The expansion of heterocyclic rings

Abstract

Of the reactions in which pyrroles and indoles are reported to undergo ring expansion, the example investigated initially - the conversion of 2-carbamyl-2-cyano-dihydroindole to 3-carbamyl-2-hydroxyquinoline - proved to be incorrect. The supposed dihydroindole compound (a reduction product of alpha-cyano-o-nitrocinnamamide) was actually 2-amino-3-carbamylquinoline (Section A). The general reaction whereby pyrroles and indoles are converted by trihalomethanes/base to 2-pyrrole and 3-indole aldehydes, and 3-halopyridines and quinolines was next examined (Section B). Three instances of the isolation of a dichloromethyl pyrrolenine or indolenine and its subsequent conversion to a pyridine or quinoline are recorded in the literature. The dichloromethyl derivative had therefore been suggested to be an intermediate for both aldehyde formation and the ring expansion. From paper chromatographic experiments the ring expansion of 3-dichloromethyl-2:3-dimethylindolenine to 3-chloro-2:4-dimethylquinoline does not appear to occur.But a product whose picrate corresponds, by analysis, to that of 3-ethoxy-2:4-dimethylquinoline (and not to 2:3-dimethylindolenine-3-aldehyde or its diethyl acetal derivative) has been obtained from the action of sodiumethoxide on 3-dichloromethyl-2:3-dimethylindolenine. This suggests that the ring expansion does occur here, possibly by means of a labile intermediary, produced during solvolysis of the dichloromethyl group. A mechanism: has been suggested, and also one for the 'direct' conversion of pyrroles and indoles to pyridines and quinolines.A preliminary kinetic investigation of the reactionof sodium ethoxide on the dichloromethyl derivative was begun.Several 2-aminoquinolines and their N-oxides, and some 3-substituted2:4-dimethylquinolines were availablefrom the work recorded in Sections A and B. The spectra ofthe N-oxides in ethanol, and aqueous hydrochloric acid andsodium hydroxide, were measured (Section C). Spectra ofthe other derivatives were measured in the first twosolvents. As previously observed, the N-oxides show abathochromic effect in ethanol and alkali, but have thesame absorption as the corresponding quinolines in acid. The general characteristics of the 2:4-dimethylquinoline series conform with published results.