SU856376A3 - Method of producing triphenylalkene derivatives - Google Patents

Abstract

Triphenylalkene derivatives of the general formula I <IMAGE> in which R is a C1-4-alkyl group and X is a halogen atom, where X has a meaning other than Cl if R is a methyl group, are obtained by dehydrogenation of a triphenyl alkanol derivative of the general formula II <IMAGE> in which R and X have the abovementioned meaning, while R1 and R2 have meanings which differ from one another and designate an H atom or an OH group. The resulting triphenylalkene derivatives inhibit to a considerable extent the growth of the hormone-dependent tumour induced by DMBA.

Description

(54) METHOD FOR PRODUCING TRIPHENYLALKENE DERIVATIVES

one

This invention relates to a process for the preparation of new triphenylalkene derivatives of general formula

phenylalkenes derivatives of the formula 1 triphenylalkanol derivative of the general formula

where R and X have the indicated meanings) R is a hydroxy group

RQ. - hydrogen,

dehydration at boiling of the reaction mixture, followed by separation of the target products in free form or in the form of their geometric isomers.

Preferred. Dehydration is preferably carried out in the presence of hydrochloric, hydrobromic, trifluoroacetic or formic acid. Geometric isomers are usually separated by fractional crystallization or chromatography.

The compounds of the invention can be used to prepare pharmaceutical preparations by converting at least one compound of general formula 1 to a pharmaceutical preparation together with non-toxic pharmacologically acceptable dilution and / or carrier.

Example 1 A solution of 135.0 g (0.355 mol) of 1,2-diphenyl-1- (p-bromophenyl) -1-butanol in 1400 ml of ethanol is boiled for 5 hours with 300 ml of 36% hydrochloric acid. The ethanol is distilled off in vacuo and the aqueous residue is extracted with several portions (1500 ml) of methylene dichloride. The organic phase is washed with water until neutral and dried. After distilling off the solvent, the crude crystalline product is recrystallized from ethanol to obtain 120 g (93%) of 1,2-diphenyl-1- (p-bromophenyl) -1-butene with m.p. 64-82С; the ratio of the Z-isomer to the E-isomer is 1: 1. After recrystallization of the product three times from isopropanol, the Z-isomer is obtained with a mp of 112-115 ° C. The mother liquor is evaporated to dryness and the residue is recrystallized from methanol twice, to obtain the E isomer with mp 89-92 ° C.

Example 2. To a solution of 320.0 (1.0 mol) of 1,2-diphenyl 1- (p-fluorophenyl) -1-butanol in 3800 ml of ethanol, 850 ml of 36% hydrochloric acid are added and the mixture is boiled 1 h. The crystalline precipitate that has precipitated from the cooled solution is filtered and washed with several portions of water until neutral. After evaporation of the mother liquor to half the original volume, an additional amount of product is obtained. After recrystallization of the crude product (2-90 g) from 90% ethanol, an isomeric mixture of 1,2-diphenyl-1- (p-fluorophenyl) -1-butene is obtained in a yield of 257.0 g (84.9%) mp 65-70 ° C, the ratio of z-isomer to E-isomer 1: 1. The mixture of isomers is separated on a silica gel column with a particle size of .0.063-0.2 mm, impregnated with silver nitrate, elution is carried out with a non-polar solvent, for example, petroleum ether or cyclohexane. From 5 g, 2.46 g (49.3%) of the 2-isomer with mp T.L.77-800С and 1.21 g (24.2%) of the el-isomer are obtained with mp. 78-81ОС.

Example 3. 30.6 g (O, 10 mol of 1,2-diphenyl-1- (p-fluorophenyl) -1-propanol are dissolved in 360 ml of ethanol and boiled for 85 hours with 85 ml of 36% hydrochloric acid. The alcohol is evaporated under vacuum, the residue is diluted with 200 ml of water and extracted with ml of chloroform. The organic phase is first washed with 100 ml of 10% sodium bicarbonate solution, then with water and dried over magnesium sulfate. The solvent is evaporated and the residue is recrystallized from ethanol 25.80 g (89.5%) of 1,2-diphenyl-1- (p-fluorophenyl) -1-propene are obtained, mp 7 6-89 C

Example 4. 30.0 g (86 mol) of 1, 2-diphenyl-1- (n-fluoro-Fenche 1-hexanol is dissolved in 300 ml of ethanol and

for 1 h, boil with 73 ml of 36% hydrochloric acid. The alcohol is evaporated in vacuo, the residue is diluted with 200 ml of water and extracted with 3x150 ml of chloroform. The organic phase is washed with 10% sodium hydrogen carbonate solution, then with water and dried. After evaporation of the solvent, the residue is recrystallized from ethanol. 24.2 g (85%) of 1,2-diphenyl-1- (P-fluorophenyl) -1-hexane are obtained, m.p.882 EO C.

Example 5. 5, O g (13 mol) 1,2-diphenyl-1- (p-bromophenyl) -1-butanol is dissolved in 60 ml of methanol and boiled for 7 hours with 7.05 ml of 5 (130 mmol ) 98% sulfuric acid. The methanol is evaporated in vacuo, the residue is dissolved in 20 ml of water and extracted with 3x20 ml of chloroform. The combined organic phase is first washed with 20 ml of a 10% sodium hydrogen carbonate solution, then with water, 2Q20 ml and dried with magnesium sulfate. The solvent is evaporated and the residue is recrystallized from ethanol. 5 4.30 g (90.5%) of 1,2-diphenyl-1- (p-bromophenyl) -1-butene, mp 65-82 ° C is obtained. The ratio of Z-isomer to E-isomer is 1: 1.

EXAMPLE 6.10.0 g (31.2 mmol) of 1,2-diphenyl-1- (P-fluorophenyl) -1-butanol is dissolved in a mixture of 100 ml of trifluoroacetic acid and 100 ml of ethanol and the solution is boiled. within half an hour. The reaction mixture was worked up according to Example 5. 8.40 g of 5 (89%) of 1, 2-d, andphenyl 1- (p-fluorophenyl) -1-butene were obtained, m.p. 65-70 ° C. The ratio of Z-isomer to E-isomer is 1: 1. Example 7. 5.0 g (14.8 mmol) of 1,2-diphenyl-1- (p-chlorophenyl) -1-butanol is dissolved in a mixture of 100 ml of 98% formic acid and 150 ml of methanol and boils t for 1 h. After treatment of the reaction mixture according to example 5, 4.15 g (88%) of 1.25-diphenyl-1- (p-chlorophenyl) -1-butene is obtained, mp 6B-79 ° C . The ratio of Z-isomer to E-isomer is 1: 1.

Example 8. 3.20 g (10 mmol) of 1, 2-diphenyl-1- (p-fluorophenyl) -1-butanol is boiled for 38 minutes in 38 ml of ethanol with 17.3 g of 57.6% perchloric acid. The crystals precipitated from the cooled solution are filtered and washed with water. 2.44 g (81%) of 1,2-diphenyl-1- (p-fluorophenyl) -1-butene are obtained, mp 67-71 ° C. Ratio

Z-isomer to E-isomer is 1: 1.

Example 9. 3.81 g (10 mmol) of 1,2-diphenyl-1- (fi-bromophenyl) -1-6 butanol is boiled for 5 hours in 46 ml

0 ethanol with 11.1 g of 48% hydrobromic acid. The alcohol is evaporated in vacuo, the residue is diluted with 20 ml of water and extracted with 3x20 ml of chloroform. United Organic

The 5 phases are washed with 20 ml of a 10% sodium bicarbonate solution, then with water and dried over magnesium sulfate. After evaporation of chloroform, the residue is recrystallized from ethanol. 3.0 g (82.5%) of 1,2-diphenyl-1- (p-brssphenyl) -1-butene is obtained, mp. 65-81 ° C. The ratio of Z-isomer to E-isomer is 1: 1.

y y and with the fact that, triphenylalkanol derivative of the general formula

.

Claims (2)

Invention Formula 1 Process for the preparation of triphenylalkene derivatives of general formula I where R is -, alkyl; j X - halogen, o with the proviso that if R is methyl, then X can only be a halogen different from chlorine or their geometric isomers, about tl and h where R and X have the indicated values at I-hydroxy group, hydrogen ,. dehydration at boiling of the reaction mixture, followed by allocation of the target products in free form or in the form of their geometric isomers. 2. Method POP.1, characterized in that the dehydration is carried out in the presence of an acid — hydrochloric, hydrobromic, hydroxyacetate or formic acid. Sources of information taken into account in the examination 1. G.E.Moussa, S.O.Abdalla, Oxidation of triaryl olefins, J.Appl. Chem. 1970, p.256.