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.
The Journal of organic chemistry