JPH1077265A - Purification of indole - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain white and highly pure indole in a high yield by dissolving and recrystallizing crude indole in a solvent. SOLUTION: This method for purifying indole comprises dissolving crude indole separated from a coal tar fraction and having a concentration of >=80%, preferably >=90%, in the solvent mixture of methanol with water at a temperature of approximately 60 deg.C lower than the boiling point of the methanol, recrystallizing the indole in the solvent, and subsequently separating the deposited indole crystals from the mother liquid. The recrystallization solvent contains the water and the methanol in a weight ratio of (0.33-1):1, preferably (0.37-0.67):1, for recovering the highly pure indole having a purity of >=99.9%. The recrystallization solvent is used in an amount of 0.5-1 weight time, preferably 0.6-0.8 weight time, that of the crude indole. The indole is useful as a raw material for medicines, agricultural chemicals and perfumes.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a white and high-purity indole by purifying a crude indole having a concentration of 80% or more separated from a coal tar fraction.

[0002]

2. Description of the Related Art Indole has a melting point of 53 ° C. and a boiling point of 253.
It is a white lobular crystal at ℃ (762 Torr), and is a compound useful as a raw material for tryptophan, one of the essential amino acids, indoline, which is a raw material for synthesizing medicinal and agricultural chemicals, or a flavor.

[0003] Conventionally, to produce high-purity indole, crude materials such as coal tar and coal liquefied oil are concentrated by distillation, and then alkali melting, azeotropic distillation, extraction, cooling crystallization, ion exchange, and the like. There is known a method for purifying crude indole crystals having a purity of about 80% separated by a method or an adsorption method.

Conventionally, the following methods (1) to (5) have been known as methods for producing crude indole by purifying crude indole. (1) A method of recovering high-purity indole by recrystallization with a paraffinic or naphthenic hydrocarbon solvent having a boiling point of 50 to 150 ° C (JP-A-57-134462). (2) A method in which a crude indole crystal is washed with an aliphatic hydrocarbon and / or an alicyclic hydrocarbon solvent and then dried (Japanese Patent Application Laid-Open No. 64-3168). (3) A method of subjecting the crude indole to a recrystallization treatment and a decolorization treatment using a paraffinic or naphthenic hydrocarbon solvent and a decolorizing agent such as activated clay (JP-A-64-56659). (4) A method for removing other impurities from crude indole with carbon dioxide in a liquid or supercritical gas state
-254660). (5) A mixture containing 50% or more of indole is supplied to a high-pressure vessel, and the mixture is pressurized to 700 to 2500 atm in the vessel to crystallize indole.
A method in which solid-liquid separation is started at 0 to 65 ° C. and high-purity indole is taken out in a solid state (JP-A-1-311062).

[0005]

In the recrystallization methods disclosed in the above (1) and (3), the amount of the paraffinic or naphthenic hydrocarbon solvent used for dissolving the indole increases, and the amount of the solvent increases. Since a distillation method is used for recovery, a large amount of heat energy is required, and there is a problem that running cost is increased. Further, in the washing method disclosed in the above (2), an indole having extremely high purity cannot be obtained when the present inventors have carried out the method. Furthermore, the methods disclosed in the above (4) and (5) have a drawback that the operation under high pressure requires a pressure-resistant vessel or a special crystallization facility, and the facility cost is high.

An object of the present invention is to solve the above-mentioned drawbacks of the prior art and to recrystallize under atmospheric pressure using a small amount of a solvent to obtain white lobular crystals and a high purity of 99.9% or more. To provide a method for purifying indole which can obtain the indole of the present invention in high yield.

[0007]

Means for Solving the Problems To achieve the above-mentioned object, the present inventors have used white crude leafy crystals which can be used as a perfume raw material by using colored crude indole separated from coal tar and at least 99.9%. A study was conducted on a method for efficiently purifying high-purity indole. As a result, if a solution in which the colored crude indole is dissolved in a mixed solvent of methanol and water is cooled and the indole crystals precipitated are separated from the mother liquor, white lobular crystals having a high purity of 99.9% or more can be obtained. We have determined that indole can be obtained and arrived at this invention.

That is, in the method for purifying indole according to claim 1 of the present invention, the crude indole having a concentration of 80% or more separated from the coal tar fraction is dissolved in a mixed solvent of methanol and water and then recrystallized. The indole crystals that precipitate are separated from the mother liquor. As described above, the crude indole having a concentration of 80% or more is dissolved in a mixed solvent of methanol and water, and the indole crystals precipitated by recrystallization are separated from the mother liquor. , The amount of indole dissolved can be ensured, and white lobular indole crystals having a high purity of 99.9% or more can be recovered.

Further, in the method for purifying indole according to claim 2 of the present invention, a mixed solvent of methanol and water in which water is 0.33 to 1.0 times by weight of methanol and a crude indole having a concentration of 80% or more are used. 0.5 to 1.0 times the weight is used. Thus, water is 0.3
By using a mixed solvent of 3 to 1.0 weight times methanol and water at 0.5 to 1.0 weight times the crude indole having a concentration of 80% or more, a high yield of 99.9% or more can be obtained. High purity white leaflet-like indole crystals can be recovered.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Crude indole used as a raw material in the present invention is obtained from a coal tar fraction by a known method such as an alkali melting method, an azeotropic distillation method, an extraction method, a cooling crystallization method, an ion exchange method or an adsorption method. It is sufficient that the indole concentration is 80% or more, preferably 90% or more. Indole concentration of 80% or more 9
If it is less than 0%, the indole concentration becomes 90% or more by the first recrystallization, and then the second recrystallization gives 9
High-purity white indole crystals of 9.9% or more can be recovered.

The recrystallization solvent used in the present invention is:
In order to recover a high-purity indole of 99.9% or more, which is a mixed solvent of methanol and water, the amount of water is preferably in the range of 0.33 to 1.0 times by weight of methanol, more preferably 0 to 3 times. 0.37 to 0.67 times by weight. The amount of the recrystallization solvent used is in the range of 0.5 to 1.0 times by weight, more preferably 0.6 to 0.8 times by weight of the crude indole. The amount of the recrystallization solvent used was 1.
When the amount exceeds 0 times by weight, the yield of indole decreases, and the amount of indole decreases.
If the amount is less than 5 times by weight, the slurry concentration of the crystals precipitated by cooling from the solution becomes too high for effective stirring, and impurities are included in the indole crystals to hinder an increase in purity. The temperature at which the crude indole is dissolved in a mixed solvent of methanol and water may be lower than the boiling point of methanol, and suitably around 60 ° C.

In the recrystallization method according to the present invention, the crude indole having a purity of 80% or more is completely dissolved in a mixed solvent of methanol and water, or the crude indole having a purity of 80% or more is dissolved in methanol. Water can also be added. The crude indole solution is cooled with stirring to around room temperature to precipitate indole crystals. As a method for separating the recrystallized indole from the mother liquor, a general solid-liquid separation method can be employed, but filtration separation is particularly preferable. When water is added after dissolving the crude indole in methanol, the purity and yield of the purified indole are unchanged and the crystal grain size is finer than when the crude indole is dissolved in a mixed solvent of methanol and water. However, there is no problem in the filtration separation.

In the case of crude indole having a concentration of 90% or more,
By performing the above-mentioned recrystallization once, it is possible to obtain a white lobule-like indole having a high purity of 99.9% or more, which can be used as a raw material for medicines, agrochemicals or fragrances. In addition, the density 80
% Or more and less than 90% of crude indole, by performing the recrystallization treatment twice, it is possible to obtain 99.9% or more of high-purity white leaflet-like indole crystals which can be used as a raw material for medicines, agrochemicals or fragrances. Can be.

[0014]

【Example】

Examples 1 to 3 As shown in Table 1, 150 g of raw material indole having an indole concentration of 95.07%, 60.0 g of methanol and 40 g of water
g, 35 g, and 30 g were placed in a separable flask having a capacity of 300 ml with a stirrer, mixed and dissolved in a water bath at 60 ° C., and then cooled to 25 ° C. while stirring in an incubator for about 1 hour to recycle the indole. After crystallization, centrifugal filtration and vacuum drying, purified indole as white lobular crystals was obtained. Table 1 shows the results of analysis of the raw indole and the purified indole by gas chromatography. The yield of the purified indole in Table 1 was calculated based on the indole in the crude indole used as a raw material.

[0015]

[Table 1]

As shown in Table 1, the purified indole obtained in Example 1 was white lobular crystals having a purity of 99.
The yield was 90% and the yield was 65.2%. The purified indole obtained in Example 2 was white lobular crystals,
The purity was 99.94% and the yield was 60.5%. further,
The purified indole obtained in Example 3 was white lobular crystals, having a purity of 99.95% and a yield of 58.3%.

Examples 4 to 6 As shown in Table 2, 150 g of raw material indole having an indole concentration of 93.87%, 65.0 g of methanol and 35 of water
g, 30 g, and 28 g were placed in a separable flask having a capacity of 300 ml with a stirrer, mixed and dissolved at 60 ° C. in a water bath, and then cooled to 25 ° C. while stirring in an incubator for about 1 hour to recycle the indole. After crystallization, centrifugal filtration and vacuum drying, purified indole as white lobular crystals was obtained. Table 2 shows the results of analyzing the raw material crude indole and the purified indole by gas chromatography. The yield of the purified indole in Table 2 was calculated based on the indole in the crude indole used as a raw material.

[0018]

[Table 2]

As shown in Table 2, the purified indole obtained in Example 4 was white lobular crystals having a purity of 99.
The yield was 55.0% with 91%. The purified indole obtained in Example 5 was white leaflet-like crystals,
The purity was 99.93% and the yield was 52.2%. further,
The purified indole obtained in Example 6 was white lobular crystals, having a purity of 99.96% and a yield of 51.4%.

Examples 7 to 9 As shown in Table 3, 150 g of crude indole as raw material having an indole concentration of 90.07%, 75.0 g of methanol and 35 of water
g, 30 g, and 28 g were placed in a separable flask having a capacity of 300 ml with a stirrer, mixed and dissolved in a water bath at 60 ° C., and then cooled to 25 ° C. in a constant temperature bath for about 1 hour to cool the indole again. After crystallization, centrifugal filtration and vacuum drying, purified indole as white lobular crystals was obtained. Table 3 shows the results of analysis of the raw indole and the purified indole by gas chromatography. Further, the yield of the purified indole in Table 3 was calculated based on the indole in the crude indole used as a raw material.

[0021]

[Table 3]

As shown in Table 3, the purified indole obtained in Example 7 was white lobular crystals having a purity of 99.
The yield was 46.2% with 91%. The purified indole obtained in Example 8 was white leaflet-like crystals,
The purity was 99.92% and the yield was 48.1%. further,
The purified indole obtained in Example 9 was white lobular crystals, having a purity of 99.93% and a yield of 49.3%. From the above results, when crude indole having a concentration of 90% or more was used as a raw material, one recrystallization operation
High-purity purified indole having a purity of 99.90% or more can be obtained as white lobular crystals.

Example 10 As shown in Table 4, 150 g of raw material indole having an indole concentration of 83.80%, 45.0 g of methanol and 30 parts of water
g was placed in a separable flask having a capacity of 300 ml with a stirrer, mixed and dissolved in a water bath at 60 ° C., and then cooled to 25 ° C. while stirring in a thermostat for about 1 hour to recrystallize indole. After filtration, the precipitate was dried under vacuum to obtain indole having a concentration of 93.79%. This concentration 93.
75 g of 79% indole, 32.5 g of methanol and 17.5 g of water are placed in a separable flask having a capacity of 300 ml with a stirrer, mixed and dissolved at 60 ° C. in a water bath, and then 25 ° C. in a thermostat for about 1 hour. The resultant was cooled with stirring to recrystallize the indole, centrifugally filtered, and then dried under vacuum to obtain purified indole as white leaflet crystals. Table 4 shows the results of analysis of the raw indole and the purified indole by gas chromatography. Table 4
The yield of the purified indole therein was calculated based on the indole in the crude indole used as a raw material.

[0024]

[Table 4]

As shown in Table 4, when crude indole having a concentration of 83.80% is used as a raw material, two recrystallization operations are performed to purify high-purity white lobular crystals with a purity of 99.90% or more. Indole can be obtained.

Comparative Examples 1 to 6 As shown in Table 5, 150 g of raw indole having an indole concentration of 95.07% was mixed with methanol, ethanol, 2-
Propanol alone or ethanol or 2-propanol and water are placed in a separable flask having a capacity of 300 ml with a stirrer, mixed and dissolved in a water bath at 60 ° C., and then stirred in a thermostat to 25 ° C. for about 1 hour. While cooling, the indole was recrystallized, filtered by centrifugation, and dried under vacuum to obtain a purified indole. Table 5 shows the results obtained by analyzing the raw crude indole and the purified indole by gas chromatography. Further, the yield of the purified indole in Table 5 was calculated based on the indole in the crude indole used as a raw material.

[0027]

[Table 5]

As shown in Table 5, in the case of Comparative Examples 1 and 3 in which ethanol and 2-propanol were used alone as solvents, pearly granular crystals were obtained, and the purity of the purified indole was 9%.
It was less than 9.0%, and the yield was in the order of 31 to 32%. Also, a mixed solvent of ethanol and water as a solvent,
Alternatively, in the case of Comparative Examples 2 and 4 using a mixed solvent of 2-propanol and water, the particles were pearl-like granular crystals, the purity of the purified indole was about 99.4%, and the yield was about 45%. . Furthermore, in the case of Comparative Example 5 using methanol alone as a solvent, the purity of the purified indole was 99.13.
% And the yield was as low as 30.8%. Furthermore, in the case of Comparative Example 6 in which 60 g of ethanol and 30 g of water were used as the solvent, compared with the above-mentioned Example 3, it was pearl-like granular crystals, and the purity of the purified indole was 99.90%, which was not much different. , The yield is lower than 10%.

[0029]

According to the present invention, a crude indole having a concentration of 80% or more is dissolved in a mixed solvent of methanol and water and recrystallized to obtain a purity of 99.9% or more of a raw material for a pharmaceutical, agrochemical or a fragrance. Can be obtained in high yield. Further, the amount of the solvent used in the present invention is 0.5 to 1.0 times the weight of the raw crude indole, which is very small as compared with the conventional method, the running cost for solvent recovery is low, and the pressure No operation or cooling operation to room temperature or lower is required, which is industrially extremely advantageous.

 ──────────────────────────────────────────────────の Continuing on the front page (72) Inventor Keizo Miki No. 3, Oaza Hikari, Kashima City, Ibaraki Prefecture Sumikin Chemical Co., Ltd. (72) Inventor Masao Kawano 3, Oji Hikari, Kashima City, Ibaraki Prefecture Sumikin Chemical Co., Ltd. In-house (72) Inventor Yasushi Yasue 3 Kashima, Ibaraki Pref.

Claims (2)

[Claims] 1. A concentration of 8 separated from a coal tar fraction
A method for purifying indole, comprising dissolving 0% or more of crude indole in a mixed solvent of methanol and water, and then recrystallizing the separated indole crystal from a mother liquor. 2. The method according to claim 1, wherein water is 0.33 to 1.0 with respect to methanol.
2. The method for purifying indole according to claim 1, wherein a mixed solvent of methanol and water in a weight ratio of 0.5 to 1.0 times the weight of the crude indole having a concentration of 80% or more is used.