Method for producing bis(alkyloxy)benzene

Abstract

To provide a production method that can yield high-purity bis(alkyloxy)benzene.SOLUTION: A method for producing bis(alkyloxy)benzene represented by formula (2) [where R is an integer of C6-20 alkyl group] includes a step for reacting benzene diol represented by formula (1) and alkyl halide in the presence of an organic solvent and potassium carbonate with a 50% average particle size of 50 μm or less.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for producing bis(alkyloxy)benzenes. [Background technology]

[0002] Bis(alkyloxy)benzenes are bis-ethers of benzenediols such as catechol and hydroquinone with aliphatic alcohols, and are known to be used as raw materials for soluble fullerene derivatives (Patent Document 1), blue electroluminescent polymers (Patent Document 2), discotic liquid crystal compounds (Patent Document 3), etc., and as color-changing temperature regulators for reversible thermochromic microcapsule pigments (Patent Document 4).

[0003] For example, Patent Document 1 describes the synthesis of 1,2-dioctyloxybenzene by reacting catechol with 1-bromooctane in the presence of potassium carbonate. However, there was a problem in that multiple side reactions also proceeded simultaneously with the target reaction, and the by-products reduced the purity of the resulting bis(alkyloxy)benzene. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2009-135237 [Patent Document 2] Japanese Patent Application Laid-Open No. 2003-183363 [Patent Document 3] Japanese Patent Application Laid-Open No. 2011-201831 [Patent Document 4] Japanese Patent Application Laid-Open No. 2007-118197 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide a method for producing bis(alkyloxy)benzene with high purity. [Means for solving the problem]

[0006] In view of the above problems, the present inventors have conducted extensive research and have found that a highly pure bis(alkyloxy)benzene can be obtained by reacting a benzenediol with an alkyl halide in the presence of potassium carbonate having a 50% average particle size of 50 μm or less, thereby completing the present invention.

[0007] That is, the present invention includes the following preferred embodiments. [1] In the presence of an organic solvent and potassium carbonate having a 50% average particle size of 50 μm or less, a solution of the compound represented by the formula (1) is prepared. [ka] and an alkyl halide. Reacting the compound represented by formula (2) [ka] [wherein R represents an alkyl group having 6 to 20 carbon atoms] A method for producing a bis(alkyloxy)benzene represented by the formula: [2] The method according to [1], wherein the benzenediol represented by formula (1) is selected from the group consisting of catechol, resorcinol, and hydroquinone. [3] The method according to [1] or [2], wherein the alkyl halide is 1-bromooctane or 1-bromooctadecane. [4] The method according to any one of [1] to [3], wherein the bis(alkyloxy)benzene represented by formula (2) is selected from the group consisting of 1,2-bis(n-octyloxy)benzene, 1,3-bis(n-octyloxy)benzene, 1,4-bis(n-octyloxy)benzene, 1,2-bis(n-octadecyloxy)benzene, 1,3-bis(n-octadecyloxy)benzene, and 1,4-bis(n-octadecyloxy)benzene. [5] The method according to any one of [1] to [4], wherein 1 mole of the benzenediol represented by the formula (1) is reacted with 1.8 to 5.0 moles of an alkyl halide. [6] The method according to any one of [1] to [5], wherein 1.5 to 5.0 moles of potassium carbonate are present per mole of the benzenediol represented by the formula (1). [7] The method according to any one of [1] to [6], wherein the benzenediol represented by the formula (1) is reacted with an alkyl halide at a temperature of 50 to 150°C. [8] The method according to any one of [1] to [7], wherein the organic solvent is N,N-dimethylformamide. [9] The method according to any one of [1] to [8], wherein the step is a step of obtaining a crude composition containing a bis(alkyloxy)benzene represented by formula (2).

[10] The method according to [9], comprising a step of distilling the bis(alkyloxy)benzene represented by formula (2) from the crude composition.

[11] The method according to [9], comprising a step of recrystallizing the bis(alkyloxy)benzene represented by formula (2) from the crude composition using a recrystallization solvent.

[12] The method according to

[11] , wherein the recrystallization solvent is one or more selected from the group consisting of xylene, toluene, heptane, cyclohexanone, methanol, ethanol, tetrahydrofuran (THF), 4-methyltetrahydropyran (MTHP), chloroform, and N,N-dimethylformamide (DMF). [Effects of the Invention]

[0008] According to the present invention, bis(alkyloxy)benzene can be obtained with high purity. DETAILED DESCRIPTION OF THE INVENTION

[0009] In the present invention, the benzenediol and alkyl halide used as reaction raw materials may be commercially available products, or may be produced by methods known to those skilled in the art.

[0010] The benzenediol used in the present invention is represented by the formula (1): [ka] It is a benzenediol represented by the formula:

[0011] Specific examples thereof include those selected from the group consisting of (1)-1: catechol, (1)-2: resorcinol, and (1)-3: hydroquinone. [ka]

[0012] Specific examples of alkyl halides used in the present invention include 1-bromohexane, 1-bromoheptane, 1-bromooctane, 1-bromononane, 1-bromodecane, 1-bromoundecane, 1-bromododecane, 1-bromotridecane, 1-bromotetradecane, 1-bromopentadecane, 1-bromohexadecane, 1-bromoheptadecane, 1-bromooctadecane, 1-bromononadecane, 1-bromoeicosane, 1-chlorohexane, 1-chloroheptane, 1-chlorooctane, 1-chlorononane, 1-chlorodecane, 1-chloroundecane, 1-chlorododecane, 1-chlorotridecane, 1-chlorotetradecane, 1-bromopentadecane, 1-bromohexadecane, 1-bromoheptadecane, 1-bromooctadecane, 1-bromononadecane, 1-bromoeicosane, 1-chlorohexane, 1-chloroheptane, 1-chlorooctane, 1-chlorononane, 1-chlorodecane, 1-chloroundecane, 1-chlorododecane, 1-chlorotridecane, 1-chlorotetradecane, 1-bromotetradecane, 1-bromohexadecane ... Examples of the bromine include at least one selected from the group consisting of 1-bromo-2-ethylhexane, 1-bromooctane ...

[0013] The alkyl halide used in the present invention is reacted preferably in an amount of 1.8 to 5.0 mol, more preferably 1.9 to 4.0 mol, still more preferably 2.0 to 3.5 mol, and particularly preferably 2.1 to 3.0 mol, per mol of the benzenediol represented by formula (1).

[0014] If the amount of alkyl halide exceeds 5.0 moles per mole of benzenediol represented by formula (1), an excess amount of alkyl halide remains, and hydroxide ions in the reaction system react with the alkyl halide to produce alcohol, which reduces production efficiency and tends to require a long time to remove the alcohol in the post-treatment step. Also, if the amount of alkyl halide is less than 1.8 moles, the production rate tends to decrease.

[0015] In the present invention, for example, the reaction of 1 mole of benzenediol represented by formula (1) with 2 moles of alkyl halide is carried out by allowing the alkyl halide to be present in an amount such that 2 moles are present per mole of benzenediol represented by formula (1).

[0016] The 50% average particle size of the potassium carbonate used in the present invention is 50 μm or less, preferably 0.1 to 40 μm, and more preferably 1.0 to 30 μm. When the 50% average particle size of the potassium carbonate is within the above range, the reaction proceeds sufficiently while side reactions are suppressed. When the 50% average particle size of the potassium carbonate exceeds 50 μm, the reaction takes a long time and the production efficiency decreases.

[0017] The amount of potassium carbonate used in the present invention is preferably 1.5 to 5.0 mol, more preferably 1.8 to 4.5 mol, still more preferably 2.0 to 4.0 mol, and particularly preferably 2.2 to 3.5 mol, per mol of the benzenediol represented by formula (1).

[0018] If the amount of potassium carbonate is less than 1.5 moles per mole of benzenediol represented by formula (1), the reaction tends to proceed insufficiently. On the other hand, if the amount of potassium carbonate is more than 5.0 moles, the conversion rate of alkyl halide to alcohol increases, and the reaction tends to proceed insufficiently.

[0019] The reaction temperature in the reaction of the benzenediol represented by formula (1) with the alkyl halide is not particularly limited, but is preferably 50 to 150° C., more preferably 70 to 130° C., and even more preferably 90 to 110° C. When the reaction temperature is within the above range, the reaction is likely to proceed sufficiently while side reactions are suppressed.

[0020] The reaction time is not particularly limited as it varies depending on conditions such as the reaction temperature, but it may be selected appropriately within the range of usually 1 to 50 hours, preferably 3 to 40 hours, and more preferably 6 to 30 hours.

[0021] Examples of organic solvents that can be used in the present invention include hydrocarbon solvents such as hexane, benzene, and toluene; ether solvents such as diethyl ether, 1,4-dioxane, diglyme, cyclopentyl methyl ether (CPME), and tetrahydrofuran (THF); ester solvents such as ethyl acetate and butyl acetate; halogenated hydrocarbon solvents such as 1,2-dichloroethane and chloroform; nitrile solvents such as acetonitrile and benzonitrile; protic polar solvents such as acetic acid, ethanol, butanol, ethylene glycol, and glycerin; and aprotic polar solvents such as acetone, N,N-dimethylacetamide (DMA), N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), and dimethyl sulfoxide (DMSO). Among these, N,N-dimethylformamide is preferred due to its excellent reaction yield. These reaction solvents are not limited to a single type, and may be a mixed solvent of two or more types. It is also preferable to dehydrate and deoxygenate the reaction solvent before use.

[0022] The amount of the organic solvent used in the present invention is preferably 1 to 30 times by mass, more preferably 3 to 20 times by mass, further preferably 5 to 15 times by mass, and particularly preferably 7 to 10 times by mass, relative to the amount of the benzenediol represented by formula (1).

[0023] In the present invention, the reaction of the benzenediol represented by formula (1) with the alkyl halide is preferably carried out under a stream or bubbling of an inert gas, or under reduced pressure, which can avoid reaction inhibition by oxygen or moisture and allow the reaction to proceed smoothly.

[0024] The inert gas may be any gas that does not inhibit the reaction, and specifically may be one or more selected from the group consisting of nitrogen, carbon dioxide, argon, helium, neon, xenon, and krypton. Of these, nitrogen is preferred because of its availability and economical value.

[0025] The inert gas may be blown into the space above the reaction liquid in a reaction vessel containing the raw materials, benzenediol represented by formula (1) and alkyl halide, or may be blown directly into the reaction liquid.

[0026] The above reaction of the benzenediol represented by formula (1) with the alkyl halide produces a compound represented by formula (2): [ka] A bis(alkyloxy)benzene represented by the formula:

[0027] Examples of the bis(alkyloxy)benzene represented by formula (2) include 1,2-bis(n-hexyloxy)benzene, 1,3-bis(n-hexyloxy)benzene, 1,4-bis(n-hexyloxy)benzene, 1,2-bis(n-heptyloxy)benzene, 1,3-bis(n-heptyloxy)benzene, 1,4-bis(n-heptyloxy)benzene, 1,2-bis(n-octyloxy)benzene, 1,3-bis(n-octyloxy)benzene, 1,4-bis(n-octyloxy)benzene, and 1,2-bis(n-nonyloxy)benzene. , 1,3-bis(n-nonyloxy)benzene, 1,4-bis(n-nonyloxy)benzene, 1,2-bis(n-decyloxy)benzene, 1,3-bis(n-decyloxy)benzene, 1,4-bis(n-decyloxy)benzene, 1,2-bis(n-undecyloxy)benzene, 1,3-bis(n-undecyloxy)benzene, 1,4-bis(n-undecyloxy)benzene, 1,2-bis(n-dodecyloxy)benzene, 1,3-bis(n-dodecyloxy)benzene, 1,4-bis(n-dodecyloxy)benzene, 1,2-bis (n-tridecyloxy)benzene, 1,3-bis(n-tridecyloxy)benzene, 1,4-bis(n-tridecyloxy)benzene, 1,2-bis(n-tetradecyloxy)benzene, 1,3-bis(n-tetradecyloxy)benzene, 1,4-bis(n-tetradecyloxy)benzene, 1,2-bis(n-pentadecyloxy)benzene, 1,3-bis(n-pentadecyloxy)benzene, 1,4-bis(n-pentadecyloxy)benzene, 1,2-bis(n-hexadecyloxy)benzene, 1,3-bis(n-hexadecyloxy)benzene oxy)benzene, 1,4-bis(n-hexadecyloxy)benzene, 1,2-bis(n-heptadecyloxy)benzene, 1,3-bis(n-heptadecyloxy)benzene, 1,4-bis(n-heptadecyloxy)benzene, 1,2-bis(n-octadecyloxy)benzene, 1,3-bis(n-octadecyloxy)benzene, 1,4-bis(n-octadecyloxy)benzene, 1,2-bis(n-nonadecyloxy)benzene, 1,3-bis(n-nonadecyloxy)benzene, 1,4-bis(n-nonadecyloxy)benzene, 1,Examples include 2-bis(n-eicosyloxy)benzene, 1,3-bis(n-eicosyloxy)benzene, 1,4-bis(n-eicosyloxy)benzene, 1,2-bis(n-ethylhexyloxy)benzene, 1,3-bis(n-ethylhexyloxy)benzene, and 1,4-bis(n-ethylhexyloxy)benzene. Among these, those selected from the group consisting of 1,2-bis(n-octyloxy)benzene, 1,3-bis(n-octyloxy)benzene, 1,4-bis(n-octyloxy)benzene, 1,2-bis(n-octadecyloxy)benzene, 1,3-bis(n-octadecyloxy)benzene, and 1,4-bis(n-octadecyloxy)benzene are preferred. The structural formulas of each are shown below.

[0028] 1,2-bis(n-octyloxy)benzene [ka] 1,3-bis(n-octyloxy)benzene [ka] 1,4-bis(n-octyloxy)benzene [ka] 1,2-bis(n-octadecyloxy)benzene [ka] 1,3-bis(n-octadecyloxy)benzene [ka] 1,4-bis(n-octadecyloxy)benzene [ka]

[0029] A crude composition containing bis(alkyloxy)benzene represented by formula (2) is obtained by reacting a benzenediol represented by formula (1) with an alkyl halide in the presence of an organic solvent and potassium carbonate having a 50% average particle size of 50 μm or less. The purity of the crude composition containing bis(alkyloxy)benzene represented by formula (2) can be further increased by purification.

[0030] The purification preferably includes a step of distilling the bis(alkyloxy)benzene from a crude composition containing the bis(alkyloxy)benzene represented by formula (2) and / or a step of recrystallizing the bis(alkyloxy)benzene represented by formula (2) in a recrystallization solvent, in terms of efficiently increasing the purity of the product.

[0031] Before the above purification operation, if necessary, washing with an aqueous medium to remove water-soluble compounds, filtration to remove insoluble foreign matter, or treatment with an adsorbent such as activated carbon to remove coloring substances, metals, etc. may be carried out.

[0032] The crude composition containing the bis(alkyloxy)benzene represented by formula (2) means a composition containing, in addition to the crude composition containing the bis(alkyloxy)benzene represented by formula (2), which is the target product, impurities such as reaction raw materials, intermediates, by-products, etc. The content of impurities varies depending on the reaction method, but is usually 1 to 25 mass % of the crude composition, and in other cases 3 to 15 mass %.

[0033] Specific impurities contained in the crude composition include residues of the raw materials such as alkyl halides and benzenediol, as well as intermediates such as monoethers of benzenediol and alkyl halides, and alcohols as by-products that are reaction products of hydroxide ions and alkyl halides.

[0034] The step of distilling the bis(alkyloxy)benzene from a crude composition containing the bis(alkyloxy)benzene represented by formula (2) is carried out by adding the crude composition to a distillation apparatus, heating it under normal pressure or under reduced pressure, and recovering the bis(alkyloxy)benzene.

[0035] The distillation is preferably carried out appropriately at a pressure of 1 to 50 hPa and a temperature of 150 to 250°C.

[0036] The recrystallization step is carried out by adding a recrystallization solvent to a crude composition containing a bis(alkyloxy)benzene represented by formula (2), raising the temperature to 50 to 150°C (depending on the solvent used) to completely dissolve the crude composition, and then lowering the temperature to 10 to 50°C with stirring to precipitate crystals of the bis(alkyloxy)benzene.

[0037] The recrystallization solvent used in the recrystallization step may be one or more selected from the group consisting of xylene, heptane, cyclohexanone, chloroform, N,N-dimethylformamide (DMF), toluene, N-methyl-2-pyrrolidone, dimethyl sulfoxide, acetonitrile, methanol, ethanol, acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, tetrahydrofuran, 4-methyltetrahydropyran, dioxane, ethyl acetate, propyl acetate, and butyl acetate. Among these, one or more selected from the group consisting of xylene, toluene, heptane, cyclohexanone, methanol, ethanol, tetrahydrofuran (THF), 4-methyltetrahydropyran (MTHP), chloroform, and N,N-dimethylformamide (DMF) are preferred because of their excellent ability to remove impurities.

[0038] The amount of the recrystallization solvent used in the recrystallization step varies depending on the type of solvent, but is preferably 1 to 30 times by mass, more preferably 5 to 20 times by mass, relative to the raw material benzenediol. If the amount of the recrystallization solvent is less than 1 time by mass relative to the benzenediol, impurities such as raw materials and by-products tend to be incorporated into the crystals, making it difficult to obtain high-purity crystals. If the amount of the recrystallization solvent is more than 30 times by mass, the yield of bis(alkyloxy)benzene may decrease significantly.

[0039] The crystals obtained by recrystallization are subjected to solid-liquid separation by conventional means such as filtration, and the target bis(alkyloxy)benzene is recovered. During solid-liquid separation, it is preferable to wash the crystals by pouring an appropriate organic solvent. The organic solvent used during solid-liquid separation is preferably one or more selected from the group consisting of methanol, ethanol, acetone, chloroform, toluene, xylene, cyclohexanone, tetrahydrofuran (THF), and N,N-dimethylformamide (DMF). The organic solvent is preferably used in an amount of 0.5 to 20 times by mass relative to the benzenediol.

[0040] The crystals recovered by solid-liquid separation can be dried by ventilation under normal pressure or by drying under reduced pressure and distilling off the solvent, thereby obtaining a highly pure bis(alkyloxy)benzene. [Example]

[0041] The present invention will be described in more detail below with reference to examples, but the present invention is not limited thereto. The abbreviations for each compound are as follows: CO-8: 1,2-bis(n-octyloxy)benzene CO-18: 1,2-bis(n-octadecyloxy)benzene RO-8: 1,3-bis(n-octyloxy)benzene RO-18: 1,3-bis(n-octadecyloxy)benzene HO-8: 1,4-bis(n-octyloxy)benzene HO-18: 1,4-bis(n-octadecyloxy)benzene

[0042] Each compound was analyzed by the following method.

[0043] CO-8 Analysis <Ultra-High Performance Liquid Chromatography (UPLC)> Instrument: Waters UPLC H-Class system Column model: ACQUITY UPLC HSS C18 1.8μm 2.1×50mm Fluid volume: 0.5 mL / min Solvent ratio: H2O (pH 2.3) / MeOH = 80 / 20 (1.5 min) → 0.5 min → 36 / 64 (3 min) → 1 min → 18 / 82 (3 min) → 1.5 min → 4 / 96 (4.5 min) gradient analysis Wavelength: 229nm Column temperature: 40℃ <Calculation method> The area percentage was calculated by using the total amount of all peak areas detected between retention times of 0.5 and 15 minutes as the denominator and the peak area of ​​each substance as the numerator. The peak position of each compound varies depending on the sample concentration, so it is difficult to generalize, but the approximate retention time (holding time) at the peak top of each compound is shown below. Catechol: 0.7 minutes CO-8: 12 minutes Monoether of catechol and 1-bromooctane: 7 minutes All other peaks were determined to be by-products.

[0044] Analysis of RO-8 <Ultra-High Performance Liquid Chromatography (UPLC)> Instrument: Waters UPLC H-Class system Column model: ACQUITY UPLC HSS C18 1.8μm 2.1×50mm Fluid volume: 0.5 mL / min Solvent ratio: H2O (pH 2.3) / MeOH = 80 / 20 (1.5 min) → 0.5 min → 36 / 64 (3 min) → 1 min → 18 / 82 (3 min) → 1.5 min → 10 / 90 (5.5 min) → 2 min → 2 / 98 (4 min) gradient analysis Wavelength: 229nm Column temperature: 40℃ <Calculation method> The area percentage was calculated by using the total area of ​​all peaks detected between retention times of 0.4 and 20 minutes as the denominator and the peak area of ​​each substance as the numerator. The peak position of each compound varies depending on the sample concentration, so it is difficult to generalize, but the approximate retention time (holding time) at the peak top of each compound is shown below. Resorcinol: 0.5 min RO-8:15 min Monoether of resorcyl and 1-bromooctane: 7 minutes All other peaks were determined to be by-products.

[0045] Analysis of the HO-8 <Ultra-High Performance Liquid Chromatography (UPLC)> Instrument: Waters UPLC H-Class system Column model: ACQUITY UPLC HSS C18 1.8μm 2.1×50mm Fluid volume: 0.5 mL / min Solvent ratio: H2O (pH 2.3) / MeOH = 80 / 20 (1.5 min) → 0.5 min → 36 / 64 (3 min) → 1 min → 18 / 82 (3 min) → 1.5 min → 4 / 96 (4.5 min) gradient analysis Wavelength: 229nm Column temperature: 40℃ <Calculation method> The area percentage was calculated by using the total amount of all peak areas detected between retention times of 0.5 and 15 minutes as the denominator and the peak area of ​​each substance as the numerator. The peak position of each compound varies depending on the sample concentration, so it is difficult to generalize, but the approximate retention time (holding time) at the peak top of each compound is shown below. Hydroquinone: 0.6 minutes HO-8:13 min Monoether of hydroquinone and 1-bromooctane: 17 minutes All other peaks were determined to be by-products.

[0046] CO-18, RO-18, HO-18 analysis <Ultra-High Performance Liquid Chromatography (UPLC)> Instrument: Waters UPLC H-Class system Column model: ACQUITY UPLC HSS C18 1.8μm 2.1×50mm Fluid volume: 0.5 mL / min Solvent ratio: MeOH = 100% Wavelength: 229nm Column temperature: 40℃ <Calculation method> The area percentage was calculated by using the total amount of all peak areas detected between retention times of 0.2 and 15 minutes as the denominator and the peak area of ​​each substance as the numerator. The peak position of each compound varies depending on the sample concentration, so it is difficult to generalize, but the approximate retention time (holding time) at the peak top of each compound is shown below. Catechol: 0.2 minutes CO-18: 10-12 minutes Monoether of catechol and 1-bromooctadecyl (intermediate): 0.7 minutes Resorcinol: 0.2 min RO-18: 12-14 minutes Monoether of resorcinol and 1-bromooctadecyl (intermediate): 0.7 minutes Hydroquinone: 0.2 minutes HO-18: 10-13 minutes Monoether of hydroquinone and 1-bromooctadecyl (intermediate): 0.6 minutes All other peaks were determined to be by-products.

[0047] CO-8 Analysis <Gas chromatography (GC)> Equipment: Shimadzu GC-2014 Column model number: G-100 1.2mm x 40m 5μm Carrier gas: He 20 mL / min Internal standard: butyl benzoate Solvent: Acetone Column temperature: 140℃

[0048] Analysis of RO-8 and HO-8 <Gas chromatography (GC)> Equipment: Shimadzu GC-2014 Column model number: G-100 1.2mm x 40m 5μm Carrier gas: He 20 mL / min Internal standard: propyl benzoate Solvent: Acetone Column temperature: 140℃

[0049] CO-18, RO-18, HO-18 analysis <Gas chromatography (GC)> Equipment: Shimadzu GC-2014 Column model number: G-100 1.2mm x 40m 1μm Carrier gas: He 20 mL / min Internal standard: dibutyl phthalate Solvent: Chloroform Column temperature: 200℃

[0050] Example 1 (Example for reference) Synthesis of CO-8 A 0.5 L four-neck flask equipped with a stirrer and temperature sensor was charged with 22.0 g (0.20 mol) of catechol (CT, Fujifilm Wako Pure Chemical Industries, Ltd.), 81.4 g (0.42 mol) of 1-bromooctane (OcBr, TCI Corporation), 60.9 g (0.44 mol) of potassium carbonate (Nippon Soda Co., Ltd., 50% mean particle size 19.38 μm), and 176.3 g of DMF (8.0 parts by mass relative to CT). The mixture was heated to 100 °C under a nitrogen stream and allowed to react at that temperature for 6 hours. After that, 7.9 g (0.04 mol) of OctBr and 5.5 g (0.04 mol) of potassium carbonate were added and the mixture was allowed to react at that temperature for an additional 3 hours to obtain a crude composition. The resulting crude composition was analyzed by UPLC. The results are shown in Table 1.

[0051] Example 2 (Example for reference) Synthesis of RO-8 A 0.5 L four-neck flask equipped with a stirrer and temperature sensor was charged with 22.0 g (0.20 mol) of resorcinol (RE, Fujifilm Wako Pure Chemical Industries, Ltd.), 81.1 g (0.42 mol) of 1-bromooctane (OcBr, TCI Corporation), 60.9 g (0.44 mol) of potassium carbonate (Nippon Soda Co., Ltd., 50% mean particle size 19.38 μm), and 176.0 g of DMF (8.0 parts by mass relative to the RE). The mixture was heated to 100°C under a nitrogen stream and allowed to react at that temperature for 3 hours. After that, 3.9 g (0.02 mol) of OcBr was added and the mixture was allowed to react at that temperature for 3 hours. After that, 7.7 g (0.04 mol) of OcBr was added and the mixture was allowed to react at that temperature for 3 hours, yielding a composition. The resulting crude composition was analyzed by UPLC. The results are shown in Table 1.

[0052] Example 3 (Example for reference) Synthesis of HO-8 A 0.5L four-neck flask equipped with a stirrer and temperature sensor was charged with 22.0g (0.20 mol) of hydroquinone (HQ, manufactured by Ube Industries, Ltd.), 96.5g (0.50 mol) of 1-bromooctane (OcBr, manufactured by TCI), 71.8g (0.52 mol) of potassium carbonate (manufactured by Nippon Soda Co., Ltd., 50% average particle size 19.38μm), and 176.3g of DMF (8.0 parts by mass relative to HQ). The mixture was heated to 100°C under a nitrogen stream and reacted at that temperature for 12 hours. After that, 19.3g (0.10 mol) of OctBr and 13.9g (0.10 mol) of potassium carbonate were added and the mixture was reacted at the same temperature for an additional 9 hours to obtain a crude composition. The resulting composition was analyzed by UPLC. The results are shown in Table 1.

[0053] Example 4: Synthesis of CO-18 A 0.5 L four-neck flask equipped with a stirrer and temperature sensor was charged with 22.0 g (0.20 mol) of catechol (CT, Fujifilm Wako Pure Chemical Industries, Ltd.), 159.9 g (0.48 mol) of 1-bromooctadecane (ODBr, TCI Corporation), 66.8 g (0.48 mol) of potassium carbonate (Nippon Soda Co., Ltd., 50% average particle size 19.38 μm), and 179.1 g of DMF (8.1 parts by mass relative to CT). The mixture was heated to 100°C under a nitrogen stream and allowed to react at that temperature for 9 hours to obtain a crude composition. The crude composition was analyzed by UPLC. The results are shown in Table 1.

[0054] Example 5: Synthesis of RO-18 A 0.5 L four-neck flask equipped with a stirrer and temperature sensor was charged with 22.0 g (0.20 mol) of resorcinol (RE, Fujifilm Wako Pure Chemical Industries, Ltd.), 166.8 g (0.50 mol) of 1-bromooctadecane (ODBr, TCI), 66.3 g (0.48 mol) of potassium carbonate (Nippon Soda Co., Ltd., 50% average particle size 19.38 μm), and 176.2 g of DMF (8.1 parts by mass relative to RE). The mixture was heated to 100°C under a nitrogen stream and allowed to react at that temperature for 6 hours to obtain a crude composition. The crude composition was analyzed by UPLC. The results are shown in Table 1.

[0055] Example 6: Synthesis of HO-18 A 0.5 L four-neck flask equipped with a stirrer and temperature sensor was charged with 22.0 g (0.20 mol) of hydroquinone (HQ, manufactured by Ube Industries, Ltd.), 201.1 g (0.60 mol) of 1-bromooctadecane (ODBr, manufactured by TCI), 85.6 g (0.62 mol) of potassium carbonate (manufactured by Nippon Soda Co., Ltd., 50% average particle size 19.38 μm), and 220.6 g of DMF (10.0 parts by mass relative to HQ). The mixture was heated to 100°C under a nitrogen stream and allowed to react at that temperature for 9 hours to obtain a crude composition. The resulting crude composition was analyzed by UPLC. The results are shown in Table 1.

[0056] Comparative Examples 1 to 4 Crude compositions were obtained in the same manner as in Examples 1 to 4, except that potassium carbonate (manufactured by Nippon Soda Co., Ltd., 50% average particle size 19.38 μm) was replaced with potassium carbonate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., 50% average particle size 481.4 μm). The results are shown in Table 2.

[0057] Example 7 (Example for reference) : CO-8 purification (distillation) The reaction solution obtained in Example 1 was cooled to 30°C and subjected to solid-liquid separation at the same temperature. The filtrate was recovered, and the solvent was distilled off from the recovered filtrate at 70°C and 5 hPa to recover the residue. 110.2 g of xylene and 44.0 g of water were added to the residue, which was then added to a 0.5 L flask equipped with a stirrer and a temperature sensor and stirred at 80°C for 30 minutes. The aqueous solution was allowed to stand until it separated into an organic layer and an aqueous layer, and the aqueous layer was then removed. 44.0 g of water was added to the remaining organic layer, stirred at 80°C for 30 minutes, and allowed to stand until the aqueous solution separated into an organic layer and an aqueous layer, after which the organic layer was removed. The organic layer was added to a recovery flask equipped with a Liebig condenser, and a stirrer was added. While stirring with a magnetic stirrer, the pressure was reduced to 4 hPa and the temperature was raised to 193 °C. Distillation was then performed under reduced pressure, and the fraction was recovered, yielding 61.7 g of 1,2-bis(n-octyloxy)benzene (CO-8) (yield: 90.7 mol%) (yield: molar amount of recovered bis(alkyloxy)benzene / molar amount of charged benzenediol). The resulting CO-8 was analyzed by UPLC and GC. The analytical results are shown in Table 3.

[0058] Example 8 (Example for reference) : Purification of RO-8 (recrystallization) The reaction solution obtained in Example 2 was cooled to 60°C and subjected to solid-liquid separation at the same temperature. The filtrate was recovered, and the solvent was distilled off from the recovered filtrate at 80°C and 10 hPa to recover the residue. 44.0 g of xylene and 44.0 g of water were added to the residue, which was then added to a 0.5 L flask equipped with a stirrer and temperature sensor and stirred at 80°C for 30 minutes. The solution was allowed to stand until the organic and aqueous layers separated, and the aqueous layer was then removed. 44.0 g of water was added to the remaining organic layer, which was then stirred at 80°C for 30 minutes. The solution was allowed to stand until the organic and aqueous layers separated, and the organic layer was then removed. The removed organic layer was added to a 0.5 L flask equipped with a stirrer and temperature sensor, and 21.9 g of xylene and 66.0 g of methanol were added. The mixture was cooled to 15°C, resulting in the precipitation of 1,3-bis(n-octyloxy)benzene (RO-8). The suspension was subjected to solid-liquid separation and washed with 66.1 g of methanol. The obtained crystals were dried at 50°C and 10 hPa to obtain 32.7 g of RO-8 crystals (yield: 48.6 mol%). The obtained RO-8 was analyzed by UPLC and GC. The analytical results are shown in Table 3.

[0059] Example 9 (Example for reference) : Purification of HO-8 (recrystallization) The reaction solution obtained in Example 3 was cooled to 60°C and subjected to solid-liquid separation at the same temperature. The filtrate was recovered, and the solvent was distilled off from the recovered filtrate at 80°C and 10 hPa to recover the residue. 65.4 g of xylene and 22.5 g of water were added to the residue, which was then added to a 0.5 L flask equipped with a stirrer and a temperature sensor and stirred at 80°C for 30 minutes. The aqueous solution was allowed to stand until it separated into an organic layer and an aqueous layer, and then the aqueous layer was removed. 22.6 g of water was added to the remaining organic layer, which was stirred at 80°C for 30 minutes. The aqueous solution was allowed to stand until it separated into an organic layer and an aqueous layer, and then the organic layer was removed. The removed organic layer was added to a 0.5 L flask equipped with a stirrer and a temperature sensor and cooled to 10°C to precipitate 1,4-bis(n-octyloxy)benzene (HO-8). The suspension was subjected to solid-liquid separation and washed with 181.6 g of methanol. The obtained crystals were dried at 50 ° C and 10 hPa to obtain 44.5 g of HO-8 crystals (yield 66.5 mol%). The obtained HO-8 was analyzed by UPLC and GC. The analytical results are shown in Table 3.

[0060] Example 10: Purification (recrystallization) of CO-18 The reaction mixture obtained in Example 4 was added with 175.9 g of water and heated to 90°C. The mixture was then added to a 1.0 L flask equipped with a stirrer and a temperature sensor. 113.7 g of water was added and the mixture was stirred at 90°C for 30 minutes. The mixture was allowed to stand until the aqueous solution separated, and the aqueous layer was then removed. 44.2 g of water, 330.5 g of xylene, and 123.4 g of cyclohexanone were added to the remaining organic layer, and the mixture was stirred at 95°C for 30 minutes. The organic layer was then allowed to stand until the aqueous solution separated, and the organic layer was then removed. The removed organic layer was added to a 0.5 L flask equipped with a stirrer and a temperature sensor and cooled to 27°C, resulting in the precipitation of 1,2-bis(n-octadecyloxy)benzene (CO-18). The suspension was subjected to solid-liquid separation and washed with 111.1 g of methanol. The resulting crystals were dried at 60°C and 10 hPa, yielding 76.7 g of CO-18 crystals (yield: 60.9 mol%). The obtained CO-18 was analyzed by UPLC and GC. The analytical results are shown in Table 4.

[0061] Example 11: Purification (recrystallization) of RO-18 The reaction mixture obtained in Example 5 was added with 178.3 g of water and heated to 90°C. The mixture was then added to a 1.0 L flask equipped with a stirrer and a temperature sensor. 177.1 g of water was added and the mixture was stirred at 90°C for 30 minutes. The mixture was allowed to stand until the aqueous solution separated, and the aqueous layer was then removed. 43.7 g of water, 351.4 g of xylene, and 177.2 g of cyclohexanone were added to the remaining organic layer, and the mixture was stirred at 90°C for 30 minutes. The organic layer was then allowed to stand until the aqueous solution separated, and the organic layer was then removed. The removed organic layer was added to a 0.5 L flask equipped with a stirrer and a temperature sensor and cooled to 35°C, resulting in the precipitation of 1,3-bis(n-octadecyloxy)benzene (RO-18). The suspension was subjected to solid-liquid separation and washed with 65.3 g of methanol. The resulting crystals were dried at 60°C and 5 hPa, yielding 94.0 g of RO-18 crystals (yield: 75.5 mol%). The obtained RO-18 was analyzed by UPLC and GC. The analytical results are shown in Table 4.

[0062] Example 12: Purification (recrystallization) of HO-18 The reaction mixture obtained in Example 6 was added with 156.2 g of water and heated to 100°C. The mixture was then poured into a 1.0 L flask equipped with a stirrer and temperature sensor. 184.4 g of water was added and the mixture was stirred at 90°C for 30 minutes. The mixture was allowed to stand until the aqueous solution separated, and the aqueous layer was then removed. 44.7 g of water, 111.1 g of xylene, and 330.8 g of cyclohexanone were added to the remaining organic layer, and the mixture was stirred at 90°C for 30 minutes. The mixture was allowed to stand until the aqueous solution separated, and the aqueous layer was then removed. 2.3 g of carborafine was added to the remaining organic layer, and the mixture was stirred at 100°C for 1 hour for decolorization. The mixture was then subjected to solid-liquid separation at the same temperature, and the carbon was removed, and the organic layer was then removed. The removed organic layer was then poured into a 0.5 L flask equipped with a stirrer and temperature sensor, and cooled to 40°C, resulting in the precipitation of 1,4-bis(n-octadecyloxy)benzene (HO-18). The suspension was subjected to solid-liquid separation and washed with 220.3 g of methanol. The obtained crystals were dried at 60 °C and 5 hPa to obtain 112.6 g of HO-18 crystals (yield 91.4 mol%). The obtained HO-18 was analyzed by UPLC and GC. The analytical results are shown in Table 4.

[0063] As shown in Tables 1 and 2, Examples 1 to 6 of the present invention, which used potassium carbonate with a 50% average particle size of 50 μm or less, showed a lower residual rate of the intermediate (monoether of benzenediol and alkyl halide), suppressed the production of by-products, and increased the production rate of the target substance, compared to Comparative Examples 1 to 4, which used potassium carbonate with a 50% average particle size of more than 50 μm. Furthermore, as shown in Tables 3 and 4, it was found that further purification such as distillation and recrystallization could significantly remove excess reaction raw materials and by-products.

[0064] [Table 1]

[0065] [Table 2]

[0066] [Table 3]

[0067] Table 4

Claims

1. In the presence of N,N-dimethylformamide and potassium carbonate having a 50% average particle size of 50 μm or less, a solution of a compound represented by the formula (1) 【Chemistry 1】 and an alkyl halide. Reacting the compound represented by formula (2) 【Chemistry 2】 [wherein R represents an alkyl group having an integer of 9 to 20 carbon atoms] A method for producing high-purity bis(alkyloxy)benzene represented by the formula: 1 mole of benzenediol represented by formula (1) is reacted with 1.8 to 5.0 moles of alkyl halide, 1.5 to 5.0 moles of potassium carbonate are present relative to 1 mole of the benzenediol represented by formula (1), and A method of reacting a benzenediol represented by formula (1) with an alkyl halide at a temperature of 50 to 150°C.

2. The method according to claim 1, wherein the benzenediol represented by formula (1) is selected from the group consisting of catechol, resorcinol and hydroquinone.

3. The method of claim 1 or 2, wherein the alkyl halide is 1-bromooctadecane.

4. The method according to any one of claims 1 to 3, wherein the bis(alkyloxy)benzene represented by formula (2) is selected from the group consisting of 1,2-bis(n-octadecyloxy)benzene, 1,3-bis(n-octadecyloxy)benzene, and 1,4-bis(n-octadecyloxy)benzene.

5. The method according to any one of claims 1 to 4, wherein the benzenediol represented by formula (1) is reacted with the alkyl halide at a temperature of 90 to 150°C.

6. The method according to any one of claims 1 to 5, wherein the step is a step of obtaining a crude composition containing a bis(alkyloxy)benzene represented by formula (2).

7. 7. The method of claim 6, further comprising the step of distilling the bis(alkyloxy)benzene represented by formula (2) from the crude composition.

8. The method according to claim 6, further comprising the step of recrystallizing the bis(alkyloxy)benzene represented by formula (2) from the crude composition using a recrystallization solvent.

9. 9. The method according to claim 8, wherein the recrystallization solvent is at least one selected from the group consisting of xylene, toluene, heptane, cyclohexanone, methanol, ethanol, tetrahydrofuran (THF), 4-methyltetrahydropyran (MTHP), chloroform, and N,N-dimethylformamide (DMF).

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