JPS63165411A - Production of crosslinked copolymer having aldehyde group - Google Patents

Abstract

PURPOSE:To readily produce the titled copolymer at a low cost, by reacting a copolymer of a haloalkyl group-containing monovinyl aromatic monomer crosslinked with a polyvinyl monomer with hexamethylenetetramine. CONSTITUTION:A copolymer of a monovinyl aromatic monomer having haloalkyl group crosslinked with a polyvinyl monomer, e.g. halomethyl group- containing polystyrene crosslinked with divinylbenzene, poly(vinylbenzyl chloride) crosslinked with divinylbenzene, etc., is reacted with hexamethylenetetramine in an amount of normally 1-1.3mol based on the above-mentioned copolymer in an aqueous medium to afford the aimed copolymer. The above-mentioned copolymer is useful as an adsorbent for beta2-microglobulin which is an etiologic substance in blood, intermediate for forming immobilized enzymes, immobilized germicides, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a method for producing a crosslinked copolymer having an aldehyde group, and more specifically, a method for producing a crosslinked copolymer having a haloalkyl group and hexamethylenetetramine. The present invention relates to a new method for producing a crosslinked copolymer having an aldehyde group, and the crosslinked copolymer having an aldehyde group produced by this method is particularly effective as an adsorbent for β2-microglobulin in blood.

Prior Art Recently, it has been known that low-molecular proteins that cannot be removed by hemodialysis etc. accumulate in the blood of renal failure or dialysis patients, and among these, β2-microglobulin frequently occurs in patients undergoing long-term dialysis As it has become clear that these substances are causative agents of amyloidosis, the development of methods for removing these substances has come to occupy an important therapeutic position.

Adsorbents are used to remove these substances. For example, activated carbon, anion exchange resins, and styrene-divinylbenzene copolymers have been used, but they have not been effective enough.

In Japanese Patent Application No. 61-160751, the present inventors disclosed that a crosslinked copolymer having an aldehyde group is β.

- It has been found that it is extremely useful as an adsorbent for microglobulin.

According to this, a copolymer crosslinked with a polyvinyl monomer is haloalkylated, and then the haloalkylated crosslinked copolymer or the crosslinked copolymer having a haloalkyl group is oxidized in the presence of dimethyl sulfoxide and a salt to form an aldehyde group. We manufacture crosslinked copolymers with

BACKGROUND ART Crosslinked copolymers having aldehyde groups crosslinked with polyvinyl monomers have been known.

As a specific example of its production, a polymer of about 1% of a low crosslinked monovinyl aromatic monomer is brominated, and then this brominated crosslinked copolymer is reacted in tetrahydrofuran and dimethylformamide to form an aldehyde. Manufactures crosslinked copolymers.

Problems to be Solved by the Invention In all of these production methods, a large amount of organic solvent is used, usually 3 to 6 times the amount of the copolymer, and it is difficult to dispose of the large amount of organic solvent after the reaction is completed. becomes a problem. Therefore, there is a need for a manufacturing method that reduces problems such as the amount of organic solvent used.

Means for Solving the Problem The present invention involves reacting a copolymer of a monovinyl aromatic monomer having a haloalkyl group crosslinked with a polyvinyl monomer and hexamethylenetetramine in an aqueous medium to produce a crosslinked copolymer having an aldehyde group. This is a new method for manufacturing bodies.

A copolymer of a monovinyl aromatic monomer having a haloalkyl group crosslinked with a polyvinyl monomer as a starting material of the present invention will be described.

The monovinyl aromatic monomer serving as the base and the polyvinyl monomer serving as the crosslinking agent are as follows.

Examples of monovinyl aromatic monomers include styrene, methylstyrene, clofrestyrene, clofrestyrene, ethylstyrene, chloroethylstyrene, vinylxylene, vinylnaphthalene, and the like.

It is also possible to copolymerize the monovinyl aromatic monomers with aliphatic monomers such as acrylonitrile, methacrylonitrile, acrylic acid, methacrylic acid, acrylic acid alkyl esters, and methacrylic acid alkyl esters.

Examples of poly and nyl monomers as crosslinking agents include polyvinyl aromatic monomers such as divinylbenzene, divinylnaphthalene, divinyltoluene, divinylxylene, trivinylbenzene, trivinylxylene, and diacrylic acid ethylene glycol ester, trimethylolpropane triacrylate, Examples include polyvinyl aliphatic monomers such as ethylene glycol dimethacrylate and butylene glycol di(meth)acrylate, diallyl adipate, and diallyl maleate. The amount of this crosslinking agent used can be arbitrarily selected.

The monomer mixture is copolymerized by a known polymerization method in the presence of additives such as a dispersant, a suspending agent, a polymerization initiator, a stabilizer, and, if necessary, a pore-forming agent that imparts porosity. Let's do it. This type of copolymer produced by known polymerization methods, particularly suspension polymerization, has a uniform particle size, and a desired particle size can be obtained by adjusting the stirring speed and the like.

It is also preferred because a copolymer with excellent strength can be obtained.

It is necessary to haloalkylate this copolymer using known procedures. For example, zinc chloride, anhydrous aluminum chloride,
A haloalkylated copolymer is obtained by treating tin chloride, iron chloride, etc. with a haloalkylating agent using a free sol fluorine catalyst. Examples of the haloalkylating agent used in this case include chloromethyl ether, chloroethyl ether, chloromethyl ethyl ether, and bromomethyl ether. Also, hydrochloric acid, thionyl chloride, as a chlorinating agent,
Halomethylation can also be achieved using a solution consisting of chlorosulfonic acid or the like, methanol, formalin, or the like. Usually, the reaction is carried out in a swollen state using an excess of haloalkylating agent, etc., and after the reaction is completed, it is necessary to remove the excess haloalkylating agent from the reaction product. After the completion of the reaction, the separated haloalkylated product can be brought into contact with water and an organic solvent compatible with the haloalkylating agent, such as alcohols such as methanol, ethanol, acetone, and dioxane, ketones, and ethers to form preferable haloalkylated particles. A crosslinked copolymer is obtained.

In addition, when it is composed of a polyvinyl monomer crosslinking agent and a monovinyl aromatic monomer such as chloromethylstyrene, chloroethylenestyrene, or chloromethylstyrene,
A crosslinked copolymer having a haloalkyl group can be obtained without going through a haloalkylation step.

Anion exchange resins having various basicities can be obtained by reacting various amines with such crosslinked copolymers having haloalkyl groups. That is, by reacting a tertiary amine such as trimethylamine or dimethylethanolamine, a strong basic anion exchange resin in the form of a quaternary ammonium salt is reacted with a secondary amine such as dimethylamine or monomethylethanolamine. A secondary amine type weakly basic anion exchange resin can be obtained by reacting a tertiary amine type or a primary amine such as monomethylamine.

The thus obtained crosslinked copolymer having a haloalkyl group is reacted with hexamethylenetetramine in an aqueous medium under heating. Hexamethylenetetramine may be used in the reaction in an amount of 1 to 2 moles, preferably 1 to 1.3 moles, based on the crosslinked copolymer.

The reaction medium is aqueous, particularly preferably under acidic conditions.

For example, 8' glacial acetic acid may be used. Since the amines and aldehydes produced during the reaction of the present invention tend to form thick bases, strong acids such as sulfuric acid or It is also important to add concentrated sulfuric acid to cause a reaction.

The reaction of the present invention is as follows: P CH2Cj2+ (CH2)eN-→[:P-C
H2・C6H12・N 4 f' + cβO[:P-
CH2'Cs HI3-N4]'+C19+6H20
→P-CHO+CH3NH2+2NH3+58CH○1NH, (1) It is estimated that the reaction mechanism is as follows.

Effects of the Invention Compared to conventional methods for producing crosslinked copolymers having aldehyde groups, the production method of the present invention does not require the use of a large amount of organic solvent as a reaction medium, and therefore post-treatment can be carried out easily. Hexamethylenetetrane and the like used as reaction reagents are relatively inexpensive, so the manufacturing cost is much lower than that of conventional methods.

The cross-linked copolymer having aldehyde groups produced by the production method of the present invention can be
It is extremely advantageous as an adsorbent for 2-microglobulin. It can also be used to produce immobilized enzymes and as an intermediate for immobilized fungicides.

Example 1 80 g of polystyrene crosslinked with divinylbenzene (crosslinking degree 3.6%/porosity 0.65e''/g),
Hexamethylenetetramine 168g, 250m
J2 of glacial acetic acid and 250 mj2 of water were added, and the mixture was refluxed for 4 hours to quench the reaction. Then, 200 m
Concentrated hydrochloric acid (1) was added and the reaction was further carried out for 1 hour.

After the reaction, the crosslinked copolymer was thoroughly washed with water, and then
% sodium carbonate aqueous solution and then water. Pale yellow beads were obtained.

This product weighed 210 g (wet).

Confirmation of aldehyde is 1700 by infrared absorption spectrum.
Stretching vibration between 620 and C of aromatic aldehyde near cm-' and 1290.1380 and C near 1195 cm-'
−〇I looked at vibration absorption.

Example 2 Poly(vinylbenzyl chloride) crosslinked with divinylbenzene (degree of crosslinking 5.4%/porosity 0°59cc/
g) 76g1 hexamethylenetetramine 168g
, 250 mJ2 of glacial acetic acid and 250 mJ of water were added, and the mixture was refluxed for 4 hours.

Next, 200 ml of concentrated hydrochloric acid was added to this reaction system, and 1 ml of concentrated hydrochloric acid was added.
A time reaction was performed. After the reaction was completed, the crosslinked copolymer was thoroughly washed with water, then with a 10% aqueous sodium carbonate solution, and then with water. Pale yellow beads were obtained.

This product weighed 195 g (wet).

The aldehyde was confirmed by infrared absorption spectrum.

That is, absorption of C=O stretching vibration of the aromatic aldehyde near 1700 cr' and 1290.1380 and C-C vibration near 1195 cm-' was observed.

Test Example The adsorbent manufactured by the present invention and the test serum (pooled serum from uremic patients) were added to a plastic tube so that the volume was 1 = 3, and the mixture was shaken for several seconds to mix the whole. The mixture was shaken at room temperature at a rate of 0 and then 2 times/sec, and the amount of β,-microglobulin in the serum was measured.

Note) β2-microglobulin was measured using a β2-microglobulin “Eiken” kit (manufactured and sold by Eiken Kagaku ■).

Claims (1)

[Claims] 1. A crosslinked copolymer having an aldehyde group, which is characterized by reacting a copolymer of a monovinyl aromatic monomer having a haloalkyl group and hexamethylenetetramine crosslinked with a polyvinyl monomer in an aqueous medium. Coalescing method. 2. The method according to claim 1, wherein the copolymer of a monovinyl aromatic monomer having a haloalkyl group crosslinked with a polyvinyl monomer is polystyrene having a halomethyl group crosslinked with divinylbenzene. . 3. Claim 1, characterized in that the copolymer of a monovinyl aromatic monomer having a haloalkyl group crosslinked with a polyvinyl monomer is poly(vinylbenzyl chloride) crosslinked with divinylbenzene. the method of.