JP3181349B2 - Polysaccharide derivative, method for producing the same, and separating agent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a polysaccharide derivative, a method for producing the same, and a separating agent.

[0002]

2. Description of the Related Art It is already known that a liquid chromatography packing material in which a polysaccharide ester and a carbamate are supported on silica gel and used as a stationary phase has excellent optical resolution. Kaihei 2-
289601). However, silica gel used as a carrier is very expensive. Also, a method for producing a finely divided cellulose ester of an aromatic or araliphatic carboxylic acid is known (JP-A-1-152101).
However, finely divided polysaccharide aromatic carbamates or polysaccharide araliphatic carbamates have been difficult to prepare due to their limited solubility and limited solvents, and have not been produced.

[0003]

Means for Solving the Problems The present inventors have conducted intensive studies to solve the above problems, and as a result, it has been found that fine polysaccharide aromatic carbamate or polysaccharide araliphatic carbamate particles can be easily obtained, and the particles are excellent. The present invention has been found to have a high resolution and a particularly high separation factor as compared with those supported on a carrier, and to be suitable for preparative liquid chromatography. That is, the present invention provides a polysaccharide derivative comprising a finely divided polysaccharide aromatic carbamate or polysaccharide araliphatic carbamate having an average particle diameter of 1 to 200 μm and a specific surface area of 0.5 to 300 m ² / g, a method for producing the same, and the polysaccharide. An object of the present invention is to provide a separating agent for separating a racemic compound or a mixture of structural isomers, which is used as a stationary phase in chromatography.

The average particle size of the polysaccharide derivative particles in the present invention varies depending on the use, but is 1 to 200 μm, preferably 3 to 20 μm for analysis, and 10 to 200 μm for fractionation.
It is. Also, in order to keep the average particle size in a very narrow range,
The separation can be performed by a conventional method, for example, sedimentation, sieving, or centrifugation using a cyclone or the like. The specific surface area of the polysaccharide derivative in the present invention is 0.5 to 300 m ² /
g, preferably 1 to 80 m ² / g. The particle shape is spherical or crushed, preferably spherical. The surface state of the particles is preferably porous or non-porous, and is preferably porous for increasing the adsorption area and improving the separation performance. As the particle size distribution, those having a narrow distribution range are preferable for use in a chromatographic separating agent.

The polysaccharide aromatic carbamate or polysaccharide araliphatic carbamate of the present invention is represented by the following formula (1) or (2): RN = C = O (1) RXN = C = O (2) (Wherein, R is a monovalent aromatic hydrocarbon group which may contain a hetero atom, and may be unsubstituted or have 1 to 12 carbon atoms.
Hydrocarbon, cyano, halogen, hydroxy, nitro, amino and di (C 1-8)
May be substituted by one or more groups selected from the group consisting of: X is carbon number 1-4
And may contain a double bond or a triple bond. )).

Examples of the monovalent aromatic hydrocarbon group represented by R include phenyl, naphthyl, phenanthryl, anthracyl, indenyl, indanyl, furyl,
Examples include groups such as thionyl, pyryl, benzofuryl, benzthionyl, indyl, pyridyl, pyrimidyl, quinolinyl, and isoquinolinyl. Examples of the substituent of the monovalent aromatic hydrocarbon group represented by R include, for example, those having 1 to 1 carbon atoms.
12 alkyl, alkoxy having 1 to 12 carbons, 1 to 1 carbon
12 alkylthio, cyano, halogen, C1-8 acyl, C1-8 acyloxy, hydroxy, C1-12 alkoxycarbonyl, nitro, amino and di (C1-8 alkyl) amino And the like.

X is a divalent hydrocarbon group having 1 to 4 carbon atoms and may contain a double bond or a triple bond. For example, methylene, ethylene, ethylidene, ethenylene, ethinylene, 1,2- or 1,3-propylene, 1,1
— Or 2,2-propylidene.

[0008] The polysaccharide in the present invention may be any of natural polysaccharides, synthetic polysaccharides and natural product-modified polysaccharides, as long as they are optically active, but preferably those having a high regularity of bonding mode. It is. For example, β-1,4 −
Glucan (cellulose), α-1,4-glucan (amylose, aminopectin, cyclodextrin), α-1,
6-glucan (dextran), β-1,6-glucan (pustulan), β-1,3-glucan (eg, curdlan, schizophyllan, etc.), α-1,3-glucan, β-1,2
-Glucan (crown gal polysaccharide), β-1,4-galactan, β-1,4-mannan, α-1,6-mannan, β-1,
2-fractan (inulin), β-2,6-fractan (levan), β-1,4-xylan, β-1,3-xylan, β-1,4-chitosan, β-1,4-N − Acetyl chitosan (chitin), pullulan, agarose, alginic acid, etc., and more preferably cellulose, amylose, β-1,4-chitosan, β-1,4-mannan, β from which a high-purity polysaccharide can be easily obtained. 1,4-xylan, inulin, chitin, chitosan and curdlan. The number average degree of polymerization of these polysaccharides (the average number of pyranose or furanose rings contained in one molecule) is 5 or more, preferably 10 or more, and there is no particular upper limit, but it is preferably 500 or less for ease of handling. .

The polysaccharide aromatic carbamate or polysaccharide araliphatic carbamate used in the present invention is represented by the above formula (1) or
It can be produced from an isocyanate represented by the formula (2) and a polysaccharide by a known method. The introduction ratio of the substituent of the polysaccharide is 10 to 100%, preferably 80 to 100%.

The finely divided polysaccharide aromatic carbamate or polysaccharide araliphatic carbamate having an average particle diameter of 1 to 200 μm and a specific surface area of 0.5 to 300 m ² / g according to the present invention is a polysaccharide aromatic carbamate or polysaccharide araliphatic carbamate. First, it is dissolved in an organic solvent, and then 0 to 0.5 times the volume of a hydrocarbon having 4 to 22 carbon atoms is added to the organic solvent, and this solution is gradually added to a sufficiently stirred aqueous solution of a surfactant. ,
The organic solvent is removed while the stirring is continued, and the solid particles are isolated, washed, and dried. The particle size of the obtained polysaccharide derivative is determined by the method described above,
It is 10 to 1000 rpm, preferably 100 to 500 rpm, and depends on the ratio of the amount of the organic solvent to the aqueous solution, the concentration of the polysaccharide derivative, the addition rate of the organic solvent, the shape of the vessel and the stirring blade.

The organic solvent used here may be any organic solvent as long as the polysaccharide carbamate is soluble, but is particularly preferably insoluble in water. In addition, a water-soluble solvent may be used by mixing with a water-insoluble solvent. The amount of the hydrocarbon added to the solution of the polysaccharide derivative dissolved in the organic solvent is 0 to 0.5 times, preferably 0.1 to 0.3 times the volume of the above organic solvent. The hydrocarbon has 2 to 22 carbon atoms, preferably 4 to 10 carbon atoms. Specific examples include butane, pentane, heptane, hexane, octane, nonane, and decane. The ratio of [organic solvent + polysaccharide derivative + hydrocarbon]: [surfactant aqueous solution] is preferably from 1:10 to 1: 1 (volume ratio).

The surfactant in the present invention is an acid, a dibasic acid to a tetrabasic acid, or a hemiester or a salt thereof, preferably an alkyl sulfate having 4 to 18 carbon atoms,
Particularly preferred is lauryl sulfate.

The finely divided polysaccharide derivative of the present invention obtained as described above is useful as a separating agent for separating a racemic compound and a mixture of structural isomers, particularly as a packing material for gas chromatography and liquid chromatography. .

[0014]

Industrial Applicability The polysaccharide derivative of the present invention is extremely useful as a functional material, and is particularly effective for separating a racemic compound and a mixture of structural isomers. Since the polysaccharide derivative of the present invention is in the form of fine particles, it does not require an expensive carrier (silica gel), can be produced in large quantities and at low cost, and has a porous surface to increase the specific surface area and increase the separation coefficient. Therefore, separation can be performed economically and efficiently.

[0015]

The present invention will be described below by way of examples.
The present invention is not limited to these examples.

Example 1 A method similar to that of Example 2 of JP-A-62-64801.
Cellulose tris (3,5-dimethyl phthalate)
The E carbamate) 8.7 g are dissolved in mesityl oxide 300 ml. This is stirred at about 400rpm 600ml 0.75
% Aqueous sodium lauryl sulfate.
While continuing stirring at the same speed, the temperature was heated to 90 ° C., the pressure was reduced, and mesityl oxide was distilled off by adding 250 ml of distilled water on the way. The residue was isolated by filtration and washed with distilled water and ethanol. The obtained powder was vacuum dried at 140 ° C. for 16 hours. The yield of the obtained powder was 8.1 g (yield 93
%)Met. The obtained powder was sieved and classified by a sedimentation method to obtain spherical particles having a diameter of 3 to 6 μm, and its specific surface area was 3.4 m ² / g (BET method).

Example 2 The powder obtained in Example 1 was packed in a column having an inner diameter of 4.6 mm and a length of 125 mm, and various racemic compounds shown in Table 1 were separated by HPLC. Table 1 shows the results.

Example 3 The same cellulose tris (3,5-dimethylphenol) as in Example 1 was used.
E carbamates) 10.0 g of mesityl oxide 250 ml, dissolved in 50ml of acetone mixed solvent, adding this to n- nonane 50ml. This solution was slowly dropped into 600 ml of 0.75% aqueous sodium lauryl sulfate solution stirred at about 400 rpm. While continuing to stir at the same speed, heat the temperature to 90 ° C and reduce the pressure.
Mesityl oxide and acetone were distilled off by adding 0 ml. The residue was isolated by filtration and washed with distilled water and ethanol. The obtained powder was vacuum-dried at 140 ° C. for 16 hours. The yield of the resulting powder was 7.83 g (78.3% yield). The obtained powder was sieved and classified by a sedimentation method to obtain spherical particles having a diameter of 3 to 8 μm.
m ² / g (BET method).

Example 4 The powder obtained in Example 3 was packed in a column having an inner diameter of 4.6 mm and a length of 100 mm, and various racemic compounds shown in Table 1 were separated by HPLC. Table 1 shows the results.

Example 5 The same cellulose tris (3,5-dimethylphenol) as in Example 1 was used.
10.0 g of phenylcarbamate) was dissolved in a mixed solvent of 250 ml of mesityl oxide and 50 ml of acetone, and 50 ml of n-nonane was added thereto. This solution was slowly dropped into 600 ml of 0.75% aqueous sodium lauryl sulfate solution stirred at about 200 rpm. While continuing to stir at the same speed, heat the temperature to 90 ° C and reduce the pressure.
Mesityl oxide and acetone were distilled off by adding 0 ml. The residue was isolated by filtration and washed with distilled water and ethanol. The obtained powder was vacuum-dried at 140 ° C. for 16 hours. The yield of the obtained powder was 8.46 g (84.6% yield). The obtained powder was sieved and classified by a sedimentation method to obtain spherical particles having a diameter of 12 to 30 μm, and the specific surface area was 1.2.
m ² / g (BET method).

Embodiment 6 The same one as in Embodiment 1 of JP-A-63-178101 is used.
Tris (3,5-dimethyl)
Phenylcarbamate) 10.0 g to 300 ml chloroform,
Dissolved in 6 ml of N, N-dimethylacetamide mixed solvent,
To this is added 40 ml of n-heptane. About 400r of this solution
The solution was slowly dropped into 600 ml of 0.75% aqueous sodium lauryl sulfate solution stirred at pm. While stirring at the same speed, the temperature was heated to 60 ° C. and the pressure was reduced, and the organic solvent was distilled off.
The residue was isolated by filtration and washed with distilled water and ethanol. The obtained powder was vacuum-dried at 90 ° C. for 20 hours. The yield of the resulting powder was 9.41 g (94.1% yield). The obtained powder is sieved and classified by a sedimentation method to obtain a diameter of 3 to 3.
6 µm spherical particles having a specific surface area of 4.3 m ² / g (B
ET method).

Example 7 The powder obtained in Example 6 was packed in a column having an inner diameter of 4.6 mm and a length of 125 mm, and various racemic compounds shown in Table 1 were separated by HPLC. Table 1 shows the results.

[0023]

[Table 1]

Mobile phase: hexane / 2-propanol = 9/1 Flow rate: 0.5 ml / min Temperature: room temperature The HPLC used was JASCO Corporation (Pump 880-PU, detector 875-UV). Also, the capacity ratio (k ₁ ') in the table,
The separation coefficient (α) is defined by the following equations.

[0025]

(Equation 1)

Example 8 The same method as in Synthesis Example 1 of JP-A-60-108751 was used.
10 g of cellulose trisphenylcarbamate produced by the method was dissolved in a mixed solvent of 250 ml of mesityl oxide and 50 ml of acetone, 50 ml of n-nonane was added, and the mixture was stirred until the cloudiness disappeared. 600ml of stirring this at about 400rpm
The solution was gradually dropped into a 0.75% aqueous sodium lauryl sulfate solution. While continuing stirring at the same speed, the temperature was heated to 40 ° C., the pressure was reduced, and the organic solvent was distilled off. The residue is isolated by filtration,
Washed with distilled water and ethanol. The resulting powder 1
Vacuum dried at 40 ° C. for 19 hours. The yield of the resulting powder was 7.2
g (72% yield). The obtained powder was sieved and classified by a sedimentation method to obtain spherical particles having a diameter of 6 to 15 μm, and its specific surface area was 5.4 m ² / g (BET method).

Example 9 The powder obtained in Example 8 was packed in a column having an inner diameter of 4.6 mm and a length of 125 mm, and various racemic compounds shown in Table 2 were separated by HPLC. Table 2 shows the results.

[0028]

[Table 2]

Mobile phase: hexane / 2-propanol = 9/1 Flow rate: 0.5 ml / min Temperature: room temperature The HPLC used was JASCO (Pump 880-PU, detector 875-UV).

Example 10 The same cellulose trisphenylcarbamate as in Example 8 ( 10 g) was dissolved in a mixed solvent of methylene oxide (250 ml) and acetone (10 ml). This is stirred at about 400 rpm.
The solution was gradually dropped into a 75% aqueous solution of sodium lauryl sulfate. While continuing to stir at the same speed, heat the temperature to 45 ° C,
The organic solvent was distilled off. The residue was isolated by filtration and washed with distilled water and ethanol. The obtained powder is kept at 80 ° C, 20
Vacuum dried for hours. The yield of the obtained powder was 9.4 g (yield
94%). The obtained powder was sieved and classified by a sedimentation method to obtain spherical particles having a diameter of 10 to 30 μm.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification code FI C08B 37/00 C08B 37/00 CK 37/02 37/02 37/04 37/04 37/06 37/06 37/08 37 / 08 A 37/16 37/16 37/18 37/18 // G01N 30/48 G01N 30/48 W C08L 1:00 3:00 5:00

Claims (8)

(57) [Claims] An average particle size of 1 to 200 μm and a specific surface area of 0.5
Polysaccharide derivatives consisting of finely divided polysaccharide aromatic carbamates or polysaccharide araliphatic carbamates having a molecular weight of up to 300 m ² / g. 2. The polysaccharide aromatic carbamate or polysaccharide araliphatic carbamate is represented by the following formula (1) or (2): RN = C = O (1) RX-N = C = O (2) ( In the formula, R is a monovalent aromatic hydrocarbon group which may contain a hetero atom, and may be unsubstituted or have 1 to 12 carbon atoms.
Hydrocarbon, cyano, halogen, hydroxy, nitro, amino and di (C 1-8)
May be substituted by one or more groups selected from the group consisting of: X is carbon number 1-4
And may contain a double bond or a triple bond. The polysaccharide derivative according to claim 1, which is a compound derived from an isocyanate represented by the formula: 3. A polysaccharide aromatic carbamate or polysaccharide araliphatic carbamate is first dissolved in an organic solvent, and then 0 to 0.5 times the volume of a hydrocarbon having 4 to 22 carbon atoms is added to the organic solvent. 2. The polysaccharide derivative according to claim 1, wherein the solution is gradually added to a sufficiently stirred aqueous solution of the surfactant, the organic solvent is removed while stirring is continued, and solid particles are isolated, washed, and dried. Manufacturing method. 4. A polysaccharide derivative comprising finely divided polysaccharide aromatic carbamate or polysaccharide araliphatic carbamate obtained by the production method according to claim 3. 5. A separating agent comprising a polysaccharide derivative according to claim 1 for separating a racemic compound and a mixture of structural isomers. 6. A separating agent comprising a polysaccharide derivative according to claim 4 for separating a racemic compound and a mixture of structural isomers. 7. The method according to claim 3, wherein the organic solvent contains mesityl oxide as a main component. 8. The mesityl oxide content of the organic solvent is 50%.
The method according to claim 7, wherein the amount is from 100 to 100% by volume.