Preparation of N1-alkyl- and N1,N1-dialkylisoquinoline-1,3-diamines and 1-alkyl- and 1-phenylisoquinolin-3-amines from the reaction of α-cyano-o-tolunitrile with lithium amides, alkyllithiums, and phenyllithium

A facile, one-step synthesis of the titled compounds from the reaction of alpha-cyano-o-tolunitrile with LiNHR, LiNRR', RLi, or PhLi is described. A mechanism is presented in which alpha-cyano-o-tolunitrile is first converted quantitatively to its ketenimine carbanion by the lithium base. The remaining aromatic cyano group on the ketenimine carbanion then undergoes nucleophilic attack by the lithium base to give an adduct that subsequently cyclizes to the titled compounds. The reaction of lithiated anilines, nitriles, methanol, and pryrrole failed, presumably due to their inability to deprotonate alpha-cyano-o-tolunitrile.