JPS63225606A - Hydrophobic crosslinked copolymer - Google Patents

Abstract

PURPOSE:To provide the title polymer having specific physical properties, excellent in mechanical strength and chemical stability, and suitable for a packing for liquid chromatography or a membrane for separation, which polymer consists of specific monomer units having a hydrophobic group and specific crosslinking units. CONSTITUTION:A hydrophobic crosslinked polymer having such physical properties that the specific surface (SA) is: 30<=SA<=1,000ml/g and the solvent retention volume (SR) is: 0.2<=SR<=3.0ml/g consists of 100pts.wt. monomer unit derived from a monomer of the formula I wherein X is a group of the formula II, and Y is H or CH3 or a monomer of the formula I wherein X is a group of the formula III, and Y is the same as above or a monomer of the formula I wherein X is a group of formula IV, and Y is the same as above (R1 is a hydrophobic group having a hydrophobic fragmental constant of 1.5 or above) or 100pts.wt. constituent monomer unit derived from a mixture of other monomer unit and one of the above monomer units and 50pts.wt. or more crosslinking unit derived from a crosslinking agent having 2 or more ethylenic double bonds and/or acethylenic triple bonds.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention provides a hydrophobic crosslinked copolymer which has excellent mechanical strength and chemical stability and is suitable for use as a packing material for liquid chromatography or a separation membrane. Regarding merging.

[Prior Art] Since liquid chromatography can separate and analyze samples under mild conditions, it is particularly suitable for separating and analyzing biological substances, and is widely used in fields such as biochemistry, medicine, and pharmacy. Separation methods for liquid chromatography include adsorption, distribution, gel filtration, and ion exchange, among which reversed-phase chromatography, which utilizes hydrophobic distribution interactions between the sample and packing material, has excellent separation performance and is widely used. has been done.

So-called OD, which has an octadecylsilyl group immobilized on the surface of silica gel, is used as a packing material for reversed phase chromatography.
Examples include gels having a skeleton of silica gel, such as S. However, gels based on silica gel have the disadvantage of being chemically unstable, as silica gel has the property of dissolving under alkaline conditions.In addition, reverse-phase packing materials based on silica gel have the disadvantage of being chemically unstable. It may strongly adsorb chemical substances such as amines and basic peptides.This is thought to be caused by silanol present on the surface of silica gel.

On the other hand, synthetic polymer gels such as gels made of a methacrylate crosslinking agent such as ethylene glycol dimethacrylate, or gels made of a copolymer of the crosslinking agent and other methacrylate monomers are also used to create hydrophobic bonds between the sample and the gel. Used in chromatography that utilizes chemical interactions. In the case of these gels, hydrophobic interactions are thought to be mainly caused by the so-called matrix part forming the polymer backbone. In this case, ODS
It has superior chemical stability compared to gels that are isostatic liquefied gels, but conversely, its separation performance is often inferior to ODS. In many cases, when a highly hydrophobic component that is particularly strongly distributed is analyzed using the gel packed in a column, the elution band width of that component becomes significantly broad.

Furthermore, gels obtained by copolymerizing a vinyl ester having a long-chain alkyl group or a methacrylic ester with a crosslinking agent are also known (Japanese Patent Application Laid-open No. 58-61463). In this gel, hydrophobic interactions are thought to be mainly caused by long-chain alkyl groups, which are side chains of the matrix part that forms the gel skeleton, but as with the synthetic polymer gel described above, the hydrophobic interactions in the distributing components It has the drawbacks of wide elution band width and low separation performance.

[Problems to be Solved by the Invention] As mentioned above, gels in which alkyl groups are bonded to the isostatic silica gel surface, such as ODS, are often used as packing materials for reversed-phase chromatography; It is unstable and has poor durability, and also has the disadvantage of easily adsorbing basic compounds. Synthetic polymer-based gels have also been used, but the elution bands of highly hydrophobic components that are strongly distributed in these gels are significantly broadened, and their separation ability is often low. or,
Since the strength of the gel is low, it may have the disadvantage that the eluent cannot be flowed at a high flow rate. Therefore, as a result of intensive studies to overcome the above-mentioned drawbacks, the present inventors found that
A hydrophobic crosslinked copolymer with high separation ability and high strength was developed, and the present invention was accomplished.

Means for Solving Problem E] That is, the present invention is represented by the general formula CH2=CXY,
Monomers where X is 0CR1 and Y is a hydrogen atom・-(I>, X is C0R1, and Y is a hydrogen atom or a methyl group...(II> II X is 0CNHR1 and Y is a hydrogen atom The monomer ・-(I
I) A monomer unit derived from any of the monomers (wherein R1 is a hydrophobic group with a hydrophobic fragmental constant of 1.5 or more), or this monomer unit and other monomers Constituent monomer units derived from a mixture of units, for example, 10 to 100% by weight of monomer units derived from any of the monomers (I>, (II), (I[I) and this 100 parts by weight of constituent monomer units consisting of 0 to 90% by weight of monomer units other than 50 parts by weight or more, 600 parts by weight
A hydrophobic crosslinking unit consisting of a crosslinking unit derived from a crosslinking agent having two or more ethylenic double bonds and/or acetylenic triple bonds of 0 or less double bonds and having the physical properties of (^) and (B) below. Polymer (hereinafter referred to as crosslinked copolymer)
It is.

(A) Specific surface area (SA) 30≦SA≦1000yd10
r(B) Solvent retention! (SR> 0.2≦SR≦3.
The monomer units derived from the monomers represented by 0d10r(I), (II), and (III) are (I>, (IF
> or (nl) represents a structure formed by polymerization or copolymerization.

Alternatively, in (I>, (II>, and represents the structure formed by

The monomers represented by general formulas (I>, (II> and (III)) have a hydrophobic group with a hydrophoric fragmental constant of 1.5 or more. Written by Rekker (R, F, Rekker) [The Hydroforpic Fragmental Constant (
The Hydrophobic FraOntent
al constant) J Elsevier Scientific Publishing ] -(Elsevier
5CcientificPublishina Co.
> (published in 1977).

Hydrophobic groups with a fragmental constant of 1.5 or more include, for example, carbon atoms of 3 to 30
The following alkyl groups can be mentioned. The alkyl group preferably has 4 to 30 carbon atoms. Other examples of the hydrophobic group having a hydrophoric fragmental constant of 1.5 or more include a group represented by the following formula (IV).

[However, -R2- is -Cn H2O- (n = 0 to 30)
and X1 to X5 are hydrogen atoms, chlorine atoms, bromine atoms,
One to five types of iodine atoms or alkyl groups having 1 to 30 carbon atoms. ] These hydrophobic groups may be present alone or in combination of two or more.

The ratio of crosslinked units to constituent monomer units is important because it greatly influences the strength of the crosslinked copolymer and the distribution characteristics in chromatography using the crosslinked copolymer.

In the present invention, the crosslinking unit is present in an amount of 50 parts by weight or more and 6000 parts by weight or less per 100 parts by weight of the constituent monomer units.

If the crosslinking unit is less than 50 parts by weight, the strength will be insufficient, which may cause problems in use.

For example, when used in high-performance liquid chromatography, it is preferable to fill a column in the form of small particles of 10 μm or less. In that case, inconveniences may occur, such as the eluent not being able to flow at a high flow rate or sometimes not flowing. The copolymer is hard, and when used as a packing material for liquid chromatography, for example, when packed in a column, the eluent can be passed at a high flow rate and rapid analysis is possible.

In addition, the ratio of crosslinking units to the constituent monomer units is 6000
If the amount exceeds 1 part by weight, the amount of hydrophobic groups in the crosslinked copolymer of the present invention is too small. For example, when the crosslinked copolymer is used as a packing material for liquid chromatography, There is a possibility that the interaction is not sufficient and the separation is insufficient.

The proportion of the crosslinking unit is preferably 80 parts by weight or more and 6000 parts by weight or less, more preferably 90 parts by weight or more and 6000 parts by weight or less, per 1000 parts by weight of the constituent monomers.

In the present invention, the crosslinking unit is an ethylenic double bond and/or
Alternatively, a crosslinking unit derived from a crosslinking agent having two or more acetylenic triple bonds can be mentioned. A crosslinking unit derived from a crosslinking agent having two or more ethylenic double bonds and/or acetylenic triple bonds refers to a structure formed by the crosslinking agent through polymerization or copolymerization.

Examples of crosslinking agents include polymethacrylates such as mono- and polyethylene glycol dimethacrylate and trimethylolpropane trimethacrylate, polyunsaturated alcohol esters such as divinyl adipate and divinyl phthalate, polyunsaturated ethers such as divinyl ether, and triallyl cyanide. Examples include crosslinking agents having a triazine ring such as nurate and triallyl isocyanurate, and preferred examples include triallyl cyanurate and triallyl in cyanurate.

Examples of monomer units other than (I>, (II) and (III) include units derived from vinyl acetate, units derived from methyl methacrylate, and the like.

Examples of methods for determining the amount of each unit in the crosslinked copolymer include the following method. For example, when a crosslinked copolymer is composed of a unit derived from a monomer (I>) and a crosslinked unit, the amount of carboxylic acid liberated by hydrolysis of the crosslinked copolymer, The amount can be determined from the amount of hydroxyl groups in the copolymer obtained and the change in weight of the hydrophobic crosslinked copolymer before and after hydrolysis.

Another method is a method of calculating from the NMR spectrum of the crosslinked copolymer.

The solvent retention amount (SR) of the crosslinked copolymer of the present invention is 0.2 to
It is in the range of 3.0d10r. SR is the amount of acetonitrile that can be contained in the pores of a crosslinked copolymer when the crosslinked copolymer is brought into equilibrium with acetonitrile, expressed as a value per dry weight of the crosslinked copolymer. In other words, S.R.
is a guideline for the weight within the crosslinked copolymer.

As the SR increases, the weight of the portion forming the skeleton per unit volume of the crosslinked copolymer, that is, the weight of the crosslinked copolymer itself, decreases relatively in an organic solvent or a mixed solvent of an organic solvent and water. Therefore, if the SR is too large, the mechanical strength of the crosslinked copolymer will decrease in an organic solvent or a mixed solvent of an organic solvent and water.

If the SR is too small, when the crosslinked copolymer is used as a packing material for liquid chromatography, the effective weight for separation will decrease, resulting in a decrease in separation ability. Therefore, it is preferable that the SR be within an appropriate range. SR is a crosslinked copolymer that has been sufficiently equilibrated with acetonitrile, is centrifuged to remove acetonitrile adhering to the surface of the crosslinked copolymer, and its weight (Wl) is measured. The weight after drying (W2) can be determined using the following formula.

Wl-W2 1 WR-yy 2X- (However, S is the specific gravity of acetonitrile. In the present invention, it was calculated using the specific gravity at 15 ° C.) When obtaining a crosslinked copolymer by polymerization, a mixture of monomers and crosslinking agent The weight can be adjusted by adding one or more organic solvents that dissolve. Generally speaking, the weight increases as the amount of organic solvent increases. In the present invention, the amount of organic solvent is 20 parts by weight per 100 parts by weight of the mixture of monomers and crosslinking agent.
More than 300 parts by weight is used. The weight can also be adjusted by adding soluble linear polymers or rubbers to the monomer and crosslinking agent mixture. In the present invention, 20 parts by weight or less is used per 100 parts by weight of the mixture of monomer and crosslinking agent.

The crosslinked copolymer of the present invention has a specific surface area of 30 to 1000 TIt/gr per unit weight of the crosslinked copolymer in a dry state. Since the crosslinked copolymer of the present invention has a high specific surface area,
For example, when a column is packed and a sample is analyzed, the crosslinked copolymer and the sample contact each other with high efficiency, and adsorption and desorption occur quickly. Therefore, the elution band width is narrow and samples can be separated sufficiently. Specific surface area (SA) is preferably 50
~1000 butts 10r.

There are various methods for measuring the specific surface area, but in the present invention, it was determined by the most common BET method using nitrogen gas. In addition, the sample used for specific surface area measurement must be sufficiently dry. In the present invention, after equilibrating the crosslinked copolymer with acetone, the specific surface area was measured after drying under reduced pressure at 60°C.

The specific surface area can be controlled by varying the ratio of monomer to crosslinker and the ratio of organic solvent to the mixture of monomer and crosslinker.

Generally, the surface increases as the ratio of crosslinker to monomer increases. In the present invention, 50 parts by weight or more of the crosslinking agent is used per 100 parts by weight of the monomer. Further, the amount of the organic solvent used is as described above.

The shape of the crosslinked copolymer of the present invention is not particularly limited, and can take any shape such as granules, membranes, threads, and lumps depending on the method of use. When used as a packing material for liquid chromatography, it is preferably granular or spherical. In that case, the particle size is not particularly limited, but the weight average particle size is usually 1 to 5.
It is in the range of 00 μm. When used as a packing material for high performance liquid chromatography, it is preferably in the range of 1 to 20 μm, and more preferably in the range of 1 to 15 μm for practical purposes.

Next, an example of a method for producing the crosslinked copolymer of the present invention will be shown. The hydrophobic crosslinked copolymer of the present invention is, for example, (I> or (II)
and 100 to 100 parts by weight of a monomer copolymerizable with (I> and (I[>) and 50 parts by weight or more. 6000
It can be obtained by copolymerizing part by weight or less of the constituent monomers and a crosslinking agent having two or more copolymerizable ethylenic double bonds and/or acetylenic double bonds.

Examples of the monomer represented by (I) include vinyl octoate, vinyl myristate, vinyl valmitate, and vinyl stearate. (Examples of the monomer represented by I[> include octyl methacrylate, lauroyl methacrylate, stearyl methacrylate, etc.) Examples of the crosslinking agent include the aforementioned crosslinking agents.

In the above copolymerization, methods such as suspension polymerization and bulk polymerization can be used, but suspension polymerization is preferred when obtaining a filler for liquid chromatography. In addition, in the above copolymerization, the surface area, weight, pore diameter, etc. of the resulting copolymer can be adjusted by adding one or more organic solvents that dissolve the mixture of monomers and crosslinking agent (hereinafter referred to as monomer mixture). can do.

Specifically, the organic solvent for dissolving the monomer mixture is as follows:
Aromatic hydrocarbons such as toluene and xylene, heptane,
Aliphatic hydrocarbons such as octane, cyclohexadi, decalin, etc., fatty acid esters such as n-butyl acetate, isobutyl acetate, n-hexyl acetate, dioctyl adipate, etc., aromas such as dimethyl phthalate, dioctyl phthalate, methyl benzoate, etc. Examples include alcohols such as group esters, butanol, heptatool, and octatool.

When carrying out suspension polymerization, an organic solvent that is difficult to dissolve in water is preferred.

The amount of the organic solvent is preferably 20 parts by weight or more and 300 parts by weight or less per 100 parts by weight of the monomer mixture.

Linear polymers or rubbers that dissolve in the monomer mixture may be added to the monomer mixture to control the weight or pore size distribution of the cross-linked copolymer or to increase the flexibility of the cross-linked copolymer. good.

Linear polymers and rubbers that dissolve in the monomer mixture include, for example, polyvinyl acetate, polystyrene, chloroprene rubber,
It refers to butadiene rubber, etc., and is used in an amount of 20 parts by weight or less, preferably 10 parts by weight or less, per 100 parts by weight of the monomer.

The type and amount of the initiator used during polymerization can be arbitrarily selected depending on the polymerization method. In normal suspension polymerization and bulk polymerization, common radical polymerization initiators are used, such as 2,2°-azobisinbutyronitrile, 2,2°-azobis-(2
, 4-dimethylvaleronitrile) and peroxide initiators such as benzoyl peroxide and lauroyl peroxide can be used.

When performing suspension polymerization, it is recommended to add a commonly used organic polymer suspension stabilizer such as polyvinyl alcohol or methyl cellulose to the aqueous phase, and if necessary, add an H buffer such as sodium phosphate. may be used together. By changing the type and amount of the suspension stabilizer or the stirring speed, the particle size of the particulate copolymer obtained by polymerization can be changed. After removing the linear polymer, residual monomer or organic solvent from the granular polymer obtained by polymerization, it can be used as a filler after being classified if necessary.

Other methods for producing crosslinked copolymers include the following method. That is, a method of introducing a hydrophobic group having a hydrophobic fragmental constant of 1.5 or more into a crosslinked copolymer having a hydrophobic group or a crosslinked copolymer having no hydrophobic group by covalent bonding. can be mentioned. The following method can be mentioned as a specific example of the above method.

For example, a crosslinked copolymer is obtained by copolymerizing a crosslinking agent such as the one described above with vinyl acetate, vinyl propionate, etc., and then the crosslinked copolymer is saponified or transesterified to introduce a hydroxyl group. It can be obtained by reacting acid chloride, isocyanate, etc. When acid chloride is reacted, a crosslinked copolymer having monomer units derived from monomer (I>) can be obtained. When isocyanate is reacted, monomer (III) can be obtained. A crosslinked copolymer having monomer units derived from the above can be obtained.

Examples of acid chlorides include butanoic acid chloride, octanoic acid chloride, stearic acid chloride, benzoyl chloride, and the like.

Examples of isocyanates include octadecyl isocyanate and phenyl isocyanate.

In this case, the surface area, weight, pore diameter, etc. of the crosslinked copolymer can be adjusted by adding an organic solvent, linear polymer, or rubber during polymerization. The amounts and types of organic solvent, linear polymer, and rubber are the same as described above. Furthermore, the same polymerization initiators used during polymerization and suspension stabilizers used during suspension polymerization as described above can be used.

[Example] Hereinafter, the content of the present invention will be specifically explained with reference to Examples.

Town Example 1 Production of polymer Vinyl stearate 10 gr triallylisocyanurate 545 gr Butyl acetate
A homogeneous mixture of 390gr and 310g of water in which a small amount of polyvinyl alcohol and sodium phosphate were dissolved.
0111 was placed in a 10J2 three-necked flask equipped with a reflux condenser, a nitrogen inlet tube, and a stirrer and thoroughly stirred, and then polymerization was carried out at 80°C for 20 hours while stirring under a nitrogen stream,
A granular hydrophobic crosslinked polymer (gel) was obtained. The gel was filtered, washed with water, extracted with acetone, and then classified to obtain a gel with a weight average particle size of 8.8 .mu.m. The specific surface area (SA
>40m/gr, solvent retention! (SR) is 1.057
/gr.

Polymer Test The gel was packed into a stainless steel column with an inner diameter of 6 mm and a length of 150111 m, and ethylene glycol and dodecanol were analyzed using an 80% methanol aqueous solution as the eluent at a flow rate of tm+/min. was 3.3 ml, and the number of theoretical plates (N) was 9,000. In addition, the elution volume of dodecanol is 26.3 ml,
The number of theoretical plates (N>) was 8300. The temperature of the column constant temperature bath at the time of measurement was 30°C, and the detector was a differential refractive detector 5E-51 (
(manufactured by Showa Denko n) was used. Also, the calculation method for the number of theoretical plates is “
According to the High Performance Liquid Chromatography Handbook (Maruzen), edited by the Kanto Branch of the Japanese Society for Analytical Chemistry.From now on, compounds such as dodecanol, which is highly hydrophobic and strongly partitions, have almost the same number of theoretical plates as ethylene glycol, which is small and does not partition very well. Furthermore, various peptides were analyzed using the packed column under the following conditions, and the results shown in Table 1 were obtained.

Analysis conditions Eluent Initial solution 0.05% TFA/)1eCN-7
5/25 Final solution 0.05% TFA/MeCN =
10/90 Linear gradient for 40 minutes from initial solution to final solution Flow rate: 0.7 ml/min Column constant temperature bath temperature: 30°C Eluent liquid delivery system: Two HPLC pumps 880 Pu were used in combination with a system controller 801-3C ( Both manufactured by JASCO Corporation) Detection LJV-280nll AUFS 0.32
Detector UVIDEC100-IV (manufactured by JASCO Corporation) Data processing device 5IC-7000B (manufactured by System Instruments) Sample loading amount 40 ggr Table 1 As shown in Table 1, various peptides were recovered at high recovery rates.

Example 2 Production of polymer Vinyl acetate 100g triallylisocyanurate 180g rButyl acetate
190 l r2.2° Water in which a homogeneous mixture of 7 gr of azobisisobutyronitrile and a small amount of polyvinyl alcohol and sodium phosphate were dissolved 1600 l
After thorough stirring, polymerization was carried out at 60°C for 16 hours with stirring under a nitrogen stream to obtain a granular polymer. Obtained.

The granular polymer was filtered, washed with water, extracted with acetone, and further dried. Next, the gel was stirred together with water 31 in which 10 g of caustic soda was dissolved in a five-pronged three-neck flask equipped with a reflux condenser, a nitrogen inlet tube, and a stirrer at 15° C. under a nitrogen stream for 20 hours to dissolve the granular polymer. After the reaction, filtration,
Washed with water and further dried. When the density of hydroxyl groups in the polymer obtained by saponification was determined, it was 0.8n+eq/gr.
It was gel. The method for measuring the density of hydroxyl groups is JP-A-57-
The method described in Japanese Patent No. 108662 was used.

Next, the polymer was placed in a 10Q three-necked flask equipped with a reflux condenser, a nitrogen inlet tube, and a stirrer together with 3ffi of pyridine in which 200 g of stearic acid chloride was dissolved, and the mixture was heated at 40° C. for 20 hours with stirring under a nitrogen stream. The polymer was reacted with stearic acid chloride. After the reaction was completed, it was filtered and washed with chloroform and acetone to obtain a hydrophobic crosslinked copolymer (gel). The weight average particle size of the obtained gel was 9.
It was a 1μ seaweed. Also, the hydroxyl group density of the gel is omeq/g
It was r. Calculated from the charging composition during polymerization, the water density after saponification, and the amount of introduced stearoyl groups,
The gel contained 45.1 parts by weight of a monomer unit having a hydrophobic group (i.e. vinyl stearate unit) and 5 parts by weight of a monomer unit other than the monomer unit having a hydrophobic group (i.e. vinyl acetate unit).
4.9 parts by weight and 120.1 parts by weight of triallyl isocyanurate units, which are crosslinking units.

The gel had a specific surface area (SA) of 160 Td/F and a solvent retention capacity (SR) of 0.52 dlOr.

Next, the gel was prepared in the same manner as in Example 1, with an inner diameter of 6111 and a length of 15.
When a 0U stainless steel column was packed and an 80% methanol aqueous solution was passed through the column at a flow rate of 211/sin for 16 hours, the pressure difference between the column inlet and outlet was constant at 40 kg/cm2. This shows that the gel is sufficiently hard.

Furthermore, when ethylene glycol and dodecanol were analyzed using a column filled with the gel under the same conditions as in Example 1, the elution volume of ethylene glycol was 2.6 ml.
The number of theoretical plates for the elution peak (N> is 4200, the elution volume of dodecanol is 16.5n+1, the number of theoretical plates for the elution peak (
N) was 4300.

Example 3 Production of polymer Vinyl acetate ioogr triallyl isocyanurate 145Qr Butyl acetate
170Qr2.2°Azobisisobutyronitrile 6
Suspension polymerization was carried out in the same manner as in Example 2, except that a homogeneous mixture of gr was used to obtain a granular polymer. After washing and drying the granular polymer in the same manner as in Example 2, it was saponified under the same conditions as in Example 2 except that 2.5 g of water in which 6 g of caustic soda was dissolved was used, and the density of hydroxyl groups was 0.4 + 1 eq.
A polymer of /l; lr was obtained. Stearic acid chloride 9
01) The polymer and stearic acid chloride were reacted in the same manner as in Example 2 except that r was used.

After the reaction, the mixture was treated in the same manner as in Example 2 to obtain a hydrophobic crosslinked copolymer (gel). The weight average particle size of the gel is 8.5μ
-It was. In addition, the hydroxyl group density of the gel is Omeq/gr.
Met. Charge composition during polymerization, hydroxyl group density after saponification,
Calculated from the amount of stearyl groups introduced, the gel contains monomer units having hydrophobic groups (i.e., vinyl stearate units>23.8 parts by weight, monomer units other than monomer units having hydrophobic groups). body units (i.e. vinyl acetate units >76
．． 2 parts by weight, and 120.0 parts by weight of triallylisocyanurate units, which are crosslinking units.

The specific surface area of the gel is 270 dlQr and holds 1 solvent! (S
R) was 0.8d10r.

Polymer Test The gel was prepared in the same manner as in Example 1 with an inner diameter of 61111. length 150
When an 80% methanol aqueous solution was passed through the column at a flow rate of 211/ff1 inch for 16 hours, the pressure difference between the column inlet and outlet was constant at 42 kmcm2.

Furthermore, when ethylene glycol and dodecanol were analyzed using a column filled with the gel under the same conditions as in Example 1, the elution volume of ethylene glycol was 2.71, the number of theoretical plates of the elution peak (N> was 4300, and the elution volume of dodecanol was 2.71, The elution volume was 18.11+, and the number of theoretical plates (N) of the elution peak was 4400.

Comparative Example 1 Production of polymer Vinyl acetate 100Qr triallyl isocyanurate 43. OQr n-butyl acetate
30gr azobisisobutyronitrile 3.6
Suspension polymerization was carried out in the same manner as in Example 2, except that a homogeneous mixture of gr was used to obtain a granular polymer. The granular polymer was washed and dried in the same manner as in Example 2, and then saponified under the same conditions as in Example 2, except that 1.5 g of water in which 9.5 g of caustic soda was dissolved was used, so that the density of hydroxyl groups was 1.5 g. 5me
A polymer of q/gr was obtained. Stearic acid chloride 20
0gr, pyridine 1.5. The polymer and stearic acid chloride were reacted in the same manner as in Example 2 except that Q was used. After the reaction, a gel was obtained by processing in the same manner as in Example 2. The weight average particle size of the gel was 9.5 μm. or,
The hydroxyl group density of the gel was OmeQ/g. Calculated from the charging composition during polymerization, the hydroxyl group density after saponification, and the amount of introduced stearoyl groups, the gel contains monomer units having hydrophobic groups (i.e., vinyl stearate units > 42
．． " ing.

The gel had a specific surface area (SA> of 1 m10r and a solvent retention capacity (SR) of 0.18 m/(llr).

Polymer Test The gel was prepared in the same manner as in Example 1 with an inner diameter of 681111. length 15
When ethylene glycol and dodecanol were analyzed under the same conditions as in Example 1 using a 0 mm stainless steel column, the elution volume of ethylene glycol was 2.8+n.
l, the number of theoretical plates (N>) for the elution peak was 4200.

On the other hand, the elution capacity of dodecanol, which is an aqueous substance, is 7.1
ml, which was smaller than that in the example. Further, the theoretical plate number (N) of dodecanol was 1200, which was significantly lower than that of ethylene glycol.

[Effects of the Invention] As explained above, the crosslinked copolymer of the present invention is highly crosslinked and hard, so when it is packed in a column and used as a packing material for liquid chromatography, for example, the eluent is It can be flowed at a high flow rate, allowing rapid analysis. In addition, fillers made of silica gel and having hydrophobic groups such as octa-decyl groups bonded to the surface are chemically unstable as described above and may adsorb basic substances, but the crosslinking material of the present invention Polymers are chemically stable and less likely to adsorb basic substances.

Further, the crosslinked copolymer of the present invention has pores necessary for separation, maintains strength, and is preferable as a packing material for liquid chromatography. Synthetic polymer-based fillers often have insufficient separation performance, and especially when analyzing components to be distributed, the elution band width of that component becomes wide.
That is, the component often has a drawback of having a low theoretical plate number.

Since the crosslinked copolymer of the present invention has a large specific surface area,
The contact efficiency with the sample is good, the adsorption and desorption of the sample is carried out quickly, and the number of theoretical plates is high even for components that are strongly distributed, and good separation can be obtained.

The polymer gel described in JP-A-58-61463 also has a long-chain alkyl group, and is used for separation by utilizing the hydrophobic interaction between the alkyl group and the sample. However, the gel described in this publication is primarily intended for use in industrial separation, and does not describe the requirements necessary for use as a packing material for high-performance liquid chromatography that requires high-performance liquid separation.

The crosslinked copolymer of the present invention is hard, has an appropriate amount of hydrophobic groups, an appropriate pore space, and has an appropriate surface area, so it is a packing material for liquid chromatography that separates using hydrophobic interactions. It is particularly suitable as a packing material for high performance liquid chromatography which requires a high degree of separation.

Claims (1)

[Claims] (1) A monomer represented by the general formula CH_2=CXY, where X is a ▲mathematical formula, chemical formula, table, etc.▼, Y is a hydrogen atom or a methyl group... (I), X is a ▲mathematical formula, There are chemical formulas, tables, etc. ▼, Monomers where Y is a hydrogen atom or methyl group... (II) Monomers where X is ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼, Y is a hydrogen atom or methyl group (III) (However, R_1 is a hydrophobic group with a hydrophobic flag tantalum constant of 1.5 or more) or a monomer unit derived from this monomer and this monomer unit. A crosslinking agent having 100 parts by weight of constituent monomer units derived from a mixture of monomer units other than monomer units, and 50 parts by weight or more of two or more ethylenic double bonds and/or acetylenic triple bonds. A hydrophobic crosslinked copolymer comprising a crosslinking unit derived from a hydrophobic crosslinked copolymer having the following physical properties (A) and (B). (A) Specific surface area (SA) 30≦SA≦1000m^2/
gr (B) Solvent retention amount (SR) 0.2≦SR≦3.0m
l/gr (2) the hydrophobic group is an alkyl group having 3 to 30 carbon atoms,
and the hydrophobic crosslinked copolymer according to claim (1), which is one or more selected from the following formula (IV). ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(IV) [However, -R_2- is -C_nH_2n- (n=0 to 30
), and X_1 to X_5 are one or more of a hydrogen atom, a chlorine atom, a bromine atom, an iodine atom, or an alkyl group having 1 to 30 carbon atoms. ]