Mechanism of the Skraup and Doebner-von Miller Quinoline Syntheses: Cyclization of α,β-Unsaturated N-Aryliminium Salts via 1,3-Diazetidinium Ion Intermediates

Article abstract of DOI:10.1021/jo00267a010

The hydrochlorides of cinnamaldehyde anils of the type ArCH=CHCH=NAr', where Ar and Ar' are phenyl or p-tolyl groups, have been shown to react between 25 deg C and 100 deg C, in a toluene suspension or in a solution of DMSO or acetonitrile, to yield 2-substituted quinolines and N-cinnamylanilines ArCH=CHCH2NHAr'.The reaction proceeds under anhydrous conditions by cyclization of the anil hydrochlorides themselves to produce ultimately 2-substituted quinolines.The kinetics of the reaction follow a first-order dependence on the anil hydrochloride.Rapid exchange occurring between dissimilar anil hydrochlorides suggests that such anil metatheses take place by way of 1,3-diazetidinium ion intermediates, which previous studies have shown would possess the requisite metastability.The foregoing experimental observations are reconciled in terms of a novel mechanism for the formation of quinolines directly from anils under acidic conditions, namely, the reversible formation of diazetidinium ions and their irreversible cyclization to quinolines.It is proposed that this pathway is the operative mechanism in the classic Skraup and Doebner-von Miller quinoline syntheses.