DE1116229B - Process for the preparation of 3-p-aminobenzenesulfonamido-6-hydroxypyridazine and its salts - Google Patents

Description

GERMAN

PATENT OFFICE

C18828IVd / 12p

REGISTRATION DATE: 20 A P R I L 1959

NOTICE THE REGISTRATION ANDOUTPUTE EDITORIAL: NOVEMBER 2, 1961

The invention relates to the production of S-p-aminobenzenesulfonamido-o-hydroxypyridazinjSowie its salts.

The new compound shows good chemotherapeutic properties. She is particularly against, among other things Coli bacteria effective. It can therefore be used as a remedy and prophylactic in humans and animals, especially used in infectious diseases of the intestine. It is like comparative experiments show with regard to their effect against coccidiosis in chicks or against coli infection in the rat intestine Clearly superior to formosulfathiazole.

The new compound is obtained by methods known per se, by making compounds the formula

> —SO ₂ NH-

N = N

> —Y

wherein X is the amino group or a nitro, azo or acylamino group or a halogen atom and Y is a reactively esterified hydroxyl group or a free mercapto group or a substituted one Mercapto or hydroxy group or, when X is a nitro, azo or acylamino group or a halogen atom represents, also means the hydroxyl group itself, in a manner known per se, the nitro, azo or acylamino group or the halogen atom converted into the free amino group and / or the reactive esterified hydroxyl group, the free mercapto group or the substituted mercapto or hydroxyl group hydrolyzed to the free hydroxyl group or p-aminobenzenesulfonamide with 3-halo-6-hydroxypyridazine converts and, if desired, obtained 3-p-aminobenzene sulfonamido - 6 - hydroxypyridazine converted into its salts or obtained salts thereof converted into the free compound.

An acylamino group is especially an acetyl, carbethoxy or dichlorophosphorylamino group.

The reduction, hydrolysis or treatment with ammonia of the nitro, azo or acylamino group or the halogen atom is carried out in a manner known per se, the reduction z. B. with catalytic excited or with nascent hydrogen, as z. B. by the action of metals Acids obtained, hydrolyzing with acidic, but preferably alkaline hydrolyzing Agents such as aqueous alkali or alkaline earth metal hydroxides.

A reactive esterified hydroxyl group is primarily a halogen atom, such as chlorine or bromine.

Method of manufacture

of S-p-aminobenzenesulfonamido-o-hydroxy-

pyridazins and its salts

Applicant:
CIBA Aktiengesellschaft, Basel (Switzerland)

Representative: Dipl.-Ing. E. Splanemann, patent attorney, Hamburg 36, Neuer Wall 10

Claimed priority:

Switzerland of April 28, 1958 (No. 58 876)

and February 19, 1959 (No. 69 785)

Dr. Jean Druey, Riehen,

and Dr. Emil Merz, Bottmingen (Switzerland),

have been named as inventors

A substituted hydroxy or mercapto group is e.g. B. an alkoxy or alkyl or benzyl mercapto group.
The conversion of Y into the free hydroxyl group happens, for. B., if Y is a halogen atom such as chlorine or bromine, by treatment with alkaline saponifying agents such as aqueous alkali. If Y is a free mercapto or substituted oxy or mercapto group, this is by hydrolysis, in the case of a free or substituted mercapto group, for. B. converted into the oxy group by treatment with aqueous acidic or alkaline agents.

A preferred embodiment of this process consists in that 3- (p-aminobenzenesulfonamido) -6-chloropyridazine with alkaline agents, e.g. B. aqueous sodium hydroxide solution treated.

In the implementation of p-aminobenzenesulfonamide with 3-halo-6-oxy-pyridazine, the p-aminobenzenesulfonamide is advantageously used in the form of a Metal salt, such as an alkali salt, or one works in the presence of such salts-forming basic condensing agents, such as B. anhydrous potash.

In the abovementioned processes, the starting materials can also be used under the reaction conditions formed or used after their manufacture without insulation. So it is z. B. possible p-aminobenzenesulfonamide with 3,6-dichloro- or 3,6-dibromo-

109 737/396

to implement pyridazine and hydrolyze the reaction product without isolation, or 3- (p-aminobenzene sulfonamido) -6-chloro or -bromopyridazine to convert into the 6-alkoxy or alkylmercapto compounds, from which, depending on the reaction conditions in the presence of hydrolyzing agents, 3- (p-aminobenzenesulfonamido) -6-oxy-pyridazine can arise.

From the new sulfonamide let yourself be in the usual Wise to win salts, such as the alkali, alkaline earth, e.g. Calcium or magnesium or aluminum salts.

The starting materials are known or can be obtained by methods known per se.

The sulfonamide obtained according to the process can as a remedy z. B. find use in the form of pharmaceutical preparations. These contain the new Substance, optionally in the form of its salts, mixed with one for entoral, parenteral or local Application of suitable pharmaceutical organic or inorganic carrier material.

The new sulfonamide can also be mixed with animal feed, ζ. B. poultry feed, or mixed with the usual extenders and thinners are used as animal feed additives.

The invention is illustrated in the following examples without intending to limit the subject matter of the invention.

example 1

143 g of 3- (p-aminobenzenesulfonamido) -6-chloropyridazine are heated to 100 to 105 ° C. for 24 hours with the addition of 900 g of 30% strength sodium hydroxide solution and 600 cm ^{3 of water.} After cooling to 20 ⁰ C and filtration with Klärkohle precipitating the product by stirring the reaction solution alkaline in 700 g of glacial acetic acid. The precipitated 3- (p-aminobenzenesulfonamido) -6-hydroxypyridazine is recrystallized from glacial acetic acid after suction, washing with cold water and drying. It melts at 243 to 244 ° C. It can be converted into its alkali, alkaline earth or aluminum salts in the usual way.

Example 2

By heating 15.7 g of 3- (p-nitrobenzenesulfonamido) -6-chloropyridazine in 90 g of 30% sodium hydroxide solution and 60 cm ^{3 of} water to 100 to 106 ° C. for 24 hours, cooling, filtering with clarified charcoal, pouring the filtrate The 3- (p-nitrobenzenesulfonamido) - 6-hydroxypyridazine obtained is ^{hydrogenated in 600 cm 3 of} glacial acetic acid at room temperature with 10% palladium-carbon as a catalyst. After the theoretical amount of hydrogen has been consumed, the catalyst is suctioned off while hot and evaporated in vacuo. The residue is recrystallized again from glacial acetic acid. The 3- (p-aminobenzenesulfonamido) -6-hydroxypyridazine described in Example 1 is obtained in this way with a melting point of 243 to 244 ° C.

Example 3

A solution of 15 g of 3- (p-aminobenzenesulfonamido) -6-methylmercaptopyridazine in 90 g of 30% strength sodium hydroxide solution and 60 cm ^{3 of} water is heated to 100 to 105 ^{° C. for 24 hours.} After cooling to 2O ⁰ C and filtration with Klärkohle precipitating the product by stirring the reaction solution alkaline in 70 g glacial acetic acid. The precipitated 3- (p-aminobenzenesulfonamido) -6-hydroxypyridazine is recrystallized from glacial acetic acid after suction, washing with cold water and drying. It melts at up to 244 ° C and is identical to the product obtained in Example 1.

Example 4

A solution of 17 g of 3- (p-acetylaminobenzoI-sulfonamido) -6-chloropyridazine in 90 g of 30% sodium hydroxide solution and 60 cm ^{3 of} water is heated to 100 to 105 ° C. for 24 hours. After cooling to 2O ⁰ C and filtration with Klärkohle precipitating the product by stirring the reaction solution alkaline in g glacial acetic acid. The precipitated 3- (p-aminobenzenesulfonamido) -6-hydroxypyridazine is recrystallized from glacial acetic acid after suction, washing with cold water and drying. It melts at 243 to 244 ° C and is identical to the product described in Example 1.

Claims (2)

Patent claims: 1. Process for the preparation of 3-p-aminobenzene sulfonamido-6-hydroxypyridazine and its Salts, characterized in that compounds of the formula I -SO ₉ NH- N = N -Y (D wherein X is the amino group or a nitro, azo or acylamino group or a halogen atom and Y denotes a reactive esterified hydroxyl group or a free mercapto group or a substituted mercapto or hydroxy group or, when X is a nitro, azo or Represents acylamino group or a halogen atom, also means the hydroxyl group itself, in an known way the nitro, azo or acylamino group or the halogen atom in the Free amino group transferred and / or the reactive esterified hydroxyl group, the free Mercapto group or the substituted mercapto or hydroxyl group to the free hydroxyl group hydrolyzed or p-aminobenzenesulfonamide with 3-Halo-6-hydroxypyridazine reacted and, if desired, obtained 3-p-aminobenzenesulfonamido-6-hydroxypyridazine converted into its salts or obtained salts thereof converted into the free compound. 2. The method according to claim 1, characterized in that the starting materials under the Reaction conditions are formed or used after their preparation without isolation will. When the registration was announced, 3 pages of the test report were laid out. © 109 737/396 10.61