THE REVERSE VILSMEIER APPROACH TO THE SYNTHESIS OF QUINOLINES, QUINOLINIUM SALTS AND QUINOLONES

N-Methylformanilide(MFA) reacts with various electron-rich alkenes in POCl3 solution to give N-methylquinolinium salts generally in good yield. The alkenes can be vinyl acetate, an aldehyde or ketone enamine (preferably the morpholine enamine), a methyl aryl ketone (reacting as its enol) or it may be generated from an alkanoamide bearing alpha-protons (which produces an alpha-chloroenamine in situ). The reaction is effective for a variety of other alkyl-, aryl- and benzyl- formanilides as well as ring substituted anilides though electron-withdrawing groups tend to inhibit cyclisation. The mechanism of the cyclisation has been elucidated and shown to involve an electrocyclic ak process. The reactions of MFA with amides in POCl3 gives 4-quinolones on alkaline workup.