The Reverse Vilsmeier Approach to the Synthesis of Quinolines, Quinolinium Salts and Quinolones

Article abstract of DOI:10.1016/0040-4020(95)00729-R

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 α-protons (which produces an α-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 electrophilic ?₆s process.The reactions of MFA with amides in POCl3 gives 4-quinolones on alkaline workup.