JPH01202658A - Filling material for liquid chromatography - Google Patents

Abstract

PURPOSE:To divide various optically active substances efficiently and moreover, to enable the parcelling and refining efficiently in a short time, by using a filling material for optical division comprising a spherical clay mineral having an optically active cation between layers. CONSTITUTION:A filling material comprises a spherical clay mineral in which an optically active cation existing as ion between layers thereof is substituted in substance. Being spherical, the filling material is so high in the filling efficiency as to be used for a fast liquid chromatography. It also fully comprises a clay mineral without use of any carrier to achieve a high identifying capacity of an optical isomer. Moreover, the spherical clay mineral can be produced simply at a low cost. Thus, this filling material permits efficient division of various optically active substances and also enables parcelling and refining efficiently in a short time.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a packing material for liquid chromatography. More specifically, it is a novel filler for liquid chromatography for optical resolution, which is made of a spherical clay mineral having optically active cations between layers. By using this material, it is possible to efficiently separate various optically active substances that are difficult to separate with conventional optical separation packings, and it is a new packing for liquid chromatography that allows for efficient preparative purification in a relatively short period of time. It is intended to provide an agent for

[Prior Art] The need to optically resolve optically active substances has become important in recent years. Optical resolution methods include methods that chemically generate diastereomers and utilize differences in their physicochemical properties, methods that use enzymes, and methods that use chromatography. Among these methods, chromatography methods utilize the differences in physical adsorption, chemical adsorption, and distribution of chiral adsorbents to both enantiomers. is being actively developed.

Packing materials for liquid chromatography for optical resolution are those in which optically active ligands are adsorbed or chemically bonded to silica gel or organic polymer powder, or in which the polymer itself is endowed with optical activity. A method has also been proposed in which interlayer ions of clay minerals are ion-exchanged with an optically active metal complex and used as a splitting agent.

[Problems to be Solved by the Invention] With these fillers for optical resolution, the substances that can be optically resolved are limited depending on each filler, and the resolution is often incomplete. Furthermore, there are problems with durability due to detachment of the ligand and swelling of the filler, and long-term use is often difficult.

When using metal complexes/clay adducts (Unexamined Japanese Patent Publication No. 61-2
04138), it is difficult to use it as a packing material for high performance liquid chromatography due to the particle size, particle size distribution, and irregular shape of the clay mineral, and it must be used in a batch method or an oven column, and efficient separation is not possible. In addition, an adsorbent made by adhering this adduct to silica gel etc.
-204562) can be used as a packing material for high-performance liquid chromatography, but the proportion of the metal complex/clay adduct required for optical resolution in the total packing material is small and there are few adsorption sites, so many substances are adsorbed. The substances that can be applied are extremely limited because they elute without being washed out. Moreover, even the applicable substances have the disadvantage that water must be included in the eluent in order to reduce the solubility in the eluent and increase the adsorption power to the filler.

As a result of intensive research in view of the above circumstances, the present inventors succeeded in producing a spherical clay mineral, and then substantially replaced the interlayer ions of the spherical clay mineral with optically active cations. The present inventors have discovered that many optically active substances can be efficiently separated and can be used for a long period of time when used as a packing material for liquid chromatography, and based on these findings, they have completed the present invention. It was.

[Means for Solving the Problems] That is, the present invention provides a packing material for liquid chromatography for optical resolution consisting of a spherical clay mineral in which the interlayer ions of the clay mineral are substantially replaced by optically active cations. This is what we provide.

Hereinafter, the configuration of the present invention will be explained in detail.

The clay mineral used in the present invention is a layered silicate mineral belonging to the genus smectite, and any clay mineral that can produce spherical clay minerals may be used, but - those with small large particles are preferable;
In this sense, the synthetic sabonite smectone (
Particularly preferred are Kunimine Kogyo Co., Ltd.) and synthetic hectorite Laponite (Laborte Co., Ltd.).

Examples of the optically active cation used in the present filler include metal complexes having an optically active site, amino acids, quaternary ammonium salts, alkaloids, etc. Among them, optically active metal complexes are particularly preferred.

The metal complex is composed of a metal ion and a ligand, and may be any complex as long as it is inert to substitution of the ligand and has optical activity based on the coordination structure. Among these, preferred are complexes that are easy to optically resolve, are stable without racemization or deterioration during use, and have a high ability to resolve optically active forms. Metal ions include nickel, ruthenium, cobalt, iron, copper, etc., and ligands include 1.10-phenanthroline and 2.2
Common compounds such as '-bipyridine and amino acids are used.

A simple method for obtaining the filler according to the present invention is to first obtain a spherical clay mineral, and then replace the exchangeable ions between the layers with optically active cations.

Spray drying is preferably used to obtain spherical clay minerals.

By using this, it is possible to easily obtain a spherical clay mineral with a relatively uniform particle size. That is, this is a method in which clay minerals are dispersed in an aqueous solvent, gelled, and then the dispersion is spray-dried.

In preparing the above gel, the concentration of clay mineral is 20
It is desirable that the amount is less than 1% by weight, and particularly preferably 1 to 10% by weight. If the concentration exceeds 20% by weight, the gel viscosity is high, making it difficult to feed the liquid to the spray nozzle during spray drying, and clogging the nozzle. Further, when preparing the above gel, it is preferable to sufficiently stir the gel so that the clay mineral is sufficiently dispersed and fff-J. If the dispersion and swelling are insufficient, the nozzle may become clogged during spray drying, and the obtained spherical clay mineral may become uneven, which is not preferable.

For spray drying, disc type, pressure nozzle type,
A general spray drying method such as a two-fluid nozzle method can be applied.

In either case, the inlet air temperature during spraying is 3.
Since it is thermally stable enough up to about 00℃, 150℃
A wide temperature range of ~300°C can be set. Further, the exhaust temperature can be determined by the flow rate of the spray from the nozzle, etc., but in general, it is sufficient to be around 100°C. The particle size of the spherical clay mineral thus obtained is 2 to 20 μm. This spherical clay mineral is used after being classified by an ordinary dry classification method, if necessary.

There are usually sodium ions between the layers of clay minerals,
Although the entire clay mineral is electrically neutralized, the interlayer ions are exchangeable and can be easily replaced with other cations. This cation exchange capacity varies depending on the type of clay mineral, but is 60 to 150 milliequivalents per 100 g of clay mineral.

As a method for exchanging interlayer cations, an optically active cation salt is dissolved in water or an organic solvent, spherical clay minerals are dispersed therein, and the mixture is stirred. Alternatively, spherical clay minerals may be dispersed in an organic solvent, and an optically active cation salt may be dissolved therein. Thereafter, the clay minerals may be separated, washed, and then dried.

As the organic solvent, common solvents such as ethanol, methanol or acetone are used.

There is no particular limit to the concentration of spherical clay minerals during production, but
When the concentration exceeds %, stirring becomes difficult and ion exchange becomes difficult to perform. The amount of optically active cations in the dispersion is desirably greater than or equal to the cation exchange capacity of the clay mineral. The temperature of the dispersion during the ion exchange reaction may be any temperature, and room temperature is usually sufficient. The drying temperature may be any temperature as long as it is below the decomposition temperature of the optically active cation.

In optical resolution using the packing material according to the present invention, the target substance may be any optically active substance as long as it is soluble in a solvent. Many organic compounds with 1,1°
-B-2-naphthol, 2,2"-diamino-1,1°
- Compounds with axial chirality such as binaphthyl,
Compounds with an asymmetric center at a heteroatom such as phenylcyclohexyl sulfoxide, fused benzene rings such as hexahelicene, tris(acetylacetonato)cobalt(I
Examples include metal complexes such as ll).

When using the present filler, a wide range of solvents R'W can be used, including water, polar solvents such as methanol and ethanol, nonpolar solvents such as chloroform, or mixtures thereof. Further, even when these eluents are used, cations do not elute, and the present packing material can be used for a long period of time.

[Effects of the Invention] The packing material according to the present invention is characterized by being spherical, and because of its spherical shape, it has a high packing efficiency, can be used as a high-performance liquid chromatography crucible packing material, and has an excellent number of theoretical plates. It has the characteristic that it can be obtained. In addition, since no carrier is used and all the fillers are composed of clay minerals, the density of sites that identify optical isomers is high.
, has extremely high ability to discriminate optical isomers. It also has the characteristics that any eluent can be used and a large number of substances can be optically resolved.

Roughly spherical clay minerals can be easily produced at low cost, and many optically active cations, such as metal complexes, are known to be easy to synthesize and optically resolve, so this filler can be easily and inexpensively obtained. It also has the characteristic of being able to

From the above, it can be said that the present packing material is extremely useful for the analysis and fractionation of optical isomers such as physiologically active substances.

[Example] Next, in order to further understand the present invention, the present invention will be explained in more detail by giving examples. The present invention is not limited to these.

Example 1 300 g of Laponite XLG is dispersed in ion-exchanged water 101 with stirring. The obtained gel was dried using a disk-type spray dryer at a disk rotation speed of 20,000 rpm.

Spray drying was carried out at an inlet air temperature of about 200°C and an exhaust temperature of about 110°C, yielding 240 g of spherical powder with a diameter of 2 to 20 μm.

This spherical clay mineral is processed using the dry classifier TARBOCLASSI.
FIHERTC-158 (manufactured by Nisshin Engineering Co., Ltd.)
60 g of powder with a particle size of 3 to 7 μm was obtained.

Δ-Ni(Phen)3” in ethanol 500ttrt
5 mmol of C12 (Phen stands for 1.10-phenanthroline) is dissolved, and 10 g of the obtained classified spherical clay mineral is dispersed therein, followed by stirring for 4 hours. Thereafter, it was filtered, washed with water, and dried at 80°C to obtain a spherical powder. A scanning electron micrograph of this product is shown in FIG.

Then, using a packer and a pump, 5 g of the powder was added to a powder with an inner diameter of 4
．． A packed column was prepared by filling a stainless steel rim with a length of 6+* and a length of 25 cm using the balanced slurry method.

This column was connected to a high-performance liquid chromatograph, ethanol was flowed as an eluent at a rate of 0.2 mL per minute, and racemic 1,1°-bi-2-naphthol was injected. Detection was performed at 250 nm using a UV detector to obtain a chromatogram.

This is shown in FIG. As shown in this figure, even if the eluent is an organic solvent that does not contain water, the 8
The body and the R body are well separated.

Example 2 Using the column prepared in Example 1, racemic tris(acetylacetonato)chromium (TIE) was analyzed under the same conditions. This chromatogram is shown in Figure 3. As shown in this figure, 6 bodies and 6 bodies are well separated.

4. Brief explanation of the figure.

FIG. 1 is a scanning electron micrograph showing the particle structure of the packing material for liquid chromatography according to the present invention.

FIG. 2 is a chromatogram obtained when racemic 1.1''-bi-2-naphthol was analyzed using the packing material of Example 1. In Figure 2, beak 1 is 1,1° - beak 2
-8 forms of naphthol, and beak 2 shows the R form.

FIG. 3 is a chromatogram when racemic tris(acetylacetonato)chromium (III) was analyzed using the packing material of Example 1. In Figure 3, beak 1 is 6 of tris(acetylacetonato)chromium(III).
Beak 2 shows six bodies.

Patent applicant Shiseido Co., Ltd.

Claims (1)

[Claims] (1) A packing material for liquid chromatography consisting of a spherical clay mineral in which interlayer ions of the clay mineral are substantially substituted with optically active cations.