CS231233B1 - A method for producing diphenyl dibenzocyclooctane derivatives - Google Patents

Abstract

The invention relates to a method for the production of diphenyl- -dibenzocyclooctanes of the general formula I in which R12a R denotes a phenyl group and r\ R^ are hydrogen atoms, or r' and 4 2 3 R denotes a phenyl group and R , R are hydrogen atoms, whereby the substituents on the chiral centers may occupy different spatial arrangements. These substances are prepared by the reaction of alpha-(2-bromomethylphenyl)phenylmethyl bromide with zinc or alkali metal iodide in a dipolar aprotic solvent, in the sense of dimerization of the transiently formed radical.

Description

The invention relates to a process for the preparation of diphenyl-dibenzocyclooctane derivatives of the general formula I

wherein R 1 and R ² denote phenyl and R ⁴ , R ⁴ are hydrogen atoms, or r 'and R ⁴ denote phenyl and R 3 are hydrogen atoms, wherein the substituents on the chiral centers may occupy different spatial arrangements.

In terms of degradation processes (oxidation), the structure of Formula I exhibits the same manifestations as lignans of the 1-aryl-tetrahydronaphthalene type, a substance with antitumor activity.

Compounds of formula (I), as defined above for R ¹ , R ² , R ⁴ and R ⁴ , are known and can be prepared by photochemical or other relatively complicated methods.

The most feasible variant for the synthesis of these compounds, based on the formation of biradicals by the decomposition of 1-phenyl-3,4-dihydrophthalazines, is believed to be expensive in the literature. Moreover, it is virtually unusable due to lack of experimental data / Sabarov S., Vasiliev N.I., Levina P.J .: 2. Obč. Ch. £ 24, 2478 (1961)].

The present inventors have now found that compounds of the formula I, having the meanings r 1, R ² , r ³ , 8, R ⁴ as mentioned above, can be advantageously prepared by reacting a compound of the formula II

with from about 1 to about 5 inol equivalents of zinc powder, preferably from about 4 mol equivalents, at temperatures from 0 ° C to the boiling point of the solvent, or from about 3 to 15 mol equivalents of alkali metal iodide, preferably 7.5 mol equivalents of sodium iodide. C to the boiling point of the solvent used. The presence of dipolar aprotic solvents has proven to be the most suitable inert medium for the reaction, and dimethylformamide is preferred for cost reasons and especially for processing the reaction mixture. After completion of the reaction, the reaction mixture is worked up by conventional methods, removal of residual zinc or iodine, non-dilution with water or dilute mineral acid, extraction with a suitable solvent and chromatographic separation.

The course of the reaction is due to the formation of intermediate 5-benzilidene-6-methylene-1,3-cyclohexadiene, which dimerizes in the form of zwitterion or biradicals to form compounds of formula I.

The starting material of formula II is a known compound (see, for example, Bream JM, Sohmutz S .: Helv. Chim. Acta 60, 2672-80 (1977)].

More detailed information on the preparation of the compounds of formula I is given in the following non-limiting example. Melting points are determined on a Kofler block and are not corrected.

3,7-Diphenyl-1,5-dibenzocyclooctane 3,4-Diphenyl-1,5-dibenzocyclooctane

a) Zn catalysis

To a solution of 1.4 g (4 mmol) of alpha- (2-bromomethylphenyl) phenylmethyl bromide in 10 ml of absolute dimethylformamide was added at 0 ° C at one time 1.04 g (16 mmol) of activated zinc. After stirring at 20-25 ° C for 6 hours, the unreacted zinc is filtered off, the filtrate is poured into 100 ml of 2 N HCl and extracted with chloroform. After drying over anhydrous sodium sulfate and evaporation of the solvent, the mixture of isomers is separated by chromatography on a column of silica gel (eluent carbon tetrachloride).

Recrystallization of uniform fractions from petroleum ether gave three diastereoisomers of 3,7-diphenyl-1,5-dibenzoeyklooctane having a melting point of 175-176 ° C, 163-165 ° C and 181-182 ° C and two diastereoisomers of 3,4-diphenyl- 1,5-dibenzocyclooctane, m.p. 203-205 ° C and 171-172 ° C.

b) catalysis Naj

To a solution of 4.5 g (30 mmol) of sodium iodide in 50 ml of absolute dimethylformamide was added dropwise 1.4 g (4 mmol) of alpha- (2-bromomethylphenyl) phenylmethyl bromide in 10 ml of dry dimethylformamide. After 3 hours, heating to 60 ° C, the reaction mixture is cooled to 20-25 ° C and 10 ml of 15% sodium dithionite solution are added, the reaction mixture is poured into 100 ml of ice water and the reaction products are extracted with chloroform. After drying and evaporation of the solvent, the mixture is worked up as above to give substances identical to those mentioned above.

Claims (2)

SUBJECT OF THE INVENTION A process for the preparation of diphenyl-dibenzocyclooctane derivatives of the general formula I R3 R < wherein R ¹ and R ² denote phenyl and R ¹ , R ¹ are hydrogen atoms, or R ¹ and R 2 are 23 denotes a phenyl group and R, R are hydrogen atoms, the substituents on the chiral centers may occupy a variety of spatial configurations, indicating the presence of a phenyl group; The process of claim 1, wherein the compound of formula II (H) is reacted with from 1 to 5 mol equivalents of zinc powder, preferably 4 mol equivalents, in an environment of dipolar aprotic solvents, preferably dimethylformamide, at temperatures ranging from 0 ° C to the boiling point of the solvent used. or with 3 to 15 mol equivalents of an alkali metal iodide, preferably 7.5 mol equivalents of sodium iodide.