Patent GB-861350-A (GB)
Title: Pharmaceutical compositions and methods for producing phenylcyclohexane compounds
Filed: 1958-02-27
Abstract: Mono - N - substituted 1 - phenylcyclohexylamines of the general formula <FORM:0861350/IV (b)/1> (wherein R is an alkyl radical of at most 4 carbon atoms, an allyl radical or an alkoxyalkyl radical of 3 to 6 carbon atoms, the alkoxy group therein containing from 1 to 3 carbon atoms) are prepared (1) by reacting a Schiffs base derived from cyclohexanone and an amine of the formula NH2R with a phenyl magnesium halide or a phenyl alkali metal compound under anhydrous conditions in an inert organic solvent and decomposing the resulting product with water; or (2) by reacting an appropriate monoN - substituted - 1 - amino - 1 - cyanocyclo - hexane with a phenyl alkali metal compound under anhydrous conditions in an inert organic solvent at 0 DEG  to 100 DEG  C. and decomposing the resulting product with water; or (3) by reacting a 1-phenyl-1-X-cyclohexane (wherein X is an alkali metal or a magnesium halide group) in an inert organic solvent under anhydrous conditions with a compound halogen-NHR or alkyl-O-NHR; or (4) by reacting a 1-phenyl-1-X-cyclohexane (wherein X is a quaternary ammonium halide group) with an amine RNH2 at an elevated temperature; or (5) by removing one or more keto groups from the cyclohexyl ring of a mono-R-substituted-1-phenylcyclohexylamine containing said keto group or groups in the cyclohexyl ring by reduction with hydrazine hydrate and alkali; or (6) by reacting 1-phenylcyclohexylamine with a compound R-halogen, preferably in an organic solvent; or (7) by reacting 1-phenylcyclohexylamine with an aldehyde or ketone which on reduction yields the group R, or with an acylating agent P-CO-Q (wherein P is a group having the same structure as R less the carbon atom attached to the nitrogen atom and Q is a halogen, an alkoxy group or an -O-CO-P group) and reducing the resulting product; or (7) for preparing 1-phenyl-cyclohexylmethylamine, by reacting 1-phenylcyclohexyl carboxamide with an alkali metal hypohalite in aqueous solution at below about 25 DEG  C., and reducing the resulting 1-phenylcyclohexyl isocyanate with lithium aluminium hydride under anhydrous conditions in an inert organic solvent; or (8) by reacting an N-(a -halobenzylidene)-R-amine under anhydrous conditions in an inert organic solvent with a compound of the formula Me-(CH2)5-Me (wherein Me is an alkali metal or a magnesium halide group) and decomposing the resulting product with water; or (9) for preparing the compounds wherein R is an alkyl or alkoxyalkyl group, by catalytically hydrogenating an N-benzyl-1-phenylcyclohexyl-R-amine to remove the benzyl group, the catalyst preferably being a palladium catalyst.  The products may be converted into acid-addition salts, a list of salt-forming inorganic and organic acids being provided. Many examples are given.  N-cyclohexylidene-ethylamine is prepared from cyclohexanone and ethylamine.  Other similar Schiffs bases containing different groups R are similarly prepared. 1-Ethylamino-cyclohexanecarbonitrile is prepared by reacting cyclohexanone, sodium metabisulphite, potassium cyanide and ethylamine.  N-(a -chlorobenzylidene)-ethylamine is prepared by refluxing N-ethylbenzamide with thionyl chloride in carbon tetrachloride.  1-Phenyl-cyclohexylamine is prepared by acid hydrolysis of N - formyl - 1 - phenylcyclohexylamine.  N - methyl - N - benzyl - 1 - phenylcyclohexylamine formate is prepared by methylating N-benzyl - 1 - phenyl - cyclohexylamine with formaldehyde and formic acid.  1-Phenyl-cyclohexylamine trimethylammonium chloride is prepared from 1-phenyl-cyclohexyl chloride and trimethylamine. 3-Phenyl - 3 - n - propylamino - cyclohexanone is prepared from 3-phenyl-2-cyclohexene-1-one and n-propylamine.  N - (1 - phenylcyclohexyl) - acetamide is prepared from 1-phenyl-cyclohexylamine and acetic anhydride.ALSO:Pharmaceutical compositions comprise a compound of the formula <FORM:0861350/VI/1> (wherein R is an alkyl radical of at most 4 carbon atoms, an allyl radical or an alkoxyalkyl radical of 3 to 6 carbon atoms, the alkoxy group therein containing from 1 to 3 carbon atoms) or a non-toxic acid-addition salt thereof, and one or more solid or liquid carriers or diluents.  They may take the form of tablets, liquid or dry-filled capsules, aqueous or non-aqueous solutions, dragees, suppositories, inhalants, jellies or sprays, and may contain preservatives and flavouring agents.  Specified salts are hydrochlorides, hydrobromides, sulphates, phosphates, succinates, benzoates, acetates, p-toluene- and benzene-sulphonates and sulphamates.