Study On Lithium - Halide Exchange Reaction And Fries Rearrangement In Microreactor

The microreactor is a novel continuous-flow reactor with high heat and mass transfer efficiency, which has received significant research attention. In microreactor, the reaction temperature, reaction time and the ratio of reactants can be accurately controlled, while can be applied to the larger production directly. Therefore, the microreactor has excellent application prospects in the field of organic synthesis.Chapter1:The structural characteristics and building units of microreactor were introduced, and the strategies and methods were presented how to build microreactor system. Combined with the application of chemical reactions, the heat and mass transfer, continuous-flow character and the ability of scale-up were reviewed.Chapter2:Lithium-halogen exchange reaction was applied in the introducing electrophilic substituents to the heteroaromatics, but the reaction temperature (-78℃) hampered this useful reaction. We have designed and constructed a set of three-injected microreactor system, which can be used rapid and efficient synthesis of the products at mild conditions successfully. Extensive reaction results revealed that such synthetic method was widely applicable for different kinds of heteroaromatics with various substituents. And the scale-up experiments were completed efficiently. Next, the two-step lithium-halogen exchange reaction was studied in a five-injected microreactor system. This system was not only avoid side reactions effectively, but also integrated multi-step reaction to carry out the reaction.Chapter3:We studied the Fries rearrangement reaction in microreactor, based on the microreactor’s ability of precise control. The reaction was carried out in microreactor successfully, and can synthesize rearrangement products and the substituted products respectively by adjusting the residence time and reaction temperature. This system can prepare substituted salicylic amide derivatives at the ambient conditions. In addition, This system also can provide a new method for synthesis an ortho electrophilic substituted products at-40℃. The experimental results were satisfactory and highlighted that the microreactor has a widely application prospects.