CN108181414A - The preparation method and applications of chiral linkage capillary electric chromatogram open tubular column - Google Patents
The preparation method and applications of chiral linkage capillary electric chromatogram open tubular column Download PDFInfo
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Abstract
The invention discloses a kind of preparation method and applications of chiral linkage capillary electric chromatogram open tubular column, belong to Packing Capillary ElectrochromatographColumns Columns field.The present invention utilizes the special construction and characterization of molecules of beta cyclodextrin, design its derivative with isocyanate group, it is bonded with amination capillary tube inner wall, is prepared for meeting electrochromatography separation requirement, method is simple, the chiral capillary electrochromatography open tubular column of good reproducibility and stability.Stationary phase is bonded to by what chemical bond consolidated on capillary tube inner wall, has better mechanical strength and stability compared to the stationary phase of coating.
Description
Technical field
The invention belongs to Packing Capillary ElectrochromatographColumns Columns fields, and in particular to a kind of chiral linkage capillary electric chromatogram
The preparation method and applications of open tubular column.
Background technology
Chirality is widely present in nature, is the essential characteristic of biosystem, but the understanding of human opponent's property substance and
Research is also very plain.In recent years, as people are to the pass in the relationships people's livelihood fields such as medicine, food, life science and environment analysis
The heart and concern, also increasingly prominent [the Analytica Chimica of chiral analysis test problems being largely present in these fields
Acta,931(2016):1-24]。
Chromatography is to be currently used in most efficient method in chiral separation detection method.Wherein, capillary electric chromatogram conduct
Efficient, the quick chromatography micro separation technique of one kind emerging in recent years, applied in chiral separation detection.But due to capillary
The limitation of electric chromatographic column (different by stationary phase form, to be divided into packed column, integral post and open tubular column) technology of preparing, limits it
Application range.Open tubular column preparation process is simple, and pillar good penetrability is not likely to produce bubble and eddy diffusivity, relative to packed column
There is higher column effect, and do not need to fire plunger, can chiral substance be realized with a kind of relatively easy and economic pattern
Efficiently separate analysis [Journal of Chromatography A, 1467 (2016):145-154].It is but general to use coating side
Open tubular column prepared by formula, stationary phase easily come off, and service life is short；And the open tubular column that bonding pattern is used to prepare, pass through chemistry
Key is bonded to what stationary phase consolidated on capillary tube inner wall, then the shortcomings that can overcoming this respect and deficiency.Therefore, it designs and prepares
Various bonding open tubular columns have become the hot spot of this field exploration.
Because of its unique structure and performance, the research as chromatographic stationary phases has received significant attention beta-cyclodextrin (β-CD)
[Journal of Pharmaceutical and Biomedical Analysis,130(2016):110-125].But as
Chiral stationary phase generally requires to carry out selective modification to it, introduces different groups, it is made to change in chiral resolution process
Its interaction force with enantiomer has more action sites with mapping physical efficiency, so as to improve the universality of its application or choosing
Selecting property.As the stationary phase of bonding open tubular column, generally require and prepare the beta-cyclodextrin derivative with functional groups.
In conclusion beta-cyclodextrin derivative of the design with functional groups, by simple operations, establishes service life
It is long, good reproducibility and stability, the preparation method of the bonding capillary open tubular column available for chiral analysis detection, it would be highly desirable to occur.
Invention content
Present invention aims to overcome that the shortcomings that existing electric chromatographic column preparation method and deficiency, and a kind of energy is provided and meets electricity
Chromatographic isolation requirement, preparation method is simple, and service life is long, good reproducibility and stability, and the electricity with chiral resolution ability
The preparation method of chromatographic column.
Specific technical solution of the present invention is as follows：
The preparation method of chiral linkage capillary electric chromatogram open tubular column, its step are as follows:
1) it is (0.25~0.45) by mass ratio：1 methyl diphenylene diisocyanate and single -6- ethylenediamines base β-ring paste
Essence is dissolved in dimethyl sulfoxide (DMSO), 4~6h of stirring at normal temperature under inert gas shielding, then adds in acetone and precipitation is precipitated, will precipitate
Object is by filtering, being dried to obtain list -6- urea bond bridging beta-cyclodextrins；
2) capillary column is rinsed with HCl solution, water and NaOH solution successively, then sealing two ends are placed certain time, then
It is rinsed with water to neutrality, continues nitrogen after being rinsed with methanol and dry up；
3) it is 70 by volume ratio:(22~25):3-aminopropyltriethoxysilane, ethyl alcohol and the aqueous mixtures of (5~8)
Injection is by the 2) capillary column of processing, sealing two ends carry out reaction at 30~45 DEG C makes capillary tube inner wall amination, instead
It should be rinsed and be dried with methanol after the completion；
4) it by single -6- urea bond bridging beta-cyclodextrins and azodiisobutyronitrile, is added in the dimethyl sulfoxide (DMSO) of certain volume,
The mass volume ratio of wherein single -6- urea bond bridging beta-cyclodextrins and dimethyl sulfoxide (DMSO) is 6~10%, is filled with after mixing by 3) place
In the capillary column of reason, sealing two ends, 40~50 DEG C of 24~48h of water-bath successively with methanol, ultrapure water, are obtained in one's hands
Property bonding capillary electrochromatography open tubular column.
Preferably, the preparation method of the list -6- ethylenediamine base beta-cyclodextrins is：It will single -6- p-toluenesulfonyls
Beta-cyclodextrin is dissolved in ethylenediamine, and white precipitate is precipitated after adding in acetone after reaction, is filtered；To sediment by being dissolved in water
The mode that addition acetone is precipitated afterwards is purified several times, and list -6- ethylenediamine base beta-cyclodextrins are obtained after purified product drying.
Further, the preparation method of the list -6- p-toluenesulfonyl beta-cyclodextrins is：Beta-cyclodextrin is dissolved in
In sodium hydroxide solution, paratoluensulfonyl chloride is then added under the conditions of cold bath, mixed liquor is stirred to react 4~6h, mistake
Filter adjusts filtrate pH=6~7 with HCl solution, is then statically placed in mixed solution under 0~4 DEG C of environment overnight, then filtering point
Sediment is separated out, sediment is recrystallized, list -6- p-toluenesulfonyl beta-cyclodextrins are obtained after recrystallized product drying.
Further, recrystallization method is：It is recrystallized 2 times with distilled water, volume ratio 1：1 acetonitrile：The mixed solution of water
Recrystallization 1 time.
Further, when preparing single -6- p-toluenesulfonyl beta-cyclodextrins, in the mixed liquor, sodium hydroxide solution
A concentration of 30%, per 100mL sodium hydroxide solutions in dissolving 5.0g beta-cyclodextrins and 1.5~1.8g paratoluensulfonyl chlorides.
Preferably, in step 2), capillary column need to be pre-processed in advance, remove the dust inside capillary column.
Preferably, in step 2), the concentration of HCl solution and NaOH solution is 1mol/L, HCl solution, water and NaOH
The washing time of solution is respectively 30min, 30min and 1h, and sealing two ends are 6h after standing time at 40 DEG C, when methanol rinses
Between be 20min.
Preferably, reaction temperature of single -6- p-toluenesulfonyl beta-cyclodextrins in ethylenediamine is 80 DEG C, the reaction time
For 4~6h.
The chiral linkage hair prepared another object of the present invention is to provide a kind of method in any of the above-described scheme
Tubule electrochromatography open tubular column.The open tubular column can be used for chiral substance to carry out chiral resolution.
The present invention in terms of existing technologies, has the advantages that：
(1) using the special construction of beta-cyclodextrin and characterization of molecules, its derivative with isocyanate group is designed, with ammonia
Base capillary tube inner wall is bonded, and is prepared for meeting electrochromatography separation requirement, method is simple, the chiral hair of good reproducibility and stability
Tubule electrochromatography open tubular column.
(2) the functionalization group such as cyclodextrin monomer, urea groups, amino is introduced into open tubular column stationary phase, is formed with more
Mechanism, the stationary phase of multi-mode effectively improve column effect and separation selectivity.
(3) increase with the access times of bonding method, the electrochromatography open tubular column with different-thickness stationary phase can be obtained,
Sample capacity is effectively improved, improves stationary phase machinery strength and stability.
Description of the drawings
Fig. 1 is the preparation flow figure of open tubular column.
Fig. 2 is the stereoscan photograph of open pipe column section prepared in embodiment 1.
Fig. 3 is the chromatographic fractionation figure of four kinds of chiral drugs of open pipe post separation prepared in embodiment 1, wherein a) to organize an ammonia
Acid, b) for brufen, c) for atenolol, d) it is Sotalol.
Specific embodiment
The present invention is further elaborated and illustrated with reference to the accompanying drawings and detailed description.Each implementation in the present invention
The technical characteristic of mode can carry out the corresponding combination under the premise of not conflicting with each other.
The present invention provides a kind of preparation method of chiral linkage capillary electric chromatogram open tubular column, technological process such as Fig. 1 institutes
Show, the specific steps are：
(1) preparation of single -6- p-toluenesulfonyl beta-cyclodextrins：
5.0g beta-cyclodextrins (β-CD) are dissolved in the sodium hydroxide solution of 100mL concentration 30%, are added in cold bath
1.5~1.8g paratoluensulfonyl chlorides are stirred to react 4~6h, filtering, and it is 6~7 to adjust filtrate pH with 1mol/L HCl solutions, is had
White precipitate is precipitated, which is positioned in refrigerator (0~4 DEG C) overnight, filtering, precipitation is recrystallized 2 times with distilled water, second
Nitrile:Water (volume ratio 1:1) recrystallize 1 time, 50 DEG C vacuum drying, obtain list -6- p-toluenesulfonyls beta-cyclodextrin (6-OTs- β -
CD)。
(2) preparation of single -6- ethylenediamine base beta-cyclodextrins
It weighs 3.0g 6-OTs- β-CD, adds in 40~50mL ethylenediamines, stirring and dissolving is reacted 4~6h at 80 DEG C, added in
White precipitate, filtering is precipitated in acetone.Precipitation is dissolved in water, and acetone is precipitated, and filtering repeats the operation 1 time, then will be deposited in 50 DEG C
Vacuum drying, obtains list -6- ethylenediamine bases beta-cyclodextrin (EDA- β-CD).
(3) preparation of single -6- urea bond bridging beta-cyclodextrins
It weighs 2.0g EDA- β-CD and 0.5~0.9g methyl diphenylene diisocyanates and is dissolved in 20mL dimethyl sulfoxide (DMSO)s
(DMSO) in, under nitrogen protection, 4~6h of stirring at normal temperature adds in acetone and precipitation, filtering is precipitated, and 50 DEG C of vacuum drying obtain final
Product --- single -6- urea bond bridgings beta-cyclodextrin (UB- β-CD), structure is：
(4) preparation of chiral linkage capillary electric chromatogram open tubular column
It must be pre-processed before capillary column use, remove dust and harmful substance inside capillary column,
It activates the silicone hydroxyl of inner wall and it is made to carry specific groups.1mol/L HCl solutions, water and 1mol/L are used in the present invention respectively
NaOH solution rinses capillary column (50 μm of i.d., 365 μm of o.d., Length：60cm) 30min, 30min and 1h, then, two
End closure places 6h at 40 DEG C, then is rinsed with water to neutrality, after methanol rinses 20min, nitrogen drying.Three second of 3- aminopropyls
Oxysilane (KH550) is the bifunctional reagent for having siloxy and amino, can be with the silicone hydroxyl of capillary tube inner wall
It chemically reacts, makes capillary tube inner wall amination.It is 70 by volume ratio:(22~25):KH550, ethyl alcohol and the water of (5~8)
Mixture is injected in above-mentioned capillary column, sealing two ends, and 30~45 DEG C of reactions are for 24 hours.After the completion of reaction, again with methanol is rinsed, nitrogen
Air-blowing is done.Column wall bonding structure is：
UB- β-CD and 0.0030g azodiisobutyronitrile (AIBN) are added in the DMSO of certain volume, wherein UB- β-
The mass volume ratio (w/v) of CD and DMSO is 6~10%, which is filled in above-mentioned capillary column, two by ultrasonic mixing
End closure, 40~50 DEG C of 24~48h of water-bath, successively with methanol, ultrapure water.Obtain a kind of hand of structure determination
Property bonding capillary open tubular column, fix phase structure be：
After being prepared into above-mentioned capillary open tubular column, the present invention uses Fourier infrared spectrograph (pellet technique) and heat
The beta-cyclodextrin derivative that weight analysis instrument prepares step (1), (2), (3) characterizes.Using scanning electron microscope to step
Suddenly the capillary open tubular column surface topography and state that prepared by (4) are characterized.
The chiral resolution experiment of chiral linkage capillary electric chromatogram open tubular column is as follows：
Using chiral linkage capillary electric chromatogram open tubular column produced by the present invention (filling length 45cm), the phosphorus of 20mmol/L
Phthalate buffer, under different buffer solution pH, the mild separation voltage of splitter, to histidine, brufen, atenolol and rope
Tetra- kinds of chiral materials of Ta Luoer carry out chiral resolution application.
With reference to embodiment, the present invention will be further described, but is not limited only to this.
Embodiment 1
In the present embodiment, the preparation method of chiral linkage capillary electric chromatogram open tubular column is as follows：
(1) preparation of single -6- p-toluenesulfonyl beta-cyclodextrins：
5.0g β-CD are dissolved in the sodium hydroxide solution of 100mL concentration 30%, 1.6g is added in cold bath to toluene
Sulfonic acid chloride is stirred to react 5h, filtering, adjusts filtrate pH 6~7 with 1mol/L HCl solutions, has white precipitate precipitation, this is mixed
It closes object to be positioned in refrigerator (0~4 DEG C) overnight, filtering, precipitation is recrystallized 2 times with distilled water, acetonitrile:Water (volume ratio 1:1) weight
Crystallization 1 time, 50 DEG C of vacuum drying, obtains list -6- p-toluenesulfonyls beta-cyclodextrin (6-OTs- β-CD).
(2) preparation of single -6- ethylenediamine base beta-cyclodextrins
It weighs 3.0g 6-OTs- β-CD, adds in 45mL ethylenediamines, stirring and dissolving reacts 4h at 80 DEG C, adds in acetone analysis
Go out white precipitate, filter.Precipitation is dissolved in water, and acetone is precipitated, and filtering repeats the operation 1 time, precipitates 50 DEG C of vacuum drying, obtains
To list -6- ethylenediamine bases beta-cyclodextrin (EDA- β-CD).
(3) preparation of single -6- urea bond bridging beta-cyclodextrins
It weighs 2.0g EDA- β-CD and 0.6g methyl diphenylene diisocyanates to be dissolved in 20mL DMSO, nitrogen protection
Under, stirring at normal temperature 5h adds in acetone and precipitation, filtering is precipitated, and 50 DEG C of vacuum drying obtain final product --- single -6- urea bond bridgings
Beta-cyclodextrin (UB- β-CD), structure is：
(4) preparation of chiral linkage capillary electric chromatogram open tubular column
Respectively with 1mol/L HCl solutions, water and 1mol/L NaOH solutions rinse capillary column (50 μm of i.d., 365 μm
O.d., Length：Then 60cm) 30min, 30min and 1h, place 6h, then be rinsed with water to neutrality at 40 DEG C of sealing two ends,
After methanol rinses 20min, nitrogen drying.It is again 70 by volume ratio:25:5 KH550, ethyl alcohol and aqueous mixtures injection capillary
In column, sealing two ends, 40 DEG C of reactions are for 24 hours.Again with methanol is rinsed, nitrogen drying.Column wall bonding structure is：
UB- β-CD and 0.0030g AIBN are added in the DMSO of certain volume, wherein UB- β-CD quality is
0.03g, DMSO volume are 0.5mL, which is filled in above-mentioned capillary column, sealing two ends by ultrasonic mixing, 40 DEG C of water
Bath is reacted for 24 hours, successively with methanol, ultrapure water.A kind of chiral linkage capillary open tubular column of structure determination is obtained,
Fixing phase structure is：
(5) step (1), (2), (3) are made using Fourier infrared spectrograph (pellet technique) and thermogravimetric analyzer
The structure and thermal stability of standby beta-cyclodextrin derivative are characterized.Using scanning electron microscope prepared by step (4)
Capillary open tubular column surface topography and state characterized.Derive the result shows that being successfully prepared for various beta-cyclodextrins
Object, and purity is high, thermal stability is good.Capillary tube inner wall is close and has equably been bonded one layer of textured substance, and thickness is in 1~2 μ
Between m (as shown in Figure 2), stationary phase is bonded to by what chemical bond consolidated on capillary tube inner wall, and the stationary phase compared to coating has
There are better mechanical strength and stability.
(6) the chiral resolution ability test of chiral linkage capillary electric chromatogram open tubular column
Using chiral linkage capillary electric chromatogram open tubular column produced by the present invention (filling length 45cm), the phosphorus of 20mmol/L
Phthalate buffer carries out chiral resolution application to four kinds of histidine, brufen, atenolol and Sotalol chiral materials.From
It can be seen that four kinds of chiral material enantiomers reach baseline separation in Fig. 3, it was demonstrated that capillary open tubular column produced by the present invention
With very strong chiral resolution ability.The electrochromatography condition that four kinds of chiral material enantiomers reach baseline separation is：
Histidine：Buffer solution pH7.0 detaches 20 DEG C of column temperature, separation voltage 15kV
Brufen：Buffer solution pH7.0 detaches 22 DEG C of column temperature, separation voltage 10kV
Atenolol：Buffer solution pH7.5 detaches 22 DEG C of column temperature, separation voltage 20kV
Sotalol：Buffer solution pH5.5 detaches 22 DEG C of column temperature, separation voltage 10kV.
Embodiment 2
In the present embodiment, the preparation method of chiral linkage capillary electric chromatogram open tubular column is as follows：
(1) preparation of single -6- p-toluenesulfonyl beta-cyclodextrins：
5.0g β-CD are dissolved in the sodium hydroxide solution of 100mL concentration 30%, 1.6g is added in cold bath to toluene
Sulfonic acid chloride is stirred to react 6h, filtering, adjusts filtrate pH 6~7 with 1mol/L HCl solutions, has white precipitate precipitation, this is mixed
It closes object to be positioned in refrigerator (0-4 DEG C) overnight, filtering, precipitation is recrystallized 2 times with distilled water, acetonitrile:Water (volume ratio 1:1) it ties again
1 time brilliant, 50 DEG C of vacuum drying obtain list -6- p-toluenesulfonyls beta-cyclodextrin (6-OTs- β-CD).
(2) preparation of single -6- ethylenediamine base beta-cyclodextrins
It weighs 3.0g 6-OTs- β-CD, adds in 45mL ethylenediamines, stirring and dissolving reacts 4h at 80 DEG C, adds in acetone and be precipitated
White precipitate, filtering.Precipitation is dissolved in water, and acetone is precipitated, and filtering repeats the operation 1 time, precipitates 50 DEG C of vacuum drying, obtains
Single -6- ethylenediamine bases beta-cyclodextrin (EDA- β-CD).
(3) preparation of single -6- urea bond bridging beta-cyclodextrins
It weighs 2.0g EDA- β-CD and 0.75g methyl diphenylene diisocyanates to be dissolved in 20mL DMSO, nitrogen protection
Under, stirring at normal temperature 5h adds in acetone and precipitation, filtering is precipitated, and 50 DEG C of vacuum drying obtain final product --- single -6- urea bond bridgings
Beta-cyclodextrin (UB- β-CD), structure is：
(4) preparation of chiral linkage capillary electric chromatogram open tubular column
Respectively with 1mol/L HCl solutions, water and 1mol/L NaOH solutions rinse capillary column (50 μm of i.d., 365 μm
O.d., Length：Then 60cm) 30min, 30min and 1h, place 6h, then be rinsed with water to neutrality at 40 DEG C of sealing two ends,
After methanol rinses 20min, nitrogen drying.It is again 70 by volume ratio:22:8 KH550, ethyl alcohol and aqueous mixtures injection capillary
In column, sealing two ends, 45 DEG C of reactions are for 24 hours.Again with methanol is rinsed, nitrogen drying.Column wall bonding structure is：
UB- β-CD and 0.0030g AIBN are added in the DMSO of certain volume, wherein UB- β-CD quality is
0.04g, DMSO volume are 0.5mL, which is filled in above-mentioned capillary column, sealing two ends by ultrasonic mixing, 40 DEG C of water
Bath reaction 36h, successively with methanol, ultrapure water.A kind of chiral linkage capillary open tubular column of structure determination is obtained,
Fixing phase structure is：
(5) step (1), (2), (3) are made using Fourier infrared spectrograph (pellet technique) and thermogravimetric analyzer
The structure and thermal stability of standby beta-cyclodextrin derivative are characterized.Using scanning electron microscope prepared by step (4)
Capillary open tubular column surface topography and state characterized.The result shows that similar to Example 1, capillary tube inner wall is close
And one layer of textured substance equably it has been bonded.
(6) the chiral resolution ability test of chiral linkage capillary electric chromatogram open tubular column
Using chiral linkage capillary electric chromatogram open tubular column produced by the present invention (filling length 45cm), the phosphorus of 20mmol/L
Phthalate buffer carries out chiral resolution application to four kinds of histidine, brufen, atenolol and Sotalol chiral materials.Four
Kind of chiral material enantiomer has reached baseline separation, it was demonstrated that capillary open tubular column produced by the present invention has a very strong chirality
Fractionation ability.
Embodiment 3
In the present embodiment, the preparation method of chiral linkage capillary electric chromatogram open tubular column is as follows：
(1) preparation of single -6- p-toluenesulfonyl beta-cyclodextrins：
5.0g β-CD are dissolved in the sodium hydroxide solution of 100mL concentration 30%, 1.8g is added in cold bath to toluene
Sulfonic acid chloride is stirred to react 6h, filtering, adjusts filtrate pH 6-7 with 1mol/L HCl solutions, has white precipitate precipitation, this is mixed
Object is positioned in refrigerator (0~4 DEG C) overnight, and filtering, precipitation is recrystallized 2 times with distilled water, acetonitrile:Water (volume ratio 1:1) it ties again
1 time brilliant, 50 DEG C of vacuum drying obtain list -6- p-toluenesulfonyls beta-cyclodextrin (6-OTs- β-CD).
(2) preparation of single -6- ethylenediamine base beta-cyclodextrins
It weighs 3.0g 6-OTs- β-CD, adds in 50mL ethylenediamines, stirring and dissolving reacts 4h at 80 DEG C, adds in acetone and be precipitated
White precipitate, filtering.Precipitation is dissolved in water, and acetone is precipitated, and filtering repeats the operation 1 time, precipitates 50 DEG C of vacuum drying, obtains
Single -6- ethylenediamine bases beta-cyclodextrin (EDA- β-CD).
(3) preparation of single -6- urea bond bridging beta-cyclodextrins
It weighs 2.0g EDA- β-CD and 0.8g methyl diphenylene diisocyanates to be dissolved in 20mL DMSO, nitrogen protection
Under, stirring at normal temperature 6h adds in acetone and precipitation, filtering is precipitated, and 50 DEG C of vacuum drying obtain final product --- single -6- urea bond bridgings
Beta-cyclodextrin (UB- β-CD), structure is：
(4) preparation of chiral linkage capillary electric chromatogram open tubular column
Respectively with 1mol/L HCl solutions, water and 1mol/L NaOH solutions rinse capillary column (50 μm of i.d., 365 μm
O.d., Length：Then 60cm) 30min, 30min and 1h, place 6h, then be rinsed with water to neutrality at 40 DEG C of sealing two ends,
After methanol rinses 20min, nitrogen drying.It is again 70 by volume ratio:25:5 KH550, ethyl alcohol and aqueous mixtures injection capillary
In column, sealing two ends, 40 DEG C of reactions are for 24 hours.Again with methanol is rinsed, nitrogen drying.Column wall bonding structure is：
UB- β-CD and 0.0030g AIBN are added in the DMSO of certain volume, wherein UB- β-CD quality is
0.03g, DMSO volume are 0.5mL, which is filled in above-mentioned capillary column, sealing two ends by ultrasonic mixing, 50 DEG C of water
Bath is reacted for 24 hours, successively with methanol, ultrapure water.A kind of chiral linkage capillary open tubular column of structure determination is obtained,
Fixing phase structure is：
(5) step (1), (2), (3) are made using Fourier infrared spectrograph (pellet technique) and thermogravimetric analyzer
The structure and thermal stability of standby beta-cyclodextrin derivative are characterized.Using scanning electron microscope prepared by step (4)
Capillary open tubular column surface topography and state characterized.The result shows that similar to Example 1, capillary tube inner wall is close
And one layer of textured substance equably it has been bonded.
(6) the chiral resolution ability test of chiral linkage capillary electric chromatogram open tubular column
Using chiral linkage capillary electric chromatogram open tubular column produced by the present invention (filling length 45cm), the phosphorus of 20mmol/L
Phthalate buffer carries out chiral resolution application to four kinds of histidine, brufen, atenolol and Sotalol chiral materials.Four
Kind of chiral material enantiomer has reached baseline separation, it was demonstrated that capillary open tubular column produced by the present invention has a very strong chirality
Fractionation ability.
Embodiment described above is a kind of preferable scheme of the present invention, and so it is not intended to limiting the invention.Have
The those of ordinary skill of technical field is closed, without departing from the spirit and scope of the present invention, various changes can also be made
Change and modification.Therefore the technical solution that all modes for taking equivalent substitution or equivalent transformation are obtained all falls within the guarantor of the present invention
In the range of shield.
Claims (10)
1. a kind of preparation method of chiral linkage capillary electric chromatogram open tubular column, which is characterized in that step is as follows:
1) it is (0.25~0.45) by mass ratio：1 methyl diphenylene diisocyanate and single -6- ethylenediamine base beta-cyclodextrins are molten
In dimethyl sulfoxide (DMSO), then 4~6h of stirring at normal temperature under inert gas shielding adds in acetone and precipitation is precipitated, sediment is passed through
It filters, be dried to obtain list -6- urea bond bridging beta-cyclodextrins；
2) capillary column is rinsed with HCl solution, water and NaOH solution successively, then sealing two ends place certain time, then use water
It rinses to neutrality, continues nitrogen after being rinsed with methanol and dry up；
3) it is 70 by volume ratio:(22~25):3-aminopropyltriethoxysilane, ethyl alcohol and the aqueous mixtures of (5~8) inject
By in the 2) capillary column of processing, sealing two ends carry out reaction at 30~45 DEG C makes capillary tube inner wall amination, has reacted
Cheng Houyong methanol is rinsed and is dried；
4) it by single -6- urea bond bridging beta-cyclodextrins and azodiisobutyronitrile, is added in the dimethyl sulfoxide (DMSO) of certain volume, wherein
The mass volume ratio of single -6- urea bond bridging beta-cyclodextrins and dimethyl sulfoxide (DMSO) is 6~10%, is filled with after mixing by 3) processing
In capillary column, sealing two ends, 40~50 DEG C of 24~48h of water-bath successively with methanol, ultrapure water, obtain chiral key
Close capillary electric chromatogram open tubular column.
2. the preparation method of chiral linkage capillary electric chromatogram open tubular column as described in claim 1, which is characterized in that described
Singly the preparation method of -6- ethylenediamine base beta-cyclodextrins is：List -6- p-toluenesulfonyl beta-cyclodextrins are dissolved in ethylenediamine,
White precipitate is precipitated after adding in acetone after reaction, filters；To sediment after being dissolved in water add acetone be precipitated by way of into
Row purifies several times, and list -6- ethylenediamine base beta-cyclodextrins are obtained after purified product drying.
3. the preparation method of chiral linkage capillary electric chromatogram open tubular column as claimed in claim 2, which is characterized in that described
Singly the preparation method of -6- p-toluenesulfonyl beta-cyclodextrins is：Beta-cyclodextrin is dissolved in sodium hydroxide solution, then cold
Paratoluensulfonyl chloride is added under water bath condition, mixed liquor is stirred to react 4~6h, is filtered, filtrate pH=is adjusted with HCl solution
6~7, then mixed solution is statically placed under 0~4 DEG C of environment overnight, then filters to isolate sediment, weight is carried out to sediment
Crystallization obtains list -6- p-toluenesulfonyl beta-cyclodextrins after recrystallized product drying.
4. the preparation method of chiral linkage capillary electric chromatogram open tubular column as described in claim 1, which is characterized in that step 2)
In, the concentration of HCl solution and NaOH solution is 1mol/L, and the washing time of HCl solution, water and NaOH solution is respectively
30min, 30min and 1h, sealing two ends are 6h after standing time at 40 DEG C, and methanol washing time is 20min.
5. the preparation method of chiral linkage capillary electric chromatogram open tubular column as claimed in claim 2, which is characterized in that single -6-
Reaction temperature of the p-toluenesulfonyl beta-cyclodextrin in ethylenediamine is 80 DEG C, and the reaction time is 4~6h.
6. the preparation method of chiral linkage capillary electric chromatogram open tubular column as claimed in claim 3, which is characterized in that recrystallization
Method is：It is recrystallized 2 times with distilled water, volume ratio 1：1 acetonitrile：The mixed solution of water recrystallizes 1 time.
7. the preparation method of chiral linkage capillary electric chromatogram open tubular column as claimed in claim 3, which is characterized in that prepare
During single -6- p-toluenesulfonyl beta-cyclodextrins, in the mixed liquor, a concentration of the 30% of sodium hydroxide solution, per 100mL hydrogen
5.0g beta-cyclodextrins and 1.5~1.8g paratoluensulfonyl chlorides are dissolved in sodium hydroxide solution.
8. a kind of chiral linkage capillary electric chromatogram open tubular column prepared according to any the method for claim 1~7.
9. a kind of purposes of chiral linkage capillary electric chromatogram open tubular column as claimed in claim 8, which is characterized in that available for pair
Chiral material carries out chiral resolution.
10. purposes as claimed in claim 9, which is characterized in that the chiral material is histidine, brufen, Ah Ti Lip river
You and Sotalol.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110508135A (en) * | 2019-07-16 | 2019-11-29 | 沈阳化工大学 | A kind of capillary electric chromatogram method separating Pantoprazole raceme |
| CN111495341A (en) * | 2020-05-09 | 2020-08-07 | 中南民族大学 | Preparation and application of novel amphoteric chiral selector CEC monolithic column |
| CN111617516A (en) * | 2020-07-10 | 2020-09-04 | 安徽师范大学 | Silica gel integral open-tube capillary column with metal wire as template and preparation method thereof |
| CN115518415A (en) * | 2022-10-08 | 2022-12-27 | 沈阳化工大学 | Capillary electrochromatography method for separating pantoprazole racemate |
| CN116159543A (en) * | 2023-01-06 | 2023-05-26 | 齐齐哈尔大学 | Preparation method and application of capillary electrochromatography open tubular column based on chiral covalent organic framework material |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040102646A1 (en) * | 2000-11-02 | 2004-05-27 | Shin Watanabe | Method of resolving optical isomers of amino acid derivative |
| CN101298042A (en) * | 2008-01-17 | 2008-11-05 | 上海第二工业大学 | Spherical ordered mesoporous silicon oxide substrate chromatograph stationary phase and preparation |
| CN103601823A (en) * | 2013-11-29 | 2014-02-26 | 北京化工大学 | Preparation method for beta-cyclodextrin chiral stationary phase |
-
2017
- 2017-12-25 CN CN201711422563.XA patent/CN108181414B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040102646A1 (en) * | 2000-11-02 | 2004-05-27 | Shin Watanabe | Method of resolving optical isomers of amino acid derivative |
| CN101298042A (en) * | 2008-01-17 | 2008-11-05 | 上海第二工业大学 | Spherical ordered mesoporous silicon oxide substrate chromatograph stationary phase and preparation |
| CN103601823A (en) * | 2013-11-29 | 2014-02-26 | 北京化工大学 | Preparation method for beta-cyclodextrin chiral stationary phase |
Non-Patent Citations (2)
| Title |
|---|
| E. HONGJUN 等: "MICROWAVE-ASSISTED PREPARATION OF A b-CYCLODEXTRIN-BASED STATIONARY PHASE FOR OPEN TUBULAR CAPILLARY ELECTROCHROMATOGRAPHY", 《ANALYTICAL LETTERS》 * |
| YONGQIN LV 等: "Preparation of novel -cyclodextrin functionalized monolith and its application in chiral separation", 《JOURNAL OF CHROMATOGRAPHY B》 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110508135A (en) * | 2019-07-16 | 2019-11-29 | 沈阳化工大学 | A kind of capillary electric chromatogram method separating Pantoprazole raceme |
| CN110508135B (en) * | 2019-07-16 | 2021-12-21 | 沈阳化工大学 | Capillary electrochromatography method for separating pantoprazole racemate |
| CN111495341A (en) * | 2020-05-09 | 2020-08-07 | 中南民族大学 | Preparation and application of novel amphoteric chiral selector CEC monolithic column |
| CN111495341B (en) * | 2020-05-09 | 2023-02-07 | 中南民族大学 | Preparation and application of amphoteric chiral selector CEC monolithic column |
| CN111617516A (en) * | 2020-07-10 | 2020-09-04 | 安徽师范大学 | Silica gel integral open-tube capillary column with metal wire as template and preparation method thereof |
| CN115518415A (en) * | 2022-10-08 | 2022-12-27 | 沈阳化工大学 | Capillary electrochromatography method for separating pantoprazole racemate |
| CN116159543A (en) * | 2023-01-06 | 2023-05-26 | 齐齐哈尔大学 | Preparation method and application of capillary electrochromatography open tubular column based on chiral covalent organic framework material |
| CN116159543B (en) * | 2023-01-06 | 2024-08-06 | 齐齐哈尔大学 | Preparation method and application of capillary electrochromatography open tubular column based on chiral covalent organic framework material |
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