CS268892B1 - Halogen derivatives of 5-hydroxy-7-oxo-7H-benzo (c) fluorene and a process for their preparation - Google Patents

Abstract

The solution relates to new halogen derivatives of 5-hydroxy-7-oxo-7H-benzo(c)fluorene, in which R is hydrogen and R is chlorine or R is bromine, serving as an intermediate step in the preparation of antineoplastically active halogen derivatives of benzo(c)fluorene. Their preparation consists in the reaction of halogen derivatives of 5-acetoxy-7-oxo-7H-benzo(c)fluorene of the general formula II (6H8) with a hydrate, preferably with sodium ethanolate, in the reaction mixture, alkoxide,

Description

The invention relates to new halogen derivatives of 5-hydroxy-7-oxo-7H-benzo(c)fluorene of the general formula I

R ²

ΟΚΟ (I),

2 12 in which R represents hydrogen and R represents chlorine or R and R represent bromine.

2

The compounds of general formula I with the above-mentioned meanings of R and R are valuable intermediates for the preparation of compounds with interesting biological effects, especially tetracyclic derivatives of benzo(c)fluorene. Benzo(c)fluorene derivatives exhibit significant antitumor, interferonogenic and antibacterial activity (Křepelka et al. Collect. Czech. Chem. Commun. 47, 1258 (1982), 47, 1857 (1982), Vančurová et al. Collect. Czech, chem. Commun. 47, 1867 (1982), Czechoslovak author's certificate No. 212 669, USA patent No. 4,661,297, Smejkal ... et al. Acta Virol. 29, 11 (1984) ) and the compounds of general formula I are important precursors in their synthesis.

The compounds of the general formula I with the above-mentioned meaning and R are prepared according to the invention from the corresponding halogen derivatives of 5-acetoxy-7-oxo-7H-benzo(c)fluorene of the general formula II

R ²

(substances of general formula II are prepared according to Czechoslovak patent certificate No. 268891), in which 12 12 '

R ¹ represents hydrogen and R 2 represents chlorine or R 3 represents bromine, by reaction with alcoholates, preferably with sodium ethanolate, while boiling the reaction mixture.

More detailed information on the preparation of compounds of general formula I will be obtained from the following example, which does not limit the scope of the invention in any way.

Example

2,11-Dibromo-5-hydroxy-7-oxo-7H-benzo(c)fluorene

To a solution of 16.3 g (0.29 mol) of potassium hydroxide in 120 ml of water was added 40 ml of ethanol and the solution was heated to 50 °C. At this temperature, 6.67 g (0.015 mol) of 2,11-dibromo-5-acetoxy-7-oxo-7H-benzo(c)fluorene was added and the reaction mixture was heated to reflux (reaction temperature 83 °C) for 4 hours.

The reaction mixture was filtered while hot and immediately acidified with concentrated hydrochloric acid to pH * 3. Violet crystals separated overnight at 5 °C, which were filtered off with suction, washed with water and dried freely in air.

To remove the remaining unreacted 5-acetoxy-7-oxo-7h-benzo(c)fluorene, the crystals were refluxed with 150 ml of chloroform for 2 hours at 70° C. After filtration, 5.5 g (82.1%) of a red-violet substance with a melting point of 266-269° C. were obtained.

2-Chloro-5-hydroxy-7-Oxo-7H-benzo(c)fluorene was prepared analogously, mp = 273-275 °C.

Claims (4)

SUBJECT OF THE INVENTION 1. Halogen derivatives of 5-hydroxy-7-oxo-7H-benzo(c)fluorene of general formula I (AND)/ 1 2 12 in which R represents hydrogen, R represents chlorine or R and R represent bromine. 2. 2,1l-Dibromo-5-hydroxy-7-oxo-7H-benzo(c)fluorene. 3. 2-Chloro-5-hydroxy-7-oxo-7H-benzo(c)fluorene. 4. A method for preparing substances according to point 1, of general formula I, characterized in that the corresponding halogen derivatives of 5-acetoxy-7-oxo-7H-benzo(c)fluorene of general formula II R ² 1 2 12 in which R denotes hydrogen and R chlorine or R ^x and R bromine, are converted by reaction with alcoholates, preferably with sodium ethanolate, under boiling of the reaction mixture to compounds of general formula I.