JPH08268957A - Production of trans-4-phenylcyclohexane-based compound - Google Patents

Abstract

PURPOSE: To obtain a compound in an industrially simple and safe operation in high yield, useful as an intermediate for liquid crystal compounds by Friedel- Crafts reaction between a specific cyclohexanecarboxylic acid and benzene or its derivative. CONSTITUTION: This compound of formula III is obtained by Friedel-Crafts reaction between (A) a 4-hydroxycyclohexanecarboxylic acid (ester) of formula I (X is H or a 1-3 alkyl) and (B) benzene or its derivative of formula II (Y is H, a 1-8C alkyl or halogen) in the presence of (C) a Lewis acid. It is preferable that the component A be prepared by hydrogenating only the aromatic ring of p-hydroxybenzoic acid or its ester of formula IV (e.g. using ruthenium- carrying carbon as hydrogenation catalyst, at 35-100 deg.C under a pressure of 20-100cm<2> /kg), the amount of the component C (e.g. aluminum chloride) to be used be 1.2-2.2 pts.mol per pt.mol of the component A, and the temperature during the Friedel-Crafts reaction 35-80 deg.C.

Description

Detailed Description of the Invention

[0001]

The present invention relates to a method for producing trans-4-phenylcyclohexanecarboxylic acid.

[0002]

2. Description of the Related Art In recent years, flat panel displays using liquid crystal have come to be used for displaying various screens such as televisions, personal computers and word processors. The physical properties of liquid crystals used in such applications include switch and
Since it has a low viscosity because it depends on the on / off time, and it may be used outdoors, it is required to have chemical stability such as light resistance and water resistance. A trans-4-phenylcyclohexane-based compound has been nominated as a useful intermediate for producing a liquid crystal compound having such characteristics.

As a method for producing a trans-4-phenylcyclohexane compound, for example, (1) biphenylcarboxylic acid is subjected to Birch reduction, and then the residual olefinic double bond is hydrogenated, followed by esterification, isomerization and hydrolysis. A method of disassembling (JP-A-54-154741),
(2) A method in which cyclohexene is reacted with acetyl chloride, then this is subjected to Friedel-Crafts reaction with benzene to give an acetyl form of phenylcyclohexane, and then oxidized with hypochlorous acid or the like (Japanese Patent Publication No. 62-40336). (3) A method is known in which butadiene and acrylic acid are subjected to a Diels-Alder reaction to synthesize 3-cyclohexenecarboxylic acid, and then benzene is subjected to a Friedel-Crafts reaction (Burchin Chemical Society Japan, Vol. 44, page 3388). .

However, the method (1) is industrially impractical because the Birch reduction must be carried out in liquid ammonia at -70 ° C. According to the method (2), the yield of acetyl compound is as low as 12%, and there is a risk of explosion due to the oxidation reaction. In the method (3), butadiene,
In addition to the high polymerizability of acrylic acid, butadiene makes air and explosive gas, which makes the handling of raw materials inconvenient.
It was difficult to produce a trans-4-phenylcyclohexane compound in a high yield by a simple and safe operation by any method.

[0005]

DISCLOSURE OF THE INVENTION The present invention provides a method for producing a trans-4-phenylcyclohexane compound in a high yield, which is easy to handle as a raw material and is industrially simple and safe. The purpose is to

[0006]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that 4-hydroxycyclohexanecarboxylic acid or its ester easily derived from p-hydroxybenzoic acid or its ester. ,
It was found that a trans-4-phenylcyclohexane compound can be produced in a high yield by a simple and safe operation by subjecting benzene or a derivative thereof to a Friedel-Crafts reaction. The present invention has been completed based on this new finding.

That is, the present invention has the general formula (1):

[0008]

Embedded image

(In the formula, X is a hydrogen atom or has 1 to 3 carbon atoms.
Represents an alkyl group of 4-hydroxycyclohexanecarboxylic acid or its ester and the general formula (2):

[0010]

[Chemical 9]

(Wherein Y represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms or a halogen atom) or a benzene derivative thereof is subjected to a Friedel-Crafts reaction in the presence of a Lewis acid. Characteristic general formula (3):

[0012]

[Chemical 10]

A method for producing a trans-4-phenylcyclohexane compound represented by the formula (wherein X and Y are the same as above), and a general formula (4):

[0014]

[Chemical 11]

(In the formula, X is a hydrogen atom or 1 to 3 carbon atoms.
Of p-hydroxybenzoic acid or an ester thereof represented by the general formula (1):

[0016]

[Chemical 12]

(In the formula, X is a hydrogen atom or 1 to 3 carbon atoms.
Of 4-hydroxycyclohexanecarboxylic acid or its ester represented by general formula (1), and then 4-hydroxycyclohexanecarboxylic acid or its ester represented by general formula (1) and general formula (2):

[0018]

[Chemical 13]

(Wherein Y represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms or a halogen atom) or a benzene derivative thereof is subjected to a Friedel-Crafts reaction in the presence of a Lewis acid. Characteristic general formula (3):

[0020]

Embedded image

The present invention relates to a method for producing a trans-4-phenylcyclohexane compound represented by the formula (wherein X and Y are the same as above).

The 4-hydroxycyclohexanecarboxylic acid represented by the general formula (1) or the ester thereof is, for example, p-hydroxybenzoic acid represented by the general formula (4) or the ester thereof in the presence of a hydrogenation catalyst. It can be easily produced by hydrogenating only the aromatic ring of the ester. In addition,
Examples of the p-hydroxybenzoic acid ester represented by the general formula (4) include methyl ester, ethyl ester, propyl ester and the like.

Examples of the catalyst used for hydrogenation include metals such as platinum, palladium, rhodium and ruthenium. Such a hydrogenation catalyst may be supported on a carrier such as porous alumina having a large surface area, silica (diatomaceous earth), carbon, titania or the like. In the present invention, it is preferable to use ruthenium-supporting carbon among such hydrogenation catalysts. The amount of the hydrogenation catalyst (in the case of a carrier-supported material, the amount of metal in the carrier-supported material) used is not particularly limited, but is usually p-hydroxybenzoic acid represented by the general formula (4) or 0.05-0.5 of the ester
It is about wt%, preferably 0.25 to 0.5 wt%. When the amount of the hydrogenation catalyst used exceeds 0.5% by weight, it is disadvantageous in terms of cost, and when it is less than 0.05% by weight, the reaction time becomes long, which is not preferable.

The reaction pressure is usually 1 to 150 cm ² / kg.
The degree is about 20 to 100 cm ² / kg. If the reaction pressure exceeds 150 cm ² / kg, a reactor with a high pressure resistance is required, which increases the equipment cost, and also 1 cm
If it is less than ² / kg, the reaction time will be long. The reaction temperature is usually about 25 to 200 ° C, preferably 35 to 100 ° C. When the reaction temperature exceeds 200 ° C, hydrogenolysis occurs, and when it is less than 25 ° C, the reaction time becomes long.

Since the hydrogenation reaction is usually carried out in a solvent, ethanol, methanol, ethyl acetate, dioxane or the like is used as the solvent.

The trans-4-phenylcyclohexane compound represented by the general formula (3) is the 4-hydroxycyclohexanecarboxylic acid represented by the general formula (1) or the ester thereof obtained by the above-mentioned production method. General formula (2)
It is produced by subjecting benzene represented by the following formula or a derivative thereof to Friedel-Crafts reaction in the presence of a Lewis acid.

Since benzene or its derivative is also used as a solvent, the amount used is represented by the general formula (1).
The amount is usually 10 parts by mole or more, preferably 10 to 30 parts by mole with respect to 1 part by mole of hydroxycyclohexanecarboxylic acid or its ester. When the amount of benzene or its derivative used is less than 10 parts by mole, the produced trans-4-phenylcyclohexane compound is 4-hydroxycyclohexanecarboxylic acid represented by the general formula (1) or its ester, In addition, the tendency of Friedel-Crafts reaction becomes stronger, which is not preferable. Examples of the benzene derivative include halogenated benzene such as chlorobenzene and bromobenzene, and alkylbenzene having a linear or branched alkyl group having 1 to 8 carbon atoms,
An optically active compound can also be used as the alkylbenzene.

As the Lewis acid, aluminum chloride, iron chloride, tin chloride, antimony chloride, boron fluoride and the like which are generally used in Friedel-Crafts reaction can be used. In the present invention, aluminum chloride is preferred. The Lewis acid used in the present invention acts as a catalyst for the Friedel-Crafts reaction, and in addition to the cis-4-phenylcyclohexane-based compound that is simultaneously produced with the trans-4-phenylcyclohexane-based compound which is the object of the present invention. Since it also has an effect of isomerizing to the trans form, it needs to be used in a larger amount than that used in a general Friedel-Crafts reaction. Usually, the amount of the Lewis acid used is 1.2 to 2. per 1 mol part of 4-hydroxycyclohexanecarboxylic acid represented by the general formula (1) or its ester.
2 parts by mole. It is preferably 1.8 to 2.2 parts by mole. When the amount of the Lewis acid catalyst used is less than 1.2 parts by mole, the starting material, 4-hydroxycyclohexanecarboxylic acid represented by the general formula (1) or its ester remains unreacted, and the cis isomer And the yield decreases. Further, if it is more than 2.2 parts by mole, quenching takes time and is economically disadvantageous.

The reaction temperature of the Friedel-Crafts reaction is
The temperature is not particularly limited and is usually room temperature (about 20 ° C.) or room temperature or higher. It is preferably 35 to 80 ° C. Usually, the Friedel-Crafts reaction is carried out at room temperature, but in the present invention, the reaction can be promoted by setting the reaction temperature to 35 ° C. or higher. The reaction temperature is preferably 80 ° C. or lower in order to prevent the decomposition reaction.

The obtained trans-4-phenylcyclohexane compound of the present invention is purified to a highly pure compound by distillation, extraction, recrystallization and the like. As a solvent for recrystallization, methanol, ethanol, acetone, ethyl acetate or the like can be used. The transformer-4 represented by the general formula (3)
The alkyl ester group of the -phenylcyclohexane compound can be converted to a carboxy group by alkaline hydrolysis or the like, or conversely, the carboxy group can be esterified to an alkyl ester group.

[0031]

Industrial Applicability According to the present invention, it is possible to provide a method for producing a trans-4-phenylcyclohexane compound in high yield by industrially simple and safe operation.

[0032]

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

Example 1 (Synthesis of methyl 4-hydroxycyclohexanecarboxylate) Ethanol 380 was placed in an autoclave having a volume of 1 liter.
103 g (0.68) of methyl parahydroxybenzoate per ml
(Mol) was dissolved, and a dispersion liquid in which 10.3 g of 5 wt% ruthenium-supporting carbon was dispersed in 50 ml of ethanol was charged. Initial hydrogen pressure 65kg / cm ² , temperature 17
Start the reaction at ℃, stop heating at 36 ℃,
While maintaining the hydrogen pressure at 100 kg / cm ² , hydrogen was supplied until the absorption of hydrogen disappeared. The temperature rose to 74 ° C. The final hydrogen uptake was 94% of theory. After the catalyst was filtered off, the solvent and low-boiling components were distilled under reduced pressure to give methyl 4-hydroxycyclohexanecarboxylate 81.6 g (purity 98% by gas chromatography, yield 79).
Mol%) was obtained. The ratio of methyl 4-hydroxycyclohexanecarboxylate in cis form to trans form is 2.
It was 7: 1.

¹ H-NMR (300 MHz, CDCl
₃ ) = 1.30ppm (m, 1H), 1.50ppm
(M, 1H), 1.66ppm (m, 5H), 2.00
ppm (m, 3H), cis-form {2.42 ppm (m, 1
H), 3.68 ppm (s, 3H), 3.89 ppm
(M, 1H)}, transformer body {2.23 ppm (m, 1H
H), 3.60 ppm (s, 1H), 3.67 ppm
(S, 3H)}.

Example 2 (Synthesis of trans-4-phenylcyclohexanecarboxylic acid) To 120 ml (1.3 mol) of benzene, 47 g (0.35 mol) of anhydrous aluminum chloride was added and heated to 43 ° C. Next, 25m of benzene so as not to exceed 60 ° C
A solution of 25 g (0.16 mol) of methyl 4-hydroxycyclohexanecarboxylate obtained in Example 1 was added dropwise to 1 (0.3 mol). After the completion of dropping, the mixture was stirred at 60 ° C. for 1.5 hours. After confirming by gas chromatography that methyl 4-hydroxycyclohexanecarboxylate as a raw material had disappeared and that all reaction products had been isomerized to methyl trans-4-phenylcyclohexanecarboxylate, the mixture was cooled to room temperature. 170g of reaction product on ice
After pouring into the mixture, it was separated, and then 50 ml of benzene was added again to the aqueous layer for extraction. The extracted organic layers were combined, washed with water, washed with a saturated aqueous solution of potassium bicarbonate and saturated sodium chloride, dried over anhydrous magnesium sulfate, and then concentrated. 28 g of crude target product was removed by distilling the concentrate off under reduced pressure.
(Boiling point 120 to 150 ° C., 5 mmHg) was obtained.

5.0 g of sodium hydroxide having a purity of 96% by weight was added to 13.0 g (0.06 mol) of the obtained crude methyl trans-4-phenylcyclohexanecarboxylate.
What melt | dissolved (0.12 mol) in 65 ml of methanol was added, and after heating-refluxing for 1 hour, it cooled to room temperature. Then it is dissolved in 150 ml of water and stirred 2.
After 60 ml of 5N hydrochloric acid was added dropwise, the mixture was stirred for 1 hour. The precipitated crystals were separated by filtration and washed twice with 100 ml of water. Further, after dissolving the crystals in 80 ml of methanol at 60 ° C.,
The mixture was allowed to cool to room temperature, further cooled to 5 ° C. and recrystallized. The precipitated crystals were separated by filtration and washed once with 20 ml of methanol at -10 ° C. The crystals were dried under reduced pressure, and trans-4-phenylcyclohexanecarboxylic acid 7.4 g (4
-Yield 49 mol% from methyl hydroxycyclohexanecarboxylate).

¹ H-NMR (300 MHz, CDCl
₃ ) = 1.56ppm (m, 4H), 2.00ppm
(D, 2H), 2.15 ppm (d, 2H), 2.40
ppm (m, 1H), 2.53 ppm (m, 1H),
7.20ppm (m, 3H), 7.30ppm (m, 2
H), 11.80 ppm (br.s, 1H).

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[Procedure amendment]

[Submission date] May 2, 1995

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0035

[Correction method] Change

[Correction content]

Example 2 (Synthesis of trans-4-phenylcyclohexanecarboxylic acid) To 120 ml (1.3 mol) of benzene, 47 g (0.35 mol) of anhydrous aluminum chloride was added and heated to 43 ° C. Next, 25m of benzene so as not to exceed 60 ° C
A solution of 25 g (0.16 mol) of methyl 4-hydroxycyclohexanecarboxylate obtained in Example 1 was added dropwise to 1 (0.3 mol). After the completion of dropping, the mixture was stirred at 60 ° C. for 1.5 hours. After confirming by gas chromatography that methyl 4-hydroxycyclohexanecarboxylate as a raw material had disappeared and that all reaction products had been isomerized to methyl trans-4-phenylcyclohexanecarboxylate, the mixture was cooled to room temperature. 170g of reaction product on ice
After pouring into the mixture, it was separated, and then 50 ml of benzene was added again to the aqueous layer for extraction. The extracted organic layers were combined, washed with water, washed with a saturated aqueous solution of potassium bicarbonate and saturated sodium chloride, dried over anhydrous magnesium sulfate, and then concentrated. The concentrate was distilled under reduced pressure to obtain 28 g of a crude target product (boiling point 120 to 150 ° C., 5 mmHg).

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical indication C07C 69/753 9546-4H C07C 69/753 D // C07B 61/00 300 C07B 61/00 300

Claims (4)

[Claims] 1. General formula (1): (In the formula, X represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms) and 4-hydroxycyclohexanecarboxylic acid or an ester thereof and the general formula (2): (Wherein Y represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms or a halogen atom), or benzene or a derivative thereof is subjected to Friedel-Crafts reaction in the presence of a Lewis acid. General formula (3): (In the formula, X and Y are the same as above), a method for producing a trans-4-phenylcyclohexane compound. 2. General formula (4): (In the formula, X represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms), only the aromatic ring of p-hydroxybenzoic acid or its ester is hydrogenated to give a compound represented by the general formula (1): ] (Wherein, X represents a hydrogen atom or an alkyl group having 1 to 3 carbon atoms), 4-hydroxycyclohexanecarboxylic acid or an ester thereof is produced, and then 4-hydroxycyclohexanecarboxylic acid represented by the general formula (1) is used. Hydroxycyclohexanecarboxylic acid or its ester and the general formula (2): (Wherein Y represents a hydrogen atom, an alkyl group having 1 to 8 carbon atoms or a halogen atom), or benzene or a derivative thereof is subjected to Friedel-Crafts reaction in the presence of a Lewis acid. General formula (3): (In the formula, X and Y are the same as above), a method for producing a trans-4-phenylcyclohexane compound. 3. The amount of the Lewis acid used is 1.2 to 2.2 parts by mole with respect to 1 part by mole of 4-hydroxycyclohexanecarboxylic acid represented by the general formula (1) or its ester. Or the manufacturing method according to 2. 4. The reaction temperature is 35 to 80 ° C.
Or the manufacturing method according to 2.