JPS6257570B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing spherical silica gel, which is used as a packing material for liquid chromatography, particularly gel permeation chromatography (GPC). When making packing materials for liquid chromatography, especially packing materials for GPC that handles samples with low to high molecular weights, such as proteins, 100 to 4000 Å
Controlled pore size ranging from 0.8 to 3 c.c./g
A silica gel with a total pore volume of . Currently, spherical silica gel has an average pore diameter of 100Å.
Products having a thickness of 300 Å, 500 Å, 1000 Å and 4000 Å are sold by Merck & Co. However, although the cause is unknown, this silica gel cannot be used in aqueous systems even if the surface is treated with an organic silane agent according to conventional methods.
As a packing material for GPC, a usable packing material could not be obtained due to poor separation performance. A method for increasing the pore size is to mix a silicate aqueous solution with an O/W type emulsifier and an oil phase that does not mix with water, and then mix it with a W/O type emulsifier and an oil phase that does not mix with water to form an O/W emulsifier. /O-type emulsion and then neutralizing it with acid (see JP-A-51-149898); emulsifying a water glass sol in a mixture of a polar solvent and a non-polar solvent and then gelling it (see JP-A-51-149898); (see Japanese Patent Application Laid-open No. 115298, 1972), or a method of calcining silica gel containing an inorganic salt (Japanese Patent Application Laid-Open No. 47-1989).
5817)). By the way, the packing material for liquid chromatography has a controlled pore diameter and total pore volume, and
It is desirable that the particles have a predetermined particle size and have a nearly perfect spherical shape, but depending on the gelation conditions,
A phenomenon in which the balls touch each other occurs. A packing material for liquid chromatography that uses silica gel as a raw material, which contains balls that are stuck together, has the disadvantage that when it is packed into a column, it causes uneven packing and has a low separation ability. Once the spheres stick together, they cannot be removed by operations such as classification, so it is important to prevent them from forming in advance. Furthermore, in order to increase the separation ability of the packing material for liquid chromatography, it is necessary to reduce the particle size. One way to reduce the particle size is to increase the stirring speed when forming water glass sol particles and when gelling the water glass sol, but there is an equipment limit to increasing the stirring speed. Therefore, it was extremely difficult to produce particles with an average particle size of 10 μm or less. In order to improve the above-mentioned drawbacks, the inventors of the present invention conducted extensive studies on the manufacturing method of silica gel, and as a result, they discovered that the particle size of silica gel can be easily adjusted by changing the viscosity of the dispersion medium, and completed this invention. did. The structure of the present invention is to emulsify a water glass sol under stirring in a dispersion medium consisting of a mixture of a hydrophobic high-viscosity solvent selected from non-polar hydrocarbons, silicone oils and vegetable oils and a hydrophobic non-polar low-viscosity solvent, A method for producing spherical silica gel characterized by gelation in this emulsified state, which further includes, as an embodiment, the viscosity of the dispersion medium, the pH of the water glass sol, an additive for adjusting the pH, and SiO ₂ of the water glass sol. This is a method for producing spherical silica gel in which the content and the amount of dispersion medium used for water glass sol are limited as necessary. An outline of a specific example of the method for producing spherical silica gel of the present invention will be explained with reference to FIGS. 1 and 2. Aqueous sodium solution is added to neutralize the sodium silicate to produce a water glass sol. On the other hand, a nonionic surfactant is added to a mixture of liquid paraffin as a hydrophobic high-viscosity solvent and n-hexane as a hydrophobic low-viscosity solvent to prepare a dispersion medium. The above-mentioned water glass sol is added to this dispersion medium and stirred to emulsify the sol, and another surfactant is added thereto to form a gel. The high boiling point solvent (high viscosity solvent) is removed from this gelled mixture by solvent extraction, and the low boiling point solvent (low viscosity solvent) can be removed by adding water and distilling. The resulting gel in the form of a water slurry is stabilized by hot water treatment, then hot filtered and washed with water, and the resulting wet cake is dried under reduced pressure and fired to obtain the silica gel product. . To explain the main steps among the above series of steps, (1) Generation of water glass sol 1 Acid The acids for neutralization include inorganic acids such as sulfuric acid, hydrochloric acid, phosphoric acid, acetic acid, trichloroacetic acid, formic acid, Organic acids such as oxalic acid are used. 2. Salt This is used for the purpose of adjusting the pore size when a gel is formed, and the type of salt used is an alkali metal salt such as sodium or potassium salt or an ammonium salt of the above-mentioned acid used for neutralization. Further, the appropriate amount of addition is such that the salt content of the water glass sol is about 10 to 30% by weight. 3 Neutralization process The amount of acid used for neutralization varies depending on the alkali content of the silicate, but the final pH is 3 to 5.
Use as much as possible. The produced water glass sol is stable in alkaline or acidic conditions, but is most unstable at pH around 7 and easily gels. Therefore, when neutralizing, rather than adding acid to the water glass sol, it is preferable to add silicate to the acid. It's good to add. Since the temperature can be 0 to 50°C, it may be room temperature. (2) Dispersion medium Depending on the type of solvent used, the dispersion medium may form a heterogeneous phase; in this case, it is preferable to add a surfactant as described below to form a homogeneous phase. The mixture ratio of a hydrophobic high viscosity solvent and a hydrophobic low viscosity solvent is such that the viscosity of the dispersion medium after mixing is 1 to 1.
Select the desired viscosity within the range of 1000CP (25°C). At that time, if you want particles with a large particle size, use a relatively high viscosity, and if you want particles with a small size,
Select to have low viscosity. Examples of solvents used as dispersion media include the following. 1 Hydrophobic high viscosity solvent A high viscosity hydrophobic solvent with a viscosity of 2CP (25°C) or higher, such as liquid paraffin, lubricating oil, hydrocarbons such as spindle oil, vegetable oils such as soybean oil and castor oil, and silicone oil. 2 Hydrophobic low viscosity solvent A water-insoluble solvent with a viscosity of 1CP (25°C) or less, such as hexane, heptane, cyclohexane, petroleum, benzene, xylene, chloroform, hydrocarbons such as carbon tetrachloride, and chlorinated hydrocarbons. . 3 Addition Amount A mixture of the above two types of solvents to obtain a desired viscosity is used as a dispersion medium, or the dispersion medium is used in an amount of 0.5 to 5 parts by weight per 1 part by weight of water glass sol. (3) Surfactant Two types of surfactants are usually used depending on the manufacturing process, but the purpose can be achieved with just one type. 1 First surfactant HLB of 1 to 6, preferably 2 to 5 is used. The ionic type is glycerin monostearate (HLB=5.5)
Since all other materials have an HLB of 12 or higher, nonionic materials such as Ionet 80 (trade name: Sanyo Chemical Industries, Ltd.) are preferred. The amount added is 0.05 to 5 wt%, preferably 0.1 to 3 wt%, based on the dispersion medium. Specific examples of surfactants used include the following.

[Table] 2 Second surfactant HLB of 6 to 18, preferably 8 to 15 can be used. Judging from the HLB value, anionic products should be used, but most anionic products contain metal ions, so
When using them, nonionic surfactants are preferred since the presence of salt in the system may affect the pore diameter and maximum volume. The amount of this surfactant added is 0.005 to 3 wt%, preferably 0.01 to 1 wt%, based on the water glass sol.
is appropriate. Specific examples of surfactants that can be used include the following.

[Table] (4) Removal of high viscosity solvent 1 If a high boiling point substance such as liquid paraffin is used as the high viscosity solvent, an extraction operation using a low boiling point hydrocarbon etc. is required. (5) Distillation with expulsion of organic solvent If the next hot water treatment is carried out while the solvents are still mixed,
Since the treatment temperature is not high enough and the hot water treatment takes a long time, it is necessary to remove the solvent. However, simply expelling only the solvent will collapse the pores of the formed silica gel, so it is necessary to add water to keep it in a water slurry state at all times. The appropriate amount of water to be added is 4 to 20 times the weight of _SiO2 . (6) Hot water treatment It takes 3 to 20 hours, preferably 5 to 15 hours under reflux conditions of 70°C or higher, preferably 80°C or higher. Hydrothermal treatment is to stabilize the pores.
This must be done before the silica gel particles are dry. Therefore, the time to perform hot water treatment is before or after filtration (separation). If carried out after filtration, a solvent expulsion distillation step is not necessary. The invention of this application will be specifically explained below with reference to Examples and Comparative Examples. Example 1 Using liquid paraffin as a high viscosity solvent and n-hexane or n-heptane as a low viscosity solvent, these were mixed in the proportions shown in Table 1, and a nonionic surfactant (Span80, manufactured by Kishida Chemical Co., Ltd.) was added to this. A dispersion medium was prepared by adding 25 parts by weight of sorbitan monooleate (trademark, main component). Next, 600 parts by weight of a sodium silicate aqueous solution with a SiO ₂ content of 18 wt% and 420 parts by weight of 20% sulfuric acid were mixed,
The obtained water glass sol (PH=4.1) was mixed with the above dispersion medium under stirring and emulsified. Next, a nonionic surfactant (Nonipol #100, trademark manufactured by Sanyo Chemical Industries, Ltd., main ingredient;
polyoxyethylene nonyl phenyl ether)
0.5 part by weight was added to effect gelation. Next, 2000 parts by volume of n-hexane was added to the gelled product, mixed, and separated into a silica gel layer and a dispersion medium layer, and liquid paraffin was transferred to the dispersion medium layer and separated. After performing such an extraction operation five times, the obtained silica gel layer was washed with water to obtain an aqueous suspension of spherical silica gel. This suspension was observed under a microscope and the average particle size was measured. The results obtained are shown in Table 1. For comparison, the same operation as in the example was carried out except that only a low viscosity solvent was used instead of a mixture of a high viscosity solvent and a low viscosity solvent (however, the total weight of the dispersion medium was constant at 1030 parts by weight). An aqueous suspension of spherical silica gel was prepared, and the average particle size was measured in the same manner as in Examples. The obtained results are also listed in Table 1.

[Table] Example 2 Using liquid paraffin as a high viscosity solvent and n-hexane as a low viscosity solvent, these were mixed to give various viscosities shown in Table 2, and the same surfactant as in Example 1 was added. A dispersion medium was prepared by adding the same proportions. Next, use this dispersion medium to increase the rotation speed of the stirrer.
Spherical silica gel was produced and the average particle size was measured in exactly the same manner as in Example 1 except that the rpm was 5000 rpm.
The results obtained are shown in Table 2.

[Table] As explained above, according to the present invention, by mixing two types of solvents and adjusting the viscosity of the dispersion medium, the particle size of the produced silica gel can be adjusted to a predetermined value, and in particular, the rotation of the stirrer is Even if the number is small, it has the effect of producing particles with a small particle size.

[Brief explanation of the drawing]

FIGS. 1 and 2 are system diagrams showing a specific example of the present invention.

Claims (1)

[Claims] 1 A water glass sol is emulsified under stirring in a dispersion medium consisting of a mixture of a hydrophobic high-viscosity solvent selected from non-polar hydrocarbons, silicone oils and vegetable oils, and a hydrophobic non-polar low-viscosity solvent, and in this emulsified state a gel is formed. 1. A method for producing spherical silica gel, characterized by: