Investigation On The Synthesis Of Quinoline And Biquinoline Derivatives

Nitrogen-containing heterocyclic compounds are very important parts of organic compounds.In view of their widespread occurrence in natural products,they have been used for a long time.So far,nitrogen-containing heterocyclic compounds have been used in many fields such as medicine,biology,pesticide and materials.With the large-scale use of people,problems such as difficult extraction,non-renewable,drug resistance and side effects are gradually exposed to people’s vision.Therefore,chemists began to study the artificial synthesis and modification of nitrogen-containing heterocyclic compounds.Quinolines and biquinolines are research hotspots among nitrogen-containing heterocyclic compounds.They have great medicinal value and material application prospects,which have been proved in helping people overcome diseases and improve living conditions in the past.Their synthesis methods are under constant development.Now,with the concept of green and sustainable development,the development of organic synthesis methods tend to be in the direction of low energy consumption,mild conditions,high atom economy and waste reduction.According to literature research,various synthetic methods have their merits,but the current research progress can not fully meet the needs of production and life.For this reason,on the basis of previous work,we have developed the new synthetic methods for 2-arylquinolines and 2,2’-biquinolines,which are more correspond with current requirements.In the introduction,we introduced the organocatalyzed synthesis of quinolines.These methods have the characteristics of catalysts stable,easy preparation and environmental friendliness;the mechanism of the I2/DMSO synergistic oxidation system and application in the construction of carbon-heteroatom bonds are summarized;the Povarov reaction and the recent development of the reaction are briefly introduced;finally,summarized the pharmaceutical activities and applications of quinolines and biquinolines.In the second chapter,we introduced the one-pot synthesis of 2-arylquinolines via in situ acid catalysis.Firstly,the examples of 2-arylquinolines constructed from 2-vinylaniline and various C1 synthons,and the cascade reactions using by-products to promote downstream reactions were briefly introduced.Our method used 2-vinylaniline as starting materials,benzyl halide as the C1 synthon,by-product HBr generated in situ as the catalyst to promote the ring formation,NMP as solvent and the reaction was heated at 140℃ without additional additives.The target product could be obtained.In this method.the amino group underwent nucleophilic substitution with benzyl halide to form secondary amine,which was then oxidized to imine at high temperature,subsequently acid-activated imine and vinyl underwent intramolecular addition to form a ring,finally,oxidative aromatization occurred to obtain the target product.This strategy provided a simple and efficient synthesis method for 2-arylquinolines.In the third chapter,we introduced one-pot two-step process for the synthesis of 2,2’-biquinolines promoted by I2/DMSO synergistic oxidation system.Firstly,three kinds of synthetic methods of biquinolines were briefly introduced.Transition metal-catalyzed coupling reactions,direct conversion of quinoline N-oxides to biquinolines and direct construction of biquinolines from simple starting materials.On the basis of the work in Chapter 2,we continued to use 2-vinylaniline as the starting material,2-methylquinoline as the C1 synthon,through iodination,Kornblum oxidation,electrocyclization and aromatization in the I2/DMSO synergistic oxidation system to obtain the target product.In this method,the hydrogen on the methyl group of 2-methylquinoline is substituted by elemental iodine to form iodide,DMSO oxidized iodide to 2-formylquinoline which then condensed with amino group to form imine.Finally,under heating conditions,electrocyclization and oxidation took place,a series of 4-phenyl-2,2’-biquinoline compounds were obtained.The system is relatively mild,avoiding traditional metal oxidants,and also provides new ideas for the synthesis of other heterocyclic compounds.In the fourth chapter,we introduced I2/DMSO promoted three-component Povarov reaction for the Synthesis of 2,2’-Biquinolines.First,the example of the construction of quinoline rings by the Povarov reaction were briefly introduced,We hope that after summarizing the previous work of other researchers,we can get some inspiration.Finally,on the basis of the work in Chapter 3,we continued to use I2/DMSO synergistic oxidation system and use 2-methylquinoline,p-toluidine and ethyl pyruvate as starting materials,a series of ethyl 6-methyl-[2,2’-biquinoline]-4-carboxylates were obtained through iodination,Kornblum oxidation and Povarov reaction.The first step of the reaction also converted 2-methylquinoline to 2-formylquinoline,then 2-formylquinoline condensed with p-toluidine to form azadiene,finally,dienophiles occurred a Mannich-like addition reaction with azadienes to form a ring obtaining the target product.This strategy synthesizes complex molecules from simple and readily available starting materials,at the same time,reduces the steps of purification and avoids the complicated post-treatment process,so that lower generation of waste,less energy consumption,and more correspond with the concept of green chemistry.