Liquid purification or separation – With means to add treating material – Chromatography
Reissue Patent
1997-09-22
2004-02-24
Therkorn, Ernest G. (Department: 1723)
Liquid purification or separation
With means to add treating material
Chromatography
C210S502100, C210S635000, C210S656000, C502S404000, C536S063000, C536S064000
Reissue Patent
active
RE038435
ABSTRACT:
The invention relates to use of a cellulose derivative having a group containing an aromatic group as a separating agent for a chemical substance. The invention method applies to separation of optical isomers, geometrical isomers and polymers having different molecular weight ranges from each other. They have not easily been separated in the state of prior arts.
Generally, the physiological activity of a racemic compound often differs from that of an optically active compound. For example, in the field of medicines, pesticides or the like, it is sometimes necessary to resolve optical isomers for the purposes of preventing adverse reactions and improving the medicinal effects per unit dose. A mixture of optical isomers has been divided by a preferential crystallization process or diastereomer process. However, variaties of the compound which can be optically resolved by these processes are limited and most of these processes require a long time. Under these circumstances, development of a convenient chromatographic resolution process has eagerly been demanded.
The chromatographic resolution of optical isomers has been investigated from old times. For instance, cellulose and a triacetate thereof have been successfully used as column-chromatographic resolving agents in optical resolution. The cellulose and cellulose triacetate are those belonging to cellulose I and cellulose triacetate I, respectively. However, substances which can be resolved by said cellulose or a derivative thereof are limited and the resolving ability of them is insufficient.
After intensive investigations, the inventors have found surprisingly that a cellulose derivative having a group containing an aromatic ring has excellent ability in separation of chemical substances and isomers, in particular optical isomers. The invention has been completed on the basis of the finding.
The invention relates to a method for separating a chemical substance from a mixture containing the same, which comprises the step of treating said mixture with a cellulose derivative having a group containing an aromatic ring, a separating agent comprising the cellulose derivative; particles of the separating agent; a packing material of the particles; and a chromatographic column filled with the agent.
Though the reasons why the cellulose derivatives having an aromatic ring used in the present invention have excellent effects for resolving the optical isomers have not been elucidated yet, it may be considered that the ordered asymmetic structure of cellulose and the aromaticity and rigidity of the aromatic group exert a great influence on the resolution of the optical isomers.
The cellulose derivative according to the invention is preferred to have a number-average degree of polymerization of 5 to 5000, preferably 10 to 1000, and particularly 10 to 500. The average degree of substitution of the cellulose derivative having an aromatic ring is defined by the following formula:
Average
degree
of
substitution
=
Number
of
substituents
in
the
molecule
Number
-
average
d
egree
of
polymerization
The average degree of substitution of the cellulose derivatives having an aromatic ring of the present invention is 1 to 3.4, preferably 1.8 to 3.2.
The unreacted hydroxyl groups in the aromatic cellulose derivative containing aromatic rings may further be esterified, carbamoylated or etherified so far as its capacity of resolving optical isomers is not damaged.
The cellulose derivative of the invention may include those in which part or all of the hydrogen atoms of the hydroxyl groups have been replaced with an aromatic group or a group containing an aromatic group. A substituent may be attached to cellulose by way of an intermediate linkage such as an ester, an ether and an urethane. The term “aromatic group” includes that derived from an aromatic ring having 6 to 20 carbon atoms, an aralkyl group having 6 to 20 carbon atoms in the aryl portion and 1 to 4 carbon atoms in the alkyl portion and a heteroaromatic ring having 3 to 20 carbon atoms. The ring may further have a substituent thereon, such as an alkyl group, nitro group, a halogen, an amino group, an alkyl-substituted amino group, cyano group, hydroxyl group and carboxyl group.
Now, the description will be made on processes for the production of the substances of the present invention. The cellulose derivatives substituted through an ester group include, cellulose benzoate for example. The esterification reaction to obtain them may be carried out by a known process, (See “Dai-Yuki Kagaku” 19, “Tennen Kobunshi Kagaku” I published by Asakura Book Store, p. 124). Examples of the esterifying agents include benzoyl derivatives having the following structures such as benzoyl chloride:
The reaction solvent may be any solvent such as pyridine and quinoline, so far as it does not inhibit the esterification reaction. Frequently a catalyst such as 4-(N,N-dimethylamino)pyridine is effective in accelerating the reaction. Other aromatic derivatives may be obtained by the esterification reaction in the same manner as described above.
The cellulose derivative substituted through an ether group may be obtained by a known process for etherifying cellulose. Generally, they are obtained by reacting cellulose with an aromatic derivative having a leaving group in the presence of a base. This process has been disclosed in, for example, N. M. Bikales, L. Segel, “Cellulose and Cellulose Derivatives” p. 807 and “Dai-Yuki Kagaku” 19 published by Asakura Book Store, p. 93. Processes for producing cellulose ethers having an aromatic ring of a high degree of substitution includes that of Husemann et al. (“Makromol. Chem,”, 176, 3269 (1975)) and that of Nakano et al. (“The Processings of ISWPC” #1983, Vol. 1, 33).
The cellulose derivatives substituted through an urethane group may be produced by a conventional process wherein an isocyanate is reacted with an alcohol to form a urethane.
For example, these compounds may be produced by reacting an isocyanate having an aromatic ring with cellulose in the presence of a Lewis base catalyst such as a tertiary amine base or a Lewis acid catalyst such as a tin compound.
The disubstituted urethanes may be synthesized in the same manner as in the above-mentioned esterification reaction using a disubstituted carbamoyl halide or the like.
In using the resolving agent of the present invention containing the cellulose derivatives having an aromatic ring as the principal component for the purpose of resolution, it is preferred to employ a chromatographic method. The preferred chromatographic methods include liquid, thin layer and gas chromatography.
In using the separating agent of the present invention in the liquid or gas chromatography, there may be employed a method wherein the aromatic ring-containing cellulose derivative is packed into a column directly or in the form supported on a carrier or a method wherein a capillary column is coated with said cellulose derivative.
Since the chromatographic separating agent is preferably in the form of granules, the aromatic ring-containing cellulose derivative to be used as the resolving agent is preferably ground or shaped into beads. The particle size which varies depending on the size of a column or plate used is generally 1 &mgr;m to 10 mm, preferably 1 to 300 &mgr;m. The particles are preferably porous.
It is preferred to support the aromatic ring-containing cellulose derivative on a carrier so as to improve the resistance thereof to pressure, to prevent swelling or shrinkage thereof due to solvent exchange or to reduce the number of theoretical plates. The suitable size of the carrier which varies depending on the size of the column or plate used is generally 1 &mgr;m to 10 mm, preferably 1 to 300 &mgr;m. The carrier is preferably porous and has an average pore diameter of 10 Å to 100 &mgr;m, preferably 50 to 50,000 Å. The amount of said c
Hatada Koichi
Nakamura Hiroyuki
Okamoto Ichiro
Okamoto Yoshio
Shibata Tohru
Daicel Chemical Industries Ltd.
Flynn ,Thiel, Boutell & Tanis, P.C.
Therkorn Ernest G.
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