On the mechanism of the Skraup-Doebner-Von Miller quinoline synthesis.
The mechanism of the formation of substituted quinolines from anilines and alpha,beta-unsaturated ketones has been studied by the use of 13C-labeled ketones in cross-over experiments. In the reaction of doubly labeled 13C(2,4) mesityl oxide, a 100% scrambling of the label in the quinoline product was observed, whereas only a small (5-10%) amount of the starting mesityl oxide showed scrambling of the label. Similarly, the reaction of triply labeled pulegone clearly shows that the label in the product is 100% scrambled, whereas the label in the starting pulegone is retained. On the basis of these studies, a mechanistic pathway for the Skraup quinoline synthesis is proposed that involves a fragmentation-recombination mechanism. The aniline component condenses with the alpha,beta-unsaturated ketone initially in a conjugate fashion, followed by a fragmentation to the corresponding imine and the ketone itself. These fragments recombine to form the quinoline product.
Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA. denmark@scs.uiuc.edu
Scott E
SE
Denmark
Srikanth
S
Venkatraman
D000814:Aniline Compounds / Q000737:chemistry; D002247:Carbon Isotopes; D006588:Hexanones; D007097:Imines; D007659:Ketones / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis*
D000814:Aniline Compounds; D002247:Carbon Isotopes; D006588:Hexanones; D007097:Imines; D007659:Ketones; D011804:Quinolines; C008374:mesityl oxide; C037219:quinoline; C023650:aniline