CN106946926A - One kind have multiple tooth ammonia carboxylic class dimer chelating agent and preparation method thereof, using and separating medium - Google Patents
One kind have multiple tooth ammonia carboxylic class dimer chelating agent and preparation method thereof, using and separating medium Download PDFInfo
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- CN106946926A CN106946926A CN201710109559.1A CN201710109559A CN106946926A CN 106946926 A CN106946926 A CN 106946926A CN 201710109559 A CN201710109559 A CN 201710109559A CN 106946926 A CN106946926 A CN 106946926A
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction
- B01D15/361—Ion-exchange
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/223—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material containing metals, e.g. organo-metallic compounds, coordination complexes
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- C—CHEMISTRY; METALLURGY
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
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- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/40—Aspects relating to the composition of sorbent or filter aid materials
- B01J2220/44—Materials comprising a mixture of organic materials
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Abstract
The invention provides one kind have multiple tooth ammonia carboxylic class dimer chelating agent and preparation method thereof, using and separating medium, the chelating agent has the structure shown in formula A, its sequestering power is strong, prepares simplicity, can be used in preparing the new separating medium using multiple tooth ammonia carboxylic class dimer as part.The present invention also provides a kind of new separating medium using multiple tooth ammonia carboxylic class dimer as part and its preparation method and application, the new separating medium its be stationary phase to be modified by the chelating agent with multiple tooth ammonia carboxylic class dimer and obtained, its synthetic method is simple, with ion-exchange chromatography and immobilized metal ion afinity chromatography double action, it can significantly improve the stability of IMAC posts.
Description
Technical field
The present invention relates to a quasi-chelate compound, and in particular to a kind of multiple tooth ammonia carboxylic class dimer chelating agent and preparation method thereof,
Using and separating medium.
Background technology
Proposed from 1975 fixed metal affinity chromatography (IMAC) concept [Porath, et al.Nature, 1975,
197-204] since, ion-exchanger and metal-chelator using ammonia carboxylic class separating medium as part are Chinese medicine, chemical industry, biological work
One of common method of the field separate purification of target composition such as journey.In the method, during separating medium is whole isolation technics
Critical material, its consumption accounts for 50% of production cost or so.For this class separating medium, fixing metal ions can be as not positive
Ion-exchanger separates some positively charged subject components under wider Acidity Range, on the other hand, using in ammonia carboxyl
N, O atom coordination, can remove the metal ion in solvent, and such separating medium has been widely used in food, oil
The multiple fields such as chemical industry, textile industry, papermaking and Extraction of Heavy Metals；In addition, securing the ammonia carboxylic class separating medium of metal ion
There can be the protein of compatibility to metal ion commonly used to separation as metal chelating column.So, this kind of separating medium both may be used
With the ion-exchange chromatography applied to subject component, the removal of metal ion can be used for the immobilized metal ion afinity chromatography of protein again.
At present, the part of IMAC column packings is main based on multiple tooth ammonia carboxylic class monomer separation medium, common are three tooth chelas
Mixture such as iminodiacetic acid (IDA), glutamic acid (Glu), asparatate (ASP)；And four tooth nitrilotriacetic acid (NTA) and
[Porath, the et al.Biochem., 1983,22 such as three carboxyl ethylenediamines (TED) and ethylenediamine tetra-acetic acid (EDTA) of five teeth：
1621].And the research in terms of ammonia carboxylic class polymer separating medium synthesis is less, and it is concentrated mainly on NTA dimers or trimerization
Synthesis [Ebright, the et al.J Am Chem., 2001,123 of body:12123；US 7371,754；Piehler,et
al.Anal Chem.,2005,77:1092；US 2008/0038750], and EDTA dimers synthesis [Mattias, et
al.WO 2011/152782 A1,PCT/SE2011/050669].With single phase ratio, dimer is produced as separating medium to target
Product have stronger ion exchange absorption, there is stronger compatibility to metal ion；It is used as IMAC post chelands, one simultaneously
Aspect improves the stability of IMAC posts, on the other hand there is stronger compatibility to large biological molecule.These above-mentioned dimers
The step of synthesis, is cumbersome, and some uncommon reagents are related in reaction, and synthetic method is only suitable to NTA or EDTA monomers.
The content of the invention
It is an object of the invention to provide a kind of chelating agent with multiple tooth ammonia carboxylic class dimer, its sequestering power is strong, system
It is standby easy, it can be used in preparing the new separating medium using multiple tooth ammonia carboxylic class dimer as part.
The present invention also aims to provide a kind of preparation method of the chelating agent with multiple tooth ammonia carboxylic class dimer, the system
Preparation Method step is brief, and reaction unit is simple, convenient experimental operation safety.
The present invention also aims to provide a kind of application of the described chelating agent with multiple tooth ammonia carboxylic class dimer, its
A kind of new separating medium using multiple tooth ammonia carboxylic class dimer as part can be provided.The separating medium is in pharmacy, environmental protection, chemical industry
It is with a wide range of applications with bioengineering field.
The present invention is to be achieved through the following technical solutions：
A kind of multiple tooth ammonia carboxylic class dimer chelating agent, the multiple tooth ammonia carboxylic class dimer chelating agent has the structure as shown in formula A：
Wherein, MC is one kind in formula B1~B5；
Wherein, B1 structural formula is：
B2 structural formula is：
B3 structural formula is：
B4 structural formula is：
B5 structural formula is：
Wherein, R is carboxylic acid ion or carboxyl.
Preferably, the R is carboxylic acid ion.
Preferably, the MC is B1.
A kind of preparation method of described multiple tooth ammonia carboxylic class dimer chelating agent, it includes step：
1) diethylenetriamine is reacted with amido protecting agent, and primary amine group is protected；
2) diethylenetriamine after primary amine group protection reacts with γ-glycidyl ether oxygen propyl trimethoxy silicane, will
Reaction product carries out pillar layer separation；
3) step 2) products obtained therefrom progress deprotection reaction, deprotection group；
4) step 3) primary amine group and the monomer ammonia carboxylic class carboxylate of products obtained therefrom react to form amido link, through column chromatography point
From obtained multiple tooth ammonia carboxylic class dimer chelating agent.
Preferably, in step 1) in, the molar ratio of the diethylenetriamine and amido protecting agent is 1:1.9~2.1；
It is further preferred that the molar ratio of the diethylenetriamine and amido protecting agent is 1：2.
Preferably, in step 1) in, the protection group protected to primary amine include tert-butoxycarbonyl, methoxycarbonyl group class,
One kind in carbethoxyl group, benzyloxycarbonyl group, trifluoroacetyl group, benzyl.Described tert-butoxycarbonyl, methoxycarbonyl group class, ethoxy
Carbonyl can be removed in acid condition, and benzyloxycarbonyl group can be removed by catalytic hydrogenolysis；The trifluoroacetyl group can be in alkali
Property under the conditions of remove.Further, in step 1) in, described amido protecting agent is Boc reagents, the Boc reagents energy
It is enough that Boc protections are carried out to primary amine.It is further preferred that the amido protecting agent includes 2- (tertbutyloxycarbonyl oxygen imido
Base) -2- benzene acetonitriles.
Preferably, in step 2) in, diethylenetriamine and γ-glycidyl ether oxygen propyl after the primary amine group protection
The molar ratio of trimethoxy silane is 1:0.6~0.8；It is further preferred that the molar ratio is 1:0.7.Preferably,
In step 2) in, the diethylenetriamine after above-mentioned primary amine group is protected is dissolved in the ethanol solution of caustic alcohol, is then added
The ethanol solution of γ-glycidyl ether oxygen propyl trimethoxy silicane, stirring is complete to reaction；It is further preferred that step
2) reaction temperature is 75~80 DEG C in, and the reaction time is 8~14h.It is further preferred that step 2) in, after the completion of reaction, instead
Answer system to adjust pH to 4~7, pass through dichloromethane extractive reaction system.
Preferably, in step 2) in, also including column chromatography purification step, wherein, used successively in column chromatography purification step
Petroleum ether, the mixture of petroleum ether and dichloromethane, dichloromethane, the mixture of dichloromethane and ethyl acetate, ethyl acetate,
The mixture of ethyl acetate and ethanol carries out gradient elution.It is further preferred that column chromatography silica gel (refined type) model：Rule
Lattice 3；Granularity：300-400 mesh.
In step 4) in, step 3) in the molar ratio of products obtained therefrom and monomer chelating agent be 1：2~3；It is further excellent
Selection of land, the molar ratio is 1:2.5.
In step 4) in, into the tetrahydrofuran solution of monomer chelating agent add step 3) in products obtained therefrom tetrahydrofuran
Solution, then adds sodium methoxide, is stirred at room temperature complete to reaction.
In step 4) in, after the completion of reaction, water is added into reaction system, is then extracted with ethyl acetate.
In step 4) in, also including column chromatography purification step, wherein, dichloromethane is used in column chromatography purification step successively
Alkane, the mixture of dichloromethane and ethyl acetate, ethyl acetate carry out gradient elution；Wherein, the dichloromethane and acetic acid second
The proportioning of the mixture of ester includes successively：8:Isosorbide-5-Nitrae:1,2:1,1:1,1:2,1:4,1:8.It is further preferred that the column chromatography
Silica gel (refined type) model：Specification 3；Granularity：300-400 mesh.
A kind of described multiple tooth ammonia carboxylic class dimer chelating agent is used to prepare point by part of multiple tooth ammonia carboxylic class dimer
From the application of medium.
A kind of separating medium using multiple tooth ammonia carboxylic class dimer as part, it has the structure as shown in formula C：
Wherein,For silica gel, MC is one kind in formula B1~B5；
Wherein, B1 structural formula is：
B2 structural formula is：
B3 structural formula is：
B4 structural formula is：
B5 structural formula is：
Wherein, R is carboxylic acid ion or carboxyl.
Preferably, the silica gel is spherical porous silica gel, and pore diameter range isParticle diameter is 1 μm~100
μm。
Compared with prior art, the present invention has following beneficial technique effect：
The chelating agent with multiple tooth ammonia carboxylic class dimer that the present invention is provided, it has the chelate group of two groups of monomer chelating agents
Group, sequestering power is strong；It can be used in preparing the new separating medium using multiple tooth ammonia carboxylic class dimer as part.Further,
When two groups of monomer chelating agents are identical, the preparation process of the dimer chelating agent is short, and reaction is simple.
The preparation method for the described chelating agent with multiple tooth ammonia carboxylic class dimer that the present invention is provided, preparation method step
Rapid brief, reaction unit is simple, convenient experimental operation safety, and the synthetic method set up simply easily is realized, and accessory substance is few, energy
The target product of high conversion high-purity is obtained, and is adapted to the preparation of most of multiple tooth ammonia carboxylic class dimer separating mediums.
The application for the described chelating agent with multiple tooth ammonia carboxylic class dimer that the present invention is provided, its can provide it is a kind of with
Multiple tooth ammonia carboxylic class dimer is the new separating medium of part, and the new separating medium has ion-exchange chromatography and metal-chelating
The dual-use function of chromatographic isolation.
A kind of new separating medium using multiple tooth ammonia carboxylic class dimer as part that the present invention is provided, with ion exchange color
Compose the dual-use function separated with immobilized metal ion afinity chromatography.With single phase ratio, dimer is respectively provided with stronger ion to subject component and handed over
Change characteristic；Dimer to the strong chelating properties of metal ion, be on the one hand conducive to improve in use medium to affine sample
The separation of product and adsorption capacity；On the other hand the stability of IMAC posts is remarkably improved, IMAC posts can be effectively improved and used
The losing issue of metal ion in journey.
Brief description of the drawings
Fig. 1 is the synthetic route chart of described multiple tooth ammonia carboxylic class dimer chelating agent.
The infared spectrum that Fig. 2 is TM1 in embodiment 1.
The 1H-NMR collection of illustrative plates that Fig. 3 is TM1 in embodiment 1.
The infared spectrum that Fig. 4 is TM2 in embodiment 2.
The 1H-NMR collection of illustrative plates that Fig. 5 is TM2 in embodiment 2.
The infared spectrum that Fig. 6 is TM3 in embodiment 3.
The 1H-NMR collection of illustrative plates that Fig. 7 is TM3 in embodiment 3.
The infared spectrum that Fig. 8 is TM4 in embodiment 4.
Embodiment
A kind of multiple tooth ammonia carboxylic class dimer chelating agent, the multiple tooth ammonia carboxylic class dimer chelating agent has the structure as shown in formula A：
Wherein, MC is one kind in formula B1~B5；
Wherein, B1 structural formula is：
B2 structural formula is：
B3 structural formula is：
B4 structural formula is：
B5 structural formula is：
Wherein, R is carboxylic acid ion or carboxyl.
Preferably, the R is carboxylic acid ion.
Preferably, the MC is B1.
A kind of preparation method of described multiple tooth ammonia carboxylic class dimer chelating agent, it includes step：
1) diethylenetriamine is reacted with amido protecting agent, and primary amine group is protected；
2) diethylenetriamine after primary amine group protection reacts with γ-glycidyl ether oxygen propyl trimethoxy silicane；
3) step 2) products obtained therefrom progress deprotection reaction, remove the blocking group of primary amine；
4) step 3) primary amine group and the ammonia carboxylic class carboxylate of products obtained therefrom react to form amido link.
Preferably, in step 1) in, the molar ratio of the diethylenetriamine and amido protecting agent is 1:1.9~2.1；
It is further preferred that the molar ratio of the diethylenetriamine and amido protecting agent is 1:2.
Preferably, in step 1) in, the protection group protected to primary amine include tert-butoxycarbonyl, methoxycarbonyl group class,
One kind in carbethoxyl group, benzyloxycarbonyl group, trifluoroacetyl group, benzyl.Described tert-butoxycarbonyl, methoxycarbonyl group class, ethoxy
Carbonyl can be removed in acid condition, and benzyloxycarbonyl group can be removed by catalytic hydrogenolysis；The trifluoroacetyl group can be in alkali
Property under the conditions of remove.Further, in step 1) in, described amido protecting agent is Boc reagents, the Boc reagents energy
It is enough that Boc protections are carried out to primary amine.It is further preferred that the amido protecting agent includes 2- (tertbutyloxycarbonyl oxygen imido
Base) -2- benzene acetonitriles.
Preferably, in step 2) in, diethylenetriamine and γ-glycidyl ether oxygen propyl after the primary amine group protection
The molar ratio of trimethoxy silane is 1:0.6~0.8；It is further preferred that the molar ratio is 1:0.7.Preferably,
In step 2) in, the diethylenetriamine after above-mentioned primary amine group is protected is dissolved in the ethanol solution of caustic alcohol, is then added
The ethanol solution of γ-glycidyl ether oxygen propyl trimethoxy silicane, stirring is complete to reaction；It is further preferred that step
2) reaction temperature is 75~80 DEG C in, and the reaction time is 8~14h.It is further preferred that step 2) in, after the completion of reaction, instead
Answer system to adjust pH to 4~7, pass through dichloromethane extractive reaction system.
Preferably, in step 2) in, also including column chromatography purification step, wherein, used successively in column chromatography purification step
Petroleum ether, the mixture of petroleum ether and dichloromethane, dichloromethane, the mixture of dichloromethane and ethyl acetate, ethyl acetate,
The mixture of ethyl acetate and ethanol carries out gradient elution.It is further preferred that column chromatography silica gel (refined type) model：Rule
Lattice 3；Granularity：300-400 mesh.
In step 4) in, step 3) in the molar ratio of products obtained therefrom and monomer chelating agent be 1：2~3；It is further excellent
Selection of land, the molar ratio is 1:2.5.
In step 4) in, into the tetrahydrofuran solution of monomer chelating agent add step 3) in products obtained therefrom tetrahydrofuran
Solution, then adds sodium methoxide, is stirred at room temperature complete to reaction.
In step 4) in, after the completion of reaction, water is added into reaction system, is then extracted with ethyl acetate.
In step 4) in, also including column chromatography purification step, wherein, dichloromethane is used in column chromatography purification step successively
Alkane, the mixture of dichloromethane and ethyl acetate, ethyl acetate carry out gradient elution；Wherein, the dichloromethane and acetic acid second
The proportioning of the mixture of ester includes successively：8:Isosorbide-5-Nitrae:1,2:1,1:1,1:2,1:4,1:8.It is further preferred that the column chromatography
Silica gel (refined type) model：Specification 3,；Granularity：300-400 mesh.
A kind of described multiple tooth ammonia carboxylic class dimer chelating agent is used to prepare point by part of multiple tooth ammonia carboxylic class dimer
From the application of medium.
In Fig. 1, PG represents amido protecting group.
With reference to specific embodiment, the present invention is described in further detail, it is described be explanation of the invention and
It is not to limit.
Embodiment 1
TM1 preparation
1.10mL (10.30mmol) diethylenetriamine (DETA) is dissolved in 20mL tetrahydrofurans in 150mL flasks, then
4.28mL (30.90mmol) triethylamine is added, 30min is stirred at 0 DEG C in low-temp reaction bath；Weigh 5.2131g
(20.60mmol) 2- (tert-Butoxycarbonyloxyimino) -2- benzene acetonitriles (Boc-on), and 60mL tetrahydrofurans are dissolved in, put
In constant pressure funnel, it is added drop-wise to dropwise in above-mentioned solution.Treat that 2- (tert-Butoxycarbonyloxyimino) -2- benzene acetonitriles drip completely
Enter in flask, continue reaction 4h in 0 DEG C in low-temp reaction bath, be then placed on and react 3h at room temperature.
1.1 thin-layer chromatographic analysis
This step reaction carries out thin-layer chromatography to each reactant, and solvent is dichloromethane (DCM):Methanol (MeOH)=9:1,
Raw material DETA RfValue is 0.16, and this is due to have three amino in DETA molecular structures, and the polarity of the material is very big, in the exhibition
Opening in agent to deploy.And Rs of another substrate raw material Boc-on in solventfIt is worth for 0.84, has one in the raw molecule
The tert-butyl group, the polarity very little of the tert-butyl group, so position of the raw material on lamellae (TLC) is higher.After question response terminates, to anti-
Answer liquid to carry out adopting point and point plate, three points are shown on TLC：Rf1=0.16 is DETA point, Rf2=0.33 is product TM1
Point, Rf3=0.84 is Boc-on point.TLC Comparative results before and after reaction find there is new material generation, this is newly-generated
Material is in DCM and MeOH 9:R in 1 solventfValue is 0.3 or so.
1.2 infrared results are analyzed
As shown in Fig. 2 wherein 3352cm-1It is the stretching vibration absworption peak of secondary amino group in TM1 molecules；2985cm-1It is methyl
And methylene stretching vibration absworption peak；1684cm-1It is secondary amino group deformation vibration the absworption peak；1710cm-1In being carbamate groups
The stretching vibration characteristic absorption peak of carbonyl；1275cm-1It is C-N key stretching vibration absworption peaks；1367cm-1It is the division of the tert-butyl group
Peak.
1.3 nuclear-magnetism interpretations of result
This experiment is taken carries out structural characterization with NMR spectrum to product, obtains product1H-NMR spectrum.Such as Fig. 3
Shown, wherein 4.969ppm is water peak；3.331ppm is non-deuteratedization solvent peak in deuterated MeOH；1.495ppm is on the tert-butyl group
H on methyl, because (Boc-NH-Et) 2NH is symmetrical structure, the chemical environment residing for six methyl is identical, is presented one very
Strong is unimodal, and the number of H atom is 18；2.678~2.710ppm is proximate to 4 H on two methylene of middle parahelium
(-NH-CH2-CH2-NH-CH2-CH2-NH-)；3.170~3.201ppm is from 4 on middle parahelium two methylene farther out
Individual H (- NH-CH2-CH2-NH-CH2-CH2-NH-)。
TM1 infrared and nuclear magnetic spectrum can be corresponding with its structure, and first can be determined in conjunction with its TLC testing result
The reaction product DETA of step protected by Boc-on after derivative (Boc-NH-Et)2The structure that NH is TM1 is correct, and expected
Reaction result is consistent, it can be concluded that first step reaction product TM1 synthesis is correct.The amido protecting reaction of the first step is selected
Classical t-butoxycarbonyl protecting group is protected to primary amine, and experiment yield is up to more than 90%, and product yield is high.In addition,
The isolation and purification method of product is simple.It is pure that reacted crude product is only achieved with very high product by the method for extracting and washing
Degree, can be directly used for the spectroscopic characterization such as nuclear-magnetism means and carries out structural characterization.
Embodiment 2
In the basic conditions, TM1 and γ-GLDP reactions generation TM2：
Measure 20mL ethanol (EtOH) to be placed in beaker, then weigh 1.3g metallic sodiums, be cut into some fritters and be placed in one,
It is transferred to after after metallic sodium completely reaction in 150mL flasks；Weighing 2.9160g (9.61mmol) TM1 and adding flask and stir makes it
It is completely dissolved；1.5mL (6.79mmol) γ-glycidyl ether oxygen propyl trimethoxy silicane (γ-GLDP) accurately is measured, is dissolved in
In 3mL ethanol, under fast stirring, instill dropwise in flask.Flask is placed in 80 DEG C of water-baths, flowed back under fast stirring
12h。
After reaction terminates, the ethanol in flask is steamed completely with Rotary Evaporators；50mL distilled water is added into flask,
EtONa is hydrolyzed；Solution is rotated again, 55 DEG C of temperature is rotated, steams the ethanol in the aqueous solution；Added into the solution
6mol/L HCl, regulation pH to acidity；The extraction of 3~4 times is carried out to the aqueous solution with 40mL dichloromethane, organic phase is obtained.Will
Organic phase is evaporated, and is had three kinds of components in the organic phase being evaporated, is respectively：γ-GLDP, TM1, TM2, remain separation.
Three of the above component is separated with column chromatography, under thin-layer chromatography detection, gradient elution is carried out to said mixture.
Common eluant, eluent such as petroleum ether (PE), dichloromethane (DCM) ethyl acetate (EA), ethanol have been investigated in elution process respectively
Etc. (EtOH) to the elution effect of three kinds of components, as a result as shown in table 1.
It is PE in eluent:DCM(15mL：Start to collect the liquid flowed out from chromatographic column tail end when 90mL), until completely
TM2 is collected, is evaporated and obtains white crystal.
γ-the GLDP of table 1, TM1 and TM2 gradient elution
2.1 thin-layer chromatographys are detected
Reaction carries out thin-layer chromatography after terminating to reaction product, and solvent is DCM:MeOH=9:1, can be clear on TLC
Clear obtains 3 points, its RfValue is respectively 0.81,0.67,0.3.R corresponding to TM1 and γ-GLDPfValue is respectively 0.3 and 0.81,
And RfIt is newly-generated material to be worth for the point corresponding to 0.67, and it is exactly target separation product TM2.
2.2 infrared results are analyzed
As shown in figure 4, wherein 3602cm-1It is the stretching vibration absworption peak of-OH in TM2 molecules；3362cm-1It is secondary amino group
Stretching vibration absworption peak；2985cm-1It is methyl and methylene stretching vibration absworption peak；1710cm-1In being carbamate groups
The stretching vibration characteristic absorption peak of carbonyl；1410cm-1It is the flexural vibrations of C-Si keys；1368cm-1It is the division peak of the tert-butyl group；
1275cm-1It is C-N key stretching vibration absworption peaks；1020cm-1It is the stretching vibration of Si-O keys.
2.3 nuclear-magnetism interpretations of result
Product TM2 structure is characterized with NMR spectrum, as shown in figure 5, wherein 7.214ppm is deuterated chlorine
Non-deuterated solvent peak in imitative；3.522~3.502ppm is proximate to 4 H on two methylene of middle tertiary amino；3.470~
3.462ppm is from 4 H on middle tertiary amino two methylene farther out；3.329ppm is the H of three oxymethyls, by
It is identical in the chemical environment residing for three methyl, it is presented one stronger unimodal, H atom number is 9；2.05ppm is-OH
1 H；1.495ppm is the hydrogen of methyl on the tert-butyl group, and the chemical environment residing for 6 methyl is identical, present one it is very strong unimodal,
H atom number is 18；0.691ppm is proximate to 2 H on the carbon of Si atoms.
TM2 nuclear-magnetism and infared spectrum can be corresponding with its structure, and second can be determined in conjunction with its TLC testing result
The reaction product structure of step is correct, consistent with expected reaction result, it can be concluded that intermediate product TM2 synthesis is accurate.
Embodiment 3
TM2 generates TM3 in the presence of trifluoroacetic acid：
Weigh 1.7940g (2mmol) TM2 to be dissolved in 10mL dichloromethane, 10mL trifluoroacetic acids (TFA) added thereto,
Reaction 2h is stirred at room temperature.
Dichloromethane solvent and part trifluoroacetic acid are separated by rotating instrument revolving, added into the material after revolving
Enter 50mL saturated sodium carbonate solutions, remove unnecessary trifluoroacetic acid, and pH value of solution is adjusted to 9~10.Extracted with 20mL dichloromethane
Take three times, aqueous phase is evaporated and uses 50mL tetrahydrofurans to dissolve.The inorganic salts insoluble in tetrahydrofuran are filtered, yellow clarification are obtained saturating
The bright aqueous solution, is evaporated, and obtains yellow oily material as TM3.
3.1 thin-layer chromatographys are detected
Reaction carries out thin-layer chromatography after terminating to reaction product, and solvent is DCM:MeOH=9:1, only at TLC origins
There is material point, show that TM2 reacts completely.
3.2 infrared results are analyzed
As shown in fig. 6, wherein 3602cm-1It is the stretching vibration absworption peak of-OH in TM3 molecules；3362cm-1It is primary amine groups
And the stretching vibration absworption peak of secondary amino group；1620cm-1It is the deformation vibration the absworption peak of primary amine groups and tertiary amino；1410cm-1It is C-
The flexural vibrations of Si keys；1275cm-1It is C-N key stretching vibration absworption peaks；1193cm-1It is the flexural vibrations of Si-O keys.
3.3 nuclear-magnetism interpretations of result
Product TM3 structure is characterized with NMR spectrum, as shown in fig. 7, wherein 4.870ppm is deuterated
Aqueous solvent peak in MeOH；4.880~4.890ppm is ehter bond and the H being connected with the carbon in both carbon of hydroxyl centre position；
3.329ppm is the H of three oxymethyls, because the chemical environment residing for three methyl is identical, and a stronger list is presented
Peak, H atom number is 9；2.933~2.844ppm is proximate to 4 H on two methylene of middle tertiary amino；2.785~
2.774ppm is from 4 H on middle tertiary amino two methylene farther out；1.884ppm is the H on-OH, and H atom number is
1；1.273~1.511 be the H on two carbon adjacent with silicon atom；1.218ppm is the H in two primary amine groups, and H numbers are 4.
1.495ppm positions are to have no peak where 18 H of methyl on the tert-butyl group in TM2, show to be deprotected successfully.
TM3 infrared and nuclear magnetic spectrum can be corresponding with its structure, and the 3rd can be determined in conjunction with its TLC testing result
The reaction product structure of step is correct, consistent with expected reaction result, it can be concluded that intermediate product TM3 synthesis is correct.
The Boc protections of amino are removed completely with trifluoroacetic acid, it is very thorough that reaction is carried out, and TM2 is fully converted into
TM3.TM3 can obtain pure intermediate product completely because the presence polarity of two symmetrical primary amine groups is remarkably reinforced by extraction,
It is easily operated.
Embodiment 4
TM3 and diethyl iminodiacetate reaction generation target product TM4, i.e. target product：
Take 0.9mL (5mmol) diethyl iminodiacetate to be dissolved in 30mL tetrahydrofurans to be placed in flask, be slowly stirred
It is lower that 1.1393g (2mmol) the TM3 solution for being dissolved in 10mL tetrahydrofurans is added dropwise in flask.0.5g is added into flask
MeONa, is stirred at room temperature 24h.
It is evaporated the tetrahydrofuran in flask, and the addition 50mL distilled water into flask；3 are extracted with 20mL ethyl acetate (EA)
It is secondary, obtain organic phase and be evaporated.Mixture after being evaporated has two kinds of components, is diethyl iminodiacetate and TM4 respectively.
Both the above component is separated with column chromatography, under thin-layer chromatography detection, gradient elution is carried out to said mixture,
Obtain the result of table 2：
It is DCM in eluent:EA(40mL:Start to collect the liquid flowed out from chromatographic column tail end when 80mL), until completely
Target product 4 (TM4) is collected into, is evaporated and obtains pale yellow oil matter.
4.1 thin-layer chromatographys are detected
Reaction carries out thin-layer chromatography after terminating to reaction product, and solvent is EA:PE=1:1, can be clearly on TLC
Obtain 3 points, its RfValue is respectively 0.58,0.11,0.00.R corresponding to TM3 and diethyl iminodiacetatefIt is worth for 0.58 He
0.00, and RfValue is that the point corresponding to 0.11 is newly-generated material, is exactly target separation product TM4.
4.2 infrared detections
As shown in figure 8, wherein 3355cm-1It is that the stretching vibration of amino and tertiary amine groups in TM4 molecules in amido link absorbs
Peak；1758cm-1It is the carbonylic stretching vibration absworption peak in amido link；1676cm-1It is the amino flexural vibrations absorption in amido link
Peak；1446cm-1It is the stretching vibration absworption peak of C-N keys in amido link；1274cm-1It is C-N keys stretching vibration absorption in tertiary amine groups
Peak；1135cm-1It is the flexural vibrations absworption peak of Si-O keys.In 3600cm-1It is-OH that, which there is a unconspicuous peak position left and right,
Stretching vibration absworption peak.
Peak position is in 1758cm at infrared results most obvious one-1There is carbonylic stretching vibration peak and at 1446 in place
The C-N key stretching vibration absworption peaks of appearance show there is amido link in molecule, therefore can speculate that target product TM4 synthesis is accurate
Really.Reaction raw materials can dissolve in tetrahydrofuran completely, and the reaction is the ammonolysis reaction of homogeneous an ammonia and ester, reaction condition temperature
It is slow with, reaction rate, amide-type product is obtained in the basic conditions, and carrying out gradient elution through column chromatography obtains pure target
Product.The TM4 finally given is exactly a multiple tooth ammonia carboxylic class dimer chelating agent, and the dimer can be modified directly in silica gel microball
Surface, so as to prepare the multiple tooth ammonia carboxylic class dimer separating medium of high intensity.
Claims (10)
1. a kind of multiple tooth ammonia carboxylic class dimer chelating agent, it is characterised in that the multiple tooth ammonia carboxylic class dimer chelating agent has such as formula A
Shown structure：
Wherein, MC is one kind in formula B1~B5；
Wherein, B1 structural formula is：
B2 structural formula is：
B3 structural formula is：
B4 structural formula is：
B5 structural formula is：
Wherein, R is carboxylic acid ion or carboxyl.
2. multiple tooth ammonia carboxylic class dimer chelating agent as claimed in claim 1, it is characterised in that R is carboxylic acid ion.
3. the preparation method of the multiple tooth ammonia carboxylic class dimer chelating agent described in claim 1, it is characterised in that the preparation method
Including step：
1) diethylenetriamine is reacted with amido protecting agent, and primary amine group is protected；
2) diethylenetriamine after primary amine group protection reacts with γ-glycidyl ether oxygen propyl trimethoxy silicane, will react
Product carries out pillar layer separation；
3) step 2) products obtained therefrom progress deprotection reaction, deprotection group；
4) step 3) primary amine group and the monomer ammonia carboxylic class carboxylate of products obtained therefrom react to form amido link, through pillar layer separation,
Multiple tooth ammonia carboxylic class dimer chelating agent is made.
4. the preparation method of multiple tooth ammonia carboxylic class dimer chelating agent as claimed in claim 3, it is characterised in that in step 1)
In, the protection group protected to primary amine includes tert-butoxycarbonyl, methoxycarbonyl group class, carbethoxyl group, benzyloxycarbonyl group, trifluoro second
One kind in acyl group, benzyl.
5. the preparation method of multiple tooth ammonia carboxylic class dimer chelating agent as claimed in claim 3, it is characterised in that in step 1)
In, described amido protecting agent is 2- (tert-Butoxycarbonyloxyimino) -2- benzene acetonitriles.
6. the preparation method of multiple tooth ammonia carboxylic class dimer chelating agent as claimed in claim 3, it is characterised in that in step 2)
In, the diethylenetriamine after primary amine group is protected is dissolved in the ethanol solution of caustic alcohol, then adds γ-glycidol ether
The ethanol solution of oxygen propyl trimethoxy silicane, stirring is complete to reaction.
7. the preparation method of multiple tooth ammonia carboxylic class dimer chelating agent as claimed in claim 3, it is characterised in that step 2) it is described
Petroleum ether, the mixture of petroleum ether and dichloromethane, dichloromethane, dichloromethane and second are used in pillar layer separation step successively
The mixture of acetoacetic ester, ethyl acetate, the mixture of ethyl acetate and ethanol carry out gradient elution；
Step 4) dichloromethane, the mixture of dichloromethane and ethyl acetate, second are used in the pillar layer separation step successively
Acetoacetic ester carries out gradient elution；Wherein, the proportioning of the mixture of the dichloromethane and ethyl acetate includes successively：8:1、4:1、
2:1、1:1、1:2、1:4、1:8。
8. the multiple tooth ammonia carboxylic class dimer chelating agent described in claim 1 is used to prepare using multiple tooth ammonia carboxylic class dimer as part
The application of separating medium.
9. a kind of separating medium using multiple tooth ammonia carboxylic class dimer as part, it is characterised in that it has the knot as shown in formula C
Structure：
Wherein,For silica gel, MC is one kind in formula B1~B5；
Wherein, B1 structural formula is：
B2 structural formula is：
B3 structural formula is：
B4 structural formula is：
B5 structural formula is：
Wherein, R is carboxylic acid ion or carboxyl.
10. as claimed in claim 9 using multiple tooth ammonia carboxylic class dimer as the separating medium of part, it is characterised in that the silicon
Glue is spherical porous silica gel, and pore diameter range isParticle diameter is 1 μm~100 μm.
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| CN113426417A (en) * | 2021-07-19 | 2021-09-24 | 西北大学 | Application of ammonia carboxylic ligand modified silica gel adsorbent to simultaneous removal of methyl orange and metal ions in dye wastewater and treatment method |
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