GB695341A - 1-(p-hydroxyphenyl)-2-(-a-methyl--g-phenyl-propylamino)-propanes and a process for the production thereof - Google Patents

Abstract

The invention comprises amines of the formula (p) HO-C6H4-CH2-CH(CH3)-NH -CH(CH3)-CH2-CH2-R, where R is phenyl or alkylphenyl; also their salts, e.g. hydrochlorides and hydrobromides. These are made by (1) dealkylating their alkyl or aralkyl ethers; (2) hydrolysis of their N- and/or O-acyl derivatives; (3) diazotizing the corresponding p-amino compounds and boiling the solution; (4) condensing p-hydroxyphenyl-acetone with 1 - phenyl - 3 - aminobutane and simultaneously or subsequently reducing the product or subjecting it to the Leuckart-Wallach reaction; (5) condensing p-hydroxyphenyl-isopropylamine with benzylacetone or benzalacetone and simultaneously or subsequently reducing the product or subjecting it to the Leuckart-Wallach reaction; (6) reacting p-hydroxyphenyl-isopropylamine or an ether thereof with a 1-phenyl-3-halobutane, and, if necessary, splitting off the ether group by boiling with mineral acids or by palladium hydrogenation. In method (1) the ether group (e.g. methyl, ethyl, benzyl, phenethyl) may be hydrolysed by boiling with hydrochloric, hydrobromic or hydriodic acid, or by treatment with aluminium chloride or Grignard compounds. If a benzyl ether is used the group may be split off by palladium hydrogenation. In method (2) the acyl group may be acetyl, benzoyl or toluenesulphonyl. The products may be separated into stereoisomeric racemates and resolved into optically active forms. In the examples the amine of the above formula (R = phenyl) is prepared (1) from its methyl ether by heating with hydrobromic acid; (2) from its benzyl ether by catalytic hydrogenation; (3) from its p-toluenesulphonyl ester by alkaline hydrolysis; (4) by diazotizing 1-(p-aminophenyl) - 2 - (a - methyl - g - phenylpropylamino) - propane; (5) by hydrogenating a mixture of p-hydroxyphenylacetone and 1-phenyl-3-aminobutane; two stereoisomers are produced; (6) by hydrogenating a mixture of 1-(p-hydroxyphenyl)-2-aminopropane and benzylacetone or benzalacetone; (7) by heating 1-(p-hydroxyphenyl)-2-aminopropane with 1-phenyl-3-bromobutane. The compounds where R is o-, m- or p-tolyl are prepared similarly. Alkyl and aralkyl ethers of compounds of the above formula are obtained by methods analogous to (5) and (6) above. Examples are given of the condensation of p-methoxyphenyl-acetone with 1-phenyl-3-aminobutane and of 1 - (p - benzyloxyphenyl)-2-aminopropane with 1-phenyl-3-bromobutane (product obtained as hydrobromide). 1 - (p - toluenesulphonyloxyphenyl) - 2 - (a - methyl - g - phenylpropylamino) - propane is made by reacting p-hydroxyphenylacetone with p-toluenesulphochloride and hydrogenating a mixture of the product with 1-phenyl-3-aminopropane. 1 - (p - Aminophenyl) - 2 - (a - methyl - g - phenylpropylamino)]propane is prepared by condensing 1-(p-nitrophenyl)-2-aminopropane with 1-phenyl-3-bromobutane and reducing the nitro group.