Facile Synthesis Of Tetrahydropyridazines And Pyridazines

Heterocyclic chemistry constitutes a major part of modern organic chemistry and has long been a research hotspot among chemists.Heterocycles,especially nitrogen heterocycles are widely favoured due to their vital biological activities.Statistics show that nitrogen heterocycles exist in 60% of U.S.FDA approved small molecule drugs up to 2014,which well demonstrates their significance.Of all the nitrogen heterocycles,tetrahydropyridazines and pyridazines belong to a class of six-membered rings with two adjacent nitrogen atoms.They not only consist in many bio-active natural products,pesticides and pharmaceuticals but are important scaffolds and pharmacophores.In addition,pyridazine derivatives have recently attracted considerable attention in the research field of materials chemistry and are believed to be highly potential building blocks.Therefore,research into the synthesis of tetrahydropyridazines and pyridazines would contribute enormously to the domains of drug discovery,crop protection and functional materials.Within this thesis,1,2-Diaza-1,3-Dienes produced in situ from ?-chlorohydrazones reacted with alkoxyallenes under reoptimized condition to afford the [4+2] cyclic adduct 1,4,5,6-tetrahydropyridazines.This renewed transformation had several merits including mildness,high efficiency,operational simplicity,wide substrate scope and viability for gram scale synthesis.Meanwhile,it was discovered that the above products could be readily converted into substituted aromatic pyridazines when subject to acidic condition in a simple and efficient manner,thus providing a facile alternative access to pyridazine derivatives.In conclusion,this thesis features an economical and practical protocol for the synthesis of tetrahydropyridazines and pyridazines whose applicability and potential for activity screening is fully evidenced by the manufacture of 29 tetrahydropyridazine derivatives and 21 pyridazine derivatives with structural characterization and verification.