JPS6028818B2 - Method for producing indole or indole derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing indole or indole derivatives.

More specifically, the present invention relates to a method for producing indole or an indole derivative by heating N-8-hydroxyethylaniline or its nuclear substituted conductor together with a reduced steel-containing catalyst. Various methods for producing indole have been proposed for a long time, and its derivatives have also been studied.

In the case of compounds having a substituent, such as a phenyl group or a methyl group, at the 2-position of the indole, excellent synthetic methods are available and industrial production is relatively easy. However, an industrially advantageous method for producing indole itself or a compound having a substituent only on the benzene ring is not yet known.
For example, a method is known in which ortho-nitrotoluene is reduced to obtain ortho-toludine, which is N-formylated and then melted with caustic alkali, followed by several steps to obtain indole. The above-mentioned methods have various drawbacks, such as problems in the quantitative balance between ortho and para isomers of the starting materials, and complicated steps such as handling of molten salts. The quantitative balance between ortho-para isomers becomes a major problem in industrial mass production, and handling of molten salts is also difficult on an industrial scale. The object of the present invention is to provide a process for producing indole or indole derivatives that does not have the above-mentioned drawbacks.

As a result of various studies on the production method of indole or indole derivatives, the present inventors found that when N-8-hydroxyethylaniline or a nuclear substituted derivative is brought into contact with a heated reduced steel-containing catalyst, the desired product can be obtained in a single reaction operation. The present invention was completed based on the discovery that

That is, in the method of the present invention, indole or an indole derivative is produced by bringing N-8-hydroxyethylaniline or its nuclear substituted product into contact with a heated reduced steel-containing catalyst.

Therefore, according to the method of the present invention, indole or an indole derivative can be produced in a single reaction operation without the above-mentioned drawbacks, and it is industrially very advantageous.

That is, the starting material for the method of the present invention is a simple method that does not have problems with ortho-para isomer balance and does not involve complicated handling steps such as molten salt. In the method of the present invention, N-8-hydroxyethylaniline, which is a raw material, can be easily obtained in high yield from aniline and ethylene oxide.

Aniline and ethylene oxide are extremely advantageous as starting materials for indole because they are available in large quantities at low cost as industrial raw materials. The starting materials for the nuclear substitution derivatives can also be obtained in exactly the same manner. The catalyst used in the method of the present invention contains reduced copper. Such a reduced copper-containing catalyst may be a single catalyst, but it is usually advantageous to use it as a multi-component catalyst, supported on a support or added with second and third components. In preparing the reduced copper catalyst, the form of copper is reduced steel or suboxide steel or a mixture thereof. The supported steel catalyst is prepared by applying a copper salt to a suitable carrier by immersion or other means and then thermally decomposing it. Suitable carriers include silica gel, pumice, silicon carbide, etc. Fused alumina can be used, but alumina with a large surface area is not preferred in terms of side reactions. Examples of multi-component catalysts include copper chromite catalysts, copper-chromite manganese monoxide catalysts, and catalysts prepared by shaping and tableting these together with keisel earth. The above catalyst is usually subjected to a reduction treatment by a conventional method before carrying out the reaction. The method of reduction treatment is, for example, by gradually increasing the temperature while flowing a gas mixture of hydrogen and an inert gas such as nitrogen to 250 to 3
This is done by keeping it at 50qo for several hours. Further, a reduced steel-containing catalyst that is reduced in the reaction system without being subjected to the reduction treatment using the above method may be used. To carry out the method of the present invention, the raw material N-8-anilinoethanol is usually vaporized and introduced into a reaction tube together with hydrogen gas or a carrier gas prepared by diluting hydrogen with an inert gas such as nitrogen or methane. , by contacting with a heated reduced steel-containing catalyst.

The feed rate of the feed material to the catalyst bed is usually equal to the liquid hourly space velocity L
When expressed in HSV, the range of 0.1 to 1 is often used.

The temperature of the catalyst bed is between 200 and 50,000, especially between 250 and 4
A range of 00qo is preferred. The type of catalyst bed is a conventional fixed bed or fluidized bed. The reaction is usually carried out at normal pressure, but may also be carried out under reduced pressure or increased pressure. The reaction product flowing out of the reactor is collected in a cooled trap, and indole or an indole derivative is obtained by a conventional method such as distillation.

Unreacted raw materials are recycled back into the reaction system as starting materials. The present invention will be explained below with reference to Examples.

Example 1 A Pyrex glass reactor with an inner light capacity of 12 h/m was equipped with 0.
Catalyst 7' having a particle size of 5 to 1.5 m/m was filled and subjected to reaction.

As a catalyst, a mixture of ammonium copper chromate and manganese carbonate was thermally decomposed, mixed with Keishi and then pressed into tablets, which was crushed and used in the reaction with a particle size within the above range. The composition of the above catalyst excluding Katsura Minato is Cu050%, Cr2Q45%
, Mm025%, and the BET surface area is 32/mm. 0.1 part of hydrogen gas, 0.1 part of nitrogen gas. The catalyst bed temperature was gradually raised from room temperature to 300 qo and kept at 300 qo for 1 hour and at 340° C. for 1 hour to reduce the catalyst.

After the reduction is completed, a mixed gas consisting of 0.5 part of hydrogen gas and 0.5 part of nitrogen gas is supplied to the reactor at a rate of 150 m/min.
8-Hydroxyethylaniline was supplied to the vaporizer at 3 I/Hr and introduced into the reaction tube for reaction. Catalyst bed temperature is 340
It was kept at ℃. Analysis of the reaction solution collected in a cooled trap during 3 to 4 hours after the start of the reaction revealed that indole 4
0%, aniline 35%, unreacted raw material 10%, and indoline 10%.

The composition of the reaction solution collected during 10 to 11 hours after the start of the reaction was 43% indole, % aniline, and 8% unreacted raw materials.
, indoline was 10%. Separate the product liquid and conduct NMR
When the spectrum was measured, the target product matched well with that of standard indole. Example 2 Particle size 0.6-1. Shoes/m range of silica gel (surface area 20
A catalyst was prepared by injecting a nitric acid steel aqueous solution into a groove with a diameter of 0 and an average pore diameter of 90 A, followed by drying at 100° C. and firing at 500° C. for 3 hours.

The amount of oxidized steel supported on the silica gel was 25M%.
The above-mentioned catalyst 7 was charged into the same apparatus as in Example 11 and subjected to reduction treatment in the same manner, and the reaction was carried out by changing only the raw material used to N-8-hydroxyethyl-ortho-toluidine.

When the collected reaction products were analyzed, the content of 7-methyl-indole was found to be %%, 7-methyl-indole 10%.
, 40% orthotoluidine, and 6% unreacted raw material.
Example 3 A caustic potassium aqueous solution was added dropwise to a mixed aqueous solution of aluminum nitrate and steel nitrate to form a co-precipitated gel of aluminum and copper, which was then washed with water, dried (100:00 am, 12:00 pm), and then fired at 450°C for 4 hours in an air atmosphere. A catalyst was prepared.

The ratio of Cu0 and AI203 in the catalyst is 1% for Cu○
, N203 was 82M%. This catalyst is applied at 0.8h/m
~1. The same reactor as in Example 1 was filled with 10 pieces of the powder crushed to 100 m/m, and 0.1 part of hydrogen gas and 0.9 part of nitrogen gas were added.
The temperature was gradually raised from 200 qo to 35 qo over 2 hours using a mixed gas consisting of 350 qo and maintained at 350 qo for 1 hour to reduce the catalyst, thereby preparing a reduced steel catalyst supported on alumina. A mixed gas consisting of 0.5 parts of hydrogen gas and 0.5 parts of nitrogen gas was supplied to the reactor at a rate of 200 units/min, and N-B-hydroxyethylaniline was supplied to the reaction tube through a vaporizer at a rate of 2 units/hour. introduced and reacted.

The catalyst bed temperature was maintained at 320 pm. Analysis of the reactor outlet liquid collected in a tube during 4 to 6 hours after the start of the reaction revealed a composition of 42% indole, 30% aniline, 4% indoline, 18% unreacted raw materials, unknown substances, and 6M%. there were.

Example 4 A granular Raney alloy (Cu/AI=50/50) was developed with a caustic soda aqueous solution, and a metallic Raney steel and a granular catalyst (1
~1.8 h/m particle size) was prepared and charged into a reactor similar to Example 1 in a nitrogen atmosphere.

Claims (1)

[Claims] 1. A method for producing indole or an indole derivative, which comprises heating N-β-hydroxyethylaniline or a nuclear substituted product thereof in the presence of a catalyst containing reduced copper.