JPS5811885B2 - Method for manufacturing a polymonovinyl aromatic compound matrix molded product having an acrylic (or methacrylic) amidomethyl group - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a novel molded article of an insoluble polymonovinyl aromatic compound having a crosslinked structure with an acrylic (or methacrylic) amidomethyl group (hereinafter simply referred to as an acrylamide methyl group).

Conventionally known insoluble chloromethylated polystyrene is a very important substance as an ion exchange resin, a matrix for enzyme immobilization, a matrix in solid phase synthesis of peptides, and the like.

However, it has recently been discovered that the chloromethyl ether used in the production of this substance is a carcinogen, and there is little hope that an alternative production route can be found. The emergence of functional polymers that can replace these is desired.

The necessary conditions for such a functional polymer are that it can be obtained relatively easily and at low cost, and that the functional groups of the polymer must be suitable for enzymes, peptide chains, or bridges when introducing them. It is possible to form a covalent bond under mild conditions with a reagent that should play a role.

The present inventors have arrived at the present invention as a result of intensive studies to find a polymer molded product that satisfies these requirements.

The present invention has the following configuration.

That is, in the present invention, a molded product made of an insoluble vinyl polymer or vinyl copolymer of a vinyl compound having an aromatic nucleus is reacted with an acrylic (or methacrylic) amide methylating agent represented by the following general formula, and at least 0.01 mole of acrylic ( or an insoluble polymonovinyl aromatic compound having an acrylic (or methacrylic) amidomethyl group, characterized by containing an acrylic (or methacrylic) amidomethyl group.
Manufacturing method for Lux type products.

"Here, R,, R2 is H or an alkyl group, and (R
4 is an alkyl group)) (R1 and R2 are the same as R1 and R2 above)).

)” The molded product of the present invention is characterized by having both a vinyl group and an amide bond.

That is, the vinyl group can undergo the addition reaction of primary and secondary amine compounds at room temperature to 100°C without a catalyst, and can undergo the addition reaction of hydroxyl groups in the presence of a basic catalyst. .

For example, when insoluble acrylamide methylated polystyrene fibers are reacted in dimethylamine or an aqueous methylamine solution at 60° C. for 10 hours, 100% of the acrylamide methyl groups are converted to aminoethylcarboxamidomethyl groups.

Furthermore, an addition reaction of about 60% occurs with ethylene glycol in the presence of an alkali hydroxide at 90° C. for 10 hours.

In addition, in reactions with enzymes and polypeptides, the internal acrylamide methyl group does not react because the molecules of the prime and polypeptide are large, but the acrylamide methyl group near the outside reacts with the amine group contained in those molecules. The addition reaction can be carried out under mild conditions.

It can also be attacked by Carbanion.

The amide bond is originally inside the molded product, which is hydrophobic and non-polar, but it provides a new polar atmosphere, helps the polar molecules that should react with the vinyl group to diffuse into the molded product, and allows the reaction to occur. is also being promoted.

This is an effect not seen in conventional chloromethylated polymers, which are less susceptible to attack by hydrophilic reagents such as sodium iminodiacetate, even though the chloromethyl group has very high reactivity.

Further, this amide bond is relatively stable against sulfuric acid, and is hardly hydrolyzed, for example, even when heated in 12N sulfuric acid at 50° C. for several hours.

The crosslinking density of the molded product of the present invention is not particularly limited, but if the density is high, the swelling property will be low, and if the density is low, the swelling property will be poor, so it is best to select it depending on the intended use.

For example, in reactions with large molecules such as immobilization of enzymes,
Molded products with high swelling properties are suitable.

However, as will be described later, there are limitations to some extent due to manufacturing technology.

The amount of acrylamide methyl groups present in the molded product of the present invention is
From a practical point of view, it is preferable that the polymer as a whole exists at a density of 0.01 mol or more, more preferably 0.2 mol or more per 1 mol of aromatic nuclei. In such a case, the density of acrylamide methyl group per mole of aromatic nucleus in the polymer in the vicinity of the surface of the molded article should be 0.2 mole or more.

The insoluble polymonovinyl aromatic compound referred to in the present invention includes an aromatic vinyl compound obtained by copolymerizing a monovinyl compound and a polyvinyl compound that acts as a crosslinking agent by a known method, and a polymonovinyl aromatic compound. There are aromatic vinyl compounds obtained by crosslinking and insolubilizing them by various methods.

Examples of methods for crosslinking and insolubilizing here include (1)
(2) A method of reacting a tribasic acid chloride or dihalide with a tribasic acid chloride or dihalide in the presence of a Friedel-Kraf catalyst, ( 3) A method of sulfone crosslinking by treatment with chlorosulfonic acid, and (4
) Methods include treatment with formaldehyde under a sulfuric acid catalyst.

However, in methods (1) to (3), the reaction occurs rapidly, making it difficult to control the reaction, and local crosslinking is likely to occur.
Furthermore, since non-aqueous reaction conditions are required, there is a drawback that the polymer is easily dissolved and the mechanical properties of the molded product are easily deteriorated.

On the other hand, the method (4) uses hydrophilic reaction conditions and the reaction proceeds slowly, making it easy to control the reaction and
This is the most suitable method for carrying out the present invention because it has the advantage of being able to crosslink more uniformly to the inside of the molded product.

As the monovinyl compound, a monovinyl compound having an aromatic nucleus represented by styrene, α-methylstyrene, vinyltoluene, vinylxylene, vinylnaphthalene, P-chlorostyrene, vinylfluorene, etc. is preferable.

In addition, as polyvinyl compounds, divinylbenzene,
Examples include divinyltoluene, divinylnaphthalene, divinyl ether, and ethylene glycol diacrylate, but preferably a polyvinyl compound having an aromatic nucleus is employed.

Examples of polymonovinyl aromatic compounds include styrene, α
-methylstyrene, vinyltoluene, vinylxylene,
A vinyl polymer of a monovinyl compound having an aromatic nucleus such as vinylnaphthalene, P-chlorostyrene, vinylfluorene, etc., a vinyl copolymer of two or more of these monomers, or a combination of these monomers with other vinyl compounds (e.g., ethylene). , propylene, vinyl acetate, vinyl chloride, methyl acrylate, acrylonitrile, allyl alcohol, vinylanisole, vinylacetophenone, etc.), or a mixture of these polymers and polyolefins.

In particular, mixing 20 to 70% polyolefin is practical because the mechanical properties are significantly improved.

Crosslink density plays a major factor in acrylamide methylation reactions.

That is, if the crosslinking density is low, the polymer may dissolve into the swelling agent, and if the crosslinking density is high, the acrylamide methylation reaction will not proceed easily.

When using a copolymer of a monovinyl compound and a polyvinyl compound that acts as a crosslinking agent, the amount of the polyvinyl compound used is used as a guideline for the crosslinking density.

The amount of polyvinyl compound used in the acrylamide methylation reaction that provides a preferable crosslink density is 0.5 to 10% by weight.

(However, in the case of MR type, it is 5 to 50% by weight.

) Furthermore, when crosslinking and insolubilizing a polymonovinyl aromatic compound, it is preferable to provide a crosslinking density that is approximately the same as the crosslinking density that was considered preferable when using the former copolymer by the method described above.

The crosslinking density given to the polymonovinyl aromatic compound is
This can be determined by the crosslinking rate.

For example, in a polymonovinyl aromatic compound containing 50 parts of polystyrene and 50 parts of polypropylene, the crosslinking rate with respect to the crosslinking density considered preferable when using the former copolymer is 15 to 100%.

Here, the crosslinking rate is a value determined by the following method.

0.5 g of the sample is immersed in 200 times the volume of toluene, shaken at room temperature for 5 hours, and then heated under reflux for 2 hours.

Next, take out the sample while it is hot, wash it with warm toluene, vacuum dry it, and calculate the weight before and after using the following formula.

Crosslinking rate - (W2/W,)xlo o (%) where Wl
: Weight of the sample before toluene extraction W2: Weight of the sample for the number of toluene extractions The molded product as referred to in the present invention is 0.5 m in at least one direction.
It means resins, fibers, or films with a length of m or less, and highly processed products thereof.

The acrylamide methylating agent used in accordance with the present invention is represented by the formula below.

Here, R,, R, is hydrogen or alkyl, and Z is.

The acrylamide methylation agent used in the present invention includes N-methylol acrylamide, N-methylol methacrylamide, carboxylic acid ester derivatives thereof, or alkyl ether derivatives thereof, N,
N'-(oxydimethylene)bisacrylamide is mentioned.

Among them, a preferable acrylamide methylating agent is N
-methylolacrylamide, N,N'-(oxydimethylene)bisacrylamide.

Suitable swelling agents for polymers include, among others, dichloromethane, carbon tetrachloride, dichloroethane, trichloroethylene, and
Dichloroethane, symmetrical tetrachloroethane, tetrachlorethylene, and other halogenated hydrocarbons, and 1
- or 2-Aliphatic or aromatic hydrocarbons substituted with nitro groups, such as nitropropane, nitroethane or nitrobenzene.

The above-mentioned swelling agents can be used individually or mixed with each other.

Preferably the swelling agent is ■- or 2-nitropropane,
An aliphatic or aromatic hydrocarbon substituted with a nitro group, such as nitroethane or nitrobenzene.

Suitable acid catalysts include Friedelkraff catalysts such as aluminum chloride, tin tetrachloride, ferric chloride, zinc chloride and especially strong organic acids such as aliphatic and aromatic sulfones such as methane, benzene and toluene sulfonic acids. Acids and strong inorganic acids, especially sulfuric acid (concentrated and fuming sulfuric acid)
It is.

Sulfuric acid is preferred as a catalyst due to its ready availability and other practical considerations.

The reaction according to the invention can be carried out at a temperature range of about 5°C to about 60°C, but preferably from about 5°C to about 30°C.

The amount of the acrylamide methylating agent is 0.2 to 5.0 mol, preferably 0.5 to 3.0 mol, per 1 mol of aromatic nucleus in the polymer.
It is advantageous to use amounts such that 0 mol is present.

(N, N'-4 oxydimethylene) bisacrylamide can be used in half of this amount.

) The amount of acid catalyst can vary within a wide range.

Generally, the acid catalyst is
．． It is advantageous to use amounts of 0 to 20.0 mol, preferably 4.0 to 14.0 mol.

The amount of swelling agent used depends on the swelling ratio with the polymer to be acrylamide methylated and the morphology of the polymer.

The swelling ratio will vary somewhat depending on the swelling agent used and the crosslink density of the polymer.

Also, regarding the change in the amount of swelling agent depending on the form of the polymer, fibrous polymers require the most amount of swelling agent.

The lower limit of the amount of swelling agent to be used is determined by the maximum amount that the polymer can soak in, and the upper limit is determined by operability and economic efficiency, and is 200 m1 to 50001 r111 per 100 g of polymer.
Preferably it is 300rrLl to 3000ml.

The acrylamide methylation reaction can be easily carried out by mixing the acrylamide methylation agent, an acid catalyst, a swelling agent, and an insoluble polymonovinyl aromatic compound molded product.

Although there is no limitation on the order in which the above reagents and polymers are mixed, it is necessary to add the reagents and polymers so that the temperature of the reaction system is maintained at 20° C. or lower.

A preferred method is to add a molded article of an insoluble polymonovinyl aromatic compound, which has been swollen with a swelling agent, to a solution in which a swelling agent, an acrylamide methylating agent, and an acid catalyst are mixed in this order.

The molded product of the present invention can be used as a matrix for enzyme immobilization, a matrix for solid phase synthesis of peptides, etc., which has not been achieved in the past, by a technically simple and inexpensive method.

Examples will be described below.

Example 1 50 parts of polypropylene (Mitsui Noblen J3HG) was used as the island component, 40 parts of polystyrene (Styron 666),
1.5 g of multicore sea-island composite fiber (number of islands: 16, single fiber fineness: 4.9 denier, tensile strength: 2.7 g/d, elongation: 40%) containing a mixture of 10 parts of polypropylene as the sea component was mixed with concentrated sulfuric acid at 70%.
5 parts, 25 parts of acetic acid, and 5 parts of paraformaldehyde.
After reacting at 80° C. for 2 hours, the fibers were washed with water and dried under vacuum to obtain 1.6 g of crosslinked fibers.

The crosslinking rate of this crosslinked fiber was 31.2%.

1.0 g of this crosslinked fiber was added to 10 mL of nitrobenzene at 3
Let it swell for 0 minutes, and add the previously prepared acrylamide methylation reaction solution (1.0 g of N,N'-(oxydimethylene)bisacrylamide, 7.0 g of concentrated sulfuric acid,
The crosslinked fibers containing this swelling liquid were added to a mixture of 10 ml of nitrobenzene (slowly mixed and dissolved so that the temperature of the solution did not exceed 20°C), stirred at 20°C for 16 hours, and then water was added until the temperature of the solution was 30°C. It was added slowly so as not to exceed the temperature.

Next, the fibers were taken out of the solution, thoroughly washed with water and methanol to completely eliminate residual nitrobenzene, and then dried to obtain 1.42 g of acrylamide methylated fibers containing 5.0% by weight of nitrogen.

The amount of acrylamide methyl groups in this acrylamide methylated fiber was determined by the amount of double bonds by the iodine monochloride method and the amount of amino groups in the aminomethylated fiber obtained after hydrolysis with concentrated hydrochloric acid. 1.31 moles of acrylamide methyl groups were introduced per mole of nucleus.

Example 2 1.0 g of crosslinked fibers prepared in the same manner as in Example 1 were swollen in 10 ml of nitrobenzene for 30 minutes.
To the acrylamide methylation reaction solution prepared in the same manner as above,
Add the crosslinked thread containing this swelling solution, and set the reaction temperature to 20°C and 40°C.
After reacting at 0° C. and 60° C. for 16 hours, the same post-treatment as in Example 1 was performed to obtain acrylamide methylated fibers.

Table 1 shows the weight, acrylamide methyl group content, and nitrogen content of this fiber.

Note that the quantitative method was the same as in Example 1.

In Table 1, No. 2 and No. 3 have a higher nitrogen content than the amount of acrylamide methyl groups.

This means that due to the high reaction temperature, some of the acrylamide methylating agents lost double bonds after the reaction, or lost double bonds before reacting.

Example 3 10 g of styrene copolymer (average particle size 100 μ) copolymerized with 2% divinylbenzene was added to 30 m of nitrobenzene.
12.5 g of the previously prepared acrylamide methylation reaction solution (N,N'-(oxydimethylene)) bisacrylamide, 100 g of concentrated sulfuric acid, and 50 ml of nitrobenzene were added to The styrene copolymer containing this swelling liquid was added to the mixture (mixed slowly so as not to exceed 20°C), and the mixture was heated to 16°C at 20°C.
After stirring for an hour, water was slowly added so that the temperature of the liquid did not exceed 30°C.

Next, the polymer was taken out of the solution, thoroughly washed with water and methanol to completely eliminate residual nitrobenzene, and then dried to obtain 17.8 g of an acrylamide methylated polymer containing 7.4% nitrogen.

Example 1 The amount of acrylamide methyl groups in this polymer was
As a result of quantitative determination in the same manner as above, it was found that 0.96 mol of acrylamide methyl group was introduced per 1 mol of aromatic nucleus in the polymer.

Example 4 Using 1.5 g of the same fiber as in Example 1, it was placed in 50 g of a reaction solution of 70 parts of concentrated sulfuric acid, 25 parts of acetic acid, and 5 parts of formaldehyde, and reacted at 80°C for 1 hour, 2 hours, 4 hours, and 6 hours. After that, the fibers were washed with water and dried under vacuum to obtain crosslinked fibers.

The crosslinking rates of these crosslinked fibers are 22.2% and 31%, respectively.
They were 2%, 40.2%, and 48.9%.

Using 1.0 g of each of the crosslinked fibers, an acrylamide methylation reaction was carried out in the same manner as in Example 1, followed by post-treatment in the same manner as in Example 1 to obtain acrylamide methylated fibers.

Table 2 shows the weight and acrylamide methyl group content of this fiber.
Shown below.

The quantitative method was the same as in Example 1.

Example 5 Various acrylamide methylated fibers were obtained in the same manner as in Example 1 except that the following agents were used in the following amounts as acrylamide methylating agents.

(1) N,N'-(oxydimethylene)bisacrylamide 1. Og(2)
N-methylolacrylamide 1.1g (3)N
-Methoxyacrylamide 1.3g Table 3 shows the weight of acrylamide methylated fibers and the amount of acrylamide methyl groups when the above three types of acrylamide methylating agents were used.

Note that the quantitative method was the same as in Example 1.

As can be seen from Table 3, it is advantageous to use N,N'-(oxydimethylene)bisacrylamide and N-methylolacrylamide as the acrylamide methylating agent.

Note that No. 1 in Table 3 corresponds to (1) above, and No. 2 corresponds to (1) above.
Boiled 3 corresponds to (2) above, and Boiled 3 corresponds to (3) above.

Claims (1)

[Scope of Claims] 1. A molded product made of an insoluble vinyl polymer or vinyl copolymer of a vinyl compound having an aromatic nucleus is reacted with an acrylic (or methacrylic) amide methylating agent represented by the following general formula, and at least 0.01 mol of 1. A method for producing an insoluble polymonovinyl aromatic compound matrix molded product having an acrylic (or methacrylic) amidomethyl group, characterized by containing an acrylic (or methacrylic) amidomethyl group. Here, R1 and R2 are H or an alkyl group, and 7 is 0
R3 (R3 is a H1 alkyl group -C-R4CR4 is an alkyl group), (R1 and R2 are the same as R1 and R2 above). )