The Construction Of Self-Organization Reaction Network:the New Methodology For The Synthesis Of Diverse Heterocycles

Self-organizatioin widely exists in the natural world, human society, living system, and other fields. In the chemical field, the traditional self-organizing research focuses on the organizational behavior of non-covalent bonds. Besides that, how to construct covalent bonds conveniently, efficiently, orderly has always been the goal of synthetic organic chemists to pursue. In order to achieve the ideal organic synthesis process, we combined molecular self-organizational behavior with the traditional cascade reaction. Substrate molecules spontaneously organized by disproportionation, parallel and convergence process for the synthesis of complicated target molecules. This "parallel convergence network model" compared to the traditional "single linear cascade reaction model" is more conform to the ideal concept of organic synthesis and it is a kind of strategy for the construction of novel molecular skeleton. At the same time, it is also an important means to expand new reaction type.Based on organic unit reactions and cascade reaction as the component of self-organization integration, we put forward several novel self-organizing reaction network strategies, and realized the synthesis of a series of novel heterocyclic compounds. The main content is as follows:In chapter one, we firstly outlined the self-organizational behavior research in all fields, and reviewed the self-organizational behavior in organic synthesis. Finally, we put forward our research topics based on the self-organizational behavior.In chapter two, based on parallel, gather response patterns existing in nature and traditional organic unit reactions, we tried to integrate multiple organic unit teactions in a reaction system. After the reaction substrates spontaneously parallel convergence processes, this strategy could build complex target molecules in one step. We termed this kind of reaction as the self-labor reaction network. With aromatic methyl ketone, benzoin and ammonium acetate as reaction substrates, molecular iodine as a catalyst in DMSO, these parallel reactions could respectively generate 2-iodo-1-phenylethanone, α-arylglyoxals, benzyl and imine. Finally, the target molecular oxazole was synthesized by gathering generated intermediates.In chapter three, we used a variety of substrates aromatic methyl ketone, phenylethylene and phenylacetylene as reaction substrates to synthesize the same intermediate α-arylglyoxals via different pathways. Subsequently, the intermediate α-arylglyoxals could react with ammonium acetate in subsequent cascade reaction to generate oxazole compounds. We successfully built the multipath convergent coupling reaction network synthesis strategy through this method. A series control experiments showed that 2-iodo-1-phenylethanone and a-arylglyoxals were the intermediates of this reaction, and multiple reactions (iodination, Kornblum oxidation and annulation) were self-sequentially assembled in one pot.In chapter four, on the basis of the chapter two, we controlled the processes of reaction by changing the reaction conditions (changing solvent from DMSO to acetonitrile, and adding some base). Multisubstituted imidazole could be obtained from the same substrates. We found another example of self-labor reaction network. Through the control experiment, we found that the change of the solvent could avoid the oxidation of aromatic methyl ketone, thereby inhibiting the generation of oxazole compounds.In chapter five, the by-product was usually known as "waste" in traditional organic reactions. However, we hypothesized that the reaction could assemble the self-labor reaction network and by-product catalyst together. This method could improve the atom economy of the reaction through the use of generated by-product from upstream domino reaction to catalyze the downstream domino reactions. Based on this thought, we used aniline, aromatic ethyl ketone and sulfur salt as reaction substrates, CuO/I2 as catalyst with ligands and DMSO as solvent in alkaline condition. CuO/I2 could catalyze the upstream reaction to generated the by-product CuI, which could catalyze the subsequent convergence process of a-arylglyoxals,2-iodoaniline and sulfur salt to synthesize the thiazole compounds.In chapter six, we used simple and available aromatic ethyl ketone and thiourea as the starting substrates to construct the complex hereroaryl thioether compounds in one pot. In this reaction, we combined two domino reactions together with the suitable conditions to build the complex hereroaryl thioether compounds in one step. We successfully built the novel multipath coupling reaction network synthesis strategy through this method. By the analysis of mechanism, this reaction could assemble multiple iodination, condensation, dehydration and hydrolysis reactions together for the synthesis of complex compounds.In chapter seven, on the basis of chapter six, we could synthesize the sulfur methyl substituted amides thiazole compounds by changing the reaction conditions (improving the reaction temperature) from the same starting substrates. We successfully built the novel self-sorting reaction network synthesis strategy through this method. In this reaction, a part of the substrate aromatic methyl ketone could react with thiourea to generate intermediate sulfur methyl amino thiazole. The other substrate aromatic methyl ketone could convert to intermediate phenylglyoxal. Finally, the two intermediates could be gathered to form the target thiazole compounds.In chapter eight, We used phenols and ketones compounds as the starting substrates, n-hexane as solvent in acidic conditions. In this reaction,2-H chromene could be obtained when using cyclohexanone as substrate,4-H chromene could be obtained when using aromatic ethyl ketone as substrate, spiro structure could be obtained when using acetone as substrate, cyclopentane structure could be obtained when using pentanone as substrate. Each kind of target molecules were confirmed by single crystal diffraction. We successfully revealed a novel diversity-oriented synthesis system.In chapter nine, inspired by C-H activation and functionalization which in the rapid development in recent years, we used ethyl benzoylacetate and free of substituent of indole as the starting material to synthesize indolo[2,3-b]carbazole through the iodination, oxidation, cyclization reactions of ethyl benzoylacetate. This reaction successfully achieved the C-H functionalization of ethyl benzoylacetate and free of substituent of indole without metal, and effectively expanded the types of C-H functionalization reaction.In chapter ten, we summarized the thesis and gave an outlook of this research topic.