Investigation On Methodology For The Synthesis Of Quinoline,Quinoxalinone,and N-Azaindene Derivatives

Aromatic ring species containing nitrogen atoms are widely present in medicinal plants and clinical drug molecules,due to important biological activities,these compounds are widely used in biomedicine,agriculture,photoelectric materials,Organic catalysis and synthetic intermediates,etc.This dissertation focuses on exploring the new synthetic methods of quinoline,quinoxalinone and N-azaindene.With the tireless efforts of scientific researchers and the development of new synthetic methods,we found that the existing synthetic methods of these compounds have some deficiencies.Such as pre-functionalization of the substrate and multi-step operations will cause redundant reaction waste and reduce the yield of the target compound,high reaction temperature,catalyst sensitive to humidity or air,low reaction selectivity,complicated post-processing and so on.We accomplished the direct dehydrogenation functionalization of quinoline,quinoxalone and coumarin through peroxidants involved free radical synthesis strategy.We constructed a series of different N-azaindene derivatives through dehydrogenation cross coupling strategy.In conclusion,we developed new synthesis methodology for quinoline,quinoxalinone,furocoumarin and N-azaindene derivatives,which can efficiently realize the rapid construction of related derivatives.In Chapter 1,we introduced the free radical reaction promoted by peroxidants,different peroxidants with catalysts participated free radical reaction was summarized in detail.Then,we gave a brief overview of the palladium and iodine catalyzed dehydrogenation cross coupling reaction.In the final part of the introduction,we introduced some important biological activities and applications of quinoline,quinoxalinone,furocoumarin and N-azaindene derivatives.In Chapter 2,we introduced N-iodosuccinimide and tert-butyl hydroperoxide involved 2-methylquinoline C(sp3)-H bond functionalization reaction.We used 2-methylquinoline and benzothiazole as starting materials,N-iodosuccinimide as catalyst,tert-butyl hydroperoxide as oxidant,and DMSO as solvent.In this synthesis method,t-butoxy and t-butoxy peroxide radicals was formed by the reaction of tert-butyl hydroperoxide with N-iodosuccinimide.Then,2-methylquinoline reacted with free radicals and generated quinoline-2-carbaldehyde,benzothiazole transformed to 2-aminothiophenol under acidic conditions.Finally,condensation and cyclization of 2-aminothiophenol with quinoline-2-carbaldehyde formed target compound.We synthesized a series of 2-azaarylbenzothiazole derivatives.Remarkable features of this work include simple operation,mild conditions and good substrate applicability.Based on the work described in Chapter 2,we have a comprehensive understanding of peroxides promoted free radical reaction.We finished the cuprous iodide and benzoyl peroxide Involved carbamoylation of quinoxalin-2(1H)-ones C(sp2)-H bond,using N-methylquinoxalinone and carbamoylhydrazide as starting materials,cuprous iodide as catalyst,benzoyl peroxide as oxidant.In this synthesis method,cuprous iodide reacted with benzoyl peroxide and furnished benzoyloxy radicals,which reacted with carbamoyl hydrazide and formed carbamoyl radical intermediate.Finally,target compounds were obtained by the addition and oxidation of carbamoyl radical with quinoxalinone.Compared to the traditional preparation of amide compounds,this synthesis method were relatively mild.Both aliphatic and aromatic substrates can form coupling products in good yield.This reaction does not need activation of the substrate or novel catalysts.In addition,we provide a new route for the amidation of a,β-unsaturated compounds.In Chapter 4,we introduced synthesis of furo[3,2-c]coumarins via I2/TBHP-mediated reaction.The reaction was performed at 90℃ with 4-hydroxycoumarin and phenylacetylene as the reaction substrate,iodine as catalyst,tert-butyl hydroperoxide as oxidant and dioxane as solvent.In this synthesis method,4-hydroxycoumarin isomerized into chromane-2,4-dione,which reacted with iodine and formed C-I bond.Finally,the breakage of C-I bod formed radical intermediate,which reacted with phenylacetylene and formed furo[3,2-c]coumarin through addition and cyclization reaction.Compared with the existing synthesis method,advantages of this process include atom-economy,commercial availability of starting materials and good functional group tolerance.In Chapter 5,we introduced CH3CO2H-prompted construction of trisubstituted pyrrolo[1,2-a]pyrazines.The reaction was performed with only 5 equivalents of acetic acid in ethanol at 120℃ without adding any additives.The trisubstituted pyrrolo[1,2-a]pyrazine derivatives were obtained in good yield.This strategy provides a green,environmental friendly and convenient operation synthesis method for the preparation of polysubstituted pyrrolo[1,2-a]pyrazine compounds.In Chapter 6,we introduced the construction of imidazo[1,2-a]pyridine biaromatic heterocyclic compounds and explored the fluorescence properties of these compounds.We used palladium acetate as catalyst,silver carbonate as oxidant,pyridine as ligand and dioxane as solvent,the reaction was performed at 100℃ under air atomosphere.The target compound was obtained in moderate to good yield.A series of C3-position heterocyclic imidazo[1,2-a]pyridine compounds were furnished by this synthesis strategy,the ultraviolet-visible absorption spectrum,fluorescence spectrum and fluorescence quantum efficiency of these compound was measured systematically.The relationship between structure and fluorescence properties was analyzed.We expect that these fluorescence structure can be further modified and may be turned into potentially useful reagents for biological imaging.