Method for producing ether compounds

Abstract

To provide a method that can produce an ether compound at high yield.SOLUTION: A method for producing a compound represented by formula (D) comprises a step of reacting a compound represented by formula (A) with a hydroxy group protection reagent in the presence of an acid catalyst (where R1-R4 independently represent H, a halogen atom, a C1-6 alkyl group, -OR5,-C(=O)-R5 or -C(=O)-O-R5, R5 is an alkyl group, Z is a tetrahydropyranyl group, R6 is a monovalent organic group).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for producing an ether compound, which is an intermediate in the production of a polymerizable liquid crystal compound. [Background technology]

[0002] Optical films containing polymers of polymerizable liquid crystal compounds, such as polarizing films and retardation films, are used in displays such as liquid crystal displays. Ether compounds having a phenolic hydroxyl group are used as intermediates of the polymerizable liquid crystal compounds.

[0003] As a method for producing the ether compound, a method is known in which hydroquinone (HYQ) as a dihydric phenol is reacted with dihydropyran (DHP), one hydroxyl group of the hydroquinone is protected with a tetrahydropyranyl group (THP), and then the resulting reaction product is reacted with an alcohol compound in the presence of a base (Patent Document 1). [ka] [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2004-262884 Summary of the Invention [Problem to be solved by the invention]

[0005] In the production of ether compounds as described in the above patent documents, further improvement in yield is desired.

[0006] Therefore, an object of the present invention is to provide a method capable of producing an ether compound in high yield. [Means for solving the problem]

[0007] As a result of intensive research to solve the above problems, the present inventors have found that the manufacturing method of the present invention can solve the above problems, and have completed the present invention. That is, the present invention includes the following preferred embodiments.

[0008] [1] Formula (A): [ka] [In formula (A), R 1 ~R 4 each independently represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may have a substituent, -OR 5 , -C(=O)-R 5 or -C(=O)-OR 5 represents R 5 represents an alkyl group which may have a substituent. and a hydroxy group-protecting reagent in the presence of an acid catalyst; After adding a base to the reaction solution (X) obtained by the reaction in the above step (1), the unreacted compound (A) is removed, and a compound of the formula (B): [ka] [In formula (B), R 1 ~R 4 is as defined in the formula (A) above, and Z represents a protecting group. and a compound (B) represented by formula (C): [ka] [In formula (C), R 1 ~R 4 and Z is as defined above in formulas (A) and (B). Step (2) of obtaining a solution (Y) containing a compound (C) represented by the formula: By subjecting the compound (B) to an etherification reaction in the solution (Y), a compound of the formula (D): [ka] [In formula (D), R1 ~R 4 and Z are as defined in formulas (A) and (B), and R 6 represents a monovalent organic group] Step (3) of obtaining a compound (D) represented by A method for producing compound (D), comprising: [2] The method according to [1], wherein the solution (Y) contains at least one organic solvent selected from the group consisting of aromatic hydrocarbon solvents, aliphatic hydrocarbon solvents, and ether solvents. [3] The method according to [1] or [2], wherein the amount of the organic solvent contained in the solution (Y) is 100% by mass or more and 1000% by mass or less, based on the total mass of the compound (B) and the compound (C). [4] The method according to any one of [1] to [3], wherein the mass ratio of the compound (B) to the compound (C) contained in the solution (Y) is 1.5 or more. [5] The method according to any one of [1] to [4], wherein the amount of the acid catalyst used in the step (1) is 0.01 mol % or more and 5 mol % or less relative to the hydroxy group-protecting reagent. [6] The method according to any one of [1] to [5], wherein the amount of the base used in the step (2) is 0.01 mol % or more and 5 mol % or less relative to the hydroxy group-protecting reagent. [7] The method according to any one of [1] to [6], wherein the amount of the base used in the step (2) is 2 moles or more per mole of the acid catalyst. [8] The method according to any one of [1] to [7], wherein the amount of the hydroxy-protecting reagent used in the step (1) is 10 mol % or more and 70 mol % or less relative to the compound (A). [9] The method according to any one of [1] to [8], wherein in the formula (B), Z represents a tetrahydropyranyl group.

[10] In the formula (D), R 1 ~R 4 represents a hydrogen atom, the method according to any one of [1] to [9].

[11] The method according to any one of [1] to

[10] , wherein the content of the compound (A) in the solution (Y) is 1% by mass or less of the solution (Y).

[12] Formula (B): [ka] [In formula (B), R 1 ~R 4 each independently represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may have a substituent, -OR 5 , -C(=O)-R 5 or -C(=O)-OR 5 represents R 5 represents an alkyl group which may have a substituent, and Z represents a protecting group. and a compound (B) represented by formula (C): [ka] [In formula (C), R 1 ~R 4 and Z is as defined in formula (B) above. A solution containing a compound (C) represented by formula (A): [ka] [In formula (A), R 1 ~R 4 is as defined in formula (B) above. The content of the compound (A) represented by the formula (I) is 1% by mass or less of the solution. [Effects of the Invention]

[0009] According to the present invention, a method for producing an ether compound in high yield can be provided. DETAILED DESCRIPTION OF THE INVENTION

[0010] Hereinafter, embodiments of the present invention will be described in detail. Note that the scope of the present invention is not limited to the embodiments described here, and various modifications can be made without departing from the spirit of the present invention.

[0011] The production method of the present invention comprises the steps of: [ka] [In formula (A), R 1 ~R 4 each independently represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may have a substituent, -OR 5 , -C(=O)-R 5 or -C(=O)-OR 5 represents R 5 represents an alkyl group which may have a substituent. and a hydroxy group-protecting reagent in the presence of an acid catalyst; After adding a base to the reaction solution (X) obtained by the reaction in the above step (1), the unreacted compound (A) is removed, and a compound of the formula (B): [ka] [In formula (B), R 1 ~R 4 is as defined in the formula (A) above, and Z represents a protecting group. and a compound (B) represented by formula (C): [ka] [In formula (C), R 1 ~R 4 and Z is as defined above in formulas (A) and (B). Step (2) of obtaining a solution (Y) containing a compound (C) represented by the formula: By subjecting the compound (B) to an etherification reaction in the solution (Y), a compound of the formula (D): [ka] [In formula (D), R 1 ~R 4 and Z are as defined in formulas (A) and (B), and R 6 represents a monovalent organic group] Step (3) of obtaining a compound (D) represented by Includes:

[0012] [Process (1)] In step (1) of the production method of the present invention, a compound (A) represented by the above formula (A) is reacted with a hydroxy group-protecting reagent in the presence of an acid catalyst.

[0013] Formula (A) used in the present invention: [ka] In the compound (A) represented by the formula: 1 ~R 4 each independently represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may have a substituent, -OR 5 , -C(=O)-R 5 or -C(=O)-OR 5 represents R 5 represents an alkyl group which may have a substituent.

[0014] Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. Examples of the alkyl group having 1 to 6 carbon atoms include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, a tert-butyl group, a pentyl group, and a hexyl group. R 5 Examples of the alkyl group that can be represented include those exemplified above as the alkyl group having 1 to 6 carbon atoms. R 1 ~R 4 and R 5 Examples of the substituent that the alkyl group represented by the formula (I) may have include an alkyl group having 1 to 20 carbon atoms, an alkenyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 20 carbon atoms, a fluorinated alkyl group having 1 to 4 carbon atoms, a cyano group, a nitro group, a halogen atom, an amino group, and a hydroxy group.

[0015] Among these, R 1 ~R 4are each independently a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. Specific examples of such compound (A) include compounds represented by the following formulae (A-1) to (A-7). [ka] Among the above compounds, R 1 ~R 4 are all hydrogen atoms, that is, a compound represented by formula (A-1), i.e., hydroquinone.

[0016] As the hydroxy group-protecting reagent (hereinafter sometimes simply referred to as "protecting reagent") used in the present invention, a wide variety of hydroxy group-protecting reagents known in the art can be used. Among them, acetal-based protecting reagents are preferred, and from the viewpoint of ease of deprotection, at least one hydroxy group-protecting reagent selected from the group consisting of 3,4-dihydro-2H-pyran, 5,6-dihydro-4-methoxy-2H-pyran, ethoxyethylene, and 2-methoxypropene is more preferred, with 3,4-dihydro-2H-pyran being even more preferred.

[0017] The amount of the hydroxy group-protecting reagent is preferably 10 mol % or more, more preferably 20 mol % or more, and preferably 70 mol % or less, more preferably 60 mol % or less, relative to compound (A). When the amount of the hydroxy group-protecting reagent is equal to or more than the above-mentioned lower limit and equal to or less than the above-mentioned upper limit, the yield of compound (B), in which only one hydroxy group of compound (A) is protected, tends to be increased.

[0018] To ensure that the hydroxy groups are sufficiently protected by the protecting reagent, the protecting reagent is usually added in an amount of about 100 mol % (molar equivalent) relative to compound (A). However, adding a molar equivalent of the protecting reagent results in the production of compound (C), in which both hydroxy groups of compound (A) are protected, which can reduce the yield of compound (B), in which only one hydroxy group is protected. Therefore, the present inventors have discovered that adding the amount of the protecting reagent in the above range to suppress further reaction between compound (B), in which only one hydroxy group is protected, and the protecting reagent leads to a high yield of compound (B).

[0019] As the acid catalyst, either an inorganic acid or an organic acid can be used. Examples of inorganic acids include sulfuric acid, hydrogen halide, and phosphoric acid, and examples of organic acids include methanesulfonic acid, p-toluenesulfonic acid, and acetic acid. However, organic acids are preferred because they tend to increase the yield of compound (B). Among organic acids, at least one organic acid selected from the group consisting of methanesulfonic acid, p-toluenesulfonic acid, pyridinium p-toluenesulfonate, and acetic acid is preferred, at least one organic acid selected from the group consisting of methanesulfonic acid, p-toluenesulfonic acid, and pyridinium p-toluenesulfonate is more preferred, and p-toluenesulfonic acid is even more preferred.

[0020] The amount of the acid catalyst is preferably 0.01 mol % or more, more preferably 0.05 mol % or more, and even more preferably 0.1 mol % or more, relative to the hydroxy group-protecting reagent, and is preferably 5 mol % or less, more preferably 1 mol % or less. When the amount of the acid catalyst is equal to or more than the lower limit and equal to or less than the upper limit, the reaction tends to proceed moderately, and the produced compound (B) is unlikely to be deprotected and return to compound (A).

[0021] The reaction system in step (1) preferably contains an organic solvent in addition to the compound (A), a hydroxy group-protecting reagent, and an acid catalyst. The organic solvent is not particularly limited as long as it is inert to the reaction, and examples thereof include aromatic hydrocarbon solvents such as toluene, xylene, benzene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and heptane; ether solvents such as diethyl ether, tetrahydrofuran, and dimethoxyethane; ketone solvents such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; nitrile solvents such as acetonitrile; and aprotic polar solvents such as dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide, and N,N-dimethylacetamide. Among these, from the viewpoint of the solubility of compound (B) and the progress of the reaction, toluene, xylene, benzene, chlorobenzene, diethyl ether, tetrahydrofuran, methyl ethyl ketone, methyl isobutyl ketone, acetonitrile, dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide, and N,N-dimethylacetamide are preferred, tetrahydrofuran, dimethyl sulfoxide, N-methyl-2-pyrrolidone, and N,N-dimethylacetamide are more preferred, and tetrahydrofuran and dimethyl sulfoxide are even more preferred. These organic solvents may be used alone or in combination.

[0022] The amount of the organic solvent is not particularly limited as long as the compound (A), the hydroxy group-protecting reagent, and the acid catalyst are sufficiently dissolved. However, from the viewpoint of sufficiently dissolving each compound to facilitate appropriate reaction and avoiding the use of an excessive amount of solvent, the amount of the organic solvent is preferably 75 parts by mass or more, more preferably 80 parts by mass or more, and preferably 500 parts by mass or less, more preferably 300 parts by mass or less, relative to the mass of the compound (A).

[0023] The reaction system in step (1) may contain additives, if necessary, in addition to the compounds other than those mentioned above.

[0024] In step (1), the method for mixing compound (A), the hydroxy group-protecting reagent, the acid catalyst, and optionally the organic solvent and other additives is not particularly limited, and examples thereof include a method of mixing predetermined amounts of each compound at once in any order, a method of mixing a portion of predetermined amounts of each compound and then mixing the remaining portion into the reaction system, a method of adding a liquid compound dropwise to a system in which a solid compound is dissolved in an organic solvent and mixing them, a method of adding a solution in which a solid compound is dissolved in an organic solvent to a liquid compound and mixing them, etc. In addition, the reaction in step (1) is preferably carried out with stirring.

[0025] To prevent oxidation of compound (A) and facilitate the reaction, step (1) is preferably carried out under an inert gas atmosphere, such as nitrogen gas or argon gas.

[0026] In one embodiment of the present invention, the reaction temperature in step (1) is not particularly limited, but is preferably from 0° C. to 80° C., more preferably from 10° C. to 60° C., and even more preferably from 20° C. to 50° C. When the reaction temperature is equal to or higher than the above-mentioned lower limit and equal to or lower than the above-mentioned upper limit, the reaction tends to proceed appropriately. The stirring time in step (1) is not particularly limited and can be determined appropriately depending on the type and ratio of the compounds used, the reaction temperature, etc., but is usually from 1 hour to 72 hours, and more preferably from 2 hours to 48 hours. If the reaction time is within this range, the reaction tends to proceed appropriately. The progress of the reaction can be confirmed by known analytical means (e.g., thin layer chromatography, high-performance liquid chromatography, gas chromatography, infrared spectroscopy, etc.).

[0027] Specifically, step (1) can be carried out, for example, by the following method. In a predetermined reaction vessel (e.g., a reaction vessel equipped with a stirrer, a temperature controller, etc.), predetermined amounts of compound (A) and an acid catalyst, optionally together with an organic solvent, are added under an inert atmosphere. The order of addition is not particularly limited. After mixing by stirring or the like at an appropriate temperature, a protecting agent is added, for example, dropwise, and the mixture is stirred at a predetermined temperature for a predetermined time.

[0028] [Process (2)] In step (2) of the present invention, a base is added to the reaction solution (X) obtained by the reaction in step (1), and then the unreacted compound (A) is removed to obtain a solution (Y) containing compound (B) and compound (C).

[0029] The reaction solution (X) obtained by the reaction of the step (1) contains compound (B) in which only one hydroxy group is protected and compound (C) in which both hydroxy groups are protected, resulting from the reaction of compound (A) with a hydroxy group-protecting reagent, unreacted compound (A), an acid catalyst, and, in some cases, an organic solvent and an additive.

[0030] Z in compound (B) and compound (C) can represent an appropriate protecting group depending on the hydroxy group-protecting reagent used. However, Z is preferably a group derived from 3,4-dihydro-2H-pyran, 5,6-dihydro-4-methoxy-2H-pyran, ethoxyethylene, or 2-methoxypropene, which are preferred hydroxy group-protecting reagents because of ease of subsequent deprotection, and more preferably a tetrahydropyranyl (THP) group derived from 3,4-dihydro-2H-pyran.

[0031] The base added to reaction solution (X) is preferably an organic base, as it tends to increase the yield of compound (D), and is preferably at least one base selected from the group consisting of pyridine, triethylamine, diazabicycloundecene, and N,N-dimethylaminopyridine, with N,N-dimethylaminopyridine being more preferred, as it tends to increase the yield of compound (D). Addition of a base can completely halt the reaction in step (1), and easily suppresses deprotection of a compound in which one hydroxy group is protected, and excessive production of a compound in which both hydroxy groups are protected.

[0032] The amount of base relative to the hydroxy group-protecting reagent is preferably 0.01 mol% or more, more preferably 0.1 mol% or more, even more preferably 1 mol% or more, and preferably 5 mol% or less, more preferably 4 mol% or less. When the amount of base relative to the protecting reagent is above the above-mentioned lower limit and below the above-mentioned upper limit, the yield tends to be stable. Furthermore, the amount of base relative to 1 mole of the acid catalyst is preferably 2 mols or more, more preferably 5 mols or more. When the amount of base relative to the acid catalyst is above the above-mentioned lower limit, it is sufficient to terminate the reaction, which is preferable. There is no particular limit on the upper limit of the amount of base relative to the acid catalyst, but to avoid the use of excessive base, it is usually 30 mols or less relative to 1 mole of the acid catalyst.

[0033] In step (2), a base is added to the reaction solution (X), and then compound (A) is removed. While the removal method is not limited, separation (solvent extraction) using a two-layer system consisting of an organic solvent and water is preferred. By performing separation using a two-layer system, unreacted compound (A), the acid catalyst, and the hydroxyl-protecting reagent can be selectively removed from the organic solvent layer.

[0034] The organic solvent used for the separation is not particularly limited. However, if a hydrophilic organic solvent is used, subsequent separation may be difficult, and replacement with a hydrophobic organic solvent may be necessary by vacuum concentration, separation, or the like. Therefore, from the viewpoint of productivity, it is preferable to use a hydrophobic organic solvent. The hydrophobic organic solvent is not particularly limited as long as it is separable from water. Examples of the hydrophobic organic solvent include aromatic hydrocarbon solvents such as benzene, toluene, xylene (o-xylene, m-xylene, p-xylene, or a mixture thereof), mesitylene, cymene, cumene, durene, chlorobenzene, diphenyl ether, anisole, and thioanisole; aliphatic hydrocarbon solvents such as heptane, octane, nonane, decane, undecane, dodecane, n-hexane, cyclohexane, and methylcyclohexane; ether solvents such as dimethyl ether, diethyl ether, and ethyl acetate; halogenated hydrocarbon solvents such as chloroform and trichloroethylene; higher alcohol solvents such as benzyl alcohol and cyclohexanol; and ketone solvents such as methyl ethyl ketone, methyl isobutyl ketone, and cyclohexanone. Among these, at least one hydrophobic organic solvent selected from the group consisting of aromatic hydrocarbon solvents, aliphatic hydrocarbon solvents, and ether solvents is preferred, aromatic hydrocarbon solvents are more preferred, and toluene is even more preferred, from the viewpoint of productivity and the tendency to increase the reaction yield of compound (D). Therefore, solution (Y), which will be described later, preferably contains at least one organic solvent selected from the group consisting of aromatic hydrocarbon solvents, aliphatic hydrocarbon solvents, and ether solvents. The hydrophobic organic solvent may be used alone or in combination of two or more. When two or more types are used in combination, the mixing ratio is not particularly limited.

[0035] Therefore, in a preferred embodiment of the present invention, after adding a base to reaction solution (X), any organic solvent used in step (1) is optionally removed by distillation under reduced pressure or the like, and then a predetermined amount of organic solvent and water are added to perform a separation operation. Alternatively, if an organic solvent was used in step (1), the organic solvent may be added without being removed, and the separation operation may be performed by adding water. Separation may be performed multiple times to transfer unreacted compound (A), acid catalyst, and hydroxyl group-protecting reagent to the aqueous layer and thoroughly remove them. Furthermore, the amounts of organic solvent and water used for separation can be adjusted appropriately depending on the amount of starting compound used, but from the viewpoint of productivity, they are preferably 100% by mass or more and 1000% by mass or less based on the total mass of the expected compounds (B) and (C).

[0036] The organic solvent layer (in solution (Y)) after separation contains compound (B) in which only one hydroxy group is protected and compound (C) in which both hydroxy groups are protected. The amount of the organic solvent contained in the solution (Y) is preferably 100% by mass or more, more preferably 200% by mass or more, and preferably 1000% by mass or less, more preferably 900% by mass or less, based on the total mass of the compound (B) and the compound (C).

[0037] By going through the steps (1) and (2), compound (B) in which only one hydroxy group is protected can be obtained in good yield. The mass ratio of compound (B) to compound (C) in solution (Y) (mass of compound (B) / mass of compound (C)) is preferably 1.5 or more, more preferably 3.0 or more. The upper limit of the mass ratio of compound (B) to compound (C) is not particularly limited, but is usually 20 or less.

[0038] Since compound (C) does not react in the next step (3), it may remain in solution (Y). However, if unreacted compound (A) remains in solution (Y), it may contribute to the formation of impurities in the next step (3), resulting in a decrease in the purity of compound (D). Therefore, it is important to remove unreacted compound (A). Conventionally, compound (A) was removed by adding an excess base after the addition of a protecting reagent to convert compounds (B) and (C) into a salt form, making them water-soluble, followed by recovery of the aqueous layer by solution separation, followed by acid crystallization and filtration. However, this method also resulted in the removal of a portion of compound (B) simultaneously with the removal of compound (A), which was found to be a factor in the decrease in the yield of compound (B). Therefore, in the production method of the present invention, compound (B) can be obtained in high yield by selectively removing only compound (A) through separation by adding water. Furthermore, compound (B) can be used in the next step without isolation, which is advantageous from the viewpoint of productivity.

[0039] Therefore, the content of compound (A) in solution (Y) is preferably 1% by mass or less, more preferably 0.5% by mass or less, based on the mass of solution (Y). When the content of compound (A) is equal to or less than the upper limit, impurities are less likely to be generated in step (3), and therefore the purity of compound (D) is likely to be high.

[0040] The present invention also encompasses a solution (Y) having an extremely low content of compound (A), obtained by the production method of the present invention, i.e., a solution containing compound (B) and compound (C), in which the content of compound (A) in the solution is 1% by mass or less of the solution.

[0041] [Process (3)] In step (3), compound (B) is subjected to an etherification reaction in the solution (Y) obtained in step (2) to obtain compound (D).

[0042] The compound used in the etherification reaction is not particularly limited, but preferred examples include alcohols which may have a substituent having 1 to 10 carbon atoms and a leaving group. Examples of the leaving group include halogen atoms such as chlorine atom, bromine atom, and iodine atom; sulfonyl groups such as mesyl group and tosyl group; and examples of the substituent include alkoxy groups such as methoxy group and ethoxy group; nitro group; cyano group; etc. Among these, from the viewpoint of availability, alcohols having 1 to 10 carbon atoms and no substituent having a leaving group are preferred, and among these, 6-chloro-1-hexanol and 6-bromo-1-hexanol are more preferred. Therefore, R in compound (D) 6 is a monovalent organic group based on the compound to be etherified with compound (B), and the type thereof is not particularly limited, but is preferably a hydroxyalkyl group having 1 to 10 carbon atoms which may have a substituent, more preferably a hydroxyalkyl group having 1 to 10 carbon atoms which has no substituent, and even more preferably -CH 12 It's OH.

[0043] In a preferred embodiment of the present invention, compound (A) is R 1 ~R 4 A compound in which R are all hydrogen atoms, i.e., hydroquinone, is preferred. 1 ~R 4 R preferably represents a hydrogen atom. 1 ~R 4 If all of the are hydrogen atoms, the subsequent synthesis reaction proceeds more easily.

[0044] The conditions for the etherification reaction in step (3) are not particularly limited, and synthesis methods known in the art can be applied. In a preferred embodiment of the present invention, for example, the etherification reaction can be carried out by adding a base (e.g., potassium carbonate), a catalyst (e.g., potassium iodide), a compound for the etherification reaction (e.g., a halogenated alcohol), and optionally a solvent to solution (Y), and mixing them at a predetermined temperature under an inert atmosphere.

[0045] After the etherification reaction, the compound (D) produced can be further purified by known methods such as column chromatography and recrystallization. The structure of compound (D) can be determined by measuring NMR spectrum, IR spectrum, mass spectrum, etc., or by performing elemental analysis.

[0046] The compound (D) obtained by the production method of the present invention can be particularly suitably used as a raw material for producing a polymerizable liquid crystal compound, which is a material for producing an optical film. For example, as will be described later, the resulting compound (D) can be reacted with an unsaturated carboxylic acid compound or a derivative thereof to obtain a polymerizable compound, which is a raw material for a polymerizable liquid crystal compound.

[0047] [Method for producing polymerizable compound] The polymerizable compound, which is a raw material for the polymerizable liquid crystal compound, can be produced by reacting the compound (D) obtained by the production method of the present invention with, for example, an unsaturated carboxylic acid compound or a derivative thereof (for example, an esterification reaction or an etherification reaction). In one preferred embodiment, compound (D) and a compound of formula (E): [ka] [In formula (E), R 7 represents a chlorine atom or a bromine atom, and R 8 represents a hydrogen atom or a methyl group] In the presence of a base, the compound is esterified with an unsaturated carboxylic acid halide (E) represented by the formula (F): [ka] [In formula (F), R 1 ~R 4 , R 6 and R 8 is as defined above] A polymerizable compound (F) represented by the following formula can be obtained.

[0048] In the above-mentioned preferred embodiment, the compound (D) produced in step (3) can be used after purification by a procedure such as crystallization, but from the viewpoint of more convenient production, a solution containing the compound (D) can also be used in the reaction as it is. The molar ratio of the compound (D) to the unsaturated carboxylic acid halide is preferably 1:1 to 1:3, more preferably 1:1 to 1:2, and even more preferably 1:1 to 1:1.3.

[0049] The type of base is not particularly limited, but examples of inorganic bases include hydroxides, carbonates, and hydrogencarbonates, and examples of organic bases include pyridine, triethylamine, diisopropylethylamine, N,N-dimethylaniline, and N,N-dimethylaminopyridine. Among these, N,N-dimethylaniline is preferred. The bases may be used alone or in combination of two or more. The amount of the base is preferably 1.0 mole or more, more preferably 1.2 moles or more, and preferably 3 moles or less, more preferably 2 moles or less, relative to 1 mole of compound (D). When the amount of the base is equal to or more than the lower limit and equal to or less than the upper limit, the reaction can proceed sufficiently while suppressing excessive use of the base.

[0050] In the above reaction, additives such as a solvent and a polymerization inhibitor may be used as needed.

[0051] Examples of the solvent include aromatic hydrocarbon solvents such as toluene, xylene, benzene, and chlorobenzene; aliphatic hydrocarbon solvents such as pentane, hexane, and heptane; ether solvents such as diethyl ether, tetrahydrofuran, and dimethoxyethane; ketone solvents such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; nitrile solvents such as acetonitrile; and aprotic polar solvents such as dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylformamide, and N,N-dimethylacetamide. Among these, aromatic hydrocarbon solvents are preferred, and toluene is more preferred. The solvents may be used alone or in combination of two or more. The amount of the solvent is not particularly limited, but is preferably 0.5 parts by mass or more, more preferably 1 part by mass or more, and preferably 50 parts by mass or less, more preferably 10 parts by mass or less, relative to 1 part by mass of the total mass of compound (D) and the unsaturated carboxylic acid compound or its derivative. When the amount of the solvent is equal to or more than the lower limit and equal to or less than the upper limit, the reaction tends to proceed sufficiently, and excessive use of the solvent can be avoided.

[0052] The polymerization inhibitor is a compound that can prevent the polymerizable compound produced from polymerizing in the system. Examples of the polymerization inhibitor include 2,6-di-tert-butyl-p-cresol (BHT), 2,2'-methylenebis(6-tert-butyl-p-cresol), 4-methoxyphenol (MEHQ), phenothiazine, triphenyl phosphite, and tris(nonylphenyl) phosphite. The polymerization inhibitor may be used alone or in combination of two or more. The amount of the polymerization inhibitor is preferably 0.01 moles or more, more preferably 0.02 moles or more, per mole of compound (D). When the amount of the polymerization inhibitor is equal to or more than the lower limit, polymerization can be sufficiently inhibited.

[0053] After the esterification reaction, the protecting group (Z) in compound (D) is deprotected. The deprotection method can be a method known in the art for deprotecting a hydroxyl group-protecting reagent. In a preferred embodiment where the protecting group (Z) is a tetrahydropyranyl group, the deprotection can be carried out, for example, by adding an acid and a large excess of methanol, ethanol, or the like.

[0054] The reaction temperature is not particularly limited, but is usually -15 to 80°C, preferably -10 to 60°C, and more preferably 0 to 40°C.

[0055] The reaction time may be adjusted appropriately depending on the reaction temperature and the like, but is usually 1 to 24 hours. The reaction is preferably carried out in an inert gas atmosphere, such as nitrogen gas or argon gas, in order to suppress polymerization of the polymerizable compound. The progress of the reaction can be confirmed by known analytical means (for example, thin layer chromatography, high performance liquid chromatography, gas chromatography).

[0056] After completion of the reaction, a post-treatment operation that is usual in the art can be carried out, and if desired, the reaction product can be purified by a known separation and purification means such as distillation, column chromatography, or recrystallization to isolate the polymerizable compound.

[0057] The structure of a compound can be identified and confirmed by using analytical means such as NMR spectrum, IR spectrum, and mass spectrum.

[0058] By the above method, a polymerizable compound useful as an intermediate for a polymerizable liquid crystal compound can be obtained in high yield. [Example]

[0059] The present invention will be described in more detail below with reference to the following examples. In the examples, "%" and "parts" mean "% by mass" and "parts by mass", respectively, unless otherwise specified.

[0060] [High-performance liquid chromatograph] The amount of each component produced in the examples was calculated from the area value of high performance liquid chromatography (HPLC). The ratio of the amount (mol) of each component produced to the amount (mol) of dihydropyran charged was defined as the yield. The high performance liquid chromatograph (HPLC) used was used for measurements under the following conditions. Measurement model: LC-20AT (Shimadzu Corporation) Column used: Kinetex 2.6 μm C18, 100 Å, 100 × 4.6 mm Column temperature: 40℃ Solution A: 0.1mM PIC TBA-HS / water Solution B: 0.1mM PIC TBA-HS / acetonitrile Gradient conditions: 0 min 2%-B 20 minutes 65.3%-B 40 minutes 100%-B 50 minutes 100%-B 50.1 minutes 2%-B 60 minutes STOP Flow rate: 1.0mL / min Injection volume: 5μL Detection wavelength: UV 220nm

[0061] Example 1 [Synthesis of compound (F-1-6)] Compound (F-1-6) was synthesized according to the following scheme: In the formula, THP represents a tetrahydropyranyl group.

[0062] [ka]

[0063] 1. Synthesis of Compound (B-1) Process (1) 104.7 g (951 mmol) of hydroquinone (A-1) and 0.09 g (0.5 mmol) of paratoluenesulfonic acid monohydrate (p-Tos) were dissolved in 125.7 g of tetrahydrofuran, stirred for 10 minutes under a nitrogen atmosphere, and kept at 35° C. 40.0 g (476 mmol) of 3,4-dihydro-2H-pyran was added dropwise to this solution over 1 hour, and the mixture was stirred for 3 hours.

[0064] Process (2) 1.66 g (14 mmol) of N,N-dimethylaminopyridine was added to the above solution and stirred for 10 minutes. The pressure was reduced to 120 hPa, the temperature was raised to 50 ° C, and tetrahydrofuran was distilled off. 209.4 g of toluene was added to the residue, and the mixture was washed four times with 209.4 g of water at 50 ° C. In this way, 277.1 g of a toluene solution of compound (B-1) was obtained. Quantitative analysis of compound (B-1) in the solution by HPLC revealed that it was 58.3 g (300 mmol, 63.1% yield based on dihydropyran), and compound (C-1) was 10.6 g (38 mmol, 8.0% yield based on dihydropyran). The content of compound (A-1) in the toluene solution was 0.2% by mass. At this time, the mass ratio of compound (B-1) to compound (C-1) in the solution was 5.5.

[0065] 2. Synthesis of Compound (D-1-6) Process (3) To 277.1 g of a toluene solution of compound (B-1) obtained in step (1), 103.7 g (750 mmol) of potassium carbonate, 10.0 g (60 mmol) of potassium iodide, 160 g of N,N-dimethylacetamide, and 57.4 g (420 mmol) of 6-chloro-1-hexanol were added, stirred for 10 minutes under a nitrogen atmosphere, and then heated to 105 °C. After stirring for 18 hours, the mixture was cooled to 65 °C and washed three times with 174.9 g of water. The pressure was then reduced to 130 hPa, and the solvent was partially removed by distillation to obtain 267.8 g of a toluene solution of compound (D-1-6). The amount of compound (D-1-6) in the solution was quantified to 82.4 g (280 mmol, 58.8% yield based on dihydropyran).

[0066] 3. Synthesis of polymerizable compound (F-1-6) To 267.8 g of the toluene solution of compound (D-1-6) obtained in step (3), 47.3 g (390 mmol) of N,N-dimethylaniline and 6.6 g (30 mmol) of 2,6-di-tert-butyl-p-cresol (BHT) were added. The mixture was stirred for 10 minutes under a nitrogen atmosphere and maintained at 25°C. 32.6 g (360 mmol) of acrylic acid chloride [compound (E-1)] was added dropwise over 1 hour and stirred for 3 hours. 17.1 g (90 mmol) of p-toluenesulfonic acid and 26.5 g of methanol were added to the solution and stirred for 1 hour. After stirring, 220.9 g of water was added three times and the organic layer was extracted. The resulting solution was cooled to room temperature, 220 g of n-heptane was added, and the mixture was stirred under ice cooling. The resulting precipitate was filtered and dried under vacuum to obtain 59.3 g (224 mmol) of compound (F-1-6). In this case, the yield of compound (F-1-6) was 74.7% based on compound (B-1).

[0067] (Comparative Example 1) [Synthesis of compound (F-1-6)] Compound (F-1-6) was synthesized according to the description in JP-A Nos. 2004-262884 and 2010-1284.

[0068] 1. Synthesis of Compound (B-1) 104.7 g (951 mmol) of hydroquinone (A-1) and 9.0 g (47.6 mmol) of paratoluenesulfonic acid monohydrate were dissolved in 1 L of diethyl ether and stirred for 10 minutes under a nitrogen atmosphere. 80.0 g (951 mmol) of dihydropyran was added dropwise to the solution over 30 minutes and stirred at room temperature for 2 hours. This solution was purified by the method described in JP 2004-262884 A to obtain 51.4 g (264 mmol, 27.8% yield based on dihydropyran) of compound (B-1).

[0069] 2. Synthesis of Compound (F-1-6) Using 50 g (257 mmol) of the compound (B-1) obtained above, 64.7 g (220 mmol, 23.8% yield based on dihydropyran) of compound (D-1-6) was obtained by the method described in JP 2010-1284 A. Furthermore, 35.7 g (135 mmol) of compound (F-1-6) was obtained by the method described in the same document. In this case, the yield of compound (F-1-6) was 52.5% based on compound (B-1).

[0070] As described above, the production method of the present invention produced compound (D) in high yield. Therefore, it was found that the polymerizable compound was also produced in high yield in the subsequent production steps. Furthermore, the production method of the present invention does not require a purification step for the obtained compound (D), and the compound (D) can be subjected to the subsequent production steps in the solution state, which is advantageous from the viewpoint of productivity.

Claims

1. Formula (A): 【Chemical 1】 [In formula (A), R １ ~R ４ each independently represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may have a substituent, -OR ５ , —C(═O)—R ５ or -C(=O)-O-R ５ represents R ５ represents an alkyl group which may have a substituent. and a hydroxyl group-protecting reagent which is an acetal, in the presence of an acid catalyst; After adding an organic base to the reaction solution (X) obtained by the reaction in the above step (1), the unreacted compound (A) is removed, and a compound of the formula (B): 【Chemistry 2】 [In formula (B), R １ ~R ４ is as defined in the formula (A), and Z represents a protecting group. and a compound (B) represented by formula (C): 【Chemistry 3】 [In formula (C), R １ ~R ４ and Z is as defined in formulas (A) and (B) above. Step (2) of obtaining a solution (Y) containing a compound (C) represented by the formula: The compound (B) is subjected to an etherification reaction in the solution (Y), thereby obtaining a compound of the formula (D): 【Chemistry 4】 [In formula (D), R １ ~R ４ and Z are as defined in formulas (A) and (B), and R ６ represents a hydroxyalkyl group having 1 to 10 carbon atoms which may have a substituent. Step (3) of obtaining a compound (D) represented by A method for producing compound (D), comprising:

2. The method according to claim 1, wherein the solution (Y) contains at least one organic solvent selected from the group consisting of aromatic hydrocarbon solvents, aliphatic hydrocarbon solvents, and ether solvents.

3. The method according to claim 1 or 2, wherein the amount of the organic solvent contained in the solution (Y) is 100% by mass or more and 1000% by mass or less with respect to the total mass of the compound (B) and the compound (C).

4. The method according to any one of claims 1 to 3, wherein the mass ratio of the compound (B) to the compound (C) contained in the solution (Y) is 1.5 or more.

5. The method according to any one of claims 1 to 4, wherein the amount of the acid catalyst used in the step (1) is 0.01 mol % or more and 5 mol % or less relative to the hydroxy group-protecting reagent.

6. The method according to any one of claims 1 to 5, wherein the amount of the base used in the step (2) is 0.01 mol % or more and 5 mol % or less relative to the hydroxy group-protecting reagent.

7. The method according to any one of claims 1 to 6, wherein the amount of the base used in the step (2) is 2 moles or more per mole of the acid catalyst.

8. The method according to any one of claims 1 to 7, wherein the amount of the hydroxy group-protecting reagent used in the step (1) is 10 mol % or more and 70 mol % or less relative to the compound (A).

9. The method according to any one of claims 1 to 8, wherein in formula (B), Z represents a tetrahydropyranyl group.

10. In the formula (D), R １ ~R ４ The method according to any one of claims 1 to 9, wherein represents a hydrogen atom.

11. The method according to any one of claims 1 to 10, wherein the content of the compound (A) in the solution (Y) is 1% by mass or less of the solution (Y).

12. Formula (B): 【Chemistry 5】 [In formula (B), R １ ~R ４ each independently represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may have a substituent, -OR ５ , —C(═O)—R ５ or -C(=O)-O-R ５ represents R ５ represents an alkyl group which may have a substituent, and Z represents a protecting group derived from an acetal-based hydroxy-protecting reagent. Compound (B) represented by formula (C): 【Chemistry 6】 [In formula (C), R １ ~R ４ and Z is as defined in formula (B). A solution containing a compound (C) represented by formula (A): 【Chemistry 7】 [In formula (A), R １ ~R ４ is as defined in formula (B). The content of the compound (A) represented by the formula (I) is 1% by mass or less of the solution.

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