CN101811034B - Synthesis and application of large-grain diameter chiral stationary phase - Google Patents
Synthesis and application of large-grain diameter chiral stationary phaseDownload PDFInfo
- Publication number
- CN101811034B CN101811034BCN2010101346155ACN201010134615ACN101811034BCN 101811034 BCN101811034 BCN 101811034BCN 2010101346155 ACN2010101346155 ACN 2010101346155ACN 201010134615 ACN201010134615 ACN 201010134615ACN 101811034 BCN101811034 BCN 101811034B
- Authority
- CN
- China
- Prior art keywords
- stationary phase
- chiral stationary
- grain diameter
- chiral
- silica gel
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
Description
Technical field
The present invention relates to the synthetic and Application Areas of cellulose family chiral stationary phase, relate in particular to a kind of synthetic and application of large-grain diameter chiral stationary phase.
Background technology
Along with deepening continuously of enantiomorph chemical research, people more and more recognize the vital role of chipal compounds aspect medicine, agricultural chemicals and other biological functional materials.The chiral separation of enantiomer is the effective means that obtains the optical purity material, chiral chromatography particularly chiral high performance liquid chromatography (chiral HPLC) is the chiral separation method that develops rapidly in recent years, both can be used for analytical separation, also can be used for preparation separates, have a extensive future in research fields such as medicine, natural product and asymmetric synthesis, more and more come into one's own.
The core of chiral chromatography is chiral stationary phase (CSPs), the polysaccharide derivates class CSPs that grows up by Okamoto etc. wherein, derivatived cellulose CSPs particularly, highly versatile, durable in use, the sample load capacity is big, be widely used in during the analysis of all kinds racemic compound or preparation split.Through consulting 1984～2009 years Chinese patent databases, discovery has following patent: (1) application number is " heterogeneous chain polymer chiral stationary phase and preparation method thereof " of 200410013305.2, heterogeneous chain polymer chiral stationary phase in this invention is formed by connecting by amido linkage or urea key by carrier and chirr polymer, carrier is a 3-aminopropyl silica gel, can be widely used in industries such as medicine, fine chemistry industry; (2) patent No. is " new chemical bonded chiral stationary phase and its production and use " of 200610002010.4; this invention uses Chiral Amine 1-phenyl-2-p-methylphenyl-ethamine and chiral amino acid condensation to make the novel chiral group; with 2-or 4-amino-3; the 5-dinitrobenzoyl makes by being chemically bonded on the carrier as the connector element of novel chiral group and spacerarm.The present invention is suitable for using chromatograph packing material, prepared stationary phase to have very strong chiral recognition ability as the high performance liquid phase separation, can realize separating to multiple chipal compounds.(3) application number is 200510046924.6 " a kind of new Pirkle type chiral stationary phase and preparation method ", and this is invented with R-(+)-1, and 1 '-binaphthylyl-2,2 '-diamines are initiator, promptly obtain the set goal product through two-step reaction.Has π-in this new Pirkle type chiral stationary phase molecular structure simultaneously to electronics both binaphthylyl and π-electrophilic both 3; 5-dinitrobenzoyl group; have a plurality of can (NH C=O), can produce certain space multistory chemical action with the site of analyte generation interaction of hydrogen bond.
Above-mentioned patent mainly is matrix with silica gel, and particle diameter is 5 μ m, and finds the patent application that＞5 μ m fillers are used for the synthetic of chirality padding and use as yet at present.
Summary of the invention
Technical problem to be solved by this invention provides a kind of expense of raw materials of silica matrix in the chiral column preparation and synthetic method of the large-grain diameter chiral stationary phase that the silica gel particle diameter is 40～60nm of reducing.
Another technical problem to be solved by this invention provides the application of this large-grain diameter chiral stationary phase.
For addressing the above problem, a kind of large-grain diameter chiral stationary phase of the present invention is characterized in that: this chiral stationary phase is the coating-type and the bonding type cellulose derivative chiral stationary phase of coating volume ratio 18～25%, and it has following structural formula,
A kind of synthetic method of aforesaid large-grain diameter chiral stationary phase may further comprise the steps:
(1) aminopropyl alkanisation silica gel is synthetic: the silica gel that at first with particle diameter is 40～60 μ m at 150～200 ℃ of following vacuum-drying 4～6h, gets activated silica gel behind hydrochloric acid activation; Then at N2Protection adds dry-out benzene, anhydrous pyridine and 3-aminopropyl triethoxysilane, successively at 75～85 ℃ of followingback flow reaction 20～24h down; After cooling, clean,, promptly get aminopropyl alkanisation silica gel at 60～80 ℃ of following vacuum-drying 4～6h;
(2) cellulose derivative is synthetic: at first with Mierocrystalline cellulose at 90～100 ℃ of following vacuum-drying 4～6h; Then at N2Protection adds anhydrous pyridine down, and at 80～100 ℃ of following reflux 12～24h; Secondly add (3, the 5-dimethyl) phenylcarbimide, behind 80～110 ℃ of followingoil bath reaction 20～48h, be cooled to room temperature, add methyl alcohol again; After behind the suction filtration, washing,, promptly get cellulose derivative at 60～80 ℃ of following vacuum-drying 12～24h;
(3) coating of chiral stationary phase: at first the cellulose derivative with described step (2) gained is dissolved in the tetrahydrofuran (THF), and ultrasonic 10～20min obtains cellulose derivative solution; Then cellulose derivative solution is joined in the aminopropyl alkanisation silica gel of gained in the described step (1), with the even 1～5min of ultrasonic dispersing; Last rotary evaporation in vacuo removes and desolvates the chiral stationary phase that can obtain.
Hydrochloric acid mass concentration in the described step (1) is 3.65%.
Dry-out benzene in the described step (1) and anhydrous pyridine are all through CaH2Dry.
Silica gel is 1: 8～12,1: 0.1～0.2,1: 0.2～0.3 with the mass volume ratio of dry-out benzene, anhydrous pyridine, 3-aminopropyl triethoxysilane respectively in the described step (1).
Mierocrystalline cellulose is 1: 20～40,1: 8～11,1: 400～600 with the mass volume ratio of anhydrous pyridine, (3, the 5-dimethyl) phenylcarbimide, methyl alcohol respectively in the described step (2).
Mierocrystalline cellulose in the described step (2) is Mierocrystalline cellulose-three (3,5-3,5-dimethylphenyl carbamate) or Mierocrystalline cellulose-three (4-aminomethyl phenyl manthanoate).
The mass volume ratio of cellulose derivative and tetrahydrofuran (THF) is 1: 40～60 in the described step (3); The mass ratio of cellulose derivative and aminopropyl alkanisation silica gel is 1: 4～6.
Aforesaid large-grain diameter chiral stationary phase is in the application of the chirality drug enantiomer being carried out in the chiral separation.
The present invention compared with prior art has the following advantages:
1, is filler matrix owing to the present invention adopts big particle diameter silica gel particle (40-60 μ m), therefore, reduced the expense of raw materials of silica matrix in the chiral column preparation effectively; Simultaneously, because the filler aperture is big, space between filler is big, reduced resistance to moving phase, so prevented that effectively high, the easy obstruction of small particle size chiral column post pressure, life-span are than shortcomings such as weak points, thereby in the application of the plain class chiral column of preparation fiber type, demonstrated bigger advantage, had good application prospects.
2, the stationary phase that adopts gained of the present invention has obtained chiral separation preferably to the propranolol hydrochloride enantiomorph under the positive condition.
Because coating-type Mierocrystalline cellulose-three (3 among the present invention, 5-3,5-dimethylphenyl carbamate) chiral stationary phase is the optically active molecule with left-handed triple (3/2) spiral type hole, in the CDMPC polymerizable molecular, polar carbamate groups and dimethylbenzene group form a spiral slot round main chain, the Proprasylyte sample molecule is adjusted conformation and is advanced in people's spiral slot, hydroxyl in its structure and amino can produce hydrogen bond action and dipole-dipole effect with the CDMPC amido linkage, there is π-π effect in phenyl ring among naphthalene nucleus and the CDMPC, thereby form associated complex with stationary phase, by the different chiral separation that reach of stability of the formed associated complex of two enantiomers.Simultaneously, because Mierocrystalline cellulose has the space structure of high-sequential, therefore, vital role has also been played in the fractionation of Proprasylyte enantiomorph.
3, synthetic route of the present invention has shortened the reaction times, thereby has improved productive rate by increasing the temperature of reaction of Mierocrystalline cellulose and (3, the 5-dimethyl) phenylcarbimide.
Description of drawings
Below in conjunction with accompanying drawing the specific embodiment of the present invention is described in further detail.
Fig. 1 is the reaction synoptic diagram of silica gel among the present invention and 3-aminopropyl triethoxysilane.
Fig. 2 is Mierocrystalline cellulose and 3 among the present invention, the reaction synoptic diagram of 5-dimethyl phenylcarbimide.
Fig. 3 is cellulosic infrared spectrogram among the present invention.
Fig. 4 is the infrared spectrogram of CDMPC among the present invention.
Fig. 5 is the Proprasylyte structure iron.
Fig. 6 is the color atlas of propranolol chiral separation.
Fig. 7 is the influence of flow velocity to the Proprasylyte resolution.
Embodiment
1 one kinds of large-grain diameter chiral stationary phase of embodiment, this chiral stationary phase is the coating-type and the bonding type cellulose derivative chiral stationary phase ofcoating volume ratio 20%, it has following structural formula,
The synthetic method of this large-grain diameter chiral stationary phase may further comprise the steps:
(1) synthetic (referring to Fig. 1) of aminopropyl alkanisation silica gel (APS): the silica gel that at first with particle diameter is 40～60 μ m is behind 3.65% the hydrochloric acid activation through mass concentration, place the 250mL three-necked bottle to adopt the dry 5h of BPZ-6033LC vacuum drying oven down, get activated silica gel at 180 ℃; Then at N2Protection adds dry-out benzene, anhydrous pyridine and 3-aminopropyl triethoxysilane down successively, adopts three-necked flask at 80 ℃ of following back flow reaction 22h; Be cooled to room temperature at last, clean with 500mL methyl alcohol, 500mL acetone, 500mL normal hexane respectively, adopt the dry 5h of BPZ-6033LC vacuum drying oven down, promptly get 6.52g aminopropyl alkanisation silica gel at 70 ℃.This product places moisture eliminator standby.
Wherein: dry-out benzene and anhydrous pyridine are all through CaH2Dry.
Silica gel is 1: 10,1: 0.15,1: 0.25 with the mass volume ratio of dry-out benzene, anhydrous pyridine, 3-aminopropyl triethoxysilane respectively.
Detect through APS being carried out infrared spectra, its result as shown in Figure 3.From the IR spectrogram as can be seen Mierocrystalline cellulose at 3346.1cm-1The absorption of place-OH is very strong.
Its results of elemental analyses is referring to table 1.
Table 1
| Analyte | C massfraction/w (C) % | H massfraction/w (H) % | N massfraction/w (N) % |
| Silica gel | 0.36 | 0.84 | 0 |
| APS | 5.27 | 1.33 | 1.25 |
The no nitrogen element of silica gel as can be seen from experimental data, and contain the nitrogen element in the results of elemental analyses of APS, illustrate that the 3-aminopropyl triethoxysilane has been bonded on the silicon hydroxyl.
(2) synthetic (referring to Fig. 2) of cellulose derivative (CDMPC): at first Mierocrystalline cellulose-three (3,5-3,5-dimethylphenyl carbamate) is placed three-necked bottle, adopt the dry 6h of BPZ-6033LC vacuum drying oven down at 90 ℃; Then at N2Protection adds anhydrous pyridine, at 90 ℃ of following reflux 18h down; Secondly add (3, the 5-dimethyl) phenylcarbimide, after 100 ℃ 35h is reacted in the oil bath of employing DF-101S heat collecting type thermostatically heating magnetic stirring apparatus down, be cooled to room temperature, pour methyl alcohol under the vigorous stirring into; After AUTOSCIENCE AP-01 VACUUM/PRESSURE PUMP suction filtration, pale solid, use the 200mL methanol wash again after, at 60 ℃ of following vacuum-drying 24h, promptly get canescence cellulose derivative solid 1.75g, productive rate 85.78%.
Wherein: Mierocrystalline cellulose is 1: 20,1: 8,1: 400 with the mass volume ratio of anhydrous pyridine, (3, the 5-dimethyl) phenylcarbimide, methyl alcohol respectively.
Detect through CDMPC being carried out infrared spectra, its result as shown in Figure 4.From the IR spectrogram as can be seen CDMPC at 3346.1cm-1The absorption peak of place-OH is very weak, illustrates that the hydroxyl on the Mierocrystalline cellulose is esterified substantially, simultaneously at 1724.3cm-1Appearance phenyl amino formyl radical-the CO absorption peak, 1615.2cm-1And 1559.7cm-1Be the skeleton structure of phenyl ring, illustrate on the Mierocrystalline cellulose-OH is substantially by (3, the 5-dimethyl) phenylcarbimide esterification.
Its results of elemental analyses is referring to table 2.
Table 2
| CDMPC | C massfraction/w (C) % | H massfraction/w (H) % | N massfraction/w (N) % |
| Measured value | 66.01 | 6.42 | 6.67 |
| Theoretical value | 65.66 | 6.18 | 6.98 |
Measured value and theoretical value are coincide better as can be seen from experimental data, and cellulosic esterification is more complete.
(3) coating of chiral stationary phase: at first CDMPC is dissolved in the tetrahydrofuran (THF), adopts the ultrasonic 12min of SK5200H ultrasonic cleaner, obtain cellulose derivative solution; Then cellulose derivative solution is joined among the APS, with the even 1～5min of ultrasonic dispersing; Adopt rotatory evaporator RE-52A rotary evaporation in vacuo to remove at last and desolvate, this process repeats 3 times, can obtain coating amount and be 20% chiral stationary phase.(volume ratio is 90 to the stationary phase of gained: 10/v: v) be homogenate and displacing liquid, in the stainless steel tube of packing under 32～35MPa pressure (150mm * 4.6mm i.d.) with normal hexane-Virahol.
Wherein: the mass volume ratio of cellulose derivative and tetrahydrofuran (THF) is 1: 50; The mass ratio of cellulose derivative and aminopropyl alkanisation silica gel is 1: 5.
After being carried out ultimate analysis, CDMPC-CSPs finds (referring to table 3): w (C) 15.55%, w (H) 2.13%, w (N) 2.04%.By N constituent content among APS (w (N) 1.25%) and the CDMPC-CSPs (w (N) 2.04%) is compared, the N constituent content on the stationary phase rises to some extent than APS, illustrates that CDMPC is coated on the APS.
Table 3
| Determinand | C massfraction/w (C) % | H massfraction/w (H) % | N massfraction/w (N) % |
| APS | 5.27 | 1.33 | 1.25 |
| CDMPC-CSPs | 15.55 | 2.13 | 2.04 |
2 one kinds of large-grain diameter chiral stationary phase of embodiment, this chiral stationary phase is the coating-type and the bonding type cellulose derivative chiral stationary phase of coating volume ratio 18%, its structural formula is with embodiment 1.
The synthetic method of this large-grain diameter chiral stationary phase may further comprise the steps:
(1) aminopropyl alkanisation silica gel (APS) is synthetic: the silica gel that at first with particle diameter is 40～60 μ m is behind 3.65% the hydrochloric acid activation through mass concentration, place the 250mL three-necked bottle to adopt BPZ-6033LC vacuum drying oven vacuum-drying 6h down, get activated silica gel at 150 ℃; Then at N2Protection adds dry-out benzene, anhydrous pyridine and 3-aminopropyl triethoxysilane, successively at 85 ℃ of following back flow reaction 20h down; Be cooled to room temperature at last, clean with 500mL methyl alcohol, 500mL acetone, 500mL normal hexane respectively,, promptly get 6.4g aminopropyl alkanisation silica gel at 60 ℃ of following vacuum-drying 6h.This product places moisture eliminator standby.
Wherein: dry-out benzene and anhydrous pyridine are all through CaH2Dry.
Silica gel is 1: 8,1: 0.1,1: 0.2 with the mass volume ratio of dry-out benzene, anhydrous pyridine, 3-aminopropyl triethoxysilane respectively.
(2) cellulose derivative is synthetic: at first Mierocrystalline cellulose-three (4-aminomethyl phenyl manthanoate) is placed three-necked bottle, at 100 ℃ of following vacuum-drying 4h; Then at N2Protection adds anhydrous pyridine down, and at 100 ℃ of following reflux 12h; Secondly add (3, the 5-dimethyl) phenylcarbimide, behind 110 ℃ of following oil bath reaction 20h, be cooled to room temperature, pour methyl alcohol under the vigorous stirring; After suction filtration, pale solid, use the 200mL methanol wash again after, at 70 ℃ of following vacuum-drying 18h, promptly get canescence cellulose derivative solid 1.71g, productive rate 89.6%.
Wherein: Mierocrystalline cellulose is 1: 30,1: 10,1: 500 with the mass volume ratio of anhydrous pyridine, (3, the 5-dimethyl) phenylcarbimide, methyl alcohol respectively.
(3) coating of chiral stationary phase:
At first CDMPC is dissolved in the tetrahydrofuran (THF), ultrasonic 10min obtains cellulose derivative solution; Then cellulose derivative solution is joined among the APS, with the even 1～5min of ultrasonic dispersing; Last rotary evaporation in vacuo removes and desolvates, and this process repeats 3 times, can obtain coating amount and be 18% chiral stationary phase.(volume ratio is 90 to the stationary phase of gained: 10/v: v) be homogenate and displacing liquid, in the stainless steel tube of packing under 32～35MPa pressure (150mm * 4.6mm i.d.) with normal hexane-Virahol.
Wherein: the mass volume ratio of cellulose derivative and tetrahydrofuran (THF) is 1: 60; The mass ratio of cellulose derivative and aminopropyl alkanisation silica gel is 1: 6.
3 one kinds of large-grain diameter chiral stationary phase of embodiment, this chiral stationary phase is the coating-type and the bonding type cellulose derivative chiral stationary phase ofcoating volume ratio 25%, its structural formula is with embodiment 1.
The synthetic method of this large-grain diameter chiral stationary phase may further comprise the steps:
(1) aminopropyl alkanisation silica gel (APS) is synthetic: the silica gel that at first with particle diameter is 40～60 μ m is behind 3.65% the hydrochloric acid activation, to place the 250mL three-necked bottle at 200 ℃ of following vacuum-drying 4h through mass concentration, activated silica gel; Then at N2Protection adds dry-out benzene, anhydrous pyridine and 3-aminopropyl triethoxysilane, successively at 75 ℃ of following back flow reaction 24h down; Be cooled to room temperature at last, clean with 500mL methyl alcohol, 500mL acetone, 500mL normal hexane respectively,, promptly get 6.45g aminopropyl alkanisation silica gel at 80 ℃ of following vacuum-drying 4h.This product places moisture eliminator standby.
Wherein: dry-out benzene and anhydrous pyridine are all through CaH2Dry.
Silica gel is 1: 12,1: 0.2,1: 0.3 with the mass volume ratio of dry-out benzene, anhydrous pyridine, 3-aminopropyl triethoxysilane respectively.
(2) cellulose derivative is synthetic: at first Mierocrystalline cellulose-three (4-aminomethyl phenyl manthanoate) is placed three-necked bottle, at 95 ℃ of following vacuum-drying 5h; Then at N2Protection adds anhydrous pyridine down, and at 80 ℃ of following reflux 24h; Secondly add (3, the 5-dimethyl) phenylcarbimide, behind 80 ℃ of following oil bath reaction 48h, be cooled to room temperature, pour methyl alcohol under the vigorous stirring; After suction filtration, pale solid, use the 200mL methanol wash again after, at 80 ℃ of following vacuum-drying 12h, promptly get canescence cellulose derivative solid 1.47g, productive rate 79.8%.
Wherein: Mierocrystalline cellulose is 1: 40,1: 11,1: 600 with the mass volume ratio of anhydrous pyridine, (3, the 5-dimethyl) phenylcarbimide, methyl alcohol respectively.
(3) coating of chiral stationary phase: at first CDMPC is dissolved in the tetrahydrofuran (THF), ultrasonic 20min obtains cellulose derivative solution; Then cellulose derivative solution is joined in the described aminopropyl alkanisation of the APS silica gel, with the even 1～5min of ultrasonic dispersing; Last rotary evaporation in vacuo removes and desolvates, and this process repeats 3 times, can obtain coating amount and be 25% chiral stationary phase.(volume ratio is 90 to the stationary phase of gained: 10/v: v) be homogenate and displacing liquid, in the stainless steel tube of packing under 32～35MPa pressure (150mm * 4.6mm i.d.) with normal hexane-Virahol.
Wherein: the mass volume ratio of cellulose derivative and tetrahydrofuran (THF) is 1: 40; The mass ratio of cellulose derivative and aminopropyl alkanisation silica gel is 1: 4.
Embodiment 4 large-grain diameter chiral stationary phase are in the application of the chirality drug enantiomer being carried out in the chiral separation.
Because Proprasylyte (its structure iron is referring to Fig. 5) is the beta-blocker of wide clinical application, contain hydroxyl in its structure, amino and ether, be to be used for CDMPC chiral separation performance evaluation one of chiral drug more widely at present, therefore, this paper uses liquid-phase chromatography method, adopts Proprasylyte that 1～3 synthetic chiral stationary phase of embodiment is carried out the chiral separation evaluation.
Wherein:
Chromatographic system comprises the star color spectrum workstation of LC-6A pump (Japanese Shimadzu company), SPD-6AV UV-detector (Japanese Shimadzu company) and analysis.
Chromatographic separation condition: chromatographic separation is all at room temperature carried out, moving phase: normal hexane: Virahol: triethylamine, ultraviolet detection wavelength: 276nm; Flow velocity is 0.3～1mL/min; Sample size: 20 μ L; Dead time (the t of chromatographic column0) with 1,3, the 5-tri-butyl benzene is measured.
Moving phase is normal hexane: Virahol: triethylamine (V: V: V)=(50～98): (2～50): (0.05～0.2%).
The Virahol massfraction keeps and splits the influence (referring to table 4) of effect in the moving phase to the Proprasylyte sample.
Table 4
As can be seen from the table, along with the minimizing of isopropanol content in the moving phase, it is big that capacity factor k ' becomes, and shows that the retention time of sample in chiral stationary phase strengthens; Simultaneously resolution increases, and the minimizing that shows the Virahol massfraction helps sample and obtains better separating effect; Separation factor alpha increases thereupon, shows that stationary phase constantly strengthens sample racemize Separation of Enantiomers.
Select chromatographic column for use: coating-type Mierocrystalline cellulose-three (3,5-3,5-dimethylphenyl carbamate) chiral column.
Take all factors into consideration analysis time and separating effect, determine normal hexane: Virahol: triethylamine (95: 5: 0.1%/v: v: v) be the optimal flow phase, flow velocity (flow rate): 0.5mL/min, the color atlas of propranolol chiral separation is seen Fig. 6.
Simultaneously, with normal hexane: Virahol: triethylamine (95: 5: 0.1%/v: v: be moving phase v), investigated flow velocity to the isolating influence of Proprasylyte.When flow velocity when 0.9mL/min is reduced to 0.5mL/min, resolution increases, and reaches baseline separation (Fig. 7).
Claims (6)
1. large-grain diameter chiral stationary phase is characterized in that: this chiral stationary phase is the coating-type and the bonding type cellulose derivative chiral stationary phase of coating volume ratio 18～25%, and it has following structural formula,
2. the synthetic method of a large-grain diameter chiral stationary phase as claimed in claim 1 may further comprise the steps:
(1) aminopropyl alkanisation silica gel is synthetic: the silica gel that at first with particle diameter is 40～60 μ m at 150～200 ℃ of following vacuum-drying 4～6h, gets activated silica gel behind hydrochloric acid activation; Then at N2Protection adds dry-out benzene, anhydrous pyridine and 3-aminopropyl triethoxysilane, successively at 75～85 ℃ of following back flow reaction 20～24h down; After cooling, clean,, promptly get aminopropyl alkanisation silica gel at 60～80 ℃ of following vacuum-drying 4～6h;
(2) cellulose derivative is synthetic: at first with Mierocrystalline cellulose at 90～100 ℃ of following vacuum-drying 4～6h; Then at N2Protection adds anhydrous pyridine down, and at 80～100 ℃ of following reflux 12～24h; Secondly add (3, the 5-dimethyl) phenylcarbimide, behind 80～110 ℃ of following oil bath reaction 20～48h, be cooled to room temperature, add methyl alcohol again; After behind the suction filtration, washing,, promptly get cellulose derivative at 60～80 ℃ of following vacuum-drying 12～24h;
(3) coating of chiral stationary phase: at first the cellulose derivative with described step (2) gained is dissolved in the tetrahydrofuran (THF), and ultrasonic 10～20min obtains cellulose derivative solution; Then cellulose derivative solution is joined in the aminopropyl alkanisation silica gel of gained in the described step (1), with the even 1～5min of ultrasonic dispersing; Last rotary evaporation in vacuo removes and desolvates the chiral stationary phase that can obtain.
3. the synthetic method of large-grain diameter chiral stationary phase as claimed in claim 2 is characterized in that: the hydrochloric acid mass concentration in the described step (1) is 3.65%.
4. the synthetic method of large-grain diameter chiral stationary phase as claimed in claim 2 is characterized in that: dry-out benzene in the described step (1) and anhydrous pyridine are all through CaH2Dry.
5. the synthetic method of large-grain diameter chiral stationary phase as claimed in claim 2 is characterized in that: the Mierocrystalline cellulose in the described step (2) is Mierocrystalline cellulose-three (3,5-3,5-dimethylphenyl carbamate) or Mierocrystalline cellulose-three (4-aminomethyl phenyl manthanoate).
6. large-grain diameter chiral stationary phase as claimed in claim 1 is in the application of the chirality drug enantiomer being carried out in the chiral separation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101346155ACN101811034B (en) | 2010-03-25 | 2010-03-25 | Synthesis and application of large-grain diameter chiral stationary phase |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101346155ACN101811034B (en) | 2010-03-25 | 2010-03-25 | Synthesis and application of large-grain diameter chiral stationary phase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101811034A CN101811034A (en) | 2010-08-25 |
| CN101811034Btrue CN101811034B (en) | 2011-11-09 |
Family
ID=42618487
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010101346155AExpired - Fee RelatedCN101811034B (en) | 2010-03-25 | 2010-03-25 | Synthesis and application of large-grain diameter chiral stationary phase |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101811034B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102172519B (en)* | 2011-03-01 | 2012-11-14 | 北京化工大学 | Silica gel bonded cellulose derivative chromatographic filler and preparation method and use thereof |
| CN105080518A (en)* | 2014-05-13 | 2015-11-25 | 中科院大连化学物理研究所淮安化工新材料研究中心 | Chemically-bonded cellulose-type chiral stationary phase and preparation method thereof |
| CN104607163B (en)* | 2015-01-26 | 2018-05-15 | 北京迪马欧泰科技发展中心 | A kind of micro- chiral adjusting cellulose chromatography stationary phase, preparation method and applications |
| CN109865505A (en)* | 2017-12-05 | 2019-06-11 | 中国科学院大连化学物理研究所 | A kind of biomass derived carbon application type chromatographic stationary phases and its preparation and application |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5403898A (en)* | 1992-05-04 | 1995-04-04 | Brigham Young University | Single arm attached cyclodextrin polysiloxanes and use thereof as chiral stationary phases in chromatographic separation of enantiomers |
| US5807482A (en)* | 1997-10-31 | 1998-09-15 | Uop Llc | Chiral stationary phase based on yohimbinic acid |
| CN101024621A (en)* | 2007-03-23 | 2007-08-29 | 四川大学 | 2-nitro-benzoyl-imino-acenaphthylene derivative compound and use thereof |
| CN101235104A (en)* | 2007-01-31 | 2008-08-06 | 北京理工大学 | Six kinds of β-cyclodextrin derivatized by α-Schiff base and its application |
- 2010
- 2010-03-25CNCN2010101346155Apatent/CN101811034B/ennot_activeExpired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5403898A (en)* | 1992-05-04 | 1995-04-04 | Brigham Young University | Single arm attached cyclodextrin polysiloxanes and use thereof as chiral stationary phases in chromatographic separation of enantiomers |
| US5807482A (en)* | 1997-10-31 | 1998-09-15 | Uop Llc | Chiral stationary phase based on yohimbinic acid |
| CN101235104A (en)* | 2007-01-31 | 2008-08-06 | 北京理工大学 | Six kinds of β-cyclodextrin derivatized by α-Schiff base and its application |
| CN101024621A (en)* | 2007-03-23 | 2007-08-29 | 四川大学 | 2-nitro-benzoyl-imino-acenaphthylene derivative compound and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101811034A (en) | 2010-08-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101811034B (en) | Synthesis and application of large-grain diameter chiral stationary phase | |
| Okamoto et al. | Chromatographic resolution: XI. Controlled chiral recognition of cellulose triphenylcarbamate derivatives supported on silica gel | |
| Li et al. | Enantioseparation performance of novel benzimido-β-cyclodextrins derivatized by ionic liquids as chiral stationary phases | |
| CN102172519A (en) | Silica gel bonded cellulose derivative chromatographic filler and preparation method and use thereof | |
| US5422004A (en) | High performance chiral selector | |
| CN101417227B (en) | Silica gel-bonded bichiral active center chromatographic packing and its application | |
| CN105622421A (en) | Preparation method and application of benzoic acid column [5] arene ester derivatives | |
| CN101992076A (en) | Chiral binaphthyl chromatogram immobile phase, and preparation method and application thereof | |
| CN103880728A (en) | Method for preparing diindolylmethane compound | |
| CN105348440B (en) | Oblongifolin C molecularly imprinted polymers and its preparation method and application | |
| CN102172518A (en) | Novel chiral chromatographic column fixed phase and preparation method thereof | |
| CN117586468A (en) | A (R)-BNBA-TP-COF polymer and its preparation method and application | |
| US4919803A (en) | Liquid chromatographic chiral stationary phase | |
| Yamamoto et al. | Enantioseparation using urea‐and imide‐bearing chitosan phenylcarbamate derivatives as chiral stationary phases for high‐performance liquid chromatography | |
| CN106680384A (en) | Ibuprofen and ketoprofen enantiomer resolution method | |
| JP6083832B2 (en) | Optically active poly (diphenylacetylene) compound, method for producing the same, and use as an optical isomer separating agent | |
| CN103113480A (en) | Amylose derivative and preparation method and application thereof | |
| CN1126628A (en) | Simulated moving bed chromatographic separation process | |
| Yashima et al. | Enantioseparation on 4‐halogen‐substituted phenylcarbamates of amylose as chiral stationary phases for high‐performance liquid chromatography | |
| CN114797809A (en) | Porous liquid gas chromatography chiral column for resolving racemic compound | |
| Tiritan et al. | Preparative enantioseparation on polysaccharide phase using microporous silica as a support | |
| Yamamoto et al. | Preparation of HPLC chiral packing materials using cellulose tris (4‐methylbenzoate) for the separation of chrysanthemate isomers | |
| US9290592B2 (en) | Poly(diphenylacetylene) compound, preparation method therefor, and use thereof as optical isomer separating agent | |
| CN104857987A (en) | Chiral imidazolinone functionalized heterogeneous catalyst and preparation method thereof | |
| CN106518813B (en) | A kind of synthetic method of glycidol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | Granted publication date:20111109 Termination date:20160325 | |
| CF01 | Termination of patent right due to non-payment of annual fee |