Studies on tertiary amine oxides. LXII. A novel formation of quinolinium methylides by the reaction of quinoline 1-oxides with active methylene compounds in the presence of an acylating agent.

Abstract

The reaction of quinoline 1-oxide with ethyl cyanoacetate and acetic anhydride in dimethylformamide (DMF) or dimethylsulfoxide (DMSO) at low temperatures was found to give quinolinium-ethoxycarbonylcyanomethylide as the main product besides the normal 2-substituted and 4-substituted products. This novel formation of N-ylide was examined under various conditions, and the following features were revealed. Acetic anhydride was most effective as acylating agent, and DMF and DMSO seemed most suitable media for the N-ylide formation. In addition to ethyl cyanoacetate, malonodinitrile, methyl cyanoacetate and benzoylacetonitrile also produced the corresponding N-ylides, but other active methylene compounds such as malonates, ethyl acetoacetate and cyanoacetamide gave no ylide, only 2-substituted or/and 4-substituted products being formed. As for aromatic N-oxide, pyridine and isoquinoline N-oxides were inert to the N-ylide formation. On the other hand, quinoline 1-oxides bearing an electrondonating group at the 4-position, i.e., lepidine, 4-methoxy-and 4-amino-quinoline 1-oxides, were highly reactive toward this type of N-ylide formation. A likely reaction mechanism was proposed.