Study On The Synthesis Of Novel Fused Pyrazole Derivative Catalyzed By Copper

Transition metal-catalyzed cross coupling reaction has been one of the hot topics in today’study of organic synthesis, it is an effective and important protocol for the construction of C-C and C-X (N, O, S, Se, etc). And the common transition metal Pd and Ni catalyzed reaction usually proceeded well, but they have some intrinsic shortcomings (for example:higher prices, toxic, and usually need unstable and higher virulent organophosphorus ligands, these defects has greatly impeded their large-scale application in organic synthesis. In recent years, copper catalyzed coupling reaction is showing more and more advantages in organic synthesis, because of its low-cost, low toxicity, etc. At present, construction of useful heterocyclic compound using copper catalyzed coupling reaction is also the currently development tendency.Benzopyrazolo[1,5-c]thiazine and pyrazolo[1,5-a]isoquinoline have been recognized as two types of important heterocyclic compounds, which have shown to interact with a variety of biologically receptors. The former has good anti-inflammatory, anti-allergic and biological activity, while the latter appear in a plethora of natural product and has attracted much attention due to the remarkable biological activities, for example, inhibitor of human topoisomerase I, the anticancer agents and novel antiherpetic reagent. Hence, the constuction of two types of heterocyclic has very important value, especially in found that their new bioactive molecules. However, current research and report about the two kinds of heterocyclic compounds are little, so to explore new methods for efficient constructing two types of compounds is of great significance.In the first chapter, we briefly reviewed the synthesis and versatile applications of pyrazole, enaminone,β-oxodithioesters; Then the application of several synthetic methods such as coupling reaction, copper catalyzed Ullmann cross-coupling in organic synthesis were introduced. In the second chapter, a new method is established that using the enaminone, hydrazine and isothiocyanate as raw material, and twenty-one unreported new benzopyrazolo[1,5-c]thiazines were high regioselectively synthesized under the catalytic system of CuBr/1,10-phenanthroline. This methord is simple and efficient and can avoid the generation of byproducts. So we successly opened up a new route to synthesis of benzopyrazolo[1,5-c]thiazine derivativesIn the third chapter, we make use of5(3)-amino-substituted3(5)-phenyl-1H-pyrazol and β-oxodithiocsters as substrates to synthesize pyrazolo[1,5-a]isoquinoline derivatives. Through research, finding that:new pyrazolo[1,5-a]isoquinoline derivatives could be facilely and efficiently synthesized from readily available materials via one-pot protocols under the ligand-free copper-catalyzed conditions, involving two processes:intermolecular coupling and intramolecular nucleophilic substitution. The reaction has many advantages, for example, good regioselective, high yield and simple post-treatment.The structures of all the target compounds were confirmed by IR,’H NMR,13C NMR and HRMS, and the plausible mechanism was also presented.