JPH0693002A - Separating agent consisting of alkoxy-substituted aromatic carbamate derivative of cellulose - Google Patents

Abstract

PURPOSE:To obtain a separating agent having good safety and separation efficiency and high ability for discriminating optical isomers and useful for separating various chemical substances by including an alkoxy substituted aromatic carbamate derivative of cellulose as an active ingredient. CONSTITUTION:The separating agent contains an alkoxy-substituted aromatic carbamate derivative of cellulose [e.g. cellulose tris(4- isopropoxyphenylcarbamate)] as an active ingredient. This separating agent is obtained by (A) reacting an alkoxy-substituted aromatic amine with phosgene to afford an alkoxy-substituted aromatic isocyanate and (B) then thermally reacting a cellulose with the resultant aromatic isocyanate in pyridine according to a conventional method to substitute H of OH group of the cellulose with a carbamoyl group of the formula (Ar is 6-10C divalent aromatic ring; R is 3-10C alkyl). Separation, especially optical resolution of various chemical substances is carried out using the separating agent in gas chromatography, liquid chromatography, thin layer chromatography and a membrane separating method.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a separating agent containing an alkoxy-substituted aromatic carbamate derivative of cellulose as an active ingredient. The separating agent of the present invention can be used for separating various chemical substances, particularly for optical resolution.

[0002]

BACKGROUND OF THE INVENTION As is well known, even if the compounds are chemically the same,
The optical isomers normally have different effects on the living body. Therefore, in the fields of medicine, agricultural chemicals, biochemistry related industries, etc., it is a very important task to prepare an optically pure compound in order to improve the drug efficacy per unit, prevent side effects and phytotoxicity, etc. ing. In order to separate a mixture of optical isomers, that is, to perform optical resolution, a preferential crystallization method or a diastereomer method has been conventionally used, but in these methods, the types of compounds to be optically resolved are limited. Also, it often takes a long time and a lot of labor. Therefore, a technique for easily performing optical resolution by a chromatography method has been strongly desired.

Studies on optical resolution by chromatographic methods have been conducted for a long time. However, the previously developed resolving agents have various problems such as poor separation efficiency, a compound to be separated requiring a special functional group, and poor stability of the separating agent. Yes,
It has been difficult to achieve satisfactory optical resolution for all compounds.

Therefore, it is possible to provide a separating agent having a chemical structure different from that of the existing separating agents, thereby having different separating characteristics from them, or having a higher ability to discriminate optical isomers. It is an object of the present invention. In particular, it aims to combine the physical and chemical properties of the substituents on the aromatic ring with novel separation properties.

[0005]

The present inventors have completed the present invention as a result of intensive research to solve the above problems. That is, the present invention provides a separating agent composed of an alkoxy-substituted aromatic carbamate derivative of cellulose in which hydrogen of a hydroxyl group of cellulose is substituted with a carbamoyl group represented by the following formula (I).

[0006]

[Chemical 2]

(In the formula, Ar is a divalent aromatic ring having 6 to 10 carbon atoms and R is an alkyl group having 3 to 10 carbon atoms.) The separating agent of the present invention is preferably an optical compound of any compound. It shows different adsorption powers for isomers.

In the above formula (I), Ar has 6 to 10 carbon atoms.
Is a divalent aromatic ring having 6 carbon atoms, R is an alkyl group having 3 to 10 carbon atoms, which may be linear or branched, and preferably has 3 to 5 carbon atoms. It is a base. When R 2 has 1 to 2 carbon atoms, the separation ability is poor and it is outside the scope of the present invention. Specific examples of the structure of -Ar-OR in formula (I) include 4-isopropoxyphenyl group and 4-isobutoxyphenyl group.

The closest known separating agent to the separating agent of the present invention is cellulose tris (methylphenyl carbamate), but the separating agent of the present invention has far superior performance. Number average degree of polymerization of cellulose in the present invention (average number of pyranose rings contained in one molecule)
Is 5 or more, preferably 10 or more, and there is no particular upper limit, but 500 or less is preferable from the viewpoint of easy handling. The alkoxy-substituted aromatic carbamate derivative of cellulose of the present invention has a hydroxyl group number of 30 to 30
100%, preferably 85 to 100%, form a carbamate bond.

For the synthesis of the alkoxy-substituted aromatic carbamate derivative of cellulose of the present invention, the usual reaction for producing urethane from alcohol and isocyanate can be directly applied. That is, the corresponding alkoxy-substituted aromatic carbamate derivative can be obtained by heating the cellulose and the alkoxy-substituted aromatic isocyanate in pyridine in a conventional manner. The alkoxy-substituted aromatic isocyanate used here can be easily synthesized by reacting the corresponding alkoxy-substituted aromatic amine with phosgene.

When the separating agent of the present invention is used for the purpose of separating a compound or its optical isomer, it is common to use a chromatographic method such as gas chromatography, liquid chromatography or thin layer chromatography. However, a membrane separation method can also be used. In order to apply the separating agent of the present invention to a liquid chromatography method, a method of filling a column as a powder, a method of coating a capillary column, a method of forming a capillary with the separating agent of the present invention and utilizing the inner wall thereof, spinning Then, a method of bundling these into a column is used, but it is common to fill the column as powder. In order to make the separating agent of the present invention into powder, it is preferable to crush it or make it into a bead form. The size of the particles depends on the size of the column used, but is 1 μm to 10 mm, preferably 1 μm to 300 μm, and the particles are preferably porous.

Further, in order to improve the pressure resistance of the separating agent, prevent swelling / shrinking due to solvent replacement, and improve the theoretical plate number, it is preferable to retain the separating agent of the present invention on a carrier. The size of the suitable 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 and has an average pore size of 10Å to 100 μm, preferably
It is between 50Å and 50000Å. The amount of the separating agent of the present invention retained is 1 to 100% by weight, preferably 5 to 50% by weight, based on the carrier.

The method of holding the separating agent of the present invention on a carrier may be a physical method or a chemical method. As a physical method, the separating agent of the present invention is dissolved in a soluble solvent,
A method in which the solvent is distilled off under reduced pressure or heating by mixing well with the carrier, or by dissolving the separating agent of the present invention in a soluble solvent and mixing well with the carrier, and then a liquid which is incompatible with this solvent. There is also a method of diffusing this solvent by stirring and dispersing it inside. In this way, when crystallizing the separating agent retained on the carrier, a treatment such as heat treatment can be performed. Further, by adding a small amount of solvent to swell or dissolve the separating agent and then distilling off the solvent again, it is possible to change the retention state and eventually the separating ability.

The carrier used in the present invention is a porous inorganic carrier or a porous organic carrier, preferably a porous inorganic carrier. Suitable as the porous inorganic carrier,
Silica, alumina, magnesia, titanium oxide, glass,
Synthetic or natural substances such as silicate and kaolin may be mentioned, and they may be surface-treated in order to improve the affinity with the separating agent. Examples of the surface treatment method include a silanization treatment using an organic silane compound and a surface treatment method by plasma polymerization. Suitable examples of the porous organic carrier include polymer compounds such as polystyrene, polyacrylamide and polyacrylate.

The developing solvent for liquid chromatography or thin layer chromatography is not particularly limited, except for a liquid which dissolves or reacts with the separating agent of the present invention. When the separating agent of the present invention is bound to a carrier by a chemical method or insolubilized by crosslinking, there is no particular limitation except for the reactive liquid. Needless to say, the separation characteristics of chemical substances or optical isomers change depending on the developing solvent, so it is desirable to study various developing solvents.

When performing thin layer chromatography,
A layer having a thickness of 0.1 to 100 mm consisting of particles having a size of about 0.1 μm to 0.1 mm and, if necessary, a small amount of binder may be formed on the support plate. When performing membrane separation, it is used as a hollow fiber or a film.

[0017]

EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

Example 1 Cellulose tris (4-isopropoxyphenylcarba)
Mate) Cellulose (0.6 g ) , pyridine (10 ml) and 4-isopropoxyphenylisocyanate (2.57 g ) were added, and the mixture was heated at 90 ° C. to 30
The reaction was carried out by heating for an hour. The content was poured into 500 ml of methanol, and the precipitate was filtered with a glass filter (G4). 60
The target product was obtained by vacuum drying at 2 ° C. for 2 hours. Yield 2.23g, 86.8% 0.75 g of the obtained cellulose tris (4-isopropoxyphenylcarbamate) was dissolved in 10 ml of THF, and the solution was added to 3.0 g of silica gel (particle size 7 μm, pore size 100 nm, 3-aminoethoxysilane treated) and shaken well. After uniformly moistening the silica gel, the silica gel was dried to prepare a separating agent. The separating agent thus obtained was packed into a stainless steel column having a length of 25 cm and an inner diameter of 0.46 cm by a slurry packing method, and an eluent was hexane / 2-propanol (90
/ 10), the flow rate was 0.5 ml / min, and the optical resolution experiment was performed. The results are shown in Table 1.

Example 2 Cellulose tris (4-isobutoxyphenylcarbamme)
In the same manner as in Example 1, cellulose was reacted with 4-isobutoxyphenyl isocyanate in pyridine to obtain cellulose tris (4-isobutoxyphenyl carbamate). Then, in the same manner as in Example 1, an optical resolution experiment was conducted using the separating agent supported on silica gel. The results are shown in Table 1.

Comparative Example 1 Cellulose tris (4-methylphenyl carbamate) Cellulose tris (4-methylphenyl carbamate)
Was used in the same manner as in Example 1 to prepare a separating agent and carry out an optical resolution experiment. The results are shown in Table 1.

[0021]

[Table 1]

Claims (1)

[Claims] 1. A separating agent comprising an alkoxy-substituted aromatic carbamate derivative of cellulose in which hydrogen of a hydroxyl group of cellulose is substituted by a carbamoyl group represented by the following formula (I). [Chemical 1] (In the formula, Ar is a divalent aromatic ring having 6 to 10 carbon atoms, and R is an alkyl group having 3 to 10 carbon atoms.)