JPH10202095A - Silica-based adsorptive separating agent, method for producing the same and filler using the same - Google Patents

Abstract

[PROBLEMS] To be used as an adsorbent for organic compounds having a low molecular weight, and to have a practical adsorption separation ability and flow rate even in a large-scale fractionation using a column of tens to hundreds of liters as a separating agent. And a method for easily and inexpensively producing the same, and a packing material for preparative chromatography using the same. The present invention relates to a silica-based adsorptive / separating agent comprising a silica granulate having a spherical surface having a diameter of 0.1 to 2 mm and having a hydrophobic surface, a method for producing the same, and preparative chromatography using the same. Filler.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a silica-based adsorbent for low molecular weight organic compounds and a silica-based adsorbent, particularly suitable for large-scale fractionation using an open column of tens to hundreds of liters or more, as a separating agent for chromatography. The present invention relates to an adsorption separation agent, a method for producing the same, and a filler using the same.

[0002]

2. Description of the Related Art ODS (trichlorooctadecyl silane) is a silica-based adsorptive / separating agent used as an adsorbent for low molecular weight organic compounds or as a separating agent for chromatography.
Silicas whose surfaces are modified with ODS silica (hereinafter referred to as “ODS silica”) are well known. However, ODS silica has a particle diameter of only about several tens μm.
In large-scale fractionation using a column having a bed capacity of several hundred liters, it is necessary to apply a large pressure in order to secure a flow rate, and a device for that purpose becomes complicated. Also, the operation of filling the column requires complicated steps. Further, since the cost is high, large-scale use in large-scale fractionation has a great economical problem.

On the other hand, inexpensive silica gel is available, but its shape is not spherical and its pore volume is not enough, so its separation ability is low, and it is difficult to use it as an adsorbent or a separation agent for chromatography. Was.

[0004] Inexpensive adsorbents include synthetic resin adsorbents, which are often used in large-scale preparative separations. These adsorbents have adsorption performance, but their pore distribution is wide, so they are not suitable for separation. However, there is a problem in that there is a problem with the properties, and depending on the material, deterioration due to an organic solvent or the like is also concerned.

[0005]

SUMMARY OF THE INVENTION The present invention has been made in view of the above problems, and has as its object the use of low molecular weight organic compounds as adsorbents and the use of dozens to hundreds as separating agents. A silica-based adsorption / separation agent capable of ensuring a practical adsorption / separation capacity and flow rate even in a large-scale fractionation using a liter column, a method for easily and inexpensively producing the same, and a method using the silica-based adsorption / separation agent It is to provide a packing material for preparative chromatography.

[0006]

The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems, and as a result, have found that the surface of a silica granule obtained by granulating silica powder into a spherical shape of 100 μm or more is polysiloxane. The present inventors have found that a silica-based adsorptive / separating agent can be easily and inexpensively obtained by hydrophobizing with a treating agent such as this, and have completed the present invention.

That is, according to the present invention, the diameter is 0.1 to 2 mm.
Is a spherical type, a silica-based adsorption / separation agent comprising a silica granulated body whose surface is hydrophobized, and a method of producing this silica-based adsorption / separation agent by granulating silica powder and hydrophobizing the surface thereof, The gist of the present invention is a filler for preparative chromatography using the silica-based adsorption separating agent.

Hereinafter, the present invention will be described in detail.

First, the silica-based adsorptive separating agent of the present invention will be described.

The silica-based adsorptive / separating agent of the present invention has a spherical shape with a diameter of 0.1 to 2 mm and is made of silica granules whose surface is hydrophobized.

Here, the diameter of the silica-based adsorptive separating agent must be in the range of 0.1 to 2 mm.
When the diameter is less than 0.1 mm, when used as a separating agent, for example, when packed in a column or the like, a high pressure must be applied to secure a flow rate, and an apparatus for that Is complicated, and the operation for filling is also undesirably complicated. 2 in diameter
In the case of exceeding mm, although it is possible to secure the flow rate, it is difficult to obtain a spherical granulated body during the granulation described below, and also during the separation operation when used as a separating agent. It is not preferable because breakage of particles or the like occurs, which may lower the flow velocity or cause clogging.

The silica-based adsorptive / separating agent of the present invention contains 0.1 to 0.1%.
Preferably, it has a pore volume of 7 cm ³ / g or more, a pore mode diameter of 6 to 20 nm, and pores of 30 nm or more occupy 20 to 50% of the total pore volume.

Here, the pore volume is 0.7 cm ³ / g
If it is above, the area effective for the adsorption of the granules will not be reduced, and the adsorption capacity will not be reduced. Moreover, the pore mode diameter is 6 to
If it is in the range of 20 nm, the resolution will not be reduced. Furthermore, pores of 30 nm or more account for 20% of the total pore volume.
If it is less than 50%, the surface area effective for adsorption may be reduced to lower the adsorbing ability, and if it exceeds 50%, the strength of the silica granules may be lowered.

The silica-based adsorptive / separating agent of the present invention has a spherical shape. The reason for this is that, for example, when a column is packed as a separating agent, a spherical particle having a relatively uniform particle diameter can have an almost close-packed structure,
This is because the flow rate can be ensured, and particles are hardly damaged during the separation operation, so that the flow rate does not decrease and clogging hardly occurs. On the other hand, non-spherical particles, such as columnar, pellet-like, and elliptical spherical particles, are not preferable because the above-described effects of the spherical particles are weakened.

The surface of the silica-based adsorptive / separating agent of the present invention is hydrophobized. This makes it possible to efficiently adsorb the substance to be separated and to increase the adsorption capacity, which is preferable. Furthermore, that the surface is hydrophobized,
As described in the method for producing a silica-based adsorptive separating agent of the present invention described below, refers to those obtained by performing a hydrophobic treatment on silica granules, and specifically, silica granules Means at least a portion that can be reached by a substance to be separated.

Next, a method for producing the silica-based adsorptive separating agent of the present invention will be described.

The process for producing a silica-based adsorptive separating agent of the present invention comprises hydrophobizing the surface of a silica granulated material obtained by granulating silica powder into a spherical shape of 100 μm or more with, for example, polysiloxane.

Here, BE of the silica powder as a starting material is used.
The T specific surface area, preferably in the range of 100 to 500 m ² / g, more preferably from 200 to 400 m ² / g. This is because the BET specific surface area is 100
If it is less than m ² / g, the adsorption capacity is small because the BET specific surface area is small, and if it exceeds 500 m ² / g, the pores are too small and may not be effective for adsorption separation. It is.

Next, the above silica powder is granulated. As the granulation method, any known method can be adopted as long as the shape of the granulated body is spherical. Among them, the tumbling granulation method is preferably used. As a device to be used, a speed mixer manufactured by Fukae Kogyo KK is used.

Here, the temperature and time are important during granulation, but the temperature is preferably from 0 to 100 ° C, more preferably from 10 to 70 ° C, and particularly preferably from 20 to 30 ° C. The time varies depending on the temperature at the time of granulation, and thus is not constant, but usually about several minutes is sufficient.

At the time of granulation, water is used as a binder. The amount of water is preferably 50 to 400 parts by weight, more preferably 100 to 200 parts by weight, based on 100 parts by weight of the raw material silica powder. A range is preferred. This range is determined in consideration of the size and pore volume of the obtained granules, and deviates from this range, and if less than 50 parts by weight, the size of the granules becomes small, and 0.7 volume
cm ³ / g or less, and if it exceeds 400 parts by weight, the size of the granules may exceed 2 mm, or the granules may be slurried and cannot be granulated. .

At the time of granulation, an organic substance such as cellulose may be added in order to improve the pore volume of the granules. In this case, the amount of the organic substance added is silica powder 1
50 parts by weight or less per 100 parts by weight is sufficient. 50
If the amount exceeds the weight part, the shape of the granules may not be maintained after the subsequent heat treatment step.
Further, a water-soluble organic binder such as an acrylic binder may be added in order to increase the strength of the granulated body and improve the operability thereafter. In this case, the amount of the organic binder to be added is 10 parts by weight or less based on 100 parts by weight of the silica powder.

The granules thus obtained are subjected to a heat treatment in order to improve the strength. As the heat treatment temperature,
The temperature may be in the range of 300 to 1000 ° C., and is preferably 500 in consideration of the case where an organic binder is added.
~ 1000 ° C. If the temperature is lower than 300 ° C., the strength of the granulated body does not increase, and water may be easily re-adsorbed on the surface of the silica powder. If the temperature exceeds 1000 ° C., sintering may occur and the pore volume may be reduced. . The time varies depending on the temperature at the time of the heat treatment, and thus is not constant, but is usually carried out under conditions of about 30 minutes to 4 hours.

In the method of the present invention, the surface of the obtained granules of silica is hydrophobized using a compound such as polysiloxane. Here, the compound for the hydrophobizing treatment is not particularly limited as long as it can hydrophobize the surface of the silica granules. For example, a halogen silane, a nitrogen-containing silane compound or silicone oil is used as a surface treating agent. Use. Further, the silica granules are brought into contact with a compound for hydrophobizing treatment, and the surface of the silica granules can be hydrophobized under the conditions generally used. However, in consideration of the performance as an adsorptive separation agent, the amount of di-n-butylamine adsorbed (hereinafter referred to as “DBA adsorbed amount”) is preferably 200 mmol / kg or less, more preferably 100 mmol / kg or less. is there.

It is known that di-n-butylamine is adsorbed to hydroxyl groups on the surface of silica ionically.
Meyer: Kautschuk, Gummi 7
[8], described in 180-182WT (1954)), D
The BA adsorption amount can be used as an indicator of the degree of hydrophobicity.

The silica-based adsorptive separation agent of the present invention described above is used, for example, in large-scale preparative chromatography using an open column of several tens to several hundred liters or more, such as preparative liquid chromatography. It is useful as a filler for chromatography, an adsorbent for low-molecular-weight organic compounds, and the like.

[0027]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

In the examples, granulation, hesperidin adsorption, BET specific surface area, pore volume, pore mode diameter, granule size, and DBA adsorption were determined by the following methods. The amount of hesperidin adsorbed was used to compare the performance as an adsorbent separating agent.

(1) Granulation A predetermined amount of silica powder was put in a granulator, and granulation was performed while supplying a binder such as water by spraying. As a granulator, a high speed mixer manufactured by Fukae Kogyo Co., Ltd. was used.

(2) Hesperidin adsorption amount 50 mg of hesperidin was added to 1N aqueous sodium hydroxide solution 2
A solution prepared by dissolving the solution dissolved in 5 ml with 50 ml of water was used as a stock solution.
A solution obtained by adding 4 ml of ethanol and 10.5 ml of water was used as a hesperidin solution. The concentration of this hesperidin solution is H
Measured by PLC and the concentration is taken as Amg / ml.
To 10 ml of this solution, precisely weigh the silica granules 0.1.
5 g was added and left for 24 hours. The concentration of hesperidin after standing was measured by HPLC, and the amount of adsorbed hesperidin was determined by the following formula as Bmg / ml.

Hesperidin adsorption (mg / g) = (A−
B) × 10 (ml) / added amount of silica granules (g) (3) BET specific surface area The BET specific surface area was measured by MONOSORB (manufactured by QUANTACHROME, USA) according to the BET one-point method.

(4) Pore Volume and Pore Mode Diameter Pore size was measured by a mercury intrusion method using a pore sizer 9320 (manufactured by MICROMERITICS) in a pressure range of 0 to 270 MPa.

(5) Granule Size The granulated sample was classified by a sieve, and the median value of the mesh size of the largest sieve was defined as the granule size.

(6) DBA adsorption amount A dry sample (250 mg) was precisely weighed, and 50 ml of a 0.002 N-di-n-butylamine solution (using petroleum benzine as a solvent) was added thereto. I left it. 5 ml of chloroform was added to 25 ml of the supernatant,
Add 2 to 3 drops of indicator (crystal violet) and titrate with a 0.01 N perchloric acid solution (acetic anhydride solution) until the color of the solution changes from purple to blue. The titration value at this time is defined as Aml. Separately perform a blank, and set the titration value to B
ml. From this, the DBA adsorption amount was determined by the following equation.

DBA adsorption amount (m · mol / kg) = 80
× (BA) f (where f is the titer of a 0.01 N perchloric acid solution) Example 1 Water 540 g was added to 540 g of a silica powder having a specific surface area of 300 m ² / g.
After granulating by a tumbling granulation method using 0 g as a binder,
Heat treatment was performed at 700 ° C. for 1 hour. The BET specific surface area, the pore volume, the pore mode diameter, and the granule size of the obtained granules of silica were measured by the above-described methods. The results are shown in Table 1. FIG. 1 shows a pore distribution diagram.
Next, the obtained silica granules were subjected to hydrophobic treatment with silicone oil. After the hydrophobization treatment, the amount of DBA adsorbed and the amount of hesperidin adsorbed were measured by the method described above,
The results are shown in Table 1. Observation of the obtained silica granules with an optical microscope revealed that the granules were spherical.

[0036]

[Table 1]

Example 2 700 g of the silica powder and 200 g of crystalline cellulose used in Example 1 were mixed with 1250 g of water and 60 g of an acrylic binder.
Was used as a binder, and granulation and hydrophobization treatment were performed in the same manner as in Example 1, and the measurement was performed. As a result, the specific surface area, pore volume, pore mode diameter, granule size, DBA adsorption amount and hesperidin adsorption amount of the obtained silica granules are shown in Table 1, and the pores of the silica granules are shown in Table 1. The distribution chart is shown in FIG. Observation of the obtained silica granules with an optical microscope revealed that the granules were spherical.

Example 3 360 g of silica powder having a specific surface area of 250 m ² / g and 100 g of crystalline cellulose were mixed with 550 g of water as a binder.
The granulation and hydrophobization treatment and the measurement were performed in the same manner as in Example 1 except that the heat treatment was performed at 500 ° C. for 1 hour. Table 1 shows the specific surface area, pore volume, pore mode diameter, granule size, DBA adsorption amount and hesperidin adsorption amount of the obtained silica granules in Table 1, and the pore distribution diagram of the silica granules is shown in FIG. 3 is shown. Observation of the obtained silica granules with an optical microscope revealed that the granules were spherical.

Comparative Example 1 540 g of the silica powder used in Example 1 was replaced with 2200 g of water.
Was used as a binder to perform tumbling granulation, but it turned into a slurry and could not be granulated.

Comparative Example 2 1350 g of silica powder having a BET specific surface area of 150 m ² / g
Was granulated in the same manner as in Example 1 using 2700 g of water as a binder. After the granulation, the granulated body heat-treated at 700 ° C. for 1 hour was subjected to a hydrophobic treatment in the same manner as in Example 1, and the measurement was further performed. Table 1 shows the specific surface area, pore volume, pore mode diameter, granule size, DBA adsorption amount and hesperidin adsorption amount of the obtained silica granules in Table 1, and the pore distribution diagram of the silica granules is shown in FIG. The results are shown in FIG. Observation of the obtained silica granules with an optical microscope revealed that the granules were spherical.

When Examples 1 to 3 and Comparative Example 2 are compared, the Example has smaller pore mode diameters, a sharper distribution of the pores, and a larger hesperidin adsorption amount than the Comparative Example. From, useful as an adsorbent and a separating agent,
It can be seen that the large adsorption capacity and the fine pore diameter are controlled.

Example 4 The silica granules obtained in Example 1 were classified and passed through a sieve having a mesh size of 200 μm.
The column was packed in a column of mm × 160 mm in length, and its separation ability was evaluated. Hesperidin solution (20 μg) using methyl p-hydroxybenzoate as an internal standard as a solution for evaluation
/ Ml) and a buffer solution of pH 7.6 as a mobile phase,
THF and acetonitrile were added at 43: 8: 3, respectively.
Was used at a ratio of 1. Measurement is at a flow rate of 0.5 m
The detection was performed at a detection sensitivity of 0.05 AUFS by absorption of ultraviolet light at 283 nm at 1 / min. The chromatographic spectrum obtained at this time is shown in FIG.

FIG. 5 shows that the sample used was sufficiently separated, indicating that the silica-based adsorptive separation agent of the present invention can be used as a packing material for chromatography.

[0044]

The silica-based adsorptive separation agent of the present invention has a sufficient pore volume, a controlled pore diameter, and a high adsorption capacity, so that it can be used for large-capacity open columns and the like.
According to the method of the present invention, such a silica-based adsorptive separation agent can be easily and inexpensively produced.

[Brief description of the drawings]

FIG. 1 is a pore distribution diagram of a granulated silica of Example 1.
In the figure, the horizontal axis represents the pore diameter (nm), and the vertical axis represents the cumulative distribution curve (cumulative pore volume (cm ³ / g)) of the pores of the silica granules on the left side. The right side shows the frequency distribution curve of the pores of the silica granules (pore volume (cm ³ / g).
/ Log (pore diameter)).

FIG. 2 is a pore distribution diagram of a granulated silica of Example 2,
In the figure, the horizontal axis represents the pore diameter (nm), and the vertical axis represents the cumulative distribution curve (cumulative pore volume (cm ³ / g)) of the pores of the silica granules on the left side. The right side shows the frequency distribution curve of the pores of the silica granules (pore volume (cm ³ / g).
/ Log (pore diameter)).

FIG. 3 is a pore distribution diagram of the granulated silica of Example 3;
In the figure, the horizontal axis represents the pore diameter (nm), and the vertical axis represents the cumulative distribution curve (cumulative pore volume (cm ³ / g)) of the pores of the silica granules on the left side. The right side shows the frequency distribution curve of the pores of the silica granules (pore volume (cm ³ / g).
/ Log (pore diameter)).

FIG. 4 is a pore distribution diagram of the granulated silica of Comparative Example 2,
In the figure, the horizontal axis represents the pore diameter (nm), and the vertical axis represents the cumulative distribution curve (cumulative pore volume (cm ³ / g)) of the pores of the silica granules on the left side. The right side shows the frequency distribution curve of the pores of the silica granules (pore volume (cm ³ / g).
/ Log (pore diameter)).

FIG. 5 is a chromatographic spectrum of Example 4, in which the horizontal axis represents the elution time in chromatography, and the vertical axis represents the amount of ultraviolet ray absorption at 283 nm, which is the detected amount.

[Explanation of symbols]

1: peak of hesperidin in the chromatographic spectrum of Example 4 2: peak of methyl p-hydroxybenzoate in the chromatographic spectrum of Example 4

Claims (4)

[Claims] 1. A silica-based adsorptive / separating agent which is spherical and has a diameter of 0.1 to 2 mm and is made of silica granules whose surface is hydrophobized. 2. The silica-based adsorptive separation agent according to claim 1, wherein the silica granules have a pore volume of 0.7 cm ³ / g or more, a pore mode diameter of 6 to 20 nm, and 20
A silica-based adsorptive separation agent, wherein the volume of pores of nm or more occupies 20 to 50% of the total pore volume. 3. The method for producing a silica-based adsorptive separation agent according to claim 1, wherein the BET specific surface area is 1%.
100 to 500 m ² / g of silica powder,
Using 50 to 400 parts by weight of water as a binder with respect to 0 parts by weight, and granulating into a spherical shape of 0.1 to 2 mm,
A method for producing a silica-based adsorptive / separating agent, comprising heat-treating at 0 ° C. 4. A packing material for preparative chromatography, comprising using the silica-based adsorptive separation agent according to claim 1 or 2.