JPH0641459B2 - Method for separating optical isomers of epoxides having multiple asymmetric carbons - Google Patents

Description

TECHNICAL FIELD OF THE INVENTION The present invention relates to an optical isomer of a three-membered ring epoxide (hereinafter simply referred to as an epoxide) having a diastereomeric relationship by having a plurality of asymmetric carbon atoms in the molecule. Regarding the separation method of.

(Prior Art) Optical isomers exist in compounds containing asymmetric carbon,
It is well known that there are many examples in which a compound having a specific configuration, which is one of the optical isomers, exhibits specific actions in various functions, particularly physiological functions. Obtaining such substances has been of great interest in recent years. And it is industrially very important to obtain a relatively simple compound having a specific configuration as a key material for synthesizing such a compound.

The epoxide has extremely high utility value as a synthetic intermediate, and it is particularly significant to obtain a specific optical isomer of this epoxide from the above meanings.

A method called Sharpless oxidation is known for the synthesis of an epoxide having a specific configuration, but it is not always a general method. In addition, recently, some simple epoxide formations with the aid of microbiological methods have been published, but these are also limited methods and inefficient methods.

The applicant of the present invention is to use the optically active 1,1,6,6-tetraphenylhexa-2,4- represented by the following general formula (I) used in the present invention.
We have proposed a simple method for the optical resolution of racemic glycidyl compounds, which are epoxides containing asymmetric carbons, using complex formation with diyne-1,6-diol derivatives. Epoxides that give rise to stereomeric relationships have not been investigated. In general, a compound containing a plurality of asymmetric carbons has an increased number of asymmetric carbons and an increased number of diastereomers, and it is very complicated and difficult to separate a specific optical isomer from them, and it is difficult to separate them efficiently. No general method is found.

(Object of the Invention) It is an object of the present invention to provide a simple method capable of separating a specific optical isomer from a mixture of optical isomers of an epoxide in which a diastereomer is present.

(Structure of the Invention) The present invention provides an optical isomer mixture of epoxides represented by the general formula (I), which has a diastereomeric relationship by having two or more asymmetric carbon atoms in the molecule. (However, in the formula (I), X and Y are an atom or a group selected from a hydrogen atom, a halogen atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group and an alkylthio group, and X and Y are the same as hexadiyne. X and Y are not the same atom or group when they are bonded at the same position with respect to the carbon of each phenyl group bonded to the carbon.) 1,1,6,6 -Tetraphenylhexa-2,4-diyne-1,6-diol derivative is contacted with to form a complex incorporating a specific optical isomer, and a plurality of asymmetric carbons characterized by separating the complex. Is a method for separating optical isomers of epoxides.

The above formula (I) compound used in the present invention is already known, and the following formula (II) compound which is a precursor is oxidatively coupled, for example, air oxidation is carried out in an acetone solution in the presence of a cuprous chloride-pyridine catalyst. Can be easily manufactured.

Further, the above formula (II) compound is produced from a corresponding ketone and acetylene by an ethynylation reaction.

Specific examples of the above formula (I) compound include 1,6-di-o-chlorophenyl-1,6-diphenylhexa-2,4-diyne-1,6-diol 1,6-di-o- Fluorophenyl-1,6-diphenylhexa-2,4-diyne-1,6-diol 1,6-di-p-chlorophenyl-1,6-diphenylhexa-2,4-diyne-1,6-diol 1 , 6-Di-pt-butylphenyl-1,6-diphenylhexa-2,4-diyne-1,6-diol 1,6-di-o-methoxyphenyl-1,6-diphenylhexa-2, 4-diyne-1,6-diol 1,6-di-p-phenylthiophenyl-1,6-diphenylhexa-2,4-diyne-1,6-diol and the like can be mentioned.

Specific examples of the epoxide having two or more asymmetric carbons, which is the object of the present invention, include 1-methyl-2,3-epoxypropyl acetate, 1-
Examples thereof include methyl-2,3-epoxybutyl acetate, 2,3-epoxycyclohexyl acetate, 2,3-epoxypropyl-2 ', 3'-epoxy-2'-methylpropyl ether.

To carry out the present invention, the epoxide and the compound of the formula (I) are directly mixed or mixed as a solution to form a complex in which a specific optical isomer is incorporated by precipitation, and this may be separated. The conditions for the complex formation reaction differ depending on the compound of formula (I) used, but the reaction is usually carried out within the range of room temperature to the reflux temperature of the solvent. The reaction time may be appropriately determined depending on the precipitation of the complex that is formed as a solid crystal.
The complex is usually produced as a compound having a molar ratio of the epoxide and the formula (I) compound of 3: 1 to 1: 3.

As the solvent used in the solution reaction, aliphatic hydrocarbons, aromatic hydrocarbons, ethers or a mixed solvent thereof is generally used.

Removal of the optical isomer from the obtained complex is carried out by filtering the precipitate formed by the reaction and purifying by recrystallization as necessary, followed by heating distillation at room temperature or under reduced pressure.
It can be easily performed by substitution with a polar solvent or chromatography.

(Effects of the Invention) The method of the present invention is different from the method of separating the diastereomers by physical means first, and then guiding the separated racemate to the derivative to optically resolve the diastereomers, which is considered as a conventional method. By directly contacting the mer mixture with the compound of formula (I), only one optical isomer can be separated as a complex, and the complex formation is extremely highly selective and complete. Also, by adding the antipode of the above-mentioned formula (I) compound to the mother liquor from which the above complex has been filtered off, a complex can be formed with the target substance of the previously introduced optical isomer, so that one pair of both pairs is formed. The palm body can be easily separated and acquired.

The produced complex can easily release the optical isomer incorporated by a method such as heating under reduced pressure, and the obtained optical isomer has extremely high optical purity.

(Example) In the following examples, * in a structural formula shows an asymmetric carbon.

Example 1 The levorotatory 1,6-di-form of the optically pure compound of formula (A) above
o-chlorophenyl-1,6-diphenylhexa-2,4-diyne-1,6-diol ([α] _D −122 °, mp 127-129)
C) 2.42 g and 1.30 g of 1-methyl-2,3-epoxypropyl acetate (threo: erythro = 64: 36), which is a diastereomeric mixture represented by the above formula (B), and a mixed solvent of ether and petroleum ether ( 1: 1) dissolve in 10 ml at room temperature
I left it for 12 hours. Crystals of the complex obtained by filtration were recrystallized once from the above mixed solvent, filtered and dried to obtain 0.76 g of colorless prism crystals. The crystals are (-)-A and threo-
(+)-B is a complex having a molar ratio of 1: 1 and a melting point of 101-103.
The specific optical rotation [α] _D (the solvent was the same in the following measurements) measured with a methanol solution at ℃ was -92.2 °.

When the above crystals are heated under reduced pressure (25 mmHg) to about 150 ° C, threo
0.16 g ([α] _D + 1.0 °) of-(+)-B was obtained.

Example 2 The same (-)-A4.83 g as in Example 1 and 1-methyl-2,3- which is a mixture of diastereomers represented by the above formula (E).
Epoxy butyl acetate (threo: erythro ＝ 9: 91) 2.88g
Was dissolved in 20 ml of the same mixed solvent as in Example 1 and left at room temperature for 12 hours. The complex crystals obtained by filtration are recrystallized twice from the above mixed solvent, filtered and dried to give colorless prism crystals 1.72.
got g. The crystals are (-)-A and erythro-(-) above.
-E is a complex having a molar ratio of 1: 1 and a melting point of 105 to 108 ° C.
It was [α] _D −104 °.

When this crystal was heated in the same manner as in Example 1, erythro-(-)-E 0.4 g ([α] _D -13.0 °) was obtained.

Example 3 The same (-)-A4.83 g as in Example 1 and 3.12 g of 2,3-epoxycyclohexyl acetate (cis: trans = 35: 65), which is a diastereomeric mixture represented by the above formula (F), were used as in Example 1. It was dissolved in 20 ml of the same mixed solvent and left at room temperature for 12 hours. Crystals of the complex obtained by filtration were recrystallized once from the above mixed solvent, filtered and dried to obtain 1.15 g of colorless prism crystals. This crystal is a complex in which the molar ratio of (-)-A and cis-(-)-F is 1: 1 and has a melting point of 125 to 127 ° C and [α].
It was _D- 122 °.

When this crystal was heated in the same manner as in Example 1, cis-(-)-
F0.28 g ([α] _D −98.1 °) was obtained.

On the other hand, when the filtrate from which the above complex has been separated is allowed to stand at room temperature for 6 hours, the molar ratio of (-)-A to trans-(+)-F is 1: 1.
The complex of was precipitated.

This complex was recrystallized twice from the above mixed solvent, filtered and dried to obtain 1.59 g of colorless needle crystals. This crystal has a melting point of 132-
It was 134 degreeC and [alpha] _D- 99.3 degree.

When this crystal is heat-treated in the same manner as above, trans-(+)-
0.39 g of F ([α] _D + 79.4 ° C.) was obtained.

Example 4 The same (-)-A as in Example 1 (4.83 g) and 2,3-epoxypropyl-2 ', 3'-epoxy-2'-methylpropyl ether (2.88 g) which is a diastereomeric mixture represented by the above formula (G). Was dissolved in 20 ml of the same mixed solvent as in Example 1 and left at room temperature for 12 hours. Crystals of the complex obtained by filtration were crystallized three times from the above mixed solvent, filtered and dried to obtain 1.39 g of colorless prism crystals. This crystal is a complex having a molar ratio of (-)-A and (-)-G of 1: 1 and a melting point of 98-10.
It was 0 degreeC and [(alpha)] _D- 97.7 degree.

When the above crystal was heated in the same manner as in Example 1, (-)-G0.31
g ([α] _D −20.2 °) was obtained.

Claims (1)

[Claims] 1. A mixture of optical isomers of epoxides having two or more asymmetric carbons in the molecule to give a diastereomeric relationship, which is an optically active 1,1,6 represented by the following general formula (I). , 6-Tetraphenylhexa-2,4-
A method for separating an optical isomer of an epoxide having a plurality of asymmetric carbons, which comprises forming a complex incorporating a specific optical isomer by contacting with a diyne-1,6-diol derivative and separating the complex. . (However, in the formula (I), X and Y are an atom or a group selected from a hydrogen atom, a halogen atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group and an alkylthio group, and X and Y are the same as hexadiyne. (X and Y are not the same atom or group when they are bonded at the same position with respect to the carbon of each phenyl group bonded to the carbon.)