DE1119869B - Process for the preparation of N- (p-aminobenzenesulfonyl) -N-acetyl-5-amino-1-phenyl-pyrazole - Google Patents

Description

GERMAN

PATENT OFFICE

REGISTRATION DAY:

C18366IVd / 12p

FEBRUARY 9, 1959

NOTICE THE REGISTRATION AND ISSUE OF THE EDITORIAL: DECEMBBR 21, 1961

The invention relates to the preparation of N- (p-aminobenzenesulfonyl) -N-acetyl-5-amino-1-phenyl-pyrazole the formula

HC CH

4 3

CH ₃

C ₈ H ₅

The new compound is obtained if you have a 5 - (Benzolsulfonamido) -1 -phenyl - pyrazole of the general formula

HC CH

C ₆ H ₅

in which R denotes the amino group or a radical which can be converted into this by reduction, in a manner known per se Way Ni-acetylated and then in Compounds with a radical R which can be converted into the amino group and these into the free amino group converts.

A radical which can be converted into the amino group by reduction is e.g. B. the nitro or azo group or an acylamino group which can be cleaved by hydrogenolysis, such as the carbobenzoxyamino group. The reduction is carried out in a manner known per se, expediently avoiding hydrolyzing conditions and higher temperatures, in order to avoid cleavage or rearrangement of the Nj _{-acetyl radical to the N 4} nitrogen atom. Reduction with hydrogen in the presence of catalysts such as noble metal catalysts, e.g. B. Palladium on charcoal.

The Nj-acetylation is carried out in the usual way Use of Nj-acetylating agents carried out. Such are especially the acid anhydrides or -halides, such as -chloride. The reaction is expedient in the presence of basic agents, such as inorganic ones or organic bases, e.g. B. alkali carbonates, or tertiary amines such as pyridine, picoline, lutidine, Collidine, trimethylamine, triethylamine, tributylamine or 1,6-bis-dimethylamino-hexane, and in the presence inert diluents, especially organic solvents such as dioxane, benzene, toluene, halo-Verf ears for production

des N- (p-aminobenzenesulfonyl) -

N-acetyl-5-amino-1-phenyl-pyrazoles

Applicant:

CIBA Aktiengesellschaft, Basel (Switzerland)

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

Claimed priority:
Switzerland of February 18, 1958 (No. 56 002)

Dr. Jean Druey, Riehen,

and Dr. Paul Schmidt, Therwil (Switzerland),

have been named as inventors

gened hydrocarbons, e.g. B. methylene chloride or chloroform, dimethylformamide, lower aliphatic Ketones, such as acetone or methyl ethyl ketone, or optionally the basic agents itself, e.g. B. pyridine or mixtures thereof, such as especially pyridine-acetone carried out. Advantageous one works in a medium that is as water-free as possible. If an acid halide is used, one can also a metal salt of sulfonamide, e.g. B. an alkali salt or, better, the silver salt, use, whereby the addition of basic agents recommended above is unnecessary. Your additional use, e.g. B. as Thinner, but nothing gets in the way.

When using 5- (p-aminobenzenesulfonamido) -1-phenyl-pyrazole, care must be taken that the reaction is carried out under mild conditions and using approximately equimolecular amounts of the reactants in order to avoid that the N _x , N ₄ - Bis-acetyl compound or the N ₄ -acetyl compound is formed by acyl migration. It is therefore advantageous to work at a low temperature, e.g. B. below 40 ⁰ C, such as between 10 and 30 ° C, and in an anhydrous medium. When using the acid halides, it is advisable to start from the metal salts of the sulfonamide, such as the silver salt.

The new compound has valuable chemotherapeutic properties. She has a strong and long lasting effect against streptococcal sepsis

109 750/549

of the mouse and also shows "very good activity against Coli bacteria in the urine and in the intestine. In addition it is practically free of unpleasant taste qualities, as often attached to sulfonamides, and can therefore be used to advantage in the manufacture of tablets and syrups.

The invention is described in the following example. The temperatures are given in degrees Celsius.

example

IO

In a flask equipped with a stirrer and thermometer, 32 g of 5- (p-amino-benzenesulfonamido) -1-phenyl-pyrazole are dissolved in 80 cm ^{3 of} acetone and 16 cm ^{3 of} dry pyridine at 20 to 25 °. While stirring, 11 g of acetic anhydride are added over the course of 10 minutes. The mixture is stirred for 5 hours and the mixture is left to stand for 10 hours. It is cm ig ^it added under stirring 100 ³ 3% aqueous ammonia and some fresh ice, after which an oily product precipitates. It is mixed with 500 cm ^{3 of} water and left to stand for 10 hours at room temperature, the oil formed gradually crystallizing. The N- (p-aminobenzene-sulfonyty-N-acetyl-S-amino-1-phenyl-pyrazole thus obtained is recrystallized from ethanol and is thus obtained in white crystals with a melting point of 178 ° to 180 °.

Claims (7)

PATENT CLAIMS: 30 1. Process for the preparation of N- (p-aminobenzenesulfonyl) -N-acetyl-5-amino-1 - phenyl-pyrazoles of the formula H ₉ N- HC CH 1 3 -SO ₂ -NC N CO CH ₃ 1/ C «H, 40 characterized in that a 5- (benzene- 45 sulfonamido) -l-phenyl-pyrazole the general
formula HC CH CrHc in which R denotes the amino group or a radical which can be converted into this by reduction, in an known way Νχ-acetylated and then in compounds with a radical R convertible into the amino group, converts this into the free amino group. 2. The method according to claim 1, characterized in that acylation is carried out with acetic anhydride. 3. Process according to Claims 1 and 2, characterized in that the reaction is carried out in Carries out the presence of a basic agent. 4. Process according to claims 1 to 3, characterized in that the reaction is carried out in Presence of an inert organic solvent under essentially anhydrous conditions performs. 5. Process according to claims 1 to 4, characterized in that the reaction is carried out in Performs acetone in the presence of pyridine. 6. Process according to claims 1 to 5, characterized in that when using des 5 - (p - aminobenzene sulfonamido) -1 - phenylpyrazole approximately equimolecular amounts of the Respondent used. 7. Process according to Claims 1 to 6, characterized in that the acylation is carried out when using 5- (p-aminobenzenesulfonamido) -l-phenyl-pyrazole at a low temperature performs. Considered publications:
German Patent No. 952 809;
British Patent No. 788 140;
HeIv. chim. Acta, 41 [1958], pp. 306-309;
Swiss medical weekly,
[1958], pp. 835 to 839 and 858 to 863. © 109 750/5 «12.