JP2808544B2 - Optically active compound and method for producing the same - Google Patents

Description

The present invention relates to a novel optically active compound and a method for producing the same. More specifically, the present invention relates to a novel optically active compound useful as a raw material for synthesizing a chiral dopant added as a component of a liquid crystal mixture or as a raw material for medicines, agricultural chemicals, and the like, and a method for producing the same.

[Prior Art] Conventionally, it has been known that a liquid crystal mixture having a high response speed can be obtained by adding a chiral compound having no optical property but having no liquid crystal properties to a smectic liquid crystal or a nematic liquid crystal. ing. Since the performance of this liquid crystal mixture varies greatly depending on the type of the optically active compound and the liquid crystal monomer used and their composition ratio or compatibility, the range of searching for liquid crystal materials is expanded,
There is an increasing demand for optically active compounds for obtaining liquid crystal mixtures meeting the respective purposes.

However, it is generally difficult to obtain optically active compounds except for amino acids, organic acids, sugars and the like which are relatively easily available by fermentation by microorganisms or as natural products. In particular, a technique for obtaining an optically active compound which is used by being added to the smectic liquid crystal or nematic liquid crystal and has high compatibility with the smectic liquid crystal or nematic liquid crystal has not been completed.

That is, the conventional method of synthesizing an optically active compound by a biochemical technique or an organic chemical technique has a narrow application range and has the following drawbacks.

For example, biochemical techniques include asymmetric synthesis using baker's yeast and dehydrogenase. In this method, the chemical yield,
The optical purity tends to be remarkably reduced, while a compound that does not dissolve in water has no significance using these methods.

As another biochemical method, there is a method of performing asymmetric transesterification reaction of tributyrin with a secondary alcohol using lipase in an organic solvent. Since the active compound is limited to butyl ester, there is a disadvantage that several steps of synthesis are required to obtain the target compound.

On the other hand, when using an organic chemistry method, the optical purity and the chemical yield are low depending on the substrate used, and the obtained optically active compounds are often limited to those having a low molecular weight. Alternatively, it is difficult to synthesize an optically active compound that can be used to prepare a liquid crystal mixture by adding to a nematic liquid crystal.

[Problems to be Solved by the Invention] One of the objects of the present invention is that an optically active compound which has good compatibility with existing smectic liquid crystals or nematic liquid crystals and can give a liquid crystal mixture having a large Ps value can be easily produced. Another object is to provide a raw material for an optically active compound, and to provide a method for easily producing the useful optically active compound.

[Means for Solving the Problems] The present invention provides a compound represented by the general formula (I): (Wherein A is a tetrahydro-2-pyranyl group or 1-
An optically active compound represented by an ethoxyethyl group) (hereinafter, the (R) -form alcohol represented by the general formula (I) is represented by (R)-(I) alcohol, and the (S) -form alcohol is represented by (S)- General formula (II): (Wherein A is a tetrahydro-2-pyranyl group or 1-
An ethoxyethyl group, wherein R ¹ represents an alkyl group having 1 to 15 carbon atoms (hereinafter, represented by formula (II)
(R)-(II) ester, (S) -form ester also referred to as (S)-(II) ester) represented by the general formula (IV): (Wherein A is a tetrahydro-2-pyranyl group or 1-
A fatty acid ester of racemic alcohol and 2,2,2-trichloroethanol represented by an ethoxyethyl group (having 2 to 16 carbon atoms in the fatty acid) or the general formula (V): H ₂ C = CR ² -O-CO- R ³ (V) (wherein, R ² is a hydrogen atom or a methyl group, and R ³ is
An alkyl group of 8) is reacted with an enzyme having esselase activity on a vinyl fatty acid ester represented by the formula:
A method for producing an optically active (R) ester compound, which comprises selectively converting only the (R) form of a racemic alcohol into an ester compound and then separating the unreacted (S) form of the alcohol, General formula (IV): (Wherein A is a tetrahydro-2-pyranyl group or 1-
Racemic alcohols represented by showing the ethoxyethyl group) and 2,2,2-trichloroethanol fatty acid esters (number of carbon atoms in the fatty acid 2 to 16) or the general formula _{(V): H 2 C =} CR 2 -O-CO- R ³ (V) (wherein, R ² is a hydrogen atom or a methyl group, and R ³ is
A mixture of vinyl fatty acid esters represented by the formula (8), wherein an enzyme having esselase activity is allowed to act on the mixture to selectively convert only the (R) form of racemic alcohol into an ester compound, And a process for producing an optically active (S) alcohol.

[Example] The optically active compound of the present invention has the general formula (I): An optically active compound represented by the following general formula (II): Which are represented by the general formula (III): (Wherein, R ¹ represents an alkyl group having 1 to 15 carbon atoms). That is, in order to lead the optically active alcohol of the general formula (I) to the optically active ester represented by the general formula (II) in which only the hydroxyl group at the asymmetric point is esterified, the hydroxyl group on the aromatic nucleus is substituted with the substituent A. Protected. The general formula (II)
The optically active ester represented by the formula (1) can easily lead to the optically active compound represented by the general formula (III) except for the substituent A alone by hydrolysis.

Therefore, the substituent A must be easily removed, and must not break the ester bond when the substituent A is removed. Therefore, in the present invention, the substituent A is limited to a tetrahydro-2-pyranyl group or a 1-ethoxyethyl group. In the case of a substituent other than these, it is difficult to obtain a compound represented by the general formula (III).

To remove the substituent A, for example, a mixed solvent of acetic acid / dioxane / water is used.

In the optically active compounds represented by the general formulas (II) and (III), R ¹ has 1 to 15 carbon atoms, preferably 2 to 2 carbon atoms.
12 alkyl groups, and the alkyl group may have an asymmetric carbon. If the carbon number of R ¹ exceeds 15, it is difficult to expect favorable performance as a liquid crystal when the compound is derived into a liquid crystal. Also, when R ¹ is other than an alkyl group, it is difficult to expect favorable performance as a liquid crystal.

The term “alkyl group” as used herein is a concept including a halogenated alkyl group in which a hydrogen atom is substituted by a halogen atom, and a group including an alkyl group having an ether bond, an ester bond, and the like. An asymmetric carbon may be present therein.

The optically active compound represented by the general formula (III) is useful as a raw material for synthesizing a chiral dopant having high compatibility with many existing liquid crystal substances. In particular, the following compounds may be mentioned as chiral dopants for smectic liquid crystals or nematic liquid crystals, and these compounds have the general formula (II)
A large Ps value can be realized in a smectic phase or a nematic phase which is produced by using the compound represented by (I) and can be considered to use the produced compound, and a desired helical pitch can be realized.

(R in the above formula is an alkyl group having 1 to 15 carbon atoms.) Furthermore, any of the optically active compounds of the present invention can be suitably used as a raw material for medicines, agricultural chemicals, fragrances and the like.

Next, a method for producing the optically active compounds represented by formulas (I) to (II) of the present invention will be described.

The optically active compound represented by the general formula (I) or (II) is represented by the general formula (IV): (Wherein, A is the same as described above). That is, the optically active alcohol represented by the general formula (I) is an alcohol of the (R) form or an alcohol of the (S) form, and the optically active ester represented by the general formula (II) is represented by the above general formula (I). Fatty acid ester corresponding to the optically active alcohol used.

In the production method of the present invention, as described above, a racemic alcohol represented by the general formula (IV) and a fatty acid ester of 2,2,2-trichloroethanol (fatty acid having 2 to 16 carbon atoms) or a general formula (V): H ₂ ^{C = CR 2 -O-CO-} R 3 (V) ( wherein, R ² is a hydrogen atom or a methyl group, R ³ is 1 to carbon atoms
The reaction with a vinyl fatty acid ester represented by the formula (8) is carried out in an organic solvent using an enzyme having esterase activity.

Since the enzyme having esterase activity selectively esterifies only the (R) form of racemic alcohol, the reaction yields (R)-(II) ester and (S)-(I) alcohol. The (R)-(II) ester is KOH, N
by hydrolysis of aOH with caustic (R)
The (S)-(I) alcohol can be converted to the (S)-(II) ester by esterification.

The method for obtaining the racemic alcohol represented by the general formula (IV) is not particularly limited, and may be any method as long as the compound can be obtained.

For example, when the substituent A in the general formula (IV) is an ethoxyethyl group, use
When the substituent A is a tetrahydro-2-pyranyl group, dihydropyran When the hydroxyl group of p-hydroxyacetophenone is protected by using and reduced with sodium borohydride or the like, a racemic alcohol represented by the general formula (IV) is obtained.

2,2,2-Trichloroethanol fatty acid ester or general formula (V): H ₂ C = CR ² —O—CO—R ³ (V) (wherein R ² is a hydrogen atom or a methyl group, R ³ Has 1 to 1 carbon atoms
The vinyl fatty acid ester represented by the formula (8) is used as an acylating agent. These, number of carbon atoms in the fatty acid of the general formula for example (II), to correspond to the value of the number of carbon atoms in R ¹ of the compound represented by (III), object by appropriately selected and used the number of carbon atoms of the fatty acid The corresponding compound is obtained.

Specific examples of the fatty acid ester of 2,2,2-trichloroethanol include, for example, 2,2,2-trichloroethyl acetate, 2,2,2-trichloroethyl butyrate,
2,2-trichloroethylheptanoate and the like.

Further, specific examples of the vinyl fatty acid ester include:
For example, isopropenyl acetate, vinyl acetate, vinyl ballate, vinyl octanoate and the like can be mentioned.

Although the reason why the fatty acid ester of 2,2,2-trichloroethanol has 2 to 16 carbon atoms in the fatty acid ester has already been described, the alkyl group (R ³ ) of the vinyl fatty acid ester represented by the general formula (V) has been described. Is 1 to 8 because
This is because it is difficult to synthesize the vinyl fatty acid ester represented by the general formula (V) having R ³ of 9 or more, which is economically disadvantageous.

The term "enzyme having esterase activity" refers to any enzyme capable of esterifying only the (R) form of the racemic alcohol represented by the general formula (IV) to an asymmetric point in an organic solvent using an acylating agent. Can be used without restrictions,
It may be derived from microorganisms, derived from animals, or commercially available, or not commercially available. Specific examples of such enzymes include, for example, Pseudomonas aeruginos, which is an enzyme derived from a microorganism.
a) such as Pseudomonas, Achromobacterium
Achromobacterium genus such as Achromobacterium viscosm, Candida cylindrace (Cand
For example, enzymes derived from microorganisms belonging to the genus Candida such as C. ida Cylindracea), and enzymes derived from animals include enzymes produced from pig pancreas, but are not limited thereto.

Commercial products of these enzymes include, for example, lipase "Amano" P (trade name, manufactured by Amano Pharmaceutical Co., Ltd.), Lipase Toyo (trade name, manufactured by Toyo Brewery Co., Ltd.), pancreatin lipase (Amano Pharmaceutical Co., Ltd.) Pancreatin lipase (product name, manufactured by Sigma), lipase B (product name, manufactured by Wako Pure Chemical Industries, Ltd.), Lipase MY (product name, manufactured by Meito Sangyo Co., Ltd.) And so on.

The organic solvent used in the production method of the present invention has the general formula (IV)
Can be used without particular limitation as long as it satisfies such requirements as dissolving the racemic alcohol and the acylating agent represented by the formula (1) and not inhibiting the enzyme activity of the enzyme having esterase activity. Specific examples of such an organic solvent include, for example, diethyl ether, methyl ethyl ether, diisopropyl ether, n-hexane, cyclohexane, n-heptane, and toluene.

The method for preparing an organic solvent containing a racemic alcohol represented by the general formula (IV), an acylating agent and an enzyme having esselase activity in the present invention is not particularly limited. For example, a racemic alcohol represented by the general formula (IV), It may be prepared by adding an agent having an esterifying activity and an enzyme having an esterase activity to an organic solvent, or may be prepared by dissolving them separately or by mixing a liquid obtained by dispersing them. It may be prepared by dissolving only those which can be obtained first and then adding other ones.

The use ratio of the racemic alcohol represented by the general formula (IV) and the acylating agent is preferably 0.5 to 2.0 mol per 1 mol of the racemic alcohol represented by the general formula (IV), and 1 to 1.5 mol. More preferably, it is used in molar. When the use ratio is less than 0.5 mol, since the molar amount is smaller than that of the (R) form of the racemic alcohol represented by the general formula (IV), all of the (R) form cannot be esterified, On the other hand, if the amount exceeds 2.0 moles, the ratio of the acylating agent used not participating in the reaction increases, so that the economic efficiency decreases.

The amount of the enzyme having an esterase activity to be used is preferably 10 to 600 g, more preferably 100 to 500 g, per 1 mol of the compound represented by the general formula (IV). When the amount used is 10 g or less, the reaction rate is low, which is economically disadvantageous. When the amount is more than 600 g, the enzyme becomes excessive in comparison with the reaction rate, which is economically disadvantageous.

Further, the ratio of the total amount of the racemic alcohol represented by the general formula (IV) and the acylating agent used is 0.1 to 50% (% by weight, based on the weight of a solution obtained by dissolving them in an organic solvent.
The same applies hereinafter), and more preferably 10 to 30%. When the use ratio is less than 0.1%, the yield is small relative to the amount of the reaction solution, which is economically disadvantageous. Also 50
%, The concentration is too high, so that the reaction rate decreases and the yield decreases.

In the production method of the present invention, to use an enzyme having an esterase activity, usually 10 ~ 40 ℃, preferably 25 ~ 30 ℃
Is employed.

The reaction time depends on the type of racemic alcohol represented by the general formula (IV) or the enzyme having esterase activity, and the general formula (I
It varies depending on the use ratio of the compound represented by V), the acylating agent and the enzyme having esterase activity, the stirring state, and the like, and cannot be specified unconditionally, but is usually 1 to 150 hours, preferably about 24 to 96 hours.

The end of the reaction is determined by gas chromatography using the general formula (I
The conversion of the racemic alcohol to the ester represented by V) is measured and is confirmed by the fact that the conversion is constant.

From the reaction mixture thus obtained, first, an enzyme having an esterase activity is removed by filtration or the like. after that,
After removing the organic solvent and the like, if necessary, it is separated into (R)-(II) ester and (S)-(I) alcohol by, for example, silica gel chromatography. further,
When the separated product contains an alcohol or the like or an unreacted acylating agent produced by the acylation reaction, the product may be purified by a method such as distillation. As a developing solvent for column chromatography, for example, a mixed solution of ethyl acetate / n-hexane (ethyl acetate / n-hexane in a volume ratio of 1/4 to 1/20), a mixed solution of chloroform / methanol (chloroform / n-hexane) It is preferable to use methanol having a volume ratio of 1/10 to 1/40).

Further, the separated enzyme having an esterase activity can be reused.

The identification is performed by measuring a ¹ H-NMR spectrum, an IR spectrum, a specific rotation, and the like.

Further, the obtained (R)-(II) ester is easily an enantiomer of (S)-(I) alcohol when hydrolyzed by an enzymatic or chemical method or the like.
(I) It can be alcohol. Further, (S)-(I) alcohol can be converted into (S)-(II) ester which is a mirror image of (R)-(II) ester by esterification.

Thus, the optically active compound represented by the general formula (I) or (II) can be obtained in a yield of 80 to 90%.

 Next, the present invention will be described based on examples.

Production Example 1 Synthesis of 1- (4- (1-ethoxyethoxy) phenyl) ethanol (i) Synthesis of 4- (1-ethoxyethoxy) acetophenone 13.6 g (0.1 mol) of p-hydroxyacetophenone and ethyl in 100 ml of diethyl ether Vinyl ether was dissolved, 1 ml of concentrated hydrochloric acid was added, the mixture was refluxed for 4 hours, and further reacted at room temperature for 16 hours. After the reaction is completed, the reaction mixture is
Was washed twice with 50 ml of a sodium hydroxide solution and then three times with water. After the ether phase was dried over magnesium sulfate, the ether was distilled off under reduced pressure to obtain 20.5 g of oily 4- (1-ethoxyethoxy) acetophenone (yield: 92).
%).

The result of ¹ H-NMR spectrum analysis of the obtained compound was as follows. ¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 1.72 (t, 3H), 1.51 (d, 3H), 2.52 (s, 3H), 3.50 (m, 1H), 3.72 (m, 1H) , 5.48 (q, 1H), 6.95 (d, 2H), 7.88 (d, 2H) (ii) 1- (4- (1-ethoxyethoxy) phenyl)
It was example in the synthesis of ethanol (i) 4-(1-ethoxyethoxy) acetophenone 15.0g (72 mmol) was dissolved in ethanol 100 ml, was NaBH ₄ 2.2 g (58 mmol) reacted for 5 hours by adding. After the completion of the reaction, ethanol was distilled off under reduced pressure, and then 200 ml of ether was added, followed by washing with diluted hydrochloric acid, water and an aqueous solution of sodium hydrogen carbonate in this order. After the ether layer was dried over magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 13.6 g of 1-.
(4- (1-Ethoxyethoxy) phenyl) ethanol was obtained (yield 90%).

The result of ¹ H-NMR spectrum analysis of the obtained compound was as follows.

¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 1.17 (t, 3H), 1.44 (d, 3H), 1.46 (d, 3H), 1.93 (s, 1H), 3.52 (m, 1H) , 3.76 (m, 1H), 4.82 (m, 1H), 5.34 (q, 1H), 6.94 (d, 2H), 7.27 (d, 2H) Example 1 1- (4-ethoxyethoxy) phenyl) ethanol Optical resolution (i) Asymmetric transesterification with 2,2,2-trichloroethyl butyrate 21 g (0.1 mol) of 1- (4- (1-ethoxyethoxy) phenyl) ethanol in 120 ml of anhydrous diethyl ether,
22.4 g (0.1 mol) of 2,2,2-trichloroethyl butyrate
And 25.2 g of Lipase P (manufactured by Amano Pharmaceutical Co., Ltd.)
Stirred at 5 ° C for 90 hours. After completion of the reaction, the lipase was removed by suction filtration, and the filtrate was concentrated and purified by silica gel chromatography (ethyl acetate / n-hexane = 1/4 (volume ratio, the same applies hereinafter)) to give the (S) form of 1- ( 9.6 g of 4- (1-ethoxyethoxy) phenyl) ethanol (yield 91
%) And (R) form of 1- (4- (1-ethoxyethoxy (phenyl) ethylbutyrate) (13.0 g, yield 93%).

The results of ¹ H-NMR analysis, 1R spectrum analysis and specific rotation analysis of the obtained compound were as follows.

1- (4- (1-ethoxyethoxy) phenyl) ethanol ((S) form) ¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 1.17 (t, 3H), 1.44 (d, 3H), 1.46 (d, 3H), 1.93 (s, 1H), 3.52 (m, 1H), 3.76 (m, 1H), 4.82 (m, 1H), 5.34 (q, 1H), 6.94 (d, 2H), 7.27 (D, 2H) FT-IR (cm ^-1 ) 3398,2974,2931,2889,1612,1512,1446,1381,1342,1238,1176,1134,1118,1076,1049,1010,954,898,837. [Α] ▲ ²⁰ _D ▼ = -36.1 ゜ (CHCl ₃ , c = 1) 1- (4- (1-ethoxyethoxy) phenyl) ethyl butyrate ((R) form) ¹ H-NMR (300 MHz, CDCl ₃ , δ value) (Ppm)) 0.90 (t, 3H), 1.19 (t, 3H), 1.47 (d, 3H), 1.49 (d, 3H), 1.62 (m, 2H), 2.27 (t, 2H), 3.51 (m, 1H), 3.76 (y, 1H), 5.35 (9, 1H), 5.84 (q, 1H), 6.94 (d, 2H), 7.26 (d, 2H) FT-IR (cm- ¹ ) 2974, 2935, 2877 , 1735,1612,1585,1512, 1454,1419,1381,1346,1288,1176,1134, 1099,1076,1060,1014,1003,941,898,833, 551 [α] ▲ 20 D = 84.0 ° _{(CHCl 3, c = 1)} (ii) 2,2,2- trichloroethyl Hebbian Tano 2,2,2 instead asymmetric transesterification 2,2,2-trichloroethyl butyrate according benzoate
-Similar method to (i) of Example 1 except that trichloroethylheptanoate was used.
9.5 g of ethoxyethoxy) phenyl) ethanol (yield 90
%) And 14.8 g of the (R) form of 1- (4- (1-ethoxyethoxy) phenyl) ethylheptanoate (yield 92
%).

The results of ¹ H-NMR analysis, IR spectrum analysis and specific rotation analysis of the obtained compound were as follows.

The results of 1- (4- (1-ethoxyethoxy) phenyl) ethanol ((S) form) ¹ H-NMR analysis and FT-IR analysis were the same as those of Example 1 (i).

_{^{[Α] ▲ 20 D ▼ =}} -36.1 ° _{(CHCl 3, c = 1)} 1- (4- (1- ethoxyethoxy) phenyl) ethyl heptanoate ((R) ^{body) 1 H-NMR (300MHz,} CDCl ₃ , δ value (ppm)) 0.84 (t, 3H), 1.19 (t, 3H), 1.24 (m, 6H), 1.47 (d, 3H), 1.49 (d, 3H), 1.58 (m, 2H), 2.28 (t, 2H), 3.49 (m, 1H), 3.76 (m, 1H), 5.35 (q, 1H), 5.83 (q, 1H), 6.94 (d, 2H), 7.25 (d, 2H) FT− IR (cm ^-1 ) 2978,2958,2931,2870,2858,1735,1612,1585,1512,1454,1419,1377,1342,1288,1238,1168,1134,1118,1099,1076,1057,1014, 1003,941,898,833,551 [α] ▲ ²⁰ _D ▼ = +69.0 Cl (CHCl ₃ , c = 1) (iii) Asymmetric transesterification with vinyl balalate Vinyl balalate instead of 2,2,2-trichloroethyl butyrate 9.8 g (93% yield) of 1- (4- (1-ethoxyethoxy) phenyl) ethanol in the (S) form was obtained in the same manner as in (i) of Example 1 except that Thus, 11.8 g (yield 94%) of 1- (4- (1-ethoxyethoxy) phenyl) ethyl valerate of the (R) form was obtained.

The results of ¹ H-NMR analysis, IR spectrum analysis and specific rotation analysis of the obtained compound were as follows.

The results of 1- (4- (1-ethoxyethoxy) phenyl) ethanol ((S) form) ¹ H-NMR analysis and FT-IR analysis were the same as those in Example 1 (i).

_{^{[Α] ▲ 20 D ▼ =}} -36.1 ° _{(CHCl 3, c = 1)} 1- (4- (1- ethoxyethoxy) phenyl) ethyl Rose Les rate ((R) ^{body) 1 H-NMR (300MHz,} CDCl ₃ , δ value (ppm)) 0.86 (t, 3H), 1.19 (t, 3H), 1.26 (m, 2H), 1.47 (d, 3H), 1.49 (d, 3H), 1.59 (m, 2H), 2.28 (t, 2H), 3.50 (m, 1H), 3.76 (m, 1H), 5.35 (q, 1H), 5.83 (q, 1H), 6.94 (d, 2H), 7.25 (d, 2H) FT- IR (cm ^-1 ) 2974,2935,2877,1735,1612,1585,1512,1454,1419,1381,1346,1288,1238,1176,1134,1099,1076,1060,1014,1003,941,898,833,551 [ _{^{α] ▲ 20 D ▼ = +}} 80.2 ° _{(CHCl 3, c = 1)} (iv) (R) body 1- (4- (1-ethoxyethoxy)
Synthesis of phenyl) ethanol 1- (4-) of the (R) form obtained in (i) of Example 1
(1-ethoxyethoxy) phenyl) ethyl butyrate
28 g (0.1 mol) of 1N potassium hydroxide in ethanol 21
After dissolving in 0 ml and reacting at room temperature overnight, the reaction mixture was concentrated under reduced pressure. 200 ml of ether was added to the residue, and the mixture was washed twice with 50 ml of a 2N aqueous solution of sodium hydroxide and further three times with water. The ether layer was dried over magnesium sulfate, and the ether was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography (ethyl acetate / n-hexane = 1 /
Purification according to 4) gave 18.9 g of the (R) form of 1- (4- (1-ethoxyethoxy) phenyl) ethanol (yield 9).
0%).

The results of ¹ H-NMR analysis, IR spectrum analysis and specific rotation analysis of the obtained compound were as follows.

The results of ¹ H-NMR analysis and FT-IR analysis were the same as those of Example 1 (i).

_{^{[Α] ▲ 20 D ▼ =}} + 36.9 ° (CHCl _3, c = 1) Example 2 (i) (S) body 1- (4- (1-ethoxyethoxy)
Synthesis of fatty acid ester of phenyl) ethanol 0.05 mol of (S) -form 1 (4- (1-ethoxyethoxy) phenyl) ethanol obtained in Example 1 was added to pyridine.
It was dissolved in 50 ml, and 0.06 mol of acid chloride of fatty acid was slowly added dropwise. After reacting for additional hours after the end of the dropping,
The reaction mixture was concentrated under reduced pressure. 100 ml of diethyl ether was added to the residue, and the mixture was washed with dilute hydrochloric acid, water, and a 10% aqueous sodium hydrogen carbonate solution. After the ether layer was dried over magnesium sulfate, the ether was distilled off under reduced pressure to give the (S) form 1-.
A fatty acid ester of (4- (1-ethoxyethoxy) phenyl) ethanol was obtained.

The results of ¹ H-NMR analysis, FT-IR analysis, and specific rotation analysis of the obtained compound were as follows.

1- (4- (1-ethoxyethoxy) phenyl) ethyl butyrate ((S) form) ¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 0.90 (t, 3H), 1.19 (t, 3H) ), 1.47 (d, 3H), 1.49 (d, 3H), 1.62 (m, 2H), 2.27 (t, 2H), 3.51 (m, 1H), 3.76 (m, 1H), 5.35 (q, 1H) , 5.84 (q, 1H), 6.94 (d, 2H), 7.26 (d, 2H), FT-IR (cm ^-1 ) 2974, 2935, 2877, 1735, 1612, 1585, 1512, 1454, 1419, 1381, 1346, 1288, 1238, 1176, 1134, 1099, 1076, 1060, 1014, 1003, 941, 898, 833, 551 [α] ▲ ²⁰ _D ▼ = -83.5 ゜ (CHCl ₃ , c = 1) The yield was 91%.

1- (4- (1-ethoxyethoxy) phenyl) ethylhexanoate ((S) form) ¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 0.85 (t, 3H), 1.19 (t, 3H), 1.27 (m, 4H), 1.47 (d, 3H), 1.49 (d, 3H), 1.59 (m, 2H), 2.28 (t, 2H), 3.50 (m, 1H), 3.76 (m, 1H) ), 5.35 (q, 1H), 5.83 (q, 1H), 6.94 (d, 2H), 7.25 (d, 2H) FT-IR (cm- ¹ ) 2978,2958,2931,2870,1735,1612,1585 , 1512,1454,1377,1342,1288,1242,1172,1122,1057,1014,945,898,833,551 [α] ▲ ²⁰ _D ▼ = -74.0 ゜ (CHCl ₃ , c = 1) In this case, the yield was 92%.

1- (4- (1-ethoxyethoxy) phenyl) ethylheptanoate ((S) form) ¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 0.84 (t, 3H), 1.19 (t, 3H), 1.24 (m, 6H), 1.47 (d, 3H), 1.49 (d, 3H), 1.58 (m, 2H), 2.28 (t, 2H), 3.49 (m, 1H), 3.76 (m, 1H) ), 5.35 (q, 2H), 5.83 (q, 1H), 6.94 (d, 2H), 7.25 (d, 2H) FT-IR (cm ^-1 ) 2978,2958,2931,2870,2858,1735,1612 , 1585,1512,1454,1419,1377,1342,1288,1238,1168,1134,1118,1099,1076,1057,1014,1003,941,898,833,551 [α] ▲ ²⁰ _D ▼ = -68.1゜ (CHCl ₃ , c = 1) The yield in this case was 90%.

1- (4- (1-ethoxyethoxy) phenyl) ethyldecanoate ((S) form) ¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 0.85 (t, 1H), 1.19 (t, 3H), 1.23 (m, 12H), 1.47 (d, 3H), 1.49 (d, 3H), 1.58 (m, 1H), 2.28 (t, 2H), 3.54 (m, 1H), 3.75 (m, 1H) ), 5.35 (q, 1H), 5.83 (q, 1H), 6.94 (d, 2H), 7.25 (d, 2H) FT-IR (cm- ¹ ) 2978, 2954, 2927, 2854, 1735, 1612, 1585 , 1512,1458,1419,1377,1300, 1288,1238,1176,1118,1076,1057, 1014,1003, 941 , 902, 833, 551 [α] ▲ 20 D ▼ = -59.0 ° (CH ₃ Cl, c = 1) The yield in this case was 93%.

(Ii) Synthesis of fatty acid ester of 1- (4-hydroxyphenyl) ethanol of (S) form 0.1 mol of fatty acid ester of 1- (4- (1-ethoxyethoxy) phenyl) ethanol was prepared by adding acetic acid / dioxane /
Dissolve in about 200 ml of a mixed solvent of water (10/5/5) and add
After stirring for an hour and distilling off the solvent under reduced pressure, (S)
Fatty acid ester of 1- (4-hydroxyphenyl) ethanol was obtained.

The results of ¹ H-NMR analysis, FT-IR analysis, and specific rotation analysis of the obtained compound were as follows.

1- (4-hydroxyphenyl) ethyl butyrate ((S) form) ¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 0.89 (t, 3H), 1.50 (d, 3H), 1.61 (m , 2H), 2.28 (t, 2H), 5.83 (q, 1H), 6.14 (broad s, 1H), 6.77 (d, 2H), 7.20 (d, 2H) FT-IR (cm ^-1 ) 3387,2970 , 2935,2873,1732,1705, 1616,1597,1516,1450,1373,1265, 1199,1172,1091,1057, 999 , 956, 941, 833, 547 [α] ▲ 20 D ▼ = -109.8 ° ( CHCl ₃ , c = 1) The yield in this case was 95%.

1- (4-hydroxyphenyl) ethylhexanoate ((S) form) ¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 0.85 (t, 3H), 1.25 (m, 4H), 1.49 ( d, 3H), 1.59 (m, 2H), 2.28 (t, 2H), 5.74 (broad s, 1H), 5.67 (q, 1H), 6.77 (d, 2H), 7.20 (d, 2H) FT-IR (Cm ^-1 ) 3371,3024,2958,2931,2870,1732,1705,1616,1597,1516,1450,1415,1357,1288,1265,1242,1222,1211,1168,1099,1057,1014,1003 , 956, 833, 729, 547 [α] ▲ 20 D ▼ = -85.0 ° (CHCl _3, c = 1) Note that the yield in this case was 89%.

1- (4-hydroxyphenyl) ethylheptanoate ((S) form) ¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 0.85 (t, 3H), 1.23 (m, 6H), 1.48 ( d, 3H), 1.57 (m, 2H), 2.28 (t, 2H), 5.83 (q, 1H), 5.91 (broad s, 1H), 6.77 (d, 2H), 7.22 (d, 2H) FT-IR (Cm ^-1 ) 3390,3024,2954,2631,2858,1732,1706,1616,1597,1516,1450,1377,1269,1222,1168,1099,1057,999,949,833,725,644,547 [Α] ²⁰ _D ▼ = -79.3− (CHCl ₃ , c = 1) The yield in this case was 92%.

1- (4-hydroxyphenyl) ethyl decanoate ((S) form) ¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 0.85 (t, 3H), 1.23 (m, 12H), 1.49 ( d, 2H), 1.58 (m, 2H), 2.28 (t, 2H), 5.51 (broad s, 1H), 5.82 (q, 1H), 6.77 (d, 2H), 7.20 (d, 2H) FT-IR (Cm ^-1 ) 3394,3024,2927,2854,1732,1705,1616,1597,1516,1450,1377,1269,1207,1168,1111,1057,999,952,833,721,547 [α] ▲ ²⁰ _D ▼ = -71.0 ° (CHCl ₃ , c = 1) The yield in this case was 88%.

(Iii) Synthesis of fatty acid ester of (R) -form 1- (4-hydroxyphenyl) ethanol Fatty acid of (R) -form 1- (4- (1-ethoxyethoxy) phenyl) ethanol obtained in Example 1 ester
0.35 mol of acetic acid / dioxane / water (10/5/5) mixed solvent
After stirring at room temperature for 2 hours, the solvent was distilled off under reduced pressure to obtain (R) -form 1- (4-hydroxyphenyl) ethanol fatty acid ester.

The results of ¹ H-NMR analysis and FT-IR analysis of butyrate and heptanoate among the obtained compounds are shown in Example 2.
(S) -form 1- (4-hydroxyphenyl) obtained
It was similar to the fatty acid ester of ethanol. The results of ¹ H-NMR analysis of the balarate were as follows.
Their specific rotations and yields are summarized in Table 1.

¹ H-NMR of valarate (300MHz, CDCl _3, δ value (ppm)) 0.85 (t, 3H), 1.26 (m, 2H), 1.47 (d, 3H), 1.59 (m, 2H), 2.28 (t, 2H), 5.71 (broad s, 1H), 5.82 (q, 1H), 6.94 (d, 2H), 7.25 (d, 2H) Production Example 2 Synthesis of 1- (4- (tetrahydro-2-pyranyloxy) phenyl) ethanol (i) Synthesis of 4- (tetrahydro-2-pyraniloxy) acetophenone 13.6 g (0.1 mol) of p-hydroxyacetophenone was added to 150 ml of dichloromethane. 3,4-dihydro-α-pyran 12.
After dissolving 5 g, 1.1 g of pyrimidium-p-toluenesulfonate was added and reacted overnight at room temperature. After the reaction,
The reaction mixture was washed three times with 50 ml of 0.5N sodium hydroxide solution and three times with water. The ether layer was dried over magnesium sulfate, and ether was distilled off under reduced pressure.
-(Tetrahydro-2-pyraniloxy) acetophenone
20.5 g was obtained (93% yield).

The result of ¹ H-NMR spectrum analysis of the obtained compound was as follows.

¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 1.68 (m, 3H), 1.86 (m, 2H), 1.98 (m, 1H), 2.53 (s, 3H), 3.60 (m, 1H) , 3.82 (m, 1H), 5.50 (t, 1H), 7.07 (d, 2H), 7.91 (d, 2H) (ii) 1- (4- (tetrahydro-2-pyraniloxy)
Synthesis of phenyl) ethanol 22.0 g (0.1 mol) of 4- (tetrahydro-2-pyranyloxy) acetophenone obtained in (i) was added to ethanol 20.
The solution was dissolved in 0 ml, and 2.3 g (58 mmol) of NaBH ₄ was added thereto and reacted for 3 hours. After completion of the reaction, ethanol was distilled off under reduced pressure, 200 ml of ether was added, and the mixture was washed with diluted hydrochloric acid, water and an aqueous solution of sodium hydrogen carbonate in this order. After the ether layer was dried over magnesium sulfate, the solvent was distilled off under reduced pressure, and 19.5 g of 1-
(4- (tetrahydro-2-pyraniloxy) phenyl)
Ethanol was obtained (88% yield).

The result of ¹ H-NMR spectrum analysis of the obtained compound was as follows.

¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 1.46 (d, 3H), 1.63 (m, 3H), 1.84 (m, 2H), 1.97 (m, 1H), 3.68 (m, 1H) , 3.89 (m, 1H), 4.83 (q, 1H), 5.39 (t, 1H), 7.02 (d, 2H), 7.27 (d, 2H) Example 31 1- (4- (tetrahydro-2-pyraniloxy) Optical resolution of phenyl) ethanol (i) Asymmetric transesterification with 2,2,2-trichloroethylbutyrate 22.2 g of 1- (4- (tetrahydro-2-pyraniloxy) phenyl) ethanol in 120 ml of anhydrous diethyl ether
(0.1 mol), 2,2,2-trichloroethyl butyrate 22.4
g (0.1 mol) and Lipase P (manufactured by Amano Pharmaceutical Co., Ltd.) 2
5.2 g was added and the mixture was stirred at 25 ° C for 90 hours. After completion of the reaction, lipase was removed by suction filtration. The filtrate was concentrated and purified by silica gel chromatography (ethyl acetate / n-hexane = 1/4) to give the (S) form of 1- (4- (tetrahydro-2).
-Pyraniloxy) phenyl) ethanol 10.2 g (yield 92
%) And the (R) form of 1- (4- (tetrahydro-2-
13.1 g (yield 91%) of pyraniloxy) phenyl) ethyl butyrate were obtained.

The results of ¹ H-NMR spectrum analysis and specific rotation analysis of the obtained compound were as follows.

1- (4- (tetrahydro-2-pyranyloxy) phenyl) ethanol ((S) form) ¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 1.46 (d, 3H), 1.63 (m, 3H) , 1.84 (m, 2H), 1.97 (m, 1H), 3.68 (m, 1H), 3.89 (m, 1H), 4.83 (q, 1H), 5.39 (t, 1H), 7.02 (d, 2H), 7.27 (d, 2H) [α] ▲ ²⁰ _D ▼ = -33.6 ゜ (CHCl ₃ , c = 1) 1- (4- (tetrahydro-2-pyraniloxy) phenyl) ethyl butyrate ((R) form) ¹ H NMR (300 MHz, CDCl ₃ , δ value (ppm)) 0.90 (t, 3H), 1.19 (t, 3H), 1.47 (d, 3H), 1.49 (d, 3H), 1.62 (m, 2H), 2.27 (T, 2H), 3.51 (m, 1H), 3.76 (m, 1H), 5.35 (q, 1H), 5.84 (q, 1H), 6.94 (d, 2H), 7.26 (d, 2H) [α] ▲ ²⁰ _D ▼ = ＋ 34.1 ゜ (CHCl ₃ , c = 1) (ii) Asymmetric transesterification with vinyl balalate 2,2,2
-10.4 g of the (S) -form 1- (4- (tetrahydro-2-pyraniloxy) phenyl) ethanol by the same method as in (i) of Example 3 except that vinylvalerate was used instead of trichloroethylbutyrate. (Yield 94%) and 13.9 g of the (R) form of 1- (4- (tetrahydro-2-pyranyloxy) phenyl) ethylvalerate (91% yield)
I got

The results of ¹ H-NMR spectrum analysis and specific rotation analysis of the obtained compound were as follows.

The result of 1- (4- (tetrahydro-2-pyranyloxy) phenyl) ethanol ((S) form) ¹ H-NMR spectrum analysis was the same as that of Example 3 (i).

_{^{[Α] ▲ 20 D ▼ =}} + 34.1 ° _{(CHCl 3, c = 1)} 1- (4- ( tetrahydro-2-Piranirokishi) phenyl) ethyl Rose Rate ((R) body) ¹ H-NMR (300MHz, CDCl ₃ , δ value (ppm)) 0.89 (t, 3H), 1.48 (d, 3H), 1.62 (m, 7H), 1.83 (m, 2H), 1.98 (m, 1H), 2.24 (t, 2H) , 3.58 (m, 1H), 3.88 (m, 1H), 5.39 (t, 1H), 5.84 (q, 1H), 7.00 (d, 2H), 7.27 (d, 2H) [α] ▲ ²⁰ _D ▼ = + 77.4 ° (CHCl ₃ , c = 1) Example 4 (i) Synthesis of (S) -form 1- (4- (tetrahydro-2-pyraniloxy) phenyl) ethyl butyrate Obtained in Example 3 ( The S) form of 1- (4- (tetrahydro-2-pyranyloxy) phenyl) ethanol (0.05 mol) was dissolved in pyridine (50 ml), and butyric acid acid chloride (0.06) was dissolved.
Mole was slowly added dropwise. After the completion of the dropwise addition, the reaction was further performed for 10 hours, and then the reaction mixture was concentrated under reduced pressure. 100ml for residue
Was added, and the mixture was washed with diluted hydrochloric acid, water, and a 10% aqueous sodium hydrogen carbonate solution. After the ether layer was dried over magnesium sulfate, the ether was distilled off under reduced pressure to obtain (S) -form 1- (4-tetrahydro-2-pyraniloxy) phenyl) ethyl butyrate (yield 90%).

The results of ¹ H-NMR spectrum analysis and specific rotation analysis of the obtained compound were as follows.

1- (4- (tetrahydro-2-pyraniloxy) phenyl) ethyl butyrate ((S) form) ¹ H-NMR (300 MHz, CDCl ₃ , δ value (ppm)) 0.89 (t, 3H), 1.48 (d, 3H), 1.62 (m, 5H), 1.83 (m, 2H), 1.98 (m, 1H), 2.24 (t, 2H), 3.58 (m, 1H), 3.88 (m, 1H), 5.39 (t, 1H) ), 5.84 (q, 1H), 7.00 (d, 2H), 7.27 (d, 2H) [α] ▲ ²⁰ _D ▼ = -80.6 (CHCl ₃ , c = 1) (ii) (S) 1 Synthesis of-(4-hydroxyphenyl) ethyl butyrate 150 ml of 1- (4-tetrahydro-2-pyraniloxy) phenyl) ethyl butyrate ((S) form) (0.1 mol)
Was dissolved in methanol, and 1.1 g of pyridinium-p-toluenesulfonate was added, followed by reaction at room temperature for 2 hours. After completion of the reaction, methanol was distilled off under reduced pressure, 200 ml of ether was added, and the mixture was washed with water. After the ether layer was dried over magnesium sulfate, the ether was distilled off under reduced pressure to give the (S) form 1-.
(4-Hydroxyphenyl) ethyl butyrate was obtained (yield 13%).

The results of ¹ H-NMR spectrum analysis and specific rotation analysis of the obtained compound were as follows.

1- (4-Hydroxyphenyl) ethyl butyrate ((S) form) The result of ¹ H-NMR spectrum analysis was the same as that of Example 2 (ii).

_{^{[Α] ▲ 20 D ▼ =}} 109.8 ° _{(CHCl 3, c = 1)} (iii) (R) Synthesis of body 1- (4-hydroxyphenyl) ethyl butyrate 1- (4- (tetrahydro-2-Piranirokishi ) Phenyl) ethyl butyrate ((R) form) (0.1 mol)
It was dissolved in ml of methanol, and 1.1 g of pyridinium / p-toluenesulfonate was added, followed by a reaction at room temperature for 2 hours.
After completion of the reaction, methanol was distilled off under reduced pressure, 200 ml of ether was added, and the mixture was washed with water. After the ether layer was dried over magnesium sulfate, the ether was distilled off under reduced pressure to give the (R) form of 1-.
(4-Hydroxyphenyl) ethyl butyrate was obtained (yield 11%).

The results of ¹ H-NMR spectrum analysis and specific rotation analysis of the obtained compound were as follows.

1- (4-Hydroxyphenyl) ethyl butyrate ((R) form) The result of ¹ H-NMR spectrum analysis was the same as that of Example 2 (iii).

[Α] ▲ ²⁰ _D ▼ = 110.1 ゜ (CHCl ₃ , c = 1) (iv) Synthesis of (R) -form 1- (4-hydroxyphenylethyl) balalate -Hydroxyphenyl) ethylvalerate was obtained. (Yield 10%) The results of ¹ H-NMR spectrum analysis and specific rotation analysis of the obtained compound were as follows.

The result of ¹ H-NMR spectrum analysis was the same as that of Example 2 (iii).

[Α] ▲ ²⁰ _D ▼ = -83.5 ゜ (CHCl ₃ , c = 1) [Effect of the Invention] The optically active compound of the present invention has good compatibility with existing smectic liquid crystals or nematic liquid crystals, and has a Ps value of It can be used to easily produce optically active compounds that can give large liquid crystal mixtures.

Further, according to the method of the present invention, the useful optically active compound of the present invention can be easily produced.

Continued on the front page (58) Fields investigated (Int. Cl. ⁶ , DB name) C07C 69/025 C07C 43/23 C07D 309/12 C12P 41/00 CA (STN) REGISTRY (STN)

Claims (5)

(57) [Claims] 1. A compound of the general formula (I): (Wherein A is a tetrahydro-2-pyranyl group or 1-
An ethoxyethyl group). 2. The general formula (II): (Wherein A is a tetrahydro-2-pyranyl group or 1-
An ethoxyethyl group, and R ¹ represents an alkyl group having 1 to 15 carbon atoms). 3. An organic solvent comprising a compound represented by the general formula (IV): (Wherein A is a tetrahydro-2-pyranyl group or 1-
Racemic alcohols represented by showing the ethoxyethyl group) and 2,2,2-trichloroethanol fatty acid esters (number of carbon atoms in the fatty acid 2 to 16) or the general formula _{(V): H 2 C =} CR 2 -O-CO- R ³ (V) (wherein, R ² is a hydrogen atom or a methyl group, and R ³ is
A mixture of vinyl fatty acid esters represented by the formula (8), which is reacted with an enzyme having an esterase activity to selectively convert only the (R) form of the racemic alcohol into an ester compound, and then reacts the unreacted (S) A method for producing an optically active (R) ester compound, comprising separating an alcohol in a form. 4. In an organic solvent, a compound represented by the general formula (IV): (Wherein A is a tetrahydro-2-pyranyl group or 1-
Racemic alcohols represented by showing the ethoxyethyl group) and 2,2,2-trichloroethanol fatty acid esters (number of carbon atoms in the fatty acid 2 to 16) or the general formula _{(V): H 2 C =} CR 2 -O-CO- R ³ (V) (wherein, R ² is a hydrogen atom or a methyl group, and R ³ is
A mixture of vinyl fatty acid esters represented by the formula (8), wherein an enzyme having an esterase activity is allowed to act on the mixture to selectively convert only the (R) form of racemic alcohol into an ester compound, A process for producing an optically active (S) alcohol. 5. An enzyme having an esterase activity is selected from the group consisting of Pseudomonas and Candida.
Genus or Achromobacterium
The method according to claim 3 or 4, wherein the method is an enzyme produced from a microorganism belonging to the genus or an enzyme produced from the pancreas of an animal.