Patent GB-1260716-A (GB)
Title: p,p'-SUBSTITUTED BENZHYDRYLIDENE BICYCLIC COMPOUNDS AND PROCESSES FOR THEIR PREPARATION
IPC: C07C39/215
Filed: 1969-03-17
Abstract: 1,260,716. Benzhydrylidene compounds. SCHERICO Ltd. 17 March, 1969 [18 March, 1968], No. 13768/69. Heading C2C. Novel benzhydrylidene compounds of the general formula  wherein A is a hydrogen or halogen atom or an alkyl group, R is a C 1-6  alkyl group, R 1  is a hydroxy or esterified hydroxy group, Q is a bicyclic moiety composed of two fused carbocyclic rings, each containing 5 or 6 ring carbon atoms, and n is 0, 1, 2 or 3, are prepared (a) by subjection of a diphenylmethane derivative of the general formula  wherein R 2  is a hydroxy group, an esterified hydroxy group or a blocked hydroxy group which is solvolysed spontaneously under the reaction conditions to form a hydroxy group, or a blocked hydroxy group which is subsequently liberated and X and Y are radicals which are capable of being eliminated under the reaction conditions to an elimination reaction leading to the removal of X and Y and the formation of a double bond between the carbon atoms to which they are attached; (b) by condensation of a diphenylmethane derivative of the general formula  with a bioyclic derivative of the general formula (R) n  - Q = V, wherein U and V are reactive radicals capable of being eliminated under the reaction conditions; (c) by condensation of a benzylidene derivative of the general formula with a benzene derivative of the general formula (d) by reduction of a compound differing from that of the first general formula above only in that each R 1  is replaced by R 2  and a keto group forms part of the bicyclic moiety; (e) by subjection of a compound differing from that of the first general formula above only in that each R 1  is replaced by R 2  and an -S- radical bridges the o- and o<SP>1</SP>-positions of the phenyl rings of the benzhydrylidene moiety to reduction with accompanying elimination of hydrogen sulphide; and (f) by subjection of a benzhydrylidene compound of the general formula wherein m is 0 or 1, p and q are each 0, 1, 2, 3 or 4, provided that the sum p + q = 3 or 4, and T and Z are reactive radicals capable of being eliminated under the reaction conditions, to intramolecular condensation; followed, if necessary, by liberation of any blocked hydroxy groups in the product; and optionally further followed by esterification of free hydroxy groups in the product, saponification of any esterified hydroxy groups in the product, or hydrogenation of any double bond present in the bicyclic moiety. 3 - Di - (p - hydroxyphenyl) - methyl - cisbicyclo[4.4.0]decane is prepared by reaction of cis-bicyclo[4.4.0]decane-3-carboxaldehyde with phenol in the presence of sulphuric acid and may be reacted with N-bromosuccinimide to form 3- [di - (p - hydroxyphenyl) - bromomethyl] - cisbicyclo[4.4.0]decane.3 - [Di - (p - methoxyphenyl) - ethoxycarbonyl] - methyl - 3 - hydroxycis-bicyclo[4.4.0]-decane is prepared by reaction of ethyl di-(p-methoxyphenyl)-acetate with 3- keto-cis-bicyclo[4.4.0]-decane in the presence of sodium methoxide. 2 - [Di - (p - methoxy phenyl - chlorosulphitomethyl]-cis-bicyclo[4.4.0]- decane is prepared by reaction of methyl cisbicyclo[4.4.0]decane-2-carboxylate with pbromoanisole and magnesium in ether, followed by addition of water to the resulting complex, and reaction of the 2-[di-(p-methoxyphenyl)- hydroxy] - methyl - cis - bicyclo[4.4.0]decane so formed with thionyl chloride. 3-[Di-(p-hydroxyphenyl) - thiol] methyl - cis - bicyclo[4.4.0]- decane is prepared by reaction of 3-[di-(phydroxyphenyl) - bromo] - methyl - cis - bicyclo- [4.4.0]decane with hydrogen sulphide. 3-(xlodo - p - methoxybenzylidene)- cis - bicyclo- [4.4.0]decane is prepared by reaction of 3-pmethoxybenzyl-cis-bicyclo[4.4.0]decane with N-bromosuccinimide and benzoyl peroxide, reaction of. the resulting 3-α,α-dibromo-pmethoxybenzyl-cis-bicyclo[4.4.0]decane with sodium iodide and treatment of the 3-α,α-diiodo - p - methoxybenzyl - cis - bicyclo[4.4.0]- decane so obtained with sodium carbonate in acetone, followed by water. 2-(p,p<SP>1</SP>-Dihydroxybenzhydrylidene) - 4 - keto - bicyclo[4.4.0]deca- 5(6)-ene is prepared by reaction of the ethylene ketal of 4-keto-bicyclo[4. 4. 0]deca-5(6)-ene-2- carboxylate with p-(2-tetrahydropyranyloxy)- bromobenzene and magnesium in tetrahydrofuran, followed by treatment with water, and may be hydrogenated in the presence of palladium to form 2-(p,p<SP>1</SP>-dihydroxybenzhydrylidene-4-keto-cis-bicyclo[4.4.0]decane. 2-(p,p<SP>1</SP>-Dimethoxybenzhydrylidene)- 8 - keto - cis - bicyclo- [4.4.0]decane is prepared by treatment of cis-2- ethoxypropionyl - 3 - ethoxyacetyl - 1 - (p,p<SP>1</SP>- dimethoxybenzhydrylidene)-cyclohexane with potassium in xylene, followed by hydrochloric acid. 2-(Di-p-methoxyphenyl-methyl)-3-keto-cisbicyclo[4.4.0]decane is prepared by reaction of 1-N-pyrrolidino-1-cyclohexene with 5-di-pmethoxyphenyl-3-keto-pentyl bromide, treatment of the resulting 2-(#-di-p-methoxyphenyl-γ- ketopentyl)cyclohexanone with sodium methoxide in methanol and hydrogenation of the 2-(di-pmethoxyphenyl - methyl) - 3 - keto - bicycle[4. 4. 0]- dec-1-ene so obtained in the presence of palladium. 3-(3,6-Dimethoxy-9-thiaxanthenylidene)- cis-bicyclo[4.4.0]decane is prepared by reaction of 3,6-dimethoxy-thiaxanthene with 3-keto-cisbicyclo-[4.4.0]-decane and butyl lithium, followed by thionyl chloride and sodium hydroxide. 2 - (p,p<SP>1</SP> - Dimethoxybenzhydrylidene) - cisbicycle[4.4.0]decane is prepared by treatment of cis - 2,3 - di - (# - bromoethyl) - 1 - (p,p<SP>1</SP> - dimethoxybenzhydrylidene)-cyclohexane with sodium in ether. Pharmaceutical compositions capable of inhibiting gestation in female mammals comprise, as active ingredient, a benzhydrylidene compound of the first general formula above, in admixture with a suitable carrier, and may be administered orally or parenterally.