Study On Synthesis Of 3-phenoxy Imidazo Heterocycles Mediated By I₂

Imidazo[1,2-a]pyridine is a privileged structural motif that is widely found in natural products and recognized as a "drug privilege" scaffold in medicinal chemistry notably from its easy access and its great stability.The functionalized products,especially the imidazo[1,2-a]pyridine derivatives with substituent at the C-3 position,often have significant biological activity and were widely applied in the field of drug discovery.Therefore,it is still of great practical significance to develop a simple,efficient and green synthetic method for imidazopyridine fused heterocyclic compounds.In addition,molecular iodine,as one of the simplest reagent,plays an important role in organic synthesis,owing to its commercial availability,low cost,and low toxicity.In this paper we have developed a facile and highly efficient protocol for the synthesis of 3-phenoxy imidazoheterocycles from readily available2-phenoxyacetophenone with 2-aminopyridine or 2-aminobenzothiazole by employing stoichiometric molecular iodine,which allows for the rapid synthesis of a wide range of 3-phenoxy imidazo heterocycles under mild conditions.Some notable hallmarks of our protocol include high yields,operational simplicity,mild reaction conditions,and metal catalyst-free.Through optimizing conditions of the reaction,such as solvent,reaction temperature,catalyst,and additives,two series of 74 compounds were finally synthesized,among them 67 were new compound that have not reported in the literature.Their structure were all identified by NMR and HRMS.Moreover,the mechanism of constructing imidazo[1,2-a]pyridine and benzo[d]imidazo[2,1-b]thiazole derivatives was proposed.