Verbesserte Synthese von 8‐Amino‐2‐methyl‐4‐phenyl‐1,2,3,4‐Tetrahydroisochinolin

Abstract

An Improved Synthesis of 8‐Amino‐2‐methyl‐4‐phenyl‐1,2,3,4‐Tetrahydroisoquinoline The regioselectivity of the reaction of 2‐nitrobenzylmethylamine (1) and styrenoxide (2) leading to a mixture of the isomeric aminoalcohols 3a and 3b has been studied. The course of the reaction strongly depends on the type of the solvent used as reaction medium. The highest selectivity (3a:3b = 9:1) was achieved with a combination of polar aprotic and protic solvents (DMFA and ethanol). 1H n.m.r. spectroscopy was used for identification of the isomers as well as for the determination of their ratio in the crude reaction mixtures. The isomer ratio remains unaffected during catalytic reduction (Ra‐Ni) of 3a/3b to a mixture of the corresponding aminoalcohols 4a and 4b. Pure 3a, 4a and 4b were independently synthesized for comparison. Cyclodehydration of crude 4a/4b mixtures gives 5 in a very good yield.