Method for producing 3-hydroxybenzoic acid long chain ester

Abstract

To provide a production method that can produce 3-hydroxybenzoic acid long-chain ester with a reduced number of steps, and at a high yield rate.SOLUTION: This invention relates to a method for producing 3-hydroxybenzoic acid long-chain ester represented by formula (2) [n is an integer of 11-23], including the step of reacting, in the presence of an organic liquid and an acid catalyst, 3-hydroxybenzoic acid with an aliphatic alcohol represented by formula (1) [where n is an integer of 11-23].SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a method for producing a long-chain 3-hydroxybenzoic acid ester. [Background technology]

[0002] Long-chain 4-hydroxybenzoic acid esters have a structure containing a hydroxyl group and a hydrophobic group, and due to this structural feature, their applications as plasticizers, pest repellents, compatibilizers, etc. have been proposed (Patent Documents 1 and 2).

[0003] Known methods for producing long-chain 4-hydroxybenzoic acid esters include a transesterification method between a short-chain 4-hydroxybenzoic acid ester and a long-chain alcohol in the presence of a metal catalyst (Patent Document 3) and a dehydration method between 4-hydroxybenzoic acid and a long-chain alcohol in the presence of a protonic acid catalyst.

[0004] However, long-chain esters of 4-hydroxybenzoic acid may have low solubility when used in various applications, and there is an increasing demand for long-chain esters of 3-hydroxybenzoic acid as an alternative.

[0005] As a method for producing a long-chain 3-hydroxybenzoic acid ester, the transesterification method or the dehydration method may be used, similarly to the method for producing a long-chain 4-hydroxybenzoic acid ester.

[0006] The transesterification method can produce a high-purity product, but since it uses a short-chain hydroxybenzoic acid ester as the raw material, it requires the prior synthesis of the raw material, resulting in a large number of total steps.

[0007] On the other hand, the dehydration method requires fewer manufacturing steps and can be produced at low cost, but the production rate is relatively low at 80 to 90%, and further improvement in the production rate is necessary for industrial-scale production. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] JP 2016-113509 A [Patent Document 2] JP 2019-199439 A [Patent Document 3] JP 2016-210699 A Summary of the Invention [Problem to be solved by the invention]

[0009] An object of the present invention is to provide a method for producing a long-chain 3-hydroxybenzoic acid ester with a small number of steps and at a high production rate. [Means for solving the problem]

[0010] In view of the above problems, the present inventors conducted intensive research and found that, in a method for dehydrating 3-hydroxybenzoic acid with a long-chain alcohol, a long-chain 3-hydroxybenzoic acid ester can be obtained in high yield by adding an organic liquid, thereby completing the present invention.

[0011] That is, the present invention includes the following preferred embodiments. [1] In the presence of an organic liquid and an acid catalyst, 3-hydroxybenzoic acid and the formula (1) [ka] [In the formula, n represents an integer of 11 to 23] With an aliphatic alcohol represented by formula (2), [ka] [n is an integer between 11 and 23] A method for producing a long-chain 3-hydroxybenzoic acid ester represented by the formula: [2] The method according to [1], wherein the organic liquid is one or more selected from the group consisting of toluene, xylene, mesitylene, anisole, hexane, heptane, octane and cyclohexane. [3] The method according to [1] or [2], wherein the organic liquid is toluene and / or xylene. [4] The method according to any one of [1] to [3], wherein the 3-hydroxybenzoic acid long-chain ester represented by formula (2) is hexadecyl 3-hydroxybenzoate. [5] The method according to any one of [1] to [4], wherein 1 mole of 3-hydroxybenzoic acid is reacted with 0.5 to 3.0 moles of an aliphatic alcohol. [6] The method according to any one of [1] to [5], wherein 0.1 to 10 parts by mass of an acid catalyst is present per 100 parts by mass of 3-hydroxybenzoic acid. [7] The method according to any one of [1] to [6], wherein 3-hydroxybenzoic acid is reacted with an aliphatic alcohol at a temperature of 100 to 150°C. [8] The method according to any one of [1] to [7], wherein the step is a step of obtaining a crude composition containing a 3-hydroxybenzoic acid long-chain ester represented by formula (2). [9] The method according to [8], comprising the steps of dissolving the crude composition in a solvent comprising a non-polar solvent, and crystallizing the resulting solution.

[10] The method according to [9], wherein the non-polar solvent is one or more selected from the group consisting of toluene, xylene, mesitylene, anisole, hexane, heptane, octane and cyclohexane.

[11] The method according to [9] or

[10] , wherein the non-polar solvent is xylene. Effect of the Invention

[0012] According to the present invention, a long-chain 3-hydroxybenzoic acid ester can be obtained at a high production rate. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] In the present invention, the 3-hydroxybenzoic acid and the aliphatic alcohol used as the reaction raw materials may be commercially available products, or products produced by methods known to those skilled in the art may be used.

[0014] The aliphatic alcohol used in the present invention has the formula (1): [ka] [n is an integer between 11 and 23] It is an aliphatic alcohol having 12 to 24 carbon atoms represented by the formula: Specific examples thereof include one or more selected from the group consisting of dodecanol, tridecanol, tetradecanol, pentadecanol, hexadecanol, heptadecanol, octadecanol, nonadecanol, icosanol, henicosanol, docosanol, tricosanol, and tetracosanol. Among these, hexadecanol is preferred because of its easy availability.

[0015] The aliphatic alcohol used in the present invention is reacted preferably in an amount of 0.5 to 3.0 mol, more preferably 0.7 to 1.5 mol, further preferably 0.8 to 1.2 mol, particularly preferably 0.9 to 1.1 mol, per mol of 3-hydroxybenzoic acid.

[0016] When the amount of the aliphatic alcohol is less than 0.5 molar equivalents per molar equivalent of 3-hydroxybenzoic acid, the production rate tends to decrease. On the other hand, when the amount of the aliphatic alcohol is more than 3.0 molar equivalents, an excessive amount of the aliphatic alcohol remains, which reduces the production efficiency and tends to require a long time to remove the aliphatic alcohol in the post-treatment process.

[0017] In the present invention, for example, the reaction of 1 molar equivalent of 3-hydroxybenzoic acid with 1.5 molar equivalents of an aliphatic alcohol is carried out by providing 1.5 molar equivalents of the aliphatic alcohol per molar equivalent of 3-hydroxybenzoic acid.

[0018] The acid catalyst used in the present invention may be one or more selected from the group consisting of p-toluenesulfonic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, sulfuric acid, hydrochloric acid, phosphoric acid, and nitric acid. In terms of availability and excellent reactivity, sulfuric acid or p-toluenesulfonic acid is preferred, and p-toluenesulfonic acid is particularly preferred in terms of excellent reactivity and by-product suppression effect. p-Toluenesulfonic acid may be a hydrate.

[0019] These catalysts may be used alone or in combination of two or more kinds.

[0020] The amount of the acid catalyst used in the present invention is not particularly limited, but is preferably 0.1 to 10 parts by mass, more preferably 1.0 to 8.0 parts by mass, and even more preferably 4.0 to 6.0 parts by mass, relative to 100 parts by mass of 3-hydroxybenzoic acid.

[0021] When the amount of the acid catalyst is less than 0.1 parts by mass relative to 100 parts by mass of 3-hydroxybenzoic acid, the reaction tends not to proceed sufficiently, whereas when the amount of the acid catalyst is more than 10 parts by mass, by-products such as dimerized ethers of aliphatic alcohols tend to be produced, which is economically disadvantageous.

[0022] In the method of the present invention, an organic liquid is added in addition to the acid catalyst, which suppresses side reactions and significantly improves the production rate.

[0023] The organic liquid is preferably one or more selected from the group consisting of toluene, xylene, hexane, heptane, octane and cyclohexane, and more preferably toluene and / or xylene because of their particularly excellent production yield.

[0024] Since the aliphatic alcohol used in the present invention is usually liquid at the reaction temperature, a solvent for dissolving the reaction raw materials is not required. Therefore, the amount of the organic liquid used in the present invention can achieve the above effect even if it is less than the amount generally used as a solvent. The amount of the organic liquid used is preferably 0.01 to 5.0 times by mass, more preferably 0.1 to 4.0 times by mass, further preferably 0.2 to 3.0 times by mass, and particularly preferably 0.4 to 2.5 times by mass, relative to 3-hydroxybenzoic acid. When the amount of the organic liquid used is within the above range, the production rate of the 3-hydroxybenzoic acid long-chain ester can be efficiently improved.

[0025] The reaction temperature in the reaction between 3-hydroxybenzoic acid and an aliphatic alcohol is not particularly limited, but is preferably 100 to 150° C., more preferably 110 to 140° C. When the reaction temperature is within the above range, the reaction is likely to proceed sufficiently while side reactions are suppressed.

[0026] The reaction time is not particularly limited since it varies depending on conditions such as the reaction temperature, but it may be appropriately selected from within the range of usually 1 to 20 hours, preferably 5 to 18 hours, and more preferably 8 to 16 hours.

[0027] In the present invention, the reaction of 3-hydroxybenzoic acid with an aliphatic alcohol is preferably carried out under a stream or bubbling of an inert gas, or under reduced pressure conditions. By carrying out the reaction under such conditions, reaction inhibition and catalyst deactivation due to oxygen or moisture can be avoided, and the reaction can proceed smoothly.

[0028] 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. Among these, nitrogen is preferred because of its availability and economical value.

[0029] The inert gas may be blown into the space above the reaction liquid in a reaction vessel containing the raw materials 3-hydroxybenzoic acid and aliphatic alcohol, or may be blown directly into the reaction liquid.

[0030] The above reaction of 3-hydroxybenzoic acid with an aliphatic alcohol produces the compound represented by the formula (2): [ka] [n is an integer between 11 and 23] The long-chain 3-hydroxybenzoic acid ester represented by the formula:

[0031] Examples of the 3-hydroxybenzoic acid long chain ester represented by formula (2) include dodecyl 3-hydroxybenzoate, tridecyl 3-hydroxybenzoate, tetradecyl 3-hydroxybenzoate, pentadecyl 3-hydroxybenzoate, hexadecyl 3-hydroxybenzoate, heptadecyl 3-hydroxybenzoate, octadecyl 3-hydroxybenzoate, nonadecyl 3-hydroxybenzoate, icosyl 3-hydroxybenzoate, henicosyl 3-hydroxybenzoate, docosyl 3-hydroxybenzoate, tricosyl 3-hydroxybenzoate, and tetracosyl 3-hydroxybenzoate. Among them, hexadecyl 3-hydroxybenzoate is preferred due to the availability of the corresponding alcohol.

[0032] The crude composition containing the 3-hydroxybenzoic acid long-chain ester represented by formula (2) obtained by the step of reacting 3-hydroxybenzoic acid with an aliphatic alcohol in the presence of an organic liquid and an acid catalyst can be purified to increase its purity.

[0033] The purification preferably includes a step of dissolving the crude composition in a non-polar solvent and a step of crystallizing the obtained solution, in order to efficiently increase the purity of the product. The crude composition after the reaction is preferably cooled from the reaction temperature to 40 to 100°C, and then subjected to the subsequent purification method.

[0034] Prior to the above purification procedure, if necessary, washing with an aqueous medium to remove water-soluble compounds, filtration to remove insoluble foreign matter, and treatment with an adsorbent such as activated carbon to remove coloring substances, metals, etc. may be carried out.

[0035] The crude composition containing the 3-hydroxybenzoic acid long-chain ester represented by formula (2) means a composition containing impurities such as reaction raw materials, catalysts, reaction by-products, etc., in addition to the crude composition containing the 3-hydroxybenzoic acid long-chain ester represented by formula (2), which is the target product. The content of impurities varies depending on the reaction method, but is usually 1 to 20 mass% in the crude composition, and in other cases is 3 to 10 mass%.

[0036] Specific impurities contained in the crude composition include the raw material 3-hydroxybenzoic acid, residues of catalysts, and the like, as well as reaction by-products such as dimerized ethers of aliphatic alcohols and sulfate esters.

[0037] In the purification method of the present invention, first, in the dissolution step, a crude composition of a long-chain 3-hydroxybenzoic acid ester is dissolved in a solvent containing a non-polar solvent.

[0038] The non-polar solvent may be one or more selected from the group consisting of benzene, toluene, xylene, ethylbenzene, diethylbenzene, propylbenzene, cumene, cymene, mesitylene, anisole, pentane, hexane, heptane, octane, cyclopentane, cyclohexane, cycloheptane, and cyclooctane.

[0039] Among these, toluene, xylene, hexane, heptane, octane and cyclohexane are preferred from the viewpoints of safety and economy, and xylene is particularly preferred from the viewpoint of its excellent ability to remove impurities.

[0040] The amount of the solvent containing the non-polar solvent is preferably 0.5 to 8 times by mass relative to the raw material 3-hydroxybenzoic acid, more preferably 1.5 to 6 times by mass. If the amount of the solvent containing the non-polar solvent is less than 0.5 times by mass relative to the raw material 3-hydroxybenzoic acid, impurities such as raw materials, catalysts, or by-products tend to be incorporated into the crystals, making it difficult to obtain high-purity crystals, and if it exceeds 8 times by mass, the yield of the 3-hydroxybenzoic acid long-chain ester may be significantly reduced. The amount of the solvent containing the non-polar solvent includes the organic liquid used in the dehydration method of 3-hydroxybenzoic acid and long-chain alcohol.

[0041] The solvent, including the non-polar solvent, may further include other solvents such as methanol, ethanol, propanol, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, and hexamethylphosphoramide.

[0042] In the dissolving step, the temperature of the solvent containing the nonpolar solvent is not particularly limited as it differs depending on the nonpolar solvent used, but is preferably 30°C to 150°C, more preferably 50°C to 120°C, and even more preferably 70°C to 100°C.

[0043] The solution in which the crude composition is dissolved is then subjected to a crystallization step.

[0044] The crystallization step is carried out at a temperature of preferably 0°C to 60°C, more preferably 5°C to 50°C, and even more preferably 10°C to 30°C with stirring.

[0045] If the crystallization temperature is below 0°C, impurities such as raw materials, catalysts, or by-products may be incorporated into the crystals, making it difficult to obtain high-purity crystals. If the crystallization temperature is above 60°C, the yield of 3-hydroxybenzoic acid long-chain esters tends to decrease.

[0046] The crystals precipitated in the crystallization step are subjected to solid-liquid separation by a conventional means such as filtration, and the target 3-hydroxybenzoic acid long-chain ester is recovered. In the solid-liquid separation, it is preferable to wash the crystals by pouring an appropriate organic solvent. As the organic solvent used in the solid-liquid separation, one or more selected from the group consisting of methanol, ethanol, 1-propanol, and 2-propanol are preferably used. The organic solvent is preferably used in an amount of 0.5 to 2 times by mass relative to 3-hydroxybenzoic acid.

[0047] The crystals recovered by solid-liquid separation can be dried in the crystalline state under reduced pressure at a temperature of less than 60°C, or heated to 70°C or higher to melt the crystals, and then the solvent can be distilled off to obtain a high-purity long-chain 3-hydroxybenzoic acid ester. EXAMPLES

[0048] The present invention will be described in detail below with reference to examples, but the present invention is not limited thereto.

[0049] Each compound was analyzed by the following method.

[0050] [High performance liquid chromatography (HPLC)] Instrument: Waters Alliance 2690 / 2996 Column model number: L-Column Flow rate: 1.0mL / min Solvent ratio: H2O (pH 2.3) / acetonitrile = 80 / 20 (10 min) → 3 min → 10 / 90 (37 min), gradient analysis Wavelength: 229nm Column temperature: 40℃

[0051] [Gas Chromatography (GC)] Equipment: GC-2014 / GC-14A manufactured by Shimadzu Corporation Column model number: G-100 Injection volume: 1.0μL Oven temperature: 260℃ Carrier gas: Helium Detector: FID

[0052] Example 1 In a 0.3L four-neck flask equipped with a stirrer, a temperature sensor, and a Dean-Stark apparatus, 42.0g (0.304 mol) of 3-hydroxybenzoic acid (3-HBA, manufactured by Tokyo Chemical Industry Co., Ltd.), 73.7g (0.304 mol) of 1-hexadecanol (CeOH), 2.1g (5 parts by mass relative to 100 parts by mass of 3-HBA) of p-toluenesulfonic acid monohydrate (PTS·H2O) and 22.0g of xylene (0.52 times by mass relative to 3-HBA) were added, and the mixture was heated to 115°C under a nitrogen stream and reacted at the same temperature for 15 hours to obtain a crude composition. The obtained crude composition was quantitatively analyzed by HPLC. The results are shown in Table 1.

[0053] Examples 2 to 5, Comparative Examples 1 and 2 A crude composition was obtained in the same manner as in Example 1, except that the conditions were changed as shown in Table 1. The obtained crude composition was quantitatively analyzed by HPLC. The results are shown in Table 1.

[0054] Example 6 A crude composition was obtained in the same manner as in Example 5, except that 1-hexadecanol was replaced with 56.6 g (0.304 mol) of 1-dodecanol and xylene was replaced with toluene. The obtained crude composition was quantitatively analyzed by HPLC. The results are shown in Table 1.

[0055] Example 7 A crude composition was obtained in the same manner as in Example 5, except that 1-hexadecanol was replaced with 99.3 g (0.304 mol) of 1-docosanol. The obtained crude composition was quantitatively analyzed by HPLC. The results are shown in Table 1.

[0056] Example 8 The crude product obtained in Example 1, the organic layer distilled during the reaction, 170.1 g of xylene, and 63.1 g of a 5% by mass aqueous solution of sodium hydrogen carbonate were added to a 0.5 L bottomless flask equipped with a stirrer and a temperature sensor, and the mixture was stirred at 80°C for 30 minutes. The obtained solution was left to stand until it was separated into an organic layer and an aqueous layer, and then the aqueous layer was extracted. 42.2 g of water was added to the remaining organic layer, washed at 80°C, and the organic layer was extracted. The organic layer extracted was added to a 0.5 L four-neck flask equipped with a stirrer and a temperature sensor, and cooled to 38°C, and 0.2 g of 99.3 area% CEMB was added as seed crystals to precipitate CEMB. The suspension was further cooled to 20°C, and then solid-liquid separation was performed and the mixture was washed with 167.6 g of a 50% by mass aqueous solution of methanol. The obtained crystals were dried at 10 hPa and 40 to 45°C to obtain crystals of hexadecyl 3-hydroxybenzoate (CEMB). The obtained CEMB was quantitatively analyzed by HPLC and GC. The results are shown in Table 2.

[0057] Example 9 The crude product obtained in Example 5, the organic layer distilled during the reaction, 84.0 g of xylene, and 42.0 g of a 5% by mass aqueous solution of sodium hydrogen carbonate were added to a 0.5 L bottomless flask equipped with a stirrer and a temperature sensor, and the mixture was stirred at 80°C for 30 minutes. The obtained solution was left to stand until it was separated into an organic layer and an aqueous layer, and then the aqueous layer was extracted. 42.0 g of water was added to the remaining organic layer, washed at 80°C, and the organic layer was extracted. The organic layer extracted was added to a 0.5 L four-neck flask equipped with a stirrer and a temperature sensor, and cooled to 38°C, and 0.2 g of 99.3 area% CEMB was added as seed crystals to precipitate CEMB. The suspension was further cooled to 20°C, and then solid-liquid separation was performed, followed by washing with 42.0 g of methanol and 147.0 g of water. The obtained crystals were dried at 10 hPa and 30 to 35°C to obtain crystals of hexadecyl 3-hydroxybenzoate (CEMB). The obtained CEMB was quantitatively analyzed by HPLC and GC. The results are shown in Table 2.

[0058] As shown in Table 1, it can be seen that the production rate of 3-hydroxybenzoic acid long-chain ester is significantly higher in Examples 1 to 7 of the present invention, which contain an organic liquid in the reaction system, compared to Comparative Examples 1 and 2, which do not contain an organic liquid. Furthermore, as shown in Table 2, it can be seen that by-products can be significantly removed by further recrystallization with a non-polar solvent.

[0059] [Table 1]

[0060] [Table 2]

Claims

1. In the presence of an organic liquid and an acid catalyst, 3-hydroxybenzoic acid and a compound represented by the formula (1) 【Chemistry 1】 [In the formula, n represents an integer of 11 to 23] With an aliphatic alcohol represented by formula (2): 【Chemistry 2】 [n represents an integer from 11 to 23] A method for producing a 3-hydroxybenzoic acid long-chain ester represented by the following formula: 1 mole of 3-hydroxybenzoic acid is reacted with 0.5 to 3.0 moles of an aliphatic alcohol, A method of reacting 3-hydroxybenzoic acid with an aliphatic alcohol at a temperature of 100 to 150°C.

2. 2. The method of claim 1, wherein the organic liquid is one or more selected from the group consisting of toluene, xylene, mesitylene, anisole, hexane, heptane, octane, and cyclohexane.

3. 3. The method according to claim 1 or 2, wherein the organic liquid is toluene and / or xylene.

4. The method according to any one of claims 1 to 3, wherein the 3-hydroxybenzoic acid long-chain ester represented by formula (2) is hexadecyl 3-hydroxybenzoate.

5. The method according to any one of claims 1 to 4, wherein 0.1 to 10 parts by weight of the acid catalyst is present per 100 parts by weight of 3-hydroxybenzoic acid.

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 3-hydroxybenzoic acid long-chain ester represented by formula (2).

7. 7. The method of claim 6, comprising dissolving the crude composition in a solvent comprising a non-polar solvent and crystallizing the resulting solution.

8. 8. The method of claim 7, wherein the non-polar solvent is one or more selected from the group consisting of toluene, xylene, mesitylene, anisole, hexane, heptane, octane, and cyclohexane.

9. 9. The method of claim 7 or 8, wherein the non-polar solvent is xylene.

Images