JP6812112B2 - Method for Purifying 4-Hydroxybenzoic Acid Long Chain Ester - Google Patents

Description

The present invention relates to a method for purifying a 4-hydroxybenzoic acid long chain ester.

4-Hydroxybenzoic acid long chain ester has a structure having a hydroxyl group and a hydrophobic group, and its use as a plasticizer, a compatibilizer, a surfactant and the like has been proposed due to its structural characteristics.

Generally, in the esterification of a compound, a raw material carboxylic acid and an alcohol are reacted in the presence of a protonic acid catalyst such as sulfuric acid, the catalyst and unreacted carboxylic acid are removed from the obtained reaction solution, and crystals are required. A method for producing by performing purification such as analysis or distillation is known (Patent Document 1).

Similarly, for esterification of 4-hydroxybenzoic acid, 4-hydroxybenzoic acid ester can be synthesized by reacting with an alcohol in the presence of an acid catalyst. However, when 4-hydroxybenzoic acid is reacted with a long-chain fatty alcohol having 16 or more carbon atoms to produce a 4-hydroxybenzoic acid long-chain ester, the raw material 4-hydroxybenzoic acid, a catalyst, etc. Remains, so a purification operation was required to obtain a high-purity target product.

In the above purification operation, it was common to melt the crude crystal containing the desired product, or dilute it with a water-insoluble solvent, and then extract it with water or alkaline water. However, even if an attempt is made to extract a crude composition of 4-hydroxybenzoic acid long chain ester containing unreacted carboxylic acid and impurities such as a catalyst by adding water or alkaline water, it is difficult to extract because the liquid separation property is extremely poor. Therefore, even when extracted, the yield and purity are low, and there is a problem that a high-purity target product cannot be obtained.

Japanese Unexamined Patent Publication No. 2014-108928

An object of the present invention is to obtain crystals of a high-purity 4-hydroxybenzoic acid long-chain ester, which can easily remove residues such as a catalyst and a reaction raw material from the crude composition of 4-hydroxybenzoic acid long-chain ester. An object of the present invention is to provide a purification method obtained in a high yield.

Another object of the present invention is to provide a purification method for obtaining crystals of 4-hydroxybenzoic acid long chain ester having a large particle size and excellent handleability.

As a result of diligent studies on a method for purifying 4-hydroxybenzoic acid long-chain ester, the present inventors dissolved the crude composition of 4-hydroxybenzoic acid long-chain ester in an organic solution, concentrated the obtained solution, and then concentrated the obtained solution. By precipitating crystals of 4-hydroxybenzoic acid long-chain ester by cooling, unreacted carboxylic acids and catalysts can be easily removed, and crystals of 4-hydroxybenzoic acid long-chain ester with high purity and large particle size can be obtained. We have found that it can be obtained in high yield, and have completed the present invention.

That is, the present invention comprises a step of dissolving a crude composition containing a 4-hydroxybenzoic acid long chain ester represented by the formula (1) in an organic solution (hereinafter referred to as a dissolution step), and a step of concentrating the obtained solution (hereinafter referred to as a dissolution step). Provided is a method for purifying a 4-hydroxybenzoic acid long chain ester, which comprises a step (hereinafter referred to as a concentration step) and a step of crystallizing the concentrated solution by cooling (hereinafter referred to as a crystallization step).

According to the present invention, unreacted carboxylic acid and catalyst can be easily removed, and crystals of high-purity 4-hydroxybenzoic acid long chain ester can be obtained in high yield by a simple operation. Further, according to the present invention, it is possible to obtain crystals of 4-hydroxybenzoic acid long chain ester having a large particle size and excellent handleability.

In the present invention, the crude composition containing the 4-hydroxybenzoic acid long chain ester represented by the formula (1) is other than the target product, the 4-hydroxybenzoic acid long chain ester represented by the formula (1). , Means a composition containing impurities such as reaction raw materials, catalysts and reaction by-products. The content of impurities varies depending on the reaction method, but is 1 to 20% by weight, preferably 3 to 10% by weight in the crude composition.

In the present invention, the 4-hydroxybenzoic acid long-chain ester represented by the formula (1), which is the object of the present invention, is an ester composed of 4-hydroxybenzoic acid and an aliphatic alcohol having 16 to 24 carbon atoms. Hexadecyl 4-hydroxybenzoate, heptadecyl 4-hydroxybenzoate, octadecyl 4-hydroxybenzoate, nonadecil 4-hydroxybenzoate, ikosyl 4-hydroxybenzoate, henikosyl 4-hydroxybenzoate, 4-hydroxybenzoic acid Included is one or more selected from docosyl, tricosyl 4-hydroxybenzoate and tetracosyl 4-hydroxybenzoate. Among these, hexadecyl 4-hydroxybenzoate is preferable.

Specific impurities contained in the crude composition include residues such as 4-hydroxybenzoic acid as a raw material and a catalyst, as well as a dimerized etheric body of a long-chain alcohol as a reaction by-product and a sulfate ester. Be done.

The method for obtaining a crude composition of 4-hydroxybenzoic acid long chain ester is not particularly limited, but is obtained by reacting 4-hydroxybenzoic acid with an aliphatic alcohol having 16 to 24 carbon atoms in the presence of a catalyst. Is better to use. Alternatively, a commercially available crude composition containing a low-purity 4-hydroxybenzoic acid long chain ester may be used.

In the purification method of the present invention, first, in the dissolution step, the crude composition of 4-hydroxybenzoic acid long chain ester is dissolved in an organic solution.

The organic solution used in the dissolution step is preferably a mixture of water and a water-soluble organic solvent. Specific examples of the water-soluble organic solvent include methanol, ethanol, 1-propanol, 2-propanol, ethylene glycol, glycerin, acetone, methyl ethyl ketone, N, N'-dimethylformamide, N-methylpyrrolidone, pyridine, tetrahydrofuran, 1, Included is one or more selected from the group consisting of 4-dioxane, acetic acid, acetonitrile and dimethylsulfoxide. Among these, methanol, ethanol, 1-propanol and 2-propanol are preferable in terms of excellent industrial productivity such as availability and drying efficiency, and methanol is more preferable in terms of particularly excellent yield.

The weight ratio of water to the water-soluble organic solvent (water / water-soluble organic solvent) depends on the type of the water-soluble organic solvent used, but is 30/70 to 1/99, preferably 20/80 to 2/98. More preferably, it is 15/85 to 3/97. When the weight ratio of water to the water-soluble organic solvent exceeds 30/70, the 4-hydroxybenzoic acid long chain ester tends to be difficult to dissolve, and when it is less than 1/99, the yield tends to decrease. ..

The amount of the organic solution is not particularly limited as long as it can dissolve the crude composition of 4-hydroxybenzoic acid long chain ester, but 4 to 4 to 4 to the crude composition of 4-hydroxybenzoic acid long chain ester. It is better to make it 7 times as heavy. When the amount of the organic solution is less than 4 times the weight of the crude composition of 4-hydroxybenzoic acid long chain ester, the 4-hydroxybenzoic acid long chain ester tends to be difficult to dissolve, and when it exceeds 7 times the weight, it tends to be difficult to dissolve. , The next concentration step tends to take time.

The temperature at which the crude composition of 4-hydroxybenzoic acid long chain ester is dissolved in an organic solution varies depending on the type of organic solution used and is not particularly limited, but is preferably 50 to 65 ° C. When the dissolution temperature is below 50 ° C, the crude composition of 4-hydroxybenzoic acid long chain ester tends to be difficult to dissolve in the organic solution, and when it is above 65 ° C, the organic solution is dissolved before the crude composition is dissolved. Since it evaporates and the amount of the organic solution decreases, the crude composition of 4-hydroxybenzoic acid long chain ester also tends to be difficult to dissolve.

The solution containing the crude composition dissolved in the organic solution is then subjected to a concentration step. The concentration step can be carried out by heating and / or reducing the pressure of the solution containing the crude composition to evaporate the organic solution. Heating and depressurization may be performed individually or in combination, but it is preferable to concentrate by heating.

The heating temperature is not particularly limited because it varies depending on the type, amount or concentration of the organic solution used, but is preferably 50 ° C. to 100 ° C., more preferably 66 ° C. to 95 ° C., and further preferably 70 ° C. to 90 ° C. Is good.

When concentrating by depressurization, the pressure at the time of depressurization varies depending on the type, amount or concentration of the organic solution used, and is not particularly limited, but it is usually preferably 30 to 50 torr.

The heating and / or depressurizing time is not particularly limited, but the yield of the desired 4-hydroxybenzoic acid long-chain ester can be improved by performing until the crystals of 4-hydroxybenzoic acid long-chain ester begin to precipitate. Is preferable.

The concentrated solution in which crystals have begun to precipitate by the concentration step is then subjected to a crystallization step.

The crystallization step is carried out by cooling the concentrated solution. The cooling conditions are not particularly limited because they vary depending on the type, amount or concentration of the organic solution used, but the cooling is performed at 5 to 30 ° C., preferably 5 to 25 ° C., more preferably 10 to 20 ° C. over 2 to 4 hours. Is good. When the cooling temperature is lower than 5 ° C., impurities are also crystallized, and the purity of the obtained 4-hydroxybenzoic acid long chain ester tends to decrease. When the cooling temperature exceeds 30 ° C., the yield of 4-hydroxybenzoic acid long chain ester tends to decrease.

The crystals precipitated by cooling are separated into solid and liquid by filtration or the like and taken out. At the time of solid-liquid separation, it is preferable to wash the crystals by appropriately pouring an organic solvent. As the organic solvent used for 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 weight based on the crude composition of 4-hydroxybenzoic acid long chain ester.

The crystals recovered by solid-liquid separation are dried under reduced pressure at a temperature of less than 50 ° C. in a crystalline state, or heated to 50 ° C. or higher to melt the crystals, and then the solvent is distilled off. , High-purity 4-hydroxybenzoic acid long chain ester can be obtained.

Hereinafter, the present invention will be described in detail with reference to Examples, but the present invention is not limited thereto.

[High Performance Liquid Chromatography (HPLC)]
Equipment: Waters Alliance 2487/2996
Column model number: L-Column
Liquid volume: 1.0 mL / min Solvent ratio: H ₂ O (pH 2.3) / CH ₃ OH = 58/42 (30 minutes) → 5 minutes → 10/90 (55 minutes), gradient analysis Wavelength: 229 nm / 254 nm
Column temperature: 40 ° C
[Gas Chromatography (GC)]
Equipment: GC-2014 / GC-14A manufactured by Shimadzu Corporation
Column model number: G-100
Injection volume: 1.0 μL
Oven temperature: 310 ° C
Carrier gas: Helium detector: FID

[Measurement of average particle size]
For the average particle size, a JISZ8801-1 standard sieve was used, and the particle size distribution was measured by a sieving method to obtain a particle size corresponding to 50% of the integrated distribution.

Reference Example 1 (Preparation of crude composition of hexadecyl 4-hydroxybenzoate)
120.4 g of hexadecanol (CeOH) was placed in a 500 mL four-necked flask equipped with a stirrer, a temperature sensor and a Dean-Stark apparatus, and the temperature was raised to 70 ° C. under a nitrogen stream. Then, 70.0 g of 4-hydroxybenzoic acid (POB), 2.3 g of p-toluenesulfonic acid monohydrate and 1.1 g of a 30 wt% hypophosphorous acid aqueous solution were added, and the temperature was raised to 130 ° C. over 1 hour. It was warmed and reacted at the same temperature for 8 hours. The resulting reaction solution was subjected to component analysis using high performance liquid chromatography (HPLC) and gas chromatography (GC). The results are shown in Table 1.

Example 1
A mixed solution was prepared by adding 475 g of methanol and 25 g of water to a 1 L four-necked flask equipped with a stirrer, a temperature sensor and a cooling tube.

100 g of the crude composition of Reference Example 1 cooled to 110 ° C. was added thereto, and the temperature was raised to 60 ° C. to dissolve the solid content. Then, the obtained solution was heated to 75 ° C., maintained at the same temperature for 60 minutes, and the heating was stopped when the solution became cloudy. Then, it was cooled to 20 ° C. over 120 minutes to precipitate crystals. The precipitated crystals were suction-filtered using Nutche, washed with 100 g of methanol, and dried under the conditions of 45 ° C. and 10 mmHg to obtain 79.3 g of crystals.

The obtained crystals were subjected to component analysis using high performance liquid chromatography (HPLC) and gas chromatography (GC), and the average particle size was measured. The results are shown in Table 1.

Example 2
81.2 g of crystals were obtained in the same manner as in Example 1 except that the mixed solution was changed to 450 g of methanol and 50 g of water. Table 1 shows the component analysis results and the average particle size of the obtained crystals.

Example 3
73.9 g of crystals were obtained in the same manner as in Example 1 except that the mixed solution was changed to 570 g of methanol and 30 g of water. Table 1 shows the component analysis results and the average particle size of the obtained crystals.

Example 4
Crystals 74.7 g were obtained in the same manner as in Example 1 except that the mixed solution was changed to 475 g of ethanol and 25 g of water. Table 1 shows the component analysis results and the average particle size of the obtained crystals.

Example 5
71.5 g of crystals were obtained in the same manner as in Example 1 except that the mixed solution was changed to 475 g of isopropanol and 25 g of water. Table 1 shows the component analysis results and the average particle size of the obtained crystals.

Comparative Example 1
A mixed solution was prepared by adding 475 g of methanol and 25 g of water to a 1 L four-necked flask equipped with a stirrer, a temperature sensor and a cooling tube.

100 g of the crude composition of Reference Example 1 cooled to 110 ° C. was added thereto, and the temperature was raised to 60 ° C. to dissolve the solid content. Then, it was cooled to 20 ° C. over 100 minutes to precipitate crystals. The precipitated crystals were suction-filtered using Nutche, washed with 100 g of methanol, and dried at 45 ° C. and 10 mmHg to obtain 43.3 g of crystals.

The obtained crystals were subjected to component analysis using high performance liquid chromatography (HPLC) and gas chromatography (GC), and the average particle size was measured. The results are shown in Table 1.

Comparative Example 2
300 g of methanol is put into a 1 L four-necked flask equipped with a stirrer, a temperature sensor and a cooling tube, 100 g of the reaction solution of the reference example cooled to 110 ° C. is added thereto, and the temperature is raised to 50 ° C. to solidify. After the minutes were dissolved, the mixture was cooled to 15 ° C. to precipitate crystals. The crystals were suction-filtered using Nutche, washed with 100 g of methanol, and dried at 45 ° C. and 10 mmHg to obtain 37.1 g of crystals. Table 1 shows the component analysis results and the average particle size of the obtained crystals.

Comparative Example 3
450 g of methanol and 50 g of water were put into a 2 L four-necked flask equipped with a stirrer, a temperature sensor and a cooling tube, and stirred at room temperature to prepare a mixed solution. 100 g of the crude composition in a molten state cooled to 110 ° C. was added and mixed by dropping over 30 minutes to precipitate crystals. After completion of the dropping, suspension washing was performed by continuing stirring at the same temperature for 1 hour. Then, the crystals were separated by filtration, washed with 100 g of methanol, and dried under the conditions of 45 ° C. and 10 mmHg to obtain 74.1 g of crystals. Table 1 shows the component analysis results and the average particle size of the obtained crystals.

Comparative Example 4
Toluene (350 g) and methanol (150 g) were placed in a 1 L four-necked flask equipped with a stirrer, a temperature sensor and a cooling tube to prepare a mixed solution.

100 g of the reaction solution of the reference example cooled to 110 ° C. was added thereto, the temperature was raised to 60 ° C. to dissolve the solid content, and then the mixture was cooled to 10 ° C., but no crystals were precipitated.

Comparative Example 5
A mixed solution was prepared by putting 250 g of methanol and 250 g of water into a 1 L four-necked flask equipped with a stirrer, a temperature sensor and a cooling tube. 100 g of the crude composition of Reference Example 1 cooled to 110 ° C. was added thereto, and the temperature was raised to 60 ° C., but the crude composition did not dissolve.

（式中、ｎは１５〜２３の整数を表す）
〔２〕式（１）で表される４−ヒドロキシ安息香酸長鎖エステルが、４−ヒドロキシ安息香酸ヘキサデシルである、〔１〕に記載の精製方法。
〔３〕有機溶液が水と水溶性有機溶媒との混合物である、〔１〕または〔２〕に記載の精製方法。
〔４〕水溶性有機溶媒がメタノール、エタノール、１−プロパノールおよび２−プロパノールからなる群から選択される１種以上である、〔３〕に記載の精製方法。
〔５〕水と水溶性有機溶媒の重量比が３０／７０〜１／９９である、〔３〕または〔４〕に記載の精製方法。
〔６〕冷却温度が５〜３０℃である、〔１〕〜〔５〕のいずれかに記載の精製方法。

As shown in Table 1, according to the present invention, residues such as reaction raw materials are removed from the crude composition of 4-hydroxybenzoic acid long chain ester, and 4-hydroxybenzoic acid long chain having high purity and large particle size is removed. The ester is obtained in high yield.
Preferred embodiments of the present invention include:
[1] A step of dissolving a crude composition containing a 4-hydroxybenzoic acid long chain ester represented by the formula (1) in an organic solution.
The step of concentrating the obtained solution, and
Step of crystallization of concentrated solution by cooling
A method for purifying a 4-hydroxybenzoic acid long chain ester, which comprises.

(In the formula, n represents an integer of 15 to 23)
[2] The purification method according to [1], wherein the 4-hydroxybenzoic acid long-chain ester represented by the formula (1) is hexadecyl 4-hydroxybenzoate.
[3] The purification method according to [1] or [2], wherein the organic solution is a mixture of water and a water-soluble organic solvent.
[4] The purification method according to [3], wherein the water-soluble organic solvent is at least one selected from the group consisting of methanol, ethanol, 1-propanol and 2-propanol.
[5] The purification method according to [3] or [4], wherein the weight ratio of water to the water-soluble organic solvent is 30/70 to 1/99.
[6] The purification method according to any one of [1] to [5], wherein the cooling temperature is 5 to 30 ° C.

Claims (3)

A step of dissolving a crude composition containing a 4-hydroxybenzoic acid long chain ester represented by the formula (1) in an organic solution, wherein the organic solution consists of water and methanol, ethanol, 1-propanol and 2-propanol. It is a mixture of one or more water-soluble organic solvents selected from the group, and the weight ratio of water to the water-soluble organic solvent is 30/70 to 1/99.
A step of concentrating the obtained solution until crystals of 4-hydroxybenzoic acid long chain ester begin to precipitate , and
A method for purifying a 4-hydroxybenzoic acid long chain ester, which comprises a step of crystallizing a concentrated solution by cooling.

(In the formula, n represents an integer of 15 to 23) The purification method according to claim 1, wherein the 4-hydroxybenzoic acid long-chain ester represented by the formula (1) is hexadecyl 4-hydroxybenzoate. The purification method according to any one of claims 1 to 2, wherein the cooling temperature is 5 to 30 ° C.