JP2022142768A - Method for producing trans-cyclohexanecarboxylic acid salt - Google Patents

Abstract

To provide a method for producing trans-cyclohexanecarboxylic acid salt at high yield.SOLUTION: A method for producing trans-cyclohexanecarboxylic acid salt includes the step of heating cis-trans-cyclohexanecarboxylic acid salt and metalhydroxide in aprotic organic solvent.SELECTED DRAWING: None

Description

TECHNICAL FIELD The present invention relates to a method for producing trans-cyclohexanecarboxylate, comprising heating cis-transcyclohexanecarboxylate and metal hydroxide in an aprotic organic solvent.

Compounds having a cyclohexane skeleton are useful as liquid crystal materials and pharmaceutical intermediates, among which trans-cyclohexanecarboxylic acid is widely used.
As a method for producing trans-cyclohexanecarboxylic acid, Patent Document 1 discloses that a mixture of cis and trans cyclohexanecarboxylic acids having a substituent at the 2- or 4-position is dissolved in an aqueous solution or an aqueous solution containing methanol at a temperature of 200. Processes are known which process with sodium hydroxide or calcium hydroxide at ~220°C. Further, Patent Document 2 discloses a method of treating a mixture of cyclohexanecarboxylic acid having a lower alkyl group as a substituent at the 2- or 4-position and a cis-trans-isomer of a derivative thereof with potassium hydroxide. It is Further, Patent Document 3 discloses a method of treating a mixture containing a cis-trans mixture of a 4-substituted-cyclohexanecarboxylic acid compound and a hydrophobic organic solvent with an alkoxide compound.

JP-A-60-258141 JP-A-10-237015 JP 2017-095420 A

However, in the method disclosed in Patent Document 1, it is necessary to apply pressure using an autoclave, and the cis-trans ratio after the reaction is as low as about 80% of the trans isomer, which poses a problem for practical use. In addition, the substituent at the 2- or 4-position of cyclohexanecarboxylic acid described in Patent Document 2 is a lower alkyl group of C8 or less or a carboxy group, and a highly hydrophobic molecule having a long-chain alkyl group or an alkoxy group at the 4-position There are no examples of application to molecules with groups.
The method disclosed in Patent Document 3 uses a polar solvent to convert an ester to a carboxylic acid with potassium hydroxide, and then hydrolyzes using an alkoxide.
Each different base should be used.

An object of the present invention is to solve the above problems and to provide a method for easily producing a trans-cyclohexanecarboxylic acid salt having an alkoxy group at the 4-position. The present invention has been achieved based on such findings, and the gist thereof is as follows.

[1] A method for producing a trans-cyclohexanecarboxylic acid salt, comprising:
Cis-trans cyclohexane carboxylate represented by the following formula (1) and the following formula (5)
It has a step of heating a metal hydroxide represented by in an aprotic organic solvent,
A method for producing a trans-cyclohexanecarboxylate represented by the following formula (2).

[In formulas (1) and (2), R represents a hydroxy group, a methyl group, an alkoxy group optionally having a substituent, or OM _1/m . M represents a metal, m represents the valence of M, n is 1 or more and 2
represents an integer of 4 or less. ]

M (OH) _m (5)
[In Formula (5), M and m are synonymous with Formula (1) and Formula (2). ]

[2] The production method according to [1], wherein the trans-isomer ratio of the trans-cyclohexanecarboxylate represented by formula (2) is 85% or more and 100% or less.
[3] Represented by the following formula (3), comprising a step of acid-treating the trans-cyclohexanecarboxylic acid salt represented by the formula (2) obtained by the production method according to [1] or [2]. A method for producing trans-cyclohexanecarboxylic acid.

[In formula (3), R and n are synonymous with formula (1) and formula (2). ]

[4] The production method according to [3], wherein the trans-isomer ratio of the trans-cyclohexanecarboxylic acid represented by the formula (3) is 90% or more and 100% or less.
[5] Any one of [1] to [4], wherein M in the formulas (1) and (2) represents at least one selected from the group consisting of alkali metals and alkaline earth metals Method of manufacture as described.
[6] The production method according to any one of [1] to [5], wherein the aprotic organic solvent includes a non-polar organic solvent.
[7] The cis-trans cyclohexanecarboxylic acid salt represented by the formula (1) is represented by the following formula (
Any one of [1] to [6], which is obtained by hydrolyzing an ester compound represented by 4) with a metal hydroxide represented by the following formula (6) in a polar solvent and concentrating it. The manufacturing method described in .

[In formula (4), R and n are the same as in formulas (1) and (2), and R ² has 1 carbon
represents an alkyl group of ∼6. ]

M(OH) _m (6)
[In formula (6), M represents a metal, and m represents the valence of M. ]

The present invention uses a mixture of cis- and trans-isomers of a cis-trans cyclohexanecarboxylate having an alkoxy group substituted at the 4-position as a starting material, whereby a trans alkoxy group-substituted at the 4-position is easily produced in a high yield. - It becomes possible to produce cyclohexane carboxylate.

Embodiments of the present invention will be described in detail below, but the present invention is not limited to the following embodiments, and can be modified in various ways within the scope of the gist thereof.

[mechanism]
The reason why the trans-cyclohexanecarboxylate in which the 4-position is substituted with an alkoxy group can be easily obtained in the production method of the present invention is as follows.
By using a cis-trans cyclohexane carboxylate in which a cis-isomer and a trans-isomer are mixed as a starting material, as shown in the following structural formula, the hydrogen atom on the base carbon of the carboxylic acid is removed by a base to form a resonance structure. As a result, cis-trans isomerization is more likely to proceed, and along with this, isomerization to the thermodynamically stable trans isomer with less steric hindrance is more likely to proceed. The cyclohexanecarboxylate represented by formula (1) in the present invention has an alkoxy group having an alkylene group at the 4-position, so compared to a compound having an alkyl group at the 4-position, the chain portion near the cyclohexyl group freedom is restricted. That is, compared to compounds having an alkyl group at the 4-position, the effect of the 4-position substituent on the carboxy group is small, the steric repulsion of both substituents in the cis form is small, and the energy difference between the cis and trans forms is small. Therefore, isomerization from the cis-form to the trans-form was thought to be difficult.
Therefore, as described in JP-A-10-237015, compared to the case where the 4-position of cyclohexanecarboxylic acid is substituted with an n-octyl group, the n-octyl group at the 4-position Cyclohexanecarboxylic acid substituted with an alkoxy group having a shorter chain length (for example, a pentanoxy group) is expected to undergo cis-to-trans isomerization more slowly. In addition, regardless of the length of the alkylene chain in the substituent R—(CH ₂ ) _n —O— at the 4-position, the trans form is superior in thermodynamic stability to the cis form, but this substitution By lengthening the alkylene chain in the group (n is 4 or more and 24 or less), the melting points of cis and trans cyclohexanecarboxylic acids tend to be higher, although there is an even-odd effect. The respective melting points of the corresponding carboxylates are also expected to be higher.
Therefore, the longer the alkylene chain in the substituent R-- ₍ CH.sub.2) _.sub.n --O--, the higher the melting point of the cis- and trans-carboxylates, and the more the cis- and trans-isomers are precipitated during the heating reaction. Therefore, it was expected that the cis-trans isomerization would become difficult to proceed.
Furthermore, due to the decrease in molecular packing associated with the lengthening of the alkylene chain at the substituent R—(CH ₂ ) _n —O—, the trans cyclohexanecarboxylate is superior to compounds having a lower alkyl group. Therefore, it was expected that the isomerization of the cis-trans isomer would become difficult to proceed.
However, the step of heating the cyclohexanecarboxylic acid salt represented by the formula (1) in an aprotic organic solvent with the addition of a metal hydroxide in the present invention reduces the trans isomerism of the compound represented by the formula (2). body ratio is 85% or more, and then the trans isomer ratio of the compound represented by formula (3), which is the acid of the compound represented by formula (2), is 90% or more, which is unexpectedly high. The result was that isomerization proceeded.
Thus, according to the production method of the present invention, in the isomerization of cis-trans-4-alkoxycyclohexanecarboxylic acid to the trans isomer, which is more difficult than the isomerization of cis-trans-4-alkylcyclohexanecarboxylic acid to the trans isomer, high trans It is possible to obtain the compound represented by the formula (2) in the isomer ratio, and further to obtain the compound represented by the formula (3) by converting it into an acid with a high trans isomer content, which reduces the cost in production. and the expression (
Liquid crystal molecules produced by using the compound represented by 3) as an intermediate are extremely useful in exhibiting high functionality.

The trans-cyclohexanecarboxylate in the present invention represents a trans cyclohexanecarboxylate, specifically represented by formula (2).

In formula (2), R represents a hydroxy group, a methyl group, an alkoxy group which may have a substituent, or OM _1/m .
M represents a metal, m represents the valence of M, and n represents an integer of 1 or more and 24 or less.

(M, m)
M in formula (2) represents a metal derived from a metal hydroxide represented by formula (5) or formula (6) described later, and includes group 1 or group 2 metal elements, specifically alkali Represents a metal or alkaline earth metal.
M is preferably at least one selected from the group consisting of alkali metals and alkaline earth metals, and among these, at least one selected from the group consisting of sodium, potassium, magnesium and calcium However, it is more preferable because it is an environmentally friendly element that has less impact on the human body and concerns about environmental pollution, and from the viewpoint of being highly basic and easy to abstract hydrogen, these are higher in the periodic table of elements. is preferred. Potassium and sodium are more preferable because they are preferable as compounds used in formula (5) or (6) described later.
In the production method of the present invention, two types of M may be used depending on the type of metal hydroxide represented by formula (5) or (6). It is preferable that M is one kind because M is likely to precipitate in a solution.
m represents the valence of M (metal) and is appropriately determined depending on the selection of M. For example, m is 1 when M is a Group 1 metal element, and m is 2 when M is a Group 2 metal element.

(R)
R in Formula (2) represents a hydroxy group, a methyl group, an alkoxy group optionally having a substituent, or OM _1/m .
Alkoxy groups include —OR ² . Examples of R ² include alkyl groups having 1 to 6 carbon atoms such as methyl group, ethyl group, propyl group, isopropyl group and butyl group. Examples of substituents that the alkoxy group may have include a fluorine atom, an alkoxy group, and the like.
An alkoxy group is preferable from the viewpoint of increasing water solubility.
R is preferably a methyl group, a hydroxy group or OM _1/m from the viewpoint of developing liquid crystallinity, and preferably a hydroxy group or OM _1/m from the viewpoint of ease of introduction of substituents.
OM _1/m represents a metal alkoxide structure in which hydrogen is abstracted from the hydroxy group by the metal hydroxide represented by formula (5) or (6). For example, m is 1 when M is a Group 1 metal element, and m is 2 when M is a Group 2 metal element.

(n)
n in Formula (2) represents an integer of 1 or more and 24 or less. Japanese Patent Application Laid-Open No. 5-125055 describes that when n is 4 or more, a liquid crystal composition having a high response speed and low temperature dependence can be obtained. From the viewpoint of using the cyclohexanecarboxylate as an intermediate for a compound exhibiting liquid crystallinity, n is preferably 4 or more. On the other hand, if the side chain is too long, association with the core portion such as the aromatic ring in the molecule is inhibited, making it difficult to exhibit liquid crystallinity. Also, from the viewpoint of ease of manufacture and cost, n is preferably 16 or less, more preferably 12 or less.

(( _CH2 ) _n )
The hydrocarbon group (CH ₂ ) _n in formula (2) may be linear or branched,
It is preferably linear. CH ₂ of (CH ₂ ) _n may be partially replaced with O,
H may be partially or wholly replaced with F.

The melting point of the trans-cyclohexanecarboxylate represented by formula (2) is preferably 30° C. or higher, more preferably 35° C. or higher. Within the above range, it tends to be solid at room temperature and easy to purify. Furthermore, in order to promote trans isomerization, it is preferable to precipitate as a solid in the step of heating in an aprotic solvent,
A melting point of 140° C. or higher is more preferable, and a melting point of 160° C. or higher is particularly preferable. Although the upper limit is not particularly limited, it is 300° C. or less.

(Trans isomer ratio of trans-cyclohexanecarboxylate represented by formula (2))
In the cis-to-trans isomerization reaction of 4-substituted-cyclohexanecarboxylic acid, even if the substituent is an alkoxy group, even if the chain length is the same as that of an alkyl group, the cis stereo Isomerization can be said to be more difficult because the energy difference between the cis and trans isomers is small due to the small contribution of the disorder.
In the industrial use of liquid crystal molecules having the trans-cyclohexanecarboxylic acid salt represented by formula (2) as an intermediate, when the cis and trans isomers are mixed, the packing of the molecules is insufficient. On the other hand, problems such as not exhibiting liquid crystallinity or narrowing the temperature range for exhibiting liquid crystals even if it does occur. There is also greater freedom of choice in terms of forming desired liquid crystal compositions by mixing other liquid crystal molecules.
The total molar isomer ratio of the cis and trans isomers contained in the trans-cyclohexanecarboxylate represented by the formula (2) after the isomerization reaction as an intermediate for the production of liquid crystal molecules is 100%.
, the purity of the trans isomer of the liquid crystal molecule using the trans-cyclohexanecarboxylate represented by the formula (2) as an intermediate is increased, and the yield of the trans isomer is increased. The trans isomer ratio is preferably 85% or more and 100% or less, and 90%
100% or less is more preferable, and 95% or more and 100% or less is even more preferable.

Although the trans-cyclohexanecarboxylic acid salt represented by formula (2) is not particularly limited, examples thereof include the following structures.

[Method for producing trans-cyclohexanecarboxylate]
The production method of the present invention comprises a step of heating the cis-trans cyclohexane carboxylate represented by formula (1) and the metal hydroxide represented by formula (5) in an aprotic organic solvent. be. The ratio of the cis-trans isomer in the mixture is not particularly limited because it is derived from the method for synthesizing the compound represented by formula (1). .

(cis-trans cyclohexane carboxylate represented by formula (1))
The cis-trans cyclohexane carboxylate in the present invention represents a mixture of cis and trans isomers.

In formula (1), R represents a hydroxy group, a methyl group, an alkoxy group which may have a substituent, or OM _1/m .
M represents a metal, m represents the valence of M, and n represents an integer of 1 or more and 24 or less.
M, m, n and R in Formula (1) have the same meanings as M, m, n and R in Formula (2), and the preferred ranges and optional substituents are also the same.

The method for obtaining the cis-trans cyclohexanecarboxylate represented by formula (1) is not particularly limited, but Recueil des Travaux Chimiques des
The method described in Pays-Bas, 1996, 115, 321-328, that is, the compound obtained by hydrogenating benzoic acid substituted with an alkoxy group at the 4-position and the metal hydroxide represented by formula (5) are reacted. Alternatively, an ester compound represented by the following formula (4) may be hydrolyzed with a metal hydroxide represented by the following formula (6) in a polar solvent and concentrated to obtain an isomer It is preferable because it is easy to raise the temperature at the time of curing.

In formula (4), R and n are the same as in formulas (1) and (2), and R ² has 1 carbon
represents an alkyl group of ∼6.

In formula (4), R ² represents an alkyl group having 1 to 6 carbon atoms. The alkyl group having 1 to 6 carbon atoms is not particularly limited, and examples thereof include methyl group, ethyl group, n-propyl group, n-butyl group, isopropyl group, isobutyl group, t-butyl group, n-pentyl group, n -hexyl group. R ² is preferably a methyl group, an ethyl group, an n-propyl group, or an n-hexyl group because the ester compound represented by the formula (4) is easily available. Since it is easy to obtain a high-purity ester compound represented, the methyl group,
Ethyl groups are more preferred.
R and n in Formula (4) have the same meanings as R and n in Formulas (1) and (2), respectively, and the preferred ranges and optional substituents are also the same.

M(OH) _m (6)
[In formula (6), M represents a metal, and m represents the valence of M. ]

M and m in Formula (6) are synonymous with M and m in Formula (1) and Formula (2), respectively. Specific examples of the metal hydroxide represented by formula (6) include sodium hydroxide, potassium hydroxide, lithium hydroxide, magnesium hydroxide, calcium hydroxide, cesium hydroxide and the like. From the viewpoint of solubility in polar solvents, potassium hydroxide and sodium hydroxide are particularly preferred.

As the polar solvent, conventionally used polar solvents can be used, and specific examples include water and alcohols such as methanol, ethanol, and isopropyl alcohol.

The method for hydrolyzing the ester compound represented by formula (4) with the metal hydroxide represented by formula (6) is not particularly limited, but examples include stirring in a mixed solvent of water and alcohol. The stirring (reaction) temperature is not particularly limited, but it is preferably 20 to 60°C, more preferably 20 to 50°C.
The stirring (reaction) temperature may be room temperature. Also, the concentration method after hydrolysis is not particularly limited, but concentration can be carried out by heating and distilling under reduced pressure.

(Metal hydroxide represented by formula (5))
M (OH) _m (5)
[In Formula (5), M and m are synonymous with Formula (1) and Formula (2). ]

When the cis-trans-cyclohexanecarboxylate represented by formula (1) is heated together with the metal hydroxide represented by formula (5) in an aprotic organic solvent, the cis-cyclohexanecarboxylate converts to trans-cyclohexanecarboxylic acid. Due to poorer molecular packing and lower melting point than the acid salt, only the cis-cyclohexanecarboxylate, which has a relatively low melting point, dissolves or melts in the solvent, and the trans-cyclohexanecarboxylate precipitates as a solid. The equilibrium inside is biased toward the increase of the trans isomer. Therefore, the isomerization rate of trans-cyclohexanecarboxylate is increased.

In Formula (5), M and m are synonymous with M and m in Formula (1) and Formula (2), respectively. Specific examples of the metal hydroxide represented by formula (5) include sodium hydroxide, potassium hydroxide, lithium hydroxide, magnesium hydroxide, calcium hydroxide, and cesium hydroxide. Potassium hydroxide and sodium hydroxide are particularly preferred from the viewpoint of solubility in solvents, and potassium hydroxide and sodium hydroxide are particularly preferred because they are highly basic and facilitate proton abstraction.

(Aprotic organic solvent)
In the present invention, the aprotic organic solvent refers to an organic solvent that does not have a group in which an oxygen atom or a nitrogen atom and a hydrogen atom are bonded, such as a hydroxyl group or an amino group. Nonpolar organic solvents, polar organic solvents, It is classified as a halogen solvent in which the hydrogen atom of a non-polar organic solvent is replaced with a halogen atom.
A non-polar organic solvent refers to a solvent composed of molecules composed of carbon and hydrogen atoms. Solvents that are aprotic and non-polar organic solvents include, for example, benzene, toluene, xylene (ortho-xylene, meta-xylene, para-xylene, or mixtures thereof), mesitylene, cymene, cumene, 3-isopropyl cumene, durene, naphthalene,
Aromatic hydrocarbon organic solvents such as biphenyl, heptane, octane, nonane, decane, undecane, dodecane, dodecene, cyclohexane, methylcyclohexane, decalin, Shellsol 71 (trade name, C10-C12 isoparaffin mixture, Shell Japan Co., Ltd.) company)
, and other aliphatic hydrocarbon organic solvents.

A polar organic solvent refers to a solvent composed of molecules containing, in addition to carbon atoms, highly polarizable atoms such as nitrogen, oxygen or sulfur atoms. Specific examples of solvents that are aprotic organic solvents and polar organic solvents include, for example, tetrahydrofuran, 1,4-dioxane, acetoxy-2-ethoxyethane, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, diphenyl ether, Ethers such as anisole, ketones such as methyl ethyl ketone, cyclohexanone, γ-butyllactone or N-methylpyrrolidinone, thioethers such as thioanisole, esters such as methyl benzoate, ethyl benzoate, and butyl benzoate, dimethyl Formamide, dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide.

A halogen solvent is a solvent composed of a molecule in which some or all of the hydrogen atoms of the molecules constituting the nonpolar organic solvent are replaced with halogen atoms, but there is no restriction on the positions and number of replacements.
Halogen solvents include, for example, dichloromethane, chloroform, carbon tetrachloride, 1,2-
Aliphatic halogen solvents such as dibromoethane, chlorobenzene, orthodichlorobenzene,
Aromatic halogen solvents such as trifluoromethylbenzene and bromobenzene can be used.

As the aprotic organic solvent in the present invention, it is desirable that the cis-cyclohexanecarboxylic acid salt has some solubility and the trans-cyclohexanecarboxylic acid salt has low solubility. Moreover, since the isomerization reaction in the present invention is likely to proceed by the heating reaction at a high temperature, it is more preferable to include an aromatic hydrocarbon-based organic solvent having a boiling point of 100°C or higher and 180°C or lower. Boiling point 100°C or higher 180
° C. or lower include toluene, xylene and mesitylene, and it is particularly preferable to include at least one selected from the group consisting of these. These may be of a single type, or may be a mixture of multiple types. Among these, mesitylene has a high boiling point and a certain degree of solubility for cis-cyclohexanecarboxylates, and low solubility for trans-cyclohexanecarboxylates, and tends to promote isomerization, and is therefore particularly preferred.

The aprotic organic solvent may contain a small amount of a protic solvent, and examples of the protic solvent include water, methanol, ethanol, isopropyl alcohol, etc., which easily dissolve the metal hydroxide represented by formula (5). Alcohols are particularly preferred. By containing these in the aprotic polar solvent, the metal hydroxide represented by the formula (5) is uniformly dissolved in the reaction solution, thereby tending to promote the isomerization reaction. be.

The aprotic organic solvent preferably has a high boiling point, preferably 100° C. or higher, more preferably 110° C. or higher. Moreover, although the upper limit of the boiling point is not particularly limited, it is preferably 180° C. or lower. When the boiling point is at least the lower limit, it tends to be easy to secure the activation energy necessary for isomerization, and when it is at most the upper limit, the viscosity of the solution during the reaction tends to be within the range where it is easy to stir. It is in. In addition, since the melting point of the solvent is below room temperature by being below the upper limit,
It is preferable because it can be handled as a liquid at room temperature in subsequent purification steps.

The step of heating the cis-trans cyclohexane carboxylate represented by formula (1) and the metal hydroxide represented by formula (5) in an aprotic organic solvent is not particularly limited.
The method of mixing the cis-trans cyclohexanecarboxylate represented by formula (1) with an aprotic organic solvent can be performed by adding the aprotic organic solvent to the cis-trans cyclohexanecarboxylate powder or vice versa. good. The mixing ratio of these is not particularly limited, but the normality (N) when the valence of the cis-trans cyclohexane carboxylate to the aprotic organic solvent is 1 is preferably 0.01 or more, and 0 .1 or more is more preferable. Also, it is preferably 10 or less, more preferably 5 or less, and even more preferably 1 or less. Within the above range, stirring and concentration tend to be easy.
Further, phase transfer catalysts such as crown ethers and tetrabutylammonium salts may be added to facilitate dissolution of the cis-transcyclohexanecarboxylate. The amount to be added can be about the same (molar amount) as that of the cis-trans-cyclohexanecarboxylate.

The conditions for heating the cis-trans cyclohexanecarboxylate represented by formula (1) in an aprotic organic solvent are not particularly limited, but the temperature is preferably 100°C or higher, and 120°C.
It is more preferable to be above. Moreover, it is preferably 220° C. or lower, more preferably 200° C. or lower. When it is at least the above lower limit, it tends to be possible to obtain sufficient activation energy for isomerization, and when it is at most the above upper limit, it tends to be possible to suppress decomposition of the salt.
Moreover, when heating above the boiling point temperature of the solvent to be used, pressure may be applied using an autoclave or the like. The pressurization conditions are preferably 1 MPa or more and 100 MPa or less, and 50 MPa
The following are more preferable. Pressurization tends to promote isomerization.
A heating means is not particularly limited, but a microwave or the like may be used.

[Method for producing trans-cyclohexanecarboxylic acid]
From the trans-cyclohexanecarboxylate represented by the formula (2) obtained through the step of heating the cis-trans cyclohexanecarboxylate represented by the formula (1) in an aprotic organic solvent, the formula (3 The method for producing the trans-cyclohexanecarboxylic acid represented by ) is not particularly limited, but preferably includes a step of acid-treating the trans-cyclohexanecarboxylic acid salt represented by formula (2).

(trans-cyclohexanecarboxylic acid represented by formula (3))

In formula (3), R and n are synonymous with formula (1) and formula (2).
R represents a hydroxy group, a methyl group, an alkoxy group which may have a substituent, or OM _1/m .
M represents a metal, m represents the valence of M, and n represents an integer of 1 or more and 24 or less.

M, m, n and R in Formula (3) are the same as M, m, n and R in Formula (2), respectively, and the preferred ranges and optional substituents are also the same.

The trans-cyclohexanecarboxylic acid represented by formula (3) has a structure in which M of the trans-cyclohexanecarboxylic acid salt represented by formula (2) is replaced with a hydrogen atom, and a preferred structure is represented by formula (2). It is a structure in which M is replaced with a hydrogen atom in the preferred structure of the represented trans-cyclohexanecarboxylic acid salt.

Further, as a specific example of the trans-cyclohexanecarboxylic acid represented by the formula (3), in specific examples of the trans-cyclohexanecarboxylic acid salt represented by the formula (2), an alkali metal and an alkaline earth metal are Substituted structures are included.

The trans-cyclohexanecarboxylic acid represented by formula (3) is produced by acid-treating the trans-cyclohexanecarboxylic acid salt represented by formula (2). Acids used for the treatment include, for example, hydrochloric acid and sulfuric acid. Using these acids, the aqueous solution containing the carboxylate is acidified to pH 6 or less.

Examples of other steps include, but are not limited to, a cooling step, a washing step, and a drying step.

The cooling step is the step after heating the cis-trans-cyclohexanecarboxylate represented by formula (1) in an aprotic organic solvent to produce the trans-cyclohexanecarboxylate represented by formula (2). Refers to the cooling process. Although the cooling method is not particularly limited, a method of stopping the supply of the heating heat source and cooling to room temperature while stirring is exemplified.
The washing step refers to a step of separating and washing the trans-cyclohexanecarboxylic acid represented by the formula (3) obtained through the acid treatment step.

(Trans isomer ratio of trans-cyclohexanecarboxylic acid represented by formula (3))
When the total amount of the molar isomer ratio of the cis and trans isomers contained in the trans-cyclohexanecarboxylic acid represented by the formula (3) is 100%, the content of the trans isomer, that is, the trans isomer ratio is 90. % or more and 100% or less is preferable from the point of obtaining liquid crystal molecules with a high trans isomer ratio in good yield, and it is more preferably 95% or more and 100% or less.

EXAMPLES The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following examples and synthetic compounds as long as the gist thereof is not exceeded. Various conditions and values of evaluation results in the following examples indicate the preferred range of the present invention as well as the preferred range in the embodiment of the present invention, and the preferred range of the present invention is the embodiment described above. can be determined by taking into account the range indicated by the preferred range in and the values in the following Synthetic Examples or the combination of the values in Examples.

[Example]
<Example 1>

3.00 g of compound A with cis/trans = 90/10 (9.5
4 mmol), 1.89 g (29.0 mmol) of KOH, and 20 mL of mesitylene to give 1
The mixture was heated to 65° C. and reacted for 8 hours. The cis/trans ratio of compound B' after completion of the reaction is 2
/98. In addition, as the reaction progressed, precipitation of solid was confirmed, and it was confirmed that the melting point of compound B' was 165° C. or higher.

<Example 2>

Into a 100 mL flask was added 3.00 g of compound C with cis/trans = 89/11 (8.
76 mmol), KOH 1.47 g (26.3 mmol), water 1.6 g (87.6 mmol)
l) and 20 mL of methanol were added and stirred at room temperature for 1 hour. After confirming that Compound C disappeared, the solvent was distilled off under reduced pressure. 30 mL of mesitylene was added to this and heated to 165°C,
The reaction was carried out for 8 hours with azeotropic removal of water. In addition, as the reaction progressed, precipitation of solid was confirmed, and it was confirmed that the melting point of compound B' was 165° C. or higher. After completion of the reaction, compound B'
The cis/trans ratio of was 13/87. The reaction solution was allowed to cool to room temperature, neutralized with 20% sulfuric acid to pH 2 or lower, and then cooled to 0°C. After filtering the precipitated solid, it was washed with water and hexane and dried to obtain 2.05 g of Compound D. Yield 75.0%, cis/t
rans was 0/100.
<Comparative Example 1>

Compound A 2.97 g (9.54 mmol), t-BuOK in a 50 mL three-necked flask
3.24 g (28.6 mmol) and 30 mL of mesitylene were added, heated to 166° C., and reacted for 8 hours while removing water azeotropically. After completion of the reaction, the cis/trans ratio of compound B' was 41/59. After cooling the reaction mixture, the reaction mixture was neutralized with 20% sulfuric acid until the pH became 2 or less, and the carboxylic acid was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated to obtain 1.79 g of Compound D. The yield was 61.0% and the cis/trans ratio was 30/70.

<Comparative Example 2>

When synthesized according to Example 1 of JP-A-2017-95420, compound D was obtained with a yield of 66%, and the cis/trans ratio was 14/86.

Examples 1 and 2 of the present application and Comparative Examples 1 and 2 demonstrate that the present invention is a method for selectively obtaining trans-cyclohexanecarboxylic acid and trans-cyclohexanecarboxylic acid in high yield.

Claims (7)

A method for producing a trans-cyclohexanecarboxylic acid salt, comprising:
Cis-trans cyclohexane carboxylate represented by the following formula (1) and the following formula (5)
It has a step of heating a metal hydroxide represented by in an aprotic organic solvent,
A method for producing a trans-cyclohexanecarboxylate represented by the following formula (2).

[In formulas (1) and (2), R represents a hydroxy group, a methyl group, an alkoxy group optionally having a substituent, or OM _1/m . M represents a metal, m represents the valence of M, n is 1 or more and 2
represents an integer of 4 or less. ]
M (OH) _m (5)
[In Formula (5), M and m are synonymous with Formula (1) and Formula (2). ] The production method according to claim 1, wherein the trans-isomer ratio of the trans-cyclohexanecarboxylic acid salt represented by formula (2) is 85% or more and 100% or less. Trans-cyclohexanecarboxylic acid salt represented by the formula (2) obtained by the production method according to claim 1 or 2, having a step of acid-treating the trans-cyclohexanecarboxylic acid salt represented by the following formula (3):
A method for producing cyclohexanecarboxylic acid.

[In formula (3), R and n are synonymous with formula (1) and formula (2). ] The trans-isomer ratio of the trans-cyclohexanecarboxylic acid represented by the formula (3) is 9.
The manufacturing method according to claim 3, wherein the content is 0% or more and 100% or less. The production according to any one of claims 1 to 4, wherein M in the formulas (1) and (2) represents at least one selected from the group consisting of alkali metals and alkaline earth metals. Method. Any one of claims 1 to 5, comprising a non-polar organic solvent as the aprotic organic solvent
The manufacturing method described in the item. The cis-trans cyclohexane carboxylate represented by the formula (1) is represented by the following formula (4)
Under a polar solvent, an ester compound represented by hydrolyzing with a metal hydroxide represented by formula (6), which is obtained by concentration, according to any one of claims 1 to 6 Production method.

[In formula (4), R and n are the same as in formulas (1) and (2), and R ² has 1 carbon
represents an alkyl group of ∼6. ]
M(OH) _m (6)
[In formula (6), M represents a metal, and m represents the valence of M. ]