and carried out derivative reaction 24 hours, then make the product precipitation with 200 ml methanol, filtering also, drying obtains cellulose derivative;
2) organic inorganic hybridization silicon ball is synthetic
after 0.13 gram cellulose derivative is dissolved in 70 ℃ of oxolanes, add successively 2 milliliters of ethyl orthosilicates and 1 ml water, add acid for adjusting pH to 3, 60 ℃ of lower cross-linking reactions 2 hours, it is in 5% the softex kw aqueous solution that the mixture that reaction is obtained splashes into 500 milliliters of 60 ℃ of mass percentage concentration, and in 60 ℃ of vigorous stirring 80 minutes, the precipitation that obtains is filtered with sand core funnel and be 50% ethanol water successively with concentration expressed in percentage by volume, the n-hexane washing, vacuum drying 8 hours, namely get 3, 5-dichlorophenyl isocyanate cellulose-derived chiral hybrid is phase fixedly.Through thermogravimetric and elemental analysis, this fixing quality percentage composition of middle cellulose derivative mutually accounts for 83%; Fixedly the phase specific area is 220m
2/ g, average pore size is 12nm.
Embodiment 5:
1) 3-methyl-5-chloro phenyl isocyanate cellulose derivative chiral silane monomer is synthetic
0.2 gram cellulose and appropriate DMA and appropriate lithium chloride are placed in there-necked flask, and 70 ℃ of lower stirring and refluxing 1 hour add 2 milliliters of anhydrous pyridines after cellulose dissolution.Add again 3.32 gram 3-methyl-5-chloro phenyl isocyanate (0.0198mol) and 0.05 gram (0.0002mol) three-(ethyoxyl silicon) propyl group isocyanate mixture, stir under 100 ℃ and carried out derivative reaction 72 hours, then make the product precipitation with 200 milliliters of ethanol, filtering also, drying obtains cellulose derivative;
2) organic inorganic hybridization silicon ball is synthetic
after 0.1 gram cellulose derivative is dissolved in 80 ℃ of pyridines, add successively 4 milliliters of two (triethoxy is silica-based) methane and 1 ml water, regulate pH to 3, 100 ℃ of lower cross-linking reactions 1 hour, it is in 10% sodium dodecyl benzene sulfonate aqueous solution that the mixture that reaction is obtained splashes into 500 milliliters of 40 ℃ of mass percentage concentration, and in 40 ℃ of vigorous stirring 120 minutes, the precipitation that obtains is filtered with sand core funnel and be 50% ethanol water successively with concentration expressed in percentage by volume, the n-hexane washing, vacuum drying 8 hours, namely get fixedly phase of 3-methyl-5-chloro phenyl isocyanate cellulose-derived chiral hybrid silicon ball.Through thermogravimetric and elemental analysis, this fixing quality percentage composition of middle cellulose derivative mutually accounts for 64%; Fixedly the phase specific area is 180m
2/ g, average pore size is 15nm.
Embodiment 6:
1) 3-methyl-5-chloro phenyl isocyanate cellulose derivative chiral silane monomer is synthetic
0.2 gram cellulose and appropriate DMA and appropriate lithium chloride are placed in there-necked flask, and 70 ℃ of lower stirring and refluxing 1 hour add 2 milliliters of anhydrous pyridines after cellulose dissolution.Add again 0.3 gram 3-methyl-5-chloro phenyl isocyanate (0.0018mol) and 0.05 gram (0.0002mol) three-(ethyoxyl silicon) propyl group isocyanate mixture, stir under 60 ℃ and carried out derivative reaction 48 hours, then make the product precipitation with 200 milliliters of ethanol, filtering also, drying obtains cellulose derivative;
2) organic inorganic hybridization silicon ball is synthetic
after 0.1 gram cellulose derivative is dissolved in 30 ℃ of chloroforms, add successively 4 milliliters of two (triethoxy is silica-based) ethane and 1 ml water, regulate pH to 2, 20 ℃ of lower cross-linking reactions 20 hours, it is in 3% the OTAC aqueous solution that the mixture that reaction is obtained splashes into 500 milliliters of 100 ℃ of mass percentage concentration, and in 100 ℃ of vigorous stirring 10 minutes, the precipitation that obtains is filtered with sand core funnel and be 50% ethanol water successively with concentration expressed in percentage by volume, the n-hexane washing, vacuum drying 8 hours, namely get fixedly phase of 3-methyl-5-chloro phenyl isocyanate cellulose-derived chiral hybrid silicon ball.Through thermogravimetric and elemental analysis, this fixing quality percentage composition of middle cellulose derivative mutually accounts for 65%; Fixedly the phase specific area is 186m
2/ g, average pore size is 15nm.
Embodiment 7:
1) p-methylphenyl isocyanates cellulose derivative chiral silane monomer is synthetic
0.2 gram cellulose and appropriate DMA and appropriate lithium chloride are placed in there-necked flask, and 70 ℃ of lower stirring and refluxing 1 hour add 2 milliliters of anhydrous pyridines after cellulose dissolution.Add again 1.33 gram p-methylphenyl isocyanates (0.01mol) and 0.05 gram (0.0002mol) three-(ethyoxyl silicon) propyl group isocyanate mixture, stir under 40 ℃ and carried out derivative reaction 55 hours, then make the product precipitation with 200 milliliters of ethanol, filtering also, drying obtains cellulose derivative;
2) organic inorganic hybridization silicon ball is synthetic
after 0.1 gram cellulose derivative is dissolved in 50 ℃ of dimethyl sulfoxide (DMSO)s, add successively 4 milliliters of two (triethoxy is silica-based) ethane and 1 ml water, regulate pH to 11, 50 ℃ of lower cross-linking reactions 10 hours, it is in 5% the Triton X-100 aqueous solution that the mixture that reaction is obtained splashes into 500 milliliters of 80 ℃ of mass percentage concentration, and in 80 ℃ of vigorous stirring 30 minutes, the precipitation that obtains is filtered with sand core funnel and be 50% ethanol water successively with concentration expressed in percentage by volume, the n-hexane washing, vacuum drying 8 hours, namely get fixedly phase of p-methylphenyl isocyanates cellulose-derived chiral hybrid silicon ball.Through thermogravimetric and elemental analysis, this fixing quality percentage composition of middle cellulose derivative mutually accounts for 62%; Fixedly the phase specific area is 182m
2/ g, average pore size is 15.5nm.
Embodiment 8:
With 3 of embodiment 4 preparations, 5-dichlorophenyl isocyanate cellulose-derived chiral hybrid silicon ball is fixing prepares with wet method dress post the chiral column that specification is 4.6mm * 150mm.The chiral column that makes is used for splitting Te Luogeer alkali
Chromatographic condition is: 35 ℃ of column temperatures; Mobile phase be n-hexane/isopropyl alcohol (90: 10, v/v); Flow velocity 0.3mL/min; Detect wavelength 254nm; Split effect and see Fig. 1 and Fig. 2.
Claims (9)
1. one kind based on the fixing preparation method of phase of the hybrid chiral of cellulose derivative, comprises step:
(1) cellulose is dissolved in N, in N-dimethylacetylamide/lithium chloride system, take anhydrous pyridine as medium, the mixture of the phenyl isocyanate derivatization reagent and three that adds not replacement or replace-(ethyoxyl silicon) propyl group isocyanates, carry out derivative reaction, add precipitating reagent to make the product precipitation after derivative reaction finishes, filtering also, drying obtains cellulose derivative;
(2) cellulose derivative in step (1) is dissolved in organic solvent, add again silane coupler to carry out cross-linking reaction, cross-linking products is added to burin-in process in aqueous surfactant solution, and the gained sediment after filtration, washing and vacuum drying obtain based on the hybrid chiral of cellulose derivative fixing mutually;
The described phenyl isocyanate derivatization reagent that does not replace or replace is
2. the fixing preparation method of phase of the hybrid chiral based on cellulose derivative according to claim 1, it is characterized in that, described three-(ethyoxyl silicon) propyl group isocyanates are 1:9-99 with the mol ratio of the phenyl isocyanate derivatization reagent that does not replace or replace.
3. the fixing preparation method of phase of the hybrid chiral based on cellulose derivative according to claim 1, is characterized in that, described precipitating reagent is methyl alcohol or ethanol.
4. the fixing preparation method of phase of the hybrid chiral based on cellulose derivative according to claim 1, it is characterized in that, described silane coupler is a kind of in ethyl orthosilicate, two (triethoxy is silica-based) methane, two (triethoxy is silica-based) ethane.
5. the fixing preparation method of phase of the hybrid chiral based on cellulose derivative according to claim 1, it is characterized in that, described surfactant is a kind of in lauryl sodium sulfate, softex kw, neopelex, OTAC, Triton X-100.
6. the fixing preparation method of phase of the hybrid chiral based on cellulose derivative according to claim 1, is characterized in that, described organic solvent is oxolane, pyridine, dimethyl sulfoxide (DMSO), chloroform or carrene.
7. the fixing preparation method of phase of the hybrid chiral based on cellulose derivative according to claim 1, is characterized in that, the condition of described derivative reaction is 40 ℃-100 ℃ reactions 24 hours-72 hours;
Perhaps, the condition of described cross-linking reaction is to react 1 hour-20 hours under 20 ℃-100 ℃;
Perhaps, described cross-linking reaction is carried out under the condition of 2-11 in the pH value.
The described hybrid chiral based on cellulose derivative of according to claim 1-7 any one fixedly phase preparation method's preparation based on the fixing phase of the hybrid chiral of cellulose derivative.
9. the fixing application in the preparation chiral chromatographic column of the hybrid chiral based on cellulose derivative according to claim 8.
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