JPH0478621B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a chromatographic packing material. More specifically, it relates to chromatographic packings used for the separation of various compounds, particularly for optical resolution.

(Prior Art and Problems) Most of the chromatographic packing materials disclosed so far for use in optical resolution are asymmetric compounds supported in various forms on inorganic carriers.
As the asymmetric compound, amino acids, saccharides, proteins, optically active polymethacrylic acid esters, optically active poly(meth)acrylic acid amides, optically active crown ethers, optically active fluorine-containing anthracene derivatives, etc. are said to be effective. The method of supporting on an inorganic carrier is a grafting method (for example, Japanese Patent Application Laid-open No.
50358 (see Japanese Patent Laid-open No. 50358) and a method of simply adsorbing and supporting (see, for example, Japanese Patent Application Laid-open No. 150432/1983).
However, the former method generally has poor reproducibility during the production of the separating agent, and the latter method has problems such as poor stability of the separating agent.

(Object of the Invention) In view of the above points, the present inventors conducted extensive studies with the aim of obtaining a stable separating agent with excellent reproducibility, particularly a separating agent for optical resolution. As a result, it was discovered that a new separating agent having a chemical structure different from conventional ones, that is, one in which an optically active epoxy compound is reacted with an inorganic carrier grafted with an aminoalkylsilane, can sufficiently achieve the above object, and the present invention has been completed. This is what led to this.

(Structure of the Invention) The present invention is a filler for optical resolution, which is obtained by grafting an aminoalkylsilane onto an inorganic carrier and reacting the graft with an optically active epoxy compound.

The novel chromatographic packing material of the present invention can be prepared by the following method. An aminoalkylsilyl group is introduced into the inorganic carrier by grafting the aminoalkylsilane and the inorganic carrier by a known method. The filler of the present invention can be obtained by subjecting this to an addition ring-opening reaction with an optically active epoxy compound in the presence of a dispersant.

Inorganic carriers used in the present invention include silica gel,
Examples include alumina and glass beads.

The aminoalkylsilane used in the present invention is represented by the following general formula [].

In the formula, X ₁ , X ₂ , and X ₃ each have a hydrogen atom and a carbon number of 1 to
20 alkyl groups, halogen atoms, hydroxy groups,
or an alkoxy group having 1 to 20 carbon atoms, or any combination thereof. R ₁ is carbon number 1-30
A group that forms a spacer and contains one or more amino groups at the end or inside. Specific examples of the aminoalkylsilane represented by the general formula [] include the following.

2-aminoethyltriethoxysilane, 3-aminopropyldimethylethoxysilane, 3-aminopropylmethyldiethoxysilane, 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane, 1-(3-aminopropyl)- 1-Methylsiler-11-crown-4,N
-Methyl-3-aminopropyltrimethoxysilane, N-methyl-3-aminopropyltriethoxysilane, N-(2-aminoethyl)-3-aminopropyltris(2-ethylhexoxy)silane, N-(2-amino ethyl)-3-aminopropyltrimethoxysilane, N-(2-aminoethyl)
-3-aminopropylmethyldimethoxysilane,
(aminoethylaminomethyl)phenethyltrimethoxysilane, 4-aminobutyltriethoxysilane, 4-aminobutyldimethylmethoxysilane, 3-aminopropyltrichlorosilane, N-
Methyl-3-aminopropyltrichlorosilane.

The optically active epoxy compound used in the present invention is represented by the following general formula [].

In the formula, * represents an asymmetric carbon. In the formula, R ₂ is a chain or cyclic alkyl group, alkenyl group, aryl group, halomethyl group, alkoxymethyl group, thioalkoxymethyl group, aryloxymethyl group, thioaryloxymethyl group, which may have a substituent, or Represents a carboxymethyl group. Specific examples of the optically active epoxy compound represented by the general formula [] include the following.

Propylene oxide, 1,2-epoxyheptane, 1,2-epoxydecane, 1,2-epoxytetradecane, 1,2-epoxyoctadecane,
Styrene oxide, epichlorohydrin, ebromohydrin, epiiodohydrin, methyl glycidyl ether, propyl glycidyl ether,
Octyl glycidyl ether, allyl glycidyl ether, triphenylmethyl glycidyl ether, 2,2,2-trifluoroethyl glycidyl ether, 2,2,2-trichloroethyl glycidyl ether, hexafluoroisopropyl glycidyl ether, phenyl glycidyl ether,
3-trifluoromethylphenyl glycidyl ether, 2,4,5-trichlorophenyl glycidyl ether, 2-chlorophenyl glycidyl ether, 2-fluorophenyl glycidyl ether, pentafluorophenyl glycidyl ether, 3,5-dimethoxyphenyl ether enyl glycidyl ether, 2,3,5-trimethylphenyl glycidyl ether, 2,4-dinitrophenyl glycidyl ether, 1-naphthyl glycidyl ether,
2-naphthyl glycidyl ether, 9-anthryl glycidyl ether, 1-anthryl glycidyl ether, 2-anthryl glycidyl ether, l-menthyl glycidyl ether, phenyl glycidyl thioether, 4-chlorophenyl glycidyl thioether, 2-naphthyl glycidyl thioether , 2-phenylbutyl glycidyl ether, 3-phenylbutyl glycidyl ether, 1-glycidyl naphthoate, glycidyl benzoate, glycidyl 2-chlorobenzoate, glycidyl 2-fluorobenzoate, glycidyl 2-iodobenzoate, 2- Glycidyl phenylbenzoate, glycidyl triphenyl acetate, glycidyl 3-phenylbutyrate, glycidyl abietate, glycidyl deoxycholate.

The amount of optically active epoxy compound is 0.01 to 0.01 by weight relative to the inorganic carrier into which aminoalkylsilyl groups have been introduced.
Use 5 times the amount, preferably 0.02 to 1 times the amount. If the amount is less than 0.01 times, the separation will be insufficient, and if the amount exceeds 5 times, the separation power will no longer be improved.

The separating agent is preferably one that dissolves the optically active epoxy compound, such as dimethyl sulfoxide, dimethyl formamide, diglyme, triglyme, dibutyl ether, benzene, toluene, chloroform, and the like.

The reaction temperature is 0 to 200°C, preferably 40 to 120°C. During the reaction, it is desirable to perform stirring so that the concentration of the optically active epoxy compound is as uniform as possible.

When performing separation using the packing material of the present invention, it is necessary to select a solvent suitable for liquid chromatography, that is, a solvent that is a good solvent for the substance to be separated and has excellent separation ability. .

(Effects of the Invention) The optical resolution filler of the present invention is effective in separating various compounds, particularly in separating optical isomers, and has excellent reproducibility and physical and chemical stability. . One of the optical isomers to be separated is selectively and strongly adsorbed by the filler of the present invention.

This will be explained in more detail below using Examples.

Example 1 R-(-)-epichlorohydrin (optical purity 99%
ee) 3-trifluoromethylphenol in 6.6g
Dissolve 4.63g at 80℃ in the presence of 0.08g piperidine.
Let it react for 6 hours. After removing excess epichlorohydrin under reduced pressure, the residue was dissolved in 40 ml of acetone, 15 g of anhydrous potassium carbonate was added thereto, and the mixture was reacted under stirring and reflux for 6 hours. After the reaction, the acetone was distilled off, and the residue was chromatographed using alumina with a benzene eluent to obtain 5.15 g of optically active (+)-3-trifluoromethylphenyl glycidyl ether (yield rate 83%, [α]
_D = +8.79°).

20g of silica gel (particle size 5μm, pore size 120Å)
After drying under reduced pressure at 120℃ for 5 hours, 18.8g of 3-aminopropyltriethoxysilane was dissolved in dehydrated toluene.
Add to the solution dissolved in 300 ml and stir under reflux for 6 hours. Filter the reaction mixture and add 300ml of toluene to the residue.
After washing with 300ml of acetone and drying at 60℃ for 12 hours, 3-aminopropylsilylated silica gel (hereinafter referred to as
It's called APS. ) was obtained. The elemental analysis values of this product were C: 4.54% and N: 1.25%.

Next, 10 g of the above APS was added to a solution of 2.0 g of the above (+)-3-trifluoromethylphenyl glycidyl ether dissolved in 40 ml of dimethylformamide, and the mixture was stirred at 80°C for 6 hours. After the reaction, the residue was washed with methanol and dried at 60°C for 12 hours to obtain the desired filler having a (+)-3-trifluoromethylphenoxy group. The elemental analysis values of this product were C: 9.30% and N: 1.07%.

The packing material obtained in this way was slurry packed into a stainless steel column with an inner diameter of 4.6 mm and a length of 300 mm.
Using this, (+)-2,2'-dihydroxy-1,1'-binaphthyl was analyzed under the following conditions, and the chromatogram shown in Figure 1 was obtained.

Temperature: room temperature Moving phase: n-hexane/1,2 dichloroethane/
Ethanol = 50:49:1 Flow rate: 1 ml/min Detector: Ultraviolet absorption meter (wavelength 254 mm) In Figure 1, peak number (1) is (-)-2,2'-dihydroxy-1,1'-binaphthyl, (2) is (+)-2,
These are the peaks of 2'-dihydroxy-1,1'-binaphthyl.

After the above analysis, 1,2-dichloroethane was used as the eluent, followed by methanol/water = 7:3, and then analysis was performed again under the same conditions using the same ternary eluent as above, and it was found to be reproducible. A chromatogram was obtained.

Example 2 In the same manner as in Example 1, in the presence of 0.07 g of piperidine, 7.0 g of R-(-)-epichlorohydrin and 2,4,
By reaction with 5.98 g of 5-trichlorophenol, 5.91 g of optically active (+)-2,4,5-trichlorophenyl glycidyl ether was obtained (yield 77
%, [α] _D = +5.75°).

Furthermore, in the same manner as in Example 1, 10 g of APS was reacted with 2.0 g of the above (+)-2,4,5-trichlorophenyl glycidyl ether to obtain (+)-2,4,
A filler having a 5-trichlorophenoxy group was obtained. The elemental analysis value of this product is C: 7.92%, N:
It was 1.09%.

The obtained packing material was slurried packed into a stainless steel column with an inner diameter of 4.6 mm and a length of 150 mm, and (±)-2,2'-dihydroxy-1,1'-binaphthyl was analyzed under the following conditions. A chromatogram was obtained.

Temperature: Room temperature Moving phase: n-hexane/1,2-dichloroethane/ethanol = 50:49:1 Flow rate: 1 ml/min Detector: Ultraviolet absorption meter (wavelength 254 mm) Peak number (1) in Figure 2 is (-) -2,2'-dihydroxy-1,1'-binaphthyl, (2) is (+)-2,
These are the peaks of 2'-dihydroxy-1,1'-binaphthyl.

In addition, the reaction of 2.0 g of (+)-2,4,5-trichlorophenyl glycidyl ether and 10 g of APS was repeated again, and the analysis was performed under the same conditions as above. As a result, the reproducibility was within the error range. A chromatogram was obtained.

[Brief explanation of the drawing]

1 and 2 are chromatograms obtained in Examples 1 and 2, respectively, where the vertical axis represents intensity and the horizontal axis represents retention time (minutes).

Claims (1)

[Claims] 1. A filler for optical resolution, which is obtained by grafting aminoalkylsilane onto an inorganic carrier and reacting it with an optically active epoxy compound.