Studics On Mcthodologies For The Synthesis Or Scveral Nitrogen-Containing Heterocylic Derivatives

Nitrogen-containing heterocycles and their derivatives have a wide range of biological activities. They have very important value of application and play significant roles in various fields of pharmaceuticals, agricultural chemicals and life sciences. Therefore, the synthesis of nitrogen-containing heterocycles and their derivatives has undoubtedly become the research hotspot in the field of organic synthesis. We aim at synthesizing several kinds of important nitrogen-containing heterocyclic derivatives which possess potential biological activities through some novel, simple and efficient methodologies. The main work presented in the dissertation can be divided into three parts:In the first chapter, we have reviewed the synthesis of pyridines and summarized several ways to build a pyridine ring. In the review part, we have also given an introduction to the present approaches to diarylpyridines, which contain the vapor-phase cyclization of acetophenone, formaldehyde, ammonia, the arylation of the pyridine nucleus with organometallic reagents, and the palladium-catalyzed direct arylation of pyridine N-oxides. We have developed a simple method for the synthesis of diarylpyridines through a cyclocondensation reaction of aromatic ketones with ammonium acetate. By controlling the steric effect of the substrates, we can selectively synthesize2,4-and2,6-diarylpyridines. Compared to the reported routes to diarylpyridines, our method has many advantages such as high efficiency, regioselectivity, no metal catalyst, cheap, readily available substractes, and needing no prefunctionalization.In the second chapter, we have reviewed the recent research progress of Pummerer reaction. There is a brief introduction about inter-and intramolecular Pummerer reaction, asymmetric Pummerer reaction, and the utilization of Pummerer reaction in the natural product total synthesis. We have developed a facile and efficient approaches to3-methylthiomethyl substituted indoles through a novel NH4OAc and CuBr(PPh3)3-induced intermolecular Pummerer reaction between indoles and dimethylsulfoxide. It has been first reported herein that indole took part in the intermolecular Pummerer reaction with dimethylsulfoxide as a nucleophile. And the reaction can not be achieved through the traditional Pummerer reaction conditions. Therefore, this NH4OAc and CuBr(PPh3)3-induced Pummerer reaction may have a sense in expanding the Pummerer reaction's scope. In addition, we have also done some researches and explorations in utilizing the3-methylthiomethyl substituted indoles products for the synthesis of other useful indole derivatives.In the last chapter, we have reviewed the latest advancements in functional groups-directed C-H activation. We have given a brief introduction to the synthesis approaches to aromatic ketones and the palladium-catalyzed sp2C-H bond oxidative coupling reactions with aldehydes in this review. We have studied the palladium-catalyzed C-C and C-O bonds formation in the aromatic ring via1,2,4-benzotriazine-directed C-H activation, and we have developed the palladium-catalyzed acylation reaction of3-aryl-1,2,4-benzotriazines with aldehydes and the approaches to the synthesis of their acetate derivatives in the AcOH/Ac2O system.1,2,4-benzotriazine, which had potent biological activities, was first used as a C-H activation directing group. It is more challenging than simple pyridine ring since it possesses two additional nitrogen atoms. Furthermore,1,2,4-benzotriazine was a precursor to the new anticancer drug TPZ, so our work may has a significance to the study of developing this kind of drug.