PL189412B1 - Novel fluorine derivative of isatin and method of obtaining same - Google Patents

Abstract

1. A new fluorine derivative of isatin, with the general formula shown in drawing, constituting an intermediate for manufacturing new fluorine derivatives 1,2-benzi-zothiazol-3- (2H) -one.

Description

The subject of the invention is a new fluoro derivative of isatin of the general formula shown in the drawing and the method of its preparation. The new fluoro isatin derivative of the general formula shown in the figure, which is 4-fluoro-7-methylisatin, is an intermediate for the preparation of new fluorinated 1,2-benzisothiazol-3- (2H) -one compounds with bactericidal activity.

Of the fluorine derivatives, the following are described in the literature: 5-fluoroisatin (VQ Yen, NP Bun-Hoi, ND Xuong: J. Org. Chem. 23 1858 (1958), 6-fluoroisatin (PW Sadler: J.Org. Chem. 21 169) (1956)), 7-fluoroisatin (CS James, RL Wain: Ann. Appl. Biol. 61 295 (1968)) These compounds are obtained by Beckmann rearrangement of the corresponding fluoroisonitrosoacetanilides, carried out in concentrated sulfuric acid at 60-70 ° C C and not exceeding 80 ° C.

The invention solves the problem of obtaining the new 4-fluoro-7-methylisatin derivative in high yield and purity by keeping the reaction temperature low and using acetone to separate its synthesis by-products.

The method of obtaining the new derivative according to the invention is based on the fact that 2-methyl-5-fluoroisonitroacetanilide is cyclized to 4-fluoro-7-methylisatin in concentrated sulfuric acid 96%, with the molar ratio of substrate to sulfuric acid 1: 15-30, preferably 1:25, the reaction is carried out with constant stirring so that the temperature does not exceed 50 ° C, then the reaction mixture is left for 2-4 hours, then heated to 50 ° C, cooled and the reaction solution is poured onto ice , a precipitate is separated, washed with water and dried at room temperature. Then, sufficient acetone to dissolve the isatin is added to the resulting reaction product, 4-fluoro-7-methylisatin, and unidentified by-products are separated, washed with acetone until a colorless acetone filtrate is obtained, then the combined acetone filtrates are concentrated under reduced pressure and the separated product precipitate is purified by recrystallization from a water-ethanol mixture, preferably 40% ethanol.

Carrying out the synthesis of 4-fluoro-7-methylisatin according to the invention allows it to be obtained with considerable yield. Moreover, the purification method used here allows obtaining the compound with chromatographic and spectral purity. The obtained compound according to

The present invention, being 4-fluoro-7-methylisatin, is used as a substrate in the synthesis of new fluorine 1,2-benzisothiazol-3- (2H) -one derivatives exhibiting bactericidal activity.

Example: 19.61 (0.1 mol) of 2-methyl-5-fluoroisonitrosoacetanilide was added to 140 ml of concentrated sulfuric acid 96%. The solution was then left for 4 hours at room temperature, then warmed to 50 ° C and cooled, then poured onto ice, the precipitate was filtered off, washed with water and air dried. 300 ml of acetone was added to the resulting reaction product, which was 4-fluoro-7-methylisatin, and unidentified by-products were separated, which were then washed with acetone. ethanol.

14.9 g (89% yield) of the product with a melting point of 231 ° were obtained. The identity was confirmed by spectral analysis data.

H ¹ -NMR (solution in DMSO) (0, ppm): 2.09, S, 3H, CH; 6.75, m, 1 H, Ar; 7.45, m, 1 H, Ar; 11.26, s, 1H, NH

IR (cm -1): 3195 NH; 1734; 1636 C = 0

Thin layer chromatographic analysis:

Stationary phase: finished plates (Merck) silica gel 40 F, dimensions 5 x 20 cm; layer thickness 0.25 mm.

Mobile phase: chloroform-methanol-acetic acid (90: 9; 1 v / v / v). An acetone solution was applied to the plate. The plate was developed over a distance of 10 cm. The chromatogram was observed in visible light, one spot with R 0.55. Apart from the product spot, no spots were seen under the UV light, which demonstrates the high purity of the compound of the invention obtained.

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Claims (2)

Patent claims 1. A new fluorine derivative of isatin, with the general formula shown in the drawing, being an intermediate for the preparation of new fluorine derivatives of 1,2-benzisothiazol-3- (2H) -one. 2. The method of obtaining a new derivative of fluorine isatin, characterized in that 2-methyl-5-fiuoroisonitroacetanilide is cyclized to 4-fluoro-7-methylisatin in concentrated sulfuric acid 96%, with a molar ratio of substrate to sulfuric acid of 1: 15- 30, preferably 1:25, the reaction being carried out with constant stirring so that the temperature does not exceed 50 ° C, then the reaction mixture is left for 2-4 hours, then heated to 50 ° C, cooled and the reaction solution is poured out. onto ice, a precipitate is separated, washed with water and dried at room temperature, then acetone is added to the resulting reaction product, 4-fluoro-7-methylisatin, in an amount sufficient to dissolve the isatin, and unidentified by-products are separated and washed with with acetone until a colorless acetone filtrate is obtained, then the combined acetone filtrate is concentrated under reduced pressure and the product precipitate is purified by recr crystallization from a water-ethanol mixture, preferably 40% ethanol.