The Hantzsch synthesis with salicylaldehyde revised. On the formation of bridged tetrahydropyridine derivatives

Abstract

The Hantzsch condensation of salicylaldehyde with ethyl acetoacetate and ammonia has been re-examined. The reaction leads primarily to a 1,4-dihydropyridine intermediate which, after isomerization, undergoes a ring closure to give a bridged 1,4,5,6-tetrahydropyridine product, or is oxidized to 4-methyl-2-(2-oxo-2H-1-benzopyran-3-yl)[1]benzopyrano[3,4-c]pyridin-5-one. Bridged tetrahydropyridines with the 8-oxa-10-azatricyclo[7.3.1.0^2,7]trideca-2,4,6,11-tetraene skeleton were found in the Hantzsch-type condensation of salicylaldehyde with malononitrile, ammonium acetate, and acetone or butan-2-one. A mechanism for these reactions is discussed.