Patent GB-1182640-A (GB)
Title: Tricyclic Compounds
IPC: C07C209/16
Filed: 1967-11-07
Abstract: 1,182,640. Dibenzo[a,d]cycloheptene derivatives. HOFFMANN-LA ROCHE & CO. 7 Nov., 1967 [8 Nov., 1966; 2 Feb., 1967], No. 40602/69 . Divided out of 1,182,639. Heading C2C. Novel dibenzo[a,d]cycloheptene derivatives of the general formula wherein the broken lines denote optional bonds, R is a chlorine or fluorine atom, R<SP>2</SP> and R<SP>3</SP> are each a chlorine or fluorine atom, X is an ethylene group or a vinylene group which may be substituted by a halogen atom, one of Y<SP>1</SP> and Y<SP>2</SP> is a hydrogen atom and the other is a hydroxy group and R<SP>1</SP> is a methyl group, are prepared (a) when Y<SP>1</SP> is a hydroxy group and Y<SP>2</SP> is a hydrogen atom (i) when R<SP>1</SP> is present, by reaction of the corresponding 5-ketone with 3-dimethylaminopropyl magnesium chloride, followed by hydrolysis or (ii) when R<SP>1</SP> is absent, by reaction of the corresponding 5-ketone with 3 - (N - methyl - N - benzyl - amino)propyl magnesium chloride, followed by hydrolysis, reaction with chloroformic acid ethyl ester and subsequent hydrolysis; or (b) when Y<SP>1</SP> is a hydrogen atom and Y<SP>2</SP> is a hydroxy group, by reaction of the corresponding 5-ketone with ethyl magnesium bromide, followed by hydrolysis, dehydration of the resulting 5-hydroxy-5-ethyl compound with acetyl chloride, treatment of the dehydration product with formic acid and hydrogen peroxide, dehydration of the resulting 5 - hydroxy - 5 - (1 - hydroxyethyl) compound with aqueous sulphuric acid, treatment of the resulting 5-acetyl compound with formaldehyde and methylamine hydrochloride or dimethylamine hydrochloride and reduction of the resulting 5-(3-methyl or dimethylaminopropionyl) compound with sodium borohydride. 1 - Fluoro - 10,11 - dihydro - 5H - dibenzo[a,d] cyclohepten-5-one is prepared by reaction of phthalic anhydride with 2-fluorophenylacetic acid, treatment of the resulting 3-(2-fluorobenzylidene)-phthalide with red phosphorus and hydriodic acid, followed by alkali, and heat treatment of the produced 2-(2-fluorophenethyl)- benzoic acid with polyphosphoric acid. 1 - Chloro - 10 (or 11)-bromo-5H-dibenzo[a,d] cyclohepten-5-one is prepared by reaction of 1 - chloro - 5H - dibenzo[a,d]cyclohepten-5- one with bromine in the presence of light, followed by dehydrobromination of the resulting 1 - chloro - 10,11 - dibromo - 10,11 - dihydro - 5H - dibenzo[a,d]cyclohepten - 5 - one. 1,10 (or 11) - Dichloro - 5H - dibenzo[a,d]cyclohepten-5-one is prepared by treatment of 1- chloro-5H-dibenzo[a,d] cyclohepten-5-one with chlorine in the presence of light, followed by dehydrochlorination of the resulting 1,10,11- trichloro - 10,11 - dihydro - 5H - dibenzo[a,d] cyclohepten-5-one. 1,3 - Dichloro - 10,11 - dihydro - 5H - dibenzo [a,d]cyclohepten-5-one is prepared by treatment of 2 - (2,4 - dichlorophenethyl) - benzoic acid with thionyl chloride, followed by aluminium chloride in carbon disulphide. 1,9 - Dichloro - 10,11 - dihydro - 5H - dibenzo [a,d]cyclohepten-5-one is prepared by reaction of 3-chlorophthalic acid anhydride and 2- chlorophenylacetic acid, reduction of the obtained 4 - chloro - 3 - (2 - chlorobenzylidene)- phthalide with red phosphorus and hydriodic acid, alkaline hydrolysis of the resulting 4-chloro- 3 - (2 - chlorobenzyl) - phthalide, dehydration of the produced 3 - chloro - 2 - [1 - hydroxy - 2 - (2- chlorophenyl)ethyl] - benzoic acid salt, reduction of the produced 3 - chloro - 2 - (2 - chlorostyryl)- benzoic acid with red phosphorus and hydriodic acid and heat treatment of the resulting 3 - chloro - 2 - (2 - chlorophenethyl) - benzoic acid with polyphosphoric acid.