JPH02262536A - Optically active compound and its production - Google Patents

Abstract

NEW MATERIAL:Optically active compounds expressed by formula I (A is tetrahydro-2-pyranyl or 1-ethoxyethyl), formula II (R<1> is 1 to 15C alkyl) and formula III. EXAMPLE:The (R)-isomers of 1-[4-(1-ethoxyethoxy)phenyl]ethanol, 1-[4-(1- ethoxyethoxy)phenyl]ethyl butyrate and 1-(4-hydroxyphenyl)ethyl butyrate. USE:A synthetic raw material for chiral dopants of liquid crystal mixtures and raw material for medicaments and agricultural chemicals. PREPARATION:An enzyme having esterase activity is reacted with a mixture of a racemic alcohol expressed by formula IV with a fatty acid ester of 2,2,2- trichloroethanol or a vinyl ester of a fatty acid expressed by formula V (R<2> is H or methyl; R<3> is alkyl) in an organic solvent to convert only the (R)-isomer of the racemic alcohol into an ester compound, which is then separated to afford the compound expressed by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] 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 the synthesis of a chiral dopant added as a component of a liquid crystal mixture or as a raw material for medicines, agricultural chemicals, etc., and a method for producing the same.

[Prior Art] It has been known that a liquid crystal mixture with a fast response speed can be created by adding a chiral compound that does not itself exhibit liquid crystallinity but has optical activity to a smectic liquid crystal or nematic liquid crystal. There is. The performance of this liquid crystal mixture varies greatly depending on the types of optically active compounds and liquid crystal monomers used, their composition ratios, and compatibility, so the scope of searching for liquid crystal materials has expanded and liquid crystal mixtures that meet each purpose can be obtained. There is an increasing demand for optically active compounds for this purpose.

However, it is difficult to manually prepare optically active compounds, except for amino acids, organic acids, sugars, etc., which are generally relatively easily obtained by fermentation with microorganisms or as natural products.

In particular, the technology for obtaining an optically active compound that is used as an additive to the smectic liquid crystal or nematic liquid crystal and has high compatibility with the smectic liquid crystal or nematic liquid crystal has not yet been completed.

That is, conventional methods for synthesizing optically active compounds using biochemical or organic chemical methods have a narrow range of applicability and have the following drawbacks.

For example, biochemical methods include asymmetric synthesis using baker's yeast and dehydrogenase, but this method tends to significantly reduce chemical yield and optical purity due to the water solubility of the substrate used. On the other hand, it is not practical to use these methods for compounds that do not dissolve in water.

Another biochemical method is to perform an asymmetric transesterification reaction between tributyrin and a secondary alcohol using lipase in an organic solvent, but this method has a very slow reaction rate, and the optical Since the active compound is limited to butyl ester, it has the disadvantage that several additional synthesis steps are required to obtain the target compound.

On the other hand, when organic chemical methods are used, the optical purity and chemical yield are low depending on the substrate used, and the optically active compounds obtained are often limited to low molecular weight ones. Alternatively, it is difficult to synthesize optically active compounds that can be added to nematic liquid crystals to prepare liquid crystal mixtures.

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

[Means for Solving the Problems] The present invention provides - formula (I): H (wherein A is a tetrahydro-2-pyranyl group or l-
(Hereinafter, the (R)-form alcohol represented by the general formula (I) is (R)-(1) alcohol, and the (S)-form alcohol is (S)). -(1) also called alcohol), -mathematical formula (■
): (wherein, ^ is a tetrahydro-2-pyranyl group or l-
An optically active compound represented by an ethoxyethyl group (R1 represents an alkyl group having 1 to 15 carbon atoms) (hereinafter, - formula (
The (R) ester represented by II) is (R)-(I
1 ester, (S) ester is also referred to as (S)-(■) ester), an optically active compound represented by the general formula (ID= (wherein, R1 represents an alkyl group having 1 to 15 carbon atoms) and in organic solvents, general 2N
: H (wherein A is a tetrahydro-2-pyranyl group or l
- ethoxyethyl group) and fatty acid esters of racemic alcohol and 2.2.2-trichloroethanol (fatty acid having 2 to 18 carbon atoms) or - formula M: H2C=CR2-0-GO-R' (Vl
(In the formula, R2 is a hydrogen atom or a methyl group, and R3 is an alkyl group having 1 to 8 carbon atoms) is treated with an enzyme having esterase activity to produce only the (R) form of racemic alcohol. The present invention relates to a method for producing an optically active compound, which comprises selectively converting into an ester compound, and then separating it from unreacted (S)-form alcohol.

[Example] The optically active compound of the present invention is an optically active compound represented by general formula (I): An optically active compound represented by general formula (■): and general formula (Iff).

It is an optically active compound represented by

- The optically active compounds represented by the formulas (I) and (I) are intermediates of the optically active compounds represented by the single formula circle. That is, the optically active alcohol of general formula (I) has the general formula [1[
) The hydroxyl group on the aromatic nucleus is protected with substituent A in order to lead to the optically active ester represented by ().

Moreover, the optically active ester represented by the formula (I) can be easily prepared by removing only the substituent A by hydrolysis, and easily forming the general formula (I
) is derived from the optically active compound represented by

Therefore, substituent A must be easily removed and must not cleave the ester bond when substituent A is removed. Therefore, in the present invention, substituent A is limited to a tetrahydro-2-pyranyl group or a 1-ethoxyethyl group. In the case of substituents other than these, it becomes difficult to obtain a compound represented by a mononumeric circle.

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

Further, in the optically active compound represented by the formula (I) or (IN), R1 has 1 to 15 carbon atoms, preferably 2 to 15 carbon atoms.
12 alkyl group, and the alkyl group may have an asymmetric carbon. When the number of carbon atoms in R1 exceeds 15, it becomes difficult to expect favorable performance as a liquid crystal when the compound is induced into a liquid crystal. Furthermore, when R1 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 that includes halogenated alkyl groups in which a hydrogen atom is substituted with a halogen atom, as well as groups having an ether bond, an ester bond, etc. in the alkyl group. Asymmetric carbon may be present therein.

The optically active compound represented by formula (8) is useful as a raw material for the synthesis of chiral dopants that are highly compatible with many existing liquid crystalline substances. In particular, the following compounds can be mentioned as chiral dopants for smectic liquid crystals or nematic liquid crystals. 6H3 (R in the above formula is an alkyl group having 1 to 15 carbon atoms) which can realize a large Ps value and a desirable helical pitch.

) Furthermore, any of the optically active compounds of the present invention can be suitably used as raw materials for medicines, agricultural chemicals, fragrances, and the like.

Next, a method for producing optically active compounds represented by general formulas [1) to (II) of the present invention will be explained.

- The optically active compound represented by formula (T) or fn) is - formula ([V).

It is produced by optically resolving racemic alcohol represented by H3H (wherein A is the same as above). That is, −
The optically active alcohol represented by the formula CI) is an (R) alcohol or an (S) alcohol, and the optically active ester represented by the formula [1[) is an optically active alcohol represented by the general formula (I). It is a fatty acid ester corresponding to alcohol.

In the production method of the present invention, as described above, a racemic alcohol represented by the formula N and a fatty acid ester of 2.2.2-trichloroethanol (fatty acid having 2 to 16 carbon atoms) are used.
or - formula M:)12C-CI'! 2-0-GO-R
” (V) (In the formula, R2 represents a hydrogen atom or a methyl group, and R3 represents an alkyl group having 1 to 8 carbon atoms.)
The reaction with the vinyl fatty acid ester represented by is carried out in an organic solvent using an enzyme having esterase activity.

An enzyme with esterase activity is a racemic alcohol (
Since only the R) isomer is selectively esterified, the (R)-(l[) ester and the (S)-(1) alcohol are exchanged by this reaction. In addition, (R)-(1) ester is KOt
(, (R)-<11 alcohols by hydrolysis using a caustic alkali such as NaOH, (S)-CI) alcohols can be converted into (S)-(I) esters by esterification.

There is no particular restriction on the method of preparing the racemic alcohol represented by the formula (1), and any method may be used as long as the compound can be obtained.

For example, if the substituent in general 2) is an ethoxyethyl group, use ethyl vinyl ether to protect the hydroxyl group of parahydroxyacetophenone, and then reduce it with sodium borohydride, etc. Racemic alcohol can be changed.

The fatty acid ester of 2,2,2-)lichloroethanol or the formula M: )12c: -CR2-0-CO-R1(V) (in the formula,
A vinyl fatty acid ester represented by R2 is a hydrogen atom or a methyl group and R3 is an alkyl group having 1 to 8 carbon atoms is used as an acylating agent. The number of carbon atoms in a fatty acid can be determined by formula CI, which corresponds to the value of the number of carbon atoms in R1 of the compound represented by (2), and by appropriately selecting and using the number of carbon atoms in a fatty acid, Compounds can be changed.

Specific examples of the fatty acid ester of 2,2.2-trichloroethanol include 2,2.2-)lichloroethyl acetate, 2.2.2-trichloroethyl butyrate, and 2.2.2-trichloroethyl. Examples include heptanoate.

Further, as specific examples of the vinyl fatty acid ester, for example, impropenyl acetate, vinyl acetate,
Examples include vinyl valerate and vinyl octanoate.

The reason why the fatty acid in the fatty acid ester of 2,2.2-trichloroethanol has 2 to 1B carbon atoms has already been explained. The reason why it is 8 is that it is difficult to synthesize a vinyl fatty acid ester represented by the formula M in which R3 is 9 or more, and it is economically disadvantageous.

The enzyme having esterase activity is not limited in any way as long as it can asymmetrically esterify only the (R) form of the racemic alcohol represented by the formula N in an organic solvent using an acylating agent. It can be used and may be of microbial origin, animal origin, commercially available or non-commercially available. Specific examples of such enzymes include enzymes of the genus Pseudomonas such as Pseudomonas aeruginosa, which are enzymes derived from microorganisms;
osa+), Achromobacterium species such as Candlda cyllandra
Examples of enzymes derived from animals include enzymes produced from microorganisms belonging to the genus Candida, such as C. cea), and enzymes produced from pig intestines, but are not limited to these.

Commercially available products of these enzymes include, for example, Lipase "Amano JP (manufactured by Amano Pharmaceuticals, trade name)" and Lipase Toyo (trade name).
Toyo Jozo ■, product name), bank creatine lipase (Ohno Pharmaceutical ■, product name), bank creatine lipase (Sigma ■, product name), Lipase B (Wako Pure Chemical Industries, product name), Lipase MY (Manufactured by Polysaccharide Industry ■, product name).

The organic solvent used in the production method of the present invention can be used without particular limitations as long as it satisfies requirements such as dissolving the racemic alcohol represented by 2N and the acylating agent and not inhibiting the enzyme activity of the enzyme having esterase activity. . Specific examples of such organic solvents include diethyl ether, methyl ethyl ether, diisopropyl ether, n-hexane, cyclohexane, n-heptane,
Examples include toluene.

In the present invention, there are no particular limitations on the method for preparing the organic solvent containing the racemic alcohol represented by the general formula, the acylating agent, and the enzyme having esterase activity. For example, -
It may be prepared by adding a racemic alcohol represented by the formula N, an acylating agent, and an enzyme having esterase activity to an organic solvent, or it may be prepared by dissolving or dispersing them separately, or by mixing a solution in which they are dispersed. Furthermore, it is also possible to prepare by first dissolving only the lacquer that is difficult to dissolve but can be dissolved by heating, and then adding other substances.

The ratio of the racemic alcohol represented by the general formula to the acylating agent is preferably 0.5 to 2.0 mol, and 1 to 1 mol, of the acylating agent per 1 mol of the racemic alcohol represented by the general formula. More preferably, .5 mol is used. If the usage ratio is less than 0.5 mol, the molar amount will be less than the (R) form of the racemic alcohol represented by the general formula, and it will not be possible to esterify all of the (R) form. Moreover, if the amount exceeds 2.0 mol, the proportion of the acylating agent used that does not participate in the reaction increases, resulting in a decrease in economic efficiency.

In addition, the amount of enzyme having esterase activity is generally 10 to 600 g per mole of the compound represented by 2N.
is preferable, and 100 to 500 g is more preferable. If the amount used is less than 10 g, the reaction rate will be slow, which is economically disadvantageous; if it exceeds 600 g, the amount of enzyme will be too much compared to the reaction rate, which will be economically disadvantageous.

Furthermore, the proportion of the total amount of racemic alcohol and acylating agent, represented by general 2N, is preferably 0.1 to 50% (wt%, the same shall apply hereinafter) based on the weight of the solution obtained by dissolving these in an organic solvent. More preferably, it is 10 to 30%. If the usage ratio is less than 0.1%, the yield will be small in relation to the amount of reaction liquid, which will be economically disadvantageous. If it exceeds 50%, the concentration is too high and the reaction rate is low, resulting in a low yield.

In the production method of the present invention, since an enzyme having esterase activity is used, the temperature is usually 10-40°C, preferably 25-40°C.
A reaction temperature of 30°C is employed.

The reaction time varies depending on the racemic alcohol represented by the general formula, the type of enzyme having esterase activity, the compound represented by the general 2, the proportions of the acylating agent and the enzyme having esterase activity, the stirring conditions, etc. Although it cannot be specified, it is usually 1 to 150 hours, preferably 24 hours.
~96 hours.

Completion of the reaction is confirmed by measuring the conversion rate of the racemic alcohol represented by the general formula to ester by gas chromatography, and when the conversion rate becomes constant.

The reaction mixture thus obtained is first filtered to remove enzymes having esterase activity. Thereafter, after removing the organic solvent and the like if necessary, the mixture is separated into (R)-(It) ester and (S)-m alcohol by, for example, silica gel chromatography. Furthermore, if the thus separated product contains alcohol or the like produced by the acylation reaction or unreacted acylating agent, it may be purified by a method such as distillation. In addition, 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) is used.
, a chloroform/methanol mixture (chloroform/methanol in a volume ratio of 1/10 to 1/40) is preferably used.

Moreover, the separated used enzyme having esterase activity can be reused.

Identification is performed by measuring IH-NMR spectrum, IR spectrum, specific optical rotation, and the like.

Furthermore, the obtained (R)-(I) ester can be easily hydrolyzed (S) by enzymatic or chemical methods.
)-(1) It can be made into (R)-m alcohol, which is the enantiomer of alcohol. In addition, (S)-(1) alcohol can be esterified into (S)-(II) ester, which is the enantiomer of (1?)-(I) ester.

In this way, the optically active compound represented by the general formula (1) or the general formula (If) can be obtained with a yield of 80 to 90%.

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

Example 1 Synthesis of l-(4-(1-ethoxyethoxy)phenyl)ethanol (04-(1-ethoxyethoxy)acetophenone synthesis 13.8 g (0.1 mol) of p-hydroxyacetophenone in 100 ml diethyl ether) and ethyl vinyl ether were dissolved, 1 ml of concentrated hydrochloric acid was added, the mixture was refluxed for 4 hours, and the mixture was further reacted at room temperature for 1θ hour.

After the reaction is complete, the reaction mixture is 0. It was washed twice with 50 ml of IN sodium hydroxide solution and three times with water. After drying the ether layer with magnesium sulfate, the ether was distilled off under reduced pressure to obtain 20.5 g of oily 4-(l-ethoxyethoxy)acetophenone (yield: 92%).

The results of IH-NMR spectrum analysis of the obtained compound were as follows.

IH-NMR (300 MHz, CD (Js, δ value (ppm)) 1.17 (t, 3H), 1.51 (s, 3H), 2.52 (s, 3H), 3.50 (s,
IH), 3.72 (m, IH), 5.48 (q,
IH), 8.95 (d, 2H), 7.8
8(d, 2H) ■ Synthesis of 1-(4-(1-ethoxyethoxy)phenyl)ethanol Add 15.0 g (72 mmol) of 4-(1-ethoxyethoxy)acetophenone obtained in (1) to 100 ml of ethanol. Dissolve and add 42.2 g of NaBH (58
mmol) and reacted for 5 hours. After the reaction was completed, ethanol was distilled off under reduced pressure, and then 200 ml of ether was added and the mixture was washed with dilute hydrochloric acid, water, and an aqueous sodium bicarbonate solution in this order. After drying the ether layer with magnesium sulfate,
The solvent was distilled off under reduced pressure to obtain 13.6 g of 1-(4-(1-ethoxyethoxy)phenyl)ethanol (yield: 9
0%).

The results of IH-NMR spectrum analysis of the obtained compound were as follows.

'H-NMR (300MHz, CDCl3.δ value (pp
m)) 1.17(t, 3H), 1.44(d, 3
H), 1.48(d, 3H), 1.93(s, [
1), 3.52 (m, LH), 3.76 (m, L
H), 4.82 (s, LH), 5.34 (q, L
H), 8.94 (d, 2H), 7.27 (d, 2
H) Example 2 Optical resolution of l-(4-(1-ethoxyethoxy)phenyl)ethanol (1) Asymmetric transesterification with 2,2.2-)lichloroethyl butyrate 1 in 120 ml of anhydrous diethyl ether -(4-(1-
ethoxyethoxy)phenyl)ethanol 21g (0
, 1 mol), 2,2.2-)lichloroethylbutyrate (22.4 g (0.1 mol)) and 25.2 g of Lipase P (manufactured by Ohno Pharmaceutical Co., Ltd.) were added, and the mixture was stirred at 25°C for 90 hours.

After the reaction was completed, lipase was removed by suction filtration, the filtrate was concentrated, and then subjected to silica gel chromatography (ethyl acetate/n
9.6 g (yield 91%) of 1-(4-(1-ethoxyethoxy)phenyl)ethanol of the (S) form and (R
) 1-(4-(1-ethoxyethoxy)phenyl)
13.0 g (yield 93%) of ethyl butyrate was obtained.

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

1-(4-(1-ethoxyethoxy)phenyl)ethanol ((S) form) 'H-NMR (300Mllz, CDCl3.δ value (p
pa+)) 1.17(t, 3!() 1.44
(d, 3H) , 1.46 (d, 3H) , 1
．． 93 (s, LH), 3.52 (m, LH)
3.76 (a+, LH), 4.82 (ff1
．． IH), 5.34 (Q, III),
6.94 (d, 211), 7.27 (d,
2+1) FT-IR (a "1) 3398.2974, 2931.2889.1B12.
1512.144B.

1381.1342.1238.117B, 1134,
1118.107B.

1049.1010.945,898,837゜[a
]%P--38,1'(CHC#3,c-1
) 1-(4-(1-ethoxyethoxy)phenyl)ethylbutyre) ((R) form) IH-NMR (300MHz, CDCfx, δ value (
ppm)) 0.90(t, 3H), 1.19(t,
3H), 1.47(d, 3H), 1.49(d,
3H), 1.62(a+, 211), 2.27(
t, 211), 3.51(i, IH), 3.
76 (a+, IH), 5.35 (q, LH),
5.84 (q, III), 0.94 (d, 2+
1), 7.20(d, 211)FT-IR(c
Ill-') 2974.2935, 2877.1735.1 & 12,
1585, 1512° 1454. 1419, 1381.
1346.1288, 117B, 1134°1099.
107B, l0GO, 1014, 1003, 941, 8
98,833° [(2] CD-+84.0' (
C1lCN3+C-1>(ii) Asymmetric transesterification with 2,2.2-trichloroethyl butanoate 2.2.2 instead of 2-trichloroethyl butyrate
．． 2.2-) 1- of the (S) form was prepared in the same manner as in Example 2 (+) except that dichloroethylhebutanoate was used.
(4-(1-ethoxyethoxy)phenyl)ethanol 9.5 g (yield 90%) and the (R) form of 1-(4
14.8 g (yield: 9296) of -(1-ethoxyethoxy)phenyl)ethylheptanoate was obtained.

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

1-(4-(1-ethoxyethoxy)phenyl)ethanol ((S) form) The results of IH-NMR analysis and FT-IR analysis were similar to those of Example 2 0).

[α] 20- -38.1' (C1!(Jx +
C-1) 1-(4-(1-ethoxyethoxy)phenyl)ethylheptanoate ((R) form) 'H-NMR (300MHz, CDCf3.6 value (pp
m)) 0.84(t, 3H), 1.19(t, :
(H), 1.24 (a+, 6H), 1.47 (d,
3H), 1.49 (d, 311), 1.58 (m
, 211), 2.28(t, 2H), 3.49(
+g, 1tl), 3.78(a+, IH), 5J
5 (q, LH), 5.83 (q, III),
8.94 (d, 2H), 7.25 (d, 2H) FT-IR (c+++-1> 2978.295+1.2931.2870, 2858
．． 1735.1812°15g5. L512,1454
,1419.1377.1342.1288゜123B
, 1168.1L34, 111B, 1099.1076
．． 1057゜1.014.1003,941,898,
833.551 [α] 20- +89. Oo (C
HCl3, C-1) (To) Asymmetric transesterification with vinyl valerate 2.2. Same as Example 2 (1) except that vinyl valerate was used instead of 2-1-lichloroethyl butyrate. By the method of (S) body 1-(4-
(1-ethoxyethoxy)phenyl)ethanol9,8
g (yield 93%) and (R) form of 1-(4-(1-ethoxyethoxy)phenyl)ethylvalerate 11.8
g (yield 94%).

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

1-(4-(1-ethoxyethoxy)phenyl)ethanol ((S) form) The results of IH-NMR analysis and FT-IR analysis were similar to those in Example 2 (1).

[a] CD--36,1' (CIC13,c
-1) 1-(4-(1-ethoxyethoxy)phenyl)
Ethyl valerate ((R) form)') I-NMR (300 MHz, CDCf3.δ value (p
pm)) 0.86(t, 311), 1.19
(t, 3) 1) , 1, H(m, 2tl)
, 1.47 (d, 3tl) , 1.49 (d
, 3H), 1.59<m, 211),
2.28 (t, 2H), 3.50 (m, I
II), 3.78 (m, l1l), 5J5
(q, III) , 5.83 (q, IH)
, 8.94 (d, 2++) , 7.25 (d,
2H) FT-IR (co+-1) 2974.2935.2877.1735.1B12,
1585.1512゜1454.1419, 1.381
,1346.1288,1238.1178°1134
．． 1099.1078.10B0,1014,1003
．． 941,898°833, 551 [α] D-+80.2° (CIICj 3.a-
1) Synthesis of (t) (R) form of 1-(4-(1-ethoxyethoxy)phenyl)ethanol 1-<4-(1) of (R) form obtained in (1) of Example 2
-ethoxyethoxy)phenyl)ethylbutyrate 28
g (0.1 mol) was dissolved in 210 ml of an ethanol solution of IN potassium hydroxide, and after reacting overnight at room temperature, the reaction mixture was concentrated under reduced pressure. 200 ml of ether was added to the residue, which was washed twice with 50 ml of 2N aqueous sodium hydroxide solution, and then three times with water. The ether layer was dried over magnesium sulfate, and the ether was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/n-hexane-114) to obtain 18.9 g of (R)-isomer-1-(4-(1-ethoxyethoxy)phenyl)ethanol (yield 90%). .

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

! ) The results of 1-NMR analysis and FT-IR analysis were similar to those in Example 2 (1).

[ffl': -+38.9° (ClICl5,
c-1) Example 3 (Synthesis of fatty acid ester of D(S) form of 1-(4-(1-ethoxyethoxy)phenyl)ethanol) The (S) form of 1-(4~) obtained in Example 2 (1-ethoxyethoxy)phenyl) 0.05 mol of ethanol and 50 m of pyridine
1, and 0.06 mol of fatty acid acid chloride was slowly added dropwise. After the dropwise addition was completed, the reaction was continued for another 10 hours, and then the reaction mixture was concentrated under reduced pressure. 100 m to the residue
1 of diethyl ether was added, and the mixture was washed with dilute hydrochloric acid, water, and 10% aqueous sodium bicarbonate solution. After drying the ether layer with magnesium sulfate, the ether was distilled off under reduced pressure.
A fatty acid ester of 1-(4-(1-ethoxyethoxy)phenyl)ethanol in the (S) form was obtained.

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

1-(4-(1-ethoxyethoxy)phenyl)ethylbutyrate ((S) form)') I-NMR (300 MHz, CD (J3.δ value (
ppm)) 0.90(t, 3H), L, 19(t,
3H), 1.47(d, 3H), 1.49(d,
3H), 1,H(11,2B), 2.27(t,
211), 3.51 (m, IH), 3.78 (
1,10) 5.35(Q, IH), 5.84(q
, IH), 8.94 (d, 211) 7.
28(d, 2H) FT-IR (Rho 1) 2974, 2935.2877, 1735. 16
12. 1585°1512, 1454. 1419
．． 13g1. 1346. 128g.

1238, 117B, 1134. 1099.
107B, l0GO.

1014, 1003. 941. 898.
833. 551 [α] 3−−83.5° (CH
Cl5, c-1) The yield in this case was 91%.

1-(4-(i-ethoxyethoxy)phenyl)ethylhexanoate ((S) form) lH-NMR (300 MHz, CDCl3.δ value (p
pffl)) 0.85(t, 311) L, 19(
t, 311), 1.27 (m, 4H) 1.47
(d, 3tl) 1.49 (d, 3H) 1.59
(i, 211), 2.28(t, 2H), 3.5
0 (m, III) 3.76 (m, IH), 5.
35 (q, 1it), 5.83 (Q, IH)
, 8.94 (d, 211) 7.25 (d, 2H) FT-[R (cm -1,) 2978, 2958.2931.2870. 1735
．． 1612°15g5.1512. 1454. 13
77, 1342.12g8゜1242, 1172.
1122. 1[)57. 1014. 945°89
8, 833. Tsukasa 51 [α]π--74.0° (ClO23, c-1) The yield in this case was 92%.

1-(4-(1-ethoxyethoxy)phenyl)ethylheptanoate ((S) form) 'H-NMR (300MHz, CDC#3, δ value (
ppm)) 0.84(t, 3H), 1.19(t,
3H) 1.24(i, B)I) , 1.47(d,
31), 1.49(d, 311), 1.58(i
, 211), 2.28(t, 2H), 3.49(
m, IH), 3.78 (+a, LH),
5.35 (q, 211) 5.83 (c+, L
H), 6.94 (d, 2H), 7.25 (d, 2
H) FT-IR (c+n-1) 2978, 295B, 2931.2870.2858
．． 1735°1812, 15g5.1512. 14
54.1419.13'l'l.

1342, 1288. 1238. 1188.113
4.111B.

1099, 107B, 1057. 1014.100
3. 941°898, 833. 551 [α] cloud--88,1° (CH(J3. c-1)
Note that the yield in this case was 90%.

1-(4-(1-ethoxyethoxy)phenyl)ethylbutyrate ((S) form)') I-NMR (300MIIz, CDCl3.δ value (ppm)) 0.85 (t, 11),
1.19(t, 311), 1.2
3(111,1211), 1.47(d, 31
1) 1.49 (d, 311) 1.58 (m
, III), 2.28 (t, 211)
3.54 (+a, illi 3.75 (n+,
l1l) 5.35 (q, 1ll), 5.8
3 (Q, IH) G, 94 (d, 2H)
, 7.25(d, 2H) FT-IR (am-1) 2978, 2954. 2927. 2854. 1
735. lG12゜1585, 1512. 14
58. 1419. 1377, 1300°1288
, 1238. 1176, 1118. 107B,
1057°1014, 1003. 941. 9
02. 833. 551ca] $-59,0° (CH
3C1, c-1) The yield in this case was 93%.

(i)) Synthesis of (S) fatty acid ester of 1-(4-hydroxyphenyl)ethanol 0.1 mol of fatty acid ester of 1-(4-(1-ethoxyethoxy)phenyl)ethanol was mixed with acetic acid/dioxane/
Approximately 200 ml of a mixed solvent of water (101515) was dissolved, stirred at room temperature for 2 hours, and the solvent was distilled off under reduced pressure to obtain the fatty acid ester of 1-(4-hydroxyphenyl)ethanol in the (S) form.

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

■-(4-hydroxyphenyl)ethyl butyrate ((
S) body) IH-NMR (300MHz, CDCl3, δ
Value (ppm)) 0.89 (1,3H), 1.50 (d
, 3H), 1.61(m, 2H), 2.28h,
2H) 5.83 (Q; IH), 6.14 (bro
ad s, 11(), 6.77(d, 2H), 7
．． 20(d, 2+1)FT-IR(cIll-') 3387, 2970.2935.2873.1732.
1705°1818, 1597.1518.1450.
1373.1265°1199, 1172.1091.
1057. 999. 956°941, 833.
547 [a] E -109,8° (ClICl3, C
= 1) Note that the yield in this case was 95%.

■-(4-hydroxyphenyl)ethylhexanoate ((S) form)! H-NMR (300Ml!z, CD (J3
, δ fdirection (ppm)) 0.85(t, 3
11) 1.25 (ffl, 411), 1.49 (
d, 311), 1.59 (++, 2H) 2.28
(t, 211), 5.74 (broad s, I
II) 5.137 (Q, IH), 6.77 (d,
21+), 7.20 (d, 211) FT-IR (cm') 3371, 3024.2958.2931.2870.
1732°1705, l5lG, 1597.151
6.1450.1415°1357, 1288.12B
5.1242. [222,12111168,109
9,1057,1014,1003,956°833,
729. 547 [Cl',,, --85,0' (CIlCfx
, c-1) Note that the yield in this case was 89%.

1-(4-Hydroxyphenyl)ethylheptanoate <(S) form)') I-NMR (300MIIZ, CD(J3, δ
Value (ppm)) 0.85 (t, 311) 1.
23(+n, 611) 1.48(d, 311)
1.57 (+n, 211) 2.28 (t,
2H) 5.83 (q, IH) 5.91 (b
road s, 1tl), fli, 77(d
, 211) 7.22 (d, 211) FT-IR (cm -1) 3390, 3024. 2954. 2931. 2
858. 1732°1706, 161G, 15
97. 1516. 1450. 1377°1269
, 1222. 11G8. 1099. 1057.
999°949, 833. 725. 6
44. 547[α] coins--79,3° (CHCl
3, C-1) The yield in this case was 92%.

1-(4-hydroxyphenyl)edyldecanoe! −
((S) body) 'H-NMR (300MIIz, CDCl3.δ value (
ppm)) 0.85 (t, 3H), 1.23 (I!
+, 12! l), 1.49(d, 211), 1.
58 (m, 21ri 2.28 (t, 2H), 5.5
1 (broad s, IH) 5.82 (Q, IH
) , 6.77 (d, 2+1) 7.20 (d, 2+
1) FT-IR (cm') 3394, 3024. 2927. 2854. 1
732. 1705°161G, 1597. 15
1B, 1450. 1377, 12B9゜120
7, 116g, 1111. 1057. 99
9. 952°833, 721. 547 [α] F −−71,0° (CI(J 3.c-1
) The yield in this case was 88%.

■Synthesis of fatty acid ester of 1-(4-hydroxyphenyl)ethanol in the (R) body Fatty acid ester of 1-(4-(1-ethoxyethoxy)phenyl)ethanol in the (R) body obtained in Example 2 0
．． Dissolve 35 mol in 700 ml of acetic acid/dioxane/water (101515) mixed solvent, stir at room temperature for 2 hours, and then evaporate the solvent under reduced pressure to obtain (R) fatty acid ester of 1-(4-hydroxyphenyl)ethanol. I got it.

The results of IH-NMR analysis and FT-IR analysis of butyrate and heptanoate among the obtained compounds were similar to the fatty acid ester of 1-(4-hydroxyphenyl)ethanol in the (S) form obtained in Example 3. there were. Further, the results of IH-NMR analysis of valarate were as shown in the figure. Their specific optical rotations and yields are summarized in Table 1.

Valarate 'H-NMR (300 MIIz, CDC
ζ3 δ value (ppm)) 0.85 ('t, 311) 1.26 (m, 21
1),, 1.47 (d, 311) 1.59 (m,
211) 2.28(t, 2H) 5.71(br
oad s, 1ll) 5.82 (Q, 1.11
), 6.94(d, 21ri7.25(d, 211)
) Table 1 Example 4 Synthesis of l-(4-(tetrahydro-2-vilanyloxy)phenyl)ethanol (+) Synthesis of 4-(tetrahydro-2-vilanyloxy)acetophenone Add p-hydroxyacetophenone to 150 ml of dichloromethane 13. 6 g (0.1 mol) and 2.5 g of 3,4-dihydro α-bilane L were dissolved, and birimidium I
)-) 1.1 g of luenesulfonate was added and the mixture was reacted overnight at room temperature. After the reaction was completed, 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 the ether was distilled off under reduced pressure to obtain 20.5 g of oily 4-(tetrahydro-2-vilanyloxy)acetophenone (yield 93%).

The results of IH-NMR spectrum analysis of the obtained compound were as follows.

'H-NMR (300 Ml!z, CD (Jx, δ
Value (ppm)) 1.68 (m, 3H), 1
．． 86(a+, 2H), 1.98(a+,
III), 2.53 (s, 311), 3.60 (m
, II(), 3.82(m, l)ri,
5.50 (t, il+), 7.07 (d,
2+1) 7.91 (d, 2H) (ii) Synthesis of 1-(4-(tetrahydro-2-vilanyloxy)phenyl)ethanol 22.0 g of 4-(tetrahydro-2-vilanyloxy)acetophenone obtained in (1) (0.1 mol) was dissolved in 200 ml of ethanol, and 2.3 g of NaBH+ (
58 mmol) was added and reacted for 3 hours. After the reaction was completed, ethanol was distilled off under reduced pressure, 200 ml of ether was added, and the mixture was washed with dilute hydrochloric acid, water, and an aqueous sodium bicarbonate solution in this order. After drying the ether layer with magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 19.5 g of 1-(4-(tetrahydro-2-vilanyloxy)phenyl)ethanol (
yield 88%).

The results of IH-NMR spectrum analysis of the obtained compound were as follows.

'H-NMR (300 MHz, CD (J3.δ value (ppm)) 1.46 (d, 3H), 1..63 (
m, 3)ri, 1.84(@, 2H), 1.97(
1, [1), 3.88CIIl, In), 3.
89Ctn, 110. 4.83((1,l1l)
5.39 (t, IH), 7.02 (d,
2+1), 7.27(d, 2H) Example 5 Optical resolution of l-(4-(tetrahydro-2-vilanyloxy)phenyl)ethanol (1) Asymmetric ester with 2,2.2-trichloroethylbutyrate 1-(4-(tetrahydro-2-vilanyloxy)phenyl)ethanol 2 to 120 ml of exchanged anhydrous diethyl ether
2.2 g (0.1 mol), 22.4 g (0.1 mol) of 2,2.2-trichloroethylbutyrate, and 25.2 g of Lipase P (manufactured by Jinkoyaku Pharmaceutical Co., Ltd.) were added, and the mixture was heated at 25°C.
Stirred for 0 hours. After the reaction was completed, the lipase was removed by suction filtration, and the filtrate was concentrated and subjected to silica gel chromatography (
Purified by ethyl acetate/n-hexane-1/4),
S) 1-(4-(tetrahydro-2-villanyloxy))
10.2 g (yield: 92%) of 1-(4-(tetrahydro-2-villanyloxy)phenyl)ethyl butyrate (yield: 92%)
%) was obtained.

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

1-(4-(tetrahydro-2-vilanyloxy)phenyl)ethanol ((S) form) IH-) IMR (300MHz, CDCl3, δ
Value (ppm)) 1.46 (d, 3H), 1.63 (
m, 3t(), 1.84(m, 211), 1.9
7(m, III) 3.88(m, 11(),
3.89 (ll, 1ll) 4.83 (q, HJ
), 5.39 (t, III), 7.02 (d,
2H), 7.27 (d, 211) [α] Amase-3
3.6° (CIICI3.c-1,) 1-(4-(tetrahydro-2-villanyloxy)phenyl)ethyl butyrate ((R) form) "H-NMR (300 MHz, CD (J3, δ value (ppm) )) 0.90(t, 38), 1.19(t
, 3H) 1.47 (d, 3H) , 1.49 (d,
311), 1.82(+a, 211), 2.27(
t, 211) 3.51(m, IH), 3.76(
i+, H()5.35(q, 11ri, 5.84(
(1, l11) 6.94 (d, 211) 7.
26(d, 21+)[α] Rent-+34.1 (C
1l (J3.cx 1 ) (i) Asymmetric transesterification with vinyl valerate 2.2. Same method as in Example 5 (i) except that vinyl valerate was used instead of 2-trichloroethylbutyrate By (S) field 1-(4
-(tetrahydro-2-pyranyloxy)phenyl)ethanol 10.4g (yield 94%) and (R) form of 1-(4-(tetrahydro-2-pyranyloxy)phenyl)ethylvalare) 13.9g (yield 94%) rate 9I%)
I got it.

The results of IH-NMR spectrum analysis and specific rotation analysis of the obtained compound were as shown.

1-(4-(tetrahydro-2-vilanyloxy)phenyl)ethanol ((S) form) The results of IH-NMR spectrum analysis are as in Example 5 (1)
The results were similar.

[a] 'e −+34.1' (C)i(J 3
．． c-1,) 1-(4-(tetrahydro-2-vilanyloxy)phenyl)ethylvalarate ((R) form) lH-NMR (300MIIz, CD (J3.δ value (ppa+)) 0.89 (t, 311), 1.
48 (d, 311) 1.62 (m, 7H)
, 1.83 (a+, 2tl) 1.98 (however,
1ll) , 2.24(t, 2+1) 3.58(
m, l1l) , 3.88(m, It()5
．． 39 (t, IH), 5.84 (Q, IH
)7.00(d, 2+1), 7.27(d,
2+1) [α] Rent -+77.4° (CIICN3
．． c-1) Example 6 (+) (S) form of 1-(4-(tetrahydro-2)
-Synthesis of (S) form of 1-(4-(tetrahydro-2-vilanyloxy)phenyl)ethanol obtained in Example 5 in 50 ml of pyridine was dissolved in 50 ml of pyridine. 0.06 mol of acid chloride was slowly added dropwise.

After the dropwise addition was completed, the reaction was continued for another 10 hours, and then 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 10% aqueous sodium hydrogen carbonate solution. After drying the ether layer over magnesium sulfate, the ether was distilled off under reduced pressure to obtain the (S) form of 1-(4-(tetrahydro-2-villanyloxy)phenyl)ethyl butyrate (yield: 9096).

The results of IH-NOR spectrum analysis and specific rotation analysis of the obtained compound were as follows.

1-(4-(tetrahydro-2-vilanyloxy)phenyl)ethylbutyrate ((S) form) 1) 1-NMR (3pOMHz, CD(J3, δ)
Value (ppm)) 0.8! It (t, 3H) 1
4B (d, 3H), 1.62 (m, 5H)
1.83 (m, 2H), 1.98 (a+, I
II) 2.24 (t, 2H), 3.58 (
a+, III) 3.1118 (+a, 1)
I) 5.39 (t, IH) 5.84 (q,
III), 7.00 (d, 211) 7.2
7 (d, 2H) (α] B −−80,8° (C
1l(J3.c-1)Q) Synthesis of (S) form of 1-(4-hydroxyphenyl)ethylbutyrate 1-(4-(tetrahydro-2-vilanyloxy)phenyl)ethyl butyrate ((S) form ) (0.1 mol) in 150 ml of methanol, pyridinium.
I)-) 1.1 g of luenesulfonate was added and reacted at room temperature for 2 hours. After the reaction was completed, methanol was distilled off under reduced pressure, 200 ml of ether was added, and the mixture was washed with water.

After drying the ether layer over magnesium sulfate, the ether was distilled off under reduced pressure to obtain (S) form of 1-(4-o hydroxyphenyl)ethyl butyrate (yield: 13%).

The results of IH-NOR spectrum analysis and specific rotation analysis of the obtained compound were as shown.

■-(4-hydroxyphenyl)ethylbutyre)((
S) body) The results of LH-NOR spectrum analysis are (1+ body) of Example 3.
) had similar results.

[a] 'r> --109,8@(ell(J 3
．． c = t> (to) Synthesis of (R) form of 1-(4-hydroxyphenyl)ethylbutyrate 1-(4-(tetrahydro-2-vilanyloxy)phenyl)ethyl butyrate ((R) form) (0 , 1 mol) in 150 ml of methanol, pyridinium p
-) 1.1 g of luenesulfonate was added and reacted at room temperature for 2 hours. After the reaction, methanol was distilled off under reduced pressure and
00ml of ether was added and washed with water. After drying the ether layer over magnesium sulfate, the ether was distilled off under reduced pressure to obtain the (R) form of 1-(4-hydroxyphenyl)ethyl butyrate (yield: 11%).

The results of IH-NOR spectrum analysis and specific rotation analysis of the obtained compound were as shown.

■-(4-hydroxyphenyl)ethyl butyrate ((
R) Body) IH-NMI? The results of spectral analysis were similar to those in Example 3 (■).

[+2] Sweet-tto, io (Cl1C13,c-1
)rN) (R) Synthesis of 1-(4-hydroxyphenylethyl)valerate Synthesis was carried out in the same manner as described above to obtain 1-(4-hydroxyphenyl)ethylvalerate. (Yield 1%) IH-NMI of the obtained compound? The results of spectral analysis and specific rotation analysis were as shown.

The results of IH-NOR spectrum analysis are shown in Example 3.
The results were similar.

[(Z] F) = −83,5° (CIIC13,
c-1) [Effects of the Invention] The optically active compound of the present invention has good compatibility with existing smectic liquid crystals or nematic liquid crystals, and can easily produce an optically active compound that can provide a liquid crystal mixture with a large Ps value. It can be used for.

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

Claims (1)

[Claims] 1 General formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, A is a tetrahydro-2-pyranyl group or 1-
An optically active compound represented by (representing an ethoxyethyl group). 2 General formula (II): ▲Mathematical formulas, chemical formulas, tables, etc.▼(II) (In the formula, A is a tetrahydro-2-pyranyl group or 1-
An optically active compound represented by an ethoxyethyl group (R^1 represents an alkyl group having 1 to 15 carbon atoms). 3 General formula (III): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) (In the formula, R^1 represents an alkyl group having 1 to 15 carbon atoms)
An optically active compound represented by 4 General formula (IV) in an organic solvent: ▲Mathematical formula, chemical formula, table, etc.▼(IV) (In the formula, A is a tetrahydro-2-pyranyl group or 1-
Racemic alcohol represented by ethoxyethyl group) and fatty acid ester of 2,2,2-trichloroethanol (fatty acid having 2 to 16 carbon atoms) or general formula (V)
: H_2C=CR^2-O-CO-R^3(V) (in the formula,
R^2 is a hydrogen atom or a methyl group, R^3 has 1 or more carbon atoms
An enzyme having esterase activity is applied to a mixture of vinyl fatty acid esters (representing the alkyl group of 8) to selectively convert only the (R) isomer of the racemic alcohol into an ester compound, and then the unreacted (S) A method for producing an optically active compound characterized by its separation from alcohol in the body. 5 Enzymes with esterase activity are found in Pseudomonas spp., Candida spp.
dida) or Achromobacterium (Ahr
5. The method for producing an optically active compound according to claim 4, wherein the enzyme is an enzyme produced from a microorganism belonging to the genus Omobacterium or an enzyme produced from animal guts.