JPH03101632A - Optically active biphenyl derivative and its production - Google Patents

Abstract

NEW MATERIAL:The compound of formula I (R is (halogen-substituted) 1-20C alkyl or alkoxyalkyl; X is HOOC or HO; (n) is 1-5: asterisk represents an asymmetric carbon atom). EXAMPLE:(-)-4-Hydroxy-4'-(1-methyl-2-propoxyethyl)biphenyl. USE:An intermediate for ferroelectric liquid crystal material. PREPARATION:A compound of formula I wherein X is HO can be produced by subjecting an optically active acylbiphenyl derivative of formula II to Baeyer- Villiger oxidation and hydrolyzing the resultant compound of formula III. Another compound of formula I wherein X is HOOC is produced by oxidizing the compound of formula II. Both of the compounds of formula II and formula III are novel.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to optically active fflA biphenyls useful as intermediates for Ia electronic materials, and a method for producing the same. More specifically, it relates to optically active biphenyl derivatives useful as intermediates for liquid crystal materials, particularly ferroelectric liquid crystal materials, and methods for producing the same. <Prior art> Various compounds have been developed as liquid crystal compounds, but there are very few ferroelectric liquid crystal materials with excellent characteristics such as high-speed response, and the development of intermediates for these liquid crystal compounds is still insufficient. Therefore, such an intermediate and an industrially advantageous manufacturing method thereof have been desired.

Problems to be Solved by the Invention> An object of the present invention is to provide an optically active biphenyl derivative useful as an intermediate for a ferroelectric liquid material having excellent properties as described above, and a method for producing the same. It is also an object of the present invention to provide an intermediate for and a method for producing the same. <! ! $! Means for Solving the Problems> That is, the present invention provides an alkyl group or an alkoxyalkyl group having a carbon number of 1 to 20 which may be substituted with a halogen atom, and X is a HOOC - or HO, n is an integer of 1 to 5, and * indicates an asymmetric carbon atom.
) and its production method. The present invention will be explained in detail below. The optically active biphenyl derivative in which X is an OH- group in the general formula (1) has the general formula (n) (wherein R2 represents a lower alkyl group, and R, n and * represent the same meanings as above). It is produced by hydrolyzing the optically active acyloxybenzene derivative shown in .). The optically active acyloxybenzene derivative represented by the above general formula (n) can also be produced by the general formula (DI). The optically active biphenyl derivative in which X is a HOOC group in the general formula (I) can be produced by oxidizing the optically active acylbiphenyl derivative represented by the general formula [■].

The optically active acylbiphenyl derivative represented by the general formula (III) is an optically active acyl biphenyl derivative represented by the general formula (V) (wherein R, R''n and * represent the same meanings as above). Biphenyl derivatives can be produced by Bayer-Billiger oxidation.The general formula (
Optically active biphenyl derivatives in which X is an OH group in 1) are also . By debenzylating a penzyloxybiphenyl derivative represented by the general formula (rV) (in the formula, R, n and * have the same meanings as above) in the presence of a hydrogenation catalyst and hydrogen (the formula Medium, R”
n and *marks have the same meanings as above. ) Optically active alcohols represented by the general formula (Vl) RY (Vl) (wherein R represents the same meaning as above, and Y represents a halogen atom or -OSOgR' group. Here, R3 represents a lower alkyl group or an optionally substituted phenyl group.) It can be produced by reacting with the alkylating agent shown below. The optically active penzyloxybiphenyl derivative represented by the general formula (fV) is represented by the general formula [■] and the above general formula [■]
The optically active ester derivative represented by the general formula (IX
)) optically active pendyloxybiphenyls represented by
Produced by reacting an alkylating agent represented by the general formula (Vl) R-y (Vl) (wherein R and Y have the same meanings as above) in the presence of a basic substance. Can be done. The general formula (V)
The optically active alcohol represented by the general formula [■] (wherein R"n and this mark represent the same meanings as above, and R
' represents a lower alkyl group. ) can be produced by hydrolyzing the optically active ester derivatives shown. (In the formula, R' n and * represent the same meanings as above.) It can be produced by acylating an optically active ester represented by the following formula. The optically active esters represented by the above general formula (IX) include an optically active alcohol derivative represented by the general formula (X)
I) RI COOH (XI) (In the formula, Rl represents the same meaning as above.) It can be produced by reacting with a carboxylic acid or a derivative thereof. The optically active alcohol derivative represented by the above general formula (X) can be produced by reducing the optically active carboxylic acid represented by the general formula (Xll). In the production of the optically active biphenyl derivative (1) in which X is one OH group by hydrolysis of the optically active acyloxybenzene derivative (n), the reaction is carried out in the presence of water, with acid or alkali being passed away. It will happen. Examples of acids used here include sulfuric acid, phosphoric acid,
Examples include inorganic acids such as hydrochloric acid, and organic acids such as toluenesulfonic acid and methanesulfonic acid. As the alkali, sodium hydroxide, potassium hydroxide, barium hydroxide, potassium carbonate, sodium carbonate or 1.8-diazabicyclo[5,4.0)? - Inorganic and organic bases such as undecene. The amount of such acid or alkali to be used is as follows. The acid is usually used in an amount of 0.02 times to 10 times the mole of the acyloxybenzene derivative (II), and the alkali is required in an amount of at least 2 times the mole, and the upper limit is not particularly limited, but preferably 10 times the mole. It is less than a mole. The reaction is usually carried out in the presence of a solvent. Such solvents include aliphatic or aromatic hydrocarbons such as methanol, ethanol, propanol, acetone, methyl ethyl ketone, chloroform, dichloromethane, toluene, xylene, hexane, heptane, ethyl ether, tetrahydrofuran, dioxane, dimethylformamide, and N-methylpyrrolidone. Examples include solvents inert to the reaction, such as ether, alcohol, ketone, amide, or halogenated hydrocarbon, and these solvents may be used alone or in combination. There are no particular restrictions on its usage. The reaction temperature is
Usually -30°C to 150°C, preferably -20°C to 10
It is 0°C. Although the reaction time is not particularly limited, the end point of the reaction is usually taken as the time when the acyloxybenzene conductor (It) is no longer detected in the reaction system. The reaction mixture thus obtained is subjected to, for example, acid precipitation,
By adding post-processing operations such as extraction, liquid separation, or concentration, an optically active biphenyl derivative in which X is an H group in the general formula (1) can be obtained. In the production of optically active acyloxybenzene derivatives (tl) by Bayer-Villiger oxidation of optically active acylbiphenyl Pl form (■), the oxidizing agents used in the reaction include peracetic acid, performic acid, methachloroperbenzoic acid, and peroxybenzene. Examples include peracids such as benzoic acid. Such a peracid can be generated, for example, from the corresponding acid and hydrogen peroxide, and while synthesizing the peracid in the reaction system,
Bayer-Villiger oxidation can also be performed. The peracid is usually an optically active acylbiphenyl derivative (I
II) is required to be at least 1 times the equivalent amount, and although there is no particular restriction on the upper limit, it is preferably 1 to 2 times the amount. In Bayer-Villiger oxidation, a solvent that is inert to the oxidation reaction is usually used. Examples of such solvents include halogenated hydrocarbon, aromatic or aliphatic hydrocarbon solvents such as dichloromethane, dichloroethane, chloroform, chlorobenzene, benzene, toluene, xylene, hexane, and cyclohexane, and these solvents may be used alone or in combination. Used in combination. The reaction temperature is usually -20°C to 130°C, preferably -10°C to 100°C. The reaction time is not particularly limited, and usually the acylbiphenyl derivative (I[+] is detected from the reaction system. The end point of the reaction is defined as the end of the reaction.
By adding usual post-treatment operations such as filtration, extraction, separation, or concentration, an optically active acyloxybenzene derivative represented by the 1M formula [■] can be obtained. In the production of an optically active biphenyl derivative (1) in which system, P d C,
PdBaSOs, palladium-based materials such as palladium black, rhodium-based materials such as Rh-C, Rh-AlO, etc., Ru
O. Examples include ruthenium-based catalysts such as SRu-C, nickel-based catalysts such as Raney nickel, and palladium-based catalysts are particularly preferably used. The hydrogenation catalyst is generally used in an amount of 0.01 to 100% by weight, preferably 0.1 to 50% by weight, based on the optically active pendyloxybiphenyl derivative (rV). Solvents include alcohols such as methanol and ethanol, dioxane,
Ethers such as tetrahydrofuran, aromatic hydrocarbons such as benzene and toluene, aliphatic hydrocarbons such as n-hexane and cyclohexane, esters such as ethyl acetate,
Examples include adhesions such as dimethylformamide, fatty acids such as acetic acid, and water, which may be used alone or in combination. The above reaction is usually carried out under normal pressure or increased pressure, and the pressure range is usually 1 to 200 atmospheres. The reaction temperature is usually 0°C to 200°C, preferably 20°C to 180°C. Although the reaction time is not particularly limited, the end point of the reaction is usually when the optically active pendyloxybiphenyl derivative (IV) is no longer detected in the reaction system or when hydrogen absorption has ceased. The reaction mixture thus obtained has f! liU,'a1i
l! , by adding usual post-treatment operations such as recrystallization, distillation or column chromatography, general formula (1)
An optically active biphenyl derivative in which X is one HO group is obtained. Acylbiphenyl Mm form (by oxidation of 113, X is H
In the production of the optically active biphenyl derivative (1), which is an OOC group, the oxidizing agent used in the reaction can be any one that oxidizes an acyl group to form a carboxylic acid without any particular restrictions; Examples of oxidizing agents include potassium dichromate, sodium dichromate, potassium permanganate, sodium permanganate, potassium hypochlorite, sodium hypochlorite, potassium hypobromite, and sodium hypobromite. An example is given. Such an oxidizing agent is 1
Although the upper limit is not particularly limited, it is preferably 10 times the actual value or less. Organic solvents can be used in this reaction, including dioxane, tetrahydrofuran,
A solvent inert to the oxidation reaction, such as N-methylpyrrolidone, is used.

The reaction temperature is usually -20 to 130°C, preferably -
Perform at 10-100℃. The reaction time is not particularly limited, and the end point of the reaction is usually taken as the time when the optically active acylbiphenyl derivative (III) is no longer detected in the reaction system. The reaction mixture obtained in this way is usually subjected to post-treatment operations such as filtration, acid precipitation, extraction, separation, or concentration to improve the optical activity in which X is one HOOC group in -a formula (r). A biphenyl derivative is obtained. Optically active alcohol l (V) and alkylating agent (Vl
) In the production of optically active acylbiphenyl V, conductor (I [I), the reaction is usually carried out in the presence of a basic substance, such as sodium hydride, Alkali metal hydrides such as potassium, alkali metals such as lithium, sodium, and potassium, alkali metal alcoholates such as sodium ethylate and sodium methylate, alkali metal carbonates such as sodium carbonate and potassium carbonate, and organic lithium such as butyl lithium. An example is given. The basic substance is required to be used in an amount of 1 equivalent or more relative to the optically active alcohol (V), and is preferably used in an amount of 3 equivalent or less, although the upper limit is not particularly limited. The alkylating agent used in this alkylation reaction is a chloride, bromide, iodide, etc. having an alkyl group having 1 to 20 carbon atoms or an alkoxyalkyl group which may be substituted with a halogen atom as exemplified below. These are halides or silicates such as methanesulfonate, ethanesulfonate, benzenesulfonate, and toluenesulfonate.
1 to 1 carbon atoms, which may be substituted with the above halogen atom
Examples of the alkyl group or alkoxyalkyl group of 20 include the following. Methyl, edyl, proyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, hebutadecyl, octadecyl, nonadecyl, eicosyl, methoxymethyl, methoxyethyl, methoxybrobyl, Methoxybutyl, methoxypentyl, methoxyhexyl, methoxyheptyl, methoxyoctyl, methoxynonyl,
Methoxydecyl, ethoxymethyl, ethoxyethyl, ethoxybrovir, ethoxybutyl, ethoxybentyl,
Ethoxyhexyl, ethoxyhebutyl, ethoxyoctyl, ethoxynonyl, ethoxydecyl, broboxymethyl, broboxyethyl, proboxybrovir, proboxybutyl, broboxybentyl, propoxyhexyl,
Proboxyhebutyl, probocyoctyl, probocynonyl, proboxydecyl, ptoxymethyl, ptoxyethyl, butoxybu pill, butoxybutyl, butoxybentyl, butoxyhexyl, butoxyhebutyl, butoxyoctyl, phthoxynonyl, butoxydecyl, pentyloxymethyl, pentyloxy Ethyl, pentyloxypropyl, pentyloxybutyl, benzyloxypentyl, benzyloxyhexyl, benzyloxyhebutyl, pentyloxyoctyl, benzyloxynonyl, pentyloxydecyl, hexyloxymethyl, hexyloxyethyl, hexyloxypropyl , hexyloxybutyl, hexyloxypentyl, hexyloxyhexyl, hexyloxyhebutyl, hexyloxyoctyl, hexyloxynonyl, hexyloxydecyl, heptyloxymethyl, hebutyloxyethyl,
Heptyloxybrobyl, hebutyloxybutyl, hebutyloxybenzyl, octyloxymethyl, octyloxyethyl, decyloxymethyl, decyloxyethyl, decyloxyprovir, l-methylethyl, l-methylbropyl, 1-methylbutyl, 2-methylbutyl,
2.3-dimethylbutyl, 2,3.3-}limethylbutyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 2.3-dimethylbentyl, 2,4-dimethylpentyl, 2,3, 3.4-tetramethylpentyl, 1-methylhexyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 2.5-dimethylhexyl, l-methylhexyl, 2-methylheptyl,
1-methyloctyl, 2-methyloctyl, 2-trihalomethylbentyl, 2-trihalomethylhexyl, 2-
Trihalomethylhebutyl, 2-haloethyl, 2-haloprobyl, 3-halobrovir, 3-halo2-methylpropyl, 2.3-dihaloprobyl, 2-halofthyl, 3-
halobutyl, 4-halobutyl, 2,3-dihalobutyl,
2.4-Dihalobutyl, 3,4-dihalobutyl, 2-halo3-methylbutyl, 2-halo3.3-dimethylbutyl, 2-halobentyl, 3-halopentyl, 4-halobentyl, 5-halobentyl, 2,4-dihalobentyl ,
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, - 6-halohexyl, 2-halohbutyl, 2-halooctyl (however, in the above examples, halo represents fluorine, chlorine, bromine or iodine), etc. In general formula (Vl), when the substituted iR is an alkyl group containing a bromine or iodine atom, sulfuric esters are generally preferably used as the alkylating agent from the viewpoint of reaction yield. However, when the substituent R is an alkyl group containing a fluorine or chlorine atom, even if the alkylating agent is bromide or iodide, it can be used without problems due to the difference in reactivity. Note that the branched alkyl group or alkoxyalkyl group among the above-exemplified alkyl groups or alkoxyalkyl groups may be an optically active alkyl group or alkoxyalkyl group having an asymmetric carbon atom. In addition, these halides (chloride, bromine or iodide) or sulfuric esters having optically active alkyl or alkoxyalkyl groups are derived from corresponding optically active alcohols, and some of these optically active alcohols are It is easily obtained by asymmetric reduction of the corresponding ketone using an asymmetric metal catalyst, a microorganism, or an enzyme. Others are naturally occurring or obtained by splitting. For example, it can be derived from the following optically active amino acids and optically active oxyacids. Alanine, parine, leucine, isoleucine, phenylalanine, serine, threonine, allothreonine, homoserine, alloisoleucine, tert. Monoleucine, 2-aminobutyric acid, norvaline, norleucine, ornithine, lysine, hydroxylysine, phenylglycine, trifluoroalanine, aspartic acid, glutamic acid, lactic acid, mandelic acid, tropic acid, 3-hydroxybutyric acid, malic acid, tartaric acid, isoprobil Malic acid etc. Such alkylating agents (
VI) is optionally used in an amount of 1 equivalent or more relative to the optically active alcohol (V), but is usually used in an amount of 1 to 5 times. Examples of reaction solvents include aliphatic or aromatic hydrocarbons such as tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, toluene, benzene, chloroform, chlorobenzene, dichloromethane, dichloroethane, carbon tetrachloride, dimethylformamide, and hexane;
Solvents inert to the reaction, such as ethers, ketones, halogenated hydrocarbons, and ξ-does, may be used alone or in combination, and the amount used is not particularly limited. Furthermore, polar solvents such as dimethyl sulfoxide, hexamethylphosphorylamide, and N-methylpyrrolidone can also be used. The reaction temperature is usually -50 to 120°C, preferably -
30~100'C. The reaction temperature is not particularly limited, and the end point of the reaction is usually determined when optically active alcohol (V) is no longer detected in the reaction system. After the reaction, an optically active acylbiphenyl derivative can be obtained by subjecting the reaction mixture to conventional post-treatment operations such as extraction, separation, or concentration.

Further, in this reaction, when Y in the alkylating agent (Vl) is iodine, silver oxide may be used instead of the basic substance. In this case, such silver oxide is an optically active alcohol (V
), and the upper limit is not particularly limited, but it is preferably 2 to 5 times the amount used. When carrying out the reaction in the presence of silver oxide, the alkylating agent {in the general formula (Vl), Y is iodo} may be optionally used in an amount of 1 equivalent or more relative to the optically active alcohol IN (V). , usually used in an amount of 2 to 10 equivalents. As the reaction solvent, the above-mentioned alkylating agents can be used, and in addition, ethers, ketones, or hydrocarbons, such as tetrahydrofuran, ethyl ether, dioxane, acetone, methyl ethyl ketone, benzene, toluene, and hexane, are inert to the reaction. Various solvents may be used alone or in combination. The reaction temperature is usually 0 to 150°C, preferably 20 to 150°C.
It is OO℃. The reaction time is usually 1 hour to 20 days. After the reaction is complete,
After removing the silver salt by filtration, by adding usual post-treatments such as extraction, separation, concentration, column chromatography or distillation, -i formula (Ill)
An optically active acylbiphenyl derivative shown in can be obtained. In the production of optically active benzyloxybiphenyl derivatives [■] by the reaction of optically active penzyloxybiphenyls [■] with alkylating agents (VI), the basic substance used in the reaction is sodium hydride. , alkali metal hydrides such as potassium hydride,
Alkali metal hydroxides or alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, organic lithium or lithium such as butyl lithium,
Examples include alkali metals such as sodium and potassium. Such a basic substance is required to be used in an amount of 1 equivalent or more relative to the optically active pendyloxybiphenyls [■], and is preferably used in an amount of 1 to 5 equivalents, although the upper limit is not particularly limited. Alkylating agent (Vl) used in this alkylation reaction
The same alkylating agent used in producing the optically active acylbiphenyl derivative represented by formula (n[) is used. Such an alkylating agent (Vl
) is optionally used in an amount of 1 equivalent or more relative to the optically active pendyloxybiphenyls [■], but it is usually used in an amount of 1 to 5 equivalents. In this reaction, a solvent is usually used, and such solvents include ethers such as tetrahydrofuran and ethyl ether, ketones such as acetone and methyl ethyl ketone, aromatic hydrocarbons such as benzene and toluene, chloroform and dichloromethane. , dichloroethane, chlorobenzene, and other halogenated hydrocarbons, and dimethylformamide, dimethylsulfoxide, hexamethylphosphorylamide, N-methylpyrrolidone, and other polar solvents. The reaction temperature is usually -50 to 120'C, preferably -30 to 100'C. The reaction time is not particularly limited, and the end point of the reaction is usually when the optically active pendyloxybiphenyl represented by the general formula (■) is no longer detected in the reaction system. After the reaction is complete, add the following to the reaction mixture: For example, by adding usual post-treatment operations such as extraction, liquid separation, concentration, etc., -a formula (I
An optically active pendyloxybiphenyl derivative represented by V) is obtained. Optically active alcohol produced by hydrolysis of ester conductor [■]! In the production of (V), the reaction is carried out using an acid or a base in the presence of water.

Examples of acids include inorganic acids such as sulfuric acid, phosphoric acid, and hydrochloric acid, and R acids such as toluenesulfonic acid and methanesulfonic acid.

Examples of the base include inorganic or 1,8-diazabisic acid (5,4,
O) Organic bases such as 7-undecene and the like can be mentioned.

Such an acid is usually used in an amount of 0.02 to 10 times the amount of the optically active ester derivative [■].

The amount of base is required to be 1 equivalent or more relative to the ester derivative [■], and there is no particular restriction on the upper limit, but usually,
Used at 5 equivalents or less. The reaction is usually carried out in the presence of a solvent, such as methanol,
Alcohols such as alcohol, propanol, ketones such as acetone and methyl ethyl ketone, chloroform,
Halogenated hydrocarbons such as dichloromethane, toluene,
Examples include solvents inert to the reaction, such as hydrocarbons such as xylene, hexane, and hebutane, ethers such as ethyl ether, tetrahydrofuran, and dioxane, and aprotic polar solvents such as dimethylformamide and N-methylpyrrolidone. ．． These solvents may be used alone or in combination, and the amount used is not particularly limited. The reaction time is not particularly limited, and the end point of the reaction is when the optically active ester derivative [■] is no longer detected in the reaction system. After completion of the reaction, the optically active alcohol represented by general formula (V) can be obtained in good yield by performing operations such as extraction, separation, and concentration on the reaction mixture, and recrystallization as necessary. Alternatively, it can be purified by column chromatography. Optically active ester! [LX
] In the production of optically active ester derivative [■] by acylation, Friedel-Crafts reaction is applied to the reaction. Examples of the acylating agent include acetic acid, acetic acid derivatives such as acetyl chloride, and acetyl bromide.The amount of these used must be at least 1 mole per mole of the optically active ester (IX). is not particularly limited, but is preferably 3 moles or less.

A catalyst is used in the reaction, and examples of such catalysts include aluminum chloride, aluminum bromide, zinc chloride, zinc bromide, titanium tetrachloride, polyphosphoric acid, and boron trifluoride.

The amount of the M medium to be used is 0.3 to 3 moles relative to the optically active ester (IX).

The reaction temperature is usually -30 to 150"C, preferably lO to
100"C.

The reaction time is not particularly limited, and the optically active ester M (
The end point of the reaction is when [X) is no longer detected in the reaction system. By performing operations such as separation, concentration, and distillation on the reaction mixture thus obtained, the optically active ester derivative represented by the general formula [■] can be obtained in good yield, and if necessary, it can be further subjected to column chromatography. Although it can be purified by graphy, etc., it can usually be used as is for the next step. Optically active esters (IX
), the carboxylic acids used in the reaction are usually lower alkyl carboxylic acid anhydrides or acid halides, such as acetic anhydride, propionic anhydride, acetic chloride or bromide, brobionic acid chloride or bromide, Examples include valeroyl chloride or promodo. A solvent may be used in this reaction, and when a solvent is used, examples of the solvent include tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone,
benzene, toluene, chloroform, dichloromethane,
Solvents inert to the reaction, such as aliphatic or aromatic hydrocarbons such as dichloroethane, chlorobenzene, carbon tetrachloride, dimethylformamide, and hexane, ethers, ketones, halogenated hydrocarbons, or aprotic polar solvents, may be used alone or in combination. There are no particular restrictions on the amount used. The amount of carboxylic acid I (XI) used in the reaction is required to be 1 equivalent or more relative to the optically active alcohol ffl conductor (X), and although the upper limit is not particularly limited, it is preferably 4 equivalents or less. The reaction is carried out in the presence of a catalyst, such as an organic or Examples include inorganic basic substances. The amount used is not particularly limited, but is usually 1 to 5 times the amount of alcohol derivative (X). When an organic acamene is used as a solvent, the amine may act as a catalyst. Further, faM such as toluenesulfonic acid, methanesulfonic acid, sulfuric acid, etc. can also be used as a catalyst. The amount of catalyst used is [J
[It depends on the combination of the catalyst used, etc., and cannot necessarily be specified, but for example, when an acid halide is used as the carboxylic acid, it is used in an amount of 1 equivalent or more relative to the acid halide. The reaction temperature is usually -30 to 100"c1, preferably -2
The temperature is 0 to 90°C.

The reaction time is not particularly limited, and the end point of the reaction is when no optically active alcohol derivative [X] is detected. After the reaction is completed, optically active esters represented by general II (IX) can be obtained in good yield by ordinary fractionation methods such as extraction, separation, concentration, distillation, etc., and if necessary, column chromatography. Although it can be purified by graphy, etc., the reaction mixture can be used as is for the next step.

Here, n of the optically active alcohol derivative (X) is 1
Regarding the compounds No. 3 to 3, their racemic forms are known as known compounds, but it is difficult to obtain optically active forms from them, and no industrially useful manufacturing method is known. It became possible to manufacture it for the first time. In the production of optically active alcohol derivatives (X) by reduction of optically active carboxylic acids, examples of reducing agents used in the reaction include lithium aluminum hydride, l-
Examples include lithium aluminum hydride of trimethoxy, aluminum hydride, diisobutylaluminum hydride, sodium trimethoxyborohydride, and sodium di(2-methoxyshethoxy)aluminum hydride. The reaction is usually carried out in the presence of a solvent. Examples of such solvents include ethers such as tetrahydrofuran, ethyl ether, dioxane, dimethoxyethane, monoglyme, diglyme, benzene, toluene, and hexane, and solvents inert to the reaction such as hydrocarbons, and these solvents may be used alone. Or used in combination. The above reaction is usually carried out under a nitrogen stream, and the reaction temperature is -8
The temperature is 0 to 100°C, preferably -10 to 80°C. The reducing agent used in the reaction is optically active carvone #IiJ
For f(XII), 0.75 or more is required,
Preferably, a magnification of 2 to 4 is used.

The reaction time is not particularly limited, and optically active carboxylic acids (
The end point of the reaction is when Xn) is no longer detected in the reaction system. After the reaction is completed, the reaction mixture is usually poured into a large amount of water, made acidic with an acid, and then subjected to post-treatment operations such as extraction, separation, or concentration to obtain the optical compound represented by general formula (X). An active alcohol derivative is obtained, which can be purified by column chromatography or the like if necessary.

The optically active carboxylic acids represented by the general formula (XII) are produced by a known method when n is 1 to 2, and n
When is 3, the corresponding known raceway compound can be produced by optical separation by adding an optically active amine or the like. When n is 4 to 5, the optically active alcohol derivative represented by general formula (X) is used, for example, PBr. Brominated with etc.
Carboxylic acid esters represented by the general formula (XI[) (wherein the * mark represents the same meaning as above and p represents 2 or 3) are obtained by malonic acid ester synthesis, and further under basic conditions. It is produced by hydrolyzing it in water and then decarboxylating it in acidic conditions. As described above, when n is 4, it is produced from n-2 optically active alcohol B form (X), and when n is 5, it is produced from n=3 optically active alcohol derivative [X]. Can be done. <Effects of the Invention> The optically active biphenyl derivative represented by the general formula (1), which is a compound of the present invention, is useful as an intermediate for liquid crystal materials, particularly ferroelectric liquid crystal materials. Furthermore, the compound can be industrially advantageously produced by the method of the present invention. Examples> Hereinafter, the present invention will be explained in more detail with reference to Examples.
The present invention is not limited to the following examples. Example 1 (+)- in a four-necked flask equipped with a stirrer and a thermometer.
4-(1-carboxyethyl)biphenyl (X l [
-1) Dissolve 67.9 g <0.3 mol) in 500 ml of toluene, and add 265 d (0.9 mol) of a toluene solution of 3.4 M sodium di(2-methoxyethoxy) aluminum hydride at 0 to 5°C. It was dropped under a stream of nitrogen gas. Thereafter, the temperature was raised to 70°C and stirred at the same temperature for 2 hours. After the reaction was completed, the reaction mixture was poured into 2 liters of water, acidified with concentrated hydrochloric acid, and extracted with toluene. The organic layer was washed with water and saturated brine in that order, and dried over anhydrous magnesium sulfate. This toluene solution was concentrated under reduced pressure, and the resulting residue was subjected to silica gel column chromatography (eluent: toluene/
(-)-4- (1-
Methyl-2-hydroxyethyl)biphenyl (X-1)
60.5g (yield 95%) ([crl M'=
14.4' (c=1, CHCIs) was obtained.

(X-1)53,Ig (0.25 mol) obtained here was dissolved in 300 ml of dichloromethane, and 39.6 mol of pyridine was dissolved.
g (0.5 mol), 4-piO IJ dinoviridi 7 0.
Add 5 g (3.4 mmol) and add 38.3 g (0.38
mol) was added dropwise. Thereafter, the temperature was raised to 30°C and stirred at the same temperature for 4 hours.

The reaction mixture was poured into 11 water, made acidic with concentrated hydrochloric acid, and then extracted with ethyl acetate. The obtained organic layer was washed successively with 5% aqueous sodium bicarbonate, water, and saturated brine, and dried over anhydrous magnesium sulfate. This ethyl acetate solution was condensed under reduced pressure (-)
-4- (1-Medi-2-acetoxyethyl)biphenyl (IX-1) 62.9 g (yield 99%) (
[αl M'=-12.0゜ (C= 1.CHC 1
3) Obtained l.

Next, 31.0 d of acetyl chloride was added to 300 d of anhydrous dichloromethane.
4 g (0.4 mol), aluminum chloride 53.4
g (0.4 mol) and stirred until most of the aluminum chloride was dissolved (about 1 hour).

Thereafter, the solution was cooled to 0~5°C and kept at the same temperature. 50.9 g (0.2
A solution of 70 d of dichloromethane (mol) was added dropwise. After stirring at the same temperature for 2 hours after the dropwise addition, the reaction mixture was poured with 500ml of water.
f and extracted with ethyl acetate. The obtained organic layer was sequentially washed with water, 5% aqueous sodium bicarbonate, and saturated brine, dried over anhydrous magnesium sulfate, and then the ethyl acetate solution was concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (eluent: toluene/ethyl acetate-10/1) to obtain (-)-4-acetyl-4'-(1-methyl-2
-acetoxyethyl)bifenyl (■-1) 50.
4 g (yield: 85%) {[α]Σ' = -10.2° (c-1, CHCIs)) was obtained. 44.5 g (0.15 mol) of (■-1) obtained here was mixed with 150 d of methanol and 45 liters of tetrahydrofuran.
d was dissolved in the mixed solvent, 20% aqueous sodium hydroxide solution 75 was added, and the mixture was stirred for 10 hours. After the reaction was completed, the reaction solution was made acidic with hydrochloric acid, and extracted with 150 d of water and 200 d of toluene. The obtained organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. This toluene solution was concentrated under reduced pressure to obtain (-)-4-acetyl-4'
- (1-methyl-2-hydroxyethyl)biphenyl (V-1) 37.5 g (yield 98%) {[α
]6°−−11.7° (c-1, CHCIs)} was obtained. Next, 25.4 g (0.1
mol), 1169.5 g (0.3 mol) of oxidation, and 85.0 g (0.5 mol) of probyl iodide were charged, and the mixture was stirred at room temperature for 10 days. Thereafter, the silver salt was filtered off from the reaction mixture, and then filtered under reduced pressure. The obtained residue was subjected to silica gel chromatography (eluent: toluene/ethyl acetate 10/1) to obtain (-)-4-acetyl 4'
-(1-methyl-2-bropoxyethyl)biphenyl (
IIl-1) 11.6 g (yield 39%) ([α
lP=9.8@(c-1,CHCIs)) was obtained. After dissolving 3.0 g (10 mol) of (III-1) obtained here in 50 M1 of anhydrous dichloromethane,
2.1 g (12 mmol) of m-chloroperbenzoic acid was added, and the mixture was stirred at room temperature for 24 hours. After the reaction is completed, the reaction mixture is filtered, and the reaction mixture is filtered. After sequentially washing aN with 5% sodium bicarbonate solution, water, and saturated saline, the organic layer was concentrated under reduced pressure to give (-)-4-acetoxy4'-(1-methyl-2-broboxyethyl)biphenyl (II-1). 3.0g (yield 95
%) {[αIg'- - 9.0" (c-1,
CHCIs)) were obtained. Next, 2.5 g (II-1) obtained here (8
mmol) methanol 30! After dissolving in d, 20
% sodium hydroxide aqueous solution 10Ilj! was added and stirred at room temperature for 2 hours. After the reaction was completed, hydrochloric acid was added to make the mixture acidic, and 100 ml of ethyl acetate was added for extraction. The organic layer was washed with water, dried over magnesium sulfate, and concentrated under reduced pressure to give (-)-4-hydroxy 4'-(
1-Methyl-2-broboxyethyl)biphenyl(1-
1) 2.2g (yield 100%) ([α]P-
−3.5° (c = 1, C H C I
x ) ) was obtained. Examples 2-4 (+)-4-(1-carboxyethyl)biphenyl (
(-)-4-(1-methyl-2-carboxyethyl)biphenyl (Xll-2
), (+)-4-(1-methyl-2'-monocarboxyedyl)biphenyl (XI[-3) or (-)-4- (
1--Methyl-3-carboxyprobyl)biphenyl (
The reaction and post-treatment were carried out in the same manner as in Example 1, except that Xn-4) was used. The results are shown in Table 1. Examples 5 to 7 Reactions and post-treatments were carried out in the same manner as in Example 1, except that the alkylating agent (■) shown in Table 2 was used. The results are shown in Table 2. Examples 8 to 10 Reactions and post-treatments were carried out in the same manner as in Example 2, except that the alkylating agent (Vl) shown in Table 3 was used. Table 3 shows the results.
It is shown in Examples 11-12 The reaction and post-treatment were carried out in the same manner as in Example 4, except that the alkylating agent (V[) shown in Table 4 was used. Table 4 shows the results.
It is shown in Example 13 (-)-4-acetyl-4'(l-methyl-4-hydroxybutyl)biphenyl (V-4) obtained in Example 4
) 14.4 g (50 mol) was placed in a four-bottle flask equipped with a thermometer and a stirring device, and 50 ml of dimethylformamide was added to dissolve it. This solution was heated to O~5
After cooling to 'C, 2.4 g of 60% sodium hydride
<60 mmol) was added and stirred at the same temperature for 1 hour. Thereafter, 16.4 g (60 mmol) of p-1-luenesulfonic acid 3-ethyl-1-xybrobyl ester was added, and the mixture was stirred at room temperature for 2 hours. After the reaction is complete, add 200% water to the reaction mixture.
d, and extracted by adding 200 m2 of toluene.
The obtained organic layer was washed with water, dried over anhydrous magnesium sulfate, and then condensed under reduced pressure fA. The resulting residue was subjected to silica gel column chromatography to obtain (-)-4-acetyl-4'-(1-methyl- 4-Ethoxyproboxybutyl)piphenyl (III-13) 9.8g (yield 62%) + [α]! '-- 2.8゜(C-1, C
HCl3)l was obtained. Example 14 (-)-4-acetyl-4'(1-methyl-2-dodecyloxyethyl)biphenyl (m-) obtained in Example 6
6) 2.8 g (6.4 mmol) of dioxane 80d solution was added to 80 ml of 20% sodium hydroxide aqueous solution.
The mixture was added to an aqueous sodium hypobromite solution prepared from 8.2 g (51.5 mmol) of bromine and stirred at room temperature for 8 hours. After the reaction was completed, 4.0 g of sodium bisulfite was added to the reaction mixture, stirred for 30 minutes, and then made acidic by adding hydrochloric acid. This mixture was extracted with 100 d of ether, and the 8!1 layer was washed with saturated brine, then dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain (-)-4-carboxy-(1-methyl-2 -dodecyloxyethyl)biphenyl (I-14) 2.6 g (yield 92%) {[α]
O = 2.4' (c = 1, C Hs
O H) ) was obtained. Example 15 (-)-4-acetyl-4'-(1-methyl-2-
(+)-4-acetyl-4' obtained in Example 3 in place of dodecyloxyethyl)biphenyl (I[I-6)
The reaction and post-treatment were carried out in the same manner as in Example 14 except for using -(1-methyl-3-propoxybrobyl)biphenyl (III-3), and (+)-4-carpoxy 4'
-(1-methyl-3-proboxyprobyl)biphenyl (1-15) (yield 90%) ([α]P=+
3.2° (Cl, CHCl3)} was obtained. Example 16 (-)-4-acetyl-4'- obtained in Example 13
(-)-4-Carboxy-4'-(1- Methyl-4-ethoxypropoxybutyl)biphenyl (I16) (yield 86%) {[αIg
"--2.7° (c=1, CHCIs) was obtained. Example 17 (-)-
4-penzyloxy-4'-(1-methyl-2-hydroxyethyl)biphenyl (■!?) 3.2 g (
10 mmol) and 3.7 g of l-bromopropane (
30 mmol) was dissolved in dimethyl sulfoxide 301II1, 0.8 g (20 mmol) of 60% sodium hydride was added, and the mixture was stirred at 80°C for 12 hours. The reaction mixture was poured into 50 ml of water and extracted with toluene. The aFJ was sequentially washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the toluene solution was concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (liquid: toluene/hexane-5/1),
(-)-4-penzyloxy-4'-(1-methyl-2
-proboxyethyl)biphenyl(IV-1 7
) 2.3g (yield 64%) {[α]! '=6.
5° (c=1, CHCI!)l was obtained.

Next, 1.8 g (5 mmol) of (IV-1 7) obtained above was dissolved in 5 d of ethyl acetate, further diluted with 50 d of ethanol, and 0.8 g of 5% Pd/C was added.
The mixture was stirred vigorously for 8 hours under a hydrogen pressure of 1-1.2 atmospheres.

After the reaction is complete, Pd/C is filtered off, the filtrate is concentrated, and (-
)-4-hydroxy-4'-(1-methyl-2-proboxyethyl)biphenyl (1-1) 1.4 g (yield 95
%) {[α]! '=-3.5° (c=1, CHC Is
)) was obtained. Examples 18 to 19 (-)-4-penzyloxy-4'-(1-
Methyl-3-hydroxybrobyl)biphenyl (■-1
8) or (-)-4-penzyloxy-4' - (
1-methyl-4-hydroxybutyl)biphenyl (■-
The reaction and post-treatment were carried out in the same manner as in Example 17, except that 19) was used. The results are shown in Table 5. Examples 20-22 (-)-4-penzyloxy-4'-(1-methyl-2
-Hydroxyethyl)biphenyl (■-17) was used as a raw material, and the reaction and post-treatment were carried out according to Example 17, except that the alkylating agent (Vl) shown in Table 6 was used in place of l-bromopropane. Ta. The results are shown in Table 6. Example 23 (10)-4-penzyloxy-4'-(1-methyl-2-hydroxyethyl)biphenyl (■-23)3.
2 g (10 mmol) in 20 m dimethylformamide
After adding 0.8 g (20 mmol) of 60% sodium hydride and stirring at room temperature for 1 hour, 7.7 g of p-toluenesulfonic acid 3-ethoxybutyl ester (
A solution of 1Od (30 mmol) in dimethylformamide was added dropwise. After the dropwise addition was completed, the temperature was raised to 50 to 60°C, and the mixture was stirred at the same temperature for 24 hours. Pour the reaction mixture into 50° of water,
It was extracted with ethyl acetate. The obtained organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. After distilling off the solvent, the resulting residue was subjected to silica gel column chromatography (eluent: #luene/ethyl acetate-10
/1) to give (+)-4-penzyloxy-4'-
(1-Methyl-2-(3-ethoxybroboxy)ethyl}biphpenyl (TV-23) 2.6 g (yield 65%)
{[α]P=+6.7' (c=1, C
HCl s)) was obtained. Obtained above (Tt/-
2 3) 2.0g (5 mmol) in methanol 50
-, add 0.4g of 5% Pd/C and hydrogen pressure 1
Stir vigorously for 8 hours under ~162 atmospheres. After the reaction is complete,
Pd/C was filtered off and the obtained filtrate was concentrated to give (+)-4
-Hydroxy-4'-(1-methyl-2-(3-ethoxyproboxy)ethyl}biphenyl(1-23)1
．． 6g (yield 100%) ( [crl !'-+ 3
．． 7° (c=1, CHCI3)l was obtained. Examples 24 to 25 (-)-4-penzyloxy-4'-(1-methyl -3-hydroxypropyl)biphenyl (■-18
) or (-)-4-penzyloxy-4' - (1
-methyl-4-hydroxybutyl)biphenyl (■-1
The reaction and post-treatment were carried out in the same manner as in Example 23, except that 9) was used as the raw material. The results are shown in Table 7. Examples 26 to 28 (+)-4-penzyloxy-4'-(1-methyl-2-hydroxyethyl)biphenyl (■-23) was used as a raw material, and p-toluene snolephonate was replaced with 3-ethoxybrobyl. The reaction and post-treatment were carried out in accordance with Example 23, except that the anolekylating agent (Vl) shown in Table 8 was used. The results are shown in Table 8. Reference Example (-)-4-hydroxy-4'-( obtained in Example 8)
1-methyl-3-bentyloxyprovinole)bipheninole (1-8) 1.25g (4mmol
) in 30 ml of anhydrous dichloromethane, 1.34 g of 4-decyloxybenzoic acid (4.8++nol)
, N, N'-dicyclohexyllupodiimide 1.1
6 g (5.6 wmol) and 0.05 g (0.3 wool) of 4-pyrrolidinopyridine were added, and the
Stir for hours. After the reaction was completed, the reaction mixture was filtered, and the organic layer was washed successively with 5% acetic acid, water, 5% aqueous sodium bicarbonate, water, and saturated brine, and then concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (eluent: toluene) to obtain (-)-4-(1-methyl-3-pentyloxybubutyr)-4'-biphenylyl 4-decyloxybenzoate 2 .18g (Yield 95%) {[α]ε●−
-2.1° (c=1, CHCI.)) was obtained. When the phase change of this material was examined under a polarizing microscope, an SmC'' phase was observed, and a ferroelectric liquid crystal material was obtained.

Claims (20)

[Claims] (1) General formula ▲ Numerical formulas, chemical formulas, tables, etc. - group, n is an integer of 1 to 5, and * indicates an asymmetric carbon atom.) An optically active biphenyl derivative represented by the following. (2) The optically active biphenyl derivative according to claim 1, wherein X is a HOOC- group. (3) The optically active biphenyl derivative according to claim 1, wherein X is a HO- group. (4) General formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^2 represents a lower alkyl group, and R, n and * mark represent the same meaning as above. Acyloxybenzene derivative. (5) Optically active acylbiphenyl derivative represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R, R^2, n, and * marks have the same meanings as above.) (6) Optically active alcohols represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^2, n, and * marks have the same meanings as above.) (7) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1 represents a lower alkyl group, R^2, n
and *marks have the same meanings as above. ) is an optically active ester derivative. (8) Optically active esters represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1, n, and * marks have the same meanings as above.) (9) General formula ▲Contains mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, n and * represent the same meanings as above. ) An optically active alcohol derivative represented by (10) An optically active benzyloxybiphenyl derivative represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R, n, and * marks have the same meanings as above.) (11) The method for producing an optically active biphenyl derivative according to claim 2, which comprises oxidizing the optically active acylbiphenyl derivative according to claim 5 in the presence of water. (12) A method for producing an optically active biphenyl derivative according to claim 3, which comprises hydrolyzing the optically active acyloxybenzene derivative according to claim 4. (13) The production method according to claim 12, wherein the optically active acyl biphenyl derivative according to claim 5 is subjected to Bayer-Billiger oxidation to obtain the optically active acyloxybenzene derivative according to claim 4. (14) The optically active alcohol according to claim 6, and the general formula RY (wherein, R represents the same meaning as above, and Y represents a halogen atom or -OSO_2R^3 group. ^
3 represents a lower alkyl group or an optionally substituted phenyl group. 14. The production method according to claim 11 or 13, characterized in that the optically active acylbiphenyl derivative according to claim 5 is obtained by reacting with an alkylating agent represented by: (15) The production method according to claim 14, wherein the optically active ester derivative according to claim 7 is hydrolyzed to obtain the optically active alcohol according to claim 6. (16) The production method according to claim 15, characterized in that the optically active ester according to claim 8 is acylated to obtain the optically active ester derivative according to claim 7. (17) Reacting the optically active alcohol derivative according to claim 9 with a carboxylic acid represented by the general formula R^1COOH (wherein R^1 represents the same meaning as above) or a derivative thereof, 17. The production method according to claim 16, characterized in that the optically active ester according to claim 8 is obtained. (18) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, n and * mark represent the same meaning as above. Claim 9
18. The production method according to claim 17, characterized in that the optically active alcohol derivative described above is obtained. (19) The method for producing an optically active biphenyl derivative according to claim 3, which comprises debenzylating the optically active benzyloxybiphenyl derivative according to claim 10 in the presence of a hydrogenation catalyst and hydrogen. (20) Optically active benzyloxybiphenyls represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, n and * represent the same meanings as above.)
The optically active benzyl compound according to claim 10 is produced by reacting an alkylating agent represented by the general formula RY (wherein R and Y have the same meanings as above) in the presence of a basic substance. The manufacturing method according to claim 19, characterized in that an oxybiphenyl derivative is obtained.