Method of producing a sodium salt of (2,6-dichlorophenyl)amide carbopentoxysulfanilic acid

Abstract

The invention relates to the field of organic chemistry and medicine, and more particularly to a method of producing synthetic biologically active derivatives of carbopentoxysulfanilic acid. The present method of producing a sodium salt of (2,6-dichlorophenyl)amide carbopentoxysulfanilic acid is characterized in that the reaction mass formed during the production of (2,6-dichlorophenyl)amide carbopentoxysulfanilic acid is agitated in a medium which is acidified with a solution of hydrochloric acid to pH 5-5.5, and the isolated precipitate may be washed with water acidified with a solution of hydrochloric acid to pH 5-5.5. This increases the yield of a sodium salt of (2,6-dichlorophenyl)amide carbopentoxysulfanilic acid to 70% (compared to a prior art yield of 32%) and also increases the purity of the target sodium salt.

Claims

1. A method of preparing a sodium salt of the (2,6-dichlorophenyl)amide of carbopentoxysulfanilic acid having the structure ##STR00006## comprising the steps of: (a) combining 2,6-dichloroaniline and pyridine; (b) adding carbopentoxysulfanilic acid chloride having the structure ##STR00007## to the mixture of step (a), acidifying the resultant mixture with a solution of hydrochloric acid to a pH of 5 to 5.5, and segregating, washing, and drying a solid precipitate, and (c) combining the solid precipitate of step (b) with sodium hydroxide in ethyl alcohol solution, removing ethyl alcohol by distillation, followed by isolating and drying the sodium salt of the (2,6-dichlorophenyl )amide of carbopentoxysulfanilic acid as a solid precipitate.

2. The method of claim 1 wherein the overall yield of the sodium salt of the (2,6-dichlorophenyl)amide of carbopentoxysulfanilic acid is 56%.

3. The method of claim 1, wherein the solution of hydrochloric acid is an aqueous solution of hydrochloric acid.

4. The method of claim 1, wherein the carbopentoxysulfanilic acid chloride is added in portions at a temperature of 85 C.

5. The method of claim 1, wherein the mixture of step (b) is stirred at 80 C. for 45 minutes prior to acidifying the mixture with a solution of hydrochloric acid to a pH of 5 to 5.5.

6. The method of claim 5, wherein the mixture is cooled to room temperature after acidifying.

7. The method of claim 1, wherein water is added to the mixture of step (b) prior to acidifying the resultant mixture with a solution of hydrochloric acid to a pH of 5 to 5.5.

8. The method of claim 1, wherein the solid precipitate of step (b) is recrystallized prior to step (c).

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) In the following, the invention will be explained with a detailed description of examples of its implementation with reference to the drawings, which specify the following:

(2) FIG. 1 shows the proton magnetic resonance spectrum of the sodium salt of (2,6-dichlorophenyl) amide of carbopentoxysulfanilic acid.

(3) FIG. 2 shows the ultraviolet spectrum of the sodium salt of (2,6-dichlorophenyl) amide of carbopentoxysulfanilic acid.

(4) FIG. 3 shows the infrared spectrum of the sodium salt of (2,6-dichlorophenyl) amide of carbopentoxysulfanilic acid.

PREFERRED EMBODIMENT

(5) The preparation of the sodium salt of (2,6-dichlorophenyl) amide of carbopentoxysulfanilic acid by the method of the invention is illustrated by an example.

(6) Phenyl isocyanate (11.5 g-0.096 mol) was mixed with pentanol (amyl alcohol) (8.5 g-0.096 mol), the reaction mass was heated, and after 1 hour the mixture solidified in the form of colorless crystals. Amyl ester of carbamic acid was obtained; the yield was about 100%.

(7) To chlorosulfonic acid (17.5 g to 0.150 mol) heated to 30 C., amyl ether of phenylcarbamic acid (2.07 g-0.010 moles) was slowly added while stirring, maintaining the temperature of the reaction mass at a level no higher than 35 C. Then the mixture was slowly heated to 50 C. and kept at a temperature of 50-55 C. for 2 hours. The resulting sulphomass was poured onto ice while stirring, keeping the temperature below 20 C. The precipitate was filtered off, washed with ice water up to the pH of filtrate 7, dried in air and then in a desiccator. Carbopentoxy sulfanilic acid chloride was obtained as a result; the yield was about 100%.

(8) To a mixture of 2,6-dichloroaniline (2.2 g to 0.0136 mol) and pyridine (3.23 g-0.0406 mol) carbopentoxysulfanilic acid chloride (6.2 g-0.0203 mol) was added in portions at the temperature of 85 C.; the reaction mass was stirred at 80 C. for 45 minutes. Then 20 ml of hot water were added to the mass, the mixture was acidified with hydrochloric acid to pH 5-5.5 and cooled to the room temperature. The resulting precipitate was filtered off, washed with water acidified with hydrochloric acid solution to a pH of 5-5.5, until the odor of pyridine disappeared, and dried. After recrystallization, the yield of the resulting (2,6-dichlorophenyl)amide of carbopentoxysulfanilic acid was 4.4 g-70%.

(9) Further, 0.232 g of sodium hydroxide (NaOH) were dissolved in 5 ml of ethyl alcohol (C.sub.2H.sub.5OH), and 4.4 g of (2,6-dichlorophenyl)amide of carbopentoxysulfanilic acid were dissolved in 30 ml of ethyl alcohol (C.sub.2H.sub.5OH). Then, the two solutions were mixed and stirred for 20 minutes, after which the ethyl alcohol was distilled off under vacuum. The remaining precipitate was dried. The final product, the sodium salt of (2,6-dichlorophenyl)amide of carbopentoxysulfanilic acid, was obtained; the yield of the product was 3.6 g-80%.

(10) The yields of the intermediate products and the final product at the individual stages were 100, 100, 70 and 80%, respectively. Thus, the total yield of sodium salt of (2,6-dichlorophenyl)amide of carbopentoxysulfanilic acid was 56%.

(11) The individuality of the target product is proved by thin-layer chromatography on Silufol UV-254 plates, carbon tetrachloride-isopropanol eluent=2:1. No impurities were detected.

(12) The structure of the synthesized product is proved by the methods of proton magnetic resonance (NMR), ultraviolet (UV) and infrared (IR) spectroscopy.

(13) The characteristic signals in the NMR spectrum are the singlet of NH group in the range of 9.7 ppm and the multiplet in the range of 6.57.5 ppm (FIG. 1).

(14) The ultraviolet absorption spectrum of the solution obtained in the range from 200 to 380 nm has a maximum of 2472 nm with an arm of (2752 nm) (FIG. 2).

(15) The characteristic absorption bands in the IR spectrum are shown in FIG. 3 (vibrations of the CH bond in the 3600.sup.cm1 range, NH in the 2900 cm.sup.1 range, CO-1700 cm.sup.1).

INDUSTRIAL APPLICABILITY

(16) The invention is implemented using common materials and equipment, resulting, according to the applicant's opinion, in compliance of the invention with the Industrial Applicability (IA) patentability criterion.