DE1189549B - Process for the preparation of the fungistatically active 5, 7-dibromo-8-benzoyloxyquinoline - Google Patents

Description

GERMAN

PATENT OFFICE

EDITORIAL

German class: 12 ρ-1/10

Number:
File number:
Registration date:
Display day:

1189 549
S73190IVd / 12p
March 28, 1961
March 25, 1965

The inventive method for production the fungistatically active compound 5,7-dibromo-8-benzoyloxyquinoline is characterized in that 5,7-dibromo-8-hydroxyquinoline is used in a manner known per se

a) with benzoic anhydride at elevated temperature in the presence of pyridine or sulfuric acid or

b) with benzoyl chloride or a mixture of benzoyl chloride and benzoic anhydride in Presence of an inert organic solvent and a tertiary amine

implements.

The process is for example performed so that S ^ S-dibromo-oxyquinoline with benzoic anhydride in the presence of concentrated sulfuric acid or pyridine to a higher temperature is preferably 130, heated to 160 ⁰ C. The reaction solution is then poured onto ice either directly or after the excess acylating agent has been distilled off. After filtering off with suction and washing with water, the corresponding ester is obtained. If benzoyl chloride or a mixture of benzoyl chloride and benzoic anhydride is used, then the 5,7-dibromo-8-oxyquinoline and the acylating agent are dissolved in an inert organic solvent, e.g. B. benzene, toluene, xylene, methylene chloride, ethylene chloride, carbon tetrachloride and pyridine or triethylamine or dimethylaniline, dissolved or slurried. The solution or mixture of the reactants is stirred at room temperature or at an elevated temperature, preferably at the boiling point temperature of the solvent used. Finally, the ester formed is isolated and purified by known methods.

The benzoyl ester of 5,7-dibromo-8-oxyquinoline prepared by the process is a solid base. He is characterized by therapeutically utilizable pharmacodynamic properties in that it has an increased Has effectiveness against pathogenic fungi and other pathogens. The new connection should be used as a disinfectant. It also serves as an intermediate product for manufacture of fungicides and medicines. In the example below, the melting point is in degrees Celsius and given uncorrected.

example

5,7-dibromo-8-benzoxyquinoline

To a suspension of 60.6 g of 5,7-dibromo-8-oxyquinoline (melting point 195 ° to 197 °), 16.0 g of pyridine and a method for producing the fungistatic
effective 5,7-dibromo-8-benzoyloxyquinoline

Applicant:

SANDOZ Aktiengesellschaft, Basel (Switzerland)

Representative:

Dr. W. Schalk, Dipl.-Ing. P. Wirth,

Dipl.-Ing. G. E. M. Dannenberg

and Dr. V. Schmied-Kowarzik,

Frankfurt / M., Große Eschenheimer Str. 39

Named as inventor:

Dr. Jany Renz,

Dr. Jean-Pierre Bourquin,

Dr. Erhard Schenker, Basel (Switzerland)

Claimed priority:
Switzerland of March 29, 1960 (3542),
dated May 11, 1960 (5398)

29.4 g of benzoyl chloride (boiling point 194 ° to 196 °) are added dropwise at room temperature with stirring ecm xylene. The batch is then carried out at a bath temperature of 140 ° with stirring for 4 hours heated to reflux. After cooling to room temperature, the pyridine hydrochloride formed is suction filtered, washed with 100 ecm benzene and the filtrate concentrated to dryness in vacuo. The crude 5,7-dibromo-8-benzoxyquinoline has a melting point of 131 ° to 139 °. After repeated Recrystallization of the substance from carbon tetrachloride gives the analytically pure 5,7-dibromo-8-benzoxyquinoline from the constant melting point 140 to 142 °.

Comparative experiments

In the following comparative tests, the fungistatic effect of the two known compounds

(I) 5,7-dibromo-8-oxychinaldine (German patent specification 852 953) and

(II) 5,7-dibromo-8-acetoxyquinoline (Belgian patent 544 024)

compared to 5,7-dibromo-8-benzoyloxyquinoline (III).

509 520/415

The test organisms used were:

Aspergillus niger,

Trichophyton interdigitalis,

Trichophyton rubrum,

Trichophyton mentagrophytes, Trichophyton gallinae.

The test was carried out with all fungi in dilution series of the substances. As a nutrient solution served light, unhopped wort made with tap water 1: 8 was diluted (dry matter content of the diluted wort: 2%) with an addition of 1% glucose. The pH is 6.4. The substance dilutions were made in double rows in tubes 5 ml each and inoculated the dilution series with suspensions of the strains, so that l ^ conidia 5 ecm each resulted. Incubation became final at 22 °, control of growth every week carried out after 3 weeks. The dilutions are given in molar concentrations.

Ver
am
manure Asperg,
Niger Trichoph.
inter-
digit. Trichoph.
rubrum Trichoph.
menta-
groph. Trichoph.
gallinae I.
II
in 50,000
400,000
500000 100,000
250,000
400,000 160,000
640,000
1,600,000 125,000
400,000
500,000 125,000
400,000
1,000,000

From the data in the table above it can be clearly seen that compounds I and II are essential are less effective than the compound III.

Claims (1)

Claim: Process for the preparation of the fungistatically active compound SJ-dibromo-S-benzoyloxyquinoline, characterized in that 5,7-dibromo ~ 8-hydroxyquinoline is used in a manner known per se a) with benzoic anhydride at elevated temperature in the presence of pyridine or sulfuric acid or b) with benzoyl chloride or a mixture of benzoyl chloride and benzoic anhydride in Presence of an inert organic solvent and a tertiary amine implements. Considered publications: German Patent No. 891,257; Patent No. 14,971 of the Office for Invention and Patents in the Soviet Zone of Occupation Germany. 509 520/415 3.65 © Bundesdruckerei Berlin