JP2536069B2 - Optically active 1-biphenylylethanol ester derivative and process for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Field of Industrial Application> The present invention relates to an optically active 1-biphenylethanol ester derivative useful as an intermediate for an organic electronic material such as a liquid crystal compound.

<Prior Art> Various compounds have been developed as liquid crystal compounds, but very few compounds have an asymmetric carbon atom directly bonded to the core (that is, biphenyl group), and the compounds are ferroelectric liquid crystal compounds. Is not known to be available.

Further, although there are very few ferroelectric liquid crystal compounds having excellent characteristics such as high-speed response and memory property, the development of intermediates for the liquid crystal compounds is still insufficient, and the intermediates and their industrially advantageous production methods are not available. Was wanted.

<Problems to be Solved by the Invention> The present invention has an optically active 1 useful as an intermediate for a ferroelectric liquid crystal compound having such an asymmetric carbon atom directly connected to the core and excellent in the above properties. -A biphenylyl ethanol ester derivative and a method for producing the same.

<Means for Solving the Problems> That is, the present invention provides a compound represented by the general formula (I): (In the formula, R represents a methyl group substituted with a halogen atom or an alkyl group having 2 to 20 carbon atoms and optionally containing a halogen atom, and R ′ represents an alkyl group having 1 to 15 carbon atoms.
The * mark indicates an asymmetric carbon atom. ) Is an optically active 1-biphenylylethanol ester derivative and a method for producing the same.

The novel optically active 1-biphenylylethanol ester derivative can be produced through the four steps described below.

The first step is the general formula (II) (In the formula, R'represents an alkyl group having 1 to 15 carbon atoms.) A ketone represented by the general formula (III) is reduced by using a reducing agent. (In the formula, R'represents an alkyl group having 1 to 15 carbon atoms). The second step is to react the alcohols represented by the general formula (III) with lower alkylcarboxylic acids. , General formula (IV) (In the formula, R'has the same meaning as described above. R "represents a lower alkyl group.) A step of obtaining a dl-ester represented by the formula: The eighth step is a dl-ester represented by the general formula (IV). Are asymmetrically hydrolyzed with an esterase having the ability to hydrolyze one of the enantiomers of the esters to give a compound of general formula (V) (In the formula, R'has the same meaning as described above. * Indicates that it is an asymmetric carbon atom.) A step of obtaining an optically active alcohol represented by the formula, and the fourth step is represented by the general formula (V). The optically active alcohols are represented by the general formula (VI) R-COOH (VI) (wherein R represents a methyl group substituted with a halogen atom or an alkyl group having a carbon number of 2 to 20 and optionally containing a halogen atom). The reaction is performed with a fatty acid carboxylic acid represented by the formula (1) or a derivative thereof to obtain the optically active 1-biphenylylethanol ester derivative represented by the general formula (I).

 The present invention will be described in detail below.

The ketones (II), which is the raw material in the first step, can be easily produced from an aromatic carboxylic acid and an alcohol as shown in the following formula, for example.

The reduction of the ketones (II) can be easily obtained by reducing the ketone with a reducing agent capable of reducing the ketone to an alcohol.

As a reducing agent in this reaction, sodium borohydride, zinc borohydride, aluminum isopropoxide, lithium-tri-t-butoxyaluminum hydride, lithium-tri-s-butylboron hydride, borane, lithium are preferred. Aluminum hydride-silica gel, alkali metal-ammonia, Raney-nickel-hydrogen, etc. are used, and the amount used is at least 1 equivalent or more relative to the starting ketones (II), and usually in the range of 1 to 10 equivalents. Is.

This reaction is usually performed in a solvent. Examples of such a solvent include tetrahydrofuran, dioxane, ethyl ether, methanol, ethanol, n-propyl alcohol, isopropyl alcohol, ethers such as toluene, benzene, chloroform, dichloromethane, halogenated hydrocarbons, and the like. Or a mixture of solvents inert to the reaction, such as alcohols and the like.

The reaction temperature is usually in the range of -30C to 150C, preferably in the range of -20C to 100C.

 The reaction time is not particularly limited.

From the reaction mixture thus obtained, an alcohol (II) is obtained by operations such as liquid separation, concentration, distillation, and crystallization.
I) can be obtained in good yield, but alcohols (II
It is not necessary to isolate I), and the reaction mixture may be directly used in the next step.

The product of the second step, dl-esters (IV), can be easily obtained by reacting an alcohol represented by the general formula (III) with a lower alkylcarboxylic acid to acylate.

In this acylation, an acid anhydride or acid halide of a lower alkylcarboxylic acid is used as the lower alkylcarboxylic acid, and specifically, acetic anhydride, acetic acid chloride or bromide, propionic anhydride, propionic acid chloride or bromide, butane anhydride. Examples thereof include acid, butyryl chloride or bromide, pentanoic acid anhydride, valeroyl chloride or bromide.

This reaction is carried out by applying a normal esterification condition and reacting with a catalyst in the presence or absence of a solvent.

In this reaction, the amount of the lower alkyl carboxylic acid to be used is at least 1 equivalent to the alcohol (III), and the upper limit is not particularly limited, but is preferably 4 or less.
It is equivalent.

When a solvent is used in this reaction, examples of the solvent include tetrahydrofuran, ethyl ether,
Acetone, methyl ethyl ketone, toluene, benzene,
An aliphatic or aromatic hydrocarbon such as chloroform, chlorobenzene, dichloromethane, dichloroethane, carbon tetrachloride, dimethylformamide, or hexane, an ether, or a solvent inert to a reaction such as a halogenated hydrocarbon is used alone or in combination. The amount used is not particularly limited.

Examples of the catalyst include dimethylaminopyridine, triethylamine, tri-n-butylamine, pyridine,
Examples include organic or inorganic basic substances such as picoline, imidazole, sodium carbonate, potassium hydrogencarbonate, etc., and the amount used is the type of lower alkylcarboxylic acid used,
It depends on the combination of catalysts used and the like, and is not necessarily specified. For example, when an acid halide is used as the lower alkylcarboxylic acid, the amount is 1 to 5 equivalent times the acid halide.

When an organic amine is used as a solvent, the amine may act as a catalyst.

Further, acids such as toluene sulfonic acid, methane sulfonic acid and sulfuric acid can also be used as a catalyst.

The reaction temperature is usually -30C to 100C, preferably -20C to 90C.

The reaction time is not particularly limited, and alcohols (II
The point at which I) disappears from the reaction system can be regarded as the reaction end point.

After completion of the reaction, usual separation means such as extraction, liquid separation,
The dl-esters (IV) can be obtained in good yield by concentration, recrystallization, etc., and this can be further purified by column chromatography etc., if necessary. Can be used as is.

The esterase-producing microorganism used in the asymmetric hydrolysis reaction in the third step may be any microorganism that produces an esterase having the ability to asymmetrically hydrolyze dl-esters (IV), and is not particularly limited. Not a thing.

The esterase in the present invention means an esterase in a broad sense including lipase.

Specific examples of such microorganisms include, for example, Enterobacter, Arthrobacter, Previbacterium, Pseudomonas, Alcaligenes, Micrococcus, Chromobacterium, Microbacterium, Corynebacterium, Bacillus, Lactobacillus, Trichoderma, Candida, Saccharomyces, Rhodotorula, Cryptococcus, Torulopsis, Pichia, Penicillium, Aspergillus,
Examples include microorganisms belonging to the genera Rhizopus, Mucor, Aureobasidium, Actinomucor, Nocardia, Streptomyces, Hansenula, and Achromobacter.

Cultivation of the above-mentioned microorganism is usually carried out according to a conventional method, and a culture solution can be obtained by carrying out a liquid solvent, for example.

For example, sterilized liquid medium [malt extract / yeast extract medium for molds and yeasts (dissolve 5 g of peptone, 10 g of glucose, 3 g of malt extract, 3 g of yeast extract in 1 of water, p
H6.5), and for bacteria, a broth containing sweetened broth (dissolving 5 g of peptone, 10 g of glucose, 5 g of meat extract, and 3 g of NaCl in water 1 to adjust pH to 7.2)] with a microorganism, usually 30 to 40
The culture is performed by performing reciprocal shaking culture at 1 ° C. for 1 to 3 days, and solid culture may be performed if necessary.

Some of these esterases originating from microorganisms are commercially available and can be easily obtained. Specific examples of commercially available esterases include the followings.

Pseudomonas lipase [Lipase P (manufactured by Amano Pharmaceuticals)], Aspergillus lipase [Lipase AP (manufactured by Amano Pharmaceuticals)], Mucor lipase [Lipase M-AP]
(Manufactured by Amano Pharmaceutical Co., Ltd.)], lipase of Candida cylindrasse [lipase MY (manufactured by each sugar industry)], lipase of the genus Alcaligenes [lipase PL (manufactured by each sugar industry)], lipase of the genus Achromobacter [lipase AL (each) Made by Sugar Industry)],
Arthrobacter lipase (Nippon Kagaku), Chromobacterium lipase (Toyo Brewing), Rhizopus derema lipase [Talipase (Tanabe Seiyaku)], Rhizopus lipase [Lipase Saiken (Osaka Bacterial Research Institute)].

Also, animal / plant esterase can be used,
Specific examples of these esterases include the following.

Steapsin, pancreatin, pig liver storage esterase, Wheat Germ esterase.

As the esterase used in this reaction, an enzyme obtained from an animal, a plant, or a microorganism is used, and the form of use is a purified enzyme, a crude enzyme, an enzyme-containing substance, a microorganism culture solution, a culture, a cell, a culture solution. In addition, they can be used in various forms, such as those obtained by treating them, as needed, and enzymes and microorganisms can be used in combination. Alternatively, it can also be used as an immobilized enzyme or immobilized bacterium immobilized on a resin or the like.

The asymmetric hydrolysis reaction is generally carried out by vigorously stirring a mixture of the raw material dl-esters (IV) and the above-mentioned enzyme or microorganism in a buffer solution.

As the buffer solution, sodium phosphate which is usually used,
A buffer solution of an inorganic acid salt such as potassium phosphate, a buffer solution of organic hydrochloric acid such as sodium acetate or sodium citrate, etc. is used, and its pH is 8 to 11 in the culture solution of an alkaliphilic bacterium or alkaline esterase, and an alkaliphilicity. A pH of 5 to 8 is preferable for a culture solution of a microorganism other than that or an esterase having no alkali resistance. The concentration is usually 0.05 to 2M, preferably 0.05 to 0.5M.

The reaction temperature is usually 10 to 60 ° C., and the reaction time is generally 10 to 70 hours, but is not limited thereto.

In addition, in the case of asymmetric hydrolysis reaction, in addition to the buffer solution, it is also possible to use an organic solvent which is inert to the reaction such as toluene, chloroform, methyl isobutyl ketone, dichloromethane, etc. Can be advantageously performed.

After completion of such asymmetric hydrolysis reaction, the asymmetric hydrolysis reaction solution is treated with, for example, methyl isobutyl ketone, ethyl acetate,
Extraction treatment with a solvent such as ethyl ether, removal of the solvent from the organic layer, and treatment of the concentrated residue by column chromatography are carried out to obtain a mixture with the optically active alcohol (V), which is an asymmetric hydrolysis product, and insoluble. It is possible to separate optically active esters which are residues of simultaneous hydrolysis.

The optically active ester obtained here may be further hydrolyzed as necessary to obtain an optically active alcohol which is an antipode to the previously obtained optically active alcohol (V).

When a lipase belonging to the genus Pseudomonas or the genus Arthrobacter is used as the lipase in this asymmetric hydrolysis reaction, an optically active alcohol (V) can be obtained with relatively high optical purity.

In the reaction for obtaining the optically active 1-biphenylylethanol ester derivative (I) from the optically active alcohol (V) (4th step), the optically active alcohol (V) is replaced with the aliphatic carboxylic acid (VI) or its derivative. It is carried out by reacting with a derivative.

In the general formula (VI), R is, for example, a halogen-substituted methyl group or an alkyl group having 2 to 20 carbon atoms and optionally containing a halogen atom.

Chloromethyl, dichloromethyl, trichloromethyl,
Ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl, 1-methylethyl, 2-methylbutyl, 2,3
-Dimethylbutyl, 2,3,3-trimethylbutyl, 2-methylpentyl, 3-methylpentyl, 2,3-dimethylpentyl, 2,4-dimethylpentyl, 2,3,3,4-tetramethylpentyl, 2 -Methylhexyl, 3-methylhexyl, 4-methylhexyl, 2,5-dimethylhexis, 2
-Methylheptyl, 2-methyloctyl, 2-trihalomethylpentyl, 2-trihalomethylhexyl, 2-trihalomethylheptyl, 2-halopropyl, 3-halo-
2-methylpropyl, 2,3-dihalopropyl, 2-halobutyl, 3-halobutyl, 2,3-dihalobutyl, 2,4-dihalobutyl, 3,4-dihalobutyl, 2-halo-3-methylbutyl, 2-halo-3 , 3-Dimethylbutyl, 2-halopentyl, 3-halopentyl, 4-halopentyl, 2,4
-Dihalopentyl, 2,5-dihalopentyl, 2-halo-
3-methylpentyl, 2-halo-4-methylpentyl,
2-halo-3-monohalomethyl-4-methylpentyl,
2-halohexyl, 3-halohexyl, 4-halohexyl, 5-halohexyl, 2-haloheptyl, 2-halooctyl (however, halo in the above alkyl group represents fluorine, chlorine, bromine or iodine) and the like.

Incidentally, these alkyl groups may be optically active groups.

Some of the optically active aliphatic carboxylic acids having these optically active groups are obtained by oxidation of the corresponding alcohol and reductive deamination of amino acids. Some can be derived from optically active amino acids and optically active oxyacids that occur naturally or are obtained by resolution, such as:

Alanine, palin, leucine, isoleucine, phenylalanine, serine, threonine, alosreonine, homoserine, alloisoleucine, tert-leucine, 2-aminobutyric acid, norvaline, norleucine, ornithine, lysine, hydroxylysine, phenylglycine, trifluoroalanine, asparagine Acid, glutamic acid, lactic acid,
Mandelic acid, tropic acid, 3-hydroxybutyric acid, malic acid, tartaric acid, isopropylmalic acid, etc.

Further, examples of the derivative of the aliphatic carboxylic acid represented by the general formula (VI) include acid anhydrides of fatty acid carboxylic acids having the alkyl groups exemplified above, and further acid halides such as acid chloride and acid bromide. .

The reaction between the optically active alcohol (V) and the aliphatic carboxylic acid (VI) or its derivative is usually carried out in the presence or absence of a solvent, generally in the presence of a catalyst.

When a solvent is used in this reaction, examples of the solvent include aliphatic or aromatic solvents such as tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, toluene, benzene, chlorobenzene, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, dimethylformamide, and hexane. Solvents which are inert to the reaction of group hydrocarbons, ethers, halogenated hydrocarbons and the like, alone or in a mixture. The amount used can be used without particular limitation.

When the above-mentioned acid anhydride or acid halide of the aliphatic carboxylic acid is used in the reaction, the amount used is required to be 1 equivalent or more times the amount of the optically active alcohol (V). Although not particularly limited, it is preferably 4 equivalents.

Examples of the catalyst include dimethylaminopyridine, triethylamine, tri-n-butylamine, pyridine,
Picoline, collidine, imidazole, sodium carbonate,
Examples thereof include organic or inorganic basic substances such as sodium methylate and potassium hydrogen carbonate. Further, an organic acid or an inorganic acid such as toluenesulfonic acid, methanesulfonic acid or sulfuric acid may be used as a catalyst.

In using such a catalyst, pyridine is particularly preferably used when, for example, an acid halide of an aliphatic carboxylic acid is used as a raw material.

The amount of the catalyst used varies depending on the type of the acid anhydride or acid halide of the aliphatic carboxylic acid and the combination of the catalyst used, and is not necessarily specified.For example, when an acid halide is used, the amount of the acid halide is It is 1 equivalent or more.

When an aliphatic carboxylic acid is used in the reaction, it is dehydrated and condensed by using the carboxylic acid in the presence of a condensing agent, usually in an amount of 1 to 2 equivalents with respect to the optically active alcohol (V). An optically active 1-biphenylylethanol ester derivative (I) can be obtained.

As the condensing agent, a carbodiimide such as N, N'-dicyclohexylcarbodiimide or N-cyclohexyl-N '-(4-diethylamino) cyclohexylcarbodiimide is preferably used, and if necessary, an organic base such as 4-pyrrolidinopyridine, pyridine or triethylamine. Are used together.

The amount of the condensing agent used is 1 to 1.2 equivalent times the carboxylic acid, and the amount of the base used is 0.01 to 0.2 equivalent times the condensing agent.

The reaction temperature is usually -30 ° C to 100 ° C, preferably -25 ° C to 80 ° C.

The reaction time is not particularly limited, and the time when the optically active alcohols (V) as the raw materials disappear can be regarded as the end point of the reaction.

After completion of the reaction, usual separation means such as extraction, liquid separation,
The optically active 1-biphenylylethanol ester derivative represented by the general formula (I) can be obtained in good yield from the reaction mixture by an operation such as concentration, and can be purified by column chromatography or the like if necessary.

<Effects of the Invention> Thus, according to the present invention, an optically active 1-biphenylylethanol ester derivative useful as an intermediate for organic electronic materials such as liquid crystal compounds and agricultural and pharmaceutical products can be obtained with high optical purity. It can be manufactured in good yield.

<Example> Hereinafter, the present invention will be described with reference to Examples.

Example 1 4′-in a four-necked flask equipped with a stirrer and a thermometer.
Ethyl acetyl-4-biphenylcarboxylate 32.2 g (0.1
2 mol), 50 ml of ethanol and 150 ml of chloroform are charged, and 2.3 g of sodium borohydride is added thereto at 15 to 25 ° C.
(0.06 mol) is added over 10 minutes.

After keeping at the same temperature for 2 hours, the reaction mixture is poured into ice water and extracted twice with 200 ml of ethyl acetate. The organic layer was washed with water and then concentrated under reduced pressure to give ethyl 4 '-(1-hydroxyethyl) -4-biphenylcarboxylate (III-
1) 30.8 g (yield 95%) was obtained.

Next, 29.7 g (0.11 mol) of (III-1) obtained here was dissolved in a mixed liquid consisting of 150 ml of toluene and 50 ml of pyridine, and 9.42 g (0.12 mol) of acetyl chloride was added thereto at 15 to 20 ° C.
Add in 2 hours. 40 to 50 ℃ for 1 hour at the same temperature
Keep it warm for 2 hours. After completion of the reaction, cool to 10 ° C or lower, add 300 ml of 3N hydrochloric acid water to separate the organic layer, and then 5
Wash successively with aqueous sodium bicarbonate and water. The organic layer was concentrated under reduced pressure and further purified by column chromatography to obtain 4 '.
33.7 g (yield 98%) of ethyl ((IV-1))-(1-acetoxyethyl) -4-biphenylcarboxylate was obtained.

20.0 g (64 mmol) of (IV-1) obtained above was added to 400 ml of 0.1M phosphate buffer (pH 7.0) and amanolipase "P".
Mix with 4g and stir vigorously at 40-45 ° C for 20 hours.

After completion of the reaction, the reaction mixture was treated with methyl isobutyl ketone 60
Extract with 0 ml. The organic layer was concentrated under reduced pressure, and the residue was purified by column chromatography using a mixed solution of hexane: ethyl acetate = 12: 1 as an eluting solvent to obtain (+)-4 '-(1-hydroxyethyl) -4-biphenylcarboxylic acid. Ethyl acid 7.
0 g [▲ [α] ²⁰ _D ▼ + 35.5 ° (c = 0.544, CHCl ₃ ), 98.
1% ee, m.p 74.4 ° C.] and ethyl (−)-4 ′-(1-acetoxyethyl) -4-biphenylcarboxylate.

(+)-4 '-(1-hydroxyethyl) obtained here
0.81 g (3 mmol) of ethyl-4-biphenylcarboxylate was dissolved in 20 ml of pyridine, 1.1 g (4 mmol) of hexadecanoyl chloride was added, and the mixture was stirred at 30-40 ° C for 1 hour. After completion of the reaction, the reaction mixture was poured into 200 ml of water and extracted with 200 ml of toluene, and the organic layer was extracted with 4N hydrochloric acid, water, 5% sodium hydrogen carbonate solution,
Wash sequentially with water. The obtained toluene layer is concentrated under reduced pressure, and the residue is purified by silica gel column chromatography (eluent toluene).

Ethyl (+)-4 '-(1-hexadecanoyloxyethyl) -4-biphenylcarboxylate 1.46 g (yield 96
%) Was obtained.

▲ [α] ²⁰ _D ▼ = + 34.1 ° (C = 1, CHCl ₃ ) mp.69-70 ° C Example 2 4′-in a four-necked flask equipped with a stirrer and a thermometer.
Acetyl-4-biphenylcarboxylic acid pentyl 37.2 g
(0.12 mol), ethanol 50 ml and chloroform 150 m
2.3 g (0.06 mol) of sodium borohydride is added thereto at 15 to 25 ° C. over 10 minutes. After incubating at the same temperature for 2 hours, the reaction mixture was poured into ice water to prepare a mixture of Example 1
The post-treatment was carried out in the same manner as in 4 '-(1-hydroxyethyl) -4-biphenylcarboxylic acid pentyl (III-2) 3
6.4 g (97% yield) was obtained.

Next, 34.4 g (0.11 mol) of (III-2) obtained here was dissolved in a mixed solution consisting of 200 ml of dichloromethane and 50 ml of pyridine, and 50 ml of a dichloromethane solution containing 9.42 g (0.12 mol) of acetyl chloride was added thereto at room temperature. Drop it. After about 2 hours, the reaction solution is poured into 300 ml of 3N hydrochloric acid, and an extraction operation is performed. The organic layer is washed successively with water, 7% aqueous sodium hydrogen carbonate and water, and dried over anhydrous magnesium sulfate. The solvent was distilled off to give 37.8 g of a pale yellow oily pentyl (IV-2) 4 '-(1-acetoxyethyl) -4-biphenylcarboxylate (yield 97
%) Was obtained.

20.0 g (56 mmol) of (IV-2) obtained above was mixed with 200 ml of 0.3 M phosphate buffer (pH 7.0), 10 ml of chloroform and 4 g of amanolipase "P" and stirred vigorously at 38-40 ° C for 24 hours. To do.

After completion of the reaction, the reaction mixture is extracted with 600 ml of ethyl acetate. The organic layer was concentrated under reduced pressure, and the residue was subjected to column chromatography separation and purification using a mixed solution of hexane: ethyl acetate = 12: 1 as an eluting solvent (+)-4 '-(1-hydroxyethyl) -4-. 7.5 g of pentyl biphenylcarboxylate
(▲ [α] ²⁰ _D ▼ + 30.3 ° (c = 1, CHCl ₃ ), 99.3% ee,
m.p70.3 [deg.] C.] and 10.3 g of pentyl (-)-4 '-(1-acetoxyethyl) -4-biphenylcarboxylate. 0.94 g (3 mmol) of pentyl (+)-4 '-(1-hydroxyethyl) -4-biphenylcarboxylic acid obtained here was dissolved in 20 ml of triethylamine, 0.67 g (5 mmol) of hexanoyl chloride was added, and the mixture was added at 60 ° C. Stir for 2 hours. After completion of the reaction, the reaction mixture is poured into 200 ml of water and extracted with 200 ml of ethyl acetate. The organic layer is washed successively with 2N hydrochloric acid, water, 5% aqueous sodium hydrogen carbonate and water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue is silica gel column chromatography (eluent toluene)
Purified by (+)-4 '-(1-hexanoyloxyethyl) -4-biphenylcarboxylic acid pentyl 1.14 g
(Yield 93%) was obtained.

▲ [α] ²⁰ _D ▼ = + 45.3 ° (C = 1, CHCl ₃ ) ▲ n ²⁰ _D ▼ = 1.5412 Example 3 4′-acetyl-4 in place of ethyl 4′-acetyl-4-biphenylcarboxylate. -(+)-4 '-(1-hydroxyethyl) was subjected to reduction, acetylation and asymmetric hydrolysis reaction and post-treatment according to Example 1 except that 20.4 g (0.05 mol) of dodecyl biphenylcarboxylate was used. -4-
Dodecyl biphenylcarboxylate 8.8g (yield 43%) [▲
[Α] ²⁰ _D ▼ + 19.2 ° (c = 1, CHCl ₃ ), mp.63-65 ° C]
And (-)-4 '-(1-acetoxyethyl) -4-
10.8 g (yield 48%) of dodecyl biphenylcarboxylate was obtained.

(+)-4 '-(1-hydroxyethyl) obtained here
1.23 g (3 mmol) of dodecyl-4-biphenylcarboxylate was dissolved in 20 ml of pyridine, and hexanoyl chloride was added.
54 g (4 mmol) was added, and the mixture was stirred at 30-40 ° C for 4 hr. After the completion of the reaction, the reaction mixture was poured into 200 ml of water and extracted with 200 ml of toluene. Thereafter, the same post-treatment and purification as in Example 1 were performed to obtain (+)-4 '-(1-hexanoyloxyethyl)- 4-Biphenylcarboxylic acid dodecyl
1.55 g (95% yield) was obtained.

▲ [α] ²⁰ _D ▼ = + 34.1 ° (C = 1, CHCl ₃ ), ▲ n ²⁰ _D
▼ = 1.5240 Example 4 In the same manner as in Example 1 except that 0.48 g (4 mmol) of 2 (S) -methylbutanoyl chloride was used in place of hexadecanoyl chloride, an acylation reaction and a post-treatment were carried out (+)- Ethyl 4 '-{1-2 (S) -methylbutanoyloxy) ethyl} -4-biphenylcarboxylate 1.13 g
(Yield 96.5%) was obtained.

▲ [α] ²⁰ _D ▼ = + 90.0 ° (C = 1, CHCl ₃ ) ▲ n ²⁰ _D ▼ = 1.5505 Example 5 In Example 2, 2 was used instead of hexanoyl chloride.
(S) -Chloro-3 (S) -methylpentanoyl chloride (0.84 g, 5 mmol) was used in the same manner as above, and the post-treatment was followed by (+)-4 '-{1-2 (S)-. Chloro-3 (S) -methylpentanoyloxy) ethyl}-
Pentyl 4-biphenylcarboxylate, 1.25 g (94% yield)
I got

▲ [α] ²⁰ _D ▼ = + 44.8 ° (C = 1, CHCl ₃ ) ▲ n ²⁰ _D ▼ = 1.5480 Example 6 4′-Acetyl-4 in place of ethyl 4′-acetyl-4-biphenylcarboxylate. -Octyl biphenylcarboxylate was reduced, acetylated and asymmetrically hydrolyzed in the same manner as in Example 1 except that 17.6 g (0.05 mol) was used and post-treated to give (+)-4 '-(1-hydroxyethyl)- Octyl 4-biphenylcarboxylate 7.1 g (40% yield) {▲
[Α] ²⁰ _D ▼ + 20.1 ° (c = 1, CHCl ₃ ), mp.69-70 ° C}
And (-)-4 '-(1-acetoxyethyl) -4-
Dodecyl biphenylcarboxylate was obtained.

(+)-4 '-(1-hydroxyethyl) obtained here
Octyl-4-biphenylcarboxylate (1.77 g, 5 mmol) and octanoic acid (1.0 g, 7 mmol) were dissolved in 20 ml of anhydrous dichloromethane to give dicyclohexylcarbodiimide 1.
6 g (8 mmol) and 4-pyrrolidinopyridine 0.1 g are added, and the mixture is stirred at room temperature for 24 hours. After completion of the reaction, after separating the generated precipitate, 200 ml of toluene was added to the liquid,
Wash sequentially with water, 5% acetic acid water, water, 5% sodium bicarbonate water, and water. The organic layer was concentrated under reduced pressure and then purified by silica gel column chromatography in the same manner as in Example 1 to obtain (+)-4 '.
2.1 g of octyl- (1-octanoyloxyethyl) -4-biphenylcarboxylate was obtained (yield 87%).

▲ [α] ²⁰ _D ▼ + 35.3 ° (c = 1, CHCl ₃ ) ▲ n ²⁰ _D ▼ = 1.5250

Claims (5)

(57) [Claims] 1. A general formula (I) (In the formula, R represents a methyl group substituted with a halogen atom or an alkyl group having 2 to 20 carbon atoms and optionally containing a halogen atom, and R ′ represents an alkyl group having 1 to 15 carbon atoms.
The * mark indicates an asymmetric carbon atom. ) An optically active 1-biphenylylethanol ester derivative represented by: 2. General formula (V) (In the formula, R'represents an alkyl group having 1 to 15 carbon atoms. * Represents an asymmetric carbon atom.) An optically active alcohol represented by the general formula (VI) R-COOH ( VI) (wherein R represents a methyl group substituted with a halogen atom or an alkyl group having 2 to 20 carbon atoms and optionally containing a halogen atom), and reacting with a fatty acid carboxylic acid or a derivative thereof. A process for producing an optically active 1-biphenylylethanol ester derivative represented by the general formula (I), characterized in that 3. General formula (IV) (In the formula, R ′ represents an alkyl group having 1 to 15 carbon atoms and R ″
Represents a lower alkyl group. ) The dl-ester represented by the formula (5) is asymmetrically hydrolyzed with an esterase having the ability to hydrolyze either one of the enantiomers of the ester to give an optically active alcohol represented by the general formula (V). And then reacting with a fatty acid carboxylic acid represented by the general formula (VI) or a derivative thereof, the optically active 1 represented by the general formula (I).
-A method for producing a biphenylyl ethanol ester derivative. 4. A general formula (III) (In the formula, R'represents an alkyl group having 1 to 15 carbon atoms.) An alcohol represented by the formula (1) is reacted with a lower alkylcarboxylic acid to obtain a dl-ester represented by the general formula (IV). Asymmetric hydrolysis using an esterase having the ability to hydrolyze either one of the enantiomers of the esters to obtain the optically active alcohols represented by the general formula (V),
Then, a method for producing an optically active 1-biphenylylethanol ester derivative represented by the general formula (I), which comprises reacting with a fatty acid carboxylic acid represented by the general formula (VI) or a derivative thereof. 5. The general formula (II) (In the formula, R ′ represents an alkyl group having 1 to 15 carbon atoms.) The ketones represented by the formula (3) are reduced with a reducing agent to obtain alcohols represented by the general formula (III), It is reacted with alkylcarboxylic acids to obtain dl-esters represented by the general formula (IV), and asymmetrically hydrolyzed with an esterase having the ability to hydrolyze only one of the enantiomers of the esters. To obtain an optically active alcohol represented by the general formula (V), and then reacting the fatty acid carboxylic acid represented by the general formula (VI) or a derivative thereof with the optically active alcohol represented by the general formula (I). Na 1
-A method for producing a biphenylyl ethanol ester derivative.