JPH01203402A - Polysaccharide carbamate derivative - Google Patents

Abstract

PURPOSE:To obtain the present derivative suitable as a packing material for optical resolution, having excellent asymmetric distinguishing ability, discrimination ability, by replacing a mixed amount of hydrogen of hydroxyl group and amino group with a specific carbamoyl group. CONSTITUTION:The aimed derivative obtained by replacing 80-100% hydrogen of hydroxyl group and amino group with a group shown by a group shown by formula I (one or more of R1-R5 are 3-8C branched-chain alkyl; with the proviso that one or more of R1-R5 are 4-8C straight-chain alkyl or 3-8C branched-chain alkyl when polysaccharide is cellulose). A cellulosic carbamate derivative having a repeating constituent unit (having preferably 10-500 polymerization degree) shown by formula II (80-100% R is shown by formula I) is preferable.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a novel polymer that is extremely useful as a functional material for, for example, optical resolution. Specifically, it is an alkyl-substituted phenyl carbamate derivative, and is an isosubstituted product of cellulose or polysaccharide.

[Prior Art and Problems to be Solved by the Invention] Cellulose triphenyl carbamate is already known to have excellent resolving ability as a liquid chromatographic filler for optical resolution (Y, Okamoto).

), 4. Kawashima and K, Hat
ada, J, Am, Chem, 5ac1106
, 5357 '84).

In the course of subsequent research on cellulose triphenyl carbamate derivatives, the present inventors discovered that alkyl-substituted phenyl carbamate derivatives are also easily obtainable and have excellent asymmetric discrimination ability as fillers for optical resolution, and have developed the present invention. completed.

[Means to solve the problem]

That is, the present invention is an alkyl-substituted phenyl carbamate of cellulose or polysaccharide. That is, it relates to an alkyl-substituted phenyl carbamate derivative of a polysaccharide in which 80% to 100% of H's in hydroxyl groups and amine groups are substituted with groups represented by the following general formula.

L'R.

At least one of them is an alkyl group having 03 to C8 branches. However, if the polysaccharide is cellulose,
At least one of R1 to R5 is a 04-C8 straight chain alkyl group or a 03-C8 branched alkyl group. The remaining 20% to 0% of the hydroxyl groups and amine groups are generally hydrogen, but some other substituents, such as 01 to C
It can also be an alkyl group of 4, etc.

Specifically, it relates to a cellulose-based carbamate derivative characterized by consisting of a repeating structural unit represented by the following general formula.

(In the formula, 80 to 100% of R is a straight chain alkyl group of 04 to C8, or 03 to
It is a C8 branched alkyl group. ) The cellulose-based carbamate derivative is one in which 80 to 100% of all hydroxyl groups contained in cellulose form carbamate bonds.

Furthermore, the present invention also includes the following polymers.

An alkyl-substituted phenyl carbamate derivative of a polysaccharide (excluding cellulose) in which 80% to 100% of H of hydroxyl groups and amine groups are substituted with groups represented by the following general formula.

(In the formula, at least one of R1-R2 is 03-C
It is an alkyl group with 8 branches. ) In the above alkyl-substituted phenylcarbamoyl group, the branched 03-C8 alkyl group includes isopropyl group,
Examples include t-butyl group.

The degree of polymerization of the cellulose derivative of the present invention is 2 to 1,00.
0, preferably 10-500. The terminal groups are hydrogen or -acid terminal groups that can be present on cellulose.

As a method for synthesizing the alkyl-substituted phenylcarbame)l conductor of cellulose according to the present invention, a conventional reaction for producing urethane from incyanate and alcohol can be applied as is.

For example, IJ (alkyl-substituted phenyl) carbamate (cellulose) can be obtained by reacting an alkyl-substituted phenyl isocyanate with cellulose in the presence of a base such as a tertiary amine or a Lewis acid catalyst such as a tin compound. Furthermore, incyanato groups can be easily synthesized by reacting phosgene with the amino groups of the corresponding aniline derivatives.

The polysaccharide in the present invention may be any optically active polysaccharide, regardless of whether it is a synthetic polysaccharide, a natural polysaccharide, or a modified natural polysaccharide, but preferably one with a highly regular bonding pattern. Examples include α-1,4-glucan (amylose, amylopectin), α-1,6-glucan (
dextran), β-1,6-glucan (pustulan)
, β-1,3-glucan (e.g. curdlan, schizophyllan, etc.), α-1,3-glucan, β-1,2-glucan (Crown Ga11 polysaccharide), β-1,4-galactan, β-1 , 4-mannan, α-1,6-mannan, β-1,2-fructan (inulin), β-2,6-
Fructan (levan), β-1,4-xylan, β-1
, 3-xylan, β-1,4-chitosan, β-1,4-
These include N-acetyl chitosan (chitin), pullulan, agarose, alginic acid, and starch containing amylose. Particularly preferred are amylose, β-1,4-chitosan, chitin, β-1,4-mannan, β-1,4-xylan, inulin, curdlan, etc., from which highly pure polysaccharides can be easily obtained. .

The number average degree of polymerization (average number of pyranose or furanose rings contained in one molecule) of these polysaccharides is 5 or more, preferably 10 or more, and although there is no upper limit, it is preferably 500 or less for ease of handling. .

The carbamoyl group constituting the carbamate derivative of the polysaccharide of the present invention is represented by the above-mentioned general formula, and 80% to 100% of the total hydroxyl groups and amino groups of the corresponding polysaccharide form a urethane bond with the carbamoyl group. It is.

For the synthesis of carbamate derivatives according to the present invention, a conventional reaction for producing urethane from alcohol and incyanate can be applied as is. For example, it can be obtained by reacting a corresponding incyanate with a polysaccharide using a Lewis base such as a tertiary amine or a Lewis acid such as a tin compound as a catalyst in an appropriate solvent. Furthermore, incyanate can be easily synthesized by, for example, allowing phosgene to act on the amine group of the corresponding aniline derivative.

The derivative of the present invention is an extremely useful substance as a functional material, and is particularly useful as a filler for optical resolution.

In order to use the carbamate l conductor of the present invention as a separating agent for the purpose of separating a mixture of compounds or a mixture of optical isomers, a gas chromatography packed with the polymer of the present invention,
Generally, chromatography methods such as liquid chromatography and thin layer chromatography are used.
In addition, membrane separation can also be performed by forming a membrane containing the polymer of the present invention.

In order to apply the carbamate derivative of the present invention as a separation agent to a liquid chromatography method, it is convenient to fill a column with the carbamate derivative as a powder. Preferably, the polymer of the invention is ground or beaded, and more preferably the particles are porous. Furthermore, it is also preferable to support a carbamate derivative on a carrier in order to improve the pressure resistance of the separation agent, prevent swelling and shrinkage due to solvent substitution, and increase the number of theoretical plates.

When used as a powder, the size of the particles and the size of the carrier vary depending on the size of the column used, but 1 μm
~1 ml11, preferably 1 μm to 300 μm. The carrier is preferably porous, with an average pore diameter of 10 to 100 μm, preferably 50 to 100 μm.
It is 50,000 eight.

The amount of carbamate derivative supported on the carrier is 1 to 100% by weight, preferably 5 to 50% by weight based on the carrier.

The method for supporting the carbamate derivative on the carrier may be a chemical method or a physical method. Physical methods include dissolving the carbamate derivative in a soluble solvent, mixing well with the carrier, and distilling off the solvent with air flow under reduced pressure or heating; or dissolving the carbamate derivative in a soluble solvent and mixing it with the carrier. There is also a method in which, after thorough mixing, the carbamate derivative is separated into a solvent insoluble to diffuse the soluble solvent. It is also possible to improve the separation ability of the separation agent obtained in this way by subjecting it to appropriate treatments such as heating, addition of a solvent, and washing.

The carrier used 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, and polyacrylate.

Suitable porous inorganic carriers include silica, alumina, magnesia, glass, kaolin, titanium oxide, and silicate. It is also possible to use a material that has been treated to improve its properties. Examples of surface treatment methods include silanization using an organic silane compound and surface treatment using plasma polymerization.

There are no particular restrictions on the developing solvent used in liquid chromatography or thin layer chromatography, as long as it dissolves or reacts with the carbamate derivative. When a carbamate derivative is bonded to a carrier by a chemical method or made insolubilized by crosslinking, there are no particular restrictions except for those that react with the carrier.

On the other hand, when performing thin layer chromatography, 0.1
μm to Q, thickness of 0.1 to 100 μm, consisting of particles of about 1 mm, and a small amount of binder if necessary.
A layer of Qi may be formed on the support plate.

In addition, when performing membrane separation, it is used as a hollow fiber or film.

〔Example〕

The present invention will be explained in detail below with reference to Examples, but the present invention is not limited to these Examples. Furthermore, the above separation effect will be shown in an application example.

Example 1 Cellulose tris (4-t-':;l' tylphenyl carbamate) was synthesized as follows.

(2) Incyanate of 4-t-butylaniline Phosgene was generated by dropping oleum under reflux of carbon tetrachloride. Once the inside of the device has been sufficiently replaced with phosgene, add 4-t-butylaniline toluene solution (4-t-butylaniline toluene solution).
t-butylaniline 6, OOg to toluene 250rd
(dissolved in toluene) was added dropwise, the temperature was gradually raised, and the reaction was carried out under toluene reflux.

Toluene was removed by atmospheric distillation and vacuum distillation.

Purify incyanate at 8362°C/6.0mmHg.

Yield: 5.61g (79.6%) ■ Synthesis of cellulose tris (4-t-butylphenyl carbamate) 0.58g of cellulose is mixed with about 80rd of pyridine! Middle 100
After stirring at °C for about 1 hour and distilling off about 30 mf of pyridine,
2.72 g of 4-t-butylphenyl isocyaner) was added and reacted at 100°C for 19 hours.

The contents were poured into methanol to precipitate, centrifuged, and dried at constant temperature at 60°C for 2 hours.

Yield: 1.56 g (67.5%) Example 2 Amylose tris (4-t-butylphenyl carbamate) was synthesized as follows.

0.51 g of amylose was stirred in about 75 d of pyridine at 100°C for 2 hours, and about 30 ml of pyridine! Distill, 4-t
-Add 2.89g of butylphenyl isocyanate to 20
The reaction was allowed to proceed for 0 hours.

The contents were poured into methanol to precipitate, filtered through a glass filter, and dried at constant temperature at 60° C. for 2 hours.

Yield: 1.18 g (55.7%) The compounds of Examples 1 and 2 above could be analyzed as follows.

Values in parentheses are calculated values Application Examples 1 and 2 The compounds obtained in Examples 1 and 2 were supported as shown below to prepare a packing material, and further a separation column was prepared.

■ Silica gel (YR
K25) was used. Cellulose and amylose tris (
4-t-butylphenylcarbamate) about 0.75g in tetrahydrofuran 10mf! It was dissolved in YRK25
2.5mf of tetrahydrofuran solution per approximately 3g
After adding it moderately and shaking well to evenly moisten the silica gel,
Vacuum aporation and vacuum drying (60°C) were performed. This operation was repeated to perform loading.

■ The packing material prepared in the separation column ■ was mixed with hexane-2-propanol (9
Particle size classification using 〇210), length 25cm, inner diameter 0.46
A cm stainless steel column was packed using a slurry packing method. The resulting separation column was used to separate the mixture of optical isomers shown in Table 1. Separation conditions and results are shown in Table 1.
Shown below.

Example 3 Cellulose tris (4-n-pentylphenyl carbamate) was synthesized as follows.

Suspend 0.88 g of cellulose in pyridine 40-
-n-pentylphenyl isocyanate 4.5g (1,
4 equivalents) and reacted at 100° C. for 24 hours. The homogeneous reaction solution was poured into 400 methanol to precipitate the product. This product was collected in a glass filter, washed with methanol, and then vacuum dried at 60° C. for 2 hours.

Yield 3.20g Yield 80.8% Elemental analysis value C67.15% 87.39% N5.
44% calculated value C69, 11% 87.60% N5.
76% Application Example 3 The optical resolution of the compound obtained in Example 3 was evaluated as follows.

0.75 g of the synthesized polysaccharide derivative was added to 1 part of tetrahydrofuran.
The solution was dissolved in 5 ml and supported on 2.98 g of silica gel (particle size: 10 μm, pore size: 4000 A, treated with 3-aminopropyltriethoxysilane). This filler has a length of 2
A 5 cm column with an internal diameter of 0.45 cm was packed by a slurry method. Separation was carried out in the same manner as in Application Example 1. The results are in Table 2
Shown below.

Table 2 Optical resolution using cellulose tris(4-n-pentylphenylcarbamate) Eluent: hexane-2-propatol (98:2),
0.5-/m+n Temperature: 25℃ (Note) The synthesized polysaccharide derivative is H1-hydrated in hexane-2-propanol (90:10), so the evaluation was performed using hexane-2-propanol (98:2). went. However, even in this solvent system, the polysaccharide derivative swelled slightly and initially
The column pressure was 40 kg/cm2 after 4 hours.
It rose to cm'. During this time, the optical rotation needle did not work properly.

Claims (1)

[Scope of Claims] 1. An alkyl-substituted phenyl carbamate derivative of a polysaccharide, in which 80% to 100% of H's in hydroxyl groups and amino groups are substituted with groups represented by the following general formula. The general formula is ▲There are mathematical formulas, chemical formulas, tables, etc.▼, and R
At least one of _1 to R_5 is C_3 to C_8
It is an alkyl group having a branch. However, when the polysaccharide is cellulose, at least one of R_1 to R_5 is a C_4 to C_8 linear alkyl group, or C_3 to
It is an alkyl group having C_8 branching. 2. A cellulose carbamate derivative characterized by comprising a repeating structural unit represented by the following general formula. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, 80 to 100% of R is ▲There are mathematical formulas, chemical formulas, tables, etc.▼, and R_1 to R
At least one of _5 is a straight chain alkyl group of C_4 to C_8 or a branched alkyl group of C_3 to C_8. ) 3 An alkyl-substituted phenyl carbamate derivative of a polysaccharide (excluding cellulose) in which 80% to 100% of the H of the hydroxyl group and amino group is substituted with a group represented by the following general formula. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, at least one of R_1 to R_5 is C_
It is an alkyl group having 3 to C_8 branches. )