JPH0321549B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing optically active 2,3-epoxy-3-methylcyclohexanones. Optically active 2,3-epoxy-3-methylcyclohexanones are important compounds as raw material intermediates for pharmaceuticals, agricultural chemicals, fragrances, and the like. The present inventors have demonstrated that optically active 1,6-di(halofenyl)-1,6-diphenyl-2,4-hexadiyn-1,6-diol is an excellent optical resolution reagent in various racemic forms. He was the first to discover this and filed a patent application as Japanese Patent Application No. 58-90077. after that,
As a result of further research, the diol was found to be 2,3-
It was discovered that the present invention has an effect of optically resolving racemic forms of epoxy-3-methylcyclohexanones very efficiently, and the present invention has been completed. That is, the present invention provides racemic 2,3-epoxy-3-methylcyclohexanones and optically active 1,6-di(halophenyl)-1,6-diphenyl-2,4-hexadiyne-1,6-diol. An optically active 2,3- Epoxy-3-
The present invention provides an industrially excellent method for producing methylcyclohexanones. The 2,3-epoxy-3-methylcyclohexanones (hereinafter sometimes simply referred to as cyclohexanones) in the present invention are represented by the following structural formula.

[Formula] (However, in the formula, R ₁ and R ₂ represent a hydrogen atom or a methyl group.) The racemic form of the cyclohexanones can be obtained by, for example, converting cyclohexenone into H ₂ O ₂ -NaOH in methanol.
It can be easily synthesized by epoxidation using In the present invention, an optically active 1,6-di(halofenyl)-1,6-diphenyl-2,4-hexadiyn-1,6-diol (hereinafter abbreviated as diacetylene diol derivative) used as a resolving reagent. ) is shown by the following structural formula. (However, in the formula, X represents a halogen atom such as chlorine or bromine.) The diacetylene diol derivative is produced by coupling optically active 1-0-halophenyl-1-phenylpropargyl alcohol having the following structure in an organic solvent (e.g., acetone) in the coexistence of cuprous chloride, pyridine, and oxygen. It can be easily synthesized by carrying out a reaction. Next, an example of its synthesis will be shown. 48 g of optically active 1-0-chlorophenyl-1-phenylpropargyl alcohol was dissolved in a mixture of 100 ml of acetone and 10 ml of pyridine, 86 mg of cuprous chloride was added, and oxygen was added to the reaction solution at a flow rate of 200 ml/hour. When the reaction is allowed to proceed for 16 hours at room temperature while passing through, pale blue crystals are precipitated. Remove the reaction solution,
Dissolve this crystal in benzene and make an equal volume of 12
After washing with % hydrochloric acid and further washing with water, the benzene layer was dried with sodium sulfate to remove benzene, resulting in optically active 1,6-dichlorophenyl-1,6-diphenyl-2,4-hexadiyne-1,6. -43 g of white crystals of diol are obtained. The melting point of the product is 175℃,
[α] ²⁵ _D is −106° (1% CH ₃ OH). The optical activity of the starting material for the above synthesis is 1.
-0-halophenyl-1-phenylpropargyl alcohol can be obtained by the method described in Japanese Patent Application No. 57-33011 and Japanese Patent Application No. 57-164969, filed earlier by the present inventors. can. In the present invention, the racemic form of cyclohexanones is usually used in an amount of 1 to 10 moles per mole of the diacetylene diol derivative, but the crystallization rate of the inclusion complex and the optical purity of the separated target cyclohexanones are Considering this, it is preferable to use 3 to 8 moles per mole of diacetylene derivative. The organic solvent to be used is preferably one that dissolves the racemic form of the cyclohexanones and has a low solubility for the formed inclusion complex. Examples of such solvents include benzene, toluene, carbon tetrachloride, chloroform, methylene chloride, ethyl acetate, methyl acetate, petroleum ether, tetrahydrofuran, and ethyl ether. When considering the optical purity of the product, an ether-petroleum ether mixed solvent (arbitrary volume ratio) is the most suitable solvent. The amount of the solvent used is preferably 2 to 10 ml per gram of optically active diacetylene diol derivative. The contact between the racemic form of cyclohexanones and the diacetylene diol derivative is usually carried out at a temperature of 10 to 50°C for 1 to 50 hours. Through this contact, one enantiomer of the racemic cyclohexanones is packaged in the diacetylene diol derivative, and the complex crystallizes. The crystallized inclusion complex of optically active diacetylene diol derivative and cyclohexanones is collected and then separated by column chromatography.
Further, by heating under reduced pressure, the desired optically active cyclohexanones can be separated from the optically active diacetylene diol derivative. At this time, the developing solvent for column chromatography and the temperature and pressure reduction degree during separation by distillation can be appropriately selected depending on the physical properties of the cyclohexanones and the like. The recovered optically active diacetylene diol derivative can be used again as a resolving agent without losing its optical purity even after the above-mentioned operations. If you want to obtain the other optically active cyclohexanones, you can use an optically active diacetylene diol derivative with opposite optical rotation as a resolving agent, and the resolving operation is no different from the procedure described above. does not change. Next, the present invention will be explained in more detail with reference to Examples, but it goes without saying that the scope of the present invention is not limited to these Examples. Example 1 Optically active (-)-1,6-di(chlorophenyl)-1,6-diphenyl-2,4-hexadiyne-1,6-diol, [α] ²⁵ _D = -122° (1%
CH ₃ OH), 59 g was dissolved in 250 ml of a mixed solvent of ether-petroleum ether (volume ratio 1:2). In this solution, 61.5 g of racemic 2,3-epoxy-3-methylcyclohexanone was dissolved and allowed to stand at room temperature for 6 hours, yielding 57 g of colorless crystals. When this crystal was subjected to X-ray diffraction and thermal analysis, it was found that it was one molecule of optically active (-)-1,6-di(chlorophenyl)-1,6-diphenyl-2,4-hexadiyne-1,6-diol. For,
Complex containing two molecules of 2,3-epoxy-3-methylcyclohexanone mp.70-73℃, [α]
^25D = 89.3 _° (1% CH ₃ OH). The crystals were placed in a distillation pot and heated under a reduced pressure of 25 mmHg.
Heated to 130℃, optically active 2,3-epoxy
17.5 g of 3-methylcyclohexanone, [α] ²⁵ _D =+32.0° (1% CH ₃ OH), optical purity 55%, was obtained. Example 2 Inclusion complex obtained by exactly the same operation as Example 1
57 g was recrystallized twice with 300 ml of a mixed solvent of ether and petroleum ether (volume ratio 1:1) to give colorless crystals, mp.72-73°C, [α] ²⁵ _D = -88.9° (1%
18 g of CH ₃ OH) was obtained. The crystals were placed in a distillation pot and heated under a reduced pressure of 25 mmHg.
Heated to 130℃, optically active 2,3-epoxy
5.5 g of 3-methylcyclohexanone, [α] ²⁵ _D = +58.3° (1% CH ₃ OH), optical purity 100%, was obtained. Example 3 Optically active (-)-1,6-di(chlorophenyl)-1,6-diphenyl-2,4-hexadiyn-1,6-diol, [α] ²⁵ _D = -122° (1%
CH ₃ OH), 51 g was dissolved in 200 ml of a mixed solvent of ether-petroleum ether (volume ratio 1:2). In this solution, 53 g of a racemic form of 2,3-epoxy-3,5-dimethylcyclohexanone was dissolved and allowed to stand at room temperature for 6 hours, yielding 47 g of colorless crystals. When this crystal was subjected to X-ray diffraction and thermal analysis, it was found that one molecule of optically active (-)-1,6-di(chlorophenyl)-1,6-diphenyl-2,4-hexadiyne-1,6-diol Te, 2
Complex containing the molecule 2,3-epoxy-3,5-dimethylcyclohexanone, mp.116-118
°C, [α] ²⁵ _D = -125° (1% CH ₃ OH). 47 g of this crystal was recrystallized twice with 500 ml of a mixed solvent of ether and petroleum ether (volume ratio 1:1) to give colorless crystals, mp. 117-118°C, [α] ²⁵ _D = -
27g of 126° (1% CH ₃ OH) was obtained. The crystals were placed in a distillation pot and heated under a reduced pressure of 25 mmHg.
Heated to 136℃, optically active 2,3-epoxy
3,5-dimethylcyclohexanone, [α] ²⁵ _D = -
136° (1% CH ₃ OH), optical purity 100%, 9 g was obtained. Example 4 Optically active (-)-1,6-di(chlorophenyl)-1,6-diphenyl-2,4-hexadiyn-1,3-diol, [α] ²⁵ _D = -122° (1%
CH ₃ OH), 60 g was dissolved in 250 ml of a mixed solvent of ether-petroleum ether (volume ratio 1:4). To this solution was added 76.4 g of 2,3-epoxy-3,5,
When the racemic form of 5-trimethylcyclohexanone was dissolved and allowed to stand at room temperature for 6 hours, 55 g of colorless crystals were obtained. When this crystal was subjected to X-ray diffraction and thermal analysis, optically active (-)-1,6-
di(chlorophenyl)-1,6-diphenyl-2,
For every molecule of 4-hexadiyne-1,6-diol, two molecules of 2,3-epoxy-3,5,5-
A complex containing trimethylcyclohexanone,
mp.133-135℃, [α] ²⁵ _D = -89.1゜ (1% CH ₃ H),
It was hot. 55 g of this crystal was recrystallized twice using 500 ml of a mixed solvent of ether and petroleum ether (volume ratio 1:1).
38 g of colorless crystals, mp, 134-136°C, [α] ²⁵ _D = -88.6° (1% CH ₃ OH), were obtained. The crystals were placed in a distillation pot under a reduced pressure of 5 mmHg.
Heated to 70℃, optically active 2,3-epoxy
3,5,5-trimethylcyclohexanone, [α]
²⁵ _D = +13.5° (1% CH ₃ OH), optical purity 100%, 12
I got g.

Claims (1)

[Claims] 1 Racemic form of 2,3-epoxy-3-methylcyclohexanones and optically active 1,6-di(halophenyl)-1,6-diphenyl-2,4-hexadiyne-1,6-diol in an organic solvent. an optically active 2,3-epoxy, which is characterized in that the complex of the diol including one enantiomer of the obtained cyclohexanone is separated, and then the inclusion complex is decomposed. Method for producing 3-methylcyclohexanones.