JPS6210985B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing indole or indole derivatives. More specifically, the present invention relates to a method for producing indole or an indole derivative by reacting anilines with ethylene glycol in the presence of a magnesium oxide-containing catalyst.

Indole is known as a raw material for the chemical industry, and has become an important substance particularly in recent years as a raw material for perfumery and amino acid synthesis.

There have been several attempts to synthesize indole, but all of them produced many by-products,
Many of them are expensive in terms of raw materials, or the process to reach indole is long and the operations are complicated.

An object of the present invention is to produce indole or indole derivatives with high selectivity in a single step using inexpensive raw materials.

As a result of intensive studies to achieve this objective, the present inventors have developed a method based on a completely new reaction that has not been previously known, that is, catalytic reaction of anilines and ethylene glycol with a catalyst containing magnesium oxide. They found that the desired product, indole or indole derivatives, can be produced with high selectivity, and completed the method of the present invention. That is, according to the method of the present invention, for example, indole is produced by catalytically reacting aniline and ethylene glycol, and by catalytically reacting para-toluidine and ethylene glycol.
5-methylindole can be obtained.

The catalyst used in the method of the invention is a catalyst containing magnesium oxide. For example, magnesium oxide alone in the form of powder, granules, lumps, scales, molded products, etc.
Alternatively, it is a mixture of magnesium oxide and other compounds, or a magnesium oxide-containing catalyst in which magnesium oxide alone or a mixture of magnesium oxide and other compounds is supported on a carrier.

Other compounds used in combination with magnesium oxide include lithium, sodium, potassium, magnesium, calcium, strontium, barium, copper, silver, mercury, aluminum, tin, iron, cobalt, nickel, chromium, manganese, lead, and molybdenum. These include halides, nitrates, sulfates, carbonates, organic acid salts, oxides, hydroxides, and metals. As the carrier for supporting magnesium oxide or magnesium oxide and other compounds, any carrier that is generally used as a carrier for supported catalysts can be used, but diatomaceous earth,
Pumice, titania, silica-alumina, alumina,
Magnesium, silica gel, activated carbon, activated clay,
Asbestos etc. are used.

A supported catalyst is prepared by supporting the catalyst substance on these carriers by a conventional method. According to the immersion method, magnesium chloride, magnesium bromide, magnesium iodide, magnesium nitrate, magnesium sulfate, magnesium hypochlorite, magnesium perchlorate, magnesium chromate, magnesium carbonate, acetic acid are added to a carrier such as activated carbon or alumina. It is produced by dissolving a water-soluble magnesium salt such as magnesium or magnesium formate in water, immersing it, drying it, and then thermally decomposing it. Alternatively, according to a precipitation method, for example, a carrier such as activated carbon or silica gel is added to an aqueous solution of a water-soluble magnesium salt as described above, and an alkaline substance is added while stirring to form a precipitate. The precipitate is prepared by separating, washing, drying and calcining. Alternatively, according to the coprecipitation method, an aqueous solution of the water-soluble magnesium salt described above and calcium, strontium, barium, copper, silver, aluminum, tin, iron,
Mix with an aqueous solution of water-soluble salts such as cobalt, nickel, silica, chromium, manganese, lead, molybdenum, etc., add acid or alkali as necessary to form a precipitate, separate the precipitate, wash, dry and Prepared by baking. In addition, there are various catalyst preparation methods, and the method for preparing the catalyst is not limited. Further, there is no particular restriction on the amount of the catalyst substance supported on the carrier, and usually an appropriate amount, for example 0.1 to 50%, of the catalyst substance may be supported depending on the carrier.

The anilines used in the present invention include aniline,
and ortho-toluidine, meta-toluidine,
para-toluidine, ortho-aminophenol,
Includes nuclear substituted derivatives of aniline such as meta-aminophenol, para-aminophenol, ortho-anisidine, meta-anisidine, and para-anisidine.

The method of the present invention can be carried out in any of the gas phase, liquid phase, or gas-liquid mixed phase. When carried out in the gas phase, it can be carried out in a fixed bed, fluidized bed or moving bed reactor, and carried out by heating a mixed gas of anilines and ethylene glycol in the presence of a catalyst containing magnesium oxide. At this time, various inert gaseous substances can be allowed to coexist as diluents for the raw material vapor. Examples of such inert gaseous substances include nitrogen gas, carbon dioxide, water vapor, and vapors of compounds inert to this reaction. Furthermore, hydrogen gas or hydrogen-containing gas may also be used as the diluent. Anilines and ethylene glycol are charged to the reactor at a ratio of 0.05 to 5 moles of ethylene glycol to 1 mole of aniline, and the liquid space velocity relative to the catalyst is 0.01 to 5 l/l-catalyst/hr. , either in vapor form beforehand or in liquid form directly into the reactor.

The reaction temperature is in the range of 200-500°C, preferably
The temperature is 250-400℃. If the temperature is below 200°C, the reaction will hardly proceed, and if it is above 500°C, a large amount of by-products will be produced, which is not preferable.

The reaction pressure may be increased pressure, normal pressure, or reduced pressure.

When carried out in a liquid phase, the reaction is carried out by heating a mixture of anilines and ethylene glycol in the presence of a catalyst consisting of magnesium oxide alone or of magnesium oxide and another compound. At this time, various inert gases and/or solvents can be used as diluents for the raw materials. As such an inert gaseous substance,
Examples include nitrogen gas, carbon dioxide gas, water vapor, and vapors of compounds inert to this reaction. Further, examples of the solvent include benzene, toluene, xylene, methanol, ethanol, isopropanol, dioxane, dimethylformamide, dimethyl sulfoxide, pyridine, N-methylpyrrolidone, trimethylamine, diethylamine, triethylamine, tripropylamine, tributylamine, diphenylamine, trifluoride, etc. Examples include organic solvents such as enylamine.

The above liquid phase reaction is carried out in a fixed bed, fluidized bed or moving bed reactor, batch type or continuous liquid phase reactor, but there are no particular limitations.

In the liquid phase reaction, the raw materials aniline and ethylene glycol are used in a ratio of 0.05 to 5 mol, preferably 0.1 to 2 mol, of ethylene glycol per 1 mol of aniline.

In addition, the amount of catalyst used in the liquid phase reaction is
Although there is no particular limit, generally 0.01 to 1 mole of raw material aniline is used as magnesium oxide.
20g, preferably in the range of 0.1-10g.

The reaction temperature of the liquid phase reaction is in the range of 200 to 500°C, preferably in the range of 250 to 400°C. If the temperature is below 200°C, the reaction will hardly proceed, and if it is above 500°C, a large amount of by-products will be produced, which is not preferable. Further, the reaction pressure may be either elevated pressure or normal pressure.

From the reaction products in these various methods,
Indole or an indole derivative can be easily separated and purified by an appropriate method, for example, a conventional method such as distillation.

The advantages of the method of the invention are as follows. First, the raw materials are very cheap, such as aniline and ethylene glycol. Second, indole or an indole derivative is produced from the raw materials in one step. Thirdly, there are very few by-products and the selectivity is very good, making it possible to obtain highly pure indole.

Hereinafter, the method of the present invention will be explained in detail with reference to Examples.

Example 1 50 ml of a cylindrical co-precipitated MgO-silica catalyst (MgO content 25% by weight) was packed into a 25 mm Pyrex glass flow-through reactor. The front part of this reactor is connected to a raw material insertion pipe and a gas introduction pipe,
It constitutes a raw material vaporization section, and the rear part is connected to a receiver via an air cooling section. The reaction section maintains the internal temperature of this reactor.
After maintaining the temperature at 325℃ and reducing the catalyst by passing hydrogen gas into the reactor for about 1 hour, the liquid hourly space velocity was reduced to 0.1l/l-catalyst/
hr, a mixed solution of 93.1 g (1 mol) of aniline and 6.2 g (0.1 mol) of ethylene glycol was inserted through the raw material insertion tube, and at the same time 10
Double the molar amount of nitrogen was passed under normal pressure. When the reaction product condensed through the reactor was analyzed using a gas chromatograph, 8.8 g of indole was produced, with a conversion rate of 83.5% and a selectivity of 90.3 based on ethylene glycol.
% of indole was obtained with very little by-products.

Example 2 In Example 1, granular MgO was used instead of the MgO-silica catalyst, and the reaction temperature was changed to 375°C.
The reaction was carried out in the same manner as in Example 1 using the same reaction apparatus as in Example 1. As a result, 8.0 g of indole was obtained. The conversion rate was 78.7% and the selectivity was 87.4% based on ethylene glycol.

Example 3 In Example 1, a MgO-alumina catalyst (MgO supported amount: 20% by weight) was used instead of MgO-silica, and the reaction temperature was set to 375°C.
The reaction was carried out in the same manner as in Example 1 using the same reactor. As a result, 8.3g of indole was obtained. Conversion rate based on ethylene glycol 83.0
%, and the selection rate was 85.6%.

Example 4 In Example 1, a MgO-catalyst (MgO supported amount: 20% by weight) was used instead of the MgO-silica catalyst.
The reaction was carried out in the same manner as in Example 1 using the same reactor as in Example 1, and using hydrogen gas in place of nitrogen gas. As a result, 9.6g of indole was obtained. The conversion rate was 90.2% and the selectivity was 90.5% based on ethylene glycol.

Example 5 Same as Example 1 except that a MgO-MnO ₂ catalyst (MgO content 50% by weight) was used instead of the MgO-silica catalyst and hydrogen gas was used instead of nitrogen gas. The reaction was carried out in the same manner as in Example 1 using the same reactor. Result: 8.3g
obtained indole. The conversion rate was 90.3% and the selectivity was 78.7% based on ethylene glycol.

Example 6 In Example 1, para-
Example 1 using 107 g (1 mol) of toluidine
The reaction was carried out in the same manner as in Example 1 using the same reactor. As a result, 1.8 g of 5-methylindole was obtained. The conversion rate was 25.8% and the selectivity was 53.7% based on ethylene glycol.

Example 7 In Example 1, para-
The reaction was carried out in the same manner as in Example 1 except that 123 g (1 mol) of anisidine was used. the result,
2.3g of 5-methoxyindole was obtained. Conversion rate 28.3%, selectivity based on ethylene glycol
It was 55.7%.

Example 8 93.1 g (1 mole) of aniline, 6.2 g (0.1 mole) of ethylene glycol, and 1 g of powdered magnesium oxide were placed in a 200 ml titanium alloy autoclave equipped with a stirrer, the air in the autoclave was expelled, and the nitrogen pressure was increased to 5 kg. /cm ² , the reaction temperature was 300°C for 30 minutes while stirring the autoclave. After the reaction, the magnesium oxide was separated from the reaction solution, and the reaction product was analyzed by gas chromatography. As a result, 7.1 g of indole was obtained. Conversion rate 80.2%, selectivity based on ethylene glycol
It was 75.7%. A small amount of indoline was obtained as a by-product.

Comparative Example 1 A reaction was carried out in the same manner as in Example 3 using α-alumina, which is the carrier of the MgO-alumina catalyst used in Example 3, as a catalyst, but no indole was detected in the reaction product.

Comparative Example 2 A reaction was carried out in the same manner as in Example 5 using MnO ₂ as a catalyst for the MgO--MnO ₂ catalyst used in Example 5, but no indole was detected in the reaction product.

Comparative Example 3 A reaction was carried out in the same manner as in Example 1 except that a cylindrical ZnO catalyst was used as a catalyst, but no indole was detected in the reaction product.

Claims (1)

[Claims] 1. A method for producing indole or an indole derivative, which comprises reacting anilines and ethylene glycol in the presence of a magnesium oxide-containing catalyst.