JPH0247550A - Manufacture of bridging copolymer grain and column filler - Google Patents

Abstract

PURPOSE:To obtain a column filler characterized by acid resistance, alkali resistance, small differences in swellings and shrinkages among various kinds of solvents by performing hydrolysis of a glycidyl group in gel grains obtained by aqueous suspension polymerization in the presence of acid which does not react with the alycidyl group. CONSTITUTION:A mixed material of, e.g., stearyl acrylate, glycidyl methacrylate, ethylene glycol dimethacrylate, toluene and azobisisobutyronitrile is suspended and stirred in the aqueous solution of methylcellulose so as to cause reaction. The formed gel grains are filtered, cleaned and dried with air. The gel grains are impregnated with methanol. Thereafter, the grains are suspended in 0.5 sulfuric acid. A glycidyl group undergoes hydrolysis, cleaning and drying. The gel grains obtained in this way have excellent acid resistance and alkali resistance and have the small differences in swellings and shrinkages among various kinds of solvents. Therefore, the gel grains are useful as a column filler for reverse-phased partition chromatography.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention provides a method for producing crosslinked copolymer particles useful as a column packing material for liquid chromatography, particularly a column packing material for reversed phase partition liquid chromatography, and Regarding column packing material.

[Conventional technology]

Conventionally, as a separation method of liquid chromatography,
Reversed phase partition chromatography is known, which separates samples based on the strength of retention due to differences in hydrophobicity, and the following are generally known as column packing materials used in reversed phase liquid chromatography. .

(1) Chemically bonded silica gel chemically modified with a silane coupling agent having octadecyl groups on the surface of silica gel [J.J. Kirkland, J.J.
D'Esteefano, Journal of Chromatography Science
5science) Volume 8, page 309,
1970] (2) Styrene-divinylbenzene copolymer particles [M.D. Greaser, D.G. Pietzanck, Analytical Chemistry (^nalytica)
l Chemistry) Volume 45, Page 1383, 19
1973] (3) Methacrylic acid ester copolymer particles having a long alkyl chain (Japanese Unexamined Patent Publication No. 1983-90533) [Problems to be solved by the invention] Of the above, the silica gel in (1) is alkali-based. The disadvantage is that the pH of the eluent is limited to 2 to 8 and cannot be used in all pH ranges.Furthermore, it is difficult to chemically bond all the silanol groups on the silica surface, and unreacted silanol Since the groups remain, there is a problem in that specific adsorption occurs for basic samples.

In addition, although the copolymer particles (2) and (3) have solved the problem related to (1) silica gel, they swell and shrink rapidly between various solvents, so it is necessary to change the eluent in the column.
There is a problem in that it is difficult to perform chromatography.

The present invention solves these problems and provides a crosslinked copolymer useful as a column packing material for reverse phase partition liquid chromatography, which has acid and alkali resistance and has small differences in swelling and shrinkage between various solvents. The purpose is to provide particles.

[Means to solve the problem]

The present invention provides a vinyl ester of an aliphatic alcohol having 6 to 24 carbon atoms or a vinyl ether (I) of an aliphatic alcohol having 6 to 24 carbon atoms, a glycidyl monovinyl ester or a glycidyl monovinyl ether (II),
It is characterized by hydrolyzing the glycidyl groups of gel particles obtained by aqueous suspension polymerization of polyvinyl ester of polyhydric alcohol or polyvinyl ether (III) of polyhydric alcohol in the presence of an acid that does not react with the glycidyl groups. The present invention relates to a method for producing crosslinked copolymer particles.

The aliphatic chain of the aliphatic alcohol used in the present invention is necessary to impart a separation function, and if the number of carbon atoms is 5 or less, the separation accuracy will be poor, and if the number of carbon atoms is 25 or more, the synthesis is difficult and is not suitable for practical use.

As the vinyl ester of an aliphatic alcohol having 6 to 24 carbon atoms or the vinyl ether (I) of an aliphatic alcohol having 6 to 24 carbon atoms used in the present invention, methacrylic acid of an aliphatic alcohol having 6 to 24 carbon atoms is used. Examples include esters, acrylic esters, and allyl ethers. Considering reactivity, alkali resistance, and easy industrial availability, stearyl methacrylate and lauryl methacrylate are preferred.

The glycidyl group of the glycidyl monovinyl ester or glycidyl monovinyl ether used in the present invention is copolymerized with a vinyl group and then hydrolyzed in the presence of an acid that does not react with the glycidyl group to generate a hydroxyl group. Due to the action of this hydroxyl group, the difference in swelling and contraction of the produced crosslinked copolymer particles can be reduced.

Examples of the glycidyl monovinyl ester or glycidyl monovinyl ether used in the present invention include glycidyl methacrylate, glycidyl acrylate, and allyl glycidyl ether, but glycidyl methacrylate is preferred in consideration of reactivity and alkali resistance.

The polyvinyl ester of polyhydric alcohol and the polyvinyl ether of polyhydric alcohol used in the present invention include:
For example, alkylene glycol divinyl esters such as ethylene glycol dimethacrylate, ethylene glycol diacrylate, propylene glycol dimethacrylate, and propylene glycol diacrylate; divinyl ester of alkylene glycol,
Di- or triacrylate of glycerin, di- or trimethacrylate of glycerin, di- or trimethacrylate of trimethylolpropane, di- or triacrylate of trimethylolpropane, di- or trimethylolmethane,
tri- or tetramethacrylate, di-, tri- or tetraacrylate of tetramethylolmethane, ethylene glycol diallyl ether, propylene glycol diallyl ether, polyethylene glycol diallyl ether,
Examples include polypropylene glycol diallyl ether, di- or triallyl ether of glycerin, di- or triallyl ether of trimethylolpropane, di-, tri- or tetraallyl ether of tetramethylolmethane, etc.; In consideration of pressure resistance, polymethacrylic acid ester of polyhydric alcohol is preferred. Among these, ethylene glycol dimethacrylate and tetramethylolmethane di, tri, or tetramethacrylate are more preferred.

Polyvinyl ester of polyhydric alcohol or polyvinyl ether of polyhydric alcohol (II[) is 5 to 70 mol%
It is preferable to use it within the range of .

If it is less than 5 mol%, the pressure resistance of the produced crosslinked copolymer particles will be poor. If it exceeds 70 mol%, the separation accuracy of the produced crosslinked copolymer particles will deteriorate.

The ratio of vinyl ester of aliphatic alcohol having 6 to 24 carbon atoms or vinyl ether of aliphatic alcohol having 6 to 24 carbon atoms (1) and glycidyl monovinyl ester or glycidyl monovinyl ether (II) is (I
If the amount of (II) is too small, the separation accuracy will be poor as a column packing material for reverse phase chromatography, and if the amount of (II) is too small, the differences in swelling and contraction of the crosslinked copolymer particles formed between the solvents will be large ( Therefore, the molar ratio of (r)/(II) is preferably in the range of 5 to 0.03.

In the present invention, vinyl ester of aliphatic alcohol having 6 to 24 carbon atoms or vinyl ether (I) of aliphatic alcohol having 6 to 24 carbon atoms, and glycidyl monovinyl ester or glycidyl monovinyl ether (II)
and the polyvinyl ester of a polyhydric alcohol or the polyvinyl ether (III) of a polyhydric alcohol are subjected to aqueous suspension polymerization in the presence of an organic solvent incompatible with water as necessary to form crosslinked copolymer particles. .

Aqueous suspension polymerization involves suspension polymerization in an aqueous medium, and water is essential as this aqueous medium, and a water-soluble organic solvent must be dissolved within the range that does not impede the stability of the suspension system. You can also use water that has been drained.

Suitable polymerization initiators for use in the present invention include benzoyl peroxide, dichlorobenzoyl peroxide, dicumyl peroxide, di-tert-butyl peroxide, 2,5-di(peroxybenzoate)hexyne-3,1, 3-bis(tert-butylperoxyisopropyl)benzene, lauroyl peroxide, tert-butyl peracetate, 2,5-dimethyl-2,
5-di(tert-butylperoxy)hexyne-3,2,5
Organic peroxides such as dimethyl-2,5-di(tert-butylperoxy)hexane and tert-butyl perbenzoate, methyl ethyl ketone peroxide, methylcyclohexanone peroxide, azobisisobutyronitrile and dimethylazodiisobutyrate There are azo compounds such as, and one or more of these can be used. The amount used is determined depending on the type of vinyl monomer, but preferably 0.1 to 4.0% by weight based on the vinyl monomer.

In addition, in the present invention, a poorly soluble phosphate as a dispersant,
Water-soluble polymeric protective colloids and the like can be added to the polymerization system.

Examples of sparingly soluble phosphates include tricalcium phosphate and magnesium phosphate. As a polymeric protective colloid,
Examples include polyvinyl alcohol, water-soluble cellulose derivatives such as alkylcellulose, hydroxyalkylcellulose, and carboxyalkylcellulose, and sodium polyacrylate. It is preferable that the sparingly soluble phosphate is used in an amount of 0.01% by weight or more based on the total amount of substances present in the polymerization system, and the water-soluble polymer protective colloid is used in an amount of 1 to 1% by weight of O,OO.

In addition, anionic surfactants are added to the polymerization system as dispersion aids for particle size adjustment, etc., and to reduce the solubility of monomers and organic solvents that are incompatible with water. A water-soluble inorganic salt can be added to the polymerization system.

Vinyl ester of aliphatic alcohol having 6 to 24 carbon atoms or vinyl ether of aliphatic alcohol having 6 to 24 carbon atoms (IL glycidyl monovinyl ester or glycidyl monovinyl ether (II), polyvinyl ester of polyhydric alcohol or polyhydric alcohol Polyvinyl ether (II[), a dispersant, a polymerization initiator, a dispersion aid if necessary, and an organic solvent incompatible with water used if necessary can be mixed in advance or each separately in an aqueous medium. Add and disperse.In this case, in order to disperse well, it is preferable to stir at high speed using a homomixer, etc., and this high-speed stirring can be carried out until the initial stage of polymerization.For subsequent polymerization, use a propeller stirrer, etc. It is carried out under the usual stirring conditions used.

The aqueous medium is a vinyl ester of an aliphatic alcohol having 6 to 24 carbon atoms, a vinyl ether (I) of an aliphatic alcohol having 6 to 24 carbon atoms, a glycidyl monovinyl ester, or a glycidyl monovinyl ether (II).
), is preferably used in an amount of 1 to 50 times by weight based on the total amount of polyvinyl ester of polyhydric alcohol or polyvinyl ether (III) of polyhydric alcohol and the organic solvent incompatible with water. In this case, the aqueous medium is , water is used, but water containing a water-soluble organic solvent dissolved therein may also be used within a range that does not impede the stability of the suspension system.

For hydrolysis of glycidyl groups in gel particles obtained by suspension polymerization, an acid that does not react with glycidyl groups is used. Such acids include sulfuric acid, perchloric acid, toluenesulfonic acid, benzenesulfonic acid, and the like. The initial concentration of the acid solution used is preferably 0.1N to 5N. If it is thinner than this, the reaction will not proceed, and if it is thicker than this, hydrolysis of the ester bond will tend to occur. The acid solution also contains at least 1 part of water.
It is preferable that the content is 0% by weight or more.

The solvent used for preparing the above acid solution is not particularly limited as long as it is compatible with acid and water and is inert to acid and glycidyl groups, and examples include acetone, methyl ethyl ketone, dioxane, tetrahydrofuran, acetonitrile, etc. However, there is no particular problem even if water is simply used as a solvent without using these solvents.

The amount of acid solution used may be sufficient to immerse the gel particles in the solvent, and may be equal to or greater than the weight of the gel. This reaction is preferably carried out at 25°C to 100°C for 3 to 10 hours. The glycidyl group that the gel particles have is
It is preferable that 80% or more is hydrolyzed.

When one glycidyl group is hydrolyzed by the action of an acid in this manner, one glycidyl group is generated.

By adding an organic solvent that is incompatible with water during polymerization, the resulting crosslinked copolymer particles can be made porous.

The water-incompatible organic solvent used in the present invention is
C with a dissolution amount of 15 g or less per 100 g of water, such as toluene, diethylbenzene, dodecane,
Isoamyl alcohol, chlorobenzene, ethyl acetate,
Examples include propyl acetate and butyl acetate. These solvents are
They may be used alone or in combination of two or more. The amount used is 0 to 300% based on the total amount of monomers.
It is preferable to be able to eat heavy weight % electricity. If the organic solvent that is incompatible with water is too small, it becomes difficult to make the resulting particles porous; if it is too large, the resulting particles tend to have a large porosity and poor pressure resistance.

The spherical particles with a particle size of 1 to 2 oum, preferably 1 to 15 μm, obtained as described above are classified as necessary,
It can be used as a column packing material for reverse phase chromatography.

〔Example〕

Next, the present invention will be explained in more detail with reference to Examples.

Example 1 (1) Polymerization reaction 40.5 g of stearyl methacrylate, 71.0 g of glycidyl methacrylate, 88.5 g of ethylene glycol dimethacrylate, 200 g of toluene.

0.1 of a mixture of 1.0 g of azobisisobutyronitrile
Suspended in a methyl cellulose aqueous solution of 2.22% by weight,
Mix for 10 minutes at room temperature under high speed stirring using a homomixer, then transfer to a regular propeller stirring device and mix at 80°C.
After reacting at °C for 6 hours, gel particles insoluble in water and organic solvents were obtained. Collect this gel from one household to another, add 21 parts of water, then 2 parts of methanol! After washing, it was air-dried. The amount of glycidyl groups in this gel (measured by the hydrochloric acid to calcium chloride method) is 2t.
It was treq/g.

(2) After impregnating 100 g of gel particles obtained in hydrolysis reaction (1) with methanol, suspending the gel particles in 1.02 g of 0.5 N sulfuric acid and incubating at 80°
The reaction was carried out at C for 8 hours. This was collected by filtration, thoroughly washed, and then dried. The amount of glycidyl groups in this gel (measured by the hydrochloric acid-calcium chloride method) was Omeq/g.

Example 2 Polymerization and hydrolysis reactions were carried out in the same manner as in Example I, except that 53.6 g of stearyl methacrylate, 71.0 g of glycidyl methacrylate, and 75.4 g of ethylene glycol dimethacrylate were used. The amount of glycidyl groups after the polymerization reaction (measured by the hydrochloric acid-calcium chloride method) is
2IIleq/g, amount of glycidyl group after hydrolysis reaction (
(measured by hydrochloric acid-calcium chloride method) was Omeq/g.

Example 3 A polymerization reaction and a hydrolysis reaction were carried out in the same manner as in Example 1, except that 67.5 g of stearyl methacrylate, 71.0 g of glycidyl methacrylate, and 61.5 g of ethylene glycol dimethacrylate were used. The amount of glycidyl groups after the polymerization reaction (measured by the hydrochloric acid-calcium chloride method) is 2
meq/g, and the amount of glycidyl groups after the hydrolysis reaction (measured by the hydrochloric acid-calcium chloride method) was Omeq/g.

Comparative Example 1 A polymerization reaction was carried out in the same manner as in Example 1, except that 53.6 g of stearyl methacrylate and 146.4 g of ethylene glycol dimethacrylate were used.

Comparative Example 2 Example 1 except that 160 g of glycidyl methacrylate and 40 g of ethylene glycol dimethacrylate were used.
Polymerization and hydrolysis reactions were carried out in the same manner as above. The amount of glycidyl groups after the polymerization reaction (measured by the calcium hydrochloride method) was 4.5 meq/g.

The amount of glycidyl groups after the hydrolysis reaction (measured by the hydrochloric acid-calcium chloride method) was Omeq/g.

Table 1 shows the degree of swelling of the gels obtained in Examples and Comparative Examples. The degree of swelling was expressed by taking 1 g of gel into a 10 d graduated cylinder, adding the solvent to a scale of 10II11, thoroughly dispersing it, and then leaving it for 72 hours.The volume of the gel was read from the scale of the graduated cylinder. From Table 1, it can be seen that except for Comparative Example 1, the difference in swelling and shrinkage due to solvent was small (and good).

Application example 1 The gel obtained in Example 2 was sorted to give 10-15
The particles had a particle size of μm and were packed into a stainless steel column with a diameter of 6.0 mm and a diameter of 150 mm. Figure 1 shows a chromatogram in which benzene, naphthalene, and anthracene were separated using this column. In FIG. 1, the symbols 1.2 and 3 indicate the elution volume peaks of benzene, naphthalene, and anthracene, respectively. The mobile phase was methanol:water [9
5:5 (volume ratio)], flow rate is 1.0%, detection is by UV
It was performed at 254 nm. Also, 100% water, 11 methanol
There were no voids in the column even when flowing 0.00%.

Application Example 2 The gel obtained in Comparative Example 2 was sorted and packed in a column in the same manner as in Application Example 1, and benzene, naphthalene, and anthracene were separated under the same conditions as in Application Example 1. The chromatogram is shown in FIG. 2, but benzene, naphthalene, and anthracene were not separated and could not be used as a reversed phase packing material.

〔Effect of the invention〕

According to the method of the present invention, it is possible to provide crosslinked copolymer particles that have excellent acid resistance and alkali resistance, have small differences in swelling and shrinkage between various solvents, and are useful as a column packing material for reversed phase partition chromatography. Can be done.

[Brief explanation of the drawing]

Figure 1 is a chromatogram obtained in Application Example 1 using gel particles produced according to Example 2 of the present invention as a filler, and Figure 2 is a chromatogram obtained using gel particles produced according to Comparative Example 2 as a filler. This is a chromatogram obtained in Application Example 2. Explanation of symbols 1...Benzene elution peak 2...Naphthalene elution peak 3...Anthracene elution peak 1 each (γL) Diagram Melt-off path amount (7rtl) Taku diagram

Claims (1)

[Scope of Claims] 1. Vinyl ester of aliphatic alcohol having 6 to 24 carbon atoms or vinyl ether of aliphatic alcohol having 6 to 24 carbon atoms (I), glycidyl monovinyl ester or glycidyl monovinyl ether (II); , characterized in that glycidyl groups of gel particles obtained by aqueous suspension polymerization of polyvinyl ester of polyhydric alcohol or polyvinyl ether (III) of polyhydric alcohol are hydrolyzed in the presence of an acid that does not react with the glycidyl groups. A method for producing crosslinked copolymer particles. 2. Vinyl ester of aliphatic alcohol having 6 to 24 carbon atoms or vinyl ether of aliphatic alcohol having 6 to 24 carbon atoms (I), glycidyl monovinyl ester or glycidyl monovinyl ether (II), and polyvinyl of polyhydric alcohol When carrying out aqueous suspension polymerization of polyvinyl ether (III) of ester or polyhydric alcohol,
2. The method for producing crosslinked copolymer particles according to claim 1, wherein polyvinyl ester of polyhydric alcohol or polyvinyl ether (III) of polyhydric alcohol is blended in an amount of 5 to 70 mol%. 3. Vinyl ester of aliphatic alcohol having 6 to 24 carbon atoms or vinyl ether of aliphatic alcohol having 6 to 24 carbon atoms (I), glycidyl monovinyl ester or glycidyl monovinyl ether (II), and polyvinyl of polyhydric alcohol When carrying out aqueous suspension polymerization of polyvinyl ether (III) of ester or polyhydric alcohol,
Vinyl ester of aliphatic alcohol having 6 to 24 carbon atoms or vinyl ether of aliphatic alcohol having 6 to 24 carbon atoms (I) and glycidyl monovinyl ester or glycidyl monovinyl ether (II) (I)/(
Claim 1 or 2, wherein II) is blended in a molar ratio of 5 to 0.03.
A method for producing the crosslinked copolymer particles described. 4. The crosslinked copolymer according to claim 1, 2 or 3, wherein the vinyl ester of an aliphatic alcohol having 6 to 24 carbon atoms or the vinyl ether (I) of an aliphatic alcohol having 6 to 24 carbon atoms is lauryl methacrylate or stearyl methacrylate. Method for producing polymer particles. 5. The method for producing crosslinked copolymer particles according to claim 1, 2, 3 or 4, wherein the glycidyl monovinyl ester or glycidyl monovinyl ether (II) is glycidyl methacrylate. 6. Claims 1, 2, 3, wherein the polyvinyl ester of a polyhydric alcohol or the polyvinyl ether (III) of a polyhydric alcohol is a polymethacrylic ester of a polyhydric alcohol.
4. The method for producing crosslinked copolymer particles according to 5. 7. A column packing material for reversed phase chromatography comprising the crosslinked copolymer particles according to claim 1.