CN103007774A

CN103007774A - Flat sheet membrane for chiral separation of amino acid and preparation method thereof

Info

Publication number: CN103007774A
Application number: CN2012105551143A
Authority: CN
Inventors: 赵义平; 张强; 李金苓; 王霞; 陈莉; 申向; 陈娇娇
Original assignee: Tianjin Polytechnic University
Current assignee: Tianjin Polytechnic University
Priority date: 2012-12-19
Filing date: 2012-12-19
Publication date: 2013-04-03

Abstract

The invention discloses a flat sheet membrane for chiral separation of amino acid, and a preparation method thereof, and relates to the field of intelligent high polymer materials. The preparation method comprises the following steps: firstly, taking L-phenylalanine (L-Phe) as the separation target, synthesizing a chiral amino acid monomer through modification, and further copolymerizing with a thermosensitive monomer N-isopropyl acrylamide (NIPAAm) so as to synthesize chiral copolymer microgel P (NIPAAm-co-AAc-L-PheEt); secondly, carrying out graft copolymerization on the NIPAAm monomer and polyvinylidene fluoride (PVDF) by using a free radical polymerization method so as to synthesize a thermosensitive membrane making substrate PVDF-g-PNIPAAm; and finally alloying the thermosensitive chiral copolymer microgel with a thermosensitive membrane making substrate solution, so as to prepare the flat sheet membrane for chiral separation of amino acid. The flat sheet membrane has the chiral recognition and separation function and can realize the efficient separation of L-Phe by controlling the ambient temperature change. The membrane provided by the invention is simple in preparation method, needs no special equipment, is low in production cost and is applicable to industrial application; and the selective overload quantity of the prepared flat sheet membrane can be up to 15-25%, and the separation coefficient (alpha) can be up to1.5-1.8.

Description

A kind of amino acid chiral separates with Flat Membrane and preparation method thereof

Technical field

The invention belongs to functional high polymer material field, particularly a kind of chiral separation film with Selective Separation amino acid chiral molecule and preparation method thereof.This film can be applicable to the phenylalanine separation field.

Background technology

Occurring in nature all contains chiral material in a lot of materials, and many chiral materials extensively are present in the medicine, and are closely related with our life.Because different enantiomer molecules has different optical activities in the chiral material, in optical property obvious difference or fully opposite is arranged, the optical property of enantiomer molecule is different thus, can produce significant difference in pharmacologically active, metabolism and toxic and side effect etc., clinical drug shows as wherein, and a kind of enantiomer molecule has certain drug action, but another kind of enantiomer molecule does not have pharmacological action, even can cause disadvantageous negative effect.Therefore, chiral separation has great importance in the medicine preparation process.

At present, the chiral resolution technology of using in laboratory or the industrial circle mainly comprises: the methods such as crystallization Split Method, chemical resolution method, Kinetic Resolution, biological Split Method, chromatogram Split Method, film separation, molecular imprinting and electrophoretic techniques.In recent years, membrane separation technique is increasingly burning hot in research and the application in chiral separation field, wherein the chiral resolution film comes the separating chiral material by chiral Recognition point to the selective absorption of different enantiomers, have energy consumption low, be easy to the advantages such as continued operation, be considered to carry out one of very potential method of extensive chiral separation, become the new focus of diffusion barrier research

The chiral resolution film can be divided into chiral resolution liquid film and chiral separation solid film by the form of film.The chiral resolution liquid film has higher selective and economy (the use chiral selector is less), but less stable, its application is limited by very large.Chiral separation solid film can overcome the deficiency of liquid film, thereby extremely this area research person's concern.But the greatest drawback of chiral separation solid film is that split process is unstable state, when the adsorption site caudacoria that reaches capacity no longer has the fractionation ability, need carry out desorb, and desorption process is controlled trouble, causes separative efficiency lower, and is difficult to possess simultaneously high flux and high selectivity.

For the separative efficiency and the applicability that improve chiral separation solid film, the R and D of intelligent chiral separation film receive much attention.Intelligence chiral separation film can produce response to environmental stimulis such as temperature, pH value, ion concentration, electric fields, can come controlled material internal void size by changing external environmental condition, realizes high selectivity, the high flux of film, improves separative efficiency.Because temperature control is relatively easy in the external environmental condition, utilizes temperature sensitive macromolecular material to have the characteristics of lower critical solution temperature (LCST), researches and develops temperature sensitive chiral separation film and then has more realistic meaning.But there is following several large problem that need solve in the temperature sensitive chiral separation film of at present research and development:

(1) preparation method of temperature sensitive chiral separation film modifies the graft modification of basal lamina material, exists the modification preparation process complicated, and stability of material variation, the grafting layer defective such as be easy to come off is difficult to realize suitability for industrialized production after the modification.

(2) Thermo-sensitive of temperature sensitive chiral separation film is obvious not, and temperature remains further to be improved to Intelligentized regulating and controlling effect and the regulation and control stability of chiral Recognition and fractionation.

(3) chiral selectivity of film, separative efficiency, flux etc. are not high, realize comparatively difficulty of stable state separation.

Phenylalanine is a kind of of a-amino acid, is one of essential amino acid, and having bioactive optical isomer is L-Phe (L-Phe).The L-Phe human body can not synthesize, and is widely used in the primary raw material of medicine and Aspartame.Phenylalanine can pass through the method preparation of microbial fermentation, proteolysis and organic synthesis.The yield that synthetic method prepares phenylalanine is low, usually extract from natural products, but chiral separating efficiency is the subject matter that restricts at present L-Phe output.

Summary of the invention

The problems referred to above for temperature sensitive chiral separation film existence, and the difficult problem of separating of the potential application of temperature sensitive chiral separation film and phenylalanine chiral molecules, the technical problem that quasi-solution of the present invention is determined is: provide a kind of amino acid chiral that the phenylalanine chiral molecules is had good adsorption and a separation function to separate with Flat Membrane and preparation method thereof.

One aspect of the present invention with L-Phe as splitting object, by modification synthesis of chiral amino acid monomer, and then with temperature sensitive monomer NIPA (NIPAAm) copolymerization, synthetic temperature sensitive Chiral Copolymer microgel P (NIPAAm-co-AAc-L-PheEt).On the other hand, adopt free radical copolymerization method with NIPAAm monomer and Kynoar (PVDF) graft copolymerization, synthetic temperature sensitive film becomes membrane matrix PVDF-g-PNIPAAm.At last, with temperature sensitive Chiral Copolymer microgel and the blend of PVDF-g-PNIPAAm copolymer solution, adopt the phase inversion preparation to have chiral Recognition and fractionation function, and can separate by the efficient amino acid chiral that separates of variations in temperature realization L-Phe that controls environment and use Flat Membrane.

A kind of amino acid chiral separation of the present invention comprises the steps: with Flat Membrane and preparation method thereof

(1) the temperature sensitive copolymer microgel of chirality is synthetic: the L-Phe esterification is generated L-Phe carbethoxy hydrochloride (L-PheEt), and then with acryloyl chloride acylation reaction synthesis of chiral monomer N-(L-1-ethoxycarbonyl-2-phenyl) acrylamide (AAc-L-PheEt).Take the there-necked flask device, add 50ml through oxolane (THF) condensing reflux except water treatment, add the NIPAAm monomer in there-necked flask, making NIPAAm concentration is 0.1～0.18mol/L.R is 0.2 adding chiral monomer AAc-L-PheEt in mass ratio, and behind 0.05～0.20g crosslinking agent MBAA, logical nitrogen gas stirrings are 30～60 minutes under 20～30 ℃, slowly be warming up to 50～70 ℃, stablized 20～40 minutes, add 0.04～0.08g initator azodiisobutyronitrile (AIBN), isothermal reaction 6～10 hours.After reaction finishes, add petroleum ether precipitation to reactant liquor, suction filtration obtains the temperature sensitive copolymer microgel of chirality P (NIPAAm-co-AAc-L-PheEt), and drying is placed on sombre place and preserves.

Described mass ratio r=AAc-L-PheEt/ (AAc-L-PheEt+NIPAAm), the i.e. ratio of the quality of AAc-L-PheEt and AAc-L-PheEt and NIPAAm quality sum.

(2) temperature sensitive film forming matter is synthetic: the PVDF powder art of getting after the 10g alkali treatment adds in the there-necked flask, logical nitrogen, the solvent N that adds 6～12 times of PVDF quality, dinethylformamide (DMF), stirring and dissolving under heating condition under 50～80 ℃ of water-baths, in the situation of logical nitrogen, add NIPAAm, the mass ratio of control PVDF powder and NIPAAm is 1: (0.5～1.25), the initiator A IBN that adds PVDF quality 1%～2.5%, after the dissolving, logical nitrogen is 10～20 minutes again, continues stirring reaction 8～12 hours fully, after reaction finishes, to add methanol extraction after the reactant liquor cooling, suction filtration washes repeatedly with distilled water, then drain to get temperature sensitive film forming matter PVDF-g-PNIPAAm, putting into 60 ℃ in baking oven, to be dried to constant weight stand-by.

(3) chiral separation is with the preparation of Flat Membrane: film forming matter PVDF-g-PNIPAAm is added fill in the container of DMF, mass percent concentration is controlled at 15%～20%, add microgel P (NIPAAm-co-AAc-L-PheEt), the mass ratio of control microgel and PVDF-g-PNIPAAm is 1: 3～10, add at last pore-foaming agent polyethylene glycol (PEG), making the mass percent concentration of PEG in mixed liquor is 5%～10%.Heat under 30～60 ℃ of conditions, stir until dissolve fully, vacuum defoamation obtained casting solution in 20～40 minutes.Casting solution is inclined on the glass plate, with glass bar striking film forming, immerse solidification forming in 25～30 ℃ the coagulating bath distilled water, until film be shaped from glass plate come off after, place again and soak 18～36 hours in the distilled water, clean with distilled water and namely obtain the chiral separation Flat Membrane.

In the described step (1), described L-PheEt building-up process is as follows: build experimental provision, comprise spherical condensation tube, 100ml there-necked flask, water bath with thermostatic control, thermometer.In there-necked flask, add the 55ml absolute ethyl alcohol, put into ice bath constant temperature at 0 ℃, slowly splash into the 5ml thionyl chloride with dropper, remain temperature under 5 ℃, stirred 1 hour, add 10g L-Phe powder, remove ice bath, naturally be warming up to room temperature, then progressively be warming up to 65 ℃, constant temperature stirred 3 hours, stopped to stir.Reaction under 85 ℃ of bath temperatures, distills out partial solvent after finishing, crystallisation by cooling, and suction filtration, with a small amount of ethanol washing, oven dry obtains the L-PheEt solid.

In the described step (1), described AAc-L-PheEt building-up process is as follows: the THF of the rear 30ml that will anhydrate first joins in the 100ml there-necked flask, takes by weighing 6g L-PheEt and adds in the flask.Prefabricated cryosel piece is smashed to pieces, made the cryosel bath and be placed on around the there-necked flask, reach liquid level and get final product, be cooled to 0 ℃.Keep system temperature slowly to drip the 7.5ml triethylamine at 0 ℃, slowly drip the 4ml acryloyl chloride, after dropwising, constant temperature progressively is warming up to room temperature after a period of time in cryosel is bathed, and stirs 1 hour, is warming up to 60 ℃ of reactions 3 hours again.After reaction finishes, add 30mL distilled water to reactant liquor, dissolve unreacted hydrochloride and acryloyl chloride, dilute solution is used 30mL chloroform extraction three times simultaneously, adds anhydrous sodium sulfate drying, boil off solvent, obtain dark yellow oily thing AAc-L-PheEt, place sombre place stand-by.

In the described step (2), the PVDF powder preparation process of described alkali treatment is as follows: add the PVDF powder of 150g in the 1LNaOH solution, add subsequently the absolute ethyl alcohol of 30ml and stir, so that PVDF fully disperses in solution.The mixed solution reaction system is placed 60 ℃ of waters bath with thermostatic control, reacted 10 minutes.The suction filtration products therefrom constantly washs with distilled water, to remove fluoride and the ethanol in the product.Gained alkali treatment PVDF powdered product is put into 60 ℃ in baking oven and is dried to constant weight after the washing.

Beneficial effect

The present invention is in the Flat Membrane preparation process, adopt and use water as the coagulating bath forming film with phase transformation method, hydrophily makes P (NIPAAm-co-AAc-L-Phe) high polymer chiral separation group to film and fenestra surface enrichment in the film forming procedure, is conducive to the sorption and desorption to chirality D-Phe.Therefore, the blend flat sheet membrane of the present invention preparation can be realized sorption and desorption to D-Phe by the height of control parting liquid temperature, and can realize the variation of membrane pore size by the height of control parting liquid temperature.(T＞LCST), the chirality adsorptivity of membrane material is adsorbed D-Phe in a large number, and L-Phe is then separated by fenestra smoothly under the high temperature, because this moment, fenestra diminished, membrane flux reduces, so be conducive to the absorption to the D-Phe enantiomer, has improved the separative efficiency of L-Phe.(T＜LCST), film reduces the adsorption capacity of D-Phe, thereby discharges the D-Phe of absorption, and this moment, fenestra increased, and membrane flux raises, and is conducive to improve the D-Phe desorption efficiency, and two kinds of enantiomers separately the most at last to reduce the parting liquid temperature.This separation process can be regulated and control by the stimulation of ambient temperature, and adsorbance is large, but the efficient selective sorption and desorption, and can alternately repeat to carry out continuously, solved the defective of traditional absorption selection type chiral resolution film.

The present invention combines with absorption selection type chiral separation solid film by the environment-responsive with intellectual material, utilizes the chiral Recognition characteristic realization of chirality high polymer to selective efficient adsorption and the desorb of chiral molecules, thereby realizes chiral resolution.The present invention integrates the temperature sensitive copolymer of chirality and the temperature sensitive Thermo-sensitive that becomes membrane matrix, strengthened the Thermo-sensitive of film, chiral separating efficiency and temperature have been improved to the Intelligentized regulating and controlling effect of chiral separation, amino acid chiral of the present invention separates selects overload quantity (e.e.%) can reach 15%-25% with Flat Membrane, and separation (α) can reach 1.5-1.8.In addition, the blend chiral separation film of the present invention's preparation utilizes into membrane matrix and the structural general character of chiral polymer, has solved the problem such as two-phase dispersion and compatibility in the blend chiral separation film preparation process.

The prepared chiral separation Flat Membrane of the present invention adopts ripe in the market PVDF to make raw material, and function monomer be the temperature sensitive raw material monomer NIPAAm of routine, membrane preparation method simply, do not need special installation, production cost low, be suitable for industrial applications.

Select the mensuration of overload quantity and separation

By selecting overload quantity (e.e.%) and separation (α) to characterize chiral Recognition and the fractionation ability of blend film, its computing formula is as follows:

e . e . % = \frac{A_{D} - A_{L}}{A_{D} + A_{L}} * 100 %

In the formula: e.e.%-selects overload quantity, %;

A _DThe peak area value of-D-phenylalanine component in chromatogram;

A _LThe peak area value of-L-Phe component in chromatogram;

α = \frac{A_{D}}{A_{L}}

In the formula: α-separation;

A _DThe peak area value of-D-phenylalanine component in chromatogram;

A _LThe peak area value of-L-Phe component in chromatogram;

The specific embodiment

The following examples can make the present invention of those skilled in the art comprehend, but do not limit the present invention in any way.

Embodiment 1:

(1) take the there-necked flask device, add 50ml through the THF condensing reflux except water treatment, add the NIPAAm monomer in there-necked flask, making NIPAAm concentration is 0.1mol/L.R is 0.2 adding chiral monomer AAc-L-PheEt in mass ratio, and behind the 0.10g crosslinking agent MBAA, logical nitrogen gas stirrings are 30 minutes under 30 ℃, slowly are warming up to 50 ℃, stablize 20 minutes, add 0.04g initator azodiisobutyronitrile (AIBN), isothermal reaction 6 hours after reaction finishes, adds petroleum ether precipitation to reactant liquor, suction filtration gets microgel P (NIPAAm-co-AAc-L-PheEt), and drying is placed on sombre place and preserves.

(2) temperature sensitive film forming matter is synthetic: the PVDF powder of getting after the 10g alkali treatment adds in the there-necked flask, and logical nitrogen adds the solvent DMF (DMF) of 6 times of PVDF quality, stirring and dissolving under heating condition under 50 ℃ of water-baths.In the situation of logical nitrogen, add NIPAAm, the mass ratio of control PVDF and NIPAAm is 1: 0.5, adds the initiator A IBN of PVDF quality 1%, fully after the dissolving, logical nitrogen is 10 minutes again, continue stirring reaction 8 hours, and after reaction finishes, will add methanol extraction after the reactant liquor cooling, suction filtration, repeatedly wash with distilled water, then drain to get PVDF-g-PNIPAAm, putting into 60 ℃ in baking oven, to be dried to constant weight stand-by.

(3) chiral separation is with the preparation of Flat Membrane: PVDF-g-PNIPAAm is added fill in the container of DMF, mass percent concentration is controlled at 15%, add microgel, the mass ratio of control microgel and PVDF-PNIPAAm is 1: 3, add at last pore-foaming agent PEG, making the mass percent concentration of PEG in mixed liquor is 5%.Heat under 30 ℃ of conditions, stir until dissolve fully, vacuum defoamation obtained casting solution in 20 minutes.Casting solution is inclined on the glass plate, with glass bar striking film forming, is immersed solidification forming in 25 ℃ the distilled water, until film be shaped from glass plate come off after, place again in the distilled water and soaked 18 hours, with the clean chiral separation Flat Membrane that namely obtains of distilled water.

It is 25% that the amino acid chiral separation that makes is selected overload quantity (e.e.%) with Flat Membrane, and separation (α) is 1.8.

Embodiment 2:

(1) take the there-necked flask device, add 50ml through the THF condensing reflux except water treatment, add the NIPAAm monomer in there-necked flask, making NIPAAm concentration is 0.13mol/L.R is 0.2 adding chiral monomer AAc-L-PheEt in mass ratio, and behind the 0.20g crosslinking agent MBAA, logical nitrogen gas stirrings are 60 minutes under 30 ℃, slowly are warming up to 70 ℃, stablize 40 minutes, add 0.08g initator azodiisobutyronitrile (AIBN), isothermal reaction 10 hours after reaction finishes, adds petroleum ether precipitation to reactant liquor, suction filtration gets microgel P (NIPAAm-co-AAc-L-PheEt), and drying is placed on sombre place and preserves.

(2) temperature sensitive film forming matter is synthetic: the PVDF powder of getting after the 10g alkali treatment adds in the there-necked flask, and logical nitrogen adds the solvent DMF (DMF) of 12 times of PVDF quality, stirring and dissolving under 50 ℃ of condition of water bath heating.Add NIPAAm in the situation of logical nitrogen, the mass ratio of control PVDF and NIPAAm is 1: 0.5, adds the initiator A IBN of PVDF quality 2.5%, and after the dissolving, logical nitrogen is 20 minutes again, continues stirring reaction 12 hours fully.After reaction finishes, will add methanol extraction after the reactant liquor cooling, suction filtration washes repeatedly with distilled water, then drains to get PVDF-g-PNIPAAm, and putting into 60 ℃ in baking oven, to be dried to constant weight stand-by.

(3) chiral separation is with the preparation of Flat Membrane: PVDF-g-PNIPAAm is added fill in the container of DMF, mass percent concentration is controlled at 16%, add microgel, the mass ratio of control microgel and PVDF-PNIPAAm is 1: 10, add at last pore-foaming agent PEG, making the mass percent concentration of PEG in mixed liquor is 6%.Heat under 40 ℃ of conditions, stir until dissolve fully, vacuum defoamation obtained casting solution in 40 minutes.Casting solution is inclined on the glass plate, with glass bar striking film forming, is immersed solidification forming in 30 ℃ the distilled water, until film be shaped from glass plate come off after, place again in the distilled water and soaked 18 hours, with the clean chiral separation Flat Membrane that namely obtains of distilled water.

It is 22% that the amino acid chiral separation that makes is selected overload quantity (e.e.%) with Flat Membrane, and separation (α) is 1.6.

Embodiment 3:

(1) take the there-necked flask device, add 50ml through the THF condensing reflux except water treatment, add the NIPAAm monomer in there-necked flask, making NIPAAm concentration is 0.15mol/L.R is 0.2 adding chiral monomer AAc-L-PheEt in mass ratio, and behind the 0.1g crosslinking agent MBAA, logical nitrogen gas stirrings are 60 minutes under 30 ℃, slowly be warming up to 50 ℃, stablized 30 minutes, and added 0.05g initator azodiisobutyronitrile (AIBN), isothermal reaction 10 hours.After reaction finishes, add petroleum ether precipitation to reactant liquor, suction filtration gets microgel P (NIPAAm-co-AAc-L-PheEt), and drying is placed on sombre place and preserves.

(2) temperature sensitive film forming matter is synthetic: the PVDF powder of getting after the 10g alkali treatment adds in the there-necked flask, and logical nitrogen adds the solvent DMF (DMF) of 12 times of PVDF quality, stirring and dissolving under heating condition under 60 ℃ of water-baths.Add NIPAAm in logical nitrogen situation, the mass ratio of control PVDF and NIPAAm is 1: 1.25, adds the initiator A IBN of PVDF quality 1.5%, and after the dissolving, logical nitrogen is 20 minutes again, continues stirring reaction 12 hours fully.After reaction finishes, will add methanol extraction after the reactant liquor cooling, suction filtration washes repeatedly with distilled water, then drains to get PVDF-g-PNIPAAm, and putting into 60 ℃ in baking oven, to be dried to constant weight stand-by.

(3) chiral separation is with the preparation of Flat Membrane: PVDF-g-PNIPAAm is added fill in the container of DMF, mass percent concentration is controlled at 18%, add microgel, the mass ratio of control microgel and PVDF-PNIPAAm is 1: 5, add at last pore-foaming agent PEG, making the mass percent concentration of PEG in mixed liquor is 10%.Heat under 40 ℃ of conditions, stir until dissolve fully, vacuum defoamation obtained casting solution in 40 minutes.Casting solution is inclined on the glass plate, with glass bar striking film forming, is immersed solidification forming in 30 ℃ the distilled water, until film be shaped from glass plate come off after, placed again in the distilled water 36 hours, with the clean chiral separation Flat Membrane that namely obtains of distilled water.

It is 21% that the amino acid chiral separation that makes is selected overload quantity (e.e.%) with Flat Membrane, and separation (α) is 1.6.

Embodiment 4:

(1) take the there-necked flask device, add 50ml through the THF condensing reflux except water treatment, add the NIPAAm monomer in there-necked flask, making NIPAAm concentration is 0.18mol/L.R is 0.2 adding chiral monomer AAc-L-PheEt in mass ratio, and behind the 0.20g crosslinking agent MBAA, logical nitrogen gas stirrings are 60 minutes under 30 ℃, slowly are warming up to 50 ℃, stablize 30 minutes, add 0.06g initator azodiisobutyronitrile (AIBN), isothermal reaction 8 hours after reaction finishes, adds petroleum ether precipitation to reactant liquor, suction filtration obtains microgel P (NIPAAm-co-AAc-L-PheEt), and drying is placed on sombre place and preserves.

(2) temperature sensitive film forming matter is synthetic: the PVDF powder of getting after the 10g alkali treatment adds in the there-necked flask, and logical nitrogen adds the solvent DMF (DMF) of 12 times of PVDF quality, stirring and dissolving under heating condition under 60 ℃ of water-baths.Add NIPAAm in the situation of logical nitrogen, the mass ratio of control PVDF and NIPAAm is 1: 1, adds the initiator A IBN of PVDF quality 1.5%, and after the dissolving, logical nitrogen is 20 minutes again, continues stirring reaction 12 hours fully.After reaction finishes, will add methanol extraction after the reactant liquor cooling, suction filtration washes repeatedly with distilled water, then drains to get PVDF-g-PNIPAAm, and putting into 60 ℃ in baking oven, to be dried to constant weight stand-by.

(3) chiral separation is with the preparation of Flat Membrane: PVDF-g-PNIPAAm is added fill in the container of DMF, mass percent concentration is controlled at 20%, add microgel, the mass ratio of control microgel and PVDF-PNIPAAm is 1: 5, add at last pore-foaming agent PEG, making the mass percent concentration of PEG in mixed liquor is 10%.Heat under 40 ℃ of conditions, stir until dissolve fully, vacuum defoamation obtained casting solution in 40 minutes.Casting solution is inclined on the glass plate, with glass bar striking film forming, is immersed solidification forming in 30 ℃ the distilled water, until film be shaped from glass plate come off after, placed again in the distilled water 36 hours, with the clean chiral separation Flat Membrane that namely obtains of distilled water.

It is 19% that the amino acid chiral separation that makes is selected overload quantity (e.e.%) with Flat Membrane, and separation (α) is 1.5.

Embodiment 5:

(1) take the there-necked flask device, add 50ml through the THF condensing reflux except water treatment, add the NIPAAm monomer in there-necked flask, making NIPAAm concentration is 0.125mol/L.R is 0.2 adding chiral monomer AAc-L-PheEt in mass ratio, and behind the 0.10g crosslinking agent MBAA, logical nitrogen gas stirrings are 45 minutes under 25 ℃, slowly are warming up to 60 ℃, stablize 30 minutes, add 0.05g initator azodiisobutyronitrile (AIBN), isothermal reaction 8 hours after reaction finishes, adds petroleum ether precipitation to reactant liquor, suction filtration obtains microgel P (NIPAAm-co-AAc-L-PheEt), and drying is placed on sombre place and preserves.

(2) temperature sensitive film forming matter is synthetic: the PVDF powder of getting after the 10g alkali treatment adds in the there-necked flask, and logical nitrogen adds the solvent DMF (DMF) of 10 times of PVDF quality, stirring and dissolving under heating condition under 60 ℃ of water-baths.Add NIPAAm in the situation of logical nitrogen, the mass ratio of control PVDF and NIPAAm is 1: 0.8, adds the initiator A IBN of PVDF quality 2.2%, and after the dissolving, logical nitrogen is 15 minutes again, continues stirring reaction 12 hours fully.After reaction finishes, will add methanol extraction after the reactant liquor cooling, suction filtration washes repeatedly with distilled water, then drains to get PVDF-g-PNIPAAm, and putting into 60 ℃ in baking oven, to be dried to constant weight stand-by.

(3) chiral separation is with the preparation of Flat Membrane: PVDF-g-PNIPAAm is added fill in the container of DMF, mass percent concentration is controlled at 16%, add microgel, the mass ratio of control microgel and PVDF-PNIPAAm is 1: 5, add at last pore-foaming agent PEG, making the mass percent concentration of PEG in mixed liquor is 10%.Heat under 40 ℃ of conditions, stir until dissolve fully, vacuum defoamation obtained casting solution in 40 minutes.Casting solution is inclined on the glass plate, with glass bar striking film forming, is immersed solidification forming in 30 ℃ the distilled water, until film be shaped from glass plate come off after, placed again in the distilled water 36 hours, with the clean chiral separation Flat Membrane that namely obtains of distilled water.

It is 17% that the amino acid chiral separation that makes is selected overload quantity (e.e.%) with Flat Membrane, and separation (α) is 1.5.

Embodiment 6:

(1) take the there-necked flask device, add 50ml through the THF condensing reflux except water treatment, add the NIPAAm monomer in there-necked flask, making NIPAAm concentration is 0.16mol/L.R is 0.2 adding chiral monomer AAc-L-PheEt in mass ratio, and behind the 0.18g crosslinking agent MBAA, logical nitrogen gas stirrings are 50 minutes under 30 ℃, slowly are warming up to 55 ℃, stablize 40 minutes, add 0.07g initator azodiisobutyronitrile (AIBN), isothermal reaction 10 hours after reaction finishes, adds petroleum ether precipitation to reactant liquor, suction filtration obtains microgel P (NIPAAm-co-AAc-L-PheEt), and drying is placed on sombre place and preserves.

(2) temperature sensitive film forming matter is synthetic: the PVDF powder of getting after the 10g alkali treatment adds in the there-necked flask, and logical nitrogen adds the solvent DMF (DMF) of 12 times of PVDF quality, stirring and dissolving under heating condition under 70 ℃ of water-baths.Add NIPAAm in the situation of logical nitrogen, the mass ratio of control PVDF and NIPAAm is 1: 1.25, adds the initiator A IBN of PVDF quality 2.5%, and after the dissolving, logical nitrogen is 20 minutes again, continues stirring reaction 12 hours fully.After reaction finishes, will add methanol extraction after the reactant liquor cooling, suction filtration washes repeatedly with distilled water, then drains to get PVDF-g-PNIPAAm, and putting into 60 ℃ in baking oven, to be dried to constant weight stand-by.

It is 15% that the amino acid chiral separation that makes is selected overload quantity (e.e.%) with Flat Membrane, and separation (α) is 1.5.

Claims

1. an amino acid chiral separates the preparation method who uses Flat Membrane, comprises the steps:

(1) the temperature sensitive copolymer microgel of chirality is synthetic: the L-Phe esterification is generated L-Phe carbethoxy hydrochloride (L-PheEt), and then with acryloyl chloride acylation reaction synthesis of chiral monomer N-(L-1-ethoxycarbonyl-2-phenyl) acrylamide (AAc-L-PheEt): take the there-necked flask device, add 50ml through oxolane (THF) condensing reflux except water treatment, in there-necked flask, add the NIPAAm monomer, r is 0.2 adding chiral monomer AAc-L-PheEt in mass ratio, then after adding crosslinking agent MBAA, logical nitrogen gas stirrings are 30～60 minutes under 20～30 ℃, slowly be warming up to 50～70 ℃, stablized 20～40 minutes, add initator azodiisobutyronitrile (AIBN), isothermal reaction 6～10 hours, after reaction finishes, add petroleum ether precipitation to reactant liquor, the suction filtration quick copolymer microgel P warm in nature (NIPAAm-co-AAc-L-PheEt) that goes smoothly, drying is placed on sombre place and preserves;

(2) temperature sensitive film forming matter is synthetic: the PVDF powder of getting after the 10g alkali treatment adds in the there-necked flask, logical nitrogen, the solvent N that adds 6～12 times of PVDF quality, dinethylformamide (DMF), stirring and dissolving under heating condition under 50～80 ℃ of water-baths, in the situation of logical nitrogen, add NIPAAm and initiator A IBN, after the dissolving, logical nitrogen is 10～20 minutes again, continues stirring reaction 8～12 hours fully, after reaction finishes, to add methanol extraction after the reactant liquor cooling, suction filtration washes repeatedly with distilled water, then drain to get temperature sensitive film forming matter PVDF-g-PNIPAAm, putting into 60 ℃ in baking oven, to be dried to constant weight stand-by;

(3) chiral separation is with the preparation of Flat Membrane: film forming matter PVDF-g-PNIPAAm is added fill in the container of DMF, add microgel P (NIPAAm-co-AAc-L-PheEt), add at last pore-foaming agent polyethylene glycol (PEG), under 30～60 ℃ of conditions, heat, stir until fully dissolving, vacuum defoamation obtained casting solution in 20～40 minutes, casting solution is inclined on the glass plate, with glass bar striking film forming, immerse solidification forming in 25～30 ℃ the coagulating bath distilled water, after film comes off from the glass plate shaping, place again and soak 18～36 hours in the distilled water, clean with distilled water and namely obtain the chiral separation Flat Membrane.

2. a kind of amino acid chiral separates the preparation method who uses Flat Membrane according to claim 1, it is characterized in that: add the NIPAAm monomer in the described step (1) in there-necked flask, making NIPAAm concentration is 0.1～0.18mol/L.

3. a kind of amino acid chiral separates the preparation method who uses Flat Membrane according to claim 1, it is characterized in that: the addition of crosslinking agent MBAA is 0.05～0.20g in the described step (1).

4. a kind of amino acid chiral separates the preparation method who uses Flat Membrane according to claim 1, it is characterized in that: the addition of initator azodiisobutyronitrile (AIBN) is 0.04～0.08g in the described step (1).

5. a kind of amino acid chiral separates the preparation method who uses Flat Membrane according to claim 1, it is characterized in that: the mass ratio of PVDF powder and NIPAAm is 1 in the described step (2): (0.5～1.25).

6. a kind of amino acid chiral separates the preparation method who uses Flat Membrane according to claim 1, it is characterized in that: the addition of initiator A IBN is 1%～2.5% of PVDF quality in the described step (2).

7. a kind of amino acid chiral separates the preparation method who uses Flat Membrane according to claim 1, it is characterized in that: in the described step (3) film forming matter PVDF-g-PNIPAAm adding is filled in the container of DMF, mass percent concentration is controlled at 15%～20%.

8. a kind of amino acid chiral separates the preparation method who uses Flat Membrane according to claim 1, it is characterized in that: the mass ratio of microgel and PVDF-g-PNIPAAm is 1: 3～10 in the described step (3).

9. a kind of amino acid chiral separates the preparation method who uses Flat Membrane according to claim 1, it is characterized in that: add pore-foaming agent polyethylene glycol (PEG) in the described step (3), the mass percent concentration that makes PEG account for mixed liquor is 5%～10%.

10. a kind of amino acid chiral of any one separates amino acid chiral that the preparation method with Flat Membrane makes and separates and use Flat Membrane according to claim 1-9, and it is characterized in that: described amino acid chiral separation comprises the steps: with the preparation method of Flat Membrane

(1) the temperature sensitive copolymer microgel of chirality is synthetic: the L-Phe esterification is generated L-Phe carbethoxy hydrochloride (L-PheEt), and then with acryloyl chloride acylation reaction synthesis of chiral monomer N-(L-1-ethoxycarbonyl-2-phenyl) acrylamide (AAc-L-PheEt): take the there-necked flask device, add 50ml through oxolane (THF) condensing reflux except water treatment, in there-necked flask, add the NIPAAm monomer, r is 0.2 adding chiral monomer AAc-L-PheEt in mass ratio, then after adding crosslinking agent MBAA, logical nitrogen gas stirrings are 30～60 minutes under 20～30 ℃, slowly be warming up to 50～70 ℃, stablized 20～40 minutes, add initator azodiisobutyronitrile (AIBN), isothermal reaction 6～10 hours, after reaction finishes, add petroleum ether precipitation to reactant liquor, suction filtration obtains the temperature sensitive copolymer microgel of chirality P (NIPAAm-co-AAc-L-PheEt), and drying is placed on sombre place and preserves;