JPH0819094B2 - Method for producing indolines - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing indolines.

Indolines have recently attracted attention as synthetic intermediate compounds for medicines, agricultural chemicals, photosensitive materials and the like.

BACKGROUND ART The following method is known for catalytically reducing indoles to obtain indolines.

A method using a copper chromite catalyst. (H.Adkins, et
al., J. Am . Chem . Soc ., 63 , 1563, (1941)) A method using a Raney nickel catalyst. (WENolan
d, et al., J. Org. Chem., 25 , 1525, (1960)) A method in which a nickel-titanium catalyst is used and salts of copper, cobalt, cadmium, iron, etc. are added. (USSR 579,2
The copper chromite catalyst of the method 70) requires a high reaction temperature of around 190 ° C and has many side reactions, so that the yield is not satisfactory. The method of reducing with a Raney nickel catalyst of the method of 1) reacts at a relatively low temperature, but the selectivity is poor, and a large amount of octahydroindole in which the indole ring is completely hydrogenated is by-produced, and the desired indoline Only low yields have been obtained. In the method using a nickel-titanium catalyst, the yield of indolines is almost satisfactory, but it is difficult to obtain the catalyst, and it is necessary to add a third substance to industrially produce indolines. In this case, it is not enough.

Problems to be Solved by the Invention The present invention provides a method for industrially and easily producing indolines by solving the above problems when producing indolines by catalytically reducing indoles with hydrogen.

Means and Actions for Solving Problems That is, the present invention relates to the general formula (1) (In the formula, R ₁ represents a kind of a substituent selected from a hydrogen atom, an alkyl group and a phenyl group, and R ₂ is a kind selected from a hydrogen atom, an alkyl group, a hydroxyalkyl group, an aminoalkyl group and an alkoxycarbonylalkyl group. In the production of indolines represented by R ₁ and R ₂ are different from each other), corresponding indoles are hydrogen-reduced in the presence of a platinum carbon catalyst and an acid. It is a method for producing indolines.

Specific examples of the indolines that can be produced by the present invention include, for example, 2-methylindoline, 2-ethylindoline, 2-phenylindoline, 3-methylindoline, 3-ethylindoline, 3-hydroxymethylindoline, 2 , 3-dihydrotryptohol, 2,3-dihydrohomotryptohol, 2,3-dihydrotryptamine and indoline-3-acetic acid ester.

The platinum-carbon catalyst used in the present invention may be generally commercially available. The weight range of platinum supported on activated carbon is preferably 2 to 10% by weight.

The acid used in the present invention may be an inorganic acid or an organic acid. As a specific example, perchloric acid, fluoroboric acid, hydrochloric acid, hydrobromic acid, sulfuric acid or the like can be used as the inorganic acid, and acetic acid or propionic acid or the like can be used as the organic acid.

The method of the present invention is carried out without solvent or in a solvent, but the solvent used is a solvent which does not undergo hydrogenation with a platinum carbon catalyst from alcohols, esters, ethers, hydrocarbons and the like. Either can be used.
Particularly, lower alcohols such as methanol, ethanol and isopropanol are suitable for the method of the present invention.

Next, the hydrogen reduction conditions for carrying out the present invention will be described. First, the platinum carbon catalyst may be used in an amount of 1 to 20% by weight, preferably 3 to 10% by weight, based on the raw material indole. The amount of acid used is
It is used in an amount of 0.2 to 5 times by mole, preferably 0.5 to 1.5 times by mole, relative to the raw material indole. A low reaction hydrogen pressure is sufficient, and the reaction at atmospheric pressure to 10 kg / cm ² gives good results on the selective production rate of indolines. Reaction temperature is room temperature to 150 ℃
In particular, it is preferable to carry out at a temperature in the range of 100 ° C. or lower. If the reaction temperature is too low, the time required for completion of the reaction is unnecessarily long, and if the reaction temperature is too high, side reactions are likely to occur and the yield of indolines decreases.

When the hydrogenation reaction of indoles is carried out by the method of the present invention, the reaction time is 1 to 10 hours.
When the conversion rate of indoles is about 95%, indolines can be obtained with a high selective production rate of indolines to indoles of 90% or more. As a by-product, octahydroindoles in which the indole ring is completely hydrogenated are produced, but the amount thereof is insignificant. The produced indolines can be separated and recovered easily by a distillation method or a method utilizing a difference in basicity.

 Hereinafter, the present invention will be described in more detail with reference to examples.

Example 1 20 g of 2-methylindole, 100 ml of methanol, 0.5 g of 5% platinum-carbon catalyst and 10 ml of 35% hydrochloric acid aqueous solution were put into a 200 ml autoclave of up and down stirring type, and after sealing and purging with hydrogen, hydrogen pressure was ^{2 to 4} kg / cm ² reaction. The mixture was stirred for 6 hours while maintaining the temperature at 50 ° C. After completion of the reaction, the reaction mixture was cooled and filtered to remove the methanol from the reaction solution, and extracted with 100 ml of toluene and 100 ml of 5% sodium hydroxide solution. It was analyzed by gas chromatography to find that 2-methylindole3.9
%, 2-methylindoline 91.7%, and 2-methyloctahydroindole 4.7%. This was distilled under reduced pressure to obtain 17.0 g of 2-methylindoline having a boiling point of 85 to 90 ° C./5 mmHg.
(Yield 83.7%) was obtained.

Example 2 In Example 1, 20 ml of 70% aqueous solution of perchloric acid was used in place of 35% aqueous solution of hydrochloric acid, and other reaction conditions were almost the same as in Example 1 except that the reduction reaction was performed at room temperature for 5.5 hours. The analysis results were 97.3% of 2-methylindoline, 1.3% of octahydro-2-methylindole and 0.1% of 2-methylindole.

Example 3 20 g of tryptohol was subjected to a reduction reaction for 12 hours at room temperature under the same reaction conditions as in Example 2, except that the reaction solution was analyzed to find that 2,3-dihydrotryptohol was 100%, No tohore was detected.

Example 4 20 g of tryptamine was subjected to a reduction reaction at room temperature for 30 hours in the same manner as in Example 2 under other reaction conditions. The analysis result of the reaction completion liquid was tryptamine 17.9% 2,3-dihydrotryptamine 78.7%, and octahydrotryptamine was not detected.

Example 5 20 g of 3-methylindole was used under other reaction conditions.
The mixture was stirred at room temperature for 14 hours in the same manner. The results of analysis of the reaction solution by gas chromatography revealed that 8-methylindolin was 84.3% and 3-methyloctahydroindole was 12.1%.
%, 3-methylindole was not detected.

Example 6 20 g of homotryptohol was subjected to a reduction reaction at room temperature for 24 hours in the same manner as in Example 2 under other reaction conditions. The analysis result of the reaction completed liquid was 2,3-dihydrohomotryptohol 87.5.
%, Octahydrohomotryptohol 5.1%, and homotryptohol 7.3%.

Example 7 20 g of methyl indole-3-acetate was subjected to a reduction reaction at room temperature for 24 hours under the same reaction conditions as in Example 2. The analysis result of the reaction completed liquid is 2,3-dihydroindole-3.
Methyl acetate 91.6% octahydroindole-3-methyl acetate 5.1% indole-3-methyl acetate 2.2%.

EFFECTS OF THE INVENTION According to the method of the present invention, indolines can be industrially easily produced with high yield.

Claims (1)

[Claims] 1. A general formula (I) (In the formula, R ₁ represents a kind of a substituent selected from a hydrogen atom, an alkyl group and a phenyl group, and R ₂ is a kind selected from a hydrogen atom, an alkyl group, a hydroxyalkyl group, an aminoalkyl group and an alkoxycarbonylalkyl group. In which R ₁ and R ₂ are different from each other), the corresponding indoles are hydrogenated in the presence of a platinum carbon catalyst and an acid. Method for producing indolines.