GB721286A — Improvements in or relating to the preparation of tetrahydroisoquinolone derivatives

USPTO Abstract

Tetrahydroisoquinolines of the general formula <FORM:0721286/IV (b)/1> (wherein Y is hydrogen or a lower alkyl or lower alkoxy group having not more than 10 carbon atoms, R1 is hydrogen, or a lower alkyl group having not more than 10 carbon atoms, and R is hydrogen, a lower alkyl group having not more than 10 carbons, a phenyl group or a benzyl group) are prepared by treating a b -phenylethyl isocyanate of the structure <FORM:0721286/IV (b)/2> or a b -phenyl ethyl carbamyl chloride of the structure <FORM:0721286/IV (b)/3> (in which Y, R and R1 are as given) with a Friedel-Crafts type of condensing agent, preferably in the presence of an inert solvent. In examples: (1) 1-phenyl hexane isocyanate in nitrobenzene is treated with anhydrous aluminium chloride to yield 3-butyl-tetrahydro isoquinolone-1. In a similar manner the following tetrahydroisoquinolones are prepared: 3-ethylfrom 1-phenylbutane isocyanate-2; 3-methylfrom b -phenyl-isopropylisocyanate; 3-benzylfrom 1 : 3-diphenylpropyl-isocyanate-2; 3-phenylfrom 1 : 2-diphenylethyl-isocyanate; 7-butylfrom b -(p-butylphenyl)-ethyl isocyanate; 3-methyl-7-methoxyfrom b -(p-methoxyphenyl) - isopropyl - isocyanate; 4 - methyl from 2 - phenylpropyl - 1 - isocyanate; 4 - ethyl-from 2-phenyl-butyl-1-isocyanate; 4-iso-propylfrom 2-phenyl-3-methylbutyl isocyanate; 7-methoxy-3 : 4-dimethylfrom 2-(p-methoxy-phenyl) - 3 - isocyanobutane; 7-butyl - 3 : 4 - dimethyl - from 2 - (p - butylphenyl) - 3 - isocyanobutane; and 4 : 8 - dimethyl-3-butyl from 2-(m-tolyl)-3-isocyanohexane; (2) b -phenyl isopropylamine in nitrobenzene is saturated with hydrogen chloride and then treated with phosgene to produce the corresponding carbamyl chloride which on treatment with aluminium chloride yields 3-methyl tetrahydro-isoquinolone-1. The 7-butyl tetrahydro-isoquinolone is similarly prepared from b -(p-butylphenyl)-ethylamine. The intermediate b -phenylethyl isocyanates are prepared from the corresponding amines by treatment with phosgene in an inert solvent. Dibenzyl carbinamine is prepared from dibenzyl ketone, formic acid and formamide; b -(p-butyl-phenyl)-ethylamine from chloromethylated butyl benzene by treatment with alcoholic potassium cyanide and reduction with Raney nickel.