SK75394A3 - Method of indoles producing - Google Patents

Abstract

In the prepn. of indoles (I) by decarboxylation of the corresp. indole-2-carboxylic acid (II), (II) is treated with HCOOH. Pref., (II) is treated with HCOOH contg. 0-50 vol. % water and heated 1-10, pref. 2-4 hrs. at 20-107, pref. 80-107 deg. C.

Description

Technical field

The invention relates to a novel process for the production of indoles by decarboxylation of the corresponding indole-2-carboxylic acids.

BACKGROUND OF THE INVENTION

The decarboxylation of indole-2-carboxylic acids was conveniently carried out by heating a solution of indole-2-carboxylic acid in a high-boiling tertiary amine to reflux (see, for example, Houben-Weyl) Mttller, Methoden der organischen Chemie; 1952, vol. 8, page 486].

Thus, 4- (5-methoxy-3-indolyl) butyric acid, intermediate (1), which is an intermediate in roxoxole synthesis, has hitherto been prepared by heating a solution of 3- (3-carboxypropyl) -5-methoxyindole-2-carboxylic acid, 3a, zlúčenina, Ν-dimethyaniline or N, N-diethylaniline at 190 ° C for 24 hours.

The disadvantage of this method is the high reaction temperature, which entails problems with the instrumentation and production is possible only in a small number of devices. Another disadvantage is also the long reaction time and hence the high energy consumption.

SUMMARY OF THE INVENTION It is an object of the present invention to provide a novel process for the production of indoles, in particular of compound (1), which does not have the above-mentioned disadvantages or to a lesser extent.

SUMMARY OF THE INVENTION

It has been found that heating a solution of compound (11) in formic acid results in a high yield of compound (1).

- 2 It is surprising because the indoles themselves are considered to be more labile to acids. This has also been shown in attempts to replace formic acid with acids other than acetic acid, dilute sulfuric acid or dilute hydrochloric acid. Either there was no reaction at all, or compound (1) was produced only in low yield with formation of by-products.

The process of the invention can also be used with other indole-2-carboxylic acids with good results.

The present invention provides a process for the preparation of indoles by decarboxylation of the corresponding indole-2-carboxylic acids, characterized in that the corresponding indole-2-carboxylic acid is reacted with formic acid.

This process uses formic acid, which preferably contains 0 to 50% water. The reaction temperature is between 20 and 107 ° C, preferably 80 and 107 ° C. At higher temperatures, a reaction time of about 1 to 10, preferably 2 to 4 hours, is required, while lower temperatures correspond to longer times.

The percentages given below are percentages by volume.

DETAILED DESCRIPTION OF THE INVENTION

Example 1

A mixture of 14.2 g of compound (11) and 120 g of 77.4% formic acid is boiled for 3 hours, then the mixture is evaporated under reduced pressure. Dilute sodium hydroxide was added to the residue. The mixture was briefly clarified with activated carbon at 40 ° C and chloic acid precipitation was performed

- 3 hydrogen to pH 1.5. The precipitated compound (1) is filtered off, washed with water and dried under reduced pressure at 50 ° C. yield:

10,9 g.

Example 2

The procedure is as described in Example 1, but using 100% formic acid. Required reaction time: 2 hours.

Example 3

The procedure is as in Example 1, but using 50% formic acid. Reaction time: 5 hours.

P r? d 1 and d 4 He works Response time: The reaction is carried out as in Example 1, but at a temperature of 80 ° C. 30 hours. Example 5 Similar to Example 1, -2-carboxylic acid. it is possible to obtain indole from indole-

P /

Claims (1)

PATENT PACKAGE A process for the preparation of indoles by decarboxylation of the corresponding indole-2-carboxylic acids, characterized in that the corresponding indole-2-carboxylic acid is reacted with formic acid.