JPH02166102A - Method for producing hydrophilic crosslinked polymer particles - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing hydrophilic crosslinked polymer particles containing hydroxyl groups.

[Conventional technology]

Conventionally, multi-am gels such as cross-linked dextran gels and agarose gels, and chemically modified silica gels have been frequently used as packing materials for aqueous liquid chromatography.
In recent years, cross-linked polyvinyl alcohol, hydroxyethyl (
Hydrophilic polymers made of (meth)acrylic acid ester polymers derived from polyhydric alcohols such as meth)acrylate copolymers, polyethylene glycol di(meth)acrylate, diglycerin (meth)acrylate, and triglycerin mono(meth)acrylate. Polymeric crosslinked polymer particles have come into use.

Furthermore, these hydrophilic crosslinked polymer particles have various uses such as plastic additives, sustained-release drug bases, powders for cosmetics, carriers for immobilized enzymes and immobilized microorganisms, and water-absorbing resins.

In this specification, (meth)acrylate and (meth)acrylic ester mean acrylate, methacrylate, acrylic ester, or methacrylic ester, respectively.

The above-mentioned hydrophilic crosslinked polymer particles can be synthesized by carrying out suspension polymerization of water-in-oil or oil-in-water type depending on the water solubility of the corresponding monomer. The latter suspension polymerization is preferred because it is difficult to obtain polymer particles with small particle diameters ranging from μ to more than 10 μ and it is difficult to select the solvent used to make the polymer particles porous. It is used in

When carrying out oil-in-water suspension polymerization of hydrophilic monomers in the coexistence of organic solvents, a large amount of electrolyte is added to the aqueous phase and the monomers are dissolved in water because the corresponding monomers have high water solubility. (Japanese Unexamined Patent Publication No. 60-55009),
In the case of a monomer having a hydroxyl group, at least a part of the hydroxyl group is protected as an ester with a fatty acid, the hydrophilicity of the monomer is weakened, the monomer is polymerized, and then the hydroxyl group is regenerated (JP-A-59-193846). or after synthesizing crosslinked polymer particles of glycidyl methacrylate, polyols are added to the oxirane ring (Japanese Patent Laid-Open No. 5
3-1087. JP-A No. 53-90991, etc.).

[Problem to be solved by the invention]

However, in the method of adding a large amount of electrolyte to the aqueous phase, the suspension stability during polymerization is inevitably impaired because the electrolyte has a negative effect on the function of the protective colloid, and when the hydroxyl group is protected as fatty acid ester, its removal In the protection step, it is inevitable that not only the protecting group but also the ester bond of the (meth)acrylate moiety undergoes hydrolysis.

[Means to solve the problem]

Therefore, the present inventors conducted intensive studies on a method for easily obtaining hydrophilic crosslinked polymer particles made of polyhydric alcohol (meth)acrylic acid ester polymers, and as a result, at least a portion of the hydroxyl groups in the monomers were They discovered that the object could be achieved by alkylsilylation and completed the present invention.

That is, the present invention involves suspension polymerization of one or more monomers in which at least a portion of the hydroxyl groups of a partially (meth)acrylic ester of a polyhydric alcohol is trialkylsilylated in an aqueous medium together with a crosslinking agent. The present invention provides a method for producing hydrophilic crosslinked polymer particles, which comprises removing the l-IJ alkylsilyl group by hydrolysis and regenerating the hydroxyl group.

The partial (meth)acrylic acid ester of polyhydric alcohol used in the present invention is 2-hydroxyethyl (
meth)acrylate, glycerol mono(meth)acrylate, diglycerin mono(meth)acrylate, triglycerin mono(meth)acrylate, tetraglycerin mono(meth)acrylate, 3-(2-hydroxyethoxy)-2-hydroxypropyl(meth)acrylate, ) acrylate, 4,7-thioxal 2,9-dihydroxynonyl (meth)acrylate, 2-glycidoxyethyl (
Polyhydric alcohol mono(meth)acrylate, diethylene glycol mono(meth)acrylate, triethylene glycol mono(meth)acrylate, tetraethylene glycol mono(meth)acrylate, sorbitol mono(meth)acrylate, pentaerythritol mono(meth)acrylate, etc. (Meth)acrylic acid esters include glycerol di(meth)acrylate, diglycerine di(meth)acrylate, diglycerine tri(meth)acrylate, triglycerine di(meth)acrylate, and triglycerine tri(meth)acrylate.
Acrylate, triglycerin tri(meth)acrylate, sorbitol di(meth)acrylate, sorbitol tri(meth)acrylate, pentaerythritol di(meth)acrylate, pentaerythritol tri(meth)acrylate
Polyhydric (meth)acrylic acid esters of polyhydric alcohols such as (meth)acrylates having hydroxyl groups are also included. These polyvalent (meth)acrylic esters can be used as crosslinking agents as described below.

Among the above partial (meth)acrylic acid esters of polyhydric alcohols, those having high hydrophilicity are particularly preferably used.

As the trialkylsilyl group of the present invention, those commonly used for protecting hydroxyl groups such as trimethylsilyl, triethylsilyl, tribubylsilyl, methyldiisopropylsilyl, and tetramethyleneisopropylsilyl groups can be used. The silylation of the hydroxyl group in the monomer can be carried out by reacting the corresponding trialkylsilyl chloride in the presence of a base such as pyridine or triethylamine, by reacting an equimolar mixture of trialkylsilyl chloride and hexaalkyldisilazane, or by reacting an equimolar mixture of trialkylsilyl chloride and hexaalkyldisilazane. trialkylsilylating agents such as N,0- and trialkylsilylacetamide, N-)alkylsilylacetamide, N,0-bistrialkylsilylcarbame), N-trialkylsilyldiethylamine or N-trialkylsilylimidazole; Silylated monomers that can be reacted may be used as they are, or monomers that can be purified by means such as vacuum distillation may be used after being purified.

As the crosslinking agent that can be used in the present invention, the above-mentioned polyhydric (meth)acrylate ester of polyhydric alcohol having a hydroxyl group converted to trialkylsilylation can be used, but in addition to that, divinylbenzene, Ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, propylene glycol di(
Polyfunctional vinyl polymerizable monomers such as meth)acrylate, 1,4-buta-ndiol di(meth)acrylate, glycerol tri(meth)acrylate, and trimethylolpropane tri(meth)acrylate can be used.

The present invention uses the above-mentioned trialkylsilyl group-containing (meth)acrylate monomer as an essential component, and the styrene-based, (meth)acrylic acid-based, and (meth)acrylic acid ester monomers that can be copolymerized with these monomers include Hydrophobic or hydrophilic monomers such as (meth)acrylamide-based monomers can be used as appropriate as long as the object of the present invention is not impaired.

The suspension polymerization in an aqueous medium of the present invention can be carried out by a known method generally used in suspension polymerization of vinyl monomers. For example, a polymerization initiator is dissolved in a solution consisting of a trialkylsilyl group-containing monomer, a crosslinking agent, and an organic solvent, and the solution is added to water containing a suspension stabilizer, followed by a polymerization reaction for a predetermined period of time with appropriate stirring and heating. to be carried out.

The size of the polymer particles can be varied by the degree of agitation. In other words, small particles of several dozen or less can be obtained by dispersing with a homogenizer, generating droplets of corresponding size by ultrasonication, etc., and polymerizing them, while larger particles can be obtained by gentle stirring in a polymerization tank. be able to. Furthermore, a so-called seed polymerization method is employed in which small-sized polymer particles are dispersed in water, and the trialkylsilyl group-containing monomer, crosslinking agent, organic solvent, and polymerization initiator used in the present invention are absorbed and polymerized. You can also. When carrying out the seed polymerization method, hydrophilic crosslinked polymer particles with uniform particle diameters can be synthesized by using polymer particles with uniform particle diameters as seeds.

Organic solvents that can be used in the present invention include benzene,
Aromatic hydrocarbons such as toluene, xylene, diethylbenzene, dodecane, decane, etc.

Aliphatic hydrocarbons such as tetradecane, n-butyl alcohol, i-butyl alcohol, n-amyl alcohol,
Alcohols such as l-amyl alcohol and n-hexyl alcohol, ketones such as methyl ethyl ketone, methyl-n-propyl ketone, and methyl isobutyl ketone, esters such as ethyl acetate, isopropyl acetate, n-butyl acetate, isoamyl acetate, etc. can be mentioned.

By changing the combination and amount of these organic solvents used, the porosity of the resulting polymer particles can be adjusted.

In the present invention, the amount of crosslinking agent used is generally in the range of 0.05 to 0.7 parts by weight, preferably in the range of 0.1 to 0.45 parts by weight, per 1 part by weight of the monomer. be. As the amount of crosslinking agent increases, the mechanical strength of the resulting particles increases, but the hydrophilicity decreases.

As the polymerization initiator used in the present invention, ordinary radical polymerization initiators can be used. Examples of these are benzoyl peroxide, dicumyl peroxide, di-t peroxide.
Examples include er t-butyl, lauroyl peroxide, azobisisobutyronitrile, dimethylazoisobutyrate, and the like.

The amount of the polymerization initiator used is preferably 0.01 to 10% by weight, particularly 0.5 to 5% by weight, based on the total of monomer and crosslinking agent.

In the present invention, commonly used suspension stabilizers such as sparingly soluble inorganic salts and water-soluble polymeric protective colloids can be used. Examples of poorly soluble inorganic salts include tricalcium phosphate, magnesium phosphate, calcium carbonate, magnesium carbonate, barium sulfate, silica, talc, bentonite, and the like. Examples of water-soluble polymeric protective colloids include polyvinyl alcohol, gelatin, alkyl cellulose, hydroxyalkyl cellulose, and sodium polyacrylate. These inorganic or organic suspension stabilizers can be used alone or in combination of two or more. The amount used is preferably 0.01% by weight or more based on the total amount of substances present in the polymerization system for poorly soluble inorganic salts, and 0.001 to 10% by weight for water-soluble polymer protective colloids. .

In addition, anionic surfactants, water-soluble inorganic salts, and the like can be added to the polymerization system in order to ensure stability of the polymerization system.

To remove the trialkylsilyl groups and regenerate the hydroxyl groups in the polymer particles obtained as described above, a commonly used method may be adopted, for example, in a lower alcohol such as methanol or ethanol. The trialkylsilyl group can be effectively removed by dispersing the compound in a solution and heating it. At this time, if an acid catalyst such as acetic acid, hydrochloric acid, or tosylic acid is present, the trialkylsilyl group can be effectively removed. It may also be reacted with tetrabutylammonium sulfate in an aprotic solvent, or with a lower alcohol in the presence of a basic catalyst such as potassium carbonate.

The particles obtained as above have a particle size of 1 to 50 JI
Spherical particles of Ias preferably 1 to 151 Hm can be used as a packing material for gel permini-silane chromatography. Furthermore, by introducing an ion exchange group, a glycidyl group, a long chain alkyl group, etc., the properties as a filler can be changed, and it can also be used as a carrier for affinity chromatography or ion exchange chromatography. In addition, the particles obtained in the above manner can be used as a plastic additive,
It can also be used as a sustained-release drug base, cosmetics, carriers for immobilized enzymes or immobilized microorganisms, water-absorbing resins, etc.

〔Effect of the invention〕

In the present invention, at least a portion of the hydroxyl groups in the partial (meth)acrylic ester of a polyhydric alcohol is trialkylsilylated to reduce its water solubility,
It has become possible to carry out suspension polymerization in an aqueous medium of monomers, which were conventionally difficult to carry out suspension polymerization in an aqueous medium due to their high water solubility. Furthermore, the trialkylsilyl group once introduced is removed under mild conditions,
It was possible to regenerate into hydroxyl groups, and it was possible to easily obtain (meth)acrylic acid ester crosslinked polymer particles of polyhydric alcohol.

〔Example〕

Next, the present invention will be described in detail based on Examples, but the present invention is not limited thereto.

Synthesis example 1 2-hydroxyethyl methacrylate) 60 g.

50 g of trimethylsilyl chloride was added dropwise to a solution consisting of 36.4 g of pyridine and 250 g of toluene over 30 minutes, and stirring was continued for 12 hours at room temperature. The precipitated pyridine hydrochloride was filtered off, and toluene was distilled off from the filtrate under reduced pressure. By distilling the residue under reduced pressure, 2
-trimethylsilyloxyethyl methacrylate was obtained. Boiling point 84'C/14mm 11g, yield 67.3g
.

Synthesis example 2 2-hydroxyethyl acrylate 64g 1 pyridine 4
60 g of trimethylsilyl chloride was added dropwise to a solution consisting of 3.7 g and 250 g of toluene over 30 minutes, and stirring was continued for 12 hours at room temperature. The precipitated pyridine hydrochloride was filtered off, and toluene was distilled off from the filtrate under reduced pressure. 2-trimethylsilyloxyethyl acrylate was obtained by distilling the residue under reduced pressure. Boiling point 75~
76'C/15mmHg, yield 45g0 Synthesis Example 3 Glycerol monomethacrylate (Blemmer GL1.
Nippon Oil & Fats ■) 50g and tetrahydrofuran 150g
Adding a mixture of 30 g of hexamethyldisilazane and 20 g of trimethylsilyl chloride to a solution consisting of
After the reaction was completed at 45"C for 8 hours, the precipitated ammonium chloride was filtered off, and the solvent and unreacted silylating agent were distilled off under reduced pressure to obtain a bistrimethylsilylated glycerol monomethacrylate. The yield was 93 g, which was used as it was in the next reaction.

Synthesis Example 4 24 g of trimethylsilyl chloride was added dropwise over 15 minutes to a solution consisting of 50 g of glycerol dimethacrylate (Blenmar MR, manufactured by NOF ■), 17.3 g of pyridine, and 250 g of toluene, and the solution was stirred at room temperature for 12 hours.
Stirring was continued for an hour. The precipitated pyridine hydrochloride was filtered off, and the filtrate was washed with 200 g of saturated saline. The organic layer was separated and dried over anhydrous magnesium sulfate. Magnesium sulfate was filtered off, and toluene was distilled off under reduced pressure from the resulting solution to obtain a monotrimethylsilylated glycerol dimethacrylate. Yield: 64g. This product was used as it was in the next reaction.

Example 1 1j equipped with a stirring device, condenser, thermometer, and nitrogen inlet tube! Polyvinyl alcohol (
1% of Gohsenol Gf (17, E Honsei Kagaku Kogyo)
300 sj of aqueous solution, 30 g of trimethylsilylated monomer obtained in Synthesis Example 1, and divinylbenzene (55% product)
5. OgSl - 15g of toluene and 0 lauroyl peroxide
．． A solution consisting of 35 g was added and stirred at room temperature for 30 minutes at a rotation speed of 350 rpm to obtain a uniform dispersion. Thereafter, a polymerization reaction was carried out at 80° C. for 8 hours while stirring at the same speed.

As a result, a dispersion of fine polymer particles with an average particle size of 100 μm was obtained. Filter out polymer particles, wash with acetone,
By drying under reduced pressure, 34 g of transparent particles were obtained.

Note that, although the filtrate obtained in the step of filtering the dispersion of polymer fine particles after the reaction was slightly cloudy, no increase in viscosity was observed. In addition, there was almost no deposit in the polymerization tank.

Next, 20 g of the polymer fine particles obtained as described above were dispersed in 95% ethanol containing a catalytic amount of acetic acid,
The trimethylsilyl group was removed by heating under reflux for 4 hours, and the polymer particles were filtered out from the dispersion, and then dried under reduced pressure to obtain the desired 2-hydroxyethyl methacrylate/divinylbenzene crosslinked polymer particles. .5 g was obtained.

Example 2 In the same apparatus as used in Example 1, a dispersion medium and a monomer solution having the same composition and amount as used in Example 1 were stirred for 5 minutes at 10.000 rpm using a homomixer. The dispersion was added thereto, and then a polymerization reaction was carried out at 80°C for 8 hours while stirring at a rotational speed of 1100 rpm+. As a result, a dispersion of fine polymer particles with an average particle size of 10 μm was obtained.

After the same post-treatment as in Example 1, the number of polymer fine particles was 32.
g was obtained.

Next, the same operation as in Example 1 was carried out to remove the trimethylsilyl group, thereby obtaining 20 g of 2-hydroxyethyl methacrylate/divinylbenzene crosslinked polymer fine particles having an average particle size of 10 μm.

Example 3 300 mj of a 1% aqueous solution of polyvinyl alcohol (Gohsenol GW-17゜Nippon Synthetic Chemical Industry type) and 30 g of the trimethylsilylated monomer obtained in Synthesis Example 2.1 Synthesis Example 4
10 g of the trimethylsilylated monomer obtained in , 20 g of toluene and 0.20 g of azobisisobutyronitrile
using a homomixer at 10.00 Or
pm for 5 minutes to obtain a monomer dispersion. This dispersion was placed in the same apparatus used in Example 1 and heated to 1100 rpm.
The polymerization reaction was carried out at 65°C for 8 hours while stirring at a rotational speed of p.

Next, the fine polymer particles were filtered from the resulting dispersion of fine polymer particles, redispersed in 95% ethanol containing a catalytic amount of acetic acid, and heated under reflux for 4 hours to remove trimethylsilyl groups.

The desired 2-hydroxyethyl acrylate/glycerol dimethacrylate crosslinked polymer particles were obtained by filtering the polymer particles from the dispersion and then drying them under reduced pressure.

The average particle size of the polymer particles was 8I1m, and the yield was 1123g.

Example 4 30 g of the trimethylsilylated monomer obtained in Synthesis Example 3, 10 g of the trimethylsilylated monomer obtained in Synthesis Example 4, 30 g of isoamyl acetate, 0.2 azobisisobutyronitrile.
Using a solution consisting of 0 g and 300 m7 of a 1% aqueous solution of polyvinyl alcohol, the same operation as in Example 3 was performed to obtain polymer fine particles, which were then treated in the same manner as in Example 1 to perform detrimethylsilylation. The desired glycerol monomethacrylate/glycerol dimethacrylate polymer particles were obtained.

The average particle size of the polymer particles was 10 μm, the yield was 20 g, and the obtained polymer particles were porous.

Comparative Example 1 The same operation as in Example 1 was performed except that 2-hydroxyethyl methacrylate was used instead of 2-trimethylsilyloxyethyl methacrylate obtained in Synthesis Example 1. As the polymerization reaction progressed, the viscosity of the solution increased, and a gel-like substance adhered to the stirring rod and the flask wall.
Granular polymer particles such as those obtained in (1) were not obtained.

Comparative Example 2 Example except that glycerol monomethacrylate was used in place of the trimethylsilylated glycerol monomethacrylate obtained in Synthesis Example 3, and glycerol dimethacrylate was used in place of the trimethylsilylated glycerol dimethacrylate obtained in Synthesis Example 4. The same operation as in 4 was performed.

Only lumpy polymer was obtained, but no polymer fine particles were obtained.

Claims (1)

[Scope of Claims] 1. One or more monomers in which at least a portion of the hydroxyl groups of a partial (meth)acrylic ester of a polyhydric alcohol is trialkylsilylated together with a crosslinking agent in an aqueous medium. A method for producing hydrophilic crosslinked polymer particles, which comprises carrying out suspension polymerization and then removing trialkylsilyl groups by hydrolysis to regenerate hydroxyl groups. 2. The method for producing hydrophilic crosslinked polymer particles according to claim 1, wherein the trialkylsilyl group is a trimethylsilyl group.