Based on a previous work that the benzyne reaction of ortho-substituted halogenobenzenes with acetonitrile gave meta-substituted benzyl cyanides as an important starting material for the syntheses of isoquinolines in a comparatively good yield, the reaction of various ortho-halogenobenzenes with nitriles, except acetonitrile, was examined for the formation of the desired meta-substituted benzyl cyanides. In this case, meta-substituted amino compounds, formed by the addition of ammonia to the benzyne intermediate, was obtained as a by-product. The benzyne reaction of halogenobenzene with other nitriles, such as phenethyl cyanide, 2-phenyl-n-butyronitrile, methylene dicyanide, and isobutyronitrile, was carried out, but the expected compounds were not obtained. Reduction of 2-(3-methoxyphenyl)propionitrile and 2-(3-benzyloxyphenyl)propionitrile gave β-methyl-3-methoxyphenethylamine and β-methyl-3-hydroxyphenethylamine, respectively, which were used as the starting materials for the synthesis of isoquinoline. Several kinds of unknown isoquinoline derivatives were obtained by phenolic cyclization or by application of Bischler-Napieralski reaction through a few steps.
