Patent GB-1160729-A (GB)
Title: Dibenzocycloheptadiene Derivatives and their Preparation
IPC: C07C65/30
Filed: 1966-12-23
Abstract: 1,160,729. Dibenzo[a,d]cycloheptene derivatives. 23 Dec., 1966 [28 Dec., 1965 (2); 25 Jan., 1966 (4)], No. 57664/66. Heading C2C. The invention comprises compounds of the Formula I and their acid addition and quaternary ammonium derivatives, wherein one of X 1  to X 6  represents a halogen atom or a cyano, trifluoromethyl, C 1-5  alkyl, C 1-5  alkoxy, C 1-5  alkylthio, C 1-5  alkanesulphinyl or C 1-5  alkanesulphonyl group and the remainder of X 1  to X 6  represent hydrogen atoms; R represents a hydrogen atom or a C 1-5  alkyl, C 1-5  alkoxy, hydroxy (C 1-5  alkoxy) C 1-5  alkyl, C 1-5  hydroxyalkyl, C 2-5  alkenyl, C 2-5  alkynyl, phenyl, phenyl- C 1-5  alkyl, phenyl-C 2-5  alkenyl, the said phenyl groups being unsubstituted or substituted by one or more halogen atoms, C 1-5  alkyl, C 1-5  alkoxy, nitro, amino or trifluoromethyl groups and the carbon atoms of the piperazine nucleus may be substituted by one or more methyl groups and their preparation by reacting an ester of the Formula II with a piperazine of the Formula III wherein Y represents a reactive ester residue; where R represents other than a hydrogen atom or a substituted or unsubstituted phenyl group, by reacting a compound of the Formula IV with an ester of the Formula Y-R<SP>1</SP> where R<SP>1</SP> has the meanings of R other than hydrogen and substituted or unsubstituted phenyl; and where one of X 1  to X 6  represents an alkanesulphinyl or alkonesulphonyl radical by oxidizing a corresponding compound of the Formula I wherein one of X 1  to X 6  represents an alkylthio or alkanesulphinyl group. Reactive esters of the Formula II may be prepared by reducing ketones of the Formula VII and esterifying the resulting secondary alcohols of the Formula VI. Cyclic ketones of the Formula VII may be prepared, where one of X 1  to X 6  represents a halogen atom or an alkyl, alkoxy, alkylthio or trifluoromethyl group by cyclization of a compound of the Formula VIII wherein the appropriate X<SP>1</SP> has the values referred to and the remainder represent hydrogen atoms; where one of X 1  to X 6  represents a cyano group by converting the compound of the Formula VII, where the corresponding "X" represents a halogen atom, into a nitrile and where one of X 1  to X 6  represents an alkanesulphinyl or alkonesulphonyl group by oxidation of the corresponding alkylthio or alkanesulphinyl compounds. Acetic acids of the Formula VIII may be prepared from benzoic acids of the Formula IX by esterification with methyl alcohol followed by reduction to the corresponding benzyl alcohol, conversion of the latter to its halide, reaction with an alkali metal cyanide and hydrolysis of the resulting nitrile. Benzoic acids of the Formula IX which conform to the Formula XIII may be prepared by reducing ketones of the Formula XIV and those which conform to the Formula XV may be prepared by reducing phthalides of the Formula XVI. 3 - Chloro - 1<SP>1</SP> - carboxybenzophenone may be prepared by reacting 3-chlorophenylmagnesium bromide with phthalic anhydride. 3 - Phenyl - 6 - chlorophthalide may be prepared by reacting 2-formyl-5-chlorobenzoic acid with phenylmagnesium bromide. 3-(2- Chlorophenyl) phthalide may be prepared similarly. 3-Phenyl-7-chlorophthalide may be prepared from 7-chlorophthalide, by bromination to give 3-bromo-7-chlorophthalide, hydrolysing the latter to 2 - formyl - 6 - chlorobenzoic acid followed by reaction with phenylmagnesium bromide. Therapeutic compositions having sedative, tranquillizing, antihistaminic, antiserotonin, antiallergic, spasmolytic, and anti-emetic properties in forms suitable for oral, parenteral or topical administration comprise the compounds of the invention with a suitable carrier.