The Application Of Continuous Flow Chemistry In The Asymmetric Reduction Of Biphenylketones

Continuous flow chemistry is a technology which provided power by the pump,and the substrates in continuous flow system were bumped into microchannels.As a new synthesis technology,it`s accurate controlled,rapid response of reaction parameters and many other advantages,not only can improve the product quality but also can guarantee purity and security.What is more,it is conducive to product industrialization;it`s high automation can reduce the intermediate manually processing steps.Heterogeneous catalyst for asymmetric catalytic synthesis of chir al compounds is also a hotspot in recent years.Guo Hua Liu group has reported a series of solid catalysts based on mesoporous silica materials,the preparation of heterogeneous catalysts were used in water phase,and the results of ketone compounds showed good catalytic performance.Chiral alcohols can be used as important raw materials or intermediates medicament,its source is mainly from ketone asymmetric reduction reaction,and the reaction conditions were mild.In a word,if the heterogeneous catalysts catalyst biphenyl compounds can be applied in continuous flow chemistry,and if the green chemical solvent can be used,then it can realize green continuous flow reaction,to be better applied to the industrialized production,based on the above basis,this paper is mainly divided into the following two parts:(1)Take the advantage of organic silicon mesoporous material has the characteristics that rich in hydroxyl on the surface,so it can load some specific metal complexes with ligand.When [Arene RuC l2]2 as a metal complexes loaded on the organic silicon mesoporous material,Synthesize three type load chiral ruthenium metal catalysts(Cat.1,Cat.2,Cat.3 respectively)and load in the reactor respectively,the selected three catalysts(Cat.1,Cat.2,Cat.3)are three typical catalysts,Cat.1 is mesoporous long channel organic catalyst;Cat.2 is mesoporous short channel organic catalyst;Cat.3 is mesoporous long channel inorganic catalyst,using the method of continuous flow chemistry to reduction phenyl acetop henone,select the best catalyst under the condition of the same temperature and flow rate and solvent,select the best catalyst as loading catalyst,and then select the best temperature,make research of the flow rate too,and then,try different typical of the substrates.The conversion can reach 99 % of the rate and the stereo selectivity is above 95 % under the condition of the flow rate of 0.6 mL/min.Finally,we has explored several typical substrates,respectively for 2 phenyl and the 3 phenyl of phe nyl acetophenone using the method of continuous flow catalytic reduction,the result convinced us that catalyst loading in the mobile phase is through the pore size of mesoporous materials,it took the advantages of the mesoporous materials.(2)We had achieved the series reaction of coupling and reduction under the flow conditions.PdPPh2 loaded on imidazole ionic liquid materials(IBOIHS)through grafting method,forming heterogeneous catalyst PdPPh2-IBOIHS(Cat.4),Cat.4 was used as the coupling catalyst;use the best reduction catalyst we have selected in the first step,and the best temperature as the reaction temperature,coupling reaction,under the condition of minimum flow rate,control the reaction conditions to get the best reaction results,extensions to the substrate at the same time,then applied to the synthesis of benyi methadone and its derivatives.Experiments results show: the continuous flow chemistry as a new synthesis technology,shows the superiority of the method of synthesis is a general method.The efficiency;rapid response;and the success of the cascade reaction of the the continuous flow chemistry,achieved the target of the traditional laboratory studies pursued.