Studies On Methodologies For The Synthesis Of Imidazo [1,2-a]Pyridine Derivatives

Imidazo[1,2-a]pyridine is fused heterocyclic skeleton from imidazole and pyridine, which is widely used in medicinal chemistry and materials science. Therefore, the construction of imidazo[1,2-a]pyridine has attracted a considerable attention of scientists all the time. In recent decades, imidazo[1,2-a]pyridine syntheses have enjoyed rich literatures and diverse synthetic strategies provide theoretical basis for our work. The thesis is mainly aiming at exploring some convenient and efficient methods to synthesize imidazole[1,2-a]pyridine derivatives, containing the following five chapters:Chapter One: Reviewing advances in synthesis of imidazo[1,2-a]pyridine. Imidazo[1,2-a]pyridine derivatives are important target molecules in organic synthesis, which are found in a lot of natural products. Many of them exhibit prominent biological activities. For nearly a century, a variety of imidazo[1,2-a]pyridine derivatives have been synthesized via hundreds of methods. Throughout the literatures, their syntheses are mainly classified into the following three categories: (1) Based on the formation of imidazole ring to; (2) Based on the formation of pyridine ring; (3) Based on the simultaneous formation of imidazole and pyridine ring. Among them, using 2-aminopyridines as the starting material is the most convenient strategy. In recent years, new organic synthesis techniques have been developed, such as solid-phase synthesis, microwave synthesis and automated continuous flow synthesis, exhibiting incomparable advantages, which have been applied to achieveing synthesis of a number of imidazo[1,2-a]pyridines.Chapter Two:Studies on methodologies for one-pot three-component synthesis of 3-nitro-2-aryl-imidazo[1,2-a]pyridines. Multicomponent reactions taking the advantage of easy operating, cost saving, atom economy, becomes one of the most effective strategies to achieve green reaction. We have developed a simple method using aminopyridines, aldehydes and nitromethane as the raw materials catalyzed by copper salts in one-pot three-component reaction to synthesize 3-nitro-2-aryl-imidazo[1,2-a]pyridines. The procedure is tolerated to many functional groups and proceeds well in moderate to good yields. It has been first reported that nitromethane as one of the carbon sources to build imidazole[1,2-a]pyridine, not only provides a carbon atom but also reserves a nitro group. Nitro group is easy for conversion that can be used to derivatize many drug molecules with specific functions. The method may have potential applications in medical chemistry.Chapter Three: Studies on methodologies for synthesis of 3-alkyl-2-aryl-imidazole[1,2-a]pyridine catalyzed by ferrous chloride. We use 2-aminopyridine compounds and (E)-(2-nitroalkyl-1-en-1-y1)benzene to successfully build 3-alky1-2-aryl-imidazole[1,2-a]pyridine through [3+2] cycloaddition eliminating the nitro group in the presence of ferrous chloride catalysts. It has rarely been reported in current literatures that (E)-(2-nitroprop-1-en-1-yl)benzene takes part in synthesizing imidazole[1,2-a]pyridine with 2-aminopyridine and (E)-(2-nitroprop-1-en-1-y1)benzene is readily accessible. In addition, When (E)-(2-nitrobut-1-en-1-y1)benzene was tested, we successed, too. Consequently, the procedure provides a simple and effective synthesis for diverse derivatives.Chapter Four: Studies on methodologies for copper acetate catalyzed-aerobic oxidative synthesis of benzo[4,5]imidazo[1,2-a]pyridine. C-H activation has become a hot topic recently, with advantages of convenience and efficiency, environmental friendliness, thus constucting heterocycles via C-H activation has drawn wide attention of researchers. Based on our previous research, we can get fused ring compounds with imidazo[1,2-a]pyridine structural unit by employing 2-aminopyridine compounds and phenyl boric acid compounds via C-H activation and C-N formation. Compared to reported routes to benzo[4,5]imidazo[1,2-a]pyridine, the method has advantages on accessible substrates, moderate reaction conditions etc. Benzo[4,5] imidazole[1,2-a]pyridine fused structure has high fluorescence activity, which can be used as photoelectric materials and applied to the genetic fluorescent tags, as a result, our work is of great significance for the synthesis of the molecular.Chapter Five: Summary of imidazole[1,2-a]pyridine and outlook on the follow-up work.