JPH08217698A - Agent for optical resolution - Google Patents

Abstract

PURPOSE: To obtain the subject agent for optical resolution, having excellent optical resolution ability, capable of widening the range of a solvent usable for optical resolution and a target compound for optical resolution, by chemically bonding an optically active polyacetylene derivative to a carrier. CONSTITUTION: This agent for optical resolution is obtained by chemically bonding an optically active polyacetylene derivative which consists essentially of a structural unit of formula I [R<1> is a group of formula II (Ar part is a 6-14C aromatic group; R<2> is a 1-5C alkyl)] and has >=5 degree of polymerization, e.g. 50-1,000 to a carrier (e.g. silica gel having 1-300μm particle diameter and 50-50,000Å). The method for chemical bonding, for example, is carried out by introducing a triple bond to the surface of the carrier and copolymerizing the carrier with the optically active polyacetylene of formula III.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to an optical resolving agent obtained by chemically bonding an optically active polyacetylene derivative to a carrier.

[0002]

2. Description of the Related Art In recent years,
The development of functional polymers aimed at molecular recognition is remarkable, and research and development of functional polymers that recognize target ions, organic low molecules and high molecular compounds by their size, shape, charge, etc. have been conducted. There is. In this field, a functional polymer that asymmetrically recognizes an optically active antipode is particularly attracting attention, and its applicability to a chromatography column packing for optical resolution, an optical resolution membrane, and a host / guest method host is searched, It has been researched and developed. Among these, the use as a chromatography column packing for optical resolution is particularly popular. It is known that the optical resolution chromatography is extremely effective as an optical resolution means because it can analyze and fractionate an optically active substance easily and easily.

The asymmetric recognition polymers that have been researched and developed so far as the packing materials for the chromatography column for optical resolution are exemplified below. Cellulose triacetate (for example, JP-A-59-1665)
No. 02), cellulose benzoate (see, for example, Japanese Patent Laid-Open No.
0-40952), cellulose carbamate (for example, JP-A-60-108751), amylose carbamate (for example, JP-A-60-226831), and other polysaccharide derivative systems. Bovine serum albumin (eg, J. Chromatogr., 264
(1983), 63-68), α ₁ -acid glycoprotein (e.g., J. Chroma
togr., 269 (1983), 71-80), ovomucoid (for example,
Protein systems such as JP-A-4-187646). Poly (meth) acrylic acid amide (for example, JP-A-5
1-81891), poly (meth) acrylic acid ester (for example, JP-A-56-142216), and the like.

However, depending on the target compound, these asymmetric recognition polymers have advantages and disadvantages in optical resolution, and the range of the target compound for each optical resolution was limited. Further, most of them are adsorbed on a support and used for optical resolution, and therefore, there is a drawback that a solvent for dissolving a polymer cannot be used. Therefore, an object of the present invention is to provide a novel optical resolving agent in order to broaden the range of compounds to be subjected to optical resolution and the usable solvent.

[0005]

Means for Solving the Problems The inventors of the present invention have solved the above-mentioned problems in the process of applying research on the novel optically active polyacetylene derivative previously filed as Japanese Patent Application No. 6-82843. Therefore, they have found that a separating agent obtained by chemically bonding this polymer to a carrier has a high optical resolution, and completed the present invention. That is, the present invention mainly comprises a structural unit represented by the following formula (I), has a degree of polymerization of 5 or more, and R ¹ in the formula (I) is a group represented by the following formula (II). The present invention provides an optical resolving agent in which an active polyacetylene derivative is chemically bonded to a carrier.

[0006]

[Chemical 4]

R ⁷ represents an aromatic group having 6 to 14 carbon atoms, and R ² represents a linear or branched alkyl group having 1 to 5 carbon atoms. The optically active polyacetylene derivative in the present invention has a chiral carbamoyl group represented by the above formula (II) in the side chain. Also,

[0008]

Embedded image

Is an aromatic group having 6 to 14 carbon atoms, and examples of the aromatic group include anthryl group, naphthyl group, phenyl group and the like, preferably naphthyl group or phenyl group. R ² is a linear or branched alkyl group having 1 to 5 carbon atoms, preferably a linear alkyl group having 1 to 3 carbon atoms, and more preferably a methyl group. The degree of polymerization of the optically active polyacetylene derivative in the present invention is 5 or more, preferably 50 to 1000.

The carrier used for the optical resolving agent of the present invention includes a porous organic carrier and a porous inorganic carrier, and a particularly preferred carrier is silica gel. Carrier particle size is 1μ
It is from m to 10 mm, preferably from 1 μm to 300 μm. The average pore diameter of the carrier surface is 10 Å ~ 100 μm, preferably 50 ~ 50,000.
It is Å.

As a method for chemically bonding the optically active polyacetylene derivative of the present invention to a carrier, a triple bond is introduced on the surface of the carrier and the carrier and the formula (III) are used.

[0012]

[Chemical 6]

There is a method of copolymerizing with an optically active acetylene derivative represented by As a method of introducing a triple bond on the surface of the carrier, for example, a compound having a triple bond such as a carbamate derivative obtained by reacting 4-hydroxyphenylacetylene with 3-triethoxysilylpropyl isocyanate, and silica gel, Examples include a method of reacting in a solvent such as benzene in the presence of a catalyst such as pyridine. Further, with a carrier having a triple bond introduced,
Examples of the copolymerization with the optically active acetylene derivative represented by the formula (III) include a method of polymerizing in the presence of an organometallic catalyst in an organic solvent such as tetrahydrofuran (THF). Examples of the organometallic catalyst used here include [R
hCl (NBD)] ₂ (NBD = norbornadiene) and the like are exemplified.

The optical resolving agent of the present invention has an excellent optical resolving ability and can be used for separating various optical isomers.
For example, various racemates such as trans-stilbene oxide, Treger base, alcohol, spiropyran derivative, crown ether derivative and the like can be optically resolved.

[0015]

The optical resolving agent obtained by chemically bonding an optically active polyacetylene derivative according to the present invention to a carrier is a novel optical resolving agent, has an excellent optical resolving ability, and can be used as a solvent for optical resolving and as an object of optical resolving. The range of compounds can be expanded.

[0016]

The present invention will be described in detail below with reference to synthesis examples and examples, but the present invention is not limited to these examples.

Synthesis Example 1 (R)-(+)-[4-ethynylphenyl 1- (1-
Synthesis of naphthyl) ethyl carbamate] 6.0 g (27 mmol) of 4-hydroxyiodinated benzene was reacted with 4.2 ml (30 mmol) of trimethylsilylacetylene in 90 ml of triethylamine in the presence of a palladium catalyst at room temperature for 2 hours, and the obtained product was silica gel. Column chromatography (eluent, diethyl ether: hexane =)
1: 2) and 1- (4-hydroxyphenyl)-
5.0 g (yield, 96%) of 2-trimethylsilylethyne was obtained. This was reacted with 79 ml of tetrabutylammonium fluoride (1.0 M (THF)) in 15 ml of THF to deprotect the trimethylsilyl group, and then the product was subjected to column chromatography on silica gel (eluent, diethyl ether).
1.9 g of 4-hydroxyphenylacetylene
(Yield, 61%) was obtained. This was reacted with 3.4 g (17 mmol) of (R)-(+)-1- (1-naphthyl) ethyl isocyanate in the presence of 0.1 ml of a catalytic amount of pyridine, and the product was subjected to column chromatography on silica gel (eluent, eluent, Chloroform), benzene-hexane (5: 1)
And recrystallized with 3.3 g (yield, 65%) of (R)-(+)-[4-ethynylphenyl 1-represented by the following formula (IV):
(1-naphthyl) ethyl carbamate] was obtained. Melting point: 132.5 to 133.5 ° C, [α] _D ²⁵ : + 69 ° (THF,
c = 0.88g / dl)

[0018]

[Chemical 7]

Synthesis Example 2 Introducing a Triple Bond on the Surface of Silica Gel 3.9 g (33 mmol) of 4-hydroxyphenylacetylene obtained by the same method as in Synthesis Example 1 was treated with 3-triethoxysilyl isocyanate in the presence of a catalytic amount of pyridine. Propyl 9.0 g (36 mm
ol) to quantitatively obtain the corresponding carbamate derivative. 80 g of benzene in 60 ml of benzene in the presence of 5 g of dried Daisogel (Si-1000) and 0.5 ml of a catalytic amount of pyridine.
The reaction was carried out overnight at 0 ° C to introduce a triple bond on the surface of silica gel. From the change in weight, it was confirmed that about 60 mg (0.033 mmol / g) of the carbamate derivative was chemically bonded on silica gel.

Example 1 An optically active polyacetylene derivative was chemically bonded to a carrier.
Preparation of optical resolving agent (R)-(+)-[4-ethynylphenyl 1- (1-naphthyl) ethylcarbamate] obtained in Synthesis Example 1.
2 g (10 mmol) and 4.0 g of silica gel having a triple bond on the surface obtained in Synthesis Example 2 were used as a catalyst [RhCl 2
(NBD)] ₂ 22.6 mg (4.9 × 10 ^-2 mmol)
Copolymerization was carried out in 20 ml at 30 ° C. for 1 hour. Silica gel was filtered with a glass filter and thoroughly washed with THF, acetone, and methanol. From the weight change, it was found that about 0.45 g of the polymer was chemically bonded onto the silica gel. Apart from this, (R)-, which did not chemically bond onto the silica gel,
2.4 g (yield 75%) of a homopolymer of (+)-[4-ethynylphenyl 1- (1-naphthyl) ethylcarbamate] (hereinafter abbreviated as polymer 1) was obtained. GPC using polystyrene as a standard sample (eluent, THF)
The number average molecular weight (Mn) of the homopolymer (Polymer 1) determined from the above was 3,000,000. ^{From 1} H-NMR, the stereoregularity of the polymer seems to be almost 100% cis-transoid. Polymer 1 was a yellow solid having a negative optical activity, had an absorption in the ultraviolet-visible region, and exhibited a circular dichroism (CD) peak in this region. It is highly possible that the main chain has a helical structure in which the main chain is twisted in one direction due to the effect of the optically active side chain. UV-VIS: (560 nm-: λ (nm) (ε) = 395 (3060), 2
68 (11860)) ¹ H-NMR and CD spectra of polymer 1 are shown in FIG.
And FIG. 2 respectively.

Application Example 1 Packing of an optical resolving agent in a chromatography column The optical resolving agent comprising the optically active polyacetylene derivative chemically bonded to silica gel, obtained in Example 1, was used for a length of 25.
A stainless steel column having a diameter of 0.46 cm and an inner diameter of 0.46 cm was packed by a known slurry packing method to obtain a chiral column.

Application Example 2 Optical Resolution of Various Racemates Using the chiral column obtained in Application Example 1, the following various racemates were optically resolved. The results are shown in Table 1. <Analysis conditions> HPLC analysis; pump, JASCO TRIROTAR-
II UV detector; JASCO 875-UV (wavelength 254n
m) Polarimetric detector; JASCO DIP-181-C column; 25 × 0.46 (id) cm Eluent A: Hexane / 2-propanol (9: 1) B: Methanol C: Hexane D: Methanol / water (9: 1) Flow rate: 0.5 ml / min Temperature: Room temperature The definitions of terms shown in the table are as follows.

[0023]

[Equation 1]

[0024]

[Chemical 7]

[0025]

[Table 1]

[Brief description of drawings]

FIG. 1 ¹ H-NM of polymer 1 obtained in Example 1
It is an R spectrum.

FIG. 2 is a CD spectrum of polymer 1 obtained in Example 1.

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Claims (3)

[Claims] 1. An optical activity mainly comprising a structural unit represented by the following formula (I), having a degree of polymerization of 5 or more, and R ¹ in the formula (I) being a group represented by the following formula (II). An optical resolution agent obtained by chemically bonding a polyacetylene derivative to a carrier. Embedded image It represents an aromatic group having 6 to 14 carbon atoms, and R ² represents a linear or branched alkyl group having 1 to 5 carbon atoms. ) 2. [Chemical formula 2] Is an anthryl group, a naphthyl group or a phenyl group,
The optical resolving agent according to claim 1, wherein R ² is a linear alkyl group having 1 to 3 carbon atoms. Claim 3: Is an naphthyl group or a phenyl group, and R ² is a methyl group.