Study On The Cyclization Of Alkynyl Quinazolinone

Quinazolinone is important nitrogen-containing heterocyclic compound.As one of the most important structural units in medicinal chemistry,quinazolinone derivatives exhibit a wide range of pharmacological activities,including anti-inflammatory,anti-tumor,anti-convulsant,sedative,anti-hypertensive,vasodilator,anti-microbial and anti-bacterial.Therefore,its synthesis and bioactive evaluation has been the research interest of a great deal of organic synthetic chemists and pharmaceutical chemists.In this thesis,we focus our studies on the metal-or trifluoroacetic-acid-catalyzed intramolecular cyclization of alkynyl-containing quinazolinones to synthesize fused quinazolinone derivatives.The major research part of the thesis consist of three parts:Part I:Focused on the gold(III)-catalyzed selective cyclization of 1-or3-alkynyl-2-pyrroles quinazolinone to synthesized the 2,3-fused quinazolinone derivatives.The results indicated that 1,2-fused quinazolinones could obtained through a 1,3-rearrangement and sequential 6-exo-trig cyclization of1-alkynyl-2-pyrrolyl quinazolinone,while 3-alkynyl-2-pyrrolyl quinazolinone undergo a directly 6-exo-dig or 7-endo-dig cyclizations to afford 2,3-fused quinazolinones.The cyclization reaction has the characteristics of mild conditions,good regioselectivity and diversity in the structure of cyclized products.The scheme provides a new synthetic strategy for the construction of 1,2-fused quinazolinone.Part II:Focused on the TFA-catalyzed selective cyclization of2-alkynyl-3-arylquinazolinone to synthesis of 2,3-fused quinazolinone derivatives.A series of 2,3-fused quinazolinones were synthesized in medium to good yields through TFA–catalyzed selective cyclization of 2-alkynyl-3-arylquinazolinone prepared from readily available isatoic anhydride and aromatic amines.The results indicated that only the 2-alkynyl-3-arylquinazolinone with a substituents of methoxy,or an ethoxy group on the meta position of the 3-aryl can undergo the cyclization reaction,suggesting that the type and position of the substituent on the 3-aryl play an important role in the cyclization reaction.Part III:Focused on the TFA-catalyzed of 2-alkynyl-3-arylquinazolinone to synthesis of 2-alkenyl-3-aryl substituted quinazolinone derivatives.When the3-position substituent of the 2-alkenyl quinazolinone is 4-bromo-3-methoxy phenyl,2-alkenyl-3-aryl quinazolinone derivatives would obtained in the TFA-catalyzed condition.Further studies proved that when the substituent of the 3-position aryl is a benzoxy group on the meta-position,a halide on the ortho-,meta-or para-of the aryl,as well as an aryl group attached to the alkynyl group,all the products of the TFA-catalyzed reaction were 2-alkenyl 3-aryl substituted quinazolinone derivatives.All the structure of the target compounds were characterized and confirmed by the ¹H NMR,¹³C NMR and HRMS.