JPS58118803A - Production of porous crosslinked polymer particle - Google Patents

Abstract

PURPOSE:To produce the titled particles useful as a GPC packing material or the like, by suspending a nonreactive organic solvent solution of a resin containing a specified silicon containing group in an aqueous medium to thereby effect the hydrolysis and condensation of the silicon-containing groups. CONSTITUTION:Porous crosslinked polymer particles are produced by suspending a nonreactive organic solvent solution of a resin containing a group of the formula (wherein Y is a hydrolyzable group, R is an inert monovalent organic group and n is 1-3) in an aqueous medium to thereby effect the hydrolysis and condensation of the groups of the above formula. According to this production process, it is possible to obtain new porous crosslinked polymer particles. In addition, especially when hydrophilic porous crosslinked polymer particles are desired, pore control, crosslinking and formation of spherical particles can be carried out efficiently. The porous crosslinked polymer particles can be used as a GPC packing material and, when modified, it can be used also as a packing material for chromatography of different types.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing porous crosslinked polymer particles.

Conventionally, porous crosslinked polymer particles include: (1) a copolymer gel of styrene and the crosslinkable monomer divinylpenze; (2) a copolymer of acrylic acid ester monomer or vinyl acetate and the crosslinkable monomer alkylene glycol divinyl ester; Gel, ■Polyvinyl alcohol and shrimp chlorhydrinteil
Copolymer gels of acrylic acid ester monomers or acrylamide and the crosslinkable monomer methylenebisacrylamide are known. Especially as a hydrophilic gel that is insoluble in water.

The aforementioned gels (1) to (4) or their partial hydrolysates are known, and are designed to contain hydrophilic groups such as hydroxyl groups and amide groups.

The first object of the present invention is to provide novel porous crosslinked polymer particles different from such known porous crosslinked polymer particles.
The purpose of

In addition, hydrophilic gel is mainly used as a separation agent for rapid separation and analysis of water-soluble substances, i.e., high performance liquid chromatography (HLC).
Since the gel is used as a filler, it must be hydrophilic and at the same time have excellent pressure resistance. Furthermore, when separating and analyzing molecules by size (GPC), there is no adsorption.

It is desirable that the separation ability is excellent and the molecular weight range that can be analyzed is wide. For this purpose, it is necessary to create a spherical microgel that is insoluble in water but hydrophilic, and has appropriately controlled crosslinking density and pore size distribution.

Conventionally, in order to produce a hydrophilic gel, there have been two methods: copolymerizing a polymerizable monomer having a group that imparts hydrophilicity to the gel, polymerizing an oil-soluble polymerizable monomer, and hydrating the resulting intermediate or final product. There are methods such as making it hydrophilic by decomposition*.

In the first method, since the polymerizable monomer having a group that imparts hydrophilicity to the gel is water-soluble, aqueous suspension polymerization cannot be performed and non-aqueous suspension polymerization is required. Since the dispersion stability of cloudy particles is poor, it is difficult to obtain porous crosslinked polymer particles with a desired particle size and to obtain spherical particles.

In the second method, since an aqueous suspension polymerization method can be employed, synthesis is relatively easy.

In order to make the produced polymer or gel hydrophilic, styrene-divinylbenzene polymer particles are treated with plasma or treated with sulfone groups.

It is often necessary to introduce a group having ion exchange properties such as a tertiary amino group, which not only complicates the process but also often limits the ability to make it hydrophilic.

A second object of the present invention is to solve these problems and provide a novel method for producing porous crosslinked polymer particles.

According to the present invention, non-hydrophilic porous crosslinked polymer particles and hydrophilic porous crosslinked polymer particles containing a large amount of hydrophilic groups can be produced.

9 This invention relates to general formula (I) -S jYnRs-n (1) (However, in formula 9, Y is a hydrolyzable group.

R is an inert monovalent organic group, and n is an integer of 1 to 3. ) The present invention relates to a method for producing porous crosslinked polymer particles, which is characterized by carrying out a hydrolysis and condensation reaction of a group represented by the following.

In the general formula TI) in the present invention, the group Y is a hydrolyzable group such as a flukoxy group having 1 to 6 carbon atoms, an acyloxy group having 1 to 6 carbon atoms, an oximo group having 1 to 14 carbon atoms, etc.2 For example, methoxy Base.

Alkoxy groups such as ethoxy and butoxy groups.

Acyloxy, -0N=C(CHI
b, -0N=C(CHs)CsHs, -0N
A group that generates a hydroxyl group by hydrolysis such as an oximo group such as -C(C1Hi)x, -NHCHs, -NHC
! Hl, and an alkylamino or arylamino group such as NH (CmHs). Substituent Y is n
If it is 2t or 3, it may be the same, or it may be stationery. The group R is an inert monovalent organic group, preferably a hydrocarbon group having 1 to 18 carbon atoms, such as methyl,
Ethyl, propyl, butyl.

It can be obtained by a method such as an alkyl group such as a tetradecyl or octadecyl group, an aryl group such as a phenyl group, a benzyl group, or a tolyl group, an aralkyl group, or an alkaryl group.

(1) General formula (I) XSiYnRs-n (set (where, XF
i is a group having a copolymerizable double bond; Y, R and n are the same as in general formula (I); ) is polymerized, or the vinyl monomer and another vinyl monomer are copolymerized. Here, as the nine-polymerization method,
Bulk polymerization, solution polymerization, etc. are optional.

The above group X is a group having a copolymerizable double bond, but 9
For example, vinyl group. Alkenyl groups such as allyl group and butyl group, cycloalkenyl groups such as cyclohexenyl group, cyclopentagenyl group, and cyclohexagenyl group, unsaturated acyloxyalkyl group such as γ-methacryloxyglobyl group, γ -Unsaturated acyloxyalkoxy group such as methacryloxyethylpropyl ether group, CH*=C(CHs
)COO(CHz)xOcHzCH(OH)C
HzO(CHz)s-, etc. Among these, the most preferred are unsaturated acyloxyalkyl groups such as γ-methacryloxypropyl group or unsaturated acyloxyalkoxy groups such as γ-methacryloxyethylpropyl ether group.

A particularly preferable compound as a vinyl monomer represented by the above general formula (group) is the general formula [)% formula% (1) (wherein X' is an alkenyl group, an unsaturated acylalkyl group, a Y company alkyl group, group or aryl group).
Among these compounds, the most preferred one is r-methacryloxypropyltrimethoxysilane.

In addition, suitable polymerization initiators include benzoyl peroxide,
Dichlorobenzoyl peroxide, dicumyl peroxide, di-tert-butyl peroxide, 2,5-cy(peroxybenzoate)hexyne-3,1,3-bis(tert-butylberoxyisoglobil)benzene, lauroyl peroxide , tert-butylberacetate.

2,5-dimethyl-25-di(tert-butylperoxy)
Organic peroxides such as hexyne-3,45-dimethyl-2,5-di(tert-butylperoxy)hexane and tert-butyl perbenzoate, methyl ethyl ketone peroxide, methyl cyclohexanone peroxide.

There are azo compounds such as azobis-imbutyronitrile and dimethylazodiisobutyrate, and one or more of these may be used. The amount to be used is determined by the type of vinyl monomer #; It is used in an amount of 0.1 to 4.0% by weight based on Lingiso=diy Banshun.

As other vinyl monomers, acrylic acid monomers and other vinyl monomers can be used.

Acrylic acid is an acrylic acid monomer.

There are methacrylic acid and their derivatives.

Examples of derivatives include alkyl acrylates such as methyl acrylate, ethyl acrylate, butyl acrylate, and lauryl acrylate.

Methyl methacrylate, ethyl methacrylate, butyl methacrylate, alkyl methacrylates such as lauryl methacrylate, 2-hydroxyethyl acrylate-I.
, 2-hydroxypropyl acrylate, hydroxyalkyl acrylate such as hydroxypropyl acrylate, acrylic acid monoester of polyhydric alcohol such as trimethylolpropane monoacrylate, trimethylolethane monoacrylate, polyethylene glycol monoacrylate, polypropylene glycol monoacrylate, etc. Acrylic acid monoester of alkylene glycol, 2-hydroxyethyl methacrylate. Hydroxy alkyl acrylates such as 2-hydroxypropyl methacrylate and hydroxybutyl methacrylate), methacrylic acid monoesters of polyhydric alcohols such as trimethylolpropane monomethacrylate and trimethylolethane monomethacrylate, polyethylene glycol monoacrylate, polypropylene glycol monomethacrylate, etc. methacrylic acid monoester of polyalkylene glycol, dialkylaminoalkyl acrylate such as diethylaminoethyl acrylate, dialkylaminoalkyl methacrylate such as diethylaminoethyl methacrylate, acrylamide, methacrylamide, glycidyl acrylate.

Glycidyl methacrylate, etc. Furthermore, the above-mentioned hydroxyalkyl acrylates, hydroxyalkyl methacrylates, acrylic acid monoesters of polyhydric alcohols, methacrylic acid monoesters of polyhydric alcohols, acrylic acid monoesters of polyalkylene glycols, and methacrylic acid monoesters of polyalkylene glycols. Examples include methyl ether, ethyl ether, clobyl ether, butyl ether, pentyl ether, and cape alkyl ether.

As vinyl monomers other than acrylic acid monomers that can be copolymerized with vinyl monomers represented by the general formula (group),
Maleic acid, hexamaric acid, itaconic acid and their acrylic or methacrylic acid derivatives and similar derivatives, vinylpyridine, vinylpyrrolidone, vinyl acetate, acrylonitrile, styrene or chlorostyrene, vinyltoluene, alpha-methylstyrene styrene There are derivatives etc.

Divinylate and ethylene glycol acrylate as part of the above vinyl monomers.

Trimethylolpropane trimethacrylate.

A crosslinkable monomer such as trimethylolpropane acrylate may be used in an amount of 2 weight or less based on the total amount. If there is too much crosslinking monomer, it will dissolve in the organic solvent and K<.

In order to make the target porous crosslinked polymer particles hydrophilic, hydroxyl groups,
It is preferable to use a monomer having a carboxyl group, an and group, an alkoxy group, etc., a monomer such as vinylpyridine, vinylpyrrolidone, vinyl acetate, etc. in an amount of 10 moles or more.

When solution polymerization is carried out in the above, there is no limit to the percentage as long as an organic solvent in which the vinyl monomer and the product polymer are soluble is selected.

For example, in the case of the reaction between an acrylic acid monomer and γ-methacryloxypropyltrimethoxysilane, methyl ethyl ketone or the like can be used. Although the polymer synthesized in this way is hydrophilic, it is insoluble in water, so it is suspended in an aqueous medium in the subsequent steps to carry out the hydrolysis and condensation reactions of the groups represented by the general formula It is possible.

(2) Vinyl polymers with functional groups such as carboxyl, hydroxyl, amide, and epoxy groups (e.g., styrene-maleic anhydride copolymer, butyl acrylate-methacrylic acid copolymer, glycidyl methacrylate-β hydroxy methacrylate) copolymers, copolymers such as butyl methacrylate-acrylamide copolymers, and other vinyl monomers mentioned above. ) K general formula (1/) X” S 1YnRs-n [) (where,
X# is a group reactive with a functional group such as a carboxyl group, a hydroxyl group, an amide group, an epoxy group, etc., and Y, R and n are the same as in general formula (1). ) is subjected to a graft reaction.

In addition, in order to make the target porous crosslinked polymer particles hydrophilic, the above-exemplified copolymer or polymer should be used as a component! ! Contains at least 10 moles of a polymerizable monomer having a group imparting aqueous properties, excluding the amount to be reacted with the general formula (ii).

The grafting point is 9, for example for an epoxy group.

For amino groups such as carboxyl groups and amine 7 groups, examples include epoxy groups and carboxyl groups.

Examples of the compound represented by the general formula y) include γ-
Chrysidoxyglobil trimethoxy N-β (aminoethyl) γ-7 Minoprobil trimethoxysila 7 (HsNCl
lMHCsHsS i (OCHs)s ), r
-Aminopropyltriethoxysilane (H2NC5Hs8i (OCmHi)s) and the like.

To illustrate the reaction method, for example, γ-glycidoxypropyltrimethoxysilane is added to a high boiling point solvent solution of a butyl acrylate-methacrylic acid copolymer such as toluene or xylene, and the mixture is heated to 80° C. or higher and stirred.

In the resin having a group represented by the general formula (1) obtained as described above, preferably the general formula (
The group represented by 1) is contained in a silicon moiety bonded to a weight ratio of 1.0 to IL3. General formula (1) in the resin
) If the number of groups represented by formula (1) is too small, crosslinking will be insufficient and the pressure resistance will be poor; if it is too large, it will be difficult to introduce the group represented by general formula (1). From the viewpoint of pressure resistance, it is preferably L4 weight - (Si portion) or more. In addition, in order to use the finally obtained porous crosslinked polymer particles as a filler for gel permeation chromatography (GPC) and obtain a GPC mode, it is preferable that the weight of the polymer is 6% by weight or less. . Even if it exceeds this range, it can be used as a packing material for affinity chromatography by further modification.

Note that the resin having a group represented by the general formula (I) above has a group represented by the general formula m in the resin.

The paper is selected by having 1.0 weight or more of phosphorus in the Kei portion.

Slightly soluble or insoluble in water.

A resin having a group represented by the general formula (1) is dissolved in a non-reactive organic solvent and suspended in an aqueous medium, and the group represented by the general formula (1) is hydrolyzed and subjected to a condensation reaction. .

As the non-reactive organic solvent, one is used that dissolves the resin having the group represented by the general formula (1), is sparingly soluble or insoluble in water, and does not dissolve the target porous crosslinked polymer particles9. for example.

Aromatic solvents such as benzene, toluene, xylene, diethylbenzene, and chlorobenzene, aliphatic or alicyclic solvents such as n-dodecane, n-octane, and cyclohexane, and ester solvents such as n-propyl acetate and n-butyl acetate. , methyl isobutyl ketone, ketone solvents such as cyclohexanone, amyl alcohol.

There are alcoholic solvents such as octyl alcohol. Alkoxy-modified organosilanes such as tetraethoxysilane can also be used. In addition.

The porous crosslinked polymer particles obtained by the present invention are sparingly soluble and insoluble in most organic solvents.

The non-reactive organic solvent is mainly used as an oil dropletizing agent and a reaction medium for suspending the resin of general formula (1) in an aqueous medium. Furthermore, it is also a pore control agent for obtaining porous crosslinked polymer particles.

Therefore, in actual use, the type and amount of the solvent should be determined by considering the solubility in the resin having the group represented by the general formula (1) and the degree of swelling of the polymer particles after crosslinking (reticulation). good.

As the non-reactive organic solvent, isoamyl alcohol, butyl acetate, cyclohexanone, and chlorobenzene are particularly preferred in terms of their functions as the oil droplet forming agent 9 reaction medium and pore control agent.

In addition, two or more of the above-mentioned non-reactive organic solvents can be used in combination to adjust the functions of the above-mentioned three types.

The non-reactive organic solvent is preferably used in an amount of 50 to 300% by weight based on the resin having the group represented by the general formula (1). If the amount of the organic solvent used is too small, the pore volume of the desired porous crosslinked polymer particles becomes too small, and if it is too large, the strength of the desired porous crosslinked polymer particles decreases.

Undesirable.

It can be added to the aqueous medium during the hydrolysis or condensation reaction separately from the organic solvent solution.

Further, in the present invention, a resin having a group represented by the general formula (1) is dissolved in a non-reactive organic solvent.

A water-soluble organic solvent such as methyl ethyl ketone or acetone may be included. Such water-soluble organic solvents may be added at other times.

If the amount is too large, the dispersion stability will be reduced during suspension, so it is preferably used in an amount of 10 parts by weight or less relative to the water in the aqueous medium. Such water-soluble organic solvents have, for example, the general formula (
The group represented by formula (1) is suspended in an organic medium, and the group represented by general formula (1) is subjected to hydrolysis and condensation reactions. This reaction can be carried out from room temperature to
F can be selected arbitrarily between 0℃, but F
The temperature is preferably 170°C or higher. Furthermore, dibutyltin dilaurate, diptyltin diacetate, zinc octoate, titanate tetranonyl ester, diptylamine, pyridine,
Silanol condensation catalysts such as pentoxide paper and fatty acids may also be used. When using a silanol condensation catalyst, it is used after being dissolved in a non-reactive organic solvent together with a resin having a group represented by general formula (1). The amount used is about 0.1 to 3 parts by weight relative to the resin.

As a dispersant for obtaining porous particles, a sparingly soluble inorganic salt such as calcium carbonate, tricalcium phosphate, magnesium phosphate, etc. is used in an amount of about 20 to 70 Heavy weight, preferably 30-50
weight, or alkylcellulose, hydroxyalkylcellulose, carboxyalkylcellulose, holly, about 0, i to 5 weight, preferably 1
5-3 weight - used. In addition to these dispersants, a dispersion aid such as an anionic surfactant such as sodium dodecylbenzenesulfonate may be used, if necessary.

The ratio of the non-reactive organic solvent solution (a) of the resin having the group represented by the general formula (1) to the aqueous medium tb+ is (a)/
(b) in a weight ratio of 1/α5 to 1/20.

It may be determined depending on the particle size distribution of the target porous crosslinked polymer particles. To adjust the particle size of the target porous crosslinked polymer particles to 1 to 30 μm (al/(bl is in the range of 1/3 to 1/100 by weight), suspension of a solvent solution in an aqueous medium is Mixing may be carried out by stirring, but it is preferable to perform high-speed stirring using a homomixer or the like before the hydrolysis and condensation reactions or until the beginning of the 9 reactions.In this case, after high-speed stirring, stirring under normal stirring. The reaction is terminated.

Next, nine examples of the present invention will be shown.

Example 1 (1) Synthesis of a resin containing a group represented by general formula (1) 100 f of methyl ethyl ketone was placed in a four-bottle flask equipped with a stirrer, a cooling tube, a nitrogen introduction tube, and a thermometer, and the temperature was raised to 70°C. In this, γ-methacryloxypropyltrimethoxysilane 50? .

β-Hydroxyethyl methacrylate 70? .

Azobisisobutyronitrile 5? A mixed solution consisting of:

(2) Production of porous crosslinked polymer particles Add 180 cyclohexanone to the entire solution obtained in (1).
Add t to form a non-reactive organic solvent solution.

Add to this ion exchange water 1.31. Tricalcium biphosphate 30? were mixed and suspended in an aqueous medium at 70° C. for 3 hours under high-speed stirring using a homomixer to proceed with hydrolysis and condensation reactions.

Thereafter, the mixture was transferred to an ordinary stirring pot and reacted at 80° C. to 90° C. for 5 hours to obtain spherical particles of a porous crosslinked polymer insoluble in organic solvents. Particle size was 1-305m. The IR spectrum (KBr method) of the obtained particles is shown in FIG. The absorption near 90051' and 107051'' in Figure 1 and the presence of silica in the ash after ashing (IR spectrum shows that it is an organic silica gel).

The porous crosslinked polymer particles thus obtained were sieved, and the gel having a particle size of 8 to 15 μm was filled into a 59zXg stainless steel column. Using this column, ethylene glycol and various polyethylene glycols were separated and analyzed by GPC. The measurement conditions were ion-exchanged water as the mobile phase, flow rate of 11 Ll/min,
The temperature was room temperature and an RI detector was used. The obtained chromatograms are summarized in FIG.

Example 2 Synthesis of books Methyl ethyl ketone 100? and raise the temperature to 70℃. Among these, γ-methacryloxypropyltrimethoxysilane 30), β-hydroxyethyl methacrylate 9)
0? A solution containing a mixture consisting of azobisisobutyronitrile 5f was obtained.

(2) Production of porous crosslinked polymer particles Add 1BOf of isoamyl alcohol to the entire amount of the solution obtained by synthesis in (1) to make a non-reactive organic solvent solution,
This was mixed with 1.3 g of ion-exchanged water and 30) tricalcium phosphate, and stirred at high speed using a homomixer at 70°C for 3 hours.

Hydrolysis and condensation reactions were carried out while suspending in an aqueous medium. After that, transfer it to an ordinary stirring pot and heat it at 80℃~90℃ for 5 minutes.
After a period of reaction, spherical particles of porous crosslinked polymer insoluble in organic solvents were obtained. Particle size was 1-30 μm.

The particles thus obtained were sieved to 8 to 15
The particles had a particle size of μm and were packed into a 5051×8-φ stainless steel column. Using this method, ethylene glycol and various polyethylene glycols were separated and analyzed separately.

The measurement conditions were ion-exchanged water as the mobile phase and a flow rate of 1 g/m i.
n, the temperature was room temperature and an RI detector was used.

The obtained chromatograms are summarized in FIG. 3.

Example 3 100 f of methyl ethyl ketone was placed in a four-bottle flask equipped with a stirrer, a condenser, a nitrogen inlet tube, and a thermometer, and the temperature was raised to 70°C. This contains 30 tons of γ-methacryloxyglobiltrimethoxysilane, 90 tons of N-vinyl-2-pyrrolidone, and 5 tons of azobisisobutyronitrile. A mixture consisting of was added dropwise.

A solution was obtained.

(2) Production of porous crosslinked polymer particles Add isoamylalcosium 30F to the entire amount of the solution obtained in (1) and use a homomixer.

Hydrolysis and condensation reactions were carried out while suspending in an aqueous medium at 70° C. for 4 hours with high speed stirring.

Thereafter, the mixture was transferred to an ordinary stirring pot and reacted at 80°C to 90°C for 4 hours to obtain porous crosslinked polymer particles insoluble in organic solvents. Particle size was 1-30 μm.

The particles thus obtained were sieved to give 8 to 15
The particles had a particle size of μm and were packed into a 5QcmXll-φ stainless steel column. Using this column, ethylene glycol and various polyethylene glycols were separated and analyzed separately. #1 Hiroshi conditions were: ion-exchanged water as the mobile phase, flow rate 1.0 sl/min, room temperature, and RI
A detector was used. The obtained chromatograms are summarized in FIG. 4.

In Figures 2 to 4, curve 1 is ethylene glycol; curve 2 is polyethylene glycol with a molecular weight of 200; curve 3 is polyethylene glycol with a molecular weight of 400; curve 4 is polyethylene glycol with a molecular weight of 600; curve 5 is polyethylene glycol with a molecular weight of 1000. and curve 6 is a chromatogram of polyethylene glycol with a molecular weight of 2000.

By the novel production method of the present invention, novel porous crosslinked polymer particles can be obtained. Moreover.

Particularly when obtaining hydrophilic porous crosslinked polymer particles, pore adjustment, crosslinking, and spheroidization of the particles can be carried out efficiently. The porous crosslinked polymer particles obtained according to the present invention can be used, for example, as a filler for GPC (particularly for hydrophilic porous crosslinked polymer particles).

This is a chromatogram obtained using another chromatographic particle that can be used as a packing material for aqueous GPC (where the mobile phase is water) and is further modified.

Explanation of symbols 1...Chromatogram of ethylene glycol 2...
Chromatogram of polyethylene glycol with a molecular weight of 200 3... Chromatogram of polyethylene glycol with a molecular weight of 400 4... Chromatogram of polyethylene glycol with a molecular weight of 600 5... Chromatogram of polyethylene glycol with a molecular weight of 1000 6... Molecular weight of 2000 Chromatogram of polyethylene glycol of

Claims (1)

[Claims] 1. General formula (1) % formula % () (In formula 9, Y is a hydrolyzable group, R is an inert monovalent organic group, and n is 1 ~3 integer)
A porous material characterized by suspending a non-reactive organic solvent solution of a resin having a group represented by the above in an aqueous medium to carry out a hydrolysis and condensation reaction of the group represented by the general formula (I). Method for producing crosslinked polymer particles. 2. The method for producing porous crosslinked polymer particles according to claim 1, wherein the resin having a group represented by general formula (11) is a resin having a hydrophilic group. 1. Claim 1 or 2, wherein the resin has a group represented by the general formula (1) bonded to the silicon moiety in an amount of 1,0 to IL3 weight. A method for producing porous crosslinked polymer particles as described in 1.