The Application Of Sp~2 C-H Functionalization In The Synthesis Of Aromatic Amines And Quinoline Derivatives

The introduction of specific groups on the arylamine or aminoquinoline benzene ring is an important component of the drug synthesis reaction and is also the focus of current organic synthesis research.The amino-substituted aromatic ring or the N-containing heterocyclic compound has high pharmacological activity and is a hot spot in current medicinal chemistry research.The specific research contents are as follows:The first chapter mainly describes the C-H functionalization reaction and the Synthesis methods of sp² C-O and C-C bond.In the second chapter,the pharmacological activities of benzofuran and its intermediates and the synthesis of O-arylhydroxylamine were reviewed.The method was designed for constructing sp² C-O bond with selectfluor as oxidant,reaction temperature of 40 ^oC,reaction time of 2 h,no metal-catalyzed.Through the oxidative coupling reaction of a series of disubstituted anilines with N-hydroxyphthalimide or N-hydroxymaleimide,the target product was synthesized in moderate to excellent yield?the highest yield is 81%?.It is a new method for synthesis of N-aryloxyimides via oxidative coupling reaction.In addition,the product could be transformed into the aryloxyamines,which is the key intermediate to prepare benzofuran derivatives,after aminolysis.In the third chapter,pharmacological properties of quinoline derivatives and the C?5?-H functionalization reaction were developed.the C?5?-H functionalization reaction of 8-acylquinoline derivatives was carried out with fac-Ir?ppy?₃ as photocatalyst,KOH as additive and blue light as light source.A series of amide-substituted quinolines reacted with BrCCl₃ to synthesize a series of8-amidoquinoline C?5?esterification products in moderate yield?the highest yield is70%?,it is a new method for constructing C?sp²?-C?sp²?bond.Then the reaction conditions were optimized.The reaction mechanism was verified by experiments.In summary,this paper has developed two synthetic routes for the aryl C?sp²?-H functionalization reaction.The C?sp²?-O bond synthesis is metel-free.This reaction owned a high atomic economy and proceeded under mild conditions,environmentally friendly;The C?5?-H functionalization of the 8-amidoquinoline derivative fills the blank of the carbonylation reaction system,excellent regioselectivity?reaction always happened on para-position of aniline?.the operation is simple and the synthesis step is short.