JPH0344085B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing a bead-like polymer obtained by modifying an epoxy group-containing spherical polymer. Polymers containing bonded epoxy groups have the potential to be applied to various fields of use by introducing various functional groups depending on their reactivity. A technique has been disclosed for producing immunoactive fine particles by reacting glycidyl acrylate (GA) or glycidyl methacrylate (GMA) polymer fine particles with an immunoactive substance having an amino group. According to this publication, polymerization is carried out in a medium that dissolves the monomer but precipitates the produced polymer, and depending on the monomer composition and selection of the polymerization medium, fine particulate GA or GMA polymers of 0.03 to 10μ can be formed. However, since such methods use organic solvents for polymerization medium, washing, etc., there are many points to be noted in terms of work environment and safety, such as odor, on an industrial scale. Also, Journal of the Chemical Society of Japan, 1979(12), p.1756-1759
discloses a method for producing a GMA spherical polymer as a substrate for producing a chelating ion exchange resin, but in order to obtain a spherical polymer, a large amount of sodium sulfate and calcium carbonate are used as dispersants along with gelatin, and the formation In order to decompose and remove calcium carbonate from the polymer, complicated operations such as adding hydrochloric acid and washing with hot water are required. In addition, in recent years, liquid chromatography has not only been used merely as an analytical method, but also in many industrial fields such as the food industry, pharmaceutical industry, synthesis and purification of chemical industry product intermediates, inorganic industry, and textile industry. Its application as one of the separation methods is progressing.
There are a wide variety of gels for liquid chromatography, such as dextran crosslinked polymer gels, acrylamide crosslinked polymer gels, crosslinked polystyrene gels, crosslinked polyvinyl acetate gels, crosslinked polyethylene glycol dimethacrylate gels, and silanol/polyoxyethylene gels. A wide range of developments have been made. However, gels with higher separation performance and processing capacity are generally more expensive; for example,
Cefdex gel (dextran cross-linked polymer gel) manufactured by Pharmacia Fine Chemical and others has excellent performance but is very expensive, which poses a problem in industrial applications where large quantities are packed into huge columns. be. As a result of intensive research to provide a bead-like polymer that is inexpensive and has high separation performance, the present inventors used a specific water-soluble polymer as a dispersant, and under specific pH and stirring conditions, By carrying out suspension polymerization, an epoxy group-containing spherical polymer having a desired particle size can be produced, and by subjecting the thus obtained polymer to acidic heat treatment under specific conditions, hydroxyl groups can be formed by ring opening of the epoxy groups, and hydroxyl groups can be formed by ring opening of the epoxy groups. The present invention was achieved based on the discovery that a bead-shaped polymer having high separation ability can be industrially advantageously provided by introducing cross-linking through intramolecular and intermolecular bonding of the groups. That is, the object of the present invention is to industrially produce hydrophilic and solvent-insoluble bead-shaped polymers into which a large amount of hydroxyl groups and crosslinks are introduced by modifying epoxy groups without the problems such as aggregation and coalescence that are peculiar to epoxy group-containing polymers. To provide law and other purposes:
The object of the present invention is to provide a method for producing bead-shaped polymers that are inexpensive and have high separation performance. Further objectives will become apparent from the detailed description of the invention that follows. The bead-shaped polymer according to the present invention for achieving the above purpose is GA or GMA (hereinafter referred to as GMA).
(M)A) alone or at least 50% by weight of G(M)
A monomer mixture consisting of A and the balance consisting of at least one other monomer is made of a monomer unit consisting essentially of an ethylenically unsaturated carboxylic acid or a salt thereof and an ethylenically unsaturated sulfonic acid or a salt thereof. After carrying out aqueous suspension polymerization under the conditions of pH 2 to 9 and stirring speed of 50 to 500 rpm in the presence of a water-soluble polymer and an oil-soluble radical polymerization initiator,
It can be advantageously produced by heat treatment at a pH of 3 or lower and a temperature of 70°C or higher. The present invention will be described in detail below. First, the epoxy group-containing spherical polymer, which is a component of the first stage, is G(M)
It is necessary to produce A alone or a monomer mixture consisting of 50% by weight or more, preferably 60% by weight or more of G(M)A and the remainder being at least one other monomer. Other monomers to be copolymerized with G(M)A include known monomers that can be copolymerized with G(M)A, such as vinyl chloride, vinyl bromide, vinyl fluoride, and vinylidene chloride. Vinyl halides and vinylidene halides; unsaturated carboxylic acids such as acrylic acid, methacrylic acid, maleic acid, itaconic acid and their salts; methyl acrylate, ethyl acrylate, butyl acrylate, octyl acrylate, methoxy acrylate Acrylic esters such as ethyl, phenyl acrylate, and cyclohexyl acrylate; Methacrylic esters such as methyl methacrylate, ethyl methacrylate, butyl methacrylate, octyl methacrylate, methoxyethyl methacrylate, phenyl methacrylate, and cyclohexyl methacrylate ; Unsaturated ketones such as methyl vinyl ketone, phenyl vinyl ketone, and methyl isopropenyl ketone; Vinyl esters such as vinyl formate, vinyl acetate, propionic vinyl acetate, vinyl butyrate, and vinyl benzoate; Methyl vinyl ether, ethyl vinyl ether, etc. Vinyl ethers; acrylamide and its alkyl substituted products; unsaturated hydrocarbon sulfonic acids such as vinylsulfonic acid, allylsulfonic acid, methallylsulfonic acid, p-styrenesulfonic acid, and their salts; styrene, α-methylstyrene, chlorostyrene Styrene and its alkyl or halogen substituted products; Allyl alcohol and its esters or ethers; Vinylpyridine, vinylimidazole,
Examples include basic vinyl compounds such as dimethylaminoethyl methacrylate; vinyl compounds such as acrolein, methacrolein, vinylidene cyanide, and methacrylonitrile. In addition, divinylbenzene, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, N,N'-ethylenebisacrylamide, divinyl succinate, diallyl succinate, vinyl methacrylate, allyl methacrylate,
By using crosslinking monomers such as triallyl dianurate and triallyl isocyanurate,
The polymer can also be actively crosslinked. The polymerization method employed in the present invention using such monomers is characterized in that aqueous suspension polymerization is carried out under specific pH and stirring conditions in the presence of a specific water-soluble polymer and an oil-soluble radical polymerization initiator. There is. That is,
Generally, when epoxy group-containing monomers are aqueous-based polymerized, the resulting polymer has strong stickiness and tends to aggregate and coalesce to form cake-like lumps. The action of the specific water-soluble polymer, stirring, and the like work together to prevent the resulting polymer from agglomerating, and to obtain uniform spherical polymer particles. The water-soluble polymer present in the polymerization system, which is a particularly important component in such a polymerization method, includes a monomer unit (component A) consisting essentially of an ethylenically unsaturated carboxylic acid or a salt thereof, and an ethylenically unsaturated It is necessary to use a water-soluble polymer containing a monomer unit consisting of sulfonic acid or a salt thereof (component B), and any water-soluble polymer that finally contains both components A and B may be used. Although a polymer obtained by a method can also be effectively used in the present invention, generally components A and B are copolymerized by a well-known method (particularly, solution polymerization using water as a polymerization medium). It can be manufactured by In addition, component A may be introduced into the polymer by hydrolyzing a copolymer of unsaturated carboxylic acid esters such as esters of acrylic acid or methacrylic acid, or by sulfonation of the polymer. It goes without saying that methods such as introducing the B component can also be adopted. In addition, the composition ratio of component A and component B in such a water-soluble polymer varies slightly depending on the copolymerization ratio of G(M)A and the types of other monomers, and it is difficult to define it uniquely. However, generally A component/B component =
The degree of polymerization of such a polymer is preferably in the range of 30-80%/70-20%, but there are no particular restrictions on the degree of polymerization, but within a practical molecular weight range, it is better to use one with a small molecular weight for ease of handling. This is advantageous and effective in preventing coalescence of the spherical polymers produced. Furthermore, depending on the type of other monomers, the water-soluble polymer may be a water-soluble polymer prepared by copolymerizing or graft polymerizing a small amount of a hydrophobic monomer such as vinylidene chloride added to components A and B. In some cases, better spherical polymers can be obtained by using coalescence, and such polymers are therefore also included within the scope of the water-soluble polymers used in the present invention. In addition, as the A component introduced into such a water-soluble polymer, unsaturated monohydric carboxylic acids such as acrylic acid, methacrylic acid, vinyl acetic acid, crotonic acid and their salts; maleic acid, fumaric acid, itacon Examples include unsaturated polyhydric carboxylic acids such as aconitic acid, citraconic acid, and mesaconic acid, and their salts; however, monomer units consisting of methacrylic acid and its salts are particularly suitable from the viewpoint of forming spherical polymers. is recommended. In addition, as component B, sulfonated unsaturated hydrocarbons and salts thereof such as sulfonated styrene, allylsulfonic acid, and methallylsulfonic acid; acrylic acid or methacrylic acid such as sulfoethyl methacrylate and sulfopropyl methacrylate; Examples include sulfoalkyl esters of acids and salts thereof. The amount of water-soluble polymer used is as follows:
Although it is difficult to define it uniquely, it is desirable to use it in an amount of 5% by weight or more based on the monomer. Also,
Along with the water-soluble polymer, polyvinyl alcohol (PVA) with a polymerization degree of 500 to 2000 and a saponification degree of 85 to 95%
Particularly good results can be obtained by using 0.1 to 5% by weight of the monomer. Further, as the oil-soluble radical polymerization initiator, it can be employed without any limitation as long as the purpose of the present invention is achieved, but the following azo compounds or organic peroxides are preferably mentioned. I can do it. For example, as an azo compound, 2,
2'-azobisisobutyronitrile, 2,2'-azobis(2-methyl-valeronitrile), 2,2'-
azobis(2,4-dimethylbutyronitrile),
2,2'-azobis(2-methylcapronitrile),
2,2'-azobis(2,3,3-trimethylbutyronitrile), 2,2'-azobis(2,4,4-
trimethylvaleronitrile), 2,2'-azobis(2,4-dimethylvaleronitrile), 2,2'-azobis(2,4-dimethyl-4-ethoxyvaleronitrile), 2,2'-azobis(2, 4-dimethyl-4-n-butoxyvaleronitrile), etc. can be used, and examples of organic peroxides include acetyl peroxide, propionyl peroxide, isobutyryl peroxide, octanoyl peroxide, and decanoyl peroxide. oxide, lauroyl peroxide, 3,5,5-
Diacyl peroxides such as trimethylhexanoyl peroxide, benzoyl peroxide, diisopropyl peroxydicarbonate, di-2-ethylhexyl peroxydicarbonate; t-butyl peroxyisobutyrate, t-
Peroxy esters such as butyl peroxy pivalate, t-butyl peroxy neodocanoate, t-butyl peroxy laurate, etc. can be used. Of course, two or more of the above oil-soluble radical polymerization initiators can also be used in appropriate combination. Although it is difficult to define the starting amount, it is generally used within the range of 0.2 to 2.0% by weight based on the monomer. Regarding the pH of the polymerization system, if the acidity is too strong, it will cause ring opening of the epoxy group during the polymerization reaction, and if the alkalinity is too strong, it will cause hydrolysis of the produced polymer, so the pH should be 2 to 9, preferably 2. It is necessary to set it within the range of ~7. In addition, the particle size of the final bead-shaped polymer is determined almost uniquely by the size of the epoxy group-containing spherical polymer, and stirring plays an important role in adjusting the particle size of the epoxy group-containing spherical polymer. The conditions must be changed depending on the shape of the blades, the presence or absence of baffles, the desired particle size, etc., and it is difficult to define them unambiguously, but the stirring speed should be approximately 50 to 500 r.pm.
It is necessary to set it within the range of . In addition, as for the shape of the blade, it is appropriate to use a wedge-shaped blade or a turbine blade because it is easy to obtain a uniform particle size distribution. The polymerization temperature depends on the type of initiator, but the higher the temperature, the more likely the ring-opening reaction of the epoxy group will occur, or the more the monomer will be emulsified and emulsion polymerization will occur, producing a latex-like fine polymer. To avoid this problem, a temperature range of approximately 80°C or lower, preferably 40 to 70°C, is recommended. Although it is desirable to use industrial water as the polymerization medium, it does not depart from the present invention to coexist a water-miscible organic solvent or electrolyte salts, if desired. The G(M)A-based spherical polymer thus obtained is
The polymer has a particle size of approximately 10μ or more, and although the gel moisture content is less than 20%, it is insoluble in solvents, so some of the epoxy groups are ring-opened and have hydrophilicity as well as intramolecular or It is presumed that intermolecular crosslinks have been introduced. Next, the spherical polymer having a particle size of approximately 10μ or more and a gel moisture content of 20% or less produced according to this polymerization method has a pH of 3 or less, preferably 2.5.
Thereafter, by heat treatment at a temperature of 70°C or higher, preferably 80°C or higher, substantially all of the epoxy groups are opened and hydroxyl groups are introduced, which is industrially advantageous.
More than 90 mol% of it exists as hydroxyl groups and the rest exists as intramolecular and intermolecular crosslinks, and the gel moisture content is 30
% or more, preferably 50% or more, of the bead-like polymer. In addition, as the acid used in the acidic heat treatment, any of inorganic acids such as nitric acid, sulfuric acid, hydrochloric acid, and phosphoric acid; and organic acids such as acetic acid, formic acid, citric acid, and malic acid can be used without any limitation. . In addition, heat treatment time is determined by heat treatment conditions (PH, temperature)
Although it is difficult to define it uniquely, it is preferable to minimize the residual amount of epoxy groups (substantially zero residual amount), and it is generally 0.5 to 0.
It is set within a range of 5 hours. Furthermore, as an aspect of such heat treatment operation, G
(M) Once separating the A-based spherical polymer from the aqueous suspension,
Either a method in which the polymer is washed and dehydrated and then reslurried in water for treatment, or a method in which a predetermined amount of acid is directly added to the polymer suspension after polymerization for treatment are possible. In this way, hydrophilicity (gel moisture content ≧30%)
Moreover, it is possible to provide bead-shaped polymers that are insoluble in solvents (i.e., hot water at 130°C and the solvent for G(M)A homopolymer) without causing problems in the working environment or safety, and without requiring complicated processes. This is a noteworthy effect of the present invention. The bead-shaped polymer according to the present invention can be widely used for various purposes such as a modifier for plastics, fibers, films, etc., but in particular, the bead-shaped polymer can be used to acylate or oxidize some of the hydroxyl groups. It can be suitably used as a gel for liquid chromatography after being alkylated. EXAMPLES The present invention will be described below in more detail with reference to Examples, but the scope of the present invention is not limited in any way by the description of these Examples. In the examples, parts and percentages are expressed on a weight basis unless otherwise specified. In addition, the gel moisture content is determined by centrifuging the polymer particles in sufficient equilibrium with deionization at 2000G.
After removing water adhering to the particle surface using a centrifugal separator, the weight (W ₁ ) of the polymer particles was measured, and then the polymer particles were dried and the dry weight (W ₂ ) was measured, and the following formula was used: It was determined by Gel water content = W ₁ - W ₂ / W ₂ × 100 (%) Example 1 20 parts of a water-soluble polymer of methacrylic acid/sodium p-styrene sulfonate = 70/30 and PVA (polymerization degree
1000, saponification degree 87%) dissolved in 778 parts of water,
The mixture was placed in a polymerization tank equipped with a paddle-type stirrer. next,
Dissolve 2 parts of 2,2-azobis-(2,4-dimethylvaleronitrile) in 200 parts of GMA, charge it to a polymerization tank, and polymerize at 60°C for 2 hours by changing the stirring conditions as shown in Table 1 below. PH=3).

[Table] The gel moisture content of the spherical polymers (No. ~) was measured and found to be 11%. Next, after filtering and washing the No. spherical polymer, it was reslurried in water adjusted to pH = 1.5 with nitric acid.
As a result of heat treatment at 80°C for 3 hours, water-swollen bead-shaped polymer (A) was obtained. The gel moisture content of this polymer (A) was 83%.
In addition, both polymers (No. and A) were heated at 130℃.
It is presumed that it is cross-linked because it does not dissolve in hot water or in organic solvents such as methyl ethyl ketone, the solvent for GMA. The obtained bead-like polymer (A) was sieved to 150
An intermediate product between mesh and 350 mesh was taken out and packed into a glass column with an inner diameter of 1.5 cm and a height of 30 cm to evaluate its performance as a gel for liquid chromatography. As a sample, 0.5 cc of an aqueous solution containing 5% each of NaCl and NaSCN was loaded into the column, and using deionized water as the eluent, the elution rate was 60 c.c./hour, resulting in 22.5 cc of NaCl and 36 c.c. of NaSCN. A concentration peak was observed at the elution volume of c., indicating almost complete separation. Example 2 The spherical polymer () produced in Example 1 was dispersed in a formic acid aqueous solution, and the acidic heat treatment conditions (PH, temperature, time) were varied as shown in Table 2 below.
Different types of bead-like polymers (B to E) were produced.
The results of measuring the gel moisture content are also listed in Table 2.

[Table] From the above table, it is understood that by employing the acidic heat treatment conditions according to the present invention, the desired bead-shaped polymer can be advantageously provided. In addition, using an aqueous solution containing 5% each of polyethylene glycol (average molecular weight 2000) and ammonium sulfate as samples, the gel performance of the bead-shaped polymer (D) was measured in Example 1.
When evaluated in the same manner as above, polyethylene glycol showed a concentration peak at 16.5 cc, and ammonium sulfate showed a concentration peak at 29 cc, indicating almost complete separation. Example 3 Example 1 (No. When polymerized in the same manner as .), a spherical polymer with an average particle size of 55 μm (gel moisture content: 13
%) was generated. Next, 80 parts of formic acid was added to the polymerization solution (PH=
1.6) and heat-treated at 95℃ for 3 hours, water-swollen bead-like polymer (F, gel moisture content: 65
%)was gotten. 5 each of macho acid, salt, sodium nitrate, and Rodin soda
% of the aqueous solution sample, the separation ability was evaluated in the same manner as in Example 1, and the elution curve shown in FIG. 1 was created.

[Brief explanation of drawings]

FIG. 1 shows the elution curve determined from Example 3.

Claims (1)

[Scope of Claims] 1. Glycidyl acrylate or glycidyl methacrylate alone or a monomer mixture consisting of 50% by weight or more of the above monomer and the remainder of at least one other monomer, which is substantially ethylenically unsaturated. In the presence of a water-soluble polymer containing a monomer unit consisting of a carboxylic acid or a salt thereof and a mixture unit consisting of an ethylenically unsaturated sulfonic acid or a salt thereof, and an oil-soluble radical polymerization initiator, at a pH of 2-9 and After aqueous suspension polymerization at a stirring speed of 50-400 r.pm,
A method for producing a bead-shaped polymer, characterized by heat treatment at a pH of 3 or lower and a temperature of 70°C or higher. 2. The manufacturing method according to claim 3, wherein the water-soluble polymer is used in an amount of 5% by weight or more based on the monomer. 3 Polymerization degree of 500-2000 and saponification degree of 85-
A method according to claim 1, in which 95% polyvinyl alcohol is present. 4. The production method according to claim 1, wherein the polymerization is carried out at a temperature of 80°C or lower. 5. Claim 1 of heat treatment for 0.5-5 hours
Manufacturing method described in section.