JPH06184106A - Production of indole or indole derivative - Google Patents

Abstract

PURPOSE:To efficiently produce indole or an indole derivative from inexpensive raw material by one stage liquid phase reaction. CONSTITUTION:In a method for producing indole or an indole derivative by reacting an anilines with a 1,2-glycol in a liquid phase, a catalyst containing (1) oxide of Si, (2) oxide of Cu, (3) one or more kinds of metal oxides selected from a group consisting of Mg, Co, Mn, Zn and Ni and (4) oxide of alkali metal is used as the catalyst.

Description

Detailed Description of the Invention

[0001]

The present invention relates to anilines and 1,2-
The present invention relates to a method for producing an indole or an indole derivative by reacting with glycols in a liquid phase.

[0002]

2. Description of the Related Art Hitherto, as a method for producing an indole derivative by a liquid phase reaction, Fischer's indole synthesis method in which phenylhydrazine is reacted with a compound having an aldehyde group has long been well known. If the aldehyde compound is other than acetaldehyde, Fischer's indole synthesis method described above can be applied and the indole derivative can be obtained in high yield, but when the aldehyde compound is acetaldehyde, the reaction does not proceed and indole is not generated. It was Ortho-
There is a method in which toluidine is reacted with formic acid to produce ortho-methyl-N-formylaniline, which is melted with potassium hydroxide to produce. In this method, the ortho-toluidine used as the starting material is usually produced in the same amount as the ortho-form and the para-form when producing it.
Therefore, the treatment of isomers coproduced as a by-product becomes a big problem in industrial production. Further, handling of solids such as alkali melting is complicated, and it is hard to say that it is suitable for industrial production.

In recent years, there has been proposed a method for producing an indole or an indole derivative by a liquid phase reaction of anilines and 1,2-glycols such as ethylene glycol. This method is attractive as an industrial production method because an indole or indole derivative can be produced in a single step using inexpensive raw materials. However, the currently proposed liquid phase reaction method has some problems in industrial implementation. For example, JP-A-56-73060 discloses a method using a Group 8 metal and / or activated carbon as a catalyst. However, in the case of base metals such as Ni, Co or Fe or activated carbon, the yield is 20% or less. When a noble metal such as Pd or Pt is used as the Group 8 metal, the yield of indoles is as high as about 60%, but the amount of the catalyst used is large and there is a problem in industrial implementation.

Japanese Unexamined Patent Publication (Kokai) No. 56-110672 discloses a method of using magnesium oxide as a catalyst. However, according to the findings of the present inventors, this catalyst has poor reproducibility of activity and is used on an industrial scale. In this case, it is difficult to stably obtain a high yield. Japanese Patent Publication No. 3-43267 discloses that various metal oxides have a catalytic action in the reaction of the present invention. Further, in JP-A-3-153665, a combination of such a specific kind of metal oxide, that is, a kind selected from the group consisting of oxides of Si and Cu and Ni, Co, Cr, Mn, Ca, Mg, Zn. It is disclosed that the use of a catalyst containing oxides of the above elements improves the yield of indole or indole derivative. However, as an industrial production method, the amount of catalyst used is still large,
Selectivity and yield are also insufficient.

[0005]

The object of the present invention is to industrially produce an indole or an indole derivative by using an inexpensive raw material such as aniline and 1,2-glycol and by a reaction in a single liquid phase. In doing so, it is to provide a method for efficiently producing an indole or an indole derivative in the presence of an improved catalyst.

[0006]

Means for Solving the Problems In producing an indole or an indole derivative from anilines and 1,2-glycols, the present inventors have found that oxides of Si, oxides of Cu, Mg, Co, Mn, The use of a catalyst containing one or more metal oxides selected from the group consisting of Zn and Ni or an alkali metal oxide yields a higher yield of indole or indole derivative than a catalyst containing no alkali metal oxide. The inventors have found that the amount of the catalyst used is significantly improved and the amount of the catalyst used is smaller, and have completed the present invention.

That is, the present invention relates to anilines and 1,2
-In the method for producing an indole or indole derivative by reacting with glycols in a liquid phase, the catalyst used is selected from the group consisting of Si oxide, Cu oxide, Mg, Co, Mn, Zn and Ni. A method for producing an indole or an indole derivative, which is a catalyst containing one or more kinds of metal oxides and alkali metal oxides. According to the present invention, for example, 5-methylindole can be obtained by reacting aniline and ethylene glycol, and by reacting para-toluidine and ethylene glycol. The anilines used in the present invention have the general formula (formula 1).

[0008]

[Chemical 1] (In the formula, R represents a hydrogen atom, a halogen atom, a hydroxyl group, an alkyl group or an alkoxy group). For example, aniline, ortho-toluidine, meta-toluidine, para-toluidine, ortho-fluoroaniline, meta-fluoroaniline, para-fluoroaniline, ortho-chloroaniline, meta-chloroaniline, para-chloroaniline, ortho-bromoaniline. ,
Meta-bromoaniline, para-bromoaniline, ortho-iodinated aniline, meta-iodinated aniline, para-iodinated aniline, ortho-aminophenol, meta-aminophenol, para-aminophenol, ortho-anisidine,
Examples include meta-anisidine, para-anisidine, orthoethoxyaniline, meta-ethoxyaniline and para-ethoxyaniline. The 1,2-glycols used in the present invention include ethylene glycol, propylene glycol, 1,2-butanediol, 1,2,4-
Examples include butanetriol, 2,3-butanediol and diethylene glycol.

Although the content of the catalyst component used in the present invention is not particularly limited, it is usually expressed by the ratio (atomic ratio) of gram atoms of each component metal to the total of gram atoms of all metals contained. Si is 5 to 99%, Cu is 1 to 60%,
Mg is 1 to 90%, Co is 1 to 60%, Mn is 1 to 60%.
%, Zn is 1 to 60%, Ni is 1 to 60%, and alkali metal is 0.001 to 3%. Further, the content of alkali metal is preferably in the range of 0.01 to 1%. The alkali metal of the catalyst of the present invention is Li, Na, K, Rb, Cs, and Na and K are preferable. The catalyst used in the present invention can be prepared by any method known in the art. For example, it can be produced by a method in which a water-soluble salt of a catalyst constituent element is hydrolyzed to a hydroxide and the resulting gel is dried and calcined, or a readily decomposable salt is thermally decomposed in air. .

In order to effectively utilize the inherent activity of these catalysts, it is a means usually used in these technical fields, but the method of supporting the catalyst of the present invention on a carrier can also be used. In that case, as the carrier, any of those generally used can be used, but usually, diatomaceous earth, pumice, titania, silica-alumina, alumina,
Magnesia, silica gel, activated carbon, activated clay, asbestos, etc. are used. The catalyst is supported on these carriers by a conventional method to prepare a supported catalyst. The amount of the catalyst supported on the carrier is not particularly limited, and is usually an appropriate amount depending on the carrier.
For example, 1 to 50 wt% of the catalyst may be supported.
The present invention is carried out in the liquid phase. The reaction is anilines and 1,
It is carried out by heating a mixture with 2-glycols in the presence of one or more catalysts selected from the above catalysts. At this time, various solvents can be coexistent as the reaction solvent. As such a solvent, for example,
Benzene, toluene, xylene, hexane, octane,
Liquid paraffin, dioxane, diphenyl ether,
Diethylene glycol dimethyl ether, dimethyl ether phthalate, diethyl phthalate, dioctyl phthalate, chlorobenzene, dichlorobenzene, dimethylformamide, dimethyl sulfoxide, pyridine, N-methylpyrrolidone, trimethylamine, diethylamine,
Examples thereof include organic solvents such as triethylamine, tripropylamine, tributylamine, diphenylamine and triphenylamine.

The reaction in the liquid phase is carried out in a fixed bed, fluidized bed or moving bed reactor, a batch type or continuous type liquid phase reactor, but is not particularly limited. In this reaction, the amounts of anilines and 1,2-glycols used as starting materials are 1,2-glycols per mole of anilines.
It is in the range of 01 to 5 mol, preferably in the range of 0.02 to 2 mol. The amount of the catalyst used in the reaction is not particularly limited, but it is usually 0.002 to 10 g, preferably 0.01 to 5 g, based on 1 mol of the starting aniline. The reaction temperature is not uniform depending on the type of raw material and the type and amount of catalyst, but is usually in the range of 100 to 500 ° C, preferably in the range of 150 to 400 ° C. The reaction time is generally 10 minutes to 10 hours, preferably 1 hour to 4 hours. The reaction pressure may be increased pressure or normal pressure. After the reaction, the product indole or indole derivative can be separated and purified from the reaction solution by a conventional method such as distillation.

[0012]

EXAMPLES The present invention will be further described with reference to the following examples.
It Example 1 An aniline was placed in a SUS autoclave equipped with a stirrer and having an internal volume of 80 ml.
Phosphorus 37.25 g (400.0 mmol), ethylene glycol 2.
48 g (40.0 mmol) and catalyst SiO prepared by coprecipitation method₂-CuO-
MgO-Na₂O (atomic ratio Si: Cu: Mg: Na = 69.9: 10.0: 20.0: 0.17)
Was charged with 0.10 g, and the air in the autoclave was purged with nitrogen gas.
Replacement, then nitrogen gas pressure 5kg / cm ²Pressed up to
Then, with stirring, react for 110 minutes at a reaction temperature of 350 ° C.
It was After the reaction, the catalyst is filtered off from the reaction solution and the reaction product is separated.
Schromatography analysis showed that
Yields 3.53 g (30.1 mmol) of
The yield of ethylene was 75% based on ethylene glycol.

Comparative Example 1 The catalyst used in Example 1 was SiO2-CuO-MgO (atomic ratio Si: Cu: M
g = 69.5: 9.8: 20.7) except that the reaction was carried out in exactly the same manner as in Example 1. As a result, the yield of indole is 61%.
Met. Thus, the use of the catalyst containing no alkali metal oxide significantly reduced the indole yield by 14%.

Examples 2 to 10 The catalysts of Example 1 were replaced with the catalysts shown in Table 1, and the reaction was carried out in exactly the same manner as in Example 1. The results are shown in Table 1 together with the results of Example 1.

[0015]

[Table 1]

Comparative Examples 2 to 4 Reactions were carried out in exactly the same manner as in Example 1 except that the catalyst shown in Table 2 was used instead of the catalyst of Example 1. The results are shown in Table 2 together with the results of Comparative Example 1.

[0017]

[Table 2]

[0018]

The method of the present invention is a one-step liquid phase reaction of aniline and 1,2-glycol, which are inexpensive raw materials,
This is an industrially extremely advantageous method that can efficiently produce an indole or an indole derivative.

Claims (4)

[Claims] 1. A method for producing an indole or an indole derivative by reacting anilines with 1,2-glycols in a liquid phase, wherein the catalyst used is an oxide of Si, an oxide of Cu, Mg, Co. A method for producing an indole or an indole derivative, which is a catalyst containing an oxide of one or more metals selected from the group consisting of Mn, Zn and Ni, and an oxide of an alkali metal. 2. The method according to claim 1, wherein the alkali metal is sodium or potassium. 3. The method according to claim 1, wherein the aniline is aniline. 4. The method according to claim 1, wherein the 1,2-glycol is ethylene glycol.