JPH0647455B2 - Silica gel filling agent - Google Patents

Description

TECHNICAL FIELD The present invention relates to a silica gel filler having a straight-chain alkyl group having 4 to 24 carbon atoms and having excellent durability.

(Prior art and problems) In general, silica gel packing has excellent performance as a packing for liquid chromatography and is actively used today, but its use in the basic region remarkably due to its acidic property. Be restricted. Further, the use of a protic solvent such as water or alcohol causes the silica gel to dissolve, resulting in deterioration. Therefore, in order to prevent deterioration to some extent, a method of using a silane coupling agent to remove acidic silanol has been used. However, even with these methods, it is difficult to completely eliminate silanol, and long-term deterioration is unavoidable due to the attack of the protic solvent on the silane treating agent. Particularly, in the case of a packing material for reversed phase liquid chromatography using a polar solvent based on silica gel, a packing material for ligand exchange type liquid chromatography, and a packing material for liquid chromatography having an amino group, This has caused a problem because the storage capacity changes with time due to deterioration.

(Means for Solving Problems) The present inventors substantially inactivate the surface silanol by reacting with the silanol on the surface of the silica gel or forming a thin film on the surface of the silica gel, and then, As a result of diligent search for compounds capable of avoiding long-term deterioration due to attack of a protic solvent on a silane treating agent by reacting with a silane coupling agent having a linear alkyl group of 24 to 24, the periodic table excluding silicon is shown. IV
By finding a group b element or elemental compound and treating it with these compounds, the carbon number of 4 to 2 which is excellent in durability
The present invention has been achieved in which a silica gel filler having a linear alkyl group of 4 is obtained.

The packing material for liquid chromatography having a linear alkyl group having 4 to 24 carbon atoms in the present invention includes general organic compounds, proteins, peptides, sugars, hydroxy compounds,
It is for separating a wide range of compounds such as basic compounds and amino acids from each other or separating optical isomers.

Examples of the silane coupling agent having a linear alkyl group having 4 to 24 carbon atoms in the present invention include octyltriethoxysilane, octyltrimethoxysilane, octyl (methyl) diethoxysilane, octyl (methyl) dimethoxysilane, and octyl (dimethyl). ) Ethoxysilane,
Octyl (dimethyl) methoxysilane, octadecyltriethoxysilane, octadecyltrimethoxysilane,
Examples of silane coupling agents having a linear alkyl group having 4 to 24 carbon atoms, such as octadecyl (methyl) diethoxysilane, octadecyl (methyl) dimethoxysilane, octadecyl (dimethyl) ethoxysilane, and octadecyl (dimethyl) methoxysilane are exemplified. It

These silane coupling agents may be used alone or in combination with these or other silane coupling agents. Further, after reacting these silane coupling agents, it is possible to eliminate the remaining hydroxyl groups by reacting them with the residual hydroxyl groups on the surface of the substrate using a silane coupling agent having higher reactivity.

The deterioration of the silica gel filler is caused by the silica gel itself being dissolved in the solvent or the bonded silane coupling agent being desorbed. Therefore, it is necessary to eliminate the exposure of silanol in order to avoid dissolution of silica gel, and to strengthen the bond in order to prevent desorption of the silane coupling agent. In order to satisfy both of them at the same time, as a result of diligent study, the periodic table excluding silicon lV
We have found a method of reacting a group b element or element compound or physically adsorbing the thin film. Titanium and zirconium are exemplified as the elements of Group IVb of the periodic table excluding silicon. In addition, as the compound, titanium chloride,
Titanium n-propoxide, titanium iso-isopropoxide, titanium n-butoxide, zirconium chloride, zirconium chloride, zirconium oxychloride,
Zirconium n-propoxide, zirconium iso-
Examples include propoxide and zirconium n-butoxide. These compounds may be used alone or as a mixture, and if necessary during the reaction with the silane coupling agent, the reaction can be facilitated by treating under a water-containing condition.

The silica gel as a base material preferably has a particle size of 1 to 100 μm and a pore size distribution peak of 10 to 2000 Å,
The shape may be spherical or crushed.

The reaction of an element or an elemental compound of Group IVb of the periodic table excluding silicon with silica gel can be carried out by dissolving the above compound in a solvent capable of dissolving it and contacting it with silica gel. By doing so, the reaction can be promoted. Further, it is preferable to add a dehydrochlorinating agent if necessary. On the other hand, when these compounds are physically adsorbed on the silica gel surface or a thin film is formed, the solvent is distilled off after contacting these compounds with the silica gel surface, and then heating is performed. It can be more or less accompanied by polymerization of the above compounds. In addition, as another method, the periodic table excluding silicon by sputtering etc.
It is also possible to form a thin film of an element of the IVV group or an elemental compound on the surface of silica gel.

Silica gel reacted with an element or an element compound of Group IVb of the periodic table excluding silicon can have a hydroxyl group on the surface by contact with water, and can be easily reacted with a silane coupling agent. The reaction with the silane coupling agent may be a conventional method, for example, heating under reflux in benzene or toluene, or a method of adding a dehydrochlorinating agent depending on the silane coupling agent may be appropriately selected.

(Effects of the Invention) The packing material for liquid chromatography having a linear alkyl group having 4 to 24 carbon atoms can be used for general organic compounds, proteins,
It is intended for the mutual separation of a wide range of compounds such as peptides, saccharides, hydroxy compounds, basic compounds, amino acids, etc. or for the separation of optical isomers, but with conventional packing materials obtained by directly reacting silane coupling agents with silica gel. The hydrogen ion concentration of the eluent can be used only in a narrow range,
Therefore, there is a problem that the separation ability is not fully exhibited. However, since the highly durable filler obtained by the present invention can use an eluent having a wider range of hydrogen ion concentration, it is expected to be applicable to the separation of a wider range of compounds. Further, it can be used as a filler for retaining optically active groups by hydrophobic interaction and performing optical resolution.

Hereinafter, the present invention will be described in detail with reference to Examples, but it goes without saying that the present invention is not limited thereto.

Synthesis Example 1 3.22 g of zirconium oxychloride octahydrate was dissolved in 100 ml of methanol, and silica gel (pore size 100
(Å, particle size 5 μm) 10 g, then triethylamine 2.1 g, and heated under reflux for 8 hours. After cooling this, it is filtered with a glass filter, and the surface is hydroxylated by washing with water, and then dried. The presence of Zr element was confirmed in the silica gel thus obtained by fluorescent X-ray analysis. This silica gel was further dried in toluene,
After reacting with 5 ml of octadecyl (dimethyl) methoxysilane by refluxing for 8 hours to effect silanization, N, O-bistrimethylsilylacetamide was further used for endcapping.

Synthesis Example 2 3.40 g of titanium n-butoxide and 50 ml of ethyl acetate
Dissolved in silica gel (pore size 100 Å, particle size 5 μ
m) 10 g was added to a suspension in 50 ml of ethyl acetate, and the mixture was heated under reflux for 8 hours. After cooling this, it is filtered with a glass filter, and the surface is hydroxylated by washing with water, and then dried. In the silica gel thus obtained, the presence of Ti element was confirmed by fluorescent X-ray analysis.
The silica gel was further reacted with 5 ml of octadecyl (dimethyl) methoxysilane in dry toluene by refluxing for 8 hours to be silanized, and then endcapped with N, O-bistrimethylsilylacetamide.

Example 1 The silanized silica gel obtained in Synthesis Example 1 was prepared to have a length of 25c.
m, an inner diameter of 0.46 cm, and packed in a stainless steel column,
When 1 ml / min of a water-acetonitrile mixed solution or a water-methanol mixed solution was made to flow as an eluent, most of the organic compounds were well separated, and the retention time of each compound was 1
It did not change for more than 200 hours.

Example 2 The silanized silica gel obtained in Synthesis Example 2 was prepared with a length of 25c.
m, an inner diameter of 0.46 cm, and packed in a stainless steel column,
When 1 ml / min of a water-acetonitrile mixed solution or a water-methanol mixed solution was made to flow as an eluent, most of the organic compounds were well separated, and the retention time of each compound was 1
It did not change for more than 200 hours.

Claims (1)

[Claims] 1. A layer of an element or an element compound of Group IVb of the periodic table excluding silicon is provided on the surface of silica gel, and then a silane coupling agent having a linear alkyl group having 4 to 24 carbon atoms is reacted. A silica gel filler characterized by the following.