SU334694A1 - METHOD FOR OBTAINING HETEROCYCLIC CARBONIC ACIDS - Google Patents

Description

It is proposed to produce new compounds - heterocyclic carboxylic acids of the formula I: 1 / M R-alkyl with 1-6 carbon atoms; X is an oxygen or sulfur atom; YI and Y2 are hydrogen or methyl; Zi and Z2 are a hydrogen, fluorine, chlorine or bromine atom, methyl, ethyl, methoxy or oxy group, or their salts. These compounds have valuable pharmacological properties. where X, YI, UZ, Zi and Za have the above values, are acylated with anhydride or hectare, a carboxylic acid anhydride of the formula P1: CHa II R - C - COOH, where R has the above values, with the isolation of the target product or its conversion into salt by conventional methods . As the carboxylic acid halide and the advantages, chlorides of bromoanhydrides are used. The reaction is carried out in the presence of Friedel-Crafts catalysts, for example aluminum chloride, chlorine) tetravalent tin, zinc chloride, concentrated sulfuric, phosphoric, polyphosphoric or pyrophosphoric acid. Acids are most often used if the acylating agent is a carboxylic anhydride. The reaction proceeds better in solvents, for example aliphatic or cycloaliphatic hydrocarbons, such as heptane or cyclohexane, or a nitrocarboxyde, such as nitromethane, nitrocyclohexane or nitrobenzene, halocarbons, such as carbon tetrachloride, ethylene chloride, a chloro-carbon, ethylene chloride, and a halogen hydrocarbons, such as carbon tetrachloride, ethylene chloride, nitro-benzene, or carbon tetrachloride. in carbon disulfide.

The initial soybean, dinene of formula II, where X is an atom of 1kplorada, can be prepared using substituted 2-allylphenolenes, for example, as follows.

Substituted 2-allylphenols are oxidized by peracetic acid. The resulting 2- {2,3-epoxypropyl) phenolenes are converted by heating to the corresponding 2,3-dig11dro-2-hydroxymethylbenzofurans, which are then oxidized to the corresponding 2,3-digndro-6-chlorobenzofuran-2carboxylic acids. So, 2,3-digndro-6-chlorobenzo-furan-2-carboxylic acid is obtained from 2-allyl-5-chlorophenol to form intermediate products: 2- (2,3-epoxypropyl) 5-chlorophenol and 2,3 -digndro-2-hydroxymethyl-6chlorobenzofuran.

Compounds of formula II can also be obtained by reducing the substitution of benzofuran-2-carboxylic acids, as appropriate, for example, with sodium amalgam. For example, 2,3-dihydro-6-methylbenzofurap-2carboxylic acid is obtained by reducing 6-methylbenzene-furan-2-carboxylic acid.

Compounds of the formula II, where X is a sulfur atom, are obtained analogously by reducing sodium amalgam with the correspondingly substituted benzo-b-tiofep-2-carboxylic acids, which are formed, for example, by carboxylation of the benzo- & - tions. Substituted benzo-6-thiophen-2-carboxylic acids are also obtained by transferring the respectively substituted o-halobenzaldehydes to 5- (halogen benzylidene) rhodanine by boiling the latter with caustic soda and, if necessary, further heating with sodium methoxide in diethylene glycol to 150 -160 ° C.

For the preparation of these salts, these acids are intermixed with organic or organic compounds.

inorganic bases, for example, alkali or alkaline earth metal hydroxides, carbonates or bicarbonates, triethanols or choline. Example 1. 25.2 g of 2,3-digdro-6-methylbenzof) fan-2-carboxylic acid are mixed with 135 ml of nitrobenzene and 69.5 g of aluminum chloride are added in 30 minutes while moving and cooling in portions, so that that the reaction temperature does not exceed

10 ° C. At the same temperature, 25 g of 2-methylenebutyl chloride are introduced in half an hour into the mixture by stirring and the whole is stirred for 5 hours in an ice bath, and then 16 hours at room temperature. Next, the mixture is poured on 500 g

 THE ACIDS And are extruded with ether, the ether solution is extracted with sodium bicarbonate solution, the aqueous solution is acidified with hydrochloric acid to a pH of 1 and extracted with ether. The 2,3-dihydro-5- {2-methylenebutyryl) -b-methylbenzofuran-2-carboxylic acid obtained after evaporation of the ether extract is purified by chromatography on a column. T. pl. acids 100-104 0.

Example 2. According to example 1, 2,3-dihydro-6-methylbenzofurap-2-carboxylic acid is nitrated in nitrobenzene in the presence of aluminum chloride with 2-methacrylic acid anhydride to form 2,3-dihydro-5- (2-methyl acrylyl) -6 -m-elbenzofurai-2-carboxylic acid, having so pl. 100-102 ° C.

A | nalogich; HY1M get the compounds listed in the table (in iBcex cases Y2 is hydrogen).

Subject invention

The method of obtaining heterocyclic carboxylic acids of the formula I:

CH,

II Z. Y R — C — CO — r S — —f — H

X Choon.

where R is alkyl with 1-6 carbon atoms;

X is an oxygen or sulfur atom; YI and Va - hydrogen atom or methyl; Zi and 1h is a hydrogen, fluorine, chlorine or bromine atom, methyl, ethyl, methoxy or ethoxy group, or their salts, characterized in that the compound of formula II:

ten

15

soon

II

20 where X, U2B2, Zi and Zg are as defined above, they are acylated by Friedel Crafts reaction with anhydride or carobonic acid halide of formula III:

CHj

II

R-C-COOH, III

where R has the above meanings, with isolation of the desired product or salt conversion by conventional methods.