Derivatization Of 2-Arylquinazolinones By Carbene Pathway

The preparation and transformation of diazo compounds have been studied for more than a century and are still in a booming stage in modern organic synthesis.Diazo compounds are easily decomposed by transition metals(such as Cu,Rh,Pd),to form metal carbene or carbenoid active intermediates by extrusion of nitrogen.These carbenoid active intermediates can participate in various organic reactions and play an important role in organic synthesis.Under the action of alkali,ethyl bromodifluoroacetate in situ form difluorocarbene active intermediates,which can participate in various organic reactions,and play an important role in the synthesis of organic compounds that containing difluoromethyl blocks.Quinazolinone derivatives are an important class of nitrogen-containing heterocyclic compounds with good biological activity and are widely used in pesticides and pharmaceuticals.It can be used as potentiating agents of doxorubicincytotoxicity,fluorescent chemosensor,biological enzyme inhibitor,and anticancer drug,etc.In this paper,it is proposed to synthesize a potentially biologically active2-arylquinazoline derivative by carbene active intermediate pathway with2-arylquinazoline compounds.In the first chapter,the recent progress in the catalytic activation of diazo compounds as carbene precursors in transition metal catalysis reactions and the synthesis of organic compounds containing difluoromethyl blocks by difluorocarbene reactive intermediates were summarized.In the second chapter of the thesis,a simple and efficient Rh(III)-catalyzed C-H activation and tandem intramolecular cyclization for the synthesis of evodiamine derivatives has been developed.Easily available diazo compounds and2-arylquinazolinones were used as starting materials.Directing C-H bond activation of 2-arylquinazolinones were taken place under the Rh(III)-catalysis,and were reacted with diazo compounds to form metal carbene active intermediate.A series of quinazolinones(evodiamine derivatives)containing hydroxyl were synthesized by carbene insertion and intramolecular cyclization reaction.This reaction proceeds with formation of C-C bond and C-N bond via C-H activation and cyclization toquinazolinone derivatives in moderate to excellent yields.The reaction showed high functional group tolerance,which provided an efficient and alternative route to quinazolinone derivatives backbone.In the third chapter,difluorocarbene active intermediates were in suit formed through the reactions of ethyl bromodifluoroacetate with potassium carbonate base,which the reacted with 2-arylquinazolinone by insertion into the hydroxyl group of the alcoholic isomer of 2-arylquinazolinone,and form a series of 4-difluoro methyl quinazolines.The method has wide substrate adaptability and provides a quick and simple method for the synthesis of 4-difluoromethoxyquinazoline derivatives.