CN104860952B - A kind of extraction separation method of high-purity cucurbit(7)uril - Google Patents
A kind of extraction separation method of high-purity cucurbit(7)uril Download PDFInfo
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- CN104860952B CN104860952B CN201510182503.XA CN201510182503A CN104860952B CN 104860952 B CN104860952 B CN 104860952B CN 201510182503 A CN201510182503 A CN 201510182503A CN 104860952 B CN104860952 B CN 104860952B
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- ZDOBFUIMGBWEAB-XGFHMVPTSA-N cucurbit[7]uril Chemical compound N1([C@H]2[C@H]3N(C1=O)CN1[C@H]4[C@H]5N(C1=O)CN1[C@H]6[C@H]7N(C1=O)CN1[C@H]8[C@H]9N(C1=O)CN1[C@H]%10[C@H]%11N(C1=O)CN([C@@H]1N(C%12=O)CN%11C(=O)N%10CN9C(=O)N8CN7C(=O)N6CN5C(=O)N4CN3C(=O)N2C2)C3=O)CN4C(=O)N5[C@H]6[C@@H]4N2C(=O)N6CN%12[C@@H]1N3C5 ZDOBFUIMGBWEAB-XGFHMVPTSA-N 0.000 title claims abstract description 66
- 238000000926 separation method Methods 0.000 title claims abstract description 26
- 238000000605 extraction Methods 0.000 title claims abstract description 12
- FJJCIZWZNKZHII-UHFFFAOYSA-N [4,6-bis(cyanoamino)-1,3,5-triazin-2-yl]cyanamide Chemical group N#CNC1=NC(NC#N)=NC(NC#N)=N1 FJJCIZWZNKZHII-UHFFFAOYSA-N 0.000 claims abstract description 44
- 239000012535 impurity Substances 0.000 claims abstract description 8
- 238000004587 chromatography analysis Methods 0.000 claims abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 87
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 230000005526 G1 to G0 transition Effects 0.000 claims description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- 238000001556 precipitation Methods 0.000 claims description 18
- 239000007864 aqueous solution Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 13
- 239000000706 filtrate Substances 0.000 claims description 9
- 239000011521 glass Substances 0.000 claims description 9
- 238000005406 washing Methods 0.000 claims description 9
- 239000002244 precipitate Substances 0.000 claims description 8
- 239000000047 product Substances 0.000 claims description 8
- 238000004366 reverse phase liquid chromatography Methods 0.000 claims description 7
- 239000003643 water by type Substances 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 6
- 238000002390 rotary evaporation Methods 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- 239000000945 filler Substances 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 238000007654 immersion Methods 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 239000000499 gel Substances 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 229920000742 Cotton Polymers 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000012141 concentrate Substances 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 239000012488 sample solution Substances 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims 2
- 238000002386 leaching Methods 0.000 claims 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 4
- 239000003960 organic solvent Substances 0.000 abstract description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 230000008929 regeneration Effects 0.000 description 7
- 238000011069 regeneration method Methods 0.000 description 7
- 241000219112 Cucumis Species 0.000 description 6
- 235000015510 Cucumis melo subsp melo Nutrition 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000012264 purified product Substances 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 150000001793 charged compounds Chemical class 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000007445 Chromatographic isolation Methods 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000002262 irrigation Effects 0.000 description 2
- 238000003973 irrigation Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 235000000832 Ayote Nutrition 0.000 description 1
- 235000009854 Cucurbita moschata Nutrition 0.000 description 1
- 240000001980 Cucurbita pepo Species 0.000 description 1
- 235000009804 Cucurbita pepo subsp pepo Nutrition 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 235000015136 pumpkin Nutrition 0.000 description 1
- 238000009418 renovation Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
Abstract
A kind of extraction separation method of high-purity cucurbit(7)uril of the present invention, the extraction separation method of the cucurbit(7)uril belonged in oversubscription chemical field, the cucurbit(7)uril containing five, hexa-atomic melon ring and a small amount of other impurities that conventional separation methods obtain is isolated and purified using RP chromatography, cucurbit(7)uril purity is set to reach 99% or more than 99%, extraction separation method of the present invention is simple and quick, mobile phase is done without using organic solvent, environment friendly and pollution-free color, obtained cucurbit(7)uril product purity is high, yield is good, chromatographic column after processing can Reusability, cost is low.
Description
Technical field
The invention belongs to the chromatography separating method in chemical field.It is exactly specifically to be isolated and purified often with RP chromatography
Rule separation method obtain containing five, the cucurbit(7)uril of hexa-atomic melon ring and a small amount of other impurities, make cucurbit(7)uril purity reach 99% or
More than 99%.
Background technology
Melon cyclisation is a new branch of science in supramolecular chemistry field, is developed so far the time of only decades, but
Its excellent physicochemical properties make its supermolecular catalysis, Supramolecular Assembling, molecular recognition, ion channel, supermolecule biology,
The fields such as nano science, supermolecule materia medica show wide application prospect.Its application also penetrates into environmental science, life simultaneously
The hot fields of the 21 centurys such as life science, material science, energy science, medicine and pharmacology.
Melon ring（Q[n]）It is a kind of supermolecule main block chemical combination generated by glycosides urea, formaldehyde under acid catalysis through dehydrating condensation
Thing.From the point of view of melon ring structure（See Figure of description 1）, melon ring is with the cyclic compound similar to pumpkin profile, has two
The cavity of end opening, its two-port size is identical, and port diameter is less than cavity diameter.Melon ring two-port is dispersed with respectively to be tied with it
Structure unit number identical carbonylic oxygen atom, while nitrogen-atoms of four times equivalent to construction unit number is dispersed with melon ring wall.It surround
In port, the stronger oxygen atom of polarity forms good key binding site, so can be with hydrophilic material, metal ion etc.
Interaction；And its cavity be it is nonpolar, hydrophobic, not only can be with inclusion organic molecule, can also be according to the big of its cavity
Guest molecule small, that selective receiving size, shape match.So far, common melon ring（Q[n]）Mainly have five,
6th, seven, eight yuan of melon rings, its structural parameters are listed in the table below 1-1.
The common several melon rings of table 1-1（Q[n]）Structural parameters
Melon ring does not dissolve in organic solvent, is insoluble in water, is soluble in sulfuric acid, hydrochloric acid etc., and acidity is bigger, and the dissolubility of melon ring is got over
Greatly.In common several melon rings, except five yuan of melon rings（Q[5]）, cucurbit(7)uril（Q[7]）There is the solubility of moderate strength in water（2
~3×10-2 mol·L-1）Outside, the solubility of other melon ring memberses（<10-5mol·L-1）It is all bad.Secondly, melon ring and hat
Ether, cyclodextrin, cup cyclic hydrocarbon are compared to having stronger structural rigidity.Both melon ring can not change shape and make with unmatched guest molecule
With, therefore melon ring has strong and single-minded coordination, the Inclusion constant of gained inclusion compound also can be very high.Furthermore melon ring has height
Symmetry is spent, so its physical property and chemical property all quite stables, show very high heat endurance and dynamics is steady
It is qualitative.
As can be seen from the above analysis, the undoubtedly application value highest of cucurbit(7)uril in common melon ring.Because it is gathered around
There is good water solubility, suitable cavity size, have preferable molecule distinguishability to most organic guest molecule, therefore
It has very big potential using value in many fields such as environment separation, pharmaceutical carrier, nano material.But point of cucurbit(7)uril
From again be most difficult.Existing literature procedure has acid-moisture footwork, glycerine partition method, cation exchange resin processes, but
It is not very high, only 90%-93% or so with the isolated cucurbit(7)uril purity of these methods, sees Figure of description 2, accompanying drawing 4
Shown, being always mixed with micro hexa-atomic melon ring and five yuan of melon rings inside cucurbit(7)uril can not remove.Impure cucurbit(7)uril will be led
Causing the solubility of cucurbit(7)uril reduces（1×10-3Mol/L, heat endurance also reduce, and greatly constrain going deep into for cucurbit(7)uril
Research.If isolating and purifying cucurbit(7)uril repeatedly with these methods, the purity of melon ring can be made to reach more than 95%, but it is strong to work
Degree is very big, and organic reagent consumption is big and yield only has 10% or so.Therefore we have invented with MCI GEL CHP 20P（It is beautiful
Company of chromatogram section of state）Reverse-phase chromatography filler is stationary phase, and the side of cucurbit(7)uril is further purified for the reverse-phase chromatography of mobile phase for water
Method, the purity of cucurbit(7)uril can be made to reach more than 99% (see Figure of description 3, accompanying drawing 5), yield 52% or so, eliminate five
First, hexa-atomic melon ring and other a small amount of impurity.It is Green Chemistry it is important that this method is very environmentally friendly, not using any has
Machine reagent, isolated impure cucurbit(7)uril part can go up post separation again after processing, recycle.
The content of the invention
It is an object of the invention to obtain a kind of very high purity up to more than 99% cucurbit(7)uril, specific separation method is such as
Under：
A kind of extraction separation method of high-purity cucurbit(7)uril of the present invention, is to be filled out with MCI GEL CHP20P reverse-phase chromatographies
Expect to isolate and purify what conventional separation methods obtained for stationary phase, water for the RP chromatography of mobile phase, containing five, hexa-atomic melon ring and less
The cucurbit(7)uril of other impurities is measured, cucurbit(7)uril purity is reached 99% or more than 99%.
A kind of extraction separation method of high-purity cucurbit(7)uril of the present invention, its extraction separation method follow these steps to carry out：
（1）Preparation of samples：The cucurbit(7)uril containing five, hexa-atomic melon ring and a small amount of other impurities that conventional separation methods are obtained
500 mg are dissolved in 30mL water, and 10min is stirred at 40 DEG C, filtering, and filtrate is standby；
（2）The preparation of chromatographic column：100g model MCI GEL CHP20P reverse-phase chromatography fillers（Chromatogram section of the U.S. is public
Department）Methanol is poured out after adding 200 mL methanol immersion 15min, 200mL redistilled waters immersion 15min is added, pours out water
After solution plus appropriate redistilled water makes stationary phase be in pulpous state, and stationary phase is poured into a diameter of 3cm, the highly glass for 50cm
In post, 1000mL redistilled waters are standby after rinsing；
（3）The above-mentioned ready 30 mL cucurbit(7)urils aqueous solution is slowly added into dropper along the tube wall of glass column
To the top of chromatographic column, while the valve for opening pillar lower end flows out solution, keeps flow velocity to treat sample solution at 1 drop/sec
After being totally immersed into stationary phase, closure piston, fill in appropriate cotton in the top of stationary phase and be pressed into some small glass blocks with
Exempting to destroy the aspect of stationary phase with mobile phase when being rinsed influences separating effect, is rushed by the use of redistilled water as mobile phase
Wash, keep flow velocity at 1 drop/sec, be that a cut is collected per 10mL, about collect 80 cuts.Silica gel thin-layer plate point
Plate follows the trail of cucurbit(7)uril, and iodine is developer；
（4）Combining step（3）In point plate be shown as the cut of pure cucurbit(7)uril, 65 DEG C of concentrated by rotary evaporations to volume are 20
ML, it is cooled to room temperature；
（5）Precipitation：200 mL methanol are added into step（4）Concentrate in white precipitate, filter, precipitation is with 20 mL
Methanol, it is placed in after the washing of 20 mL acetone in vacuum desiccator；
（6）Drying：By step（5）The dry 12h of 70 DEG C of product, produce cucurbit(7)uril sterling.
Above-mentioned amount of samples changes, and remaining reagent, chromatographic column fixed phase dosage also change in proportion therewith.
The method that above-mentioned impure cucurbit(7)uril cut recycles is：Combining step（3）Midpoint board is shown as impure seven yuan
The cut of melon ring, 65 DEG C of concentrated by rotary evaporations to volume are 20 mL, are cooled to after room temperature and add 200 mL methanol and obtain white precipitate,
Filter, 20 mL methanol of precipitation, be placed in after the washing of 20mL acetone in vacuum desiccator, 70 DEG C of dry 12h produce impure
Cucurbit(7)uril product, the inside mainly contain five, hexa-atomic melon ring.4 grams of the sample is weighed, adds 500mL redistilled waters stirring 30
Precipitation is filtered to remove after min, filtrate is 20mL in 65 DEG C of concentrated by rotary evaporations to volume, and 200mL methanol is added after being cooled to room temperature
White precipitate is obtained, is filtered, precipitation uses 20mL methanol, and 20mL acetone is placed in vacuum desiccator after washing respectively, 70 DEG C of dryings
12h produces cucurbit(7)uril first time purified product, then weighs through 2 grams of sample once after purification, adds 15mL 2.5mol/L
HCl, filtering, filtrate have precipitation and produced after standing overnight, be filtered to remove precipitation, and adding 150mL methanol in filtrate produces white
Precipitation, filter, precipitation uses 20mL methanol, and 20mL acetone is placed in vacuum desiccator after washing respectively, and 70 DEG C of dry 12h were both obtained
The secondarily purified product of cucurbit(7)uril, for purity about 90% or so, the product can be as the raw material of chromatographic isolation, through chromatogram point
From obtaining higher purity after purification（99%）Cucurbit(7)uril.
The renovation process of above-mentioned chromatographic column is：With 1mL/min flow velocity, volume ratio is 20% acetic acid aqueous solution 600mL
Rinse chromatographic column after, then with redistilled water 2000mL rinse can make chromatogram column regeneration, carry out separation next time.Work as color
Compose when using more than 6 times of post, it is necessary to thoroughly cleaned, regenerated, ensure the recovery in chromatograph stationary-phase stuffing aperture, specifically
Method is as follows：Fixed irrigation flow rate is 1mL/min, successively with the acetic acid aqueous solution 600mL of volume ratio 20%, redistilled water
2000mL, the methanol aqueous solution 400mL of volume ratio 20%, the methanol aqueous solution 400mL of volume ratio 50%, volume ratio 80%
Methanol aqueous solution 400mL, pure methanol 400mL, methanol aqueous solution 400mL, the 1000mL redistilled water of volume ratio 50% rinse
After chromatographic column, you can make chromatogram column regeneration.
Effect：Separation method is quick, and mobile phase, environment-friendly and green, obtained cucurbit(7)uril product are done without using organic solvent
Purity is high（99%）, yield is good（52%）.The recyclable processing Posterior circle of isolated impure cucurbit(7)uril uses, same ground colour
Post also renewable recycling after processing is composed, has saved cost.
Brief description of the drawings
Fig. 1：The structure of melon ring.Wherein left figure represents the structure of melon ring, and a in right figure in melon ring structure represents the outer of melon ring
Footpath, b represent the internal diameter of melon annular space chamber, and c represents melon central port diameter, and d represents the height of melon ring.
Fig. 2：Impure cucurbit(7)uril（Q[7]）Nucleus magnetic hydrogen spectrum figure.Cucurbit(7)uril in figure1H H NMR spectroscopies show that three groups are total to
Shake peak, i.e., on its cellular construction methylene on Ha, Hc two groups of doublets and methine one group of Hb it is unimodal, in δ=5.5
Moving nearby has small peak, shows to be mixed with five yuan or hexa-atomic melon ring in cucurbit(7)uril, and baseline is not straight enough.From its area integral
Ratio can obtain the purity obtained after cucurbit(7)uril is handled with conventional method about 90% or so.
Fig. 3：High-purity cucurbit(7)uril（Q[7]）Nucleus magnetic hydrogen spectrum figure.Cucurbit(7)uril in figure1H H NMR spectroscopies show three groups
Formant, i.e., on its cellular construction methylene on Ha, Hc two groups of doublets and methine one group of Hb it is unimodal, without other miscellaneous
Mass peak, baseline straightening, show that its purity of the cucurbit(7)uril of separation can reach more than 99%.
Fig. 4：Impure cucurbit(7)uril（Q[7]）Mass spectrogram.The molecular ion peak of cucurbit(7)uril：1185.4（Q[7]+Na+）,
Five yuan of melon rings 853.4（Q[5]+Na+）With hexa-atomic melon ring 1019.5（（Q[6]+Na+）Molecular ion peak.
Fig. 5：High-purity cucurbit(7)uril（Q[7]）Mass spectrogram.The molecular ion peak of cucurbit(7)uril：1805（Q[7]+Na+）.
Embodiment：
The extraction separation of the high-purity cucurbit(7)uril of embodiment 1.
（1）Preparation of samples：The cucurbit(7)uril containing five, hexa-atomic melon ring and a small amount of other impurities that conventional separation methods are obtained
500mg is dissolved in 30mL water, and 10min is stirred at 40 DEG C, filtering, and filtrate is standby；
（2）The preparation of chromatographic column：100g model MCIGEL CHP20P reverse-phase chromatography fillers（Chromatogram section of the U.S. is public
Department）Methanol is poured out after adding 200 mL methanol immersion 15min, 200mL redistilled waters immersion 15min is added, pours out water
After solution plus appropriate redistilled water makes stationary phase be in pulpous state, and stationary phase is poured into a diameter of 3cm, the highly glass for 50cm
In post, 1000mL redistilled waters are standby after rinsing；
（3）The above-mentioned ready 30 mL cucurbit(7)urils aqueous solution is slowly added into dropper along the tube wall of glass column
To the top of chromatographic column, while the valve for opening pillar lower end flows out solution, keeps flow velocity to treat sample solution at 1 drop/sec
After being totally immersed into stationary phase, closure piston.Fill in appropriate cotton in the top of stationary phase and be pressed into some glass blocks in order to avoid
The aspect of stationary phase is destroyed when being rinsed with mobile phase influences separating effect.It is rinsed by the use of redistilled water as mobile phase,
Flow velocity is kept at 1 drop/sec, is that a cut is collected per 10mL, about collects 80 cuts.Silica gel thin-layer plate point plate chases after
Track cucurbit(7)uril, iodine are developer；
（4）Show that the cut of pure cucurbit(7)uril is the 8th to the 20th cut according to a plate, merge the 8th to the 20th cut and amount to
130mL solution, 65 DEG C of concentrated by rotary evaporations to volume are 20 mL, are cooled to room temperature；
（5）Precipitation：200 mL methanol are added into step（4）Concentrate in white precipitate, filter, precipitation is with 20 mL
Methanol, it is placed in after the washing of 20 mL acetone in vacuum desiccator；
（6）Drying：By step（5）The dry 12h of 70 DEG C of product after obtain cucurbit(7)uril sterling 260mg, yield 52%,
Through1H NMR and mass spectroscopy, purity 99%, see Figure of description 3 and 5.
The recycling of 2 impure cucurbit(7)uril of embodiment.
Repeatedly merge burble point plate in embodiment 1 and be detected as the cut of impure cucurbit(7)uril and amount to 2000mL, 65 DEG C of revolvings
It is 50 mL to be concentrated into volume, is cooled to after room temperature and adds 400 mL methanol and obtain white precipitate, filters, 20 mL first of precipitation
Alcohol, it is placed in after the washing of 20mL acetone in vacuum desiccator, 70 DEG C of dry 12h produce impure cucurbit(7)uril product, the inside master
To contain five, hexa-atomic melon ring.Sample 4g is weighed, adds after 500mL redistilled waters stir 30 min and is filtered to remove precipitation,
Filtrate is 20mL in 65 DEG C of concentrated by rotary evaporations to volume, and addition 200mL methanol obtains white precipitate after being cooled to room temperature, filters, sinks
20mL methanol is used in shallow lake, and 20mL acetone is placed in vacuum desiccator after washing respectively, and 70 DEG C of dry 12h produce cucurbit(7)uril first
Secondary purified product.Sample 2g once after purification is weighed again, adds 15mL 2.5mol/L HCl, filtering, after filtrate stands overnight
Have precipitation to produce, be filtered to remove precipitation, adding 150mL methanol in filtrate produces white precipitate, filters, precipitation uses 20mL first
Alcohol, 20mL acetone are placed in vacuum desiccator after washing respectively, and 70 DEG C of dry 12h both obtain the secondarily purified product of cucurbit(7)uril, pure
For degree about 90% or so, the product can obtain higher purity as the raw material of chromatographic isolation after chromatographic separation and purification
（99%）Cucurbit(7)uril.
The regeneration of the chromatographic column of embodiment 3
The regeneration of chromatographic column：With 1mL/min flow velocity, the acetic acid aqueous solution 600mL that volume ratio is 20% rinses chromatographic column
Afterwards, chromatogram column regeneration can be made by then being rinsed with redistilled water 2000mL, separation next time be carried out, when the use of chromatographic column
During more than 6 times, it is necessary to thoroughly cleaned, regeneration, the recovery in guarantee chromatograph stationary-phase stuffing aperture, specific method is as follows：
Fixed irrigation flow rate is 1mL/min, successively with the acetic acid aqueous solution 600mL of volume ratio 20%, redistilled water 2000mL, volume
Methanol aqueous solution 400mL than 20%, the methanol aqueous solution 400mL of volume ratio 50%, the methanol aqueous solution of volume ratio 80%
400mL, pure methanol 400mL, after methanol aqueous solution 400mL, the 1000mL redistilled water of volume ratio 50% rinses chromatographic column,
Chromatogram column regeneration can be made.
Claims (2)
1. a kind of extraction separation method of high-purity cucurbit(7)uril, it is characterised in that with MCI GEL CHP20P reverse-phase chromatography fillers
For stationary phase, water for the RP chromatography of mobile phase isolate and purify that conventional separation methods obtain containing five, hexa-atomic melon ring and a small amount of
The cucurbit(7)uril of other impurities, cucurbit(7)uril purity is set to reach 99% or more than 99%.
A kind of 2. extraction separation method of high-purity cucurbit(7)uril according to claim 1, it is characterized in that extraction separation side
Method follows these steps to carry out：
（1）Preparation of samples：The cucurbit(7)uril 500 containing five, hexa-atomic melon ring and a small amount of other impurities that conventional separation methods are obtained
Mg is dissolved in 30mL water, and 10min is stirred at 40 DEG C, filtering, and filtrate is standby；
（2）The preparation of chromatographic column：100g model MCIGEL CHP20P reverse-phase chromatography fillers, add the leaching of 200 mL methanol
Methanol is poured out after bubble 15min, 200mL redistilled waters immersion 15min is added, adds appropriate second distillation after pouring out the aqueous solution
Water makes stationary phase be in pulpous state, and stationary phase is poured into a diameter of 3cm, highly in 50cm glass column, 1000mL second distillations
Water is standby after rinsing；
（3）The above-mentioned ready 30 mL cucurbit(7)urils aqueous solution is slowly added into color with dropper along the tube wall of glass column
The top of post is composed, while the valve for opening pillar lower end flows out solution, keeps flow velocity at 1 drop/sec, treats sample solution whole
After being immersed in stationary phase, closure piston；Fill in appropriate cotton in the top of stationary phase and be pressed into some glass blocks so as not to
The aspect of stationary phase is destroyed when mobile phase is rinsed influences separating effect；It is rinsed, keeps by the use of redistilled water as mobile phase
Flow velocity is that a cut is collected at 1 drop/sec, per 10mL, about collects 80 cuts；Silica gel thin-layer plate point plate tracking seven
First melon ring, iodine are developer；
（4）Combining step（3）Midpoint board is shown as the cut of pure cucurbit(7)uril, and 65 DEG C of concentrated by rotary evaporations to volume are 20 mL, cold
But to room temperature；
（5）Precipitation：200 mL methanol are added into step（4）Concentrate in white precipitate, filter, precipitation is with 20 mL first
Alcohol, it is placed in after the washing of 20 mL acetone in vacuum desiccator；
（6）Drying：By step（5）The dry 12h of 70 DEG C of product produce the sterling of cucurbit(7)uril；
Above-mentioned amount of samples changes, and remaining reagent, chromatographic column fixed phase dosage also change in proportion therewith.
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| GB0922623D0 (en) * | 2009-12-23 | 2010-02-10 | Cambridge Entpr Ltd | Methods for the purification of cucurbituril |
| JP2012246240A (en) * | 2011-05-26 | 2012-12-13 | Sumitomo Bakelite Co Ltd | Method for producing bi-functionalized cucurbit[7]uril |
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Application publication date: 20150826 Assignee: Tianjin Xiehe Bojing Medical Diagnostic Technology Co.,Ltd. Assignor: Beijing Legend Yousheng Culture Media Co.,Ltd. Contract record no.: X2024980004128 Denomination of invention: A method for extracting and separating high-purity seven element melon rings Granted publication date: 20171114 License type: Common License Record date: 20240409 |