JP2907602B2 - Optically active fluorinated alcohol - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an optically active fluorinated alcohol, and more particularly to various chemicals, industrial chemicals,
The present invention relates to an optically active fluorine-containing alcohol useful as a raw material for ferroelectric liquid crystals.

[0002]

2. Description of the Related Art
Various optically active alcohols having a fluoroalkyl group on an asymmetric carbon are known. For example, J. O
rg. Chem., Vol. 52, No. 15, p. 3211 (1987)

[0003]

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(Wherein Ph represents a phenyl group). Also, Japanese Patent Application Laid-Open No. 2-4
No. 9742 discloses that

[0005]

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An optically active fluorinated alcohol having a cyclopropane ring represented by the formula: And J. Org. Chem., Vol. 56, No. 1, p. 2-4 (1991)

[0007]

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A fluorine-containing alcohol represented by the formula: Further, JP-A-3-11025 discloses that

[0009]

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A fluorine-containing alcohol represented by the formula (1) is disclosed. Under such circumstances, the present inventors have conducted intensive studies with the aim of developing optically active fluorinated alcohols that are promising as new types of liquid crystals and the like.

[0011]

As a result, a novel compound in which a fluoroalkyl group having a large electron-withdrawing property is bonded to an asymmetric carbon having a cycloalkyl group is suitable for the above object, Further, they have found that such a compound can be obtained with high optical purity by asymmetric hydrolysis using an enzyme. The present invention has been completed based on such findings. That is, the present invention provides a compound represented by the general formula (I)

[0012]

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(Wherein Rf is a trifluoromethyl group,
Difluoromethyl group, chlorodifluoromethyl group or
Shows a pentafluoroethyl group . The present invention provides an optically active fluorine-containing alcohol represented by the following formula:

[0014] In the general formula (I), Rf is, triflic
Oromethyl group, difluoromethyl group, chlorodifluoro
A methyl group or a pentafluoroethyl group , preferably a trifluoromethyl group. In the fluorinated alcohol of the present invention, these fluoroalkyl groups are bonded to an asymmetric carbon having a cycloalkyl group. here,
As the cycloalkyl group bonded on the asymmetric carbon, a cyclopentyl group is preferable.

The fluorinated alcohol represented by the general formula (I) of the present invention can be produced by various methods. For example, it can be produced by the following method.
First, an aldehyde represented by the general formula (II) Rf-CHO (II) (where Rf is the same as described above) and a general formula (III)

[0016]

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Is reacted with a Grignard reagent represented by the following formula (IV):

[0018]

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(Wherein Rf is the same as described above) to obtain a racemic fluorine-containing alcohol represented by the formula: In this production method, examples of the aldehyde represented by the general formula (II) used as a starting material include CF ₃ C
HO, CHF ₂ CHO, CClF ₂ CHO, C ₂ F ₅ CHO and the like can be used. The above reaction is carried out in a solvent such as diethyl ether or tetrahydrofuran at -78 ° C to normal temperature. Further, as another method described above, a fluorine-containing alkyl ester represented by the general formula (V) RfCOOR ¹ ... (V) (wherein Rf is the same as above and R ¹ represents an alkyl group) Reacting with a Grignard reagent represented by the above general formula (III) to obtain a compound of the general formula (VI)

[0020]

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(In the formula, Rf is the same as described above.) After reducing to a ketone represented by the formula, the fluorinated alcohol represented by the general formula (IV) can also be obtained. In this production method, examples of the fluorinated alkyl ester represented by the general formula (V) used as a starting material include CF ₃ CO ₂ C ₂ H ₅ and CHF ₂ CO ₂ C
_{2 H 5, CClF 2 CO 2} CH 3, C 2 F 5 CO 2 C 2 H 5 and the like can be used.

In the reduction of the ketone represented by the general formula (VI), a reducing agent usually used for reducing a C ＝ O bond to a CHOH bond, for example, sodium borohydride, lithium aluminum hydride, secondary chloride Tin or the like can be used.

Next, the obtained fluorinated alcohol represented by the general formula (IV) is converted into a compound represented by the general formula (VII) R ² COX (VII) (where R ² is an alkyl group or Represents a phenyl group,
X represents a halogen. By reacting with an acid halide represented by the general formula (VIII)

[0024]

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(Wherein Rf and R ² are the same as described above). Here, specific examples of the acid halide used as the acylating agent include acetyl chloride, propionyl chloride, isobutyroyl chloride, octanoyl chloride, benzoyl chloride, acetyl bromide, and propionyl bromide. The resulting acylated product represented by the general formula (VIII) is subjected to asymmetric hydrolysis using an enzyme to give the general formula (I)

[0026]

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(In the formula, Rf is the same as described above.) The optically active fluorinated alcohol of the present invention represented by the formula (1) can be obtained. At the same time, the general formula (IX)

[0028]

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(Wherein Rf and R ² are the same as described above). As the enzyme used in the asymmetric hydrolysis reaction using this enzyme, various enzymes can be used as long as they are so-called hydrolases. For example, Lipase PS, Lipase MY,
Lipase OF, cellulase and the like can be mentioned. The optically active ester (IX) can be converted into the fluorinated alcohol of formula (I) and the enantiomer by chemical hydrolysis or asymmetric hydrolysis by another enzyme.

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[0031]

[0032]

[0033]

[0034]

[0035]

[0036]

EXAMPLES Next, the present invention embodiment, in more detail
explain. Example 1 Synthesis of (+)-2,2,2-trifluoro-1-cyclopentylethanol

(A) 14.2 g of ethyl trifluoroacetate
To 100 ml of a solution of (100 mmol) of diethyl ether, 80 ml of a diethyl ether solution of a Grignard reagent prepared from 11.8 ml (110 mmol) of bromocyclopentane was added dropwise at -78 ° C. After reacting for 16 hours, 1N-hydrochloric acid was added to stop the reaction. After extraction with diethyl ether, distilled water
Washed with brine and dried over anhydrous magnesium sulfate
Thereafter, the solvent was distilled off to obtain a crude purified product of trifluoromethylcyclopentyl ketone.

(B) The crude product obtained in the above (a) was dissolved in 50 ml of ethanol, and 1.13 g (30 mmol) of sodium borohydride was dissolved in ethanol solution 5.
It was added dropwise at 0 ° C. to the solution suspended in 0 ml. After reacting at room temperature for 23 hours, ethanol is distilled off
The reaction was stopped by adding 1N hydrochloric acid,
Extracted by tell. After washing with distilled water and saturated saline,
After drying over magnesium sulfate and evaporating the solvent,
Isolated and purified by distillation to 2,2,2-trifluoro -1
-6.8 g of cyclopentylethanol (40.8 mmol)
I got

(C) Compound 1.6 obtained in (b) above
In 30 ml of a 7 g (10 mmol) methylene chloride solution, 1.2 ml of pyridine and 1 ml of acetyl chloride were added.
Milliliter (14.1 mmol) was added and reacted at room temperature for 18 hours. The reaction was quenched by the addition of 1N- hydrochloric acid salt
After extraction with methylene chloride, wash with distilled water and saturated saline.
Was. After drying over anhydrous magnesium sulfate, the solvent was distilled off.
Thereafter, the residue was purified by column chromatography to obtain 0.94 g (4.5 mmol) of an acetylated product.

(D) The acetylated product obtained in the above (c) is suspended in 50 ml of distilled water, and lipase M
1.13 g of Y was added and stirred at 40 ° C. The pH was maintained at 6 to 7 while adding a 1N aqueous sodium hydroxide solution to 8.5.
Allowed to react for hours. The reaction solution was filtered through celite to remove the enzyme. After separating the oil phase and washing with saturated saline, anhydrous sulfuric acid
Dried over magnesium acid. After evaporating the solvent, the silica
Alcohol and acetyl by gel column chromatography
The purified product was separated and purified . 0.06 g of optically active alcohol
And 0.22 g of unreacted acetylated product was obtained. The specific rotation and optical purity of the obtained alcohol were as follows.

[Α] _D ²⁵ = 18.7 ° (c = 0.71; CHCl ₃ ) Optical purity 90% ee Physical properties are shown below. Molecular formula C ₇ H ₁₁ F ₃ O ¹ H-NMR (CDCl ₃ ); δ (ppm) 1.3 to 2.0 (m, 8H), 2.1 to 2.3 (m, 1H) 3.8 (dq, J = 7.0, 7.0 Hz, 1H ) ¹⁹ F-NMR (based on CFCl ₃ ) δ; (ppm) -78.1 (d, J = 7.0 Hz) IR (neat) (cm ⁻¹ ) 3400, 2980, 2890

Example 2 Example 1 was repeated except that the enzymes were changed as shown in Table 1.
The asymmetric hydrolysis reaction was carried out in the same manner as described above. The results obtained are shown in Table 1 together with the results of Example 1.

[0043]

[Table 1]

[0044]

[Table 2]

[0045]

According to the present invention, a novel optically active compound having a fluoroalkyl group having a large electron-withdrawing property and a cycloalkyl group on an asymmetric carbon can be obtained. These compounds are expected to be widely used as raw materials for enzyme inhibitors, bioactive substances, anticancer agents, ferroelectric liquid crystals, and the like.

──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Mitsunori Takeda 4th Towada, Kamisu-cho, Kashima-gun, Ibaraki Pref. Kashima Oil Company Kashima Refinery (56) References Org. Chem. , 1980, 45 (8), p. 1379-1382 J.P. C. S. Chem. Comm. , 1978, p. 456-457 (58) Fields investigated (Int. Cl. ⁶ , DB name) C07C 31/44 CA (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] 1. A compound of the general formula (I) ( Wherein , Rf is a trifluoromethyl group,
Tyl, chlorodifluoromethyl or pentafluoro
Represents a roethyl group . An optically active fluorinated alcohol represented by). 2. The method of claim 2, wherein the fluorinated alcohol is 2,2,2-triol.
A fluoro-1-cyclopentyl ethanol.
2. The optically active fluorine-containing alcohol according to 1.