Microwave-Assisted Synthesis Of Imidazo[2,1-b]Thiazole Derivatives

Imidazo[2,1-b]thiazoles represent an important class of heteroaromatic compounds, which possess biological activities in the medicinal chemistry and bioorganic chemistry and interesting optical properties in material chemistry. It’s valuable to aim on the preparation of imidazo[2,1-b]thiazole derivatives, since such researches could be helpful for scientists to screen potential "drug-like" molecules and modify the optical properties of some functional materials, Rencently, C-H functionalization catalyzed by transition metal has attracted worldwide attention and been extensively explored. This strategy has currently been used as a powerful tool for the formation of numerous (hetero)arene C-C bond. On the basis of our previous research works on MAOS (Microwave-assisted Organic Synthesis), this thesis is focused on the convenient synthesis of imidazo[2,1-b]thiazoles with controlled microwave irradiation. The context includes the following three parts:Chapter1:The development and its application on heterocycle ring synthesis of microwave-assisted organic synthesis (MAOS) are reviewed, and the progress of palladium catalyzed C-H functionalization of heterocyclic compounds is summarized. In addition, current situation of microwave promoted C-H functionalization towards heterocycles under palladium catalysis is briefly inrtoducted. Finally, the subject and content of the thesis are drawn forth.Chapter2:Under microwave irradiation, a range of arylimidazo[2,1-b]thiazoles have been prepared by a one-step rapid cyclization of an array of substituted phenacyl bromides and2-aminothiazoles in the presence of inorganic bases. After the cyclocondensation conditions screened, such as solvents, bases, temperatures, reaction times, reactant ratios and so on, the target compounds could be acquired in yields of65-96%within15min. This method has the advantages of short reaction time, few procedures, high yield, as well as relatively broad substrate scope. Thus, it provides a practive access to synthesize similar molecules.Chapter3:Using unprotected imidazo[2,1-b]thiazoles of5-phenyl substituted in imidazole moiety and versatile aryl bromides as starting materials, a series of poly-aryl substituted imidazo[2,1-b]thiazole derivatives have been effectively synthesized via palladium catalyzed regioselective arylation under microwave irradiation. To achieve the optimal reaction conditions, the effects of various palladium catalysts, ligands, bases and solvents were evaluated. Then, the optimal conditions were established and the substrate scope was further extended. Under this transformation,29new coupling products were ultimately synthesized and their structures were characterized by1H NMR,13C NMR, IR and HRMS and confirmed by X-ray single crystal diffraction analysis. Density functional theory (DFT) calculations demonstrate this regioselctive arylation of imidazo[2,1-b]thiazoles undergo a CMD pathway, which is well consistent with our experimental results. Compared with the previous synthetic methods reported in literatures, this new protocol uses readily available materials as reagents under non-inert conditions and is atom-economic, efficient, site-selective, high-yielding, tolerant to a number of functional groups on the aryl bromide.