WO2017090656A1

WO2017090656A1 - Method for producing trans-cyclohexanecarboxylic acid

Info

Publication number: WO2017090656A1
Application number: PCT/JP2016/084740
Authority: WO
Inventors: 憲之飛田; 大川　春樹
Original assignee: 住友化学株式会社
Priority date: 2015-11-27
Filing date: 2016-11-24
Publication date: 2017-06-01
Also published as: KR20180088667A; JP2017095420A; JP6720512B2; CN108290813A

Abstract

Provided is a method for producing a trans-4-substituted-cyclohexanecarboxylic acid under mild conditions with high yield. A method for producing a trans-4-substituted-cyclohexanecarboxylic acid (1-A), involving a step of heating a mixture containing a cis-trans mixure (1-1) of a 4-substitued-cyclohexanecarboxylic acid compound, a base and a hydrophobic organic solvent. The base comprises at least one compound selected from the group consisting of a hydroxide, a hydride and an alkoxide compound.

Description

Process for producing trans-cyclohexanecarboxylic acid

The present invention relates to a process for producing trans-cyclohexanecarboxylic acid.

In recent years, as a liquid crystal material that can be applied to an optical film such as a polarizing plate or a retardation plate used in a flat panel display (FPD), a compound including a structure derived from cycloalkane has been attracting attention. As an intermediate for producing the material, trans-4-substituted cyclohexanecarboxylic acid is preferably used.
As a method for producing trans-4-substituted cyclohexanecarboxylic acid, a mixture of a cis isomer and a trans isomer 4-substituted cyclohexanecarboxylic acid ester is heated to 200 ° C. in the presence of an excess strong base with a mixed solvent of alcohol and water. A method (see Non-Patent Document 1) is known.

In the conventional production method, severe pressure conditions are required, and the yield of trans-4-substituted cyclohexanecarboxylic acid is not sufficient.
An object of the present invention is to provide a method capable of producing a trans-4-substituted cyclohexanecarboxylic acid in a high yield under mild conditions.

That is, the present invention provides the following [1] to [8].

[1] A formula (1-A) comprising a step (1) of heating a cis-trans mixture of a 4-substituted-cyclohexanecarboxylic acid compound represented by formula (1-1), a mixture containing a base and a hydrophobic organic solvent A process for producing trans-4-substituted-cyclohexanecarboxylic acid represented by

[In Formula (1-1), R ¹ represents a hydrogen atom or an alkyl group having 1 to 20 carbon atoms.
In Formula (1-1) and Formula (1-A), J ¹ represents a halogen atom, a hydroxyl group, or an amino group.
n represents an integer of 1 to 20. ]
[2] The production method according to claim 1, wherein the base contains at least one selected from the group consisting of hydroxide, hydride and alkoxide compound.
[3] The production method according to claim 1 or 2, wherein the base is an alkoxide compound.
[4] The production method according to any one of claims 1 to 3, wherein the base is 1.1 molar equivalents or more based on the compound represented by the formula (1-1).
[5] The method according to any one of claims 1 ~ 4 J ¹ is a hydroxyl group.
[6] The production method according to any one of [1] to [5], wherein the heating is performed at 140 ° C to 180 ° C.
[7] The production method according to any one of [1] to [6], wherein the heating is performed at a boiling point or less of the hydrophobic organic solvent.
[8] The method according to any one of [1] to [7], wherein the heating is performed at 0.8 to 1.2 atmospheres.

According to the present invention, it is possible to produce trans-cyclohexanecarboxylic acid with high yield.

In the production method of the present invention, a mixture containing a compound represented by the formula (1-1) (hereinafter sometimes referred to as “compound (1-1)”), which is a cis-trans mixture, a base and a hydrophobic organic solvent is heated. A process for producing trans-4-substituted-cyclohexanecarboxylic acid represented by the formula (1-A) (hereinafter sometimes referred to as “compound (1-A)”).

In formula (1-1), R ¹ represents an alkyl group having 1 to 20 carbon atoms, preferably an alkyl group having 1 to 10 carbon atoms.
In formula (1-1) and formula (1-A), J ¹ represents any one of the group consisting of a halogen atom, a hydroxyl group and an amino group. n represents an integer of 1 to 20.

Examples of R ¹ include a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an isopropyl group, an isobutyl group, a t-butyl group, an n-pentyl group, and an n-hexyl group. Since the compound (1-1) is easily available, a methyl group, an ethyl group, an n-propyl group and an n-hexyl group are preferable, and a compound (1-1) having a high purity as a raw material is available. Since it is easy, a methyl group and an ethyl group are more preferable.

N represents an integer from 1 to 20. N> 8 is preferable because the melting points of the compound (1-1) and the compound (1-A) are high, and n is more preferably 8 <n <14 because it is cheaper. N is particularly preferably 11 because of excellent solubility.

J ¹ represents a halogen atom, a hydroxyl group, or an amino group. Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom, and a fluorine atom and a chlorine atom are preferable because the compound is stable.

In the amino group, one or more hydrogen atoms constituting the amino group may be substituted with an alkyl group. Examples of the amino group include —NH ₂ group, dimethylamino group, diethylamino group, dipropylamino group, dibutylamino group, dihexylamino group, morpholinyl group, piperidinyl group, pyrrolidinyl group and the like. A dimethylamino group is preferred because the production of the compound (1-1) is easy.

J ¹ is preferably a hydroxyl group.

Compound (1-1) is obtained by catalytic hydrogenation of the compound represented by Compound (2-1), and can be obtained according to the method described in Recueil des Travaux Chimiques des Pays-Bas, 1996,115,321-328. it can.

[In formula (2-1), R ¹ , J ¹ and n represent the same meaning as described above. ]

Examples of the catalyst used for catalytic hydrogenation include a palladium catalyst, a ruthenium catalyst, a platinum catalyst, a nickel catalyst, and a rhodium catalyst. Among these, a palladium catalyst, a platinum catalyst, a ruthenium catalyst, and a rhodium catalyst are preferable because the aromatic ring is easily hydrogenated, and a ruthenium catalyst is preferable because the catalyst is inexpensive.

The catalyst is preferably supported on carbon, alumina, or silica, and preferably contains moisture because it can be handled safely. The catalyst is more preferably ruthenium-carbon because of its excellent reaction activity.

Examples of solvents used for catalytic hydrogenation include methanol, ethanol, isopropanol, tetrahydrofuran, methylcyclohexane and the like. Tetrahydrofuran and methylcyclohexane are preferred because the compound (2-1) is difficult to transesterify, and methylcyclohexane is more preferred because it can be safely handled as a compound.

The solvent used for the catalytic hydrogenation is preferably 100 parts by weight or more with respect to 100 parts by weight of the compound (2-1). The solvent is more preferably 150 parts by weight or more because the reaction proceeds uniformly, and particularly preferably 150 parts by weight or more and 600 parts by weight or less because the volumetric efficiency of the reaction kettle is high and removal is easy.

In the case of catalytic hydrogenation, an acid such as acetic acid, formic acid or hydrochloric acid may be added to the above solvent.

The hydrogen pressure for catalytic hydrogenation is usually 1 MPa to 15 MPa. The hydrogen pressure is preferably from 1 MPa to 10 MPa because there are few side reactions, and more preferably from 4 MPa to 10 MPa because the reaction yield is high. The reaction temperature is preferably 50 ° C. to 200 ° C., more preferably 50 ° C. to 120 ° C. because there are few side reactions, and particularly preferably 70 ° C. to 120 ° C. because the reaction rate is fast.

The reaction solution may be used in the step (1) as it is in the solution after removing the catalyst by catalytic hydrogenation after the catalytic hydrogenation, or may be used in the step (1) by distilling off the reaction solvent. Good. Since the operation is simple, it is preferable to use the solution in the step (1) as it is without removing the reaction solvent.

When R ¹ is an alkyl group, step (1) may be performed after hydrolysis of the carboxylic acid ester and then R ¹ is converted to a hydrogen atom, or step (1) is performed without hydrolysis. The compound (1-A) may be obtained while converting R ¹ to a hydrogen atom.

In the step (1), a hydrophobic organic solvent itself or a solvent containing a hydrophobic organic solvent is used.
Examples of the hydrophobic organic solvent include aromatic systems such as benzene, toluene, xylene (orthoxylene, metaxylene, paraxylene, or a mixture thereof), mesitylene, cymene, cumene, durene, chlorobenzene, diphenyl ether, anisole, and thioanisole. Examples include organic solvents, hydrocarbon organic solvents such as heptane, octane, nonane, decane, undecane, dodecane, cyclohexane and methylcyclohexane. When using a hydrophobic organic solvent whose boiling point at normal pressure is lower than the temperature required for the isomerization reaction, a pressurized container such as an autoclave is required, and therefore a solvent having a boiling point higher than the reaction temperature should be used. preferable. In that case, a pressurized container such as an autoclave is not necessary, and the pressure is preferably 0.8 to 1.2 atm, more preferably 0.9 to 1.1 atm. .

The base used for isomerization includes at least one selected from the group consisting of hydroxides, hydrides and alkoxide compounds.
Examples of the hydroxide include lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide and the like.
Examples of the hydride include sodium hydride, potassium hydride, calcium hydride and the like.
Examples of the alkoxide compound include sodium methoxy, ethoxy sodium, i-propoxy sodium, t-butoxy sodium, and t-butoxy potassium.
As the base, an alkoxide compound is preferable because the reaction mass properties tend to be better, and t-butoxy sodium or t-butoxy potassium is more preferable.

When the above-mentioned base is used in a solvent, the reaction solution becomes heterogeneous, so increasing the surface area of the base is effective for increasing the reaction rate. For this reason, for example, base pellets may be crushed and used, or water may be added and dissolved to form a two-layer reaction solution with an organic solvent. Further, a phase transfer catalyst other than a polymer having an oxyethylene unit such as crown ether or polyethylene glycol may be added. Examples of such a phase transfer catalyst include a tetraalkylammonium salt, and a tetrabutylammonium salt is more preferable.

The base is preferably at least 1.1 molar equivalents relative to 1 mole of compound (1-1). Since a neutralization reaction is required when taking out as carboxylic acid after reaction, 1.1 to 5 molar equivalents are preferable, and 1.1 to 4 molar equivalents are more preferable.

The reaction temperature is usually 120 ° C. or higher, preferably 140 ° C. or higher and 180 ° C. or lower, more preferably 150 ° C. or higher and 170 ° C. or lower, which is not unreasonable in terms of equipment.

The reaction time is preferably 1 minute to 24 hours, more preferably 1 to 12 hours, and further preferably 2 to 10 hours.

The trans isomer obtained in the above step (1) is obtained by precipitation as a salt. Therefore, it is preferable to carry out the step (2) in order to take out the compound (1-A).

Examples of the step (2) include the following two methods.
The first method is described below. First, the salt of the compound (1-A) precipitated from the reaction solution is collected by filtration, dispersed in water, and neutralized. The precipitated solid is collected by filtration and washed with an organic solvent to remove the remaining cis form.

For neutralization, inorganic acids such as hydrochloric acid and sulfuric acid are preferably used.

Examples of the organic solvent include aromatic solvents such as toluene, xylene and benzene, aliphatic saturated hydrocarbon solvents such as n-heptane, n-hexane, n-pentane and n-octane, chloroform, dichloromethane, trichloroethane and chlorobenzene. The halogen type | system | group solvent of these is mentioned. As the mixed solvent, a plurality of the above solvents may be combined, or a mixed solvent in which a good solvent of the compound (1-A) and an aliphatic saturated hydrocarbon solvent such as n-hexane, n-pentane and n-octane are combined. But you can.

As a good solvent for the compound (1-A), ester solvents such as ethyl acetate, butyl acetate and ethyl lactate, ether solvents such as diethyl ether and tetrahydrofuran, halogen solvents such as chloroform, dichloromethane and trichloroethane, methyl isobutyl ketone And ketone solvents such as methyl ethyl ketone. Of these, ester solvents and halogen solvents are preferred because of their high acid stability and easy distillation, and ester solvents are more preferred.

As a solvent for washing, since the trans purity and yield of the compound are high, a mixed solvent of an aromatic solvent and an aliphatic saturated hydrocarbon solvent, a mixed solvent ester solvent of a halogen solvent and an aliphatic saturated hydrocarbon solvent, A mixed solvent of an aliphatic saturated hydrocarbon solvent is preferred. From the viewpoint of environmental compatibility, a mixed solvent of an aromatic solvent and an aliphatic saturated hydrocarbon solvent, and a mixed solvent of an ester solvent and an aliphatic saturated hydrocarbon solvent are more preferable.

Next, the second method is described below. The reaction solution is neutralized after adding the good solvent and water. After recovering the organic layer containing the compound (1-A) which is a carboxylic acid form, the compound (1-A) can be taken out by crystallization with a saturated hydrocarbon solvent which is a poor solvent and filtering.

For neutralization, inorganic acids such as hydrochloric acid and sulfuric acid are preferably used. Since the solubility of the compound (1-A) in an aromatic solvent is low, a salt may be removed by adding a good solvent as appropriate before or during neutralization and separating with water. The neutralization is more preferably performed after adding a good solvent and water.

Examples of the poor solvent include cyclic saturated hydrocarbon solvents such as cyclohexane and methylcyclohexane, and aliphatic saturated hydrocarbon solvents such as n-heptane, n-hexane, n-pentane and n-octane. Of the above solvents, aliphatic saturated hydrocarbon solvents are preferred, and n-heptane is more preferred.

The second method is preferable because a higher purity compound (1-A) can be obtained and filterability is excellent.

Furthermore, in the second method described above, the filtrate at the time of crystallization can be recovered and reused in the step (1) again.

The above filtrate contains the cis form of compound (1-A) and compound (1-A), but the filtrate may be concentrated under reduced pressure and step (1) may be performed again, or step (1) without concentration. ) May be added, and the poor solvent may be distilled off by heating.

Examples of the compound (1-1) preferably used include the following compounds (1-1-1) to (1-1-24).

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto. In the examples, “%” and “part” are, respectively, mass% and part by mass unless otherwise specified.

Example 1

10 g of cis / trans = 8/2 compound (A) obtained by the method described in Recueil des Travaux Chimiques des Pays-Bas, 1996, 115, 321-328, 80 g of methylcyclohexane, 2.5 g of potassium hydroxide and 55% water 1.4 g of an aqueous solution of n-tetrabutylammonium oxide was mixed and stirred at 65 ° C. for 8 hours. After cooling to 25 ° C., the mixture was allowed to stand to remove the oil layer, and 50 g of mesitylene and 10.7 g of 20% sulfuric acid were added and stirred for 30 minutes. The water layer was removed by allowing to stand, and washing with water was repeated until the pH reached 4 or more. After dehydration using Molecular Sieves 3A, 50 g of mesitylene was added and 9.8 g of potassium t-butoxy was added. The light boiling component was removed while gradually heating, and the mixture was heated to 160 ° C. and stirred for 8 hours. At this time, the reaction mass was white slurry. After cooling to 60 ° C., 30 g of water and 21.5 g of 20% sulfuric acid were added and stirred for 30 minutes. The water layer was removed by allowing to stand, and washing with water was repeated until the pH reached 4 or more. After cooling at 0 ° C., the precipitated solid was filtered and dried to obtain 8.5 g of Compound (B). The yield was 93%.

(Example 2)
10 g of cis / trans = 8/2 compound (A) obtained by the method described in Recueil des Travaux Chimiques des Pays-Bas, 1996, 115, 321-328, 80 g of methylcyclohexane, 2.5 g of potassium hydroxide and 55% water 1.4 g of an aqueous solution of n-tetrabutylammonium oxide was mixed and stirred at 65 ° C. for 8 hours. After cooling to 25 ° C., the mixture was allowed to stand to remove the oil layer, and 50 g of mesitylene and 10.7 g of 20% sulfuric acid were added and stirred for 30 minutes. The water layer was removed by allowing to stand, and washing with water was repeated until the pH reached 4 or more. After dehydration using Molecular Sieves 3A, 50 g of mesitylene was added, and 5.0 g of potassium hydroxide was added. The light boiling component was removed while gradually heating, and the mixture was heated to 160 ° C. and stirred for 8 hours. At this time, the reaction mass was in a state where a viscous solid was precipitated. After cooling to 60 ° C., 30 g of water and 21.5 g of 20% sulfuric acid were added and stirred for 30 minutes. The water layer was removed by allowing to stand, and washing with water was repeated until the pH reached 4 or more. After cooling at 0 ° C., the precipitated solid was filtered and dried to obtain 8.5 g of Compound (B). The yield was 93%.

(Comparative Example 1)
In the method described in Recueil des Travaux Chimiques des Pays-Bas, 1996, 115, 321-328, the target product, trans-cyclohexanecarboxylic acid, is synthesized in a yield of 60%.

From the above, it can be seen that the present invention is an excellent method for obtaining trans-cyclohexanecarboxylic acid in a high yield.

Claims

Represented by the formula (1-A) including the step (1) of heating the cis-trans mixture of the 4-substituted-cyclohexanecarboxylic acid compound represented by the formula (1-1) and the mixture containing the base and the hydrophobic organic solvent. Process for producing trans-4-substituted-cyclohexanecarboxylic acid.

[In Formula (1-1), R 1 represents a hydrogen atom or an alkyl group having 1 to 20 carbon atoms.
In Formula (1-1) and Formula (1-A), J 1 represents a halogen atom, a hydroxyl group, or an amino group. n represents an integer of 1 to 20. ]
The production method according to claim 1, wherein the base contains at least one selected from the group consisting of hydroxides, hydrides and alkoxide compounds.
The production method according to claim 1 or 2, wherein the base is an alkoxide compound.
The production method according to any one of claims 1 to 3, wherein the base is 1.1 molar equivalents or more based on the compound represented by the formula (1-1).
The production method according to any one of claims 1 to 4, wherein J 1 in the formula (1-1) and the formula (1-A) is a hydroxyl group.
The production method according to any one of claims 1 to 5, which is a step of heating at 140 ° C to 180 ° C.
The process according to any one of claims 1 to 6, wherein the step (1) is a step of heating at a boiling point or less of the hydrophobic organic solvent.
The process according to any one of claims 1 to 7, wherein the step (1) is heated at 0.8 to 1.2 atm.