CN1472003A - Aromatic hydrocarbon linked silica gel solid phase and its preparation and use - Google Patents
Aromatic hydrocarbon linked silica gel solid phase and its preparation and use Download PDFInfo
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- CN1472003A CN1472003A CNA031281974A CN03128197A CN1472003A CN 1472003 A CN1472003 A CN 1472003A CN A031281974 A CNA031281974 A CN A031281974A CN 03128197 A CN03128197 A CN 03128197A CN 1472003 A CN1472003 A CN 1472003A
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- calixarenes
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Abstract
A stationary phase of calicanee bonded silica gel for the liquid or electric chromatography is disclosed, which is prepared through solid-phase condensation reaction between calicanee sodium phenolate and halopropyl bonded silica gel in nitrogen or argon gas at 110-120 deg.c under existance of quaternary ammonium salt as phase-transfer catalyst. Its advantage is high stability.
Description
Technical field
The present invention relates to fixedly phase and its production and use of a kind of calixarenes bonded silica gel.
Background technology
Chromatography has critical role in modern compartment analysis, be widely used in chemistry, biology, medicine and pharmacology, life science and environmental science, becomes requisite research means.Separation system becomes increasingly complex, particularly the compartment analysis of actual sample is had higher requirement mutually to chromatographic technique especially chromatographic stationary, commercial at present silica gel and modified silica-gel kind are very abundant, but are the fixing requirement that can not satisfy compartment analysis mutually of reverse-phase chromatography of representative with octadecyl silane (ODS).Therefore, the development of the chromatographic stationary phase of high selectivity and exploitation are one of core contents of chromatographic field research." the exclusive type " of high selectivity is fixing mutually of a great variety, mainly contains: for satisfying the chiral stationary phase that drug enantiomer separates needs; Adapt to biochemical protein bonded stationary phase of separating; Based on the fixing phase of crown ether, cyclodextrin, calixarenes of supermolecule effect and the molecular imprinting stationary phase of obligatory type.
Protein is the big molecule of natural chirality, has the height stereoselectivity with the interaction of part, enzyme etc.Protein bonded stationary phase has unique advantage: most enantiomers do not need derivatization just can directly split; Also comparatively desirable to fractionation with physiological activator.But protein bonded stationary phase bonded amount is little at present, cost is high, service life is shorter.Crown ether is the manually synthetic big acyclic polyether compound with certain ring cavity of a class.The separation of crown ether bonded stationary phase mainly optionally forms host-guest inclusion complex with cation or polar compound based on crown ether, and the stability of Different Complex there are differences, thereby reaches Selective Separation.Because the synthetic difficulty of the crown ether of crown ether, especially derivatization, thus this class fixedly the phase progress is slow.Cyclodextrin bonded fixing is the novel fixedly phase that closely grows up during the last ten years mutually, also is the maximum important chiral stationary phase of a class of research.Twentieth century is since the nineties, and derivatized cyclodextrin bonded stationary phase has obtained developing rapidly and much commercializations are arranged.Cyclodextrin is carried out chemical modification, introduce various groups, improve separation selectivity, enantiomer is carried out the focus that chiral resolution is still research.But cyclodextrin ring cavity volume size is single, and related object object mainly is limited to neutral molecule.Molecularly imprinted polymer fixedly phase (MIPs) is the inspiration that is subjected to the antibody of enzyme to have the characteristics of shape selective, grow up based on the host-guest effect, and be mainly used in the fixedly phase of chiral resolution.MIPs has " memory " function to the stereochemical structure of microsphere, and predetermined host-guest molecule is had high selectivity, and this is that traditional chiral column is not available.To prepare difficulty mutually big and this class is fixing, and separate object is single, " memory " function poor reproducibility, thereby use limited.
Calixarenes is the macrocyclic compound that a class is formed by connecting by methylene by phenol units.Can form inclusion compound with neutral molecule and ion, be described as the third generation supramolecular chemistry host molecule after crown ether and cyclodextrin.Be subjected to paying close attention to widely in fields such as ISE, catalysis, L B film separation, enzyme simulations.At chromatographic field, reported first such as Mangia are adsorbed on right-tert-butyl group cup [8] aromatic hydrocarbons successfully separates alcohols, chlorohydrocarbon, and aromatic compound on the red diatomite.Since the nineties, the application of calixarenes in chromatogram constantly makes progress.1993, Park etc. are used for high performance liquid chromatography to calixarenes first, sulfonation cup [6] added to flow mutually,, successfully separated metoxyphenol, amino-phenol and nitrophenol position isomer based on the stability difference of solute with calixarenes formation host-guest inclusion compound.1994, beginnings such as Shohat adopted calixarenes to make the position isomer that additive separates chlorophenol, benzenediol, methylaniline in HPCE.Cheng Jieke etc. are additive with sulfonation cup [4] aromatic hydrocarbons, have separated nitrophenol, amino-phenol and benzenediol isomers, and post is imitated up to 3 * 10
5Plate/rice.Report shows that calixarenes has remarkable advantages at aspects such as separating PAHs, benzene two the position of substitution isomers, amino-acid ester, dipeptides, base, nucleosides and Acidity of Aikalinity medicine, has showed the application potential of calixarenes in separation science.Yet, the calixarenes poor solubility, when making additive, strong UV absorption Interference Detection makes it to use limited in addition, and the research of calixarenes bonded stationary phase becomes the main flow of development thereupon.
The preparation method of the calixarenes bonded stationary phase of being reported has following several: the addition of silicon hydrogen, the addition of mercapto hydrogen and condensation reaction.This several method all is to make the calixarenes silylating reagent by derivative reaction earlier, prepares bonded stationary phase by the silica gel Silanization reaction then.Course of reaction is long, and is consuming time, various organic intermediates, calixarenes silylating reagent purification process complexity.Glennon etc. have prepared esterification cup [4] arenes selectivity ground by the addition of silicon hydrogen and have separated alkali metal ion, find that cup [4] aromatic hydrocarbons is to Na
+Have very high selectivity, its reservation is far longer than other ion.Subsequently, they adopt the addition of mercapto hydrogen to prepare esterification cup [6] aromatic hydrocarbons again.We successively use N-(β-aminoethyl)-γ-aminopropyl MTES (WD-53) and γ-[(2 respectively in the laboratory, 3)-and epoxy third oxygen] the third oxygen trimethoxy silane (KH560) synthesized right-tert-butyl group cup [4] [6] [8] aromatic hydrocarbons bonded stationary phase as coupling agent, and studied them in the application that separates aspects such as PAHs, position isomer, nucleosides, base, sulfanilamide (SN) and quinolone medicine.In addition, Krauss and Thomass etc. have systematically studied the application of cup [4] [6] [8] aromatic hydrocarbons in HPLC respectively.Its fixing patented method that all adopts mutually is synthetic, and concrete synthetic route and technology are not provided.
Summary of the invention
The present invention provides fixedly phase and its production and use of a kind of calixarenes bonded silica gel over against the problems referred to above exactly, and gained is the phase stability height fixedly, be applicable to high performance liquid chromatography, micro column liquid chromatography and capillary electric chromatogram, and method for making is simpler.
Technical scheme provided by the invention is: a kind of calixarenes bonded silica gel is phase fixedly, and its structural formula is
N=4 in the formula～8; Bu
tBe the tert-butyl group.
The present invention also provides the fixedly preparation method of phase of above-mentioned calixarenes bonded silica gel, in the presence of the phase transfer catalyst quaternary ammonium salt, with calixarenes sodium phenolate and halopropyl bonded silica gel in nitrogen or argon gas in 110～120 ℃ through solid phase condensation reaction, make the silica gel bonded fixedly phase of required calixarenes.
Above-mentioned calixarenes sodium phenolate is a reactant with sodium hydride and calixarenes, is solvent with the dry toluene, makes under 40～100 ℃ of conditions.
Above-mentioned calixarenes comprises calixarenes parent and derivative thereof.
Fixing high performance liquid chromatography, micro column liquid chromatography or the capillary electric chromatogram separating filler of can be used as mutually of calixarenes bonded silica gel of the present invention.
The present invention adopts the solid phase surface successive reaction to prepare calixarenes bonded stationary phase.Halopropyl bonded silica gel (according to the prior art preparation) is a kind of low pole, weak hydrophobic fixedly phase, can also be as the further synthetic bonded stationary phase that contains various functional groups of intermediate.The present invention prepares calixarenes bonded stationary phase with halopropyl silica gel and calixarenes sodium phenolate by solid phase condensation reaction; The calixarenes bonded stationary phase stability that connects by ehter bond is high, on fixing phase molecule structural design, adopt three hydrophobic short chains of methylene to connect and to play three-dimensional shielding action to the silica gel surface silanol group, reduce the silanol effect of bonded silica gel, improve the chromatographic peak symmetry.Gained is fixing to be applicable to high performance liquid chromatography, micro column liquid chromatography and capillary electric chromatogram mutually, and method for making is simpler.
The specific embodiment
Calixarenes bonded silica gel of the present invention is fixing can be obtained by the described course of reaction of following formula mutually:
X=Cl, Br, I n=4～8 one, preparation activated silica gel
Take by weighing a certain amount of silica gel in a round-bottomed flask, add 3mol/L hydrochloric acid, silica gel weight (g) and hydrochloric acid volume (mL) are than being 1: 10～1: 15.Refluxed 24 hours, filter with G-4 molding sand core funnel while hot, solid repeatedly with secondary water washing to neutral, and with acetone washing three times, disperse prior to drying by the fire under the infrared lamp to silica gel, again in baking oven 160 ℃ the baking more than 10 hours, taking-up places drier to be chilled to room temperature, it is gone in the drying pistol water-bath heating rapidly, vacuum drying at least 16 hours is faced and is used preceding taking-up.Two, the preparation of halopropyl bonded silica gel
In the 250ml three-neck flask, add the new dry toluene (dry toluene with sodium metal reflux the preparation that dewaters) that steams, add activated silica gel fast, pipette a certain amount of coupling agent (halopropyl three second (first) TMOS) with pipette again.Under drying nitrogen (nitrogen is in advance through the concentrated sulfuric acid and the calcium chloride drying) protection, magnetic agitation (at a slow speed).Silica gel quality (g): coupling agent (mmoL): dry toluene (mL) is generally: 10: 50: 500, drip 3 new triethylamines that steam, oil bath is warming up to 110～120 ℃ rapidly, reaction 24 hours (the condenser pipe upper end adds the drying tube of anhydrous calcium chloride) under reflux state, use G-4 sand core funnel suction filtration while hot, solid with toluene, acetone, methyl alcohol, water, acetone washing, gets the halopropyl bonded silica gel successively, vacuum drying (100 ℃) 8 hours is stored in the drier standby.Three, the preparation of calixarenes sodium phenolate
Take by weighing a certain amount of pre-dry calixarenes in the 250ml three-neck flask, add a certain amount of new steaming dry toluene, load onto nitrogen ingress pipe and calcium chloride tube, feed nitrogen, begin to stir (at a slow speed), add sodium hydride powder (perishable in the air) rapidly, oil bath, constant temperature add thermal agitation 2h to 50-60 ℃, get calixarenes sodium phenolate suspension, pipette, extract upper strata liquid is used for subsequent reactions.Four, the fixedly preparation of phase of calixarenes bonded silica gel
Add phase transfer catalyst and halopropyl bonded silica gel in the calixarenes sodium phenolate rapidly, quicken to stir, and be warming up to 110～120 ℃, reaction is 48 hours under the reflux state.Stop reaction, filter with the G-4 sand core funnel while hot, and with the toluene wash of heat 2～3 times, use acetone, methyl alcohol, redistilled water, acetone washed twice more successively, infrared lamp is dried down, fixedly the phase crude product.Five, flotation
Get a 50mL beaker, add 30mL and analyze pure methyl alcohol, add fixedly phase crude product again, ultrasonic wave was handled 5 minutes, left standstill the tipping supernatant liquor about 2 hours, add same amount methyl alcohol and ultrasonic again,, check flotation effect upper strata liquid microexamination, adjust flotation number of times and methanol usage, general flotation 3～4 times is filtered, wash with acetone, oven dry (100 ℃) gets the fixing mutually pure product of calixarenes bonded silica gel, and vacuum gun placed drier standby in dry 8 hours.Six, raw material rate of charge
Activated silica gel (g): coupling agent (mmol): calixarenes (mmol): sodium hydride (mmol): phase transfer catalyst (mmol) cup [8] aromatic hydrocarbons is generally: 1: 5: 0.2: 1.0: 0.4 glasss of [6] aromatic hydrocarbons were generally: 1: 5: 0.3: 1.2: 0.4 glasss of [4] aromatic hydrocarbons are generally: 1: 5: 0.4: solvent was pressed in 1.4: 0.4: silica gel (g): solvent (mL) is: 1: 50
According to the structure of calixarenes, above-mentioned amount ratio can be done suitable adjustment.
Embodiment: adopting chloropropyl triethoxysilane is that coupling agent and TBAB are phase transfer catalyst, and right-tert-butyl group cup [8] aromatic hydrocarbons is raw material, and Kromasil 5 μ m spherical silica gels are matrix, the silica gel bonded fixedly phase of preparation calixarenes.Prepare right-tert-butyl group cup [8] aromatic hydrocarbons bonded stationary phase by one to four step.Analyze and elemental analysis through infrared spectrum, heat, this fixedly is combined to success.
With chloropropyl silica gel and KBr compressing tablet is reference, and computer carries out background rejection, FTIR spectrum that must right-tert-butyl group cup [8] aromatic hydrocarbons bonded stationary phase.Spectrum shows: ν 2961.5cm
-1ν 2929.7cm
-1ν 2847.0cm
-1The stretching vibration absworption peak of saturated C-H; ν 1599.1cm
-1ν 1577.7cm
-1ν 1487.6cm
-1Phenyl ring skeletal vibration absworption peak; ν 1477.9cm
-1ν 1384.3cm
-1CH
2, CH
3The flexural vibrations peak; ν 809.9cm
-1To the dibasic characteristic absorption peak of benzene.The characteristic absorption band basically identical of result and right-tert-butyl group cup [8] aromatic hydrocarbons.Heat analysis shows: fixing weightlessness 11.32% mutually conforms to substantially with the bonding reaction weightening finish.Results of elemental analyses sees the following form:
Table 1. pair-tert-butyl group cup [8] aromatic hydrocarbons bonding phase bonding concentration bonding phase C (%) H (%) bonding concentration (mmolg
-1) CBS 8.98 2.12 0.06CPS 3.21 0.38 0.10 are attached: fixing phase surface calixarenes concentration: α=W/M (μ molg
-1)
W is fixing phase surface calixarenes weight (g), and M is the calixarenes molal weight, and α is fixing phase surface calixarenes concentration (μ molg
-1).α is 60～200 μ molg
-1(relevant) with the calixarenes structure.
The present invention prepares halopropyl bonded silica gel amboceptor earlier, intermediate after filtration, the washing, remove excessive reactant and accessory substance; Reduce complicated operations such as organic intermediate separation and purification.Again halopropyl silica gel and calixarenes sodium phenolate are prepared calixarenes bonded stationary phase by solid phase condensation reaction.The calixarenes phenolic hydroxyl group is transformed into sodium salt under the NaH effect, get upper strata liquid and remove excessive N aH and NaOH accessory substance, prevents the erosion of highly basic to silica matrix, and the permeability of post obviously improves; The adding of phase transfer catalyst improves reactivity and speed.
The fixing purposes in high performance liquid chromatography of the present invention: (4.6 * 150mm) are used for compartment analysis to load the stainless steel performance liquid chromatographic column by homogenate method high pressure.
(60: be the phase that flows 40v/v), toluene is solute, and recording right-tert-butyl group cup [8] aromatic hydrocarbons bonded silica gel (CBS) post effect is 24000 tower slope/m with methanol-water.Under identical dress post and the chromatographic condition, the post of chloropropyl bonded silica gel (CPS) and ODS post is imitated and to be respectively 19000,15000 column plates/m.The CBS post is to the separation of the especially alkaline amine of isomers, and separating rate is fast, the chromatographic peak symmetry, and post is imitated high.It is 12000 column plates/m and on ODS, it is 11500 column plates/m that post is imitated that the nitrophenol isomers is imitated at the CBS upper prop; The phenylenediamine isomers is on CBS, and it is 19600 column plates/m that its post is imitated; And corresponding on the ODS post, it is 6800 column plates/m that post is imitated.Separate peak shape from alkali solute, the symmetrical factor of solute on CBS, CPS, ODS post is respectively 1.00-1.30,1.20-1.80,1.17-3.20.Obviously improved the ODS post polar isomer splitter has been imitated the not high phenomenon that reaches the alkaline matter hangover.This may be because right-ring cavity that tert-butyl group cup [8] aromatic hydrocarbons is big plays excellent shielding effect to the silicon hydroxyl.Separate actual sample as hormone.Separating rate is doubled than the ODS post, and organically-modified agent content greatly reduces, and has avoided the ODS post to separate the shortcoming that the hormone sample needs gradient elutions.Therefore, it is fast that the calixarenes bonded silica gel of the present invention preparation is fixedly compared traditional ODS post analysis speed, and separation chromatography peak (no matter sour neutral and alkali sample) symmetry has obviously been improved ODS to the basic species conditions of streaking; And stable performance, fixing being difficult for mutually run off applicable pH range 2-7.
Claims (5)
1. the fixing phase of a calixarenes bonded silica gel, its structural formula is:
N=4 in the formula～8; Bu
tBe the tert-butyl group.
2. the fixing preparation method of phase of the described calixarenes bonded silica gel of claim 1, it is characterized in that: in the presence of the phase transfer catalyst quaternary ammonium salt, with calixarenes sodium phenolate and halopropyl bonded silica gel in nitrogen or argon gas in 110～120 ℃ through solid phase condensation reaction, make the silica gel bonded fixedly phase of required calixarenes.
3. method according to claim 2 is characterized in that: above-mentioned calixarenes sodium phenolate is a reactant with sodium hydride and calixarenes, is solvent with the dry toluene, makes under 40～100 ℃ of conditions.
4. according to claim 2 or 3 described methods, it is characterized in that: calixarenes is a calixarenes parent or derivatives thereof.
5. the described calixarenes bonded silica gel of claim 1 is fixing mutually as high performance liquid chromatography, micro column liquid chromatography or capillary electric chromatogram separating filler.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100391833C (en) * | 2006-07-31 | 2008-06-04 | 华南理工大学 | Preparation method of calixarene nano-functional material |
| CN102489275A (en) * | 2011-12-26 | 2012-06-13 | 郑州大学 | Phenylalanine-substituted calix [4] arene bonded silica gel stationary phase, preparation method thereof, and application thereof |
| CN102489274A (en) * | 2011-12-26 | 2012-06-13 | 郑州大学 | Alanine substituted calix[4]arene bonded silica stationary phase and preparation method and application thereof |
| CN103007905A (en) * | 2012-11-15 | 2013-04-03 | 郑州大学 | Tetraazacalix [2] arene [2] triazine bonded silica gel solid phase extraction material, preparation method and application thereof |
-
2003
- 2003-06-24 CN CN 03128197 patent/CN1204963C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100391833C (en) * | 2006-07-31 | 2008-06-04 | 华南理工大学 | Preparation method of calixarene nano-functional material |
| CN102489275A (en) * | 2011-12-26 | 2012-06-13 | 郑州大学 | Phenylalanine-substituted calix [4] arene bonded silica gel stationary phase, preparation method thereof, and application thereof |
| CN102489274A (en) * | 2011-12-26 | 2012-06-13 | 郑州大学 | Alanine substituted calix[4]arene bonded silica stationary phase and preparation method and application thereof |
| CN102489274B (en) * | 2011-12-26 | 2013-07-10 | 郑州大学 | Alanine substituted calix[4]arene bonded silica stationary phase and preparation method and application thereof |
| CN102489275B (en) * | 2011-12-26 | 2013-07-10 | 郑州大学 | Phenylalanine-substituted calix [4] arene bonded silica gel stationary phase, preparation method thereof, and application thereof |
| CN103007905A (en) * | 2012-11-15 | 2013-04-03 | 郑州大学 | Tetraazacalix [2] arene [2] triazine bonded silica gel solid phase extraction material, preparation method and application thereof |
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| CN1204963C (en) | 2005-06-08 |
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