JP2727685B2 - Optically active biphenyl derivative and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to, for example, optically active substituted biphenyls which are useful as intermediates for organic electronic materials, and to a method for producing the same.

More specifically, the present invention relates to an optically active biphenyl derivative useful as an intermediate of a liquid crystal material, particularly a ferroelectric liquid crystal material, and a method for producing the same.

<Prior art> Various compounds have been developed as liquid crystal compounds, but there are very few ferroelectric liquid crystal materials having excellent characteristics such as high-speed response, and the development of intermediates of the liquid crystal compounds is not yet sufficient. Therefore, an intermediate and an industrially advantageous production method thereof have been desired.

<Problem to be Solved by the Invention> An object of the present invention is to provide an optically active biphenyl derivative which is useful as an intermediate of a ferroelectric liquid crystal material excellent in the above-mentioned properties, and a method for producing the same. An object of the present invention is to provide an intermediate and a method for producing the intermediate.

<Means for Solving the Problems> That is, the present invention provides a compound represented by the general formula [I]: (Wherein, R represents an alkyl group or an alkoxyalkyl group optionally substituted with a halogen atom having 1 to 20 carbon atoms,
X represents a HOOC- or HO- group, n represents an integer of 1 to 5, and * represents an asymmetric carbon atom. ) And a method for producing the same.

 Hereinafter, the present invention will be described in detail.

The optically active biphenyl derivative in which X is a HO- group in the general formula [I] is a compound of the general formula [II] (Wherein, R ² represents a lower alkyl group, and R, n, and * have the same meanings as described above.) The compound is produced by hydrolyzing an optically active acyloxybenzene derivative represented by the following formula:

The optically active acyloxybenzene derivative represented by the general formula (II) is represented by the general formula (III) (Wherein, R, R ² , n and * represent the same meanings as described above). The compound can be produced by Bayer-Villiger oxidation of an optically active acylbiphenyl derivative represented by the formula:

The optically active biphenyl derivative wherein X is an OH-group in the general formula [I] is also represented by the general formula [IV] (Wherein, R, n and * have the same meanings as described above). The benzyloxybiphenyl derivative is also debenzylated in the presence of a hydrogenation catalyst and hydrogen.

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 [III].

The optically active acylbiphenyl derivative represented by the general formula [III] is represented by the general formula [V] (Wherein, R ² , n, and * represent the same meanings as described above) and an optically active alcohol represented by the general formula [VI] RY [VI] (where R is the same as defined above) means represents, Y is the reaction of the halogen atom or represents an -OSO ₂ R ³ group. wherein R ³ is an alkylating agent represented by.) representing a lower alkyl group or an optionally substituted phenyl group Can be manufactured.

The optically active benzyloxybiphenyl derivative represented by the general formula (IV) is represented by the general formula (VII): (In the formula, n and * represent the same meanings as described above.)
Produced by reacting an alkylating agent represented by the general formula [VI] RY [VI] (wherein R and Y have the same meanings as described above) in the presence of a basic substance. Can be.

The optically active alcohol represented by the general formula [V] can be produced by the general formula [VIII] (Wherein, R ^2, n and * mark represent the same meaning as above, R ¹
Represents a lower alkyl group. ) Can be produced by hydrolyzing the optically active ester derivative represented by

The optically active ester derivative represented by the general formula (VIII) is represented by the general formula (IX) (Wherein, R ¹ , n and * represent the same meanings as described above). The compound can be produced by acylating an optically active ester represented by the formula:

The optically active esters represented by the general formula [XI] are represented by the general formula [X] (Wherein, n and * represent the same meanings as described above) and an optically active alcohol derivative represented by the general formula [X
I] R ¹ COOH [XI] (wherein, R ¹ has the same meaning as described above), or a carboxylic acid or a derivative thereof.

The optically active alcohol derivative represented by the general formula [X] is a compound represented by the general formula [XII] (In the formula, n and * represent the same meaning as described above.) The compound can be produced by reducing an optically active carboxylic acid represented by the formula:

In the production of the optically active biphenyl derivative [I] wherein X is an OH- group by hydrolysis of the optically active acyloxybenzene derivative [II], the reaction is carried out using an acid or an alkali in the presence of water. Will be

Examples of the acid used here include inorganic acids such as sulfuric acid, phosphoric acid and hydrochloric acid, and organic acids such as toluenesulfonic acid and methanesulfonic acid.

Examples of the alkali include inorganic and organic bases such as sodium hydroxide, potassium hydroxide, barium hydroxide, potassium carbonate, sodium carbonate, and 1,8-diazabicyclo [5,4,0] 7-undecene.

The amount of the acid or alkali used is as follows.

The acid is usually used in an amount of 0.02 to 10 times the mol of the acyloxybenzene derivative [II], and the alkali is required to be at least 2 times or more, and the upper limit is not particularly limited, but is preferably 10 times or less. It is.

 The reaction is usually performed in the presence of an organic solvent.

Such solvents include methanol, ethanol, propanol, acetone, methyl ethyl ketone, chloroform, dichloromethane, toluene, xylene, hexane,
Heptane, ethyl ether, tetrahydrofuran, dioxane, dimethylformamide, aliphatic or aromatic hydrocarbons such as N-methylpyrrolidone, ethers, alcohols, ketones, amides or solvents inert to the reaction of halogenated hydrocarbons and the like are exemplified, These solvents are used alone or as a mixture.

 The amount used is not particularly limited.

Reaction temperature is usually −30 ° C. to 150 ° C., preferably −20 ° C.
~ 100 ° C.

Although the reaction time is not particularly limited, the reaction end point is usually defined as when the acyloxybenzene derivative [II] is no longer detected from the reaction system.

The reaction mixture thus obtained is subjected to, for example, post-treatment operations such as acid precipitation, extraction, liquid separation or concentration, whereby an optically active biphenyl derivative in which X is a HO- group in the general formula [I] is obtained. Is obtained.

In the production of the optically active acyloxybenzene derivative [II] by Bayer-Villiger oxidation of the optically active acylbiphenyl derivative [III], oxidizing agents used in the reaction include peracetic acid, formic acid, methacryloperbenzoic acid,
Peracids such as perbenzoic acid are exemplified.

Such a peracid can be generated, for example, from the corresponding acid and hydrogen peroxide, and Bayer-Villiger oxidation can be performed while synthesizing the peracid in the reaction system.

The peracid is usually required to be at least 1 equivalent equivalent to the optically active acylbiphenyl derivative [III], and the upper limit is not particularly limited, but preferably 1 to 2 equivalents is used.

In the Bayer-Villiger oxidation, a solvent inert to the oxidation reaction is usually used.

Examples of such a solvent include halogenated hydrocarbon solvents such as dichloromethane, dichloroethane, chloroform, chlorobenzene, benzene, toluene, xylene, hexane, and cyclohexane, and aromatic or aliphatic hydrocarbon solvents.These solvents may be used alone or Used mixed.

The reaction temperature is usually -20C to 130C, preferably -10C.
C. to 100C.

The reaction time is not particularly limited, and the reaction end point is usually defined as the time when the acylbiphenyl derivative [III] is no longer detected from the reaction system.

After completion of the reaction, the reaction mixture is subjected to a usual post-treatment operation such as removal of excess peracid, filtration, extraction, liquid separation or concentration, thereby obtaining an optically active acyloxybenzene derivative represented by the general formula (II). Is obtained.

In the production of the optically active biphenyl derivative [I] in which X is an OH- group by debenzylation of the benzyloxybiphenyl derivative [IV], PtO ₂ , Pt
-C such as platinum-based, Pd-C, Pd-BaSO 4, palladium black, etc. palladium-based, Rh-C, Rh-Al 2 O 3 or the like rhodium of, R
Examples include ruthenium-based catalysts such as uO ₂ and Ru—C, and nickel-based catalysts such as Raney nickel. In particular, palladium-based catalysts are preferably used.

The hydrogenation catalyst is usually used in an amount of 0.01 to 100% by weight, preferably 0.01 to 100% by weight, based on the optically active benzyloxybiphenyl derivative [IV].
0.1 to 50% by weight is used.

As the solvent, methanol, alcohols such as ethanol, dioxane, ethers such as tetrahydrofuran,
Benzene, aromatic hydrocarbons such as toluene, n-hexane, aliphatic hydrocarbons such as cyclohexane, esters such as ethyl acetate, amides such as dimethylformamide,
Examples thereof include fatty acids such as acetic acid and water, and these may be used alone or as a mixture.

The above reaction is usually carried out at normal pressure or under pressure, and the pressure range is usually 1 to 200 atm.

The reaction temperature is usually 0 ° C to 200 ° C, preferably 20 ° C to 180 ° C.
° C.

Although the reaction time is not particularly limited, the reaction end point is usually defined as when the optically active benzyloxybiphenyl derivative [IV] is no longer detected from the reaction system or when the absorption of hydrogen is stopped.

The reaction mixture thus obtained is subjected to a usual post-treatment operation such as filtration, concentration, recrystallization, distillation or column chromatography to give X in the general formula [I].
Is an OH- group, whereby an optically active biphenyl derivative is obtained.

X is H by oxidation of the acylbiphenyl derivative [III].
In the production of the optically active biphenyl derivative [I], which is an OOC- group, any oxidizing agent used in the reaction can be used without any particular limitation as long as it can oxidize an acyl group to a carboxylic acid. Examples of the oxidizing agent include potassium dichromate, sodium dichromate, potassium permanganate, sodium permanganate, potassium hypochlorite, sodium hypochlorite, potassium hypobromite, and sodium hypobromite. Is exemplified.

Such an oxidizing agent is used in an amount of 1 equivalent or more based on the optically active acylbiphenyl derivative [III], and the upper limit is not particularly limited, but is preferably used in an amount of 10 equivalents or less.

In this reaction, an organic solvent can be used,
As such a solvent, a solvent inert to the oxidation reaction such as dioxane, tetrahydrofuran, N-methylpyrrolidone, or the like is used.

The reaction temperature is usually -20 to 130 ° C, preferably -10 to 1
Perform at 00 ° C.

The reaction time is not particularly limited, and the reaction end point is usually defined as the time when the optically active acylbiphenyl derivative [III] is not detected from the reaction system.

The reaction mixture thus obtained is usually filtered,
By adding post-treatment operations such as acid precipitation, extraction, liquid separation or concentration, an optically active biphenyl derivative in which X is a HOOC- group in the general formula [I] can be obtained.

Optically active alcohols [V] and alkylating agents [VI]
Active Acylbiphenyl Derivatives [II
In the production of I), the reaction is usually performed in the presence of a basic substance. Examples of the basic substance include alkali metal hydrides such as sodium hydride and potassium hydride, and alkali metals such as lithium, sodium, and potassium. Examples thereof include metals, alkali metal alcoholates such as sodium ethylate and sodium methylate, alkali metals such as sodium carbonate and potassium carbonate, and organic lithium such as butyllithium.

Such a basic substance is required to be at least 1 equivalent equivalent to the optically active alcohol [V], and the upper limit is not particularly limited, but is preferably 3 equivalents or less.

The alkylating agent used in this alkylation reaction may be a chloride, bromide, iodide or the like having an alkyl group or an alkoxyalkyl group having 1 to 20 carbon atoms which may be substituted with a halogen atom as exemplified. Halides or sulfates such as methanesulfonate, ethanesulfonate, benzenesulfonate, and toluenesulfonate.

1 carbon atom which may be substituted by the above halogen atom
Examples of the alkyl group or alkoxyalkyl group of -20 include the following.

Methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxy Butyl, methoxypentyl, methoxyhexyl, methoxyheptyl, methoxyoctyl, methoxynonyl, methoxydecyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, ethoxypentyl, ethoxyhexyl, ethoxyheptyl, ethoxyoctyl, ethoxynonyl, ethoxydecyl, Propoxymethyl, propoxyethyl, propoxypropyl, pyropoxybutyl, pyropoxypentyl, pyropoxyhexyl , Propoxyheptyl, propoxyoctyl, propoxynonyl, propoxydecyl, butoxymethyl, butoxyethyl, butoxypropyl, butoxybutyl, butoxypentyl, butoxyhexyl, butoxyheptyl, butoxyoctyl, butoxynonyl, butoxydecyl, pentyloxymethyl, pentyloxy Ethyl, oentyloxypropyl, pentyloxybutyl, pentyloxypentyl, pentyloxyhexyl, pentyloxyheptyl, pentyloxyoctyl, pentyloxynonyl, pentyloxydecyl, hexyloxymethyl, hexyloxyethyl,
Hexyloxypropyl, hexyloxybutyl, hexyloxypentyl, hexyloxyhexyl, hexyloxyheptyl, hexyloxyoctyl, hexyloxynonyl, hexyloxydecyl, heptyloxymethyl, heptyloxyethyl, heptyloxypropyl, heptyloxybutyl, heptyloxy Pentyl,
Octyloxymethyl, octyloxyethyl, decyloxymethyl, decyloxyethyl, decyloxypropyl, 1-methylethyl, 1-methylpropyl, 1-methylbutyl, 2-methylbutyl, 2,3-dimethylbutyl, 2,3,3 -Trimethylbutyl, 1-methylpentyl,
2-methylpentyl, 3-methylpentyl, 2,3-dimethylpentyl, 2,4-dimethylpentyl, 2,3,3,4-tetramethylpentyl, 1-methylhexyl, 2-methylhexyl, 3-methylhexyl , 4-methylhexyl, 2,
5-dimethylhexyl, 1-methylheptyl, 2-methylheptyl, 1-methyloctyl, 2-methyloctyl, 2-trihalomethylpentyl, 2-trihalomethylhexyl, 2-trihalomethylheptyl, 2-haloethyl, 2-halopro Pill, 3-halopropyl, 3-halo-
2-methylpropyl, 2,3-dihalopropyl, 2-halobutyl, 3-halobutyl, 4-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, 5-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, 6-halohexyl, 2-haloheptyl, 2-halooctyl (where halo is fluorine, chlorine, bromine or Represents iodine).

In the case where the substituent R in the general formula [VI] is an alkyl group containing a bromine or iodine atom, in general, sulfates are preferably used as the alkylating agent from the viewpoint of the 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 any problem due to a difference in reactivity.

In addition, the branched alkyl group or alkoxyalkyl group among the alkyl groups or alkoxyalkyl groups exemplified above may be an optically active alkyl group or alkoxyalkyl group having an asymmetric carbon atom.

The halides (chloride, bromide or iodide) or sulfates having these optically active alkyl groups or alkoxyalkyl groups are derived from the corresponding optically active alcohols. It can be easily obtained by asymmetric metal catalyst of ketone or asymmetric reduction using microorganism or enzyme. Some are naturally occurring or obtained by resolution. For example, it can be derived from the following optically active amino acids and optically active oxyacids.

Alanine, valine, leucine, isoleucine, phenylalanine, serine, threonine, allothreonine, homoserine, alloisoleucine, tert.-leucine, 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, isopropyl malic acid and the like.

Such an alkylating agent [VI] is optional 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 equivalents.

As the reaction solvent, for example, tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, toluene, benzene, chloroform, chlorobenzene, dichloromethane, dichloroethane, carbon tetrachloride, dimethylformamide, aliphatic or aromatic hydrocarbons such as hexane, ether, ketone, A solvent inert to the reaction, such as a halogenated hydrocarbon or an amide, is used alone or in combination, and the amount used is not particularly limited. Further, a polar solvent such as dimethylsulfoxide, hexamethylphosphorylamide, N-methylpyrrolidone and the like can also be used.

The reaction temperature is generally -50 to 120 ° C, preferably -30 to 1
00 ° C.

The reaction temperature is not particularly limited, and the reaction end point is usually defined as the time when the optically active alcohol [V] is no longer detected from the reaction system.

After the reaction, an optically active acylbiphenyl derivative can be obtained by subjecting the reaction mixture to a usual post-treatment operation such as extraction, liquid separation or concentration.

In the reaction, when Y of the alkylating agent [VI] is iodine, silver oxide can be used instead of the basic substance.

In this case, the silver oxide is required to be at least 1 equivalent equivalent to the optically active alcohol [V], and the upper limit is not particularly limited, but is preferably 2 to 5 equivalent times.

When the reaction is carried out in the presence of silver oxide, the alkylating agent {in the general formula [VI], where Y is iodine} may be any one equivalent or more equivalent to the optically active alcohol [V]. Usually, 2 to 10 equivalents are used.

As the reaction solvent, the above-mentioned alkylating agents can also be used, and in addition, for example, tetrahydrofuran, ethyl ether, dioxane, acetone, methyl ethyl ketone,
Solvents inert to ethers such as benzene, toluene, hexane, etc., ketones or hydrocarbons may be used alone or as a mixture.

The reaction temperature is generally 0 to 150 ° C, preferably 20 to 100 ° C.
It is.

 The reaction time is usually 1 hour to 20 days.

After completion of the reaction, the silver salt is removed by filtration, followed by ordinary post-treatments, for example, extraction, liquid separation, concentration, column chromatography or distillation, to give an optical activity represented by the general formula (III). Acyl biphenyl derivatives can be obtained.

In the production of the optically active benzyloxybiphenyl derivative [IV] by the reaction between the optically active benzyloxybiphenyls [VII] and the alkylating agent [VI], sodium hydride, Alkali metal hydrides such as potassium hydride, alkali metal hydroxides or alkaline earth metal hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide; alkali metal carbonates such as sodium carbonate and potassium carbonate; Organic lithium or lithium, sodium,
Examples thereof include alkali metals such as potassium.

Such a basic substance is required to be at least 1 equivalent equivalent to the optically active benzyloxybiphenyl [VII], and the upper limit is not particularly limited, but is preferably used at 1 to 5 equivalent times.

Alkylating agent [VI] used in this alkylation reaction
The same alkylating agents used when producing the optically active acylbiphenyl derivative represented by the general formula [III] are used.

Such an alkylating agent [VI] may be used in an amount of 1 equivalent or more relative to the optically active benzyloxybiphenyls [VII], but is usually used in an amount of 1 to 5 equivalents.

In the reaction, a solvent is usually used. Examples of the solvent include tetrahydrofuran, ethers such as ethyl ether, ketones such as acetone and methyl ethyl ketone, benzene, aromatic hydrocarbons such as toluene, chloroform, dichloromethane, dichloroethane, and the like. Examples thereof include halogenated hydrocarbons such as chlorobenzene, and polar solvents such as dimethylformamide, dimethylsulfoxide, hexamethylphosphorylamide, and N-methylpyrrolidone.

The reaction temperature is generally -50 to 120 ° C, preferably -30 to 1
00 ° C.

The reaction time is not particularly limited, and the reaction end point is usually determined when the optically active benzyloxybiphenyl represented by the general formula [VII] is not detected from the reaction system.

After completion of the reaction, the reaction mixture is subjected to a general post-treatment operation such as extraction, liquid separation, and concentration, thereby obtaining a compound of the general formula [I
V], an optically active benzyloxybiphenyl derivative is obtained.

In the production of the optically active alcohols [V] by hydrolysis of the ester derivative [VIII], the reaction is carried out using an acid or a base in the presence of water.

Examples of the acid include an inorganic acid such as sulfuric acid, phosphoric acid, and hydrochloric acid, and an organic acid such as toluenesulfonic acid and methanesulfonic acid.

Examples of the base include inorganic or 1,8-diazabicyclo [5,4,0] 7 such as sodium hydroxide, potassium hydroxide, barium hydroxide, potassium carbonate and sodium carbonate.
-Organic bases such as undecene.

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

The base is required to be at least 1 equivalent times the ester derivative [VIII], and the upper limit is not particularly limited, but is usually used at 5 equivalent times or less.

The reaction is usually performed in the presence of a solvent. Examples of such a solvent include alcohols such as methanol, ethanol and propanol, acetone, ketones such as methyl ethyl ketone, chloroform, halogenated hydrocarbons such as dichloromethane, toluene, and the like. Xylene, hexane, hydrocarbons such as heptane, ethyl ether, tetrahydrofuran,
Solvents inert to the reaction, such as ethers such as dioxane, or aprotic polar solvents such as dimethylformamide and N-methylpyrrolidone are exemplified. These solvents are used alone or as a mixture, and the amount used is not particularly limited.

The reaction time is not particularly limited, and the time when the optically active ester derivative [VIII] is no longer detected from the reaction system is defined as the reaction end point.

After completion of the reaction, an optically active alcohol represented by the general formula [V] can be obtained in a high yield by adding operations such as extraction, liquid separation, and concentration to the reaction mixture, and if necessary, re-use the alcohol. It can also be purified by crystallization or column chromatography.

In the production of the optically active ester derivative [VIII] by acylation of the optically active ester [IX], the Friedel-Crafts reaction is applied to the reaction.

Examples of the acylating agent include acetic acid derivatives such as acetic acid, acetyl chloride and acetyl bromide, and the amount of these used is at least 1 mole times the amount of the optically active esters [IX]. Although not particularly limited, it is preferably not more than 3 mole times.

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

The amount of catalyst used is relative to the optically active esters [IX].
It is 0.3 to 3 times the molar amount.

The reaction temperature is usually −30 to 150 ° C., preferably −10 to 100 ° C.
It is.

The reaction time is not particularly limited, and the time when the optically active ester [IX] is no longer detected from the reaction system is defined as the reaction end point.

Separation, concentration,
By adding an operation such as distillation, the optically active ester derivative represented by the general formula [VIII] can be obtained in good yield, and can be further purified by column chromatography or the like if necessary. Can be used with

In the production of the optically active esters [IX] by the reaction of the optically active alcohol derivative [X] with the carboxylic acids [XI], the carboxylic acids used in the reaction are usually anhydrides or acids of lower alkyl carboxylic acids. A halide is used, for example, acetic anhydride, propionic anhydride, acetic chloride or bromide, prionic chloride or bromide, valeroyl chloride or bromide and the like.

In this reaction, a solution may be used, and when a solvent is used, examples of the solvent include tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, benzene, toluene, chloroform, dichloromethane, dichloroethane, chlorobenzene, carbon tetrachloride, Dimethylformamide, aliphatic or aromatic hydrocarbons such as hexane, ethers, ketones, halogenated hydrocarbons or solvents that are inert to the reaction such as aprotic polar solvents are used alone or as a mixture. There is no particular limitation.

The carboxylic acid [XI] used in the reaction is required to be at least 1 equivalent times the optically active alcohol derivative [X], and the upper limit is not particularly limited.
Equivalent times or less.

The reaction is carried out in the presence of a catalyst, such as dimethylaminopyridine, triethylamine, tri-n-butylamine, pyridine, picoline, imidazole, sodium carbonate, sodium methylate,
Organic or inorganic base substances such as potassium bicarbonate can be mentioned.

Although the amount of use is not particularly limited, it is usually 1 to 5 equivalents with respect to the alcohol derivative [X].

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

Further, acids such as toluenesulfonic acid, methanesulfonic acid, and sulfuric acid can be used as the catalyst.

The amount of the catalyst used varies depending on the type of the carboxylic acid [XI] and the combination of the catalyst to be used, etc., and cannot necessarily be specified. For example, when an acid halide is used as the carboxylic acid, 1 equivalent equivalent to the acid halide is used. Used above.

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

The reaction time is not particularly limited, and the time when the optically active alcohol derivative [X] is no longer detected is regarded as the reaction end point.

After completion of the reaction, usual separation means, for example, extraction, liquid separation,
The optically active esters represented by the general formula [XI] can be obtained in good yield by operations such as concentration and distillation, and can be purified by column chromatography or the like, if necessary. Can be used as is.

Here, among the optically active alcohol derivatives [X], for compounds in which n is 1 to 3, their racemates are known as known compounds, but it is difficult to obtain an optically active form therefrom, A particularly useful production method is not known, and production can be achieved for the first time by the present invention.

In the production of the optically active alcohol derivative [X] by reduction of the optically active carboxylic acid, examples of the reducing agent used in the reaction include lithium aluminum hydride, lithium aluminum trimethoxyhydride, aluminum hydride, diisobutyl aluminum hydride, Sodium trimethoxyborohydride, sodium di (2-methoxyethoxy) aluminum hydride and the like.

 The reaction is usually performed in the presence of a solvent.

Examples of such a solvent include solvents that are inert to the reaction of ethers such as tetrahydrofuran, ethyl ether, dioxane, dimethoxyethane, monoglyme, diglyme, benzene, toluene, hexane and the like, and hydrocarbons, and these solvents may be used alone or as a mixture. Used as

The above reaction is usually performed under a nitrogen stream, and the reaction temperature is-
It is 80-100 degreeC, Preferably it is -10-80 degreeC.

The reducing agent used in the reaction is required to be 0.75 equivalent or more, preferably 2 to 4 equivalents, based on the optically active carboxylic acid [XII].

The reaction time is not particularly limited, and the time when the optically active carboxylic acid [XII] is no longer detected from the reaction system is defined as the reaction end point.

After the completion of the reaction, the reaction mixture is usually poured into a large amount of water, acidified with an acid, and then subjected to a post-treatment operation such as extraction, liquid separation or concentration to obtain an optical compound represented by the general formula [X]. An active alcohol derivative is obtained, and can be purified by column chromatography or the like, if necessary.

The optically active carboxylic acid represented by the general formula [XII] is produced by a known method when n is 1 to 2,
When n is 3, a corresponding known racemate can be produced by optical resolution using an optically active amine or the like.

When n is 4 to 5, the optically active alcohol derivative represented by the general formula [X] is brominated with, for example, PBr ₃ or the like, and then synthesized with a malonic ester to form the general formula [XIII]. (Wherein, * represents the same meaning as described above, and p represents 2 or 3.). A carboxylic acid ester represented by the following formula is obtained, further hydrolyzed under basic conditions, and then decarboxylated under acidic conditions. It is manufactured by having

As described above, when n is 4, n = 2 from the optically active alcohol derivative [X], and when n is 5, n = 3.
From the optically active alcohol derivative [X].

<Effect of the Invention> The optically active biphenyl derivative represented by the general formula [I], which is a compound of the present invention, is useful as an intermediate of a liquid crystal material, particularly a ferroelectric liquid crystal material. Further, the compound can be industrially advantageously produced by the method of the present invention.

<Example> Hereinafter, the present invention will be described in more detail with reference to examples, but 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 (XII-
1) 67.9 g (0.3 mol) was dissolved in 500 ml of toluene,
At ml5 ° C., 265 ml (0.9 mol) of a 3.4 M sodium di (2-methoxyethoxy) aluminum hydride solution in toluene was added to N _2.
The solution was dropped under an air current. Then, the temperature was raised to 70 ° C,
Stirred for hours.

After completion of the reaction, the reaction mixture was poured into 2 l of water, acidified with concentrated hydrochloric acid, and extracted with toluene. The organic bath was washed with water and saturated saline in this order, and dried over anhydrous magnesium sulfate. This toluene solution was concentrated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (eluent: toluene / ethyl acetate = 5/1) to give (-)-4- (1-methyl-2-hydroxyethyl). Biphenyl (X-1) 6
0.5g (95% yield) ％ ▲ [α] ²⁰ _D ▼ = -14.4 ° (c = 1, C
HC1 ₃ )｝ was obtained.

53.1 g (0.25 mol) of (X-1) obtained here was dissolved in 300 ml of dichloromethane, and 39.6 g (0.5 mol) of pyridine was added.
0.5 g (3.4 mmol) of pyrrolidinopyridine were added and
While maintaining the temperature at ℃ 10 ° C., 38.3 g (0.38 mol) of acetic anhydride was added dropwise thereto. Thereafter, the temperature was raised to 30 ° C., and the mixture was stirred at the same temperature for 4 hours.

The reaction mixture was poured into 1 water, acidified with concentrated hydrochloric acid, and extracted with ethyl acetate. The obtained organic layer was washed with 5% aqueous sodium hydrogen carbonate, water and saturated saline in this order, and dried over anhydrous magnesium sulfate. The ethyl acetate solution was Shio圧concentrated (-) - 4- (1-methyl-2-acetoxyethyl) biphenyl (IX-1) 62.9g (99 % _{^{yield) {▲ [α] 20 D}} ▼
= -12.0 ° (c = 1, CHC1 3) was obtained}.

Next, 31.4 g of acetyl chloride in 300 ml of anhydrous dichloromethane
(0.4 mol) and 53.4 g (0.4 mol) of aluminum chloride, and aluminum chloride is almost dissolved (about 1 hour)
Until it is stirred.

Thereafter, the solution was cooled to 0 to 5 ° C., and a solution of 50.9 g (0.2 mol) of (IX-1) obtained above in 70 ml of dichloromethane was added dropwise while maintaining the same temperature. After stirring at the same temperature for 2 hours after the dropwise addition, the reaction mixture was poured into 500 ml of water and extracted with ethyl acetate. The obtained organic layer was washed with water, 5% aqueous sodium hydrogen carbonate and saturated brine in that order, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (eluent: toluene / ethyl acetate = 10/1) to give (-)-4-acetyl-4 '-(1-methyl-2-acetoxyethyl) biphenyl (VIII- 1) 50.4 g (yield 85%) ｛[α] ²⁰ _D ▼
= -10.2 ° (c = 1, CHC1 3) was obtained}.

44.5 g (0.15 mol) of (VIII-1) obtained here was dissolved in a mixed solvent of 150 ml of methanol and 45 ml of tetrahydrofuran, 75 ml of a 20% aqueous sodium hydroxide solution was added, and the mixture was stirred for 10 hours. After the completion of the reaction, the reaction solution was acidified with hydrochloric acid, and water 15
0 ml and 200 ml of toluene were added for extraction. The obtained organic layer was washed with water and saturated saline in this order, and dried over anhydrous magnesium sulfate. The toluene solution was concentrated under reduced pressure to obtain (−)
37.5 g of 4-acetyl-4 '-(1-methyl-2-hydroxyethyl) biphenyl (V-1) (98% yield)
[Alpha] was obtained _{^{20 D ▼ = -11.7 ° (c}} = 1, CHC1 3)}.

Next, 25.4 g (0.1 mol) of (V-1) obtained here, silver oxide
69.5 g (0.3 mol) and 85.0 g (0.5 mol) of propyl iodide were charged and stirred at room temperature for 10 days. Thereafter, the silver salt was separated from the reaction mixture by filtration and concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography (eluent; toluene / ethyl acetate = 10/1) to give (-)-4-acetyl-
11.6 g (39% yield) of 4 '-(1-methyl-2-propoxyethyl) biphenyl (III-1) ％ ▲ [α] ²⁰ _D ▼ =-
Was obtained 9.8 ° (c = 1, CHC1 3)}.

After dissolving 3.0 g (10 mmol) of (III-1) obtained in 50 ml of anhydrous dichloromethane, m-chloroperbenzoic acid was added.
2.1 g (12 mmol) was added and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, the reaction mixture was filtered, and the organic layer was washed with 5% aqueous sodium bicarbonate,
After washing with water and saturated saline in this order, the organic layer was concentrated under reduced pressure, and 3.0 g of (-)-4-acetoxy-4 '-(1-methyl-2-propoxyethyl) biphenyl (II-1) was obtained (yield 95).
^{%) {▲ [α] 20} D ▼ = -9.0 ° (c = 1, CHC1 3)} was obtained.

Next, 2.5 g (8 mmol) of (II-1) obtained above was dissolved in 30 ml of methanol, and 10 ml of a 20% aqueous sodium hydroxide solution was added thereto, followed by stirring at room temperature for 2 hours. After completion of the reaction, the mixture was acidified with hydrochloric acid, and extracted with 100 ml of ethyl acetate. The organic layer was washed with water, dried over magnesium sulfate, and concentrated under reduced pressure to give (-)-4-hydroxy-4 '-(1-methyl-2-propoxyethyl) biphenyl (I-1) 2.2 g (100% yield) ｛▲ [α] ²⁰ _D ▼
= -3.5 ° (c = 1, CHC1 3) was obtained}.

Examples 2 to 4 Instead of (+)-4- (1-carboxyethyl) biphenyl (XII-1), (-)-4- (1-methyl-2-) was used.
(Carboxyethyl) biphenyl (XII-2), (+)-
Same as Example 1 except that 4- (1-methyl-2-carboxyethyl) biphenyl (XII-3) or (-)-4- (1-methyl-3-carboxypropyl) biphenyl (XII-4) is used. The reaction and work-up were carried out. The results are shown in Table 1.

Examples 5 to 7 The reaction and post-treatment were carried out in the same manner as in Example 1 except that the alkylating agent (VI) shown in Table 2 was used. Table 2 shows the results.
Shown in

Examples 8 to 10 The reaction and post-treatment were carried out in the same manner as in Example 2 except that the alkylating agent (VI) shown in Table 3 was used. Table 3 shows the results.
Shown in

Examples 11 to 12 The reaction and post-treatment were carried out in the same manner as in Example 4 except that the alkylating agent (VI) shown in Table 4 was used. Table 4 shows the results.
Shown in

Example 13 (-)-4-acetyl-4 '-(1-
Methyl-4-hydroxybutyl) biphenyl (V-4)
14.4 g (50 mmol) 4 equipped with thermometer and stirrer
The mixture was charged in a one-necked flask, and dissolved by adding 50 ml of dimethylformamide. After cooling the solution to 0-5 ° C,
% Sodium hydride (2.4 g, 60 mmol) was added, and the mixture was stirred at the same temperature for 1 hour. Then, p-toluenesulfonic acid 3
-16.4 g (60 mmol) of ethoxypropyl ester was added and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction mixture was poured into 200 ml of water, and extracted by adding 200 ml of toluene.The obtained organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Subjected to column chromatography, (-)-4-acetyl-4 '
9.8 g (62% yield) of-(1-methyl-4-ethoxypropoxybutyl) biphenyl (III-13) ｛▲ [α] ²⁰ _D ▼ =
-2.8 obtain ° a _{(c = 1, CHC1 3)} }.

Example 14 (-)-4-acetyl-4 '-(1-
Methyl-2-dodecyloxyethyl) biphenyl (III
-6) 2.8 g (6.4 mmol) of dioxane in 80 ml
80 ml of 0% aqueous sodium hydroxide solution and 8.2 g of bromine (51.5
Mmol), and the mixture was stirred at room temperature for 8 hours. After completion of the reaction, 4.0 g of sodium hydrogen sulfite was added to the reaction mixture, and the mixture was stirred for 30 minutes, and then acidified by adding hydrochloric acid. This mixture is mixed with ether 10
Extract with 0 ml, wash the organic layer with saturated saline, and then
After drying over anhydrous magnesium sulfate and concentrating under reduced pressure, (-)-
2.6 g (92% yield) of 4-carboxy- (1-methyl-2-dodecyloxyethyl) biphenyl (I-14)
[Alpha] was obtained _{^{20 D ▼ = -2.4 ° (c}} = 1, CHC1 3)}.

Example 15 It was obtained in Example 3 in place of (-)-4-acetyl-4 '-(1-methyl-2-dodecyloxyethyl) biphenyl (III-6). (+)-4-acetyl-4 '
The reaction and post-treatment were carried out in the same manner as in Example 14 except for using-(1-methyl-3-propoxypropyl) biphenyl (III-3), to give (+)-4-carboxy-4'-
(1-methyl-3-propoxypropyl) biphenyl
(I-15) (Yield 90%) ｛▲ [α] ²⁰ _D ▼ = + 3.2 ° (c
= 1, to obtain a CHC1 _3)}.

Example 16 (-)-4-acetyl-4'- obtained in Example 13
The reaction and post-treatment were carried out in the same manner as in Example 15 except that (1-methyl-4-ethoxypropoxybutyl) biphenyl (III-13) was used, to give (-)-4-carboxy-4 '.
-(1-Methyl-4-ethoxypropoxybutyl) biphenyl (I-16) (86% yield) ％ ▲ [α] ²⁰ _D ▼ = -2.7
° was obtained _{(c = 1, CHC1 3)} }.

Example 17 (−) in a four-necked flask equipped with a thermometer and a stirrer
3.2 g (10 mmol) of -4-benzyloxy-4 '-(1-methyl-2-hydroxyethyl) biphenyl (VII-17) and 3.7 g (30 mmol) of 1-bromopropane were dissolved in 30 ml of dimethyl sulfoxide, 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 organic layer was washed with water and saturated saline in this order, dried over anhydrous magnesium sulfate, and then this toluene solution was concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (eluent: toluene / hexane = 5/1),
(-)-4-benzyloxy-4 '-(1-methyl-2
-Propoxyethyl) biphenyl (IV-17) 2.3 g (yield
64%) {▲ [α] 20 D ▼ = -6.5 ° (c = 1, CHC1 3)} was obtained.

Next, 1.8 g (5 mmol) of (IV-17) obtained above was dissolved in 5 ml of ethyl acetate, further diluted with 50 ml of ethanol, and 0.8 g of 5% Pd / C was added. Stir vigorously for 8 hours.

After completion of the reaction, Pd / C was separated by filtration, and the filtrate was concentrated to give (−)
1.4 g of 4-hydroxy-4 '-(1-methyl-2-propoxyethyl) biphenyl (I-1) (95% yield)
[Alpha] was obtained _{^{20 D ▼ = -3.5 ° (c}} = 1, CHC1 3)}.

Examples 18 to 19 (-)-4-benzyloxy-4 '-(1-methyl-
Instead of (2-hydroxyethyl) biphenyl (VII-17), (-)-4-benzyloxy-4 '-(1-methyl-3-hydroxypropyl) biphenyl (VII-18) or (-)-4- The reaction and post-treatment were carried out in the same manner as in Example 17, except that benzyloxy-4 '-(1-methyl-4-hydroxybutyl) biphenyl (VII-19) was used. The results are shown in Table-5.

Examples 20 to 22 (-)-4-benzyloxy-4 '-(1-methyl-
Using 2-hydroxyethyl) biphenyl (VII-17) as a starting material, the reaction and post-treatment were carried out according to Example 17, except that the alkylating agent (VI) shown in Table 6 was used instead of 1-bromopropane. went. The results are shown in Table-6.

Example 23 (+)-4-benzyloxy-4 '-(1-methyl-2
-Hydroxyethyl) biphenyl (VII-23) 3.2 g (10
Mmol) in 20 ml of dimethylformamide,
Add 0.8 g (20 mmol) of sodium hydride and add
After stirring for an hour, a solution of 7.7 g (30 mmol) of p-toluenesulfonic acid 3-ethoxypropyl ester in 10 ml of dimethylformamide was added dropwise. After completion of the dropwise addition, the temperature was raised to 50 to 60 ° C, and the mixture was stirred at the same temperature for 24 hours. The reaction mixture was poured into 50 ml of water and extracted with ethyl acetate. The obtained organic layer was washed with water and saturated saline in this order, and dried over anhydrous magnesium sulfate. After evaporating the solvent, the obtained residue was subjected to silica gel column chromatography (eluent: toluene / ethyl acetate = 10/1) to give (+)-4-benzyloxy-4 '.
-{1-Methyl-2- (3-ethoxypropoxy) ethyl} biphenyl (IV-23) 2.6 g (65% yield)
²⁰ _D ▼ = + 6.7 to give ° a _{(c = 1, CHC1 3)} }.

2.0 g (5 mmol) of (IV-23) obtained above was treated with methanol
Dissolve in 50 ml, add 0.4 g of 5% Pd / C, and add hydrogen pressure
Stir vigorously for 8 hours under atmospheric pressure.

After completion of the reaction, Pd / C was filtered off, and the obtained filtrate was concentrated to give (+)-4-hydroxy-4 '-{1-methyl-2-.
(3-ethoxypropoxy) ethyl @ biphenyl (I-
23) 1.6 g (100% yield) ｛▲ [α] ²⁰ _D ▼ = + 3.7 ° (c
= 1, to obtain a CHC1 _3)}.

Examples 24 to 25 (+)-4-benzyloxy-4 '-(1-methyl-
Instead of (2-hydroxyethyl) biphenyl (VII-23), (-)-4-benzyloxy-4 '-(1-methyl-3-hydroxypropyl) biphenyl (VII-18) or (-)-4- The reaction and post-treatment were carried out in the same manner as in Example 23 except that benzyloxy-4 '-(1-methyl-4-hydroxybutyl) biphenyl (VII-19) was used as a raw material. The results are shown in Table-7.

Examples 26 to 28 (+)-4-benzyloxy-4 '-(1-methyl-
According to Example 23 except that 2-hydroxyethyl) biphenyl (VII-23) was used as a raw material and the alkylating agent (VI) shown in Table 8 was used instead of 3-ethoxypropyl p-toluenesulfonate. The reaction and after-treatment were performed. The results are shown in Table-8.

Reference Example (-)-4-hydroxy-4'- obtained in Example 8
1.25 g (4 mmol) of (1-methyl-3-pentyloxypropyl) biphenyl [I-8] was added to 30 ml of anhydrous dichloromethane.
In water, 1.34 g of 4-decyloxybenzoic acid (4.8 mmo
l), N, N'-dicyclohexylcarbodiimide 1.16g
(5.6 mmol), 0.05 g (0.3 mmo) of 4-pyrrolidinopyridine
l) was added and the mixture was stirred at room temperature for 8 hours. After completion of the reaction, the reaction mixture was filtered, and the organic layer was washed with 5% acetic acid, water, 5% aqueous sodium bicarbonate,
After washing with water and saturated saline in this order, the mixture was concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (eluent: toluene) to give (-)-4- (1-methyl-
3-pentyloxypropyl) -4'-biphenylyl 4
-Decyloxybenzoate 2.18 g (95% yield)
Was obtained ^{{[α] ▲ 20 D ▼} = -2.1 ° (c = 1, CHC1 3)}. When the phase change of this product was examined under a polarizing microscope,
An SmC ^* phase was observed, and a ferroelectric liquid crystal material was obtained.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification number Agency reference number FI Technical indication location C07C 49/83 8114-4H C07C 49/83 Z 51/16 2115-4H 51/16 65/24 2115 −4H 65/24 67/42 67/42 69/157 69/157 // C07M 7:00

Claims (20)

(57) [Claims] (1) General formula (Wherein, R represents an alkyl group or an alkoxyalkyl group optionally substituted with a halogen atom having 1 to 20 carbon atoms,
X represents a HOOC- or HO- group, n represents an integer of 1 to 5, and * represents an asymmetric carbon atom. ) An optically active biphenyl derivative represented by the formula: 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 (Wherein, R ² represents a lower alkyl group, and R, n, and * have the same meanings as described above.) 5. The general formula (In the formula, R, R ² , n and * mark have the same meanings as described above.) 6. The general formula (Wherein, R ² , n and * have the same meanings as described above). 7. The general formula (Wherein, R ¹ represents a lower alkyl group, and R ² , n, and * have the same meanings as described above.) 8. The general formula (Wherein, R ¹ , n and * represent the same meanings as described above). 9. The general formula (In the formula, n and * represent the same meaning as described above.) 10. The general formula (In the formula, R, n and * have the same meanings as described above.) An optically active benzyloxybiphenyl derivative represented by the formula: 11. The process for producing an optically active biphenyl derivative according to claim 2, wherein the optically active acylbiphenyl derivative according to claim 5 is oxidized in the presence of water. 12. The method for producing an optically active biphenyl derivative according to claim 3, wherein the optically active acyloxybenzene derivative according to claim 4 is hydrolyzed. 13. The process according to claim 12, wherein the optically active acylbiphenyl derivative according to claim 5 is subjected to Bayer-Villiger oxidation to obtain the optically active acyloxybenzene derivative according to claim 4. 14. An optically active alcohol according to claim 6, wherein R is the same as defined above, and Y is a halogen atom or a --OSO ₂ R ³ group. Wherein R ³ represents a lower alkyl group or an optionally substituted phenyl group.) To obtain the optically active acylbiphenyl derivative according to claim 5. 14. The production method according to claim 11 or 13, wherein 15. The process 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 process according to claim 15, wherein the optically active ester according to claim 8 is acylated to obtain the optically active ester derivative according to claim 7. 17. The reaction of the optically active alcohol derivative according to claim 9 with a carboxylic acid represented by the general formula R ¹ COOH (wherein R ¹ has the same meaning as described above) or a derivative thereof. 17. The process according to claim 16, wherein the optically active esters according to claim 8 are obtained. 18. The general formula (Wherein, n and * represent the same meanings as described above).
18. The production method according to claim 17, wherein the optically active alcohol derivative according to the above is obtained. 19. The process for producing an optically active biphenyl derivative according to claim 3, wherein the optically active benzyloxybiphenyl derivative according to claim 10 is debenzylated in the presence of a hydrogenation catalyst and hydrogen. . 20. A general formula (In the formula, n and * represent the same meanings as described above.)
11. The optically active benzyl according to claim 10, which is reacted with an alkylating agent represented by the general formula RY (wherein R and Y have the same meanings as described above) in the presence of a basic substance. 20. The production method according to claim 19, wherein an oxybiphenyl derivative is obtained.