JPH0245436A - Production of optically active compound - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a method for producing an optically active compound, and particularly to a method for producing an optically active compound.
Conventionally, optically active phenyl alcohol, etc. (Ar represents a substituted or unsubstituted phenyl group, R represents an alkyl group having 1 to 4 carbon atoms), which is useful as a medicine, fragrance, or a starting material thereof. As a method for producing optically active compounds such as alcohols, an optical resolution method in which diastereomeric salts are repeatedly fractionally recrystallized has been mainly used.

[Problems to be Solved by the Invention] The optical resolution method has drawbacks such as requiring time for separation, such as saponification treatment followed by esterification treatment, and the operation is complicated and requires skill.

Moreover, conventional optical resolution methods such as the diastereomer method
There is also the problem that it is difficult to apply this method to the optical resolution of compounds without amino groups or carboxyl groups, such as those represented by the general formula (1).

The present invention solves the above-mentioned conventional problems, and easily and efficiently resolves the optically active compound represented by the general formula (R).
An object of the present invention is to provide a method for producing an optically active compound that can obtain an optically active compound with high optical purity.

[Means for Solving the Problems] The method for producing an optically active compound of the present invention is represented by the general formula (Ar represents a substituted or unsubstituted phenyl group, R represents an alkyl group having 1 to 4 carbon atoms). A racemic compound of the compound is brought into contact with an optically active dicarboxylic acid having an axially asymmetric structure or a salt thereof to form an clathrate, thereby resolving the racemic compound, and then decomposing the clathrate. Features.

That is, the present inventors have made extensive studies on the method for producing the optically active compound represented by the above general formula (I), and have found that an optically active carboxylic acid having a subaxial "symmetric structure" or a salt thereof, Since a clathrate can be selectively formed with either the (+) or (-) isomer of the compound represented by the above general formula (I), by decomposing the formed clathrate, have discovered that the optically active compound represented by the above general formula (1) can be resolved in high yield, and have completed the present invention.

The present invention will be explained in detail below.

The optically active compound targeted by the present invention has the general formula % (f), where Ar represents a phenyl group or a phenyl group having a substituent, R is an alkyl group having 1 to 4 carbon atoms,
Specifically, methyl group, ethyl group, n-propyl group, i-
Represents a propyl group, n-butyl group, and t-butyl group.

In the present invention, the above compound (hereinafter referred to as "
Sometimes referred to as "phenyl alcohol compounds." )
Although the racemate may be prepared by any known method, it is advantageous to synthesize it from the corresponding ketones. A specific production method includes a method in which ketones are reacted with hydrogen gas in the presence of a platinum catalyst according to the following reaction formula.

(In the formula, Ar and R represent the same thing as defined in general formula (1).) Optically active dicarboxylic acid having an axially asymmetric structure used in the present invention or a salt thereof (hereinafter referred to as r optically active axially asymmetric dicarboxylic acid) (sometimes referred to as "acids") are compounds that selectively and efficiently react with either the (+) or (-) form of the racemic form of the compound represented by the general formula (1). There is no particular limitation as long as it can form a clathrate compound, but for example, optically active 1,1°-binaphthyl-2,2°-dicarboxylic acid represented by the following general formula (rl) or its Salt is an example.

(In the formula, M represents H, Na, NH4, etc.) Among these, optically active 1.1゛-binaphthyl-2,2゛-
Dicarboxylic acid (M=H in the above formula (!I)) is
For example, the method described in Japanese Patent Application No. 63-9281 involves contacting the racemic form of 1.1°-binaphthyl-2,2°-dicarboxylic acid with prussin in an organic solvent and separating the resulting diastereomers. After that, it can be easily obtained by a method of decomposition.

In carrying out the present invention, first, a racemate of a phenyl alcohol compound as a starting material and an optically active axially asymmetric dicarboxylic acid are mixed in an organic solvent and reacted to obtain a clathrate compound. The mixing ratio varies depending on the type of clathrate compound obtained, but for example, (R,5)-1-phenylpropanol and (s)-t,io-binaphthyl-2
゜When reacting with 2°-dicarboxylic acid, the mixing ratio (molar ratio) is (R,5)-1-phenylpropanol: (S)-1,1°-binaphthyl-2,2°-dicarboxylic acid. It is preferable that acid=1:0.5-5.0. The organic solvent is not particularly limited as long as it can dissolve these compounds, but benzene, acetone, etc. can generally be used. The amount of these organic solvents to be used is such that the racemic form of the phenyl alcohol compound and the optically active axially asymmetric dicarboxylic acid are uniformly mixed and can react efficiently to form an clathrate compound. good. If the amount of organic solvent used is too large, the amount of organic solvent to be removed for separation of the obtained clathrate compound will be too large, which is unfavorable not only from the viewpoint of solvent cost but also from the operational viewpoint. Therefore, the amount of organic solvent used is generally 50 to 55% per 10 g of the racemic phenyl alcohol compound.
It is preferable to set it to about 00 m1.

The reaction temperature is 0 to 50°C, usually room temperature, and the reaction time is 1 to 72 hours, usually 6 to 24 hours. On this occasion,
In some cases, gentle stirring is performed to control the size of the precipitated clathrate crystals, but in most cases, it is sufficient to leave the mixture still. During the standing, part of the organic solvent may be distilled off as necessary to increase the efficiency of precipitation of the clathrate compound. By allowing the mixture to stand in this manner, a precipitate of the clathrate compound can be obtained, which is fractionated by conventional methods such as filtration and centrifugation.

Note that in the present invention, a solvent is not necessarily required,
In some cases, an inclusion compound can be obtained by directly adding and mixing an optically active axially asymmetric dicarboxylic acid to a racemic compound of a phenyl alcohol compound.

The resulting clathrate compound contains either the (R) form or the (S) form of the phenyl alcohol compound, depending on the type of optically active axially asymmetric dicarboxylic acid used, the solvent used, and the type of racemate. It is something that Therefore, by decomposing this clathrate compound, either the (R) form or the (S) form of the phenyl alcohol compound contained therein can be separated.

To decompose the clathrate, for example, the clathrate can be
Dissolve in an alkaline aqueous solution such as aOH. Thereafter, this solution is extracted with an organic solvent such as diethyl ether to extract the desired optically active phenyl alcohol compound from the organic phase, and the solvent is distilled off to separate it.

The concentration of the alkaline aqueous solution used to decompose the clathrate compound is not particularly limited, but usually 0.4 to 30% by weight is used. There is also no limit to the amount used, but generally 20 to 10 g of the clathrate compound is used.
Approximately 0 mβ is used. This decomposition reaction temperature is 10~50℃
Usually, room temperature and reaction time of about 5 to 60 minutes are sufficient.

Since the optically active axially asymmetric dicarboxylic acids produced by the decomposition remain in the aqueous phase during extraction, they can be crystallized by adding an appropriate acid, separated and recovered, and reused.

By the way, when the clathrate compound is fractionated, the other phenyl alcohol compound, either the (R) form or the (S) form, contained in the hot liquid is separated from the optically active axially chiral dicarboxylic acids and the clathrate compound. It is unclear whether they do not form, or whether they do not precipitate because of their high solubility, but in some cases, by distilling off the organic solvent of the r liquid and concentrating it, crystals may be precipitated, or this may be further combined with the above method. It can be easily recovered by similar decomposition and extraction treatments.

[Function] The phenyl alcohol compound represented by formula (I) has either its racemic (S) form or (R) form in a stable clathrate with an optically active axially asymmetric dicarboxylic acid. Form compounds efficiently. Therefore, by contacting the racemic form of a phenyl alcohol compound with an optically active axially asymmetric dicarboxylic acid, either the (S) form or the (R) form of the racemic form can be efficiently resolved as an inclusion compound. can. By decomposing this clathrate, either the (S) form or the (R) form in the clathrate can be easily recovered.

Note that the other phenyl alcohol compound, either the (S) form or the (R) form, can be easily obtained from the liquid solution from which the clathrate compound has been separated.

Therefore, according to the method of the present invention, a racemic form of a phenyl alcohol compound can be easily and efficiently optically resolved by a simple operation, and an optically active phenyl alcohol compound with high optical purity can be obtained.

In the present invention, the optically active axially asymmetric dicarboxylic acids used to produce the clathrate compound can be recovered and reused.
Extremely economical.

[Examples] Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to the following Examples unless it exceeds the gist thereof.

Example 1 0.64 g (1,9 mmon) of (S)-1,1°-binaphthyl-2,2°-dicarboxylic acid and (R,5)-1-
Phenylpropatool 0.56g (3.7mmof)
Mixed with 40mj! of benzene. This solution was concentrated until the volume was reduced to half, and then left at room temperature overnight. As a result, colorless crystals were precipitated.

The precipitated crystals were separated in a furnace and washed with benzene. The amount of crystals collected after washing was 0.74 g. This crystal'
As a result of analysis with HN, M, and R, the obtained crystal was 1.1°
-Binaphthyl-2゜2゜-dicarboxylic acid and 1-phenylpropanol in a molar ratio of 2:! It was presumed to be a clathrate compound containing Also, the melting point of this crystal is 156.2~15
8.6℃, the specific light intensity is [α]o'-28,2゜(C1,
0, methanol).

Next, the crystals of this clathrate compound were decomposed in a 5% by weight aqueous NaOH solution, and then extracted with diethyl ether. After separating the organic phase, diethyl ether was distilled under reduced pressure.
11 g of (R)-1-phenylpropatol enrichment was obtained. The specific light intensity of this object is [α] 5 + 40.9° (
Dan 1.0. benzene) and was 90% (R) somatic.

On the other hand, from the furnace liquid obtained by furnace separation of the clathrate compound crystals,
Benzene was distilled under reduced pressure to obtain 0.43 g of (S)-t-phenylpropanol enriched product. The specific light intensity of this material is [α3g'-11,1° (C1,0, benzene),
It was a product enriched with 25% (S) body.

Example 2 IB-pulverized (S)-(
-)-1,1'-binaphthyl-2,2°-dicarboxylic acid (host) 5113 mg (1,50 mmol) and α-
Propylbenzyl alcohol (Guest 4495mg (
3,OOmnoj2) was added, and about 5 mft of hexane was added to suspend it. Thereafter, the crystals were left to stand for 12 hours, separated in a furnace, and air-dried to measure the yield (yield: 591.2 mg). 'HNMR of this crystal confirmed that the guest was included in the host (inclusion ratio; hostniguest=2
:1).

Next, the obtained inclusion complex was decomposed and purified by a method similar to the recrystallization method, the inclusion guest was recovered, and the yield and optical rotation were measured. Yield: 101.5 mg, optical rotation: [α]l! '
+za, 6@ (tan2.3.benzene), and the optical purity was 63.3%e,e.

[Effects of the Invention] As detailed above, according to the method for producing an optically active compound of the present invention, an optically active phenyl alcohol compound with high optical purity can be produced easily and efficiently with simple operations and at low cost. It is confirmed that this method can be obtained in high yield.

The obtained phenyl alcohol compound can be used as agricultural chemicals, pharmaceuticals,
It is also extremely useful as a lilac- or jasmine-like fragrance, or as a starting material for their synthesis.

Claims (1)

[Claims] (1) General formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼・・・(I) (Ar is a substituted or unsubstituted phenyl group, R is a carbon number of 1 to
4 represents an alkyl group. ) The racemic form of the compound represented by is contacted with an optically active dicarboxylic acid having an axially asymmetric structure or a salt thereof to form an clathrate, thereby resolving the racemic form, and then dividing the clathrate. A method for producing an optically active compound characterized by decomposition.