Patent GB-959313-A (GB)
Title: Diphenylalkane derivatives and process for their manufacture
Filed: 1961-01-30
Abstract: The invention comprises substituted diphenylalkanes of the general formula: <FORM:0959313/C2/1> wherein R1 represents a hydrogen atom or a hydroxy or methoxy group and R2 represents a hydroxy or methoxy group, and acid addition salts thereof, and the preparation of the above diphenylalkanes and the salts by any of the following methods:-(a) phenylacetone is hydrogenated in the presence of an amine of the general formula: <FORM:0959313/C2/2> wherein R1 and R2 have the above significance; (b) an amine of the general formula in the previous method is reacted with a 1-phenyl-2-halogeno-propane or a 1-phenyl-2-halogeno-propene in the presence of an agent binding hydrogen halide, and when the reaction is carried out with a 1-phenyl-2-halogeno-propene hydrogenating the compounds so obtained which are of the general formula: <FORM:0959313/C2/3> <FORM:0959313/C2/4> wherein R1 and R2 have the above significance; (3) an aldehyde of the general formula: <FORM:0959313/C2/5> wherein R1 and R2 have the above significance, is hydrogenated in the presence of 1-phenol-2-amino-propane; (4) a compound of the general formula: <FORM:0959313/C2/6> wherein R1 and R2 have the above significance, is hydrogenated; (5) a suitably substituted diphenyl methane or diphenyl acetonitrile is condensed in the presence of agents capable of splitting off hydrogen halide with an amine of the formula: <FORM:0959313/C2/7> wherein R3 represents a hydrogen atom or a benzyl group and Hal represents a halogen atom and, when a substituted diphenyl acetonitrile is used, a hydrogen atom is substituted for the nitrile group in the cyano compound produced by reaction with sodamide or by hydrolysis of the nitrile group to form a carboxyl group with subsequent decarboxylation and, when R3 represents a benzyl group, the benzyl group is split off from the N-benzyl compound by catalytic hydrogenation; (6) a b ,b  diphenyl propionic acid amide of the formula: <FORM:0959313/C2/8> wherein R1 and R2 have the above significance, is reduced to the corresponding amine; (7) a compound of the first general formula above wherein R1 and/or R2 represent hydroxy groups is methylated; (8) a compound of the first general formula above wherein R1 and/or R2 represent methoxy groups is demethylated; and (9) a salt prepared by any of the above methods is converted to the corresponding free base, or a free base prepared by the said methods is converted into an acid addition salt.  Therapeutic compositions having activity on cardiac and blood vascular circulation contain as the active ingredient substituted diphenyl alkanes of the first general formula above or a salt thereof.  The compositions may be administered parenterally or orally.  b ,b -Diphenyl-propionic acid amides of the previous general formula above wherein R1 and R2 have the above significance, are prepared by reacting 1-phenyl-2-amino-propane with the required carboxylic acid chlorides. 1-(m-Methoxyphenyl)-1-phenyl-3-aminopropane is prepared by condensing the methyl ester of cyanoacetic acid with m-methoxybenzaldehyde to form a -cyano-b -(m-methoxyphenyl)-acrylic acid methyl ester, reacting this compound with phenylmagnesium bromide, alkaline hydrolysing the resulting ester, decarboxylating the resulting carboxylic acid to form b -(m-methoxyphenyl)-b -phenyl-propionitrile and hydrogenating this compound. By a similar method 1-(m-methoxyphenyl) -1-(p-methoxyphenyl)-3-aminopropane is prepared via b -(m-methoxyphenyl)-b -(p-methoxyphenyl)-propionitrile.  1 - Phenyl - 2 - [31 - (m - methoxyphenyl) -31-phenylpropene-(31)-yl-(11) ]-amino-propane is prepared by dehydrating 1-phenyl-2-[31-(m-methoxyphenyl) - 31 - phenyl - 31 - hydroxy-propyl-(11)]-amino-propane with p-toluenesulphonic acid.