JPH0475217B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a separating agent, and particularly to a separating agent containing a substituted aromatic ester derivative of polysaccharide as an active ingredient. [Industrial Application Field] The separating agent of the present invention can be used for the separation of all chemical substances, especially for optical resolution. As is well known, optical isomers of the same chemical compound usually have different effects on living organisms. Therefore, in fields such as medicine, agrochemicals, and biochemistry-related industries, improvements in medicinal efficacy per unit,
The preparation of optically pure compounds has become an extremely important issue for the purpose of preventing side effects and drug damage. Conventionally, preferential crystallization methods and diastereomer methods have been used to separate optically isomeric mixtures, that is, optically resolve them, but these methods limit the types of compounds that can be optically resolved, and also require long It often takes time and a lot of effort. Therefore, there is a strong need for a technique for easily performing optical resolution using chromatography. [Prior Art] Research on optical resolution using chromatography has been conducted for some time. However, conventionally developed separation agents have problems such as poor separation efficiency and the need for special functional groups in the target compound.
There are also various problems such as poor stability of the separating agent, making it difficult to perform satisfactory optical resolution on all compounds. [Object of the invention] Therefore, a separating agent that has a chemical structure different from existing separating agents, and thereby has different separating properties or a higher optical isomer discrimination ability. It is an object of the present invention to provide. In particular, the physical properties of substituents on aromatic rings,
It seeks to link chemical properties to novel separation properties. [Structure of the Invention] The present invention uses a separation agent containing a substituted aromatic ester derivative of cellulose (excluding aromatic aliphatic esters and aromatic esters having an atomic group having a conjugated π bond system) as an active ingredient. This will achieve the above objectives. The separating agent of the present invention preferably exhibits different adsorption powers for optical isomers of some compound. The polysaccharide used in the present invention is cellulose, and its number average degree of polymerization (-average number of pyranose or furanose rings contained in the molecule) is 5 or more, preferably 10 or more, and there is no particular upper limit, but it is 500 or less. This is preferable from the viewpoint of ease of handling. (Ester group) The substituted aromatic ester of the present invention is an ester of a carboxylic acid containing an aromatic group in which one or more hydrogen atoms of the aromatic group are replaced with one or more types of atoms or atomic groups. The alcohol moiety consists of the polysaccharide mentioned above. However, as a substituted aromatic ester derivative,
Excludes aromatic aliphatic esters and aromatic esters having an atomic group with a conjugated π-bond system skeleton. The aromatic ester is one in which an average of 30 to 100%, preferably 85 to 100%, of the total number of hydroxyl groups possessed by the polysaccharide forms an ester with the carboxylic acid. Hydroxyl groups not applicable to the above may exist as free hydroxyl groups, but may also be esterified, etherified, or carbamated to the extent that the separating power of the separating agent is not lost. (Synthesis method) To explain the polysaccharide esterification method for obtaining the polysaccharide derivative used in the present invention, for example, the production of substituted benzoic acid esters can be carried out by conventionally known methods (for example, Asakura Shoten "Daikai Kagaku 19,
(See page 124 of “Natural Product Polymer Chemistry I”). Examples of the esterifying agent include benzoyl derivatives having the following structure, and the most common one is benzoyl chloride. Any reaction solvent may be used as long as it does not inhibit the esterification reaction, such as pyridine or quinoline. often 4-
Catalysts such as (N,N-dimethylamino)pyridine are effective in accelerating the reaction. It can also be obtained by reacting a corresponding carboxylic acid anhydride or carboxylic acid with a suitable dehydrating agent on a polysaccharide. Other ester derivatives of the present invention can be synthesized according to the method for synthesizing substituted benzoic acid esters described above. (How to use) In order to use the separation agent of the present invention for the purpose of separating compounds and their optical isomers, chromatography methods such as gas chromatography, liquid chromatography, and thin layer chromatography may be used. is common, but membrane separation can also be performed. In order to apply the separation agent of the present invention to liquid chromatography, there are methods such as filling a column as a powder, coating a capillary column, forming a capillary with the separation agent, and utilizing the inner wall of the separation agent. Methods include spinning the fibers and bundling them into columns, but it is common to form them into powder. In order to make the separating agent into powder, it is preferable to crush it or form it into beads. The particle size varies depending on the size of the column and plate used, but is 1 μm to 10 mm, preferably 1 μm to 300 μm.
The particles are preferably porous. Further, in order to improve the pressure resistance of the separating agent, prevent swelling and shrinkage due to solvent substitution, and improve the number of theoretical plates, it is preferable to hold the separating agent on a carrier. The appropriate size of the carrier varies depending on the size of the column or plate used, but is generally 1 μm to 10 mm, preferably 1 μm to 300 μm. The carrier is preferably porous, with an average pore size of 10 Å to 100 μm, preferably 50 Å to 50,000 Å. The amount of the separating agent retained is 1 to 100% by weight based on the carrier;
Preferably it is 5 to 50% by weight. The separating agent may be retained on the carrier by either a chemical method or a physical method. As a physical method,
A method in which the separating agent is dissolved in a soluble solvent, mixed well with the carrier, and the solvent is distilled off by air flow under reduced pressure or heating, or after the separating agent is dissolved in a soluble solvent and mixed well with the carrier. Another method is to disperse the solvent by stirring and dispersing it in a liquid that is incompatible with the solvent. When crystallizing the separation agent held on the carrier in this manner, a treatment such as heat treatment can be performed. Furthermore, by adding a small amount of solvent to once swell or dissolve the separating agent, and then distilling off the solvent again, it is possible to change the retention state and thus the separating ability. The carrier may be a porous organic carrier or a porous inorganic carrier, preferably a porous inorganic carrier. Suitable porous organic carriers include polymeric substances such as polystyrene, polyacrylamide, polyacrylate, and the like. Suitable porous inorganic carriers include synthetic or natural materials such as silica, alumina, magnesia, titanium oxide, glass, silicates, and kaolin, which may be surface-treated to improve compatibility with the separation agent. You may also do this. Examples of surface treatment methods include silanization using an organic silane compound and surface treatment using plasma polymerization. The developing solvent for liquid chromatography or thin layer chromatography is not particularly limited, except for a liquid that dissolves or reacts with the separating agent. When the separation agent is bonded to a carrier by a chemical method or made insolubilized by crosslinking, there are no restrictions except for the reactive liquid. Needless to say,
Since the separation characteristics of chemical substances or optical isomers change depending on the developing solvent, it is desirable to consider various developing solvents. On the other hand, when performing thin layer chromatography,
The separating agent consists of particles of about 0.1 μm to 0.1 mm, and if necessary, a small amount of binder, with a thickness of 0.1 to 100 mm.
layer may be formed on the support plate. When performing membrane separation, it is used as a hollow fiber or film. (Effects of the Invention) The separating agent containing the substituted aromatic ester of the present invention as an active ingredient is effective in separating various compounds, and is particularly effective in separating optical isomers, which have been extremely difficult to separate in the past. One of the optical isomers to be separated is more strongly adsorbed by the separating agent. In particular, this separating agent is intended to improve the desired separation effect, especially optical resolution effect, by changing the separation and adsorption properties of the corresponding unsubstituted separating agent with a substituent. For example, when comparing tribenzoate esters of cellulose and their chlorine-substituted products, Traeger base, which is not optically resolved in tribenzoate, is resolved in tris-4-chlorobenzoate with an α value of 1.25. Furthermore, benzoin, which exhibits α1.14 in tribenzoate, exhibits α1.26 in tris-3-chlorobenzoate, and is better resolved. Similarly, Tris-3,5,
When dichlorobenzoate is used, benzoin, 2
- Phenylcyclohexanone, mandelamide, etc. are optically resolved much better than when using tribenzoate. Although it is not possible to completely explain the relationship between these significant changes in separation properties and substitution, it is important to note that the substituents change the shape of the molecule, and that the physical and chemical properties of the substituents themselves (polarizability, hydrogen bonding, etc.) It is thought that this is due to a complex combination of the following: The present invention has revealed that substituents have an extremely effective effect on modifying the separation characteristics of a separating agent, and it has become possible to develop separating agents having various characteristics. Such effects are naturally expected for various separation agents having polysaccharides other than cellulose in their skeletons. EXAMPLES The present invention will be described in detail below with reference to Examples, but the present invention is not limited to these Examples.
The definitions of terms used in the examples are as follows. Capacity ratio (k') = [(retention time of enantiomer) - (dead time)] / (dead time) Separation coefficient (α) = Capacity ratio of more strongly adsorbed enantiomer / weaker adsorbed enantiomer Volumetric resolution (Rs) = 2 x (distance between the two peaks of the more strongly adsorbed enantiomer and the more weakly adsorbed enantiomer)/sum of the band widths of both peaks Synthesis example 1 Silica beads (Merck LiChrospher
Put 10g of SI1000) into a 200ml round-bottom flask with branches,
After vacuum drying in an oil bath at 120°C for 3 hours, N ₂ was added. 100 ml of toluene distilled with C _a H ₂ was added to the silica beads. Next, 3 ml of diphenyldimethoxysilane (Shin-Etsu Chemical KBM202) was added, stirred, and reacted at 120°C for 1 hour. 3 to 5 more
After distilling off ml of toluene, the mixture was reacted at 120°C for 2 hours.
Pass through a glass filter and add 50ml of toluene.
The mixture was washed three times with 50 ml of methanol and vacuum dried at 40° C. for 1 hour. Next, about 10 g of the silica beads were placed in a 200 ml round bottom flask, and after vacuum drying at 100°C for 3 hours,
After returning to normal pressure and reaching room temperature, N ₂ was added. 100 ml of distilled toluene was added to the dried silica beads. Next, the trimethylsilylating agent N,O-Bis-
1 ml of (trimethylsilyl)acetamide was added, stirred, and reacted at 115°C for 3 hours. Next, after passing through a glass filter and washing with toluene,
Vacuum dried for hours. Synthesis Example 2 Cellulose triacetate (manufactured by Daicel Chemical Industries, Ltd.) with a number average degree of polymerization of 110 and a degree of substitution of 2.97 was dissolved in 1 part acetic acid (manufactured by Kanto Chemical), 5.2 ml of water and 5 ml of concentrated sulfuric acid were added, and the mixture was heated at 80°C for 30 minutes. Allowed time to react. The reaction solution was cooled, and the sulfuric acid was neutralized with an excess aqueous magnesium acetate solution. The solution was placed in water in Step 3 to precipitate cellulose triacetate having a lower molecular weight. The mixture was separated using a glass filter (G3), further dispersed in water (1), separated, and dried under vacuum. The product was purified by repeating twice an operation of dissolving the product in methylene chloride and reprecipitating it in 2-propanol, and then drying. The product is cellulose triacetate based on IR and NMR spectra, and the number average molecular weight determined by vapor pressure osmosis is 7900.
The number average degree of polymerization was 27. Vapor pressure osmometry is a paper pressure osmometer.
Chloroform-1 as solvent using CORONA117
It was measured using a mixed solvent of % ethanol. Cellulose triacetate thus obtained
60 g was dispersed in 200 ml of 2-propanol, and 60 ml of 100% hydrazine hydrate (manufactured by Hanui Chemicals) was slowly added dropwise while stirring gently. After the suspension was kept at 60°C for 3 hours, the cellulose produced was filtered out using a glass filter, washed repeatedly with acetone, and then dried under vacuum at 60°C. No absorption based on carbonyl groups near 1720 cm ^-1 was detected in the IR spectrum of the product, which matched that of cellulose. Synthesis Example 3 (Synthesis of cellulose tris-3-chlorobenzoate) 3.0 g of cellulose obtained in Synthesis Example 2 and 0.05 g of 4-dimethylaminopyridine (manufactured by Aldrich) were suspended in a mixed solution of 50 ml of pyridine and 15 ml of triethylamine. The mixture was made cloudy, 25 g of m-chlorobenzoyl chloride (manufactured by Aldrich) was added, and the mixture was kept at 100°C for 6 hours.
The reaction solution was added to ethanol, and the precipitate formed was filtered, washed repeatedly with ethanol, and dried in vacuum.
9.1 g of product was obtained. The infrared spectrum of this product shows the absorption attributed to the ester moiety (1740 cm ^-1 ,
1250 cm ^-1 ) was observed, but no absorption derived from O-C stretching vibration was observed, indicating that it was a trisubstituted product. Synthesis Example 4 (Synthesis of cellulose tris-3,5-dichlorobenzoate) Add thionyl chloride to 20 g of 3,5-dichlorobenzoic acid.
49.4 g and 0.21 ml of pyridine were added, and the mixture was kept under reflux for 2 hours. Excess thionyl chloride was then removed by distillation, dry hexane was added to the residue, insoluble materials were filtered off from the resulting solution, and the hexane was removed under reduced pressure to crystallize the remaining liquid. 3,5-dichlorobenzoyl chloride was given quantitatively. 1.0 g of cellulose obtained in Synthesis Example 2 was added to the above 3,5-
11.6g of dichlorobenzoyl chloride and 25g of pyridine
ml, triethylamine 4.3 ml, and 4-dimethylaminopyridine 50 mg and kept at 100° C. for 5 hours to react. The reaction solution was added to ethanol, and the precipitated cellulose tris-3,5-dichlorobenzoate was filtered off, washed with ethanol, and dried under vacuum. The product showed an absorption characteristic of the ester bond in its infrared spectrum, which was attributed to the free hydroxyl group.
It showed no absorption near 3500 cm ^-1 and was concluded to be a trisubstituted product. Synthesis Example 5 (Synthesis of cellulose tris-4-chlorobenzoate) 2.43 g of cellulose obtained in Synthesis Example 2 was mixed with 50 g of pyridine.
ml, 20 ml of triethylamine, and 200 mg of 4-dimethylaminopyridine, and reacted with 15.75 g of 4-chlorobenzoyl chloride at 110° C. for 8 hours with stirring.
The product was added to 500 ml of methanol, and the resulting precipitate was separated, washed with water and methanol, then dissolved in benzene, added to ethanol, and purified by reprecipitation.
The product vacuum-dried separately showed absorption characteristic of esters in its infrared spectrum, but no absorption around 3500 cm ^-1 attributed to free hydroxyl groups was observed, suggesting that it is a trisubstituted product. Example 1 1.2 g of cellulose tris-3-chlorobenzoate obtained in Synthesis Example 3 was dissolved in 7.5 ml of dichloromethane, 7.5 ml of the solution was absorbed into 3.2 g of silica beads obtained in Synthesis Example 1, and the mixture was heated under reduced pressure. By removing the solvent, a powdery support was obtained. Example 2 Cellulose Tris-3,5 obtained in Synthesis Example 4
-1.2 g of dichlorobenzoate was dissolved in 7.5 ml of dichloromethane, and 3.2 g of the silica beads obtained in Synthesis Example 1 were absorbed with 7.5 ml of the solution. The solvent was removed under reduced pressure to obtain a powdery support. Example 3 Cellulose tris-4-chlorobenzoate obtained in Synthesis Example 5 was supported on silica beads in exactly the same manner as in Example 2 to obtain a powder-like supported material. Application Example 1 The silica beads supporting cellulose tris(3-chlorobenzoate) obtained in Example 1 were packed into a stainless steel column with a length of 25 cm and an inner diameter of 0.46 cm by a slurry method. The high performance liquid chromatography machine used was TRIROTAR-SR manufactured by JASCO Corporation, and the detector used was UVIDEC-V. Table 1 shows the results of resolution of various racemates.

【table】

[Table] Application example 2 Cellulose tris (3,5
-dichlorobenzoate) was packed into a stainless steel column with a length of 25 cm and an inner diameter of 0.46 cm using a slurry method. The high-performance liquid chromatography machine used was TRIROTAR-SR manufactured by JASCO Corporation.
UVIDEC-V was used as a detector. Table 2 shows the results of resolution of various racemates.

[Table] Application Example 3 The silica beads supporting cellulose tris (4-chlorobenzoate) obtained in Example 3 were packed into a stainless steel column with a length of 25 cm and an inner diameter of 0.46 cm by a slurry method. The high-performance liquid chromatography machine used was TRIROTAR-SR manufactured by JASCO Corporation, and the detector used was UVIDEC-V. Table 3 shows the results of resolution of various racemates.

[Table] Comparative Example 1 Table 4 shows the results of dividing various racemates using silica beads supporting cellulose trisbenzoate prepared in exactly the same manner as in Examples 1, 2, and 3.
It was shown to.

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[Table] Synthesis Example 6 (Synthesis of p-octyloxybenzoic acid chloride) 23.2 g of p-octyloxybenzoic acid was added to benzene.
After adding 100 ml of the mixture, 12 ml of thionyl chloride was slowly added dropwise at room temperature, and the temperature was raised to 75°C until no more foaming occurred. After distilling off benzene and thionyl chloride, it was completely dried under vacuum. Synthesis Example 7 (Synthesis of cellulose tris-p-octyloxybenzoate) 1 g of cellulose obtained in Synthesis Example 2 was mixed with 50 ml of pyridine.
After adding 13.9 g of p-octyloxybenzoic acid chloride, the mixture was reacted at 90°C for 5 hours. After cooling, the reaction product was added to ethanol to precipitate it,
After washing with ethanol, it was vacuum dried. The dried product was dissolved in methylene chloride, filtered through a G-3 glass filter, and the solution was added to ethanol for precipitation.
It was thoroughly washed with ethanol and dried. The resulting cellulose-p-octyloxybenzoate was dissolved in methylene chloride, applied to a rock salt cell, dried, and measured. Almost no absorption based on the OH groups of cellulose was observed in the infrared absorption spectrum. Example 4 1.2 g of cellulose tris-p-octyloxybenzoate obtained in Synthesis Example 7 was dissolved in 7.5 ml of dichloromethane, filtered with a G-3 glass filter, and mixed with 3.5 g of silica beads obtained in Synthesis Example 1. death,
The solvent was removed from this under reduced pressure to obtain a powdery carrier. Application Example 4 Using the support obtained in Example 4, Traeger base was optically resolved in exactly the same manner as in Application Example 1. This compound, which was not resolved by cellulose tribenzoate, showed a separation coefficient of 1.37 and was resolved. Synthesis Example 8 The molecular weight reduction of cellulose triacetate in Synthesis Example 2 was carried out in exactly the same manner except that the reaction time was changed to 2 hours. Next, the obtained cellulose triacetate was hydrolyzed in exactly the same manner as in Synthesis Example 2 to obtain cellulose. Synthesis Example 9 (Synthesis of cellulose tris p-methylbenzoate) 2.9 g of cellulose obtained in Synthesis Example 8 was mixed with 50 g of pyridine.
After adding a solution of 24.9 g of p-methylbenzoyl chloride and 5 g of benzene, the mixture was reacted at 80°C for 1.5 hours and at 100°C for 3 hours. After cooling, the reaction product was added to ethanol to precipitate, washed thoroughly with ethanol, and dried. The dried product was dissolved in methylene chloride and filtered through a G-3 glass filter, and then the solution was added to ethanol to precipitate, washed well with ethanol, and dried. The produced cellulose p-methylbenzoate was dissolved in methylene chloride, applied to a rock salt cell, dried, and measured.The infrared absorption spectrum showed the following:
Almost no absorption based on cellulose's OH was observed. Synthesis Example 10 (Synthesis of cellulose tris m-methylbenzoate) Synthesis Example 9 except that m-methylbenzoic acid chloride was used instead of p-methylbenzoic acid chloride
Cellulose tris m-methylbenzoate was synthesized in exactly the same manner. Synthesis Example 11 (Synthesis of p-ethylbenzoic acid chloride) After adding 125 ml of benzene to 19.03 g of p-ethylbenzoic acid, 15 ml of thionyl chloride was slowly added dropwise at room temperature, and the temperature was raised to 75-80°C. The mixture was heated until p-ethylbenzoic acid was completely dissolved and no more foaming occurred. Then, benzene and thionyl chloride were completely distilled off under reduced pressure to obtain p-ethylbenzoic acid chloride. Synthesis Example 12 (Synthesis of cellulose tris p-ethylbenzoate) 1.5 g of cellulose obtained in Synthesis Example 8 was mixed with 50 g of pyridine.
ml of p-ethylbenzoic acid chloride obtained in Synthesis Example 11 by dispersing it in a mixed solution of 11.6 ml of triethylamine.
1.5 at 80℃ after adding a solution of 14.1g and 5g of benzene.
The reaction was carried out at 100°C for 3 hours. After cooling, the reaction product was added to ethanol to precipitate, washed thoroughly with ethanol, and dried. The dried product was dissolved in methylene chloride and filtered through a G-3 glass filter, and then the solution was added to ethanol to precipitate, washed well with ethanol, and dried. The produced cellulose p-ethylbenzoate was dissolved in methylene chloride, applied to a rock salt cell, dried, and measured. In the infrared spectrum, almost no absorption based on the OH of cellulose was observed. Synthesis Example 13 (Synthesis of cellulose tris p-t-butylbenzoate) 2.3 g of cellulose obtained in Synthesis Example 8 was dissolved in pyridine 50
ml, triethylamine (11.6 ml), and a solution of 25.1 g of pt-butylbenzoic acid chloride and 5 g of benzene was added thereto.
The reaction was carried out at ℃ for 3 hours. After cooling, the reaction product was added to ethanol to precipitate, washed thoroughly with ethanol, and dried. The dried product was dissolved in methylene chloride and filtered through a G-3 glass filter, and then the solution was added to ethanol to precipitate, washed well with ethanol, and dried. The produced cellulose pt-butylbenzoate was dissolved in methylene chloride, applied to a rock salt cell, dried, and measured. In the infrared spectrum, almost no absorption based on the OH of cellulose was observed. Synthesis Example 14 (Synthesis of cellulose tris p-fluorobenzoate) 2.8 g of cellulose obtained in Synthesis Example 8 was mixed with 50 g of pyridine.
After adding a solution of 25 g of p-fluorobenzoic acid chloride and 5 g of benzene, the mixture was reacted at 80° C. for 1.5 hours and at 100° C. for 3 hours. After cooling, the reaction product was added to ethanol to precipitate, washed thoroughly with ethanol, and dried. The dried product was dissolved in methylene chloride and filtered through a G-3 graph filter, and then the solution was added to ethanol to precipitate, washed well with ethanol, and dried. The infrared absorption spectrum obtained by dissolving the produced cellulose p-fluorobenzoate in methylene chloride, applying it to a rock salt cell, drying it, and measuring it shows the following:
Almost no absorption based on cellulose's OH was observed. Synthesis Example 15 (Synthesis of cellulose tris p-methoxybenzoate) 2.6 g of cellulose obtained in Synthesis Example 8 was mixed with 50 g of pyridine.
After adding a solution of 25 g of p-methoxybenzoyl chloride and 5 g of benzene, the mixture was reacted at 80°C for 1.5 hours and at 100°C for 3 hours. After cooling, the reaction product was added to ethanol to precipitate, washed thoroughly with ethanol, and dried. The dried product was dissolved in methylene chloride and filtered through a G-3 glass filter, and then the solution was added to ethanol to precipitate, washed well with ethanol, and dried. The infrared absorption spectrum obtained by dissolving the produced cellulose p-methoxybenzoate in methylene chloride, coating it on a rock salt cell, drying it, and measuring it shows:
Almost no absorption based on cellulose's OH was observed. Synthesis re-16 (synthesis of 3,4-dimethylbenzoic acid chloride) 19.7 g of 3,4-dimethylbenzoic acid and 125 g of benzene
ml, add 15 ml of thionyl chloride slowly and dropwise at room temperature, raise the temperature to 75-80℃, and add 3,4 ml of thionyl chloride.
-Heating was continued until the dimethylbenzoic acid was completely dissolved and no foaming occurred. Benzene and thionyl chloride were then completely distilled off under reduced pressure. Synthesis Example 17 (Synthesis of cellulose tris-3,4-dimethylbenzoate) 1.5 g of the cellulose obtained in Synthesis Example 8 was dissolved in 50% pyridine.
ml and triethylamine (11.6 ml), and a solution of 14.1 g of 3,4-dimethylbenzoic acid chloride and 5 g of benzene was added thereto, and then at 80°C for 1.5 hours.
The reaction was carried out at 100°C for 3 hours. After cooling, the reaction product was added to ethanol to precipitate, washed thoroughly with ethanol, and dried. Dissolve the dried material in methylene chloride,
After filtering through a G-3 glass filter, the solution was added to ethanol to precipitate, washed thoroughly with ethanol, and dried. The produced cellulose 3,4-dimethylbenzoate was dissolved in methylene chloride, applied to a rock salt cell, dried, and measured. In the infrared absorption spectrum, almost no absorption based on the OH of cellulose was observed. Example 5 1.0 g of cellulose tris p-methylbenzoate obtained in Synthesis Example 9 was dissolved in 7.1 ml of methylene chloride,
The mixture was mixed with 3.5 g of the silica beads obtained in Synthesis Example 1, and the solvent was removed from the mixture under reduced pressure to obtain a powdered support. Example 6 Using the cellulose tris m-methylbenzoate obtained in Synthesis Example 10, a powdery support was obtained in the same manner as in Example 5. Example 7 Using the cellulose tris p-ethylbenzoate obtained in Synthesis Example 12, a powder-like carrier was obtained in the same manner as in Example 5. Example 8 Using the cellulose tris pt-butyl benzoate obtained in Synthesis Example 13, a powdery support was obtained in the same manner as in Example 5. Example 9 Using the cellulose tris p-fluorobenzoate obtained in Synthesis Example 14, a powdery support was obtained in the same manner as in Example 5. Example 10 Using the cellulose tris p-methoxybenzoate obtained in Synthesis Example 15, a powdered carrier was obtained in the same manner as in Example 5. Example 11 Using the cellulose tris 3,4-dimethylbenzoate obtained in Synthesis Example 17, a powdery support was obtained in the same manner as in Example 5. Application example 5 When Traeger base was optically resolved using the support obtained in Example 5 in exactly the same manner as in Application example 1, this compound, which was not resolved by cellulose tribenzoate, showed a separation coefficient (α) of 7.14, and the separation was successful. It was done. Also, trans stilbene oxide,
When benzoin and 2-phenylcyclohexanone ethotoin were optically resolved, their respective separation coefficients were 1.39, 1.29, 1.35, and 1.23. Application Example 6 Using the support obtained in Example 6, trans-stilbene oxide,
When Traeger base was optically resolved, the respective separation coefficients were 1.74 and 2.07. Application Example 7 Using the support obtained in Example 7, Traeger base was optically resolved in exactly the same manner as in Application Example 1, and the separation coefficient was 1.58. Application Example 8 Using the support obtained in Example 8, Traeger base was optically resolved in the same manner as in Application Example 1 except that a solution of ethanol:water = 9:1 was used as the mobile phase. showed 1.66. Application Example 9 Using the support obtained in Example 9, trans-stilbene oxide was optically resolved in exactly the same manner as in Application Example 1, and the separation coefficient was 1.31. Application example 10 Using the support obtained in Example 10, trans-stilbene oxide, Traeger base, and benzoin were optically resolved in exactly the same manner as in Application example 1, and the respective separation coefficients were 1.35, 2.51, and 1.17.
showed that. Application Example 11 Using the support obtained in Example 11, trans-stilbene, Traeger base, and 2-phenylcyclohexanone were optically resolved in exactly the same manner as in Application Example 1, and the respective separation coefficients were 1.34 and 2-phenylcyclohexanone.
It showed 2.19 and 1.27. Synthesis Example 18 (Synthesis of cellulose tris-p-methoxybenzoate) In the same manner as in Synthesis Example 3, cellulose for Merck column chromatography and p-methoxybenzoyl chloride were reacted to obtain 2.6 g of a product. In the infrared spectrum of this product, a remarkable absorption attributed to the ester moiety was observed at 1728 cm ^-1 ;
No absorption derived from O-C stretching vibration was observed, indicating that it was a trisubstituted product. The degree of polymerization determined by GPC was 200. Example 12 1.0 g of cellulose tris-p-methoxybenzoate obtained in Synthesis Example 18 was dissolved in 7.5 ml of dichloromethane, 7.5 ml of the solution was absorbed into 3.2 g of silica beads obtained in Synthesis Example 1, and the mixture was heated under reduced pressure. By removing the solvent, a powdery support was obtained. Synthesis Example 19 (Synthesis of Cellulose Tris-m-Methylbenzoate) In the same manner as in Synthesis Example 3, cellulose for Merck column chromatography and m-methylbenzoyl chloride were reacted to obtain 2.3 g of a product. In the infrared spectrum of this product, a remarkable absorption attributed to the ester moiety was observed at 1729 cm ^-1 .
No absorption derived from O-C stretching vibration was observed, indicating that it was a trisubstituted product. The degree of polymerization determined by GPC was 200. Example 13 0.9 g of cellulose tris-m-methylbenzoate obtained in Synthesis Example 19 was dissolved in 7.5 ml of dichloromethane, 7.5 ml of the solution was absorbed into 3.2 g of silica beads obtained in Synthesis Example 1, and the mixture was heated under reduced pressure. By removing the solvent, a powdery support was obtained. Synthesis Example 20 (Synthesis of Cellulose Tris-p-Methylbenzoate) In the same manner as in Synthesis Example 3, cellulose for Merck column chromatography and p-methylbenzoyl chloride were reacted to obtain 2.4 g of a product. In the infrared spectrum of this product, a remarkable absorption attributed to the ester moiety was observed at 1730 cm ^-1 ;
No absorption derived from O-C stretching vibration was observed, indicating that it was a trisubstituted product. The degree of polymerization determined by GPC was 200. Example 14 0.9 g of cellulose tris-p-methylbenzoate obtained in Synthesis Example 20 was dissolved in 7.5 ml of dichloromethane, 7.5 ml of the solution was absorbed into 3.2 g of silica beads obtained in Synthesis Example 1, and the mixture was heated under reduced pressure. By removing the solvent, a powdery support was obtained. Synthesis Example 21 (Synthesis of cellulose tris-p-tert-butylbenzoate) In the same manner as in Synthesis Example 3, cellulose for Merck column chromatography and p-tert-butylbenzoyl chloride were reacted to obtain 3 g of a product. In the infrared spectrum of this product, a remarkable absorption attributed to the ester moiety was observed at 1731 cm ^-1 ;
No absorption derived from O-C stretching vibration was observed, indicating that it was a trisubstituted product. The degree of polymerization determined by GPC was 200. Example 15 1.13 g of cellulose tris-p-tert-butylbenzoate obtained in Synthesis Example 21 was dissolved in 7.5 ml of dichloromethane, and 7.5 ml of the solution was absorbed into 3.2 g of silica beads obtained in Synthesis Example 1. A powder-like supported material was obtained by removing the solvent under reduced pressure. Synthesis Example 22 (Synthesis of cellulose-p-fluorobenzoate) In the same manner as in Synthesis Example 3, cellulose for Merck column chromatography and p-fluorobenzoyl chloride were reacted to obtain 2.4 g of a product. In the infrared spectrum of this product, a remarkable absorption attributed to the ester moiety was observed at 1734 cm ^-1 .
No absorption derived from O-C stretching vibration was observed, indicating that it was a trisubstituted product. The degree of polymerization determined by GPC was 200. Example 16 0.93 g of cellulose tris-p-fluorobenzoate obtained in Synthesis Example 22 was dissolved in 7.5 ml of dichloromethane, 7.5 ml of the solution was absorbed into 3.2 g of silica beads obtained in Synthesis Example 1, and the mixture was heated under reduced pressure. By removing the solvent, a powdery support was obtained. Application Examples 12 to 16 Table 5 shows the results of optical resolution of the various racemates shown in Table 5 using the supports obtained in Examples 12 to 16 in the same manner as in Application Example 1. In addition, only in Application Example 15, hexane-2/propanol (98:2) was used as the eluent.

【table】

【table】

Claims (1)

[Claims] 1. A separation agent containing a substituted aromatic ester derivative of cellulose (excluding aromatic aliphatic esters and aromatic esters having an atomic group having a conjugated π-bond system) as an active ingredient.