A versatile new synthesis of quinolines and related fused pyridines. Part 8. Conversion of anilides into 3-substituted quinolines and into quinoxalines

Abstract

Anilides (4)(ArNHCOCH2R) are readily converted into 2-chloro-3-R-quinolines (5) under Vilsmeier conditions and the 2-chloro-group may be removed with zinc and acetic acid yielding 3-substituted quinolines (7). When N-nitrosodialkylamines are used in place of dimethylformamide as the Vilsmeier agent, the anilides are converted into 2-chloroquinoxalines in low yields. Several by-products are formed and the mechanisms have been explored. Thus, the formation of ethyl N-arylcabamate from the corresponding propionanilide is shown to involve an C→O alkyl migration related to a Wolff rearrangement, while N-arylformimidoyl dichloride (18), nitriles, and isocyanides are derived from C–C cleavage of the substituted side-chain. Variation of the acid chloride component of the Vilsmeier reagent or of the solvent was generally unproductive though use of phosphoryl bromide instead of the chloridecaused conversion of anilides into bromoquinolines in low yields.