JPH0459047A - Adsorbent - Google Patents

Abstract

PURPOSE:To obtain an adsorbent having high separative power and capable of optical resolution of ceramic mixture by using, as an adsorbent carrier, a cross-linked polymer free from skin layer or having extremely thin skin layer on the surface. CONSTITUTION:The cross-linked polymer as an adsorbent carrier is composed of porous grains and its surface area is regulated to 1-2000m<2>/g, and further, the grain surface is free from skin layer or has skin layer as thin as <=300Angstrom thickness, if any. This cross-linked polymer is allowed to hold a polymer giving adsorptive power. The resulting adsorbent is capable of high-efficiency separation by adsorption and also ion exchange, distribution, etc., and particularly, it can efficiently resolve a ceramic mixture in optical resolution.

Description

[Detailed Description of the Invention] <Field of Application for Industry 1-> The present invention is particularly suitable for making it possible to industrially produce optically active substances by optical resolution of racemic mixtures by chromatography. The present invention relates to a novel adsorbent for optical resolution having high optical resolution ability and a method for producing the same.

The present invention also relates to an adsorbent having advanced separation performance suitable for ion exchange, partition, adsorption, hydrophobic, affinity and molecular exclusion chromatography and separation of biopolymers and the like.

<Prior Art> Optical resolution, ie, a method of resolving a racemic mixture of optical antipodes into its respective optical antipodes, is used in the pharmaceutical, agrochemical, and food industries. Therefore, the usual industrial resolution method is to convert the racemic mixture into a mixture of diastereomers and to resolve the diastereomer mixture according to the differences in their physical properties. In addition to this method, methods of resolving racemic mixtures by chroma 1-craphy have been actively researched in recent years.

The chromatographic separation method uses an optically active adsorbent, for example, a porous silica gel, a cellulose derivative such as cellulose 1-helacetate, or an optically active poly(
Methods using a coating of methacrylate (1-rephenylmethyl) methacrylate-1 or a porous silica gel bonded to optically active polyacrylamide are known as stationary phases (for example, Yoshio Okamoto Funseki No. ,
2 (1,990) P.

96).

<Problem to be solved by the invention> By converting into a mixture of diastereomers, the difference in physical properties between them 1. There are only one type of racemic mixture that can be separated.

In addition, in the chroma1-craphy separation method, the optically active adsorbent used as the stationary phase is determined by It is low-temperature and has sufficient performance for 21-industrial use. Furthermore, there are also problems in terms of durability and ease of manufacture when used as a main beam.

The purpose of the present invention is to provide a novel adsorbent having advanced separation performance suitable for ion exchange, distribution, adsorption, hydrophobicity, affinity and molecular exclusion chroma 1 to chroma optical resolution, and dispersion of biopolymers, etc. shall be.

In particular, the present invention improves the separation function of the supported optically active polymer component and increases the amount of the supported polymer in an adsorbent comprising an optically active polymer supported on a crosslinked polymer phase. The object of the present invention is to provide a novel adsorbent for optical resolution that has a high separation ability even under a high load of a racemic mixture.

<Means for Solving the Problems> Firstly, in order to solve these problems, the present inventors have developed crosslinked polymers made of optically active synthetic polyamino acids on a crosslinked polymer carrier. They have discovered that it has unprecedented performance as an adsorbent for gamma splitting, etc., and have proposed it (see Japanese Patent Publication No. 63-53855).

Furthermore, as a result of research on the adsorbent obtained by the above method, the present inventors found that the crosslinked polymer carrier obtained by the conventional method has a thick skin layer formed on its surface. It has been found that it is desirable to eliminate the presence of such a skin layer as much as possible, since the skin layer affects the loading of the polymer that provides adsorption capacity. Then,
It was discovered that by adjusting the type and amount of the diluent used during polymerization of the crosslinked polymer carrier, it is possible to produce a carrier with no skin Bd or even with an extremely thin carrier, and the carrier without a skin layer obtained in this way Add adsorption capacity to 1
5) It was discovered that an adsorbent supporting a polymer exhibits high separation performance, and that the separation ability is not impaired even if a larger amount of polymer is supported depending on the application, and the present invention was achieved based on this finding.

The present invention provides an adsorbent in which a polymer capable of imparting adsorption ability is supported on a crosslinked polymer carrier, wherein the carrier is a porous particle, the surface area is 1 to 2000%/g, and the particle surface There is no skin layer or even if there is; 300 people J-”
This invention relates to an adsorbent characterized by being a crosslinked polymer under J.

The present invention will be explained in detail below.

In the present invention, the crosslinked polymer carrier may be any carrier capable of supporting a polymer capable of imparting adsorption ability through craft polymerization or the like, and is appropriately selected from styrene (meth)acrylic crosslinked polymers.

For example, a copolymer of chloromethylstyrene-styrene-divinylbenzene, a copolymer of acrylamide 1-1 methylene bisacrylamide 1, glycidyl (meth)acryle-1 to ethylene glycol di(meth)acrylate 1
copolymer of vinylbenzyl glycicyl ether-vinyl hensen, vinylbenzyl glycicyl ether-ethylene glycol cyclo(meth)acrylate-1
copolymer to ethylene glycol di(meth)acrylate-1, p-1,-butoxystyrene-divinylbenzene copolymer, glycerin mono(meth)acrylate-1 to -divinylbenzene copolymer, Kasa is an example.

The degree of crosslinking of the crosslinked polymer carrier is usually 15% or more.
00% or less, preferably 20% or more and +99.5% or less. The degree of crosslinking referred to here is expressed by the weight ratio of crosslinkable monomers to all polymerizable monomers.

In addition, in order to obtain an adsorbent with high separation ability, the physical structure of the crosslinked polymer carrier must be porous, especially one with an area of 1 to 2000 m / g, and the surface of the carrier should be porous. There is no skin layer, or if there is one, the redness is 300 Å or less. Furthermore, in order to increase the amount of polymer supported with adsorption capacity, a crosslinked polymer carrier without a skin layer is particularly preferred. The thickness of Sugin J (77) can be determined by observing the cross section of the dried crosslinked polymer *1'L using an electron microscope.

Specifically, for example, if the cross-sectional area of the cross-linked polymer particles is
It is determined by determining the thickness of the skin layer at five arbitrary points in the photomicrograph and averaging it.

The skin layer in the present invention refers to a surface dense layer that is clearly different from the internal porous structure that can be determined by electron microscopy.

When the particle surface of a crosslinked polymer carrier having such a skin layer is observed at a magnification of 100,000 times using a scanning electron microscope, it is clear that 1. It has a smooth surface, which is different from the co-porous structure.

One-boat fishing for porous carriers! In method A, for example, a porous type polymer can be made into a porous type polymer by adding a suitable surfactant to the monomer and a diluent through phase separation 1 between the polymer and diluent produced during the polymerization process. ! Alternatively, polymerization is carried out by coexisting linear polymers such as polystyrene, polymethylstyrene, polymethyl acrylate, etc. in the monomer phase 1 and 1, and then the linear polymers are extracted and removed from the resulting spherical shells. There are methods to use a porous carrier.

When producing a porous crosslinked polymer carrier by suspension polymerization, a general shikoskin layer may be formed depending on the properties of the bath and the type of dispersion stabilizer, or it may be formed during the polymerization process. If there is significant phase separation between the diluent and the diluent,
In addition, when polymerization is carried out by coexisting a linear polymer in a monomer phase, the formation of a porous carrier on the surface of a porous carrier occurs when the concentration of the linear polymer in the monomer phase is high, causing phase separation from the polymer. There are many.

Therefore, in the present invention, as the diluent and linear polymer added during the production of the crosslinked polymer, those that have good compatibility with the crosslinked polymer to be produced are selected within the range of making the produced crosslinked polymer porous, or these diluents are selected. The agent and the linear polymer are compatible with the crosslinked copolymer (5
By adjusting these ratios to d and 1, or by using other diluents with good compatibility, it is possible to obtain the targeted porous crosslinked polymer without a skin layer.

For example, when producing a chloromethylstyrene-styrene-dihinylhensen copolymer, if 7 volumes of a mixed solution of 1 to toluene and n-1<decane are used as a diluent, the resulting polymer and A skin layer is formed when the ratio of ``L-characteristic (strong ■) - dodecane is large in the sum of .

Further, when only [1]-]hedecane is used as a diluent, the thickness of the skin layer is further increased.

In addition, when a linear alcohol is used as a diluent in the production of glycerin monomethacrylate-1-diheel-Hensen copolymer, as the number of carbon atoms in the primary alcohol increases, the resulting polymer The skin layer is formed by using the phase-separable polyester 41 and the latecanol having 14 carbon atoms.

In order to obtain a high separation performance in an adsorbent formed by supporting a polymer capable of adsorption on a crosslinked polymer carrier, the carrier must have *1γ without a skin layer on its surface. Alternatively, it is necessary to use carrier particles having a thickness of 300 mm or more. When a carrier having a thick skin layer is used, the polymer capable of imparting adsorption ability is mainly supported only on the surface, resulting in poor separation performance. When the reaction conditions are made stricter to increase the supported amount, the surface of the carrier is secretly coated with a polymer capable of imparting adsorption ability, and the interior of the porous carrier is not utilized, resulting in a significant reduction in the usable effective surface area and significant separation performance. descend.

In the present invention, by using a carrier with no skin layer or with a very thin skin layer, the polymer capable of imparting adsorption ability is uniformly supported on the surface and inside of the carrier, thereby reducing the amount of the supported amount. However, it is possible to maintain high separation performance.

The cross-linked polymer carrier used in the present invention is usually spherical, and is obtained by supporting a cross-linked polymer with a narrow particle size distribution (1γ molecules), which imparts adsorption ability. The adsorbent also has a narrow particle size distribution, and a high theoretical plate number can be obtained especially when used in the Kara 13 Taloma Claffy method, which is advantageous.

The size of the cross-linked polymer particles may vary depending on the intended use; generally, the particle size should be 1.-10001 Lm. In particular, as optically active polymers, for example, optically active polyamino acids, or poly(( meth)acrylamide.More specifically, poly(N''-hensyl-F, -curcumin), poly(N-1-phenylethyl (meth)acrylamide 1), and poly(N-(hensyl-F, -curcumin)). 1-xycarbonylmethyl)(meth)acrylamide F
) etc. Polymer fireflies capable of imparting adsorption ability,
The method of supporting the crosslinked polymer carrier may be a chemical method or a physical method. Physical methods include dissolving a polymer capable of imparting the adsorption ability in a soluble solvent, mixing well with the phase, and distilling off the solvent with an air stream under reduced pressure or heating; There is also a method of dissolving the polymer etc. that can be applied in a soluble solvent, thoroughly mixing it with the carrier, stirring and dispersing it in a liquid that is incompatible with the solvent, and then distilling off the solvent. The chemical method may vary depending on the type of polymer, etc. that can provide the adsorption ability to be supported, or may be appropriately selected from methods known per se. A method of bonding a polymer capable of imparting adsorption ability having a reactive functional group to a carrier having a group that reacts with the functional group through a polymer-polymer reaction, and There are methods such as bonding polymers capable of imparting adsorption ability through polymerization as shown in Graph 1.

The amount of the polymer supported on the cross-linked polymer IR1 that provides adsorption capacity is preferably from 5 to 70% by weight, particularly preferably from 10 to 60% by weight. The loading amount mentioned here is
The adsorption capacity occupied in the obtained adsorbent is expressed as the weight percentage of units derived from the obtained polymer.

The polymer produced according to the above method is used as an adsorbent, but before use, 7. Generally speaking, there are batch methods and column chromatography methods for evaluating the performance of Seiko 1. When performing high degree separation such as separation of optically active substances, it is preferable to perform evaluation by Color 11 chromatography.

Normally, the power column chromatography method is carried out in a first step. First, the adsorbent is suspended in the medium used for elution, and the suspension is transferred to the column. Dissolve the anti-separation paraboloid in a small amount of solvent, inject this solution into two parts of the column, then pass the eluent through this column, and collect the eluate from column 11 in the usual manner. Collect separately.

In the case of racemic mixtures, the degree of resolution of the racemates can usually be determined by measuring the optical rotation of each fraction.

The adsorbent of the present invention has advanced separation performance suitable for separation of ion exchange, partitioning, adsorption, hydrophobicity, affinity and molecular exclusion chromatography, optical resolution, and separation of biopolymers, etc.

In particular, when the adsorbent of the present invention is used for optical resolution, it is possible to efficiently separate many kinds of racemic mixtures, and in particular, it is possible to treat highly concentrated racemic mixture solutions. Furthermore, it is possible to process a larger amount of racemic mixture at one time per unit volume of adsorbent than conventional methods. It is also suitably used when separating and removing optical antipodes partially present as impurities in optically active substances.

When separating a racemic mixture into optically active substances using the adsorbent of the present invention, there are two methods: batch method and column chromatography, but it is usually advantageous to use column chromatography. be.

The separation method using column chromatography is the same as the method described above as the evaluation method. At this time, the solvent used for column filling and elution varies depending on the type of compound to be separated and the type of adsorbent, but there are no particular restrictions as long as the solvent dissolves or reacts with the adsorbent. Particularly in the case of optical resolution, in general, it is necessary to sufficiently resolve the target compound and use a solvent that swells the adsorbent. :1 selected. Specific examples of such solvents include aromatic hydrocarbons such as 1-luene and xylene, ethers such as diethyl ether, dioxane, teI-rahydrofuran, and t-butyl methyl ether, dichloroethane, trichloromethane, and carbon tetrachloride. These halogenated hydrocarbons can be used alone or in a 1':1 ratio. In addition, solvents that do not swell the adsorbent, such as hydrocarbons such as pentane and hegisane, ethanol, 2-
Alcohols such as propatool, water, etc. can also be used by partially mixing them with the organic solvent that swells the adsorbent.

<Action> Adsorption onto cross-linked polymer carrier 1! -5. In the adsorbent supporting the polymer that can be obtained, the surface area of the conjugate is 1
By using carrier particles with a particle size of ~2000+rr/g and no skin layer on the surface of the particles or even if there is a skin layer, the resulting adsorbent can be used for ion exchange, distribution, , adsorption, hydrophobicity, affinity and molecular exclusion chromatography, optical resolution, and separation of biopolymers, etc. 1゜In particular, /llI, ,E〕 adsorbent has a high resolution, Shows high optical separation ability even under high loading of racemic mixtures. The use of the adsorbent according to the invention therefore makes it possible to industrialize the optical resolution of racemic mixtures by chromatography.

<Examples> The present invention will be specifically explained in the following examples and application examples, but the present invention is not limited only to these examples and application examples.

Devitrification 11- Chlormethylstyrene 0.5 g, 55% Cyhinyl/＼
99.5g (crosslinking agent) -? ], 67g, 100g of 1 helton as a diluent
, 78 liquid to which 50 g of Tochican was added was added to a solution of 7.5 g of polyvinyl alcohol and 750 g of water. After stirring this mixture for 30 minutes at 2000 rpm,
About 150 revolutions/minute for 8 hours at nitrogen flow F80°C1. The mixture was stirred to perform suspension polymerization. Filter the resulting crosslinked polymer,
After washing with deionized water, acetone, l-toluene, and methanol, it was dried under reduced pressure at about 80°C. The obtained crosslinked Bommer was a truly spherical cotton gamma molecule that was insoluble in ordinary organic solvents. This item is Flowsorb 2 manufactured by Micromeritics.
At! by nitrogen adsorption method using 300! The determined surface area was 551 2/g, and the surface area was determined by mercury intrusion method using O1 Hepore 9200 manufactured by Micromeritics.
It was a porous cross-linked polymer with a determined pore volume of 47 mQ/g.

Next, in order to examine the surface structure of the crosslinked polymer particles, scanning electron microscopy was performed. The surface deposition was carried out using Ion Coater 1B-3 manufactured by Eiko Engineering Co., Ltd., using Targetera 1 of Au (60%) Pd (40%).
25 at a voltage of 4 kV and a current of 6 mA.
I did it for seconds. The scanning electron microscope used was an I-S-900. When observed at a magnification of 100,000 times, as shown in FIG. 1, this material was porous up to the surface of the grain 4, and there was no skin layer.

Next, 54 g of 2-ethylhexanol was added to 12.0 g of the crosslinked polymer, and the mixture was heated in an ultrasonic cleaner for about 30 minutes while stirring at about 300 revolutions/min to form a slurry solution. Add 9.14 g of hexamethylene diamine to the slurry solution,
The mixture was stirred at 150 rpm for 4 hours in a nitrogen atmosphere at 90°C to convert the chloromethyl groups in the crosslinked polymer to N-(aminohexyl)aminomethyl groups. After the reaction, the crosslinked polymer was collected by filtration and treated with acetone, 0.1N hydrochloric acid, deionized water, and 0.1N hydrochloric acid. ] After sequentially washing with an aqueous solution of N-hydroxide 1 to RI 11, deionized water and methanol, it was dried in a vacuum oven at 80'C for 8 hours. The nitrogen content of this thing is 0
．． 120 weight h (%).

Obtained aminated crosslinked polymer carrier 1. Og is converted into L-glutamic acid-γ-methyl ester-N-carphonic anhydride (
3°44 g of γ-ML (hereinafter referred to as -NCA), dichloroethane (hereinafter referred to as 1-: I) 16], :1
mQ, and stirred at 25°C for 10 hours, and further stirred at 30°C for 20 hours to polymerize NCA.

After the polymerization reaction, the poly(γ-methyl-1.-curtamer 1
12.6g of ethylene chlorohydrin and 0.7g of concentrated sulfuric acid as a catalyst were added to the supported crosslinked polymer dispersion (hereinafter referred to as PMLG), stirred at 60°C for 3 hours, and then the reaction system The mixture was reduced in pressure and stirred for an additional 34 hours while distilling off the methanol purified by the reaction together with the solvent to carry out transesterification. After the reaction, poly(γ
-2-chloroethyl-L-glutame-1-) (hereinafter PCT
The supported crosslinked polymer (referred to as EG) was collected by filtration, washed successively with EDC, acetone, methanol and water, and dried under reduced pressure.

T] CTEG-supported crosslinked polymer 10. Pencil amine 600 inches, dispersed in L, 60°C trowel 30
The mixture was stirred for an hour and amitrilysis was performed. After the reaction, poly(γ-N-hensyl-L-curtamine) (hereinafter referred to as PB L
The supported crosslinked polymer (referred to as GN) was collected by filtration, washed sequentially with methanol and acetone, and purified.

In the infrared absorption spectrum 1 Herre, the absorption of ester around 1740G-1 disappeared and the absorption of Ami1~ around 1650CIll- increased, indicating that the ester of the polyamino acid side chain was converted to hensylamide. .

100 g of the PBI, GNN-supporting crosslinked polymer was mixed with 70.0 m Q of dioxane, and 10.0 m Q of acetic anhydride. A solution of OK was dispersed and stirred at 30'C for 24 hours to protect the terminal amino group from the acetyl group. After the reaction, the polyamino acid-supported crosslinked polymer with terminal amino groups protected was collected by filtration, and purified by washing successively with dioxane, acetone and methanol. The elemental analysis values of this product were as follows.

C: 82.67 (%) H near, 68 N: 3.05 nitrogen content (β), and the supported amount of polyamino acid is estimated to be 23.1% by weight.

Missing ■-2- 55% cross-linking agent, 80% instead of divinylbenzene
A crosslinked polymer was synthesized in the same manner as in Example 1 except that divinylbenzene was used, and j)'l was released.

The surface area of this crosslinked polymer is 609rrr/g and the pore volume is 1. ．． It was 68 mD,/g.

In addition, when observed with a scanning electron microscope at a magnification of 100,000 times, it was found that there was no skin layer on the particle surface (second
figure).

Using this cross-linked polymer, a polyamino acid-supported cross-linked polymer was synthesized using the same method as in Example below.

The elemental analysis values of this product were as follows.

C: 82° 56 (%) H near, 52 N: 3.02 From the nitrogen content, the amount of polyamino acid supported is estimated to be 2z, 9%.

3. A crosslinked polymer was synthesized in the same manner as in Example 1 except that 75 g of toluene and 75 g of n-dodeno J were used as diluents, and j and le were separated.

The surface area of this crosslinked polymer was 459 m/g, and the pore volume was 1.6], m Q /g. Furthermore, the absence of a skin layer on the surface was confirmed by observation using a scanning electron microscope.

A polyamino acid-supported crosslinked polymer was synthesized using the crosslinked polymer in the same manner as in Example 1. The elemental analysis values of this product were as follows.

C: 82.66 (%) T(: 7.58 N: 2.68 From the nitrogen content, the amount of polyamino acid supported is estimated to be 20.3%.

Example-4 55% divinylbenzene was used instead of 80% divinylbenzene as the frame+G 71'l, and 1 to 10% divinylbenzene was used as the diluent.
A crosslinked polymer was synthesized in the same manner as in Example T except that 75 g of luene and 75 g of n-totican were used.

I boxed the car. The surface area of this crosslinked polymer is 488nζ/g
There was. Furthermore, the absence of a skin layer on the surface was confirmed by observation using a scanning electron microscope at a magnification of 100,000 times.

A polyamino acid-supported crosslinked polymer was synthesized in the same manner as in Example 1 using the crosslinked polymer. The elemental analysis values of this product were as follows.

C: 83.86 (%) 1-1:1゜66 N: 2.45 From the nitrogen-containing dragon, the amount of polyamino acids supported was 18.56
Estimated to be % by weight.

Chlormethylstynone 1.0g, 80% Cibinylhenzen (crosslinking agent) 99g, Hensilveroxy I'],
, 67 g, toluene]OOg as a diluent, 50 g of n-dodecane added to 7 volumes of hair, polyvinyl alcohol 7
．． 5 g and 750 g of water. This mixture was dispersed in the same manner as in Example] and polymerized to synthesize and isolate a crosslinked polymer. The surface area of this crosslinked polymer was 431 J/g. Further, the absence of a skin layer on the surface was confirmed by observation using a scanning electron microscope at a magnification of 10,000 times.

Furthermore, 1.2.0 g of the obtained crosslinked polymer was added to Example 1-
It was aminated in the same way. The nitrogen content of this thing is 0°09
It was 0% by weight.

Obtained aminated crosslinked polymer carrier9. Og to γMLG
-NCA6.67g, EDC] was dispersed in a solution of 88.0mQ, stirred at 25°C for 10 hours, and then further stirred at 30°C.
The mixture was stirred at C for 20 hours to polymerize NCA. After the polymerization reaction, the PML G-supported crosslinked polymer dispersion was subjected to sequential reactions in the same manner as in Example 1 to obtain a polyamino acid supported crosslinked polymer. The elemental analysis values of this product were as follows.

C: 78.2G (%) Hnear, 33N: 4.87 Based on the nitrogen content, the amount of polyamino acid supported is estimated to be 36.9% by weight.

9.0 g of aminated crosslinked polymer carrier obtained in Example 5
γ-MLG-NCA12.39g, EDC25fi.

The mixture was dispersed in 6 mfl of solution, stirred at 25°C for 10 hours, and further stirred at 30°C for 20 hours to polymerize NCA.

After the polymerization reaction, the PML G-supported crosslinked polymer dispersion was subjected to sequential reactions in the same manner as in Example 1 to obtain a polyamino acid supported crosslinked polymer. The elemental analysis values of this product were as follows.

C: 75.99 (%) H near, 18 N: 6.25 Based on the nitrogen content, the amount of polyamino acid supported is estimated to be 47.4% by weight.

1 needle L chloromethylstyrene 1.0g, 80% divinylbenzene (crosslinking agent) 99g, pensoyl peroxy 1 to 1.6
j[, 75 g of toluene as a diluent, 7 g of n-dodecane
7.5g of polyhinyl alcohol,
Added to a solution of 750 g of water. This mixture was dispersed and polymerized in the same manner as in Example] to synthesize a crosslinked polymer! l'
-tuft. The surface area of this crosslinked polymer is 4:3
It was 1++i'/g. Furthermore, the absence of a skin layer on the surface was confirmed by observation using a scanning electron microscope at a magnification of 100,000 times.

Furthermore, 12.0 g of the obtained crosslinked polymer was aminated in the same manner as in Example 1. The nitrogen content of this product is 00 (110
% by weight.

/l) After converting the aminated crosslinked polymer carrier into a PMLG supported crosslinked polymer in the same manner as in Example 6, reactions were carried out sequentially to convert the polyamino acid 11'l supported crosslinked polymer into 1('
P. The elemental analysis values of this product were as follows.

C: 76.90 (%) H near, 19 N: 5.99 Nitrogen-containing 11 or I), polyamino acid loading is 46.7
% and 1) determined.

', X, node-valve 18 chloromethylstyrene 1. Og, 80% divinylbenzene (crosslinking agent) 99 g, pensoyl peroxy 1 to 1, .
A solution prepared by adding 50 g of l-toluene and 100 g of n-dodecane as diluents to 67 g of polyhinyl alcohol 7.
5 g and 750 g of water. This mixture was dispersed and polymerized in the same manner as in Example 1, and a crosslinked polymer was synthesized and isolated. The surface area of this crosslinked polymer was 40 Or&/g, and the pore volume was 1.6+, mQ/g.

Next, in order to examine the surface structure of the crosslinked polymer particles, magnification was measured using a scanning electron microscope in the same manner as in Example 1.
Table 1 ■ Observation at 00,000x magnification (Figure 3) and particle cross section using Hitachi Transmission Electron Microscope T (-9000) at 2300x magnification.
Observations were made at 0x (Fig. 4) and 78,000x (Fig. 5). As a result, the thickness of the skin layer was 200 to 300 layers.

Furthermore, 12.0 g of the obtained crosslinked polymer was aminated in the same manner as in Example 1. The nitrogen content of this product was 0.040% by weight.

The obtained aminated cross-linked polymer carrier was converted into a PML G-supported cross-linked polymer in the same manner as in Example 6, and subsequent reactions were carried out to obtain a polyamino acid-supported cross-linked polymer. The elemental analysis values of this product were as follows.

C: 81.34 (%) H near, 63 N: 3.30 Based on the nitrogen content, the amount of polyamino acid supported is estimated to be 25% by weight.

- Glycerin monomethacrylate-1 to 40.0 g, 80% divinylhensen (Hv + > 60.0 g, pensoyl peroxyl; '1.67 g, n-octatool 150 g as a diluent) Calcium chloride 22
5g of polyvinyl alcohol, 7.5g of polyvinyl alcohol, and 750g of water. This mixture was stirred for 30 minutes at 1800 rpm and then heated at 80°C under nitrogen for 8 hours.
Suspension polymerization was carried out by stirring at -50 revolutions/minute. The resulting crosslinked polymer was collected by filtration, washed with deionized water, acetone, l-toluene, and methanol, and then dried under reduced pressure at about 80°C. Is the obtained crosslinked polymer a normal organic one? There were 11 truly spherical particles that were insoluble in the ff medium. The surface area of this crosslinked polymer is 278 m7/g and the pore volume is 1.30 m
It was Q/g. In addition, the absence of skin 1~ on the surface was confirmed by observation with a scanning electron microscope.
S)-N (1-phenylethyl]-methacrylamide 1
~8.0 g of 1,000 mash and 1~24.0 g of methyl ethyl kene
8.0 g of the porous polymer particles were added to the solution dissolved in the solution, and the porous polymer particles were left to stand at room temperature for 1 hour to impregnate the particles. Then, it was dispersed in 100.8 g of water. Further, 12.6 mff of a 0°5N-HN O3 aqueous solution was added to this polymer particle dispersion, and then heated to 50°C under nitrogen. Then 0.05N (NH4) 2Ce (No, ),
Aqueous solution], 2.6rnQ was added and left as is for 6 hours, 1-
Polymerization was carried out by stirring at 50 revolutions/minute. After that, ]0
Polymerization was stopped by adding 50 rnQ of a 4-1.degree.

The produced polymer was collected by filtration, washed successively with hot water, methanol, ascent and I. luene, and purified.

The infrared absorption spectrum of the produced polymer was 1650c.
Absorption derived from the optically active polymer Ami 1 ~ supported near +n-1 was measured at 1151. The elemental analysis values of this product were as follows.

C Near 5.54 (%) H Near, 65 N: 2.54 When divided from the nitrogen content, the supported amount of polyamide 1 ~ is 34
, 3% by weight.

In this case, the adsorbent produced in Example 1 was packed into a stainless steel column under the following conditions. A Shimadzu high-performance liquid chromatography pump LC8A was used as the packing pump. A large bunker manufactured by Gascro Industries was used. In addition, liquid feeding was performed using a constant flow method.

Column: inner diameter 7.6nwn x height 500 +nn+
Filling liquid: methanol Flow rate: 8 mQ/min Temperature: room temperature This adsorbent could be filled without any problem under the above-mentioned filling conditions, and no problem of compaction occurred. Next, using this packed column, Dan 1 on 5-isopropyl was subjected to chromatography.
Optical resolution of a racemic mixture of ~in (hereinafter referred to as IPH) was performed. A semi-preparative liquid chromatograph manufactured by Waters was used for liquid delivery and detection. The chromatography conditions are as follows.

Eluent: (1) (1~luene/diA-xane=
50150 (volume ratio) mixture) (2) (Toluene/isopropanol 80/20 (
(volume ratio)) (3) (+ toluene/dioxane - 75/25
(weight ratio)) Flow rate: ], , Om Q 7 minutes Temperature: 10'C, 20'C (Application example 9) Detection: Differential refractive index detector and optical rotation detector Sample amount =
Table 1 shows the optical resolution results of a racemic mixture of 1.0% J volume 200 μQIPH by Chroma 1 to Graphie.

The retention capacity ratio and numerator 6'lt coefficient in the table are calculated from the following formula:
I calculated 1.

Table 1 T.

T+: (+) -I I)H retention time■'-:
(-)-■pn retention time U-,,: The difference between the retention time of l-luene and It shows that the optical resolution increases as the size increases.

Application Examples 2 to 7 The adsorbents produced in Examples 2 to 4 and 6 to 8 were packed into a stainless steel column under the same conditions as in Application Example 1, and partitioned.

Table 1 shows the optical resolution results of the racemic mixture of DingPH.

Summer Endowment-8 - The adsorbent produced in Example 9 was packed into a stainless steel column under the same conditions as in Application Example 1, and partitioned.

Table 2 shows the results of optical resolution of the racemic mixture of 1.1'-binane 1--1.

Comparative Examples in Table 2 A cross-linked polymer was synthesized and isolated in the same manner as in Example 1 except that 00 g of n-1 to Detrimonium was used as a diluent.

The surface area of this crosslinked polymer was 222 m2/g, and the pore size was 0.53 mQ/g.

Further, by observing the surface with a scanning electron microscope at a magnification of 100,000 times, it was found that there was a skin J~ on the particle surface (FIG. 6). Furthermore, when the cross section of the particle was observed using a transmission electron microscope at a magnification of 23,000 times (Figure 7) and 78,000 times (Figure 8) in the same manner as in Example 8, it was found that there was a skin layer on the surface with a thickness of approximately 2,000 A. It turned out that.

Using this crosslinked polymer, a polyamino acid-supported crosslinked polymer was synthesized in the same manner as in Example].

The elemental analysis values of this product were as follows.

C: 83.81 (%) H: 8.07 N: 2.65 The amount of polyamino acids supported is estimated to be 20.1% by weight from the nitrogen-starved rats.

The adsorbent was loaded under the same conditions as in Application Example 1.Next, the racemic mixture of IPH was optically resolved in the same manner as in Application Example 1, and the results shown in Table 3 were obtained.

These results show that the adsorbent obtained using a carrier with a thick skin layer does not have high separation performance even when the amount of polyamino acid supported is 20% by weight.

Table 3 <Effects of the Invention> By making the carrier surface area and particle surface area of the present invention have only one skin or a very thin skin, high-performance adsorption separation is possible, and ion exchange, distribution, adsorption, hydrophobicity, affinity It can be used for molecular exclusion chromatography, optical resolution, biopolymers, etc., and can efficiently resolve many types of racemic mixtures, especially in high concentration racemic mixture solutions. can be processed. In addition, it is possible to treat a large amount of racemic mixture per unit volume of adsorbent, and it also has the effect of being able to separate and remove trace amounts of optically active substances mixed in optically active substances.

Therefore, the adsorbent of the present invention has a high separation ability and has a high optical resolution ability even when a racemic mixture is loaded highly,
This method has the excellent effect of making it possible to industrialize the optical resolution of racemic mixtures by chroma 1 photography.

- Electron micrograph showing the particle structure of the carrier.

Claims (1)

[Claims] (1) In an adsorbent in which a polymer capable of imparting adsorption ability is supported on a crosslinked polymer carrier, the carrier is a porous particle with a surface area of 1 to 2000 m^2/g, and An adsorbent characterized in that it is a crosslinked polymer having no skin layer or, if present, a skin layer of 300 Å or less.