JPS59224692A - Optically active 1, 6-diphenyl-2, 4-hexadiyen-1, 6-diol derivative and its preparation - Google Patents

Abstract

NEW MATERIAL:An optically active compound shown by the formula I (R is butyl, tolyl, naphthyl, or halogenated phenyl). EXAMPLE:(-)-1, 6-Di(o-chlorophenyl)-1, 6-diphenyl-2, 4-hexadiyen-1, 6-diol. USE:An agent for optical resolution. The compound and various kinds of racemic modifications for inclusion compounds, and in the reaction, it includes only one antipode. PREPARATION:An optically active phenylpropargyl alcohol derivative shown by the formula II is dimerized in the presence of pyridine, CuCll and O2.

Description

Detailed Description of the Invention The present invention is directed to a novel optically active compound, a 1.6-diphenyl-2,4-hexadiyn-1,6-diol derivative (hereinafter referred to as a diacetylene diol derivative). ) and its manufacturing method.

Conformist J vs.! (The diastereomer method using an optically active resolving reagent is commonly used industrially to resolve the UI-mi form.

Commonly used conventional resolving agents include optically active amines such as brucine, optically active acids such as camphorsulfonic acid, and optically active alcohols such as menthol. After forming a salt or ester with the racemate to be resolved to obtain diastereomers, separate each diastereomer by performing fractional crystallization using the difference in solubility, and then neutralize or hydrolyze this. This method separates each enantiomer of the desired racemic body. However, conventional resolving agents are often naturally produced and are expensive and difficult to obtain in large quantities. Furthermore, depending on the type of resolving reagent, the number of racemic forms that form diastereomers is limited. , development of resolution reagents with various optical activities is desired.

Purpose and Structure of the Invention In view of the above-mentioned circumstances, the present inventors have carried out intensive research with the aim of finding a new optically active compound, and as a result, have discovered a novel optically active compound represented by the following general formula (I): -Diphenyl-2,4-hexadiyne-1,6-thiol derivative was successfully synthesized.

(In the formula, 1 represents a butyl group, a tolyl group, a naphthyl group, or a halogenated phenyl group.) The optically active diacetylene diol derivative of the above JI & formula (1) has the general formula (n) pyridine, an optically active sonylpropargyl alcohol derivative represented by
It can be produced by trimerization in the coexistence of cupric chloride and oxygen.

The optically active diacetylene diol derivative of general formula (1) described above can be produced from the corresponding ketone in the following manner.

Therefore, first, the corresponding ketone υ of general formula (III) (wherein R is as defined above) and sodium acetylide (
A racemic body of the phenylpropargyl alcohol derivative represented by the general formula (II>) is synthesized by reacting NaC=CH) in liquid ammonia under close pressure, and then this racemic body is synthesized by, for example, the method previously described by the present inventors. Patent Application No. 1983-33011 (1tJi filed on March 4, 1981)
and Patent Application No. 164969 (September 24, 1982)
After contacting l-brucine and β-spartine in an R'14 medium according to the method described in the specification, and separating the obtained diastereomers using the difference in solubility,
By decomposition, the optically active phenylpropargyl alcohol derivative of the general formula (11) can be obtained.

The optically active phenylpropargyl alcohol derivative of the general formula (It) can also be prepared by reacting the racemic form of the phenylpropargyl alcohol derivative of the general formula (II) with acetic anhydride or acetic chloride to obtain a corresponding 0-acetylphenylpropargyl alcohol derivative. After synthesizing (racemic body), only one enantiomer is asymmetrically hydrolyzed in the presence of an esterase produced by a microorganism of the genus Hafrus or Rhodotorula to obtain the desired optically active phenyl. Propargyl alcohol derivatives can be obtained.

Next, the optically active phenylpropargyl alcohol derivative of the general formula (II) thus obtained is dissolved in an organic solvent and trimerized in the presence of pyridine, cupric chloride and oxygen. -JI&An optically active diacetylene diol derivative of formula (I) can be synthesized. Examples of the organic solvent for dissolving the optically active phenylpropargyl alcohol derivative (hereinafter referred to as the bemonoacetylene alcohol derivative) of the general formula (II) include acetone, methylalnyl, edyl alcohol, [methyl, Examples include ethyl acetate, dimedyl sulfoxide, benzene, toluene, 4aR2 carbon, chloroform, methylene chloride, ethyl ether, tetrahydrofuran, etc.
Most preferred is acetone.

Its use is optically active monoacetylene alcohol Lo
g, 10 to 50 mj2 is suitable, preferably 10 to 25 mj2. A catalytic amount of cuprous chloride (1/20 to 1/100 mol) is added to the optically active monoacetylene alcohol derivative solution prepared in this way, and pyridine is further added at a volume ratio of 1/10 to 1150 to the organic solvent. The reaction is allowed to proceed at room temperature for 10 to 20 hours while blowing oxygen at a rate of 50 to 300 mβ/hour.

After the reaction, the organic solvent is removed, the residue is washed with petroleum ether, and the crystals are collected by filtration. The optically active diacetylene diol represented by the general formula (1) can be obtained by dissolving the crystals in benzene, washing with hydrochloric acid water or sulfuric acid water, and then drying the benzene layer to remove the benzene. The optically active diacetylene diol thus obtained forms inclusion compounds with various racemic pairs and includes only one enantiomer at that time, so it has uses as a new optical resolution agent. Those that form clathrate compounds with this optically active diacetylene diol include malic acid, mandelic acid, pipecolic acid, carvone, menthol, pantoyl lactone, β-lactones, β-lacta, A[・γ
-lactone frequent, γ-lactams, δ-lactone frequent, δ-
Examples include lactams, ε-lactones, ε-lactams, sulfoxides, and ketones. Of these,
In the case of 4- to 7-membered rings, lactams, ketones, sulfoxides, menthol, pantoyl lactone, etc., only one enantiomer is selectively included and crystallized.

Describing the separation conditions in detail, the charged amounts of the optically active form of (-) to diacetylene diol and the racemic compound to be separated are 1:4 to 1.0 expressed in molar ratio. :
I 2 O is suitable, and if the crystallization rate and optical purity are taken into consideration, it is sufficient to provide 4 mol of the racemic compound per 1 mol of diacetylene diol. As the separation solvent, one that dissolves the diacetylene diol and the racemic compound and in which the formed clathrate compound has a low solubility is preferable. Such solvents include tetrahydrofuran,
Methyl alcohol is suitable for the separation of men-heher and pantoyllactone, methyl alcohol is suitable for the separation of sulfoxides, and ether-petroleum ether mixed solvent is suitable for the separation of ketones. The division temperature is room temperature, and the time required for crystallization is 10 to 48 hours for lactones and lactams, and for pantoyl lactone,
4 days to IO days with l-menthol, 2 days with sulleboxide buccal
~172 hours, and 5 to 15 hours for ketones. To isolate the desired optically active guest molecule from the clathrate compound, there are two methods: vacuum distillation, column chromatography, and exchange of the guest compound, which method may be selected depending on the guest molecule.

EXAMPLES The present invention will be described in detail below, but it goes without saying that the scope of the present invention is not limited to these Examples.

Example: 1% molasses by weight in a shoulder flask, corn steeple force -
2.5% by weight, ammonium sulfate 0.5% by weight and inorganic salts mixture (MgSO4.7H2020g, FeSO4
・7t1205g, CaCl, 22g, MnCl
2・4H200,2g, NaMoO4211,00
,1,g and distilled water containing 10,1g of NaC16) 1m
I! After sterilizing 1.00 ml of medium (pH 7.0) containing 11 Togawa Lula Minuta (IFO-03
78) was seeded with two platinum earplugs from a slant culture medium and incubated at 30'C for 94 hours.
Culture was performed with back and forth shaking for hours. The microbial cells isolated by centrifugation from this culture solution were washed twice with distilled water, and 1 q of washed microbial cells were obtained. This was further freeze-dried to obtain 1 q of freeze-dried bacterial cells.

50μ of this freeze-dried bacterial cell is 20mI! water (pH 7
, O) to V, cloudy, 0.5% by weight of 0-acetyl-1
-o-#y [Ja phenyl-I-phenylpropal n-hebutane i$100ml! The mixture was mixed and suspended and reacted at 30° C. for 48 hours with stirring.

The bacterial cells were separated from the reaction solution, the aqueous layer and the n-hebutane layer were separated, and the n-hebutane layer was dried with Glauber's salt, and then the II-heptane was removed. The remaining crystals were subjected to column chromatography using Wako Gel C-300 and developed with a column chromatogram to remove the hydrolysis product 1-0-corophenyl-1-phenylpropargyl alcohol and unreacted 0-propargyl alcohol.
-Each acetyl derivative was separated. The former [αg (C
ll30) 11%) was -129°.

48 g of optically active (-)-1-o-chlorophenyl-1-phenyl-propargyl alcohol thus obtained
was dissolved in a mixture of 100 m6 acetone and 10 mβ pyridine, 862 nyr of cuprous chloride was added, and 20 Q of oxygen was added.
The reaction was carried out at room temperature for 16 hours while passing through the reaction solution at a flow rate of mI2/h. Acetone and pyridine were removed from the reaction solution, and the resulting pale blue crystals were dissolved in benzene, washed with a 12% aqueous hydrochloric acid solution, and then with water, and the benzene layer was dried with sodium sulfate. When benzene was removed, 4 white crystals were found.
3g was obtained. This is 1,6-di(chlorophenyl)-
1,6-diphenyl-2,4-hexadiyne-1,6-
diol, [α] origin - -122° (1% CI +
3011), the melting point was 127-129°C.

Examples 2 to 6 Various derivatives of optically active 1-phenylpropargyl alcohol synthesized according to the method described in Example 1 were subjected to a trimerization reaction in exactly the same manner as in Example 1.

The α resistance and melting point of each diacetylene diol derivative obtained are shown in Table 1.

Table-1 Example Village Melting point (℃) [αg ＜
Cll3ol (1%) 11r 140~1
42-129.

5 t-('4+19- 168~169
+ 56.9゜Example 4- Optically active (-)-1,6-di(o-chlorophenyl)-1,6-diphenyl-2,4-hexadiyne-1,6-diol synthesized in Example 1 [ α〕τ−−122′ (
30 g of CI+3011 1%) was dissolved in 75 mj2 of tetrahydrofuran. When 26 g of racemic γ-valerolactone was dissolved in this solution and left at room temperature for 2 days, white crystals were precipitated.

The crystals were collected by filtration and petroleum ether methyl alcohol (3
: After washing with the mixed solvent of L) and drying, put it in a distillation pot, and 2
When heated to 80°C under reduced pressure of 11 g, 7.6 g of optically active T-valerolactone was obtained.

[α Fort - + 10.7° (neat).

Example 8 The optically active (-)-1,6-di(o-) synthesized in Example 2
chlorophenyl)-1,6-'; Phenyl-2,4-hexadiyne-1,6-diol (10 g) was dissolved in 30 ml of methyl alcohol, 8.2 g of methyl ethyl sulfoxide was dissolved in this /8 solution, and the mixture was heated to room temperature. When left for 2 days, white crystals were obtained. This was collected by filtration and dried to give a melting point of 102-116°C and [α]. --31,4°
(1% C113011) of methyl niger sulfoxide 2
An inclusion compound zg containing molecules was obtained. This was placed in a distillation pot and heated to 100° C. under a reduced pressure of 20 mlH to isolate optically active methylniere sulfoxide.

Example 9 When optical resolution of α-amino-ε-caprolactam was attempted in the same manner as in Example 1, α-amino-ε-caprolactam was clathrated by standing at room temperature for 48 hours. Crystals of the clathrate were obtained.

The crystals were subjected to column chromatography using ethyl acetate as a developing solvent, and the optically active α-amino-ε=-Cub II
lactam was confirmed.

Example 10 Optically active (-)-1,6-di(0-chlorophenyl) to 1,6-diphenyl-2,4-hexadiyn-I,
19.2 g of 6-diol and 17.8 g of 3-methylschiff 1:1 hex-none were mixed with ether petroleum ethyl (volume ratio 1:l) mixed solvent IC10m! ! 6 at room temperature.
When the mixture was left to stand for a while, white crystals were precipitated. After collecting the crystals by filtration, they were re-crystallized using a mixed solvent of ether and petroleum ether (volume ratio 1:1). After repeating the recrystallization operation twice, the precipitated crystals were collected by filtration. 11.6 g of crystals of the clathrate thus obtained were placed in a distillation vessel and distilled under closed pressure to obtain 3.3 g of optically active (+)-3-methylcyclohexanone. Cαt is +9.5° (CH
C131%).

° Patent applicant Ube Industries Co., Ltd. patent application agent Patent attorney Akira Aoki Patent attorney Kazuyuki Nishidate Patent Attorney Ishi 1) Takashi Patent attorney Akira Yamaguchi

Claims (1)

[Scope of Claims] (2) Optically active 1.
6-diphenyl-2,4-hexadiyne-1,6-diol derivative. 2. A light 13-propargyl alcohol derivative represented by the general formula (IT) (where R represents a butyl group, a tolyl group, a naphthyl group, or a halogenated phenyl group) is mixed with pyridine, cupric chloride, and oxygen. An optically active 1,6-diphenyl-2゜4- compound represented by the general formula (1) (wherein R is as defined above), which is characterized by being trimerized in the coexistence of
A method for producing a 1-pheasant diyne-1,6-diol derivative.