KR800001311B1 - Process for producing indoline derivatives - Google Patents

Abstract

Indolines(I), useful as an intermediate for pharmaceuticals and dyes, were prepd. by cyclization of O-halogen phenethylamine compd.(II; X = halogen atom) in the presence of Cu catalyst and ammonia. Thus, 157 g o-chlorophenethylamine was reacted with 375 g ammonia(NH4OH 67.5 %) at 150≰C for 4 hr in autoclave in the presence of copper chloride (CuCl 3%) to give 106 g indoline(yield 89.1 %).

Description

Method of preparing indolin

The present invention relates to a process for producing indorin.

은 농약, 의약, 염료 및 기타의 원료인 인돌

의 중간체, 혹은 인돌린 유도체의 원료 등으로서 사용되지만, 그 제조법으로써, 0-니트로 페네틸 알콜을 아연과 염화 칼슘으로 환원해서 생성되는 0-아미노페네틸 알콜을 염산의 존재하에서 페환(閉環)시키는 방법이, 그 한 방법으로써 알려져 있다.Guilin

Is an indole which is a raw material of pesticides, medicines, dyes and other

Although it is used as an intermediate of the compound or a raw material of an indolin derivative, etc., as a preparation method, 0-aminophenethyl alcohol produced by reduction of 0-nitro phenethyl alcohol with zinc and calcium chloride is phenyl ringed in the presence of hydrochloric acid. The method is known as one method.

However, in this method, phenethyl alcohols are weak to heat, and in the reaction, there is a drawback that by-products of the polymer and deterioration of the catalyst, and high purity indrin could not be obtained in good yield.

The present inventors have conducted various studies on the method of obtaining indolin with high purity and high yield by eliminating the defects of the prior art, and found that the 0-halogen phenethylamine compound can be used as a raw material to achieve the purpose. The invention was achieved.

That is, the present invention in the presence of a cocatalyst and ammonia,

(Where X represents a halogen atom)

It is represented by the above general formula, and is a method of producing indline by ring-closing a 0-halogenphenethylamine compound.

The above process is used in the method of the present invention, and the halogen atoms of the 0-halogen phenethylamines are chlorine, cancelled, arsenic, urea, and practically, for example, 0-chlorophenethylamine, 0-bromine phenethyl The use of amines is preferred.

In addition, the catalyst used in the present invention is a copper catalyst and is acceptable as long as it supplies copper ions to the reaction system. Any of inorganic inorganic compounds or organic acid salts, such as metals, may be used. For example, copper chloride, brittle copper, jade (Iii) copper, nitrous oxide, copper oxide, copper hydroxide, copper cyanide, copper nitrate, lactic acid copper, copper hydroxide, copper acetate. Thus, as the usage-amount of a catalyst, it is good to use 0.1-20 weight% of Cu, Preferably it is 1-5 weight% with respect to a raw material.

The reaction of the present invention proceeds in the presence of ammonia, but is usually carried out in liquid ammonia, aqueous ammonia solution or ammonia-alcohol solution and preferably 2-20 times the raw material, preferably 3-5 times.

Further, the reaction is preferably carried out under pressurization at 200 ° C. or lower, preferably 100-150 ° C., for about 1-4 hours since the reaction temperature is too high to generate a dealkylation reaction by-product.

Subsequently, the result of analyzing the reaction product obtained by using a 0-colol phenethylamine (OCPA) by changing the type of catalyst and the amount of use, changing the amount of ammonia water used, the reaction temperature and the time by gas chromatography method. It is shown to the following table | surface to be followed.

(Cu ₂ O ₄ in the table indicates the second copper acid)

As shown in the table, it is clear that according to the method of the present invention, indolin is obtained in high purity and high yield.

As described above, in the present invention, since 0-halogenphenethylamines are subjected to ring-closure reaction in the presence of a cocatalyst and ammonia, there is no formation of side reaction products as in the conventional method. In addition, the effect of the product can be easily produced with high purity and high yield. Examples are described below.

Example 1

157 g of 0-cololphenethylamine (purity 99.0%) was added to the pressurized reactor with 4.7 g of cuprous chloride (3% as CuCl for raw materials) and 375 g of ammonia water (67.5% as NH ₄ OH for raw materials) as a catalyst. The reaction was carried out at 150 ° C. for 4 hours. After completion of the reaction, the reaction solution was analyzed by gas chromatography.

OCPA 0.1% Indole 3.3% Indorin 95.8%

It was. This solution was distilled off and 106g of pure indorine was obtained. The yield was 89.1% of the theoretical amount.

Example 1

The liquid composition was carried out under the same conditions as in Example 1 except that the starting material was 0-bromphenethylamine.

Raw material 0.1% Indole 3.2% Indorin 95.5%

And the yield of indorin after distillation was 89.7%.

Example 3

The catalyst was made of cupric acid, which was tested under the same conditions as in Example 1.

Raw material 4.7% Indorin 89.0% Indole 2.0%

And the yield of indorin after distillation is 80.1%.

Claims (1)

In the presence of a cocatalyst and ammonia

(In the general formula, X represents a halogen atom.) A process for producing indolin, wherein the 0-halogenphenethylamine compound represented by the above general formula is subjected to a ring-closure reaction.