JPH0578539B2 - - Google Patents

Description

[Detailed description of the invention]

(Technical field of the invention) The present invention relates to β-dichlorohydrin ester (1-
The present invention relates to a method for optically resolving hydroxy-2,3-dichloropropane (carboxylic acid ester). (Prior Art) β-dichlorohydrin ester is an important substance as an intermediate in the synthesis of various derivatives and as a precursor of epichlorohydrin which can be easily obtained from it. In recent years, it is well known that one optical isomer of chemical substances with physiological functions has a special meaning, and completely optically resolved optical isomers are the key materials for the synthesis of such physiologically functional substances. It is of great significance to obtain pure optical isomers of β-dichlorohydrin ester or dichlorohydrin or epichlorohydrin directly derived therefrom. The optically active β-dichlorohydrin ester is
Recently, a method for obtaining one enantiomer by microbiological means has been published, and examples of enzymatic resolution have also been reported. However, the former method is extremely inefficient and unreasonable in that only one enantiomer can be obtained. Furthermore, the latter example has very low optical purity. Additionally, as a general method for resolving racemates, there is also a chemical method in which derivatives are synthesized by preferentially reacting only one enantiomer through an asymmetric reaction with a specific chemical substance that has an asymmetric group. However, no attempt of this kind has been made for β-dichlorohydrin or its ester. The present inventors have proposed an alkyl substituent group using a derivative of 1,1,6,6-tetraphenylhexa-2,4-diyne-1,6-diol of the compound of the general formula () used in the present invention. We have already reported that it is possible to completely optically resolve cyclic ketones with however,
This method has not been used to resolve chain compounds such as those of the present invention. As a result of further studies on the above method, the present inventors discovered that this method is very effective for the optical resolution of β-dichlorohydrin esters, and thus arrived at the present invention. (Object of the Invention) An object of the present invention is to provide a method for easily and completely optically resolving racemic β-dichlorohydrin ester. (Structure of the Invention) The present invention involves contacting racemic β-dichlorohydrin ester with an optically active compound to form a complex incorporating only one enantiomer of β-dichlorohydrin ester. In this method, optically active 1,1,6,6- A complex incorporating one of the enantiomers of the β-dichlorohydrin ester is formed by acting with a derivative of tetraphenylhexa-2,4-diyne-1,6-diol, and this complex is separated. This is a characteristic method for optical resolution of β-dichlorohydrin ester.

[Chemical formula] (However, in the formula (), X is a halogen atom located at the ortho or para position.) Unlike methods that preferentially synthesize and resolve derivatives of complexes, complex formation is performed extremely highly selectively and completely.
β-dichlorohydrin ester, which is one enantiomer, can be easily released from this complex by a method such as heating under reduced pressure, and the other enantiomer can be released from the mother liquor after filtering the complex. Also concentrated,
It can also be obtained in high purity through operations such as distillation, and both enantiomers can be obtained easily and in high purity. The acid component forming the β-dichlorohydrin ester that is the object of the present invention is acetic acid, propionic acid or butyric acid. The above compound of formula () used in the present invention is already known, and can be obtained by oxidative coupling of the compound of formula () below as a precursor, for example, by air oxidation in an acetone solution in the presence of a cuprous chloride-pyridine catalyst. It can be easily manufactured.

[Image Omitted] The above compound of formula () can also be produced by a reaction to form ethynyl from the corresponding ketone and acetylene. Specific examples of the above formula () compounds 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 and the like can be mentioned. In the present invention, a complex is formed from the racemic β-dichlorohydrin ester and the compound of formula () by directly mixing them or by mixing them in the form of a solution. The conditions for the complex-forming reaction vary depending on the compound of formula () used, but it is usually carried out in the range of room temperature to the reflux temperature of the solvent. The reaction time may be determined as appropriate based on the precipitation of the complex formed as solid crystals. The complex is usually produced as a compound in which the molar ratio of β-dichlorohydrin ester to the compound of formula () is 3:1 to 1:3. The solvent used in the above reaction is generally aliphatic hydrocarbons, directional group hydrocarbons, ethers, or a mixed solvent thereof. In order to extract the optically active β-dichlorohydrin ester from the complex obtained above, the precipitate formed by the reaction is filtered, and if necessary, after purification by recrystallization, it is purified at room temperature or under reduced pressure. The optically active β-dichlorohydrin ester, which is one of the enantiomers, can be easily released and isolated by heating distillation, substitution with a polar solvent, chromatography, etc. In addition, by concentrating and distilling the unreacted liquid or mother liquor after filtering off the complex, the other enantiomer, β-
Dichlorohydrin ester can be separated and obtained. (Effects of the Invention) According to the present invention, both optically active enantiomers can be easily obtained from racemic β-dichlorohydrin ester, and each optically active β-dichlorohydrin ester obtained has extremely high optical purity. Examples Example 1 Optically pure levorotatory 1,6-di-o-chlorophenyl-1,6-diphenylhex-2,4-
Diyne-1,6-diol ([α] _D −122°,
mp127-129℃) 4.83g (0.01 mol) and racemic 1-acetoxy-2,3-dichloropropane 3.42
g (0.02 mol) in 10 ml of ether and 10 ml of petroleum ether
ml of mixed solvent and left at room temperature for 12 hours. The obtained crystals were collected by filtration and recrystallized once from the above mixed solvent to obtain 3.31 g of colorless prismatic crystals [complex with the above compound in a molar ratio of 1:1, melting point 93-95°C, [α] _D −
86.8° (methanol)] was obtained. This crystal was heated to about 150°C under reduced pressure (25mmmmHg) to create a dextrorotatory 1-
Acetoxy-2,3-dichloropropane 0.87g
([α] _D +18.6° (methanol)) was obtained. On the other hand, the solvent of the mother liquor obtained by filtering off the crystals was evaporated, and the residue was distilled under reduced pressure to obtain 2.10 g of levorotatory 1-acetoxy-2,3-dichloropropane ([α] _D -
2.85° (methanol)) was obtained. The levorotatory 1-acetoxy-2,3- obtained above
2.10 g of dichloropropane and dextrorotatory 1,6-di-o
-chlorophenyl-1,6-diphenylhexa-
2,4-diyne-1,6-diol ([α] _D +
122°) was dissolved in 20 ml of the same mixed solvent of ether and petroleum ether as above and allowed to stand at room temperature for 12 hours to precipitate a complex. This precipitated complex was recrystallized once using the above mixed solvent to obtain 2.54 g of a complex with [α] _D +86.8°. The crystals were heated and distilled under reduced pressure in the same manner as above to obtain 0.64 g of levorotatory 1-acetoxy-2,3-dichloropropane [α] _D -18.6°.

Claims (1)

[Scope of Claims] 1. An optically active 1,1,6,
6,-Tetraphenylhexa-2,4-diyne-
The above β-
A method for optical resolution of β-dichlorohydrin ester, which comprises forming a complex incorporating one enantiomer of dichlorohydrin ester and separating this complex. [Chemical formula] (However, in formula (), X is a halogen atom located at the ortho or para position.)