Studies On The Five And Six-Membered Cyclization Reactions Based On Chalcones

Chalcone derivatives have been found in many natural products which have shown many interesting features regarding pharmacological and physiological activities as well as widely applied in organic synthesis.Cyclization reactions,oxidation reactions etc.based on chalcones are important strategies in the field of organic chemistry.Efficient transformations without a metal catalyst are of great value,and organic transformations catalyzed by molecular iodine have attracted considerable attention in recent years because it’s less expensive and environmental-friendly than transition metals,and lack of residual metallic impurities.In this article,novel cyclization and oxidation reactions have been developed for the efficient synthesis of poly-substituted imidazo [1,2-a] pyridines via tandem reaction induced by iodine and the formation of multisubstituted cyclohexa-1,3-dienamine promoted by AlCl₃ based on chalcones.The article is divided into five chapters including a series of 64 target compounds designed and synthesized,among which 57 structures were new compounds.It could be described as following:1.I2-promoted oxidative amination was developed for the synthesis of a series of 21 polysubstituted 3-arylimidazo[1,2-a]pyridines from chalcones and 2-aminopyridines.We have developed a mild and highly regioselective methodology for the preparation of substituted 3-arylimidazo[1,2-a]pyridines from readily available starting materials and have surveyed the reaction conditions,such as various additives,addition order,solvents,temperature,ratio of iodine and so on.The results showed that the optimal parameters were as follows: Charge 2-aminopyridines dropwise to a mixture of chalcones and additive Na₂CO₃ in DCM for 1h then 2 equiv.iodine was added at 40 °C in ambient air stirring for 8h and obtained corresponding products in 55%-83% yields.All of these products were new compounds.Moreover,the reaction between chalcones and 2-aminopyridines mediated by iodine under solvent-free high-speed vibration milling（HSVM）conditions has been surveyed.The reaction conditions have been optimized as well,and a total of 9 parallel 3-arylimidazo[1,2-a]pyridines were synthesized in 53-64% yields under the optimal reaction conditions.2.A unique and efficient approach towards the synthesis of substituted 2-arylimidazo[1,2-a]pyridines with the same starting materials as the first portion via I2?Induced aerobic oxidative coupling in a one-pot procedure has been developed.The optimized reaction conditions were as follows: a mixture of chalcones,1.6 equiv.2-aminopyridines,1 equiv.AlCl₃ and 2 equiv.molecular iodine in chlorobenzene refluxed for 16 h under an O2 atmosphere and obtained 22 corresponding products in 56%-82% yields.3.We have developed a novel protocol for the synthesis of multisubstituted 1,3-cyclohexadienes via a one-pot direct cyclization reaction between chalcones and β-enamines promoted by AlCl₃.We have discussed and selected the reaction parameters,the optimal reaction conditions of the cycloaddition of chalcone and β-enamino ester were obtained using 1 equiv.AlCl₃ in dry toluene at 80 °C for 8 h,a series of 21 products were obtained in 44-95% yields.All of these products were new compounds.