JPS6138462A - Preparation of packing material for liquid chromatography - Google Patents

Abstract

PURPOSE:To prepare a packing agent for liquid chromatography (LC) excellent in separation capacity, by subjecting a mixure consisting of glycidyl monovinyl ester and a crosslinkable monomer to aqueous suspension polymerization in the presence of 1,2-dichlorethane being a diluent to split and make an epoxy group hydrophilic. CONSTITUTION:A monomer mixture based on glycidyl monovinyl ester or glycidyl monovinyl ehter and a crosslinkable monomer is subjected to aqueous suspension polymerization in the presence of 1,2-dichloroethane being a diluent. After the diluent in polymer particles are extracted and removed, an epoxy group is split to be made hydrophilic. Because the compatibility of the diluent with the monomer and the formed polymer is excellent, a uniform fine pore size can be formed in each particle and a porous packing agent for LC excellent in separation capacity can be prepared in an industrially benefidial manner.

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Field of Industrial Application The present invention relates to a method for producing a liquid chromatography (LC) moonlight m agent.

Cron Conventional technology Currently, LC is an indispensable method in the fields of analysis and separation of non-volatile substances, and its market is rapidly expanding, and competition among companies to develop it is becoming fiercer. It is known that one way to adjust the separation power of such LC is to change the shape and amount of pores in the filler. Exclusively means of varying the amount of However, when the crosslinking density is increased, the polymer particles become denser and the pore size becomes smaller, resulting in a decrease in separation ability, and when the crosslinking density is lowered, the mechanical strength of the polymer particles decreases, making it difficult to increase the speed of LC. It becomes an obstacle.

Therefore, as described in Japanese Patent Publication No. 57-31925, for example, vinyl acetate is diluted by using an organic solvent, such as nitromethane or toluene, as a diluent, which is compatible with the monomer but has poor compatibility with water. A method has been proposed for producing a hard and porous polyvinyl alcohol gel through aqueous suspension polymerization together with a crosslinking agent, saponification, and post-crosslinking steps.

In addition, a method for manufacturing a hydrophilic gel useful as a filler for LC by aqueous suspension polymerization of a monomer containing an epoxy group to prepare a spherical polymer, and then ring-opening modification of the epoxy group has been disclosed in Japanese Patent Application. It is disclosed in Japanese Patent Publication No. 177140/1982, and cyclohexanol, chlorope/se/etc. are exemplified as diluents to be present during polymerization.

e→ Problem to be solved by the invention In order to produce a gel with large pore volume and high mechanical strength, it is necessary to introduce a crosslinked structure and coexist with a diluent during polymerization. Suitable diluents differ depending on the type of monomers constituting the diluent.

In particular, in the method of manufacturing a hydrophilic gel by forming an epoxy group-containing rod-shaped polymer and then ring-opening modification of the epoxy group, a large number of pores with a large pore volume and a small pore diameter are produced. It is very difficult to form a spherical body having a spherical shape, and in fact, even using the diluent described in JP-A-58-177140, it was not possible to give a satisfactory result, and the examples of the publication The exclusion limit molecular weight of the gel shown in is extremely large, ranging from tens of thousands to hundreds of thousands, indicating that the pore size is large.

2) Means for Solving the Problems The purpose of the present invention is to produce a mechanically collapsible, uniform and microporous filler for LC. The monomer mixture as the main component is subjected to aqueous suspension polymerization in the presence of 1.2 dichloroethano as a diluent, the diluent in the obtained polymer particles is extracted and removed, and the epoxy groups are ring-opened. , which can be industrially advantageously achieved by means of hydrophilization.The present invention will be described in detail below. First, the monomer used in the present invention must be selected from glycidyl monovinyl ester or glycidyl monovinyl ether. Examples of glycidyl monovinyl esters or glycidyl monovinyl ethers include glycidyl esters of monovinyl carboxylic acids having 3 to 12 carbon atoms or glycidyl ethers of monovinyl alcohols having 3 to 12 carbon atoms, among which glycidyl acrylate and glycidyl methacrylate. , allyl glycidyl ether, methallyl glycidyl ether, etc. can be mentioned as suitable examples.

In addition, the crosslinkable monomers include divinylbenze/, ethylene glycol diacrylate, ethylene glycol dimethacrylate, flobile/glycol diacrylate, propylene glycol dimethacrylate, polyethylene glycol dimethacrylate, polypropylene glycol dimethacrylate, and glycerin. diacrylate,
Glycerin dimethacrylate, N,? Examples include %-methylenevinacrylamide, divinyl succinate, diallyl succinate, vinyl methacrylate, allyl methacrylate, triallyl cyanurate, etc., but some of them cause specific adsorption as packing materials for LC. It is preferable to have a problem-free structure, and from this point of view, it is desirable to use di- or tri-(meth)acrylates of polyhydric alcohols among the above-mentioned crosslinkable monomers.

In addition, there is no problem in using together with the above-mentioned monomer, which is the main component, other monomers that can be copolymerized with the monomer. Examples of such other monomers include vinyl halides. and halogenated vinyliso 7, ethylenically unsaturated 11-hydrocarboxylic acids and their salts, ethylenically unsaturated sulfohepta acids and their salts, methyl (meth)acrylate, ethyl (meth)acrylate, butyl (meth)acrylate, Examples include (meth)acrylic acid esters such as polyoxyalkyleno(meth)acrylate, acrylamide, vinyl acetate, and the like.

Next, it is necessary that the diluent which forms the central component of the present invention is 1,2-dichloroethane. In some cases, the porous structure may be controlled (especially by increasing the pore size).
There is no problem in using other organic solvents for this purpose.

The amount of such diluent to be used needs to be changed depending on the field of application of the filler, the required pore volume (porosity), pore diameter, etc.Although it is difficult to define it unambiguously, it is generally It is desirable to set the weight ratio of the diluent to the diluent to be in the range of 10/1 to 1/1, more preferably 571 to 115.

In addition, the monomer concentration in the polymerization system is generally such that the total amount of monomers and diluent and water are in a weight ratio of 5/100 to 120/
100, preferably 20/100~l Oo,'i
It is important to set it within the range of 00! ,tL.

Seventh, the polymerization conditions can be set as appropriate within the range of temperature 40 to 9 degrees Celsius, preferably 50 to 70 degrees Celsius, and time 0.5 to 5 hours. Known oil-soluble radical polymerization initiators such as compounds and organic peroxides can be used.

Since the polymer particles produced in this way contain a diluent inside, it is necessary to extract and remove them, and such methods include dissolving them in water and using a diluent such as methanol, ethanol, propatool, acetone, etc. After extracting and removing with a solvent that dissolves , it is washed with water.

The polymer particles from which the diluent has been removed are made hydrophilic by ring-opening the epoxy groups they contain.

There are no restrictions on the method as long as the epoxy group is converted into a hydrophilic group, and the following methods are appropriately selected depending on the application.

For example, inorganic acids such as nitric acid, sulfuric acid, hydrochloric acid, phosphoric acid; formic acid,
Paternity to hydroxyl group by hydrolysis with organic acids such as acetic acid, hydroxyacetic acid, pen/zenesulfonate, toluenesulfonate, etc., an-T: = 7 Also, haethylamine, diethylamine, triethylamine, ethanolamine, jetanolamine/, Modification to amino groups by reaction with amines such as triethanolamine, oxalic acid, succinic acid,
Examples include modification to a carboxylic acid group by reaction with a dicarboxylic acid such as 7-dipic acid; modification to a sulfonic acid group by reaction with acidic sulfurous acid.

Thus, particle sizes generally range from 5 to 300. a, gel moisture content 3
A present aqueous gel having properties of 0 to 2000%, preferably 50 to 500% and suitable as a filler for LC can be produced industrially and advantageously.

(g) Effect: By following the method of the present invention as described above (in particular, using a specific compound as the diluent βJ), the compatibility between the diluent, the monomer, and the produced polymer is improved. It is possible to form a uniform pore size in the particles, thereby making the particles porous without impairing mechanical strength, and finally providing an LC packing material with excellent separation ability. it is conceivable that.

(c) Examples The present invention will be explained in more detail by 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 moisture content is determined by applying the polymer particles sufficiently equilibrated with deionized water to a centrifugal separator with a centrifugal effect of 2000G to remove water attached to the particle surface, and then measuring the weight (Wl). The weight after drying the polymer particles (W
2) was measured and determined by the following formula.

Example 1 Methacrylic acid/sodium p-styrene sulfonate = 70
/80 water-soluble polymer and 2 parts of polyvinyl alcohol (polymerization degree i o o o, saponification degree 8796).
It was dissolved in 78 parts of water and charged into a polymerization tank equipped with a seed type stirrer.

Next, glycidyl methacrylate (GMA), ethylene glycol dimethacrylate (EGMA) and 1,2-
2.2'-Azobis-(2
, 4-dimethylvaleronitrile) and polymerize +
V, under stirring conditions of 300 r, p, m, 6
Aqueous suspension polymerization was carried out at 0 for 2 hours.

After filtering, washing, and dehydrating the obtained polymer particles, the diluent in the polymer particles was extracted and removed with methanol, and the remaining methanol was washed with water, and then suspended in a 5% formic acid aqueous solution. The epoxy groups in the polymer particles were ring-opened by reacting at 90°C for 3 hours.

Table 1 also shows the results of measuring the average particle diameter and gel moisture content of the obtained polymer particles.

(Note) No, l i Ant a treatment omitted.

Next, the polymer particles (Nos. 2 and 4) were separated into 150-mesh and 350-mesh intermediates, which were packed into a glass column with an inner diameter of 1.5 cm and a height of 3 Q cm. The performance as a filler for LC was comparatively evaluated. Bovine serum albumin 5% and ammonium sulfate 2.59 as samples
Water-soluble g containing 6! Load 0.5 cc into the column,
Using deionized water as the eluent and operating at an elution rate of 50 CC/hour, the elution curves shown in FIGS. 1 and 2 were created.

From the table above and Figures 1 and 2. By varying the amount of DCE, the gel water content (pore i in the polymer particles)
It is clearly understood that the product of the present invention can be easily controlled and that the product of the present invention has excellent separation ability.

For No. 4, the exclusion limit molecular weight using polyethylene glycol was examined and found to be 5.000, suggesting that the particles have a gel-like structure.

Furthermore, this polymer particle was
As a result of filling a stainless steel column and performing end pressure tenuto, the relationship between flow rate and pressure showed linearity even at a pressure of 10 K9 / d G, and the relationship between flow rate and pressure was 10 K9 / cl G.
It was confirmed that the product had pressure resistance exceeding the above.

Example 2 Example 1 (No. 4) except that allyl glycidyl ether was used instead of GMA and the polymerization time was 60 x 8 hours.
) Hydrophilic polymer particles were obtained under the same conditions.

The gel moisture content was 195%, and it was confirmed that the gel had almost the same separation ability as Example 1 (No. 4).

Example 3 In the same manner as in Example 1, G M A / E G M
Aqueous suspension polymerization was carried out at A/DCE=50150/400 to obtain a spherical polymer. Next, the diluent was extracted using Ashitono, and the mixture was thoroughly washed with water.

This polymer was treated with diethylamide 7z0 maintained at 60'c.
% water bath and reacted with stirring for 3 hours to obtain a hydrophilic gel with a gel moisture content of 230%. This gel had a pressure resistance of 10 Kq/clG or more.

(G) Effect By adjusting the amount of diluent present in the polymerization system,
A special feature of the present invention is that it provides an industrially advantageous means for producing an LC filler that is uniform, microporous, has excellent mechanical strength, and can exhibit excellent separation performance. It is an effect.

[Brief explanation of the drawing]

FIG. 1 shows the elution curves obtained from Example 1 (No. 2), and FIG. 2 shows the elution curves obtained from Example 1 (No. 4). ) ■a Utne) 1t'' (・su* z @ Ji wo fox) Gihi, Jin (=c)

Claims (1)

[Claims] 1. Aqueous suspension polymerization of a monomer mixture containing glycidyl monovinyl ester or glycidyl monovinyl ether and a crosslinkable monomer as a main component in the presence of 1,2-dichloroethane as a diluent, A method for producing a packing material for liquid chromatography, which comprises extracting and removing the diluent in the obtained polymer particles, and then ring-opening the epoxy groups to make them hydrophilic. 2. Claim 1 in which di- or tri-(meth)acrylate of polyhydric alcohol is used as the crosslinking monomer
Manufacturing method described in section.