Oxygen-Directing Hydrocarbon-Activated Derivatization Of Quinazolinones

Quinazolinone derivatives exhibit a wide range of biological and pharmacological activities,such as anti-tumour,anti-microbial,anti-inflammatory and anti-viral.Many marketed drugs such as methaqualone,thaqualone,avloquone,chloroquine,quinacrine,fluprodione,tiaclavasta and raltitrexed bear core structure of quinazolinone.Consequently,tremendous efforts have been devoted to the synthesis and functionalization of quinazolinones.In the past decades,transition metal-catalyzed C-H bond activation/functionalization of quinazolinones for the synthesis of fused quinazolinones have been witnessed immense progress.However,reports in this realm,N atom was used usually as the directing group for these transformations,and oxygen is seldom reported as the directing group.In addition,benzofuran compounds show strong biological activities,such as anti-oxidant,anti-tubercular and anti-bacterial.Over the past few years,tremendous efforts have been devoted towards the development of efficient protocols for the construct of benzofurans and especially their late-stage C-H derivatization.We envision that hybrid molecules bearing both quinazolinone and benzofuran sekeltons may be bestowed with enhanced or synergetic biological and physical characteristics.Thus,this thesis focuses on the development methods for late-stage derivatization of quinazolinone and benzofuran by transition metal-catalyzed C-H activation.The main points are as follows:In part one,we developed a promising protocol for the synthesis of5,6-diphenylpyrano[2,3,4-de]quinazolines.The O-directing rhodium-catalyzed C-H activation of 2-alkyled quinazolinone and annulation with alkynes produced the corresponding 2-alkyl-5,6-diphenylpyrano[2,3,4-de]quinazolines in good yields with widely substrate adaptability.The results indicated that electron-donate group such as methyl or methoxyl on the mother benzene ring of quinazoline have strong promote effect on the reaction.In part two,we described a highly efficient synthetic protocol to quinazolinone-benzofuran-based polyheterocyclic hybrids.The Rh(III)/Cu(II)-catalyzed double cross-dehydrogenation coupling reaction of 3-aryl quinazolinone and benzofurans,followed tandem intramoleclar cyclization to give the corresponding9-(benzofuran-2-yl)-11H-benzofuro[3’,2’:3,4]quinolino[2,1-b]quinazolin-11-one with good yields and widely substrate adaptability.Furthermore,the synthesized products exhibit a orange-colored emission in the solids,which indicated the potential application.