JPH0764811B2 - Indian refining method - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for purifying indole.

[Conventional technology and its problems]

Indole is a compound of white scale-like crystals with a melting point of 53 ° C, which has been known for a long time, and has been used as a raw material for the synthesis of tryptophan, which is one of the essential amino acids, and a fragrance. In particular, since tryptophan has recently attracted attention as a "third amino acid", a method for inexpensively producing a large amount of indole, which is a raw material thereof, has been studied.

The present inventors investigated a method for producing a indole by subjecting aniline and ethylene glycol to a gas phase catalytic reaction in the presence of a catalyst to separate a purified indole from a reaction product and purify it. The reaction product contains aniline used in excess and indole which is a target product, and side products, and a distillation method which is generally known as a first-stage separation method was adopted. Batch distillation was carried out under reduced pressure, but indole fraction contained many kinds of by-products with close boiling points, albeit little by little, to obtain a high-purity product of perfume grade (purity 99% or more). I couldn't.

Therefore, the recrystallization method was adopted as the second-stage separation method. For the selection of the recrystallization solvent, the solubility of indole in the solvent was used as a criterion, and a single solvent or a mixed solvent having a solubility at room temperature of 5% by weight or less was used. According to it, the indole derivative, which is a by-product, shows an affinity for indole crystals having similar properties during precipitation of indole crystals, even after having sufficient solubility in the solvent, and even after the washing operation of the adherent liquid. It was found that the expected purification value could not be obtained, which hindered the improvement of the purity of indole.

A prior art similar to the above is found in JP-A-57-134462, but in the present invention, methylindoles are mentioned as a substance that inhibits the improvement of purity, and the concentration of methylindoles is set to 4 before the recrystallization. It is disclosed that the content needs to be not more than weight%.

[Means for solving problems]

Under the circumstances, the present inventors have conducted intensive studies on a recrystallization method having a wider application range and a good indole recovery rate, and as a result, the present invention has been completed.

That is, the present invention, when the crude indole is purified by a recrystallization method, the crude indole and the solvent are brought into contact with each other in a liquid state or a solid-liquid state to form two phases of a solvent phase in which the indole is extracted and a crude indole phase, A method for purifying indole characterized in that a liquid obtained by separating a purified indole crystal from the solvent phase is used as a solvent, and the crude indole phase is circulated to a purification step in the preceding stage.

The crude indole in the present invention is not particularly limited in its production method, and may be any as long as it contains an indole derivative as an impurity and contains indole as a main component, for example, indole synthesis reaction solution, distilled indole. Examples include a fraction and an extract containing indole as a main component separated by an extraction method.

The indole concentration in the above crude indole is 60 to 99% by weight, preferably 80 to 98% by weight, and the concentration of the indole derivative contained therein is 20% by weight or less, preferably 10% by weight or less.

Regarding the solvent in the present invention, taking into consideration the recovery rate in recrystallization (yield) and the washing step of the separated crystal which is a conventional method in the recrystallization method, the solubility of indole in the solvent at room temperature is 5% by weight or less. It is preferred to choose from some. With respect to the solubility of indole in a single solvent, preferable conditions for the above are paraffinic solvents such as hexane, heptane and octane; naphthene type solvents such as cyclohexane and methylcyclohexane, which may be used in combination. It can be used because it meets the above conditions.

On the other hand, aromatic solvents such as benzene and toluene; alcohols such as methanol, ethanol and isopropyl alcohol; ketones such as acetone and methyl ethyl ketone; esters such as ethyl acetate; ethers such as ethyl ether, 1,4-dioxane and tetrahydrofuran. Since the solubility of indole in them is high, they are not suitable for use alone. However, for example, when alcohols, ketones or ethers which are compatible with water and in which indole is only slightly soluble are selected, and a mixing ratio is selected to form a mixed system with water, an indole having a preferable indole solubility is obtained. Can be obtained and used.

As a boundary condition for bringing the above crude indole and the solvent into contact with each other in a liquid or solid state, for example, the melting point of indole is 53 ° C. in terms of temperature, but in the presence of a solvent, a melting point may be lowered, At that temperature, the indole will change from solid to liquid, and the melting point drop will be further increased depending on the impurity concentration of the crude indole, and the boundary condition may become 15 ° C or lower from the melting point. .

The ratio of the crude indole and the solvent in the present invention is generally the temperature at which the crude indole and the solvent are brought into contact with each other in liquid or solid-liquid state, and it is necessary to preliminarily charge the crude indole in an amount equal to or more than the amount of indole to be extracted into the solvent. The crude indole excess is 5% by weight or more, preferably 10% by weight or more.
In this way, the crude indole is charged in an amount not less than the extraction amount of the solvent and partially left as a solid or liquid, so that in the remaining crude indole phase, indole having a stronger affinity to the crude indole phase than to the solubility in the solvent phase. Derivatives can be incorporated. As a result, the concentration of the dissolved indole derivative in the solvent is suppressed to a low level as compared with the case of dissolving the crude indole in the solvent, which is advantageous when the purified indole is deposited and separated.

Further, when the filtrate obtained by separating and separating the purified indole is repeatedly used as an extraction solvent for the crude indole, because of the equilibrium due to the distribution ratio of the indole derivative between the crude indole phase and the solvent phase,
It is also advantageous because it has a function of controlling the concentration of impurities in the solvent used repeatedly. Since the indole derivative accumulates in the crude indole phase by the extraction, it is necessary to extract a part or all of the indole derivative for purification. Industrially, there is usually a purification process of indole such as distillation before the recrystallization process.
By returning the crude indole phase to the process, it can be economically purified.

In the present invention, the temperature at which the crude indole and the solvent are brought into liquid or solid-liquid contact is usually 35 to 70 ° C., and after the crude indole and the solvent are brought into liquid or solid-liquid contact, the crude indole phase As a method for separating the indole-extracted solvent phase from the indole, a filtration method or a sedimentation method is usually used in the case of solid-liquid contact, and a liquid separation method is used in the case of liquid-liquid contact.

In the present invention, as a method for precipitating a purified indole crystal from the solvent phase from which indole is extracted, there are an ordinary cooling method, a concentration method and the like, but the cooling method is preferable in order to suppress contamination of impurities. In addition, a filtration method is usually used to separate the precipitated purified indole crystals, but not only the purified indole crystals are scaly in shape and have a high liquid content, but also liquid filterability due to clogging by crystals. It is liable to be defective, and it is difficult to obtain a sufficient effect even if the crystal is washed after the separation, and it is necessary to consider it in operation.

In the present invention, the above-mentioned separated solution of the purified indole crystals can be repeatedly used as an extraction solvent for the crude indole, but since the indole having a saturated solubility at the time of precipitation of the purified indole crystals is dissolved in the separated solution, the next extracted fraction Almost all of them can be precipitated as crystals, which is very advantageous in terms of recovery rate (yield).

〔Example〕

Hereinafter, the present invention will be specifically described with reference to Reference Examples, Examples and Comparative Examples. In the following, "part" and "%" are based on weight. The indole and impurities were analyzed by gas chromatography.

Reference Example Aniline and ethylene glycol were subjected to a gas phase catalytic reaction in the presence of a known catalyst to obtain an indole synthesis reaction solution. This synthetic reaction solution was distilled under the following conditions using a batch distillation column with 19 theoretical plates to obtain an indole fraction (crude indole). The analytical values of this crude indole are summarized in Table 1.

-Aniline fraction: overhead pressure 9-12 mmHg overhead temperature 61-74 ° C reflux ratio 0.2-indole fraction: overhead pressure 7-10 mmHg overhead temperature 124-133 ° C reflux ratio 4.0 Example 1 In the above reference example Using the obtained crude indole, liquid-liquid separation and recrystallization with n-hexane were carried out by the following method (Experiment 1
~ 5). The analytical values and yields of the purified indole crystals obtained by recrystallization are summarized in Table-1.

(Experiment 1) The crude indole 25 obtained in the reference example was placed in a 500 ml Erlenmeyer flask.
And n-hexane (200 parts) were mixed and heated in a water bath at 40 ° C, a part of the crude indole became liquid and separated into two liquids. The n-hexane layer was transferred to another container by decantation and allowed to cool to room temperature, then cooled to 5 ° C and the precipitated crystals were filtered. The crystals were washed with 20 parts of n-hexane which had been cooled to 5 ° C. twice, and dried in a desiccator at room temperature under reduced pressure overnight.
A pure indole crystal was obtained. The crude indole layer remaining in the Erlenmeyer flask after decanting and separating the n-hexane layer was used in Experiment 2 below.

(Experiment 2) In Experiment 1, the washing liquid was added to the filtrate obtained by filtering the purified indole crystals to make 200 parts. In a 500 ml Erlenmeyer flask, this solution was mixed with the crude indole layer obtained in Experiment 1 and 20 parts of the crude indole obtained in Reference Example and heated in a water bath at 40 ° C. The subsequent operations were performed in exactly the same manner as in Experiment 1 to obtain a purified indole crystal, a filtrate, a washing solution and a residual crude indole layer. Further, the filtrate, the washing solution, and the remaining crude indole layer were used in Experiment 3 below.

(Experiments 3 to 5) The same operations as in Experiment 2 were repeated to obtain a purified indole crystal, a filtrate, a washing solution, and a residual crude indole layer. After the end of experiment 5, the crude indole layer remaining in the Erlenmeyer flask was analyzed and the indole purity was 86%.

Example 2 Using the crude indole obtained in the above Reference Example, liquid-liquid separation with methylcyclohexane and recrystallization were performed by the following methods (Experiments 6 to 10). The analytical values and yields of the purified indole crystals obtained by recrystallization are summarized in Table-2.

(Experiment 6) The crude indole 25 obtained in the reference example was placed in a 500 ml Erlenmeyer flask.
When 200 parts of methylcyclohexane were mixed and heated in a water bath at 30 ° C, a part of the crude indole became liquid and separated into two liquids. The methylcyclohexane layer was transferred to another container by decantation, allowed to cool to room temperature, cooled to 1 ° C, and the precipitated crystals were filtered. The crystals were washed with methylcyclohexane which had been cooled to 1 ℃.
Parts were used twice, and drying was carried out by leaving them in a desiccator at room temperature under reduced pressure overnight to obtain purified indole crystals. The crude indole layer remaining in the Erlenmeyer flask after decanting and separating the methylcyclohexane layer was used in Experiment 7 below.

(Experiment 7) In Experiment 6, the washing liquid was added to the filtrate obtained by filtering the purified indole crystals to make 200 parts. In a 500 ml Erlenmeyer flask, this solution was mixed with the crude indole layer obtained in Experiment 6 and 20 parts of the crude indole obtained in Reference Example and heated in a water bath at 30 ° C. The subsequent operations were performed in exactly the same manner as in Experiment 6 to obtain a purified indole crystal, a filtrate, a washing solution and a remaining crude indole layer. Further, the filtrate, the washing solution, and the remaining crude indole layer were used in Experiment 8 below.

(Experiments 8 to 10) The same operations as in Experiment 7 were repeated to obtain a purified indole crystal, a filtrate, a washing solution, and a remaining crude indole layer. After the end of Experiment 10, the crude indole layer remaining in the Erlenmeyer flask was analyzed, and the indole purity was 81%. From this, it was confirmed that impurities were concentrated in the crude indole layer during decantation.

Example 3 Crude indole 25 obtained in Reference Example in a 500 ml Erlenmeyer flask
And 200 parts of 35% ethanol aqueous solution were mixed and heated in a water bath at 45 ° C, a part of the crude indole became liquid and separated into two liquids. The ethanol aqueous solution layer was transferred to another container by decantation and allowed to cool to room temperature, then cooled to 5 ° C and the precipitated crystals were filtered. The crystals were washed with 20 parts of 35% ethanol aqueous solution which had been cooled to 5 ° C. twice, and dried in a desiccator at room temperature under reduced pressure overnight to obtain purified indole crystals. The purity of the obtained purified indole crystal was 99.4%.

Comparative Example Using the crude indole obtained in the above Reference Example, recrystallization with methylcyclohexane was performed by the following method (Experiments 11 to 1).
5). The analytical values of the purified indole crystals obtained by recrystallization are summarized in Table 3.

(Experiment 11) The crude indole 18 obtained in the reference example was placed in a 500 ml Erlenmeyer flask.
And 200 parts of methylcyclohexane were mixed and heated in a water bath at 30 ° C., the crude indole was completely dissolved to form a uniform solution. The solution was allowed to cool to room temperature, then cooled to 1 ° C., and the precipitated crystals were filtered. The crystals were washed twice with 20 parts each of methylcyclohexane that had been cooled to 1 ° C., and dried in a desiccator at room temperature under reduced pressure overnight to obtain purified indole crystals.

(Experiment 12) In Experiment 11, the washing liquid was added to the filtrate obtained by filtering the purified indole crystals to make 200 parts. In a 500 ml Erlenmeyer flask, 18 parts of the crude indole obtained in Reference Example was mixed with this solution and heated in a water bath at 30 ° C. Subsequent operations were exactly the same as in Experiment 11 to obtain a purified indole crystal, a filtrate and a washing solution. Further, the filtrate and the washing solution were used in the following Experiment 13.

(Experiments 13 to 15) The same operations as in Experiment 12 were repeated to obtain a purified indole crystal, a filtrate and a washing solution, respectively.

[Effects of the Invention] By carrying out the method of the present invention, the indole derivative in the side reaction product, which has been difficult to separate in the past, can be separated easily and to a higher concentration. It is also a useful method in the technical field to which the present invention belongs, since it is possible to contribute to the above, and it is possible to obtain effects such as energy saving and improvement of recovery rate (yield) by repeatedly using the recrystallization solvent.

 ─────────────────────────────────────────────────── --Continued from the front page Examiner Tomoko Saeki (56) References JP 58-121270 (JP, A) JP 57-134462 (JP, A)

Claims (1)

[Claims] 1. When purifying crude indole by a recrystallization method, the crude indole and a solvent are brought into contact with each other in a liquid or solid state,
Forming two phases of a solvent phase in which indole is extracted and a crude indole phase, using a liquid obtained by separating a purified indole crystal from the solvent phase as the solvent, and circulating the crude indole phase to the purification step of the preceding stage A method for purifying indole characterized by: