SU399107A1 - - Google Patents

Description

METHOD OF OBTAINING

Heterocyclic Carboxylic Acids

one

This invention relates to a process for the preparation of new compounds - heterocyclic carboxylic acids of formula I

COOH10

where R is lower alkyl;

X is an atom of oxygen, sulfur, imino- or methyliminohydrin;

Y is an atom of hydrogen, fluorine, chlorine, bromine or methyl,

Zj and 7-2 are hydrogen, fluorine, chlorine, bromine, lower alkyl or alkoxy groups,

or their salts, which are used as biologically active substances in the manufacture of pharmaceuticals.

The method is based on the well-known in organic synthesis of the reaction of splintered alkylsulfinic acid under the action of aqueous alkali on sulfone.

The proposed method for the preparation of compounds of formula I is that the compound of formula I

CH-5Pg-P. I hch / zt y

R-.-IH-r-.fi

where R, X, Y, Zi and Z2 are the indicated values and Kg is lower alkyl,

boil in a hydroxyl-containing solvent in the presence of a weak base to isolate the target product or salt it in the usual manner.

As weak bases, solutions of acetate acetate or sodium hydroxide or sodium carbonate are used, and as

aliphatic solvents are used in water and in acids;

Compound general formula

II can be obtained action :, hydrogen peroxide or

peracid, iiaopHJicp peracetic acid, in the presence of an organic solvent, e.g. secondary -amino groups to a sulfide radical.

The derived compound Mannich is obtained by starting from the corresponding heterocyclic carboxylic acid by alkylation according to the Friedel-Crafts reaction to position 5 in nitrobenzene with aliphatic carboxylic acid chloride and the subsequent action of formaldehyde or paraformaldehyde on a secondary organic base.

Example.

A. To 6-methyl-5- 2- {methylsulfonylmethyl) butyryl-benzofuran-2-carboxylic acid, 10 ml of water and 5 ml of a saturated solution of sodium hydrogen carbonate are added and the resulting solution is boiled for 1.5 hours . After this time has elapsed, the reaction mixture is cooled, acidified with concentrated hydrochloric acid to a pH of 2-3, stirred for 30 minutes, the crystals precipitated as a result of acidification are filtered, dried under vacuum and recrystallized from benzene. After recrystallization, 0.5 g of 6-methyl-5 (2-methylenebutyryl) -benzofuran-2-carboxylic acid, m.p. 141 - 142 ° C.

B. The 6-methyl-5-2- (methylsulfonylmethyl) -butyryl-benzofuran-2-carboxylic acid used as starting compound is prepared as follows.

6.8 g of 6-methyl- (dimethylaminomethyl) -butyryl-benzofuran-2-carboxylic acid hydrochloride (m.p. 187-188 ° C) is dissolved in 200 ml of water, 4.04 g of carbonic acid are added in portions sodium, a continuous current of methyl mercaptan is passed through the solution while the temperature of the reaction mixture is raised to 90 ° C and maintained at this temperature for 2 hours. After the indicated period of time, methyl mercaptan is stopped to pass, the resulting solution is cooled and the pH of the solution is adjusted to 2-3 with concentrated hydrochloric acid. The precipitated as a result of acidification with concentrated hydrochloric acid is filtered off, dried in vacuo and recrystallized from a small amount of ethyl ester of acetic acid. After recrystallization, 5.2 g of 6-methyl-5- 2- (methylthiomethyl) -butyryl-benzofuran-2-carboxylic acid, m.p. 151 - 150 ° C.

3.1 g of 6 - methyl - - (methylthiomethyl) -butyryl-benzofuran-2 - carboxylic acid are suspended in 15 ml of glacial acetic acid. The resulting suspension is dropwise mixed with 3.6 g of 40% peracetic acid under ice cooling in such a way that

the temperature of the reaction mixture remained constant and was 15–20 ° C. Then the reaction mixture is stirred for 15 hours at room temperature, the precipitated crystalline mass is filtered off. 6-methyl-5- 2- (methylsulfonylmethyl) -butyryl-benzofuran-2-carboxylic acid is obtained, which, after recrystallization from a mixture of solvents consisting of ethyl acetate and dioxane, m.p. 201-203 ° C.

The following compounds are prepared analogously:

5- (2-methylenebutyryl) -benzofuran-2-carboxylic acid, so pl. 128-129 ° C.

3,4-dichloro-5- (2-methylenebutyryl) -benzofuran-2-carboxylic acid, so pl. 210-211 ° C.

1-methyl-3,4-dichloro-5- (2-methylenebutyryl) indole-2-carboxylic acid, so pl. 163-164 ° C;

4 - methyl - 5- (2 - methylenebutyryl) - benzofuran-2-carboxylic acid, so pl. 159-160 ° C;

6-methyl-5- (2-methylenebutyryl) -benzofuran-2-carboxylic acid, so pl. 141 - 142 ° C.

4,6-dimethyl-5- (2-methylenebutyryl) -benzofuran-2-carboxylic acid, so pl. 208-210 ° C;

4-chloro-5- (2-methylenepropionyl) -benzothiophene-2-carboxylic acid, so pl. 239-241 ° C;

6-methyl-5- (2 - methylenepropionyl) - benzofuran-2-carboxylic acid, so pl. 185-186 ° C;

6-methyl-5- (2-methylenevaleroyl) -benzofuran-2-carboxylic acid, so pl. 160-162 ° C;

6-methyl-5- (2-methylene-3-methylbutyryl) benzofuran-2-carboxylic acid, so pl. 153-154 ° C;

6-methoxy-5- (2 - methylenepropionyl) - benzofuran-2-carboxylic acid, so pl. 169-170 ° C;

6-methoxy - 5- (2-methylenebutyryl) -benzofuran-2-carboxylic acid, so pl. 153-156 ° C;

6-ethoxy-5- (2-methylenebutyryl) -benzofuran-2-carboxylic acid, so pl. 143-144 ° C;

6-ethyl-5- (2-methylenebutyryl) benzofuran-2-carboxylic acid, so pl. 121 - 122 ° C;

6-chloro-5- (2-methylenebutyryl) -benzofuran-2-carboxylic acid, so pl. 188-189 ° C;

4-chloro-5- (2-methyle.nbutiryl) -benzofuran2-carboxylic acid, so pl. 156-158 ° C;

3,6-dimethyl - 5- (2 - methylenebutyryl) -benzofuran-2-carboxylic acid, so pl. 153-154 ° C.

Subject invention

The method of obtaining heterocyclic carboxylic acids of the formula I

SNS

//

R-C-CO- /

-2- -V y- COOH

where R is lower alkyl;

X is an oxygen atom, sulfur, iminotil imino group;

Y is a hydrogen, fluorine, chlorine or methyl atom; Zi and Z2 - ma, lower

where R, X, Y, Zi and Zg have the indicated meanings and R2 is lower alkyl,

boil in a hydroxyl-containing solvent in the presence of a weak base to isolate the target product or salt it in the usual manner. a hydrogen atom, fluorine, chlorine, a broalkyl or alkoxy group, JH —SOs — R. R-CH-CO-T / or their salts, characterized in that the compound of formula II