JPH11116518A - New optically active hydroquinone derivative and production of the same and separation of optical isomer using the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound useful for host compound in separation of optically active compounds serving many uses for chemical specialties such as pharmaceuticals and agrochemical. SOLUTION: The compound is 1,4-bis (3-(2-chlorophyl)-3-hydroxy-3-phenyl)-1 propynyl}-1-4-dihydroxycyclohexa-2,5-diene expressed by the formula. The compound is obtained by carrying out the reaction of an optically active 1-(2- chloro)-1-phenyl-2-propyn-1-ol and 2,5-dicyclohexadiene-1,4-dione under nitrogen atmosphere in the presence of butyllithium in a proper solvent such as tetrahydrofuran, diethyl ether, etc., at low temperature.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel optically active hydroquinone derivative, a method for producing the same, and a method for separating optical isomers using the same. INDUSTRIAL APPLICABILITY The hydroquinone derivative according to the present invention and the optically active compound separated by using the hydroquinone derivative have high utility value in the field of fine chemistry mainly for medicines and agricultural chemicals.

[0002]

2. Description of the Related Art As one of the methods for separating optical isomers, a host-guest method using an inclusion compound is known. The optical isomer separation method using an clathrate compound is an industrially excellent method in terms of high resolving power and easy operation. Many optically active host compounds have been synthesized so far, and many separation examples using such host compounds have been found (NTS
Published "Basic and Application of Inclusion Compounds").

However, a problem of optical resolution using an inclusion compound is that selectivity is greatly different due to a slight difference in structure between a host compound and a compound to be optically resolved (guest compound) (Journal of Chemical Society). Perkin Transaction 2,1971-1975 (19
91)). At present, a search experiment on a small scale is the simplest and most efficient method for finding an optimal host-guest pair. Therefore, it is desirable to synthesize many host compounds in advance in order to efficiently find the optimum host-gesture pair.

Accordingly, an object of the present invention is to provide a novel optically active compound useful as a host compound, a method for producing the same, and an optical isomer separation method using the same.

[0005]

Means for Solving the Problems The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have found that 2,5-cyclohexadiene-1,4-dione and its derivatives and optically active 1-.
It has been found that a novel optically active hydroquinone derivative can be obtained by reacting (2-chlorophenyl) -1-phenyl-2-propyn-1-ol. Further, they have found that this novel optically active hydroquinone derivative has the ability to incorporate a guest compound and the ability to resolve optical properties, and have completed the present invention.

That is, the present invention provides an optically active 1,4-bis {(3- (2-chlorophenyl) -3-hydroxy-3-phenyl) -1-propynyl}-represented by the following formula (I): 1,4-dihydroxycyclohexa-2,5-diene.

[0007]

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Further, the present invention provides an optically active 1,4-bis {(3- (2-chlorophenyl) represented by the following formula (II):
-3-Hydroxy-3-phenyl) -1-propynyl}
-1,4-dihydroxy-2,3,5,6-tetrachloro-cyclohexa-2,5-diene.

[0009]

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Further, the present invention provides an optically active 1,4-bis {(3- (2-chlorophenyl) represented by the following formula (III):
-3-Hydroxy-3-phenyl) -1-propynyl}
-1,4-dihydroxy-2,3,5,6-tetrabromo-cyclohexa-2,5-diene.

[0011]

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Further, the present invention provides an optically active 1- (2-chlorophenyl) -1-phenyl-2-propyn-1-ol, 2,5-cyclohexadiene-1,4-dione,
Reacting 2,3,5,6-tetrachloro-2,5-cyclohexadiene-1,4-dione or 2,3,5,6-tetrabromo-2,5-cyclohexadiene-1,4-dione It is intended to provide a method for producing an optically active hydroquinone derivative represented by the above formulas (I) to (III).

Further, the present invention relates to the above-mentioned compounds of the formulas (I) to (III)
The present invention provides an optical isomer separation method characterized by separating an optical isomer using an optically active hydroquinone derivative represented by the following formula:

[0014]

Embodiments of the present invention will be described below in detail.

The optically active 1,4-bis} (3- (2-chlorophenyl) represented by the above formula (I) according to the present invention.
-3-Hydroxy-3-phenyl) -1-propynyl}
-1,4-Dihydroxycyclohexa-2,5-diene (hereinafter abbreviated as optically active hydroquinone derivative (I)) can be produced by the following method.

That is, optically active 1- (2-chlorophenyl) -1-phenyl-2-propyn-1-ol,
By reacting 2,5-cyclohexadiene-1,4-dione in the presence of butyllithium, an optically active hydroquinone derivative (I) can be obtained.

This reaction is preferably carried out under a nitrogen atmosphere in a suitable solvent such as tetrahydrofuran or diethyl ether at a low temperature.

Also, the optically active 1,4-bis {(3- (2-chlorophenyl) -3-hydroxy-3-phenyl) -1-propynyl} -1,4 represented by the above formula (II)
-Dihydroxy-2,3,5,6-tetrachloro-cyclohexa-2,5-diene (hereinafter abbreviated as optically active hydroquinone derivative (II)) and 1,4-bis} represented by the above formula (III) (3- (2-chlorophenyl) -3-hydroxy-3-phenyl) -1-propynyl} -1,4
-Dihydroxy-2,3,5,6-tetrabromo-cyclohexa-2,5-diene (hereinafter abbreviated as optically active hydroquinone derivative (III)) is also used under the above-mentioned conditions.
(2-chlorophenyl) -1-phenyl-2-propyn-1-ol and 2,3,5,6-tetrachloro-2,
5-cyclohexadiene-1,4-dione or 2,3
5,6-tetrabromo-2,5-cyclohexadiene-
It is obtained by reacting with 1,4-dione.

The optical isomer separation method of the present invention is a method of separating optical isomers using the optically active hydroquinone derivative (I), (II) or (III) obtained by the above-mentioned production method. However, as a typical method, there is a method in which one optically active substance is separated from a racemic compound using an optically active hydroquinone derivative (I), (II) or (III) as a host compound.

Specifically, first, the optically active hydroquinone derivative (I), (II) or (III) is mixed with a racemic compound to form a crystal containing one optically active substance and the optically active hydroquinone derivative. Any method may be used to form the crystals. For example, the optically active hydroquinone derivative and the racemic compound may be dissolved in a suitable solvent at a molar ratio of about 1: 8 to 8: 1 under heating if necessary. A method of forming crystals by cooling or gradually adding a solvent having low solubility, a method of suspending in hexane or water, and a method of directly mixing an optically active hydroquinone derivative and a racemic compound in a mortar.

Next, the desired optically active substance is separated from the crystals obtained as described above. Any method may be used as the method of separation, for example, a method of separating a target optically active substance having a lower boiling point than the optically active hydroquinone derivative by heating the crystal under reduced pressure, or a method of column chromatography. A method of separating an optically active substance and the like can be mentioned.

Further, the obtained crystal is recrystallized, or the compound to be separated is separated, and then the crystal is formed again using the optically active hydroquinone derivative, whereby the optical purity of the separated optically active substance is obtained. Can also be improved.

The compounds to be optically resolved by the optical isomer separation method of the present invention include functional groups such as carbonyl, carboxyl, hydroxyl, amino, amide, epoxy, ether, and sulfonyl groups. A racemic compound is mentioned, and specifically, 2-methylpiperazine, 1,2-diaminopropane, 1-phenylethanol, 2-methylcyclopentanone and the like are mentioned.

[0024]

The optically active hydroquinone derivative according to the present invention has optical resolution. Further, the optically active hydroquinone derivative can be repeatedly used, and is an industrially useful compound.

[0025]

EXAMPLES The present invention will now be described specifically with reference to examples, but the present invention is not limited to these examples.

Example 1 In a methanol-dry ice bath, (-)-1- (2- (2-)) was added to a mixed solution of 62 ml of a 1.66 M n-butyllithium / n-hexane solution and 5 ml of anhydrous tetrahydrofuran (THF).
(Chlorophenyl) -1-phenyl-2-propyne-1-
An anhydrous THF solution containing all (10.0 g, 0.04 mol) (20 m
l) was slowly added dropwise. After stirring for 1 hour,
Cyclohexadiene-1,4-dione (2.16 g, 0.02mo
An anhydrous THF solution (75 ml) containing l) was slowly added dropwise. After stirring for 12 hours, diluted hydrochloric acid was added, and the mixture was extracted with toluene. The extracted organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The resulting solid was recrystallized from toluene to give (-)-1,4-bis {(3-
(2-Chlorophenyl) -3-hydroxy-3-phenyl) -1-propynyl} -1,4-dihydroxy-cyclohexa-2,5-diene (hereinafter abbreviated as compound (1)) (7.6 g, 0.013 mol) was gotten. Specific rotation, elemental analysis value and melting point are as follows.

Specific rotation: [α] _D = -90.2 ° (c 0.51, methanol) Elemental analysis: analytical value C 73.11, H 4.28, calculated value C 72.85, H 4.42 Melting point: 193-195 ° C. The procedure of Example 1 was repeated, except that 2,3,5,6-tetrachloro-2,5-cyclohexadiene-1,4-dione was used instead of 5-cyclohexadiene-1,4-dione. ) -1,4-Bis {(3- (2-chlorophenyl) -3-hydroxy-3-phenyl) -1-propynyl} -1,4-dihydroxy-2,3,5,6-
Thus, tetrachloro-cyclohexa-2,5-diene (hereinafter abbreviated as compound (2)) was obtained. Specific rotation, elemental analysis value and melting point are as follows.

Specific rotation: [α] _D = -51.9 ° (c 1.1, methanol) Elemental analysis: Analytical value C 59.21, H 3.15, Calculated value C 59.13, H 3.03 Melting point: 189-191 ° C. (-) Was obtained in the same manner as in Example 1 except that 2,3,5,6-tetrabromo-2,5-cyclohexadiene-1,4-dione was used instead of 5-cyclohexadiene-1,4-dione. -1,4-bis {(3- (2-chlorophenyl) -3-hydroxy-3-phenyl) -1-propynyl} -1,4-dihydroxy-2,3,5,6-
Thus, tetrabromo-cyclohexa-2,5-diene (hereinafter abbreviated as compound (3)) was obtained. Specific rotation, elemental analysis value and melting point are as follows.

Specific rotation: [α] _D = -48.1 ° (c 0.51, methanol) Elemental analysis: Analytical value C 47.66, H 2.48, Calculated value C 47.56, H 2.44 Melting point: 185-187 ° C. Example 4 Example Compound (2) (0.52 g, 0.71 mmol) obtained in Step 2 and 2-methylpiperazine represented by the following formula (IV) (0.29
g, 2.84 mmol) was dissolved in toluene (10 ml) by heating, and then allowed to stand at room temperature for 12 hours.
1: 2 complex (0.55) of the (+) form of the compound represented by (IV)
g) was obtained. When the crystals were heated to 200 ° C. under reduced pressure (15 mmHg), 2-methylpiperazine having a specific rotation [α] _D of + 5.4 ° (c 0.35, methanol) was obtained. This specific rotation corresponded to 100% ee.

[0030]

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Example 5 The compound (2) (0.52 g, 0.71 mmol) obtained in Example 2 and 1,2-diaminopropane (0.1%) represented by the following formula (V) were used.
21 g, 2.84 mmol) was dissolved in toluene (10 ml) by heating, and the mixture was allowed to stand at room temperature for 12 hours to give the compound (2) and the (+) form of the compound represented by the following formula (V) in a ratio of 1: 2. Complex (0.
55 g) were obtained. When the compound (2) and the compound represented by the following formula (V) are separated by heating the crystal under reduced pressure, the specific rotation [α] _D is + 32.1 ° (c 0.37, benzene). 2-Diaminopropane was obtained. This specific rotation corresponded to 100% ee.

[0032]

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Example 6 The compound (2) (0.52 g, 0.71 mmol) obtained in Example 2 and 1-phenylethanol (0.35 g) represented by the following formula (VI) were used.
g, 2.84 mmol) was dissolved in toluene (10 ml) by heating, and then allowed to stand at room temperature for 12 hours.
A 1: 2 complex (0.55) of the (-) form of the compound represented by (VI)
g) was obtained. The compound (2) is separated from the compound represented by the following formula (VI) by heating the crystals under reduced pressure. The specific rotation [α] _D is −35.2 ° (c 0.52, methanol). Ethanol was obtained. This specific rotation was equivalent to 95% ee.

[0034]

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Example 7 Compound (2) (0.52 g, 0.71 mmol) obtained in Example 2 and 2-methylcyclopentanone (0.28 g, 2.84 mmol) represented by the following formula (VII) were dissolved in toluene ( 10 ml), and left to stand at room temperature for 12 hours to obtain a 1: 2 complex (0.55 g) of the compound (2) and the (-) form of the compound represented by the following formula (VII). Was. The compound (2) and the compound represented by the following formula (VII) are separated by heating the crystal under reduced pressure. The specific rotation [α] _D is -91.7 ° (c 0.35, methanol). Cyclopentanone was obtained. This specific rotation was equivalent to 83% ee.

[0036]

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──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07C 29/42 C07C 29/42 // C07C 29/78 C07C 29/78 C07M 7:00

Claims (6)

[Claims] 1. An optically active 1, represented by the following formula (I):
4-bis {(3- (2-chlorophenyl) -3-hydroxy-3-phenyl) -1-propynyl} -1,4-dihydroxycyclohexa-2,5-diene. Embedded image 2. An optically active 1, represented by the following formula (II):
4-bis {(3- (2-chlorophenyl) -3-hydroxy-3-phenyl) -1-propynyl} -1,4-dihydroxy-2,3,5,6-tetrachloro-cyclohexa-2,5- Diene. Embedded image 3. An optically active 1, represented by the following formula (III):
4-bis {(3- (2-chlorophenyl) -3-hydroxy-3-phenyl) -1-propynyl} -1,4-dihydroxy-2,3,5,6-tetrabromo-cyclohexa-2,5-diene . Embedded image 4. An optically active 1- (2-chlorophenyl)
-1-phenyl-2-propyn-1-ol and 2,5
-Cyclohexadiene-1,4-dione, 2,3,5
6-tetrachloro-2,5-cyclohexadiene-1,
4-dione or 2,3,5,6-tetrabromo-2,
The method for producing an optically active hydroquinone derivative according to any one of claims 1 to 3, wherein 5-cyclohexadiene-1,4-dione is reacted. 5. An optical isomer separation method, comprising separating an optical isomer using the optically active hydroquinone derivative according to claim 1. 6. The method for separating optical isomers according to claim 5, wherein an optically active hydroquinone derivative is used as a host compound, and one optically active substance is separated from the racemic compound.