JPH0429652B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an adsorbent for optical resolution comprising cellulose triacetate supported on a carrier. The object of the present invention is to provide an adsorbent for optical resolution that has a wide range of uses, particularly for thin layer chromatography and column chromatography. It is known that cellulose or some cellulose derivatives have an optical resolution ability as an adsorbent for column chromatography, and in particular, crystalline microcrystalline cellulose triacetate, carboxymethylcellulose, cellulose, etc. have been known.
Furthermore, the present inventors have already discovered that good separation can be observed even with crystalline cellulose triacetate. (Patent Application No. 58-39555) However, these cellulose-based adsorbents
It had the following drawbacks. (1) Poor pressure resistance when used in column chromatography. (2) When used for chromatography, changing the eluent may cause swelling or shrinkage. (3) Low resolution due to small number of theoretical plates. As a result of intensive research to overcome these drawbacks, the present inventors have discovered an adsorbent for optical resolution that has excellent pressure resistance, hardly swells or shrinks due to solvent exchange, and has a good degree of separation. . That is, the present invention relates to an adsorbent for optical resolution comprising cellulose triacetate supported on a carrier. The cellulose triacetate constituting the adsorbent for optical resolution of the present invention has a number average degree of polymerization of 5 to 5000, preferably 5 to 200, and more preferably 5 to 70.
It is. Cellulose triacetate before being supported may be amorphous cellulose triacetate, whether the main crystalline part is cellulose triacetate in the form of cellulose triacetate or the main crystal part is cellulose triacetate in the form of cellulose triacetate. Cellulose acetate may also be used, but
When cellulose triacetate is dissolved and supported, the crystalline portion is considered to be cellulose triacetate in the form of cellulose triacetate. Regarding the definition of the type or type of cellulose or cellulose triacetate referred to in the present invention, see, for example, Migita,
It is described on pages 188-189 of the first volume of ``Wood Chemistry'' edited by Yonezawa and Kondo (published by Kyoritsu Publishing Co., Ltd.). The cellulose triacetate type used in the present invention is G.
It can be synthesized by the method of Hesse et al. (G. Hesse,
R. Hagel: Chromatographia, 6, 277 (1973);
G. Hesse, R. Hagel: ibid., 9 62 (1976); G.
Hesse, R. Hagel: Liebigs Ann.Chem., 1976,
996). That is, microcrystalline cellulose may be acetylated in a heterogeneous system. Cellulose triacetate can also be obtained by acetylating cellulose in the form or form to form cellulose triacetate, which is then crystallized to cellulose triacetate in the crystalline form. The oxidation reaction may be a homogeneous reaction or a heterogeneous reaction, and the reaction can be carried out by a conventionally known method. Amorphous cellulose triacetate can be obtained by acetylating cellulose in a homogeneous manner or by dissolving cellulose triacetate in a suitable solvent and precipitating it. The acetylation reaction can be carried out by a conventionally known method. For example, there is a method described in Natural Polymer Chemistry, Asakura Shoten "Oganikagaku" 19. The carrier constituting the adsorbent for optical resolution of the present invention is
The porous organic carrier or porous inorganic carrier is a polymeric material made of polystyrene, polyamide, polyacrylate, or the like. Porous inorganic supports include synthetic or natural materials such as silica, alumina, magnesia, titanium oxide and glass, silicates, kaolin. Preferred are silica (silica gel) and glass. Surface treatment may be performed to improve affinity with cellulose triacetate. Examples of surface treatment methods include silane treatment using an alkylsilane compound and plasma polymerization treatment using plasma. The size of the carrier varies depending on the column or plate used, but it is 1 μm.
~10 mm is preferred, more preferably 1 μm ~
It is 300 μm. The average diameter of the pores is preferably 10 Å to 100 μm, more preferably 50 Å to 50,000 Å. The method for supporting cellulose triacetate on a porous carrier may be a chemical method or a physical method. As a physical method, for example, 1 to 100% by weight, preferably 5 to 50% by weight of cellulose triacetate based on the carrier is dissolved in a solvent, mixed well with the carrier, and the solvent is distilled off by reducing pressure, heating, or air flow. leave Furthermore, when crystallizing adsorbed cellulose triacetate,
Treatments such as heat treatment can be performed. Another method is to dissolve cellulose triacetate in a solvent,
There is also a method of thoroughly mixing with a carrier, stirring and dispersing in a liquid that is incompatible with the solvent, and diffusing the melt. When using the adsorbent for optical resolution of the present invention for optical resolution, a solvent normally used for chromatography can be used if it is supported by a chemical method, but if it is supported physically, If cellulose triacetate is dissolved in the solvent, it cannot be used. Compounds to be optically resolved by the adsorbent for optical resolution of the present invention are compounds having an asymmetric center or compounds with molecular asymmetricity, and the adsorbent for optical resolution of the present invention can separate optical isomers. Any material may be used as long as either one is more strongly adsorbed. EXAMPLES The present invention will be described in detail below with reference to Examples, but the present invention is not limited to these Examples.
In addition, the measurement methods of measurement values and the meanings of terms in Examples and Comparative Examples are as follows. 1 Degree of polymerization 1-1 Vapor pressure osmosis method Paper pressure osmometer
Measurement was performed using CORONA 117 using a mixed solvent of chloroform and 1% ethanol as the solvent. 1-2 Viscosity method Dichloromethane-methanol (9:1) was used as a solvent, the reduced viscosity of a 0.2% solution was approximated as [η], and calculation was performed using Km = 5.65×10 ^-4 . Degree of polymerization = [η]/Km 2 Quantification of free hydroxyl groups Carl J. Malm (Anal.
After treatment with a large excess of phenyl isocyanate in pyridine at 90°C for 30 minutes and purification by reprecipitation, the absorption intensity at 272 nm of the ultraviolet absorption spectrum revealed that phenylcarbamoyl groups produced by the reaction between hydroxyl groups and phenyl isocyanate I calculated the amount. A value of 705 was used as the molar extinction coefficient of the phenylcarbamoyl group. This value was determined from cellobiose heptaacetate carbanilate.
The data obtained were expressed as weight percent of water dispersion groups in the original cellulose triacetate. Definition of capacity ratio (k'), separation coefficient (α), and resolution (R _s ) Capacity ratio (k') = [(retention time of enantiomer) - (dead time)] / dead time separation coefficient (α) = Capacity ratio of enantiomer that is more strongly adsorbed/
Volumetric resolution of the more weakly adsorbed enantiomer (R _s ) = 2 × (distance between the two peaks of the more strongly adsorbed enantiomer and the weaker adsorbed enantiomer) (bands of both peaks) Synthesis Example 1 Cellulose triacetate produced by normal homogeneous acetylation (number average degree of polymerization 110 by vapor pressure osmosis)
Molecular weight distribution/=2.45, free hydroxyl group content 0.35
%) was swollen in 1.4 acetic acid, 23.2 ml of acetic anhydride, 7.0 ml of sulfuric acid, and 8.4 ml of water were added, and swelled for 5 hours at 80 g.
The reaction was carried out at ℃. Thereafter, the mixture was cooled with ice water, and the sulfuric acid was neutralized with 86.8 g of a 26% aqueous magnesium acetate solution.
The resulting solution was added to a mixed solvent of -isopropanol to precipitate cellulose acetate, separated, and dried. The obtained cellulose triacetate was dissolved in methanol-
The average degree of polymerization was 23 based on the viscosity in a methylene chloride (1:9) mixed solvent. Also, the free hydroxyl group content is 0.8
It was %. Example 1 Silica beads (Li Chrospher manufactured by Merck)
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 introduced. 100 ml of toluene distilled with CaH 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. moreover,
After 2 to 5 ml of toluene was distilled off, the reaction was carried out at 120°C for 2 hours. Passed through a glass filter and added 50% toluene.
3 times with 50 ml of methanol and 3 times with 50 ml of methanol, and vacuum-dried at 40° C. for 1 hour. Next, about 10 g of silica beads were placed in a 200 ml round-bottomed flask with side arms, vacuum dried at 100° C. for 3 hours, the pressure returned to normal pressure, and after the temperature reached room temperature, N ₂ was introduced. 100ml 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, it was filtered through a glass filter, washed with toluene, and dried under vacuum for about 4 hours. 1.6 g of cellulose triacetate obtained in Synthesis Example 1 was dissolved in 10 ml of methylene chloride and filtered through a G-3 glass filter. Silanized silica beads
Mix 3.5 g and 5.5 ml of the cellulose triacetate solution,
The solvent was distilled off under reduced pressure, and cellulose triacetate was coated on silane-treated silica beads. This was used as a filler for optical resolution. Comparative Example 1 The cellulose triacetate obtained in Synthesis Example 1 was dissolved in acetone, the insoluble portion was removed by pressure filtration, and water was added to an extent that no precipitate was formed.
The solvent was distilled off using a rotary evaporator.
The obtained white powder was dried under reduced pressure. This was used as a filler for optical resolution. Application Example 1 The cellulose acetate obtained in Comparative Example 1 was pulverized in ethanol by applying ultrasonic waves at 28 KHz, and then the particle size was classified based on the difference in the sedimentation rate of the cellulose acetate. 25cm long cellulose acetate with slow sedimentation rate.
A stainless steel column with an inner diameter of 0.46 cm was packed using the slurry method. Let this be a column. The filler obtained in Example 1 also had a length of 25 cm and an inner diameter of
A 0.46 cm stainless steel column was packed using the slurry method. Let this be a column. Using these columns, optical resolution of each racemate shown in Table 1 was tested. The liquid chromatograph machine used was a TRI manufactured by JASCO Corporation.
ROTAR SR was used, and the detector used was UVIDEC-100-IV manufactured by JASCO Corporation. The flow rate was measured at 0.2 ml/min. The solvent for the column is ethanol,
When replacing with hexane-isopropanol (9:1), the volume of the packing material changed and the column efficiency decreased. In the case of the column, ethanol and hexane-isopropanol (9:1) were used, and almost no volume change was observed due to solvent replacement. Furthermore, after using the column for 100 hours, a gap was formed at the top of the column and the number of plates decreased slightly, but the number of plates did not decrease in the column. The number of columns and columns for benzene is 576
It was found that the column had a much higher number of plates, with 5,700 plates. The results in Table 1 show that for trans-stilbene oxide and Traeger base, the separation coefficient α is slightly larger for the column, but the resolution R _s is larger for the column.
It can be seen that the column is a better column.
Other racemates could be resolved when using a column with hexane-isopropanol (9:1).

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Claims (1)

[Claims] 1. An adsorbent for optical resolution made by holding cellulose triacetate on a carrier.