JPH0699133B2 - Method for producing silica gel for liquid chromatography - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing silica gel for liquid chromatography.

Silica gel has higher mechanical strength than polymer-based fillers such as crosslinked dextran and polyacrylamide.
It is widely used as a packing material for liquid chromatography because it hardly swells or shrinks due to changes in pH, ionic strength, eluent composition, etc.

Liquid chromatography is classified into four types of adsorption type, partition type, ion exchange type and molecular sieve type according to the principle of separation, and the properties of the packing material used therefor are also different.

That is, in the adsorption type, it is silica gel or so; in the distribution and ion exchange types, silica gel is chemically bonded to an organic compound such as an organic silane compound or an alcohol compound; in the molecular sieve type, it is silica gel or the organic compound. Are used by chemically bonding.

[Conventional technology]

Conventionally, as silica gel, spherical silica gel and crushed silica gel are known. Spherical silica gel is superior to crushed silica gel in its performance and use characteristics.

Further, among spherical silica gel, when it is used as a packing material for liquid chromatography, it is required to strictly control physical properties such as average particle diameter, surface area, average pore diameter and pore volume. That is, the average particle size is 10 to 50 μm,
Surface area 300-500m ² / g, average pore diameter 80-120Å, pore volume 0.
A spherical silica gel having a physical property of 8 to 1.2 ml / g is desired.

However, such silica gel is not easy to manufacture and expensive.

Conventionally, the following methods are known as methods for obtaining spherical silica gel.

(1) JP-A-60-71515 describes a method in which a water glass sol is emulsified in an organic solvent containing a first surfactant and then a second surfactant is added to form a gel. Has been done.

In this method, since the organic solvent used for emulsification and silica gel are separated, a distillation step is required, which is economically disadvantageous.

Further, the physical properties of the obtained gel are not specified, and its usefulness as a packing material for liquid chromatography is unknown.

(2) Japanese Patent Publication No. 54-9588 describes a method of forming spherical particles by using a colloidal silica and a polymerizable organic material miscible with water as a binder.

What is obtained by this method is a mixture of silica sol particles and an organic material, and to obtain silica gel, at 500 ° C. or higher,
Moreover, the polymerized organic material must be removed by a sintering process for 4 hours or more. Further, the physical properties of the obtained gel are determined by the kind of the raw material colloidal silica, and it is difficult to control the desired gel physical properties.

(3) A spray drying method is known as a method for obtaining a spherical gel without using the above-mentioned organic solvent or organic material.

JP-A-53-65293 proposes a method of spray drying silica sol. However, when the present inventors carried out this method, it was found that the product was likely to be silica gel having a spherical shape but a hollow or a large depression.

When silica gel having such hollows or large dents is used as a packing material for liquid chromatography, its strength is not sufficient, and it is likely to break or spread the separated sample, which is not preferable.

Japanese Examined Patent Publication (Kokoku) No. 43-7012 discloses that a sodium silicate solution is gelled with gaseous carbon dioxide and aged, and then treated with sulfuric acid and spray-dried to give a surface area of 300 to 1000 m ² / g of 0.5.
A method for obtaining silica gel with a pore volume of ~ 1.25 cc / g is described.

In this method, since the carbon dioxide gas is used, it is not easy to control the reaction and it is difficult to control the physical properties of the resulting silica gel.

Japanese Examined Patent Publication No. 47-3446 discloses a method of reacting an aqueous solution of an alkali metal silicate with a mineral acid to form a silica hydrosol having a pH of 9.6 to 10.9, gelling it, and further reacting with the mineral acid to prepare an acidic silica gel slurry and spray-drying. Has been reported.

In this way, according to the example, silica gels with very large surface areas of 740 m ² / g to 965 m ² / g are obtained. Such high surface area silica gel generally has micropores of 50 Å or less. When it is intended to be used as a packing material for liquid chromatography, such micropores are not very effective for separation and cause the strength of silica gel to be reduced.

Furthermore, in JP-B-47-35676, sodium silicate and sulfuric acid are mixed at 23 to 50 ° C. to prepare a mixed solution having a pH of 9.8 to 10.4, in which a hydrogel slurry is formed, and the pH after aging is set to 3 or less. A method is described in which the pH is lowered, the pH is raised to 8-10.2.

The silica gel obtained in this way is according to the examples
It has a pore volume of 0.9-1.15 ml / g with a surface area of 194-560 m ² / g, but the average pore size is not specified.
Further, as described above, there are many aging steps and the operation is complicated. In any of the methods of JP-B-43-7012, 47-3446, and 47-35676, it is an essential requirement to carry out the gel formation step on the alkali side, but the present inventors similarly make gel formation on the alkali side. When a slurry was used, although the cause was unknown, it was found that a gel that was very brittle was often obtained, and that the surface was likely to have many irregularities or a mixture of irregularly shaped particles other than spherical particles. Such silica gel is
Although there is no problem as an ordinary desiccant, when considering its use as a packing material for liquid chromatography, the packing efficiency is lowered, which is not preferable.

[Problems to be solved by the invention]

An object of the present invention is to provide a method for producing silica gel having a high performance as a packing material for liquid chromatography, which has a smoother surface, a smoother surface, and does not contain irregularly shaped particles, as compared with the above-mentioned conventional technique. To provide.

[Means for solving problems]

The gist of the present invention is to obtain silica gel by spray-drying a hydrogel slurry obtained by reacting an aqueous solution of an alkali metal silicate with an aqueous solution of a mineral acid. To produce active silicic acid having a SiO ₂ concentration of 6.5 to 11.5 wt% at pH 3.0 to 4.0 b. Gelling the silicic acid under stirring c. Reacting with an aqueous ammonia solution, Washing with water d. Wet grinding of the obtained hydrogel e. Spray drying, contact with an aqueous solution of mineral acid, and then drying, which is a method for producing silica gel for liquid chromatography. The details are described below. To do.

Examples of the alkali metal silicate used in the present invention include sodium silicate and potassium silicate, and sodium silicate is generally used. As the mineral acid, sulfuric acid, hydrochloric acid, nitric acid or the like can be used.

Any method may be used as a method of generating active silicic acid, but a method of dropping an alkali metal silicate into a mineral acid under stirring is preferable.

At this time, it is necessary to adjust each concentration and mixing ratio of the alkali metal silicate and the mineral acid so that the final pH is 3.0 to 4.0 and the SiO ₂ concentration is 6.5 to 11.5 wt%.

The pH value has a great influence on the gelation time, and if the pH value is less than 3, it takes a long time to gel, which is not practical. If the pH value exceeds 4, the gelation proceeds rapidly and silicic acid is stably prepared. Becomes difficult.

The SiO ₂ concentration of the produced silicic acid has a significant effect on the average pore size of the finally obtained silica gel. That is, the SiO ₂ concentration is
If it is less than 6.5 wt%, the average pore size of silica gel obtained is 80.
When it is less than Å and the SiO ₂ concentration exceeds 11.5 wt%, the average pore diameter of the obtained silica gel exceeds 120 Å and the gel has low strength.

The active silicic acid production temperature can be carried out in the range of 5 to 60 ° C,
Particularly, 30 to 50 ° C is preferable and practical. Generation temperature is 5
If it is less than ℃, it takes a long time to gel, and if it exceeds 60 ℃, the gelation proceeds rapidly and it becomes difficult to stably generate active silicic acid.

The aqueous solution of active silicic acid thus obtained is gelled under stirring to form a silica hydrogel slurry.

The temperature of gelation is not particularly limited, but at low temperature it takes a long time to complete gelation, and at high temperature, gelation progresses rapidly and uniform stirring becomes difficult, so 20-50 ° C is suitable. Is. In addition, generally, the lower the gelling temperature is, the slower the gelling rate is and the easier the stirring is. Therefore, for example, the gelation is started at 20 ° C., the slurry is formed, and then the temperature is raised to 80 ° C. to complete the gelation. A method is also possible.

The stirring means may be any as long as it can crush the hydrogel generated when the activated silicic acid is gelated to generate a hydrogel slurry, and a normal paddle type stirring blade can also be used. If necessary, a high speed stirrer or a kneader can be used.

An aqueous ammonia solution is added to the produced silica hydrogel slurry to cause a reaction. At this time, the concentration of the slurry is not particularly limited, but since a high concentration causes a high viscosity and stirring becomes difficult, and a low concentration is economically disadvantageous, a SiO ₂ concentration of 5 to 10 wt% is appropriate.

The higher the pH of the ammonia-treated solution, the larger the average pore size of the final silica gel produced, and the smaller the surface area. For example, by setting this pH to 8.0-9.0, you can make them 8.0-120Å and 300-500 m ² / g respectively.
Can be adjusted to.

The reaction temperature is not particularly limited, but 60 to 90 ° C. is appropriate because a low temperature requires a long time to complete the reaction.

After completion of the reaction, the product is washed with water and excess water to remove by-produced alkali metal salts. If spray drying is performed without removing the by-product salt, crystals of the salt precipitate in the obtained silica gel,
Pore tends to be uneven.

The obtained overcake is dispersed in water and then wet-milled.

This grinding process has a great influence on the particle surface state and shape of the final silica gel. That is, the surface is smooth,
The pulverization treatment is indispensable in order to obtain silica gel in which irregular shaped particles are not mixed. Any pulverization method may be used as long as it is a wet method, and for example, a ball mill, a vibration mill, a stirring ball mill, a rod mill, a friction disk mill, a stone mill colloid mill, or the like can be used.

Spherical silica gel can be obtained by spray-drying the pulverized silica hydrogel slurry thus obtained. As the spray dryer, a nozzle type, a disc type, and a two-fluid system are generally used, and any type can be used, but the disc type is suitable when a gel having a particle size of about 10 to 50 μm is desired.

The hot air temperature for drying may be 100 to 300 ° C.

The spherical silica gel obtained by spray drying is subsequently treated with an aqueous mineral acid solution.

This treatment is particularly important when an organic compound is chemically bonded to silica gel to separate ionic substances such as nucleic acids, amino acids and amines into partition type, ion exchange type and molecular sieve type. That is, when the above-mentioned separation was tried using the silica gel obtained without this acid treatment, it was often difficult to carry out sufficient separation because adsorption or exclusion of the separated sample was often caused.

Although the mechanism of action of mineral acid on silica gel is unknown, it was found that the reduction of the separation ability due to such adsorption or exclusion can be remarkably improved by carrying out the acid treatment.

As the mineral acid, sulfuric acid, hydrochloric acid, nitric acid or the like can be used.

As a treatment method, silica gel may be dispersed in a mineral acid aqueous solution with stirring, or may be left standing. In order to make the effect of this treatment sufficient, it is desirable to adjust the concentration of the aqueous mineral acid solution so that the pH of the dispersion becomes 4 or less.

Room temperature is sufficient as the treatment temperature, but heating may be used. A treatment time of 30 minutes or more can achieve a sufficient effect.

The silica gel thus treated with acid is washed with water and then dried.

According to the method described above, it is possible to obtain silica gel having a smooth surface and high performance as a packing material for liquid chromatography in which irregular particles are not mixed.

〔The invention's effect〕

As apparent from the above description, according to the present invention, without using an organic solvent or an organic material, without requiring complicated operations, the surface is smooth and inexpensive and a mixture of irregularly shaped particles can be obtained by a simple method. It is possible to obtain high-performance silica gel as a packing material for liquid chromatography, which does not have any material.

Next, the present invention will be described more specifically by way of examples.

Example 1 500 g of a sulfuric acid aqueous solution having a concentration of 15 wt% was supplied to a reaction tank installed in a 50 ° C. constant temperature tank. While stirring the sulfuric acid aqueous solution with a paddle type stirring blade, a sodium silicate aqueous solution with a SiO ₂ concentration of 12 wt% is approximately 1260
g was added to prepare active silicic acid having a SiO ₂ concentration of 8.6 wt% at pH 3.5. After about 10 minutes, the aqueous silicic acid solution thickened and gelation started. At this time, stirring was continued to complete gelation while crushing the hydrogel to obtain a silica hydrogel slurry.

Pure water and an aqueous ammonia solution having a concentration of about 8 wt% were added to the silica hydrogel slurry to adjust the SiO ₂ concentration to about 6 wt% and the pH to 8.0, and then the reaction was carried out at 80 ° C. for 2 hours.

After the reaction, wash with excess water, disperse in water, wet pulverize with Dyno-Mill (Willie A. Bakofen), and then use a disk type spray dryer with inlet hot air temperature 100 ° C and outlet hot air temperature 60 ° C. Spray dried.

The silica gel thus obtained was suspended in a sulfuric acid aqueous solution, acid-treated at room temperature for about 1 hour at pH 3.0, and then washed with water,
Dry overnight at 0 ° C.

The obtained silica gel was spherical and had a smooth surface, and almost no irregular particles were mixed.

Regarding the physical properties, as shown in Table 1, it was suitable as a packing material for liquid chromatography.

Furthermore, in order to investigate the performance when an organic compound is chemically bonded to silica gel, the silica gel obtained by the above method was used.
g and 120 ml of xylene, 12 g of octadecyltrichlorosilane was added, and the mixture was reacted at 60 ° C. for 3 hours. After the reaction was completed, the product was washed with xylene, then with methanol, and then dried at 80 ° C. overnight. The obtained gel was packed in a column (diameter 7.8 mm x length 300 mm), and the elution behavior of 1-methylnicotinamide was examined using a 3 wt% aqueous methanol solution as a mobile phase. It was a high-performance filling material.

Example 2 100 g of a sulfuric acid aqueous solution having a concentration of 15 wt% was supplied to a reaction tank installed in a 20 ° C. constant temperature tank. About 285 g of a sodium silicate aqueous solution having a SiO ₂ concentration of 12 wt% was added while stirring the sulfuric acid aqueous solution with a paddle type stirring blade to prepare an active silicic acid having a SiO ₂ concentration of 8.9 wt% at pH 4.0. After about 50 minutes, the aqueous silicic acid solution started to gel. The hydrogel is crushed by stirring to make it into a gel, and then to 80 ℃.
The temperature was raised to and gelation was completed.

The silica hydrogel slurry obtained is subsequently treated in Example 1.
Silica gel was obtained by performing the same operation as.

The obtained silica gel was spherical and had a smooth surface, and almost no irregular particles were mixed. Regarding the physical properties, as shown in Table 1, it was suitable as a packing material for liquid chromatography.

Further, as in Example 1, the chemical bond of octadecyltrichlorosilane was chemically bound and the elution behavior of 1-methylnicotinamide was examined. As a result, there was almost no adsorption of the sample and it was a high performance as a packing material for liquid chromatography.

Comparative Example 1 About 200 g of a sulfuric acid aqueous solution having a concentration of 15 wt% and about 341 g of an aqueous sodium silicate solution having a SiO ₂ concentration of 12 wt% were added, and the SiO ₂ concentration was about 1 at pH 4.0.
It was carried out under the same conditions as in Example 2 except that 2.6 wt% of active silicic acid was obtained.

The silica gel obtained was spherical and had a smooth surface, and there was no mixture of irregularly shaped particles, but as shown in Table 1, the average particle diameter and pore size were large, and the pore volume was large and relatively weak.

Comparative Example 2 An experiment was conducted in the same manner as in Example 2, except that 446 g of sodium silicate having a SiO ₂ concentration of 7.5 wt% was added to prepare active silicic acid having a SiO ₂ concentration of 6.1 wt% at pH 4.0. .

The silica gel obtained had a spherical shape, a smooth surface, and no irregular-shaped particles mixed therein, but as shown in Table 1, it had a small pore size and a small pore volume.

Comparative Example 3 Same as Example 2, but without adding ammonia,
The treatment was carried out at pH 6 overnight at 80 ° C.

The silica gel obtained had a spherical shape and a smooth surface, and almost no irregular particles were mixed, but the pore size was small as shown in Table 1.

Comparative Example 4 It was carried out in the same manner as in Example 1, but without wet grinding.

Although the obtained silica gel was spherical, it had irregularities on the surface and had irregular particles mixed therein.

Comparative Example 5 The procedure of Example 1 was repeated except that the acid treatment was not performed.

The obtained silica gel was spherical and had a smooth surface, and there was no mixture of irregularly shaped particles. The physical properties were desirable as shown in Table 1, but octadecyltrichlorosilane was chemically bonded in the same manner as in Example 1 to give 1
As a result of investigating the elution behavior of -methylnicotinamide, the sample was not adsorbed on the gel and could not be eluted, and sufficient performance as a packing material for liquid chromatography could not be expressed.

Claims (1)

[Claims] 1. A method for obtaining silica gel by spray drying a silica hydrogel slurry obtained by reacting an aqueous solution of an alkali metal silicate with an aqueous solution of a mineral acid. A. To produce active silicic acid with a SiO ₂ concentration of 6.5 to 11.5 wt% at pH 3.0 to 4.0 b. Gel the silicic acid under stirring c. React with an aqueous ammonia solution and wash with excess water D. The hydrogel obtained is wet-milled, e. Spray-dried, then brought into contact with an aqueous solution of a mineral acid, and then dried, and the method for producing silica gel for liquid chromatography.