JPS6134463A - Manufacture of gel for liquid chromatography - Google Patents

Abstract

PURPOSE:To improve the durability and separastion performance, by processing polymer particles mainly composed of glycidyl monovinyl ester or glycidyl monovinyl ether in a water medium acidified by organic monocarboxylic acid. CONSTITUTION:Glycidyl monovinyl ether or glycidyl monovinyl ether monomer of glycidyl acrylate, aryl glycidyl ether or the like and vinyl halide, insaturated carboxylic acid or the like polymerizable with the monomer are used and suspension polymerized to obtain a spherical polymer containing an epoxy group. Then, the polymer undergoes an acid processing in a water medium acidified by organic monocarboxylic acid of the formula (wherein, R represents H or 1-4C alkyl group or alkylene group) and the epoxy groups in the polymer particles are opened in the ring to introduce a hydroxide group. The gel for liquid chromatography thus obtained is inexpensive and has a better durability and a high separation performance.

Description

Detailed Description of the Invention (a) Industrial Application Field The present invention relates to a method for producing a gel for liquid chromatography (hereinafter referred to as liquid chromatography), and more specifically, the present invention relates to a method for producing a gel for liquid chromatography (hereinafter referred to as liquid chromatography), and more specifically, it relates to a method for producing a gel for liquid chromatography (hereinafter referred to as liquid chromatography). It relates to a method for producing a gel for liquid chromatography having durability and good separation performance by modifying the epoxy groups in the polymer and introducing hydroxyl groups therein.

p) Conventional technology - In recent years, liquid chromatography has been used not only as a means of analysis, but also in many 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 industrial separation means is progressing, and such gels for liquid chromatography include dextrane crosslinked polymer, 1% gel, acrylamide crosslinked polymer gel, crosslinked polystyrene gel, and crosslinked polyvinyl acetate gel. , cross-linked polyethylene glycol dimethacrylate gel, silanol polyoxyethylene gel, and a wide variety of other products have been developed. However, gels with high separation performance and high throughput are generally expensive; Problem to be Solved by the Invention As a result of intensive research aimed at providing a bead-shaped polymer that is inexpensive and has high separation performance, the present inventors have developed a spherical polymer containing an epoxy group. We discovered that by subjecting the coalescence to acidic heat treatment under specific conditions, a hydroxyl group is introduced by ring opening of the jepoxy group, and that a liquid chromatography gel with high separation ability can be provided industrially advantageously. -108422
However, it was found that the separation ability may gradually decrease with long-term use. After various studies on the cause of this, we found that the As a result of further detailed investigation, it was found that by using an acid with a specific structure, there was almost no decrease in separation ability even during long-term use, making it possible to use it under harsh industrial conditions. It has been found that it is possible to produce a gel for liquid chromatography that has stable performance even under low conditions.

That is, an object of the present invention is to provide a method for producing a gel for liquid chromatography that is inexpensive, has good durability, and has high separation performance.

B.) Means for Solving the Problems The object of the present invention described above is to obtain polymer particles containing glycidyl monovinyl ester or glycidyl monovinyl ether as a main component by acidifying them with an organic monocarboxylic acid represented by the following general formula. The epoxy groups in the polymer particles are treated in an aqueous medium to ring-open and introduce hydroxyl groups.The present invention will be described in detail below. First, the epoxy group-containing polymer used in the present invention is glycidyl monovinyl ester Manufactured using glycidyl monovinyl ether as the main component. Incidentally, examples of glycidyl monovinyl ester or glycidyl monovinyl ether include glycidyl esters of monovinyl carboxylic acids having 3 to 12 carbon atoms or glycidyl ethers of monovinyl alcohols having 8A to 12 carbon atoms, among which glycidyl acrylate and glycidyl methacrylate. , allyl glycidyl ether, methallyl glycidyl ether, etc. can be mentioned as suitable examples.

It should be noted that there is no problem in using other monomers that can be copolymerized with the above-mentioned monomer, which is the main component, as appropriate. Examples of such other monomers include vinyl chloride, bromide, etc. Vinyl halides and vinylidene halides such as vinyl, vinyl fluoride, and vinylidene chloride; Unsaturated carboxylic acids such as acrylic acid, methacrylic acid, maleic acid, and Ikuco7r11, and their salts; Methyl acrylate, ethyl acrylate, Acrylic acid esters such as ethyl acrylate, octyl acrylate, methoxyethyl acrylate, phenyl acrylate, and cyclohexyl acrylate; methyl methacrylate, ethyl methacrylate, butyl methacrylate, octyl methacrylate, methoxyethyl methacrylate, methacrylic acid Methacrylic acid esters such as phenyl and cyclohexyl methacrylate; unsaturated ketones such as methyl vinyl ketone, phenyl vinyl ketone, and methyl isopropenyl ketone; vinyl formate, divinyl acid, vinyl propionate, vinyl butyrate, vinyl benzoate, etc. Vinyl esters; Vinyl ethers such as methyl vinyl ether and ethyl vinyl ether; Acrylamide and its alkyl substituted products; Unsaturated hydrocarbon sulfonic acids such as vinyl sulfonic acid, allylsulfonic acid, methallylsulfonic acid, and p-styrene sulfonic acid; Salts; Styrene and its alkyl- or halogen-substituted products such as styrene, α-methylstyrene, and chlorostyrene; Allyl alcohol and hiso esters or honeycills; Basic vinyl compounds such as vinylpyridine, vinylimidazole, and dimethylaminoethyl methacrylate; Acrolein, methacrolein/
, vinylidene cyanide, allyl methacrylate, and the like. If necessary, cyhinylbenzene, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, N,Nl-methylenebisacrylamide, The polymer can also be actively crosslinked by using crosslinkable monomers such as divinyl succinate, diallyl succinate, vinyl methacrylate, allyl methacrylate, triallyl cyanurate, and triallyl isocyanurate.

By using such monomers and carrying out suspension polymerization in a medium that does not dissolve the resulting polymer, an epoxy group-containing spherical polymer can be obtained. The polymerization medium is not particularly limited as long as it does not adversely affect the polymerization reaction and does not promote ring opening of the epoxy group in the polymerization system.
Presence of a water-soluble polymer containing a monomer unit consisting of an unsaturated carboxylic acid or a salt thereof bonded to a monomer unit consisting of an ethylenically unsaturated sulfonic acid or a salt thereof, which is easy to handle and economical. This can be advantageously carried out by using an oil-soluble radical initiator.

The ethylenically unsaturated carboxylic acids or salts thereof to be introduced into the water-soluble polymer include unsaturated carboxylic acids such as acrylic acid, methacrylic acid, vinyl acetic acid, and crotonic acid; acid, itacon #
I, unsaturated polycarboxylic acids such as aconitic acid, citraconic acid, mesaconic acid, and their salts, etc., but monomer units consisting of methacrylic acid and its salts are particularly preferred from the viewpoint of forming spherical polymers. is recommended. Also, ethylenic unsaturated sulfonic acids or their salts, sulfonated styrene, allylsulfonic acid, methallylnurphonic acid, and other nurphonated unsaturated hydrocarbons and their salts;
Examples include sulfoalkyl nucleates of acrylic or methacrylic acid, such as nulphoethyl methacrylate and sulfopropyl methacrylate, and salts thereof.

Although it is difficult to define the amount of the water-soluble polymer to be used, it is desirable to use it in an amount of 5% by weight or more based on the monomer.

Furthermore, examples of the oil-soluble radical polymerization initiator include the following azo compounds or organic peroxides. For example, the azo compounds include 2,2I-azobisisobutyronitrile, 2,21-azobis(2-methyl-valeronitrile), 2,2'-azobis(2,4-dimethylbutyronitrile), 2. 2'-azobis(2-methylcapronitrile), 2,2'-azobis(2,3.8-)dimethylbutyronitrile), 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 organic peroxide Examples include acetyl peroxide, propionyl peroxide, isobutyryl peroxide, octanoyl peroxide,
Diacyl peroxides such as decanoyl peroxide, lauroyl peroxide, 8,5.5-)limethylhexanoyl peroxide, benzoyl peroxide, diisoproyl peroxydicarbonate, di-2-ethylhexyl peroxydicarbonate; t-butyl peroxyisobutyrate, t-butyl peroxy pivalate, t-butyl peroxyneodocaate,
Peroxyene ethers such as -butyl peroxylaurate and the like can be used.

The particle size of the final gel is determined almost exclusively by the size of the epoxy group-containing polymer particles, and the size of the polymer particles obtained by suspension polymerization is determined by the stirring conditions during polymerization. The stirring conditions are controlled so that the particle size is 10 to 300μ, which is suitable for use as a gel for liquid chromatography.

Such a suitable aqueous suspension means is described in further detail in Japanese Patent Application No. 104735/1983 filed by the present applicant.

Next, the acid treatment method which is a central component of the present invention will be described. The acid treatment method has a pH of 8 or less, preferably 2.
5 or less, and preferably at a temperature of 50'C or higher, preferably 60'C or higher, in an aqueous medium.As the acid used during such treatment, an organic monocarboxylic acid represented by the general formula below is adopted. This is particularly important.

Examples of the organic monocarboxylic acids that can be used include formic acid, acetic acid, propionic acid, crotonic acid, nephric acid, caproic acid, etc. Among them, formic acid, acetic acid, and propionic acid give good results, This acidic treatment makes it possible to produce a liquid chromatography gel with excellent separation stability, especially for long-term use.

In addition, the treatment time varies depending on the acidic treatment conditions (p) (and temperature), and is difficult to define unambiguously, but it is preferable to minimize the amount of remaining epoxy groups, and it is approximately 0.
．． It is set within the range of 5 to 5 hours.

Furthermore, such acid treatment operations include a method in which an epoxy group-containing polymer is once separated from a liquid obtained by polymerization, washed, and dehydrated, and then treated by re-nullifying in water, and a method in which a polymer suspension after aqueous polymerization is treated. Any of the methods of treatment by directly adding a predetermined amount of acid to is possible.

By the above-mentioned method, a hydrophilic and solvent-insoluble gel having a gel moisture content of preferably 30% or more and suitable as a gel for liquid chromatography can be produced with industrial advantage.

The reason why it is possible to provide a hydrophilic gel that exhibits excellent durability and separation ability by 9% when using the specific organic monocarboxylic acid according to the present invention as the acid used in fI9 action acidic treatment can be provided industrially advantageously has been fully elucidated. Although it has not yet been determined, it is estimated as follows.

When using an inorganic acid such as nitric acid or sulfuric acid, it is assumed that some of the anionic groups of the inorganic acid will be added to the polymer, causing further deterioration during use as a liquid chromatography gel. When using an acid having two or more carboxyl groups, it is estimated that some of the nucleic acids will be added to the polymer and carboxyl groups will be introduced into the gel, which will have an undesirable effect on separation performance. Ru. In addition, when using an organic aliphatic monocarboxylic acid with a carbon number exceeding the upper limit of the present invention, the catalytic effect for ring-opening the epoxy group and effectively introducing the hydroxyl group will be reduced, making it difficult for industrial use. It is inappropriate as a manufacturing method.

(F) EXAMPLES The present invention will be described in more detail with reference to Examples below, 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 water content is determined by measuring the weight (W) of polymer particles that have been sufficiently equilibrated with deionized water, passing them through a centrifugal separator with a centrifugal effect of 2000 G to remove water adhering to the surface of the particles, and then measuring the weight (W) of the polymer particles. After drying the polymer particles, the weight after drying (W
2) was measured and determined by the following formula.

Example 1 Methacrylic acid/p-styrene sodium sulfonate 70/
20 parts of a water-soluble polymer of No. 80 was dissolved in 780 parts of water and charged into a polymerization tank equipped with a seed stirrer. Next, 2 parts of 2,2-azobis-(2,4-dimethylvaleronitrile) was dissolved in 200 parts of glycidylmegcrylate and charged into a polymerization tank.
CX was polymerized for 2 hours.Next, 50 parts of formic acid was added to this, and the mixture was treated with stirring for 90"cX, resulting in water swelling.
Mar was obtained. This polymer has a gel water content of 9,296% and is insoluble in hot water of % ISO'c or in organic solvents such as methyl ethyl ketone or alcohols, which are the solvents for GMA, so it is assumed that it is crosslinked. Presumed.

The obtained bead-like polymer was sieved to take out an intermediate product of 150 mesh and 850 mesh, and the inner diameter was 1.5 cm.
The performance as a gel for liquid chromatography was evaluated by packing it into a glass column of m x height 30 (7).
a2SO4, NaC1! , 5 each of NaN03NaSCN
A column was charged with 5 cc of an aqueous solution Q containing 5 % of Q, and the column was operated at an elution rate of 6 Q and cc/hour using deionized water F as an eluent, and a separation curve as shown in Figure 1 was obtained. .

Even after repeating the separation operation 80 times, the separation curve showed almost no change.

In contrast, a bead-shaped polymer (gel moisture content: 286%
) was similarly evaluated. The results are shown in Figure 2.

As can be seen from these results, when formic acid was used as the acid, there was almost no change in separation ability even after repeated use 80 times, whereas when sulfuric acid, which is strictly an inorganic acid, was used, the initial It is understood that although it shows a good separation ability similar to that when formic acid is used, the separation ability decreases after repeated use 30 times.

Example 2 Gel moisture I! was prepared under the same conditions as Example 1 except that acetic acid was used instead of formic acid. An 88% hydrophilic gel was produced.

This gel showed the same performance as Example 1 using formic acid, and no change was observed even after repeated use 80 times.

(G) Effects of the Invention Thus, it is possible to obtain an industrially advantageous liquid chromatography gel that is inexpensive, has excellent separation ability, and has good durability without changing its separation ability even after long-term industrial use. A notable effect of the present invention is that it has been able to provide a production method, and the appearance of such a means will play a large role in the field of industrial separation applications.

[Brief explanation of the drawing]

FIG. 1 shows the separation curve according to the present invention obtained from Example 1, and FIG. 2 shows the separation curve according to the comparative gel (solid line: 1
The dotted line indicates the number of uses (after 30 uses). 11 Kiri Urushimei () (C no Hiroya Ar-arm (C02

Claims (1)

[Claims] 1. Polymer particles containing glycidyl monovinyl ester or glycidyl monovinyl ether as a main component are treated in an aqueous medium acidified with an organic monocarboxylic acid represented by the following general formula; A method for producing a gel for liquid chromatography, which comprises introducing a hydroxyl group by ring-opening an epoxy group in particles. General formula: RCOOH (where R is H or C_1-_4
represents an alkyl group or an alkylene group. 2. The manufacturing method according to claim 1, which uses polymer particles having a particle size of 10 to 300 μm. 3. The production method according to claim 1, wherein formic acid, acetic acid, or propionic acid is used as the organic monocarboxylic acid. 4. The manufacturing method according to claim 1, in which the pH is acidified to 3 or less. 5. The manufacturing method according to claim 1, in which treatment is performed at a temperature of 50° C. or higher. 6. Glycidyl (as glycidyl monovinyl ester)
The manufacturing method according to claim 1, which uses meth)acrylate. 7. The production method according to claim 1, wherein (meth)allyl glycidyl ether is used as the glycidyl monovinyl ether.