The Synthesis Of Quinazolinone And Indolizinone Derivatives Based On C-C Bond Cleavage

This dissertation focused on new synthetic methods of the quinazolinone and indolizinone derivatives, including the following two parts:In the first part, we updated the synthetic methods of 2-substituted quinazolinone derivatives. Cu Br2-catalyzed domino reactions of 2-halobenzamide with α-substituted benzylamine, along with the cleavage of C-C bonds to construct 2-aryl quinazolinones was investigated. The influence of catalysts, solvents and temperature on the yields was studied. The domino reactions achieved N-(α-substituted) benzylation, benzylic C-H amidation, and C-C(or C-H) bond cleavage, without the addition of any ligand and additive. In order to understand the mechanism of this reaction, the intramolecular C–C bond cleavage of the key intermediates 2, 2-substituted-2,3-dihydroquinazolin-4(1H)-ones was studied. And we found the trend for the bond-cleavage in the order of: H > alkyl > methyl > phenyl > substituted aryl. 2-aminobenzamide and formaldehyde as raw materials, even if there are not any catalysts and additives, also will separate into further dehydrogenation aromatization product.In the second part, the copper salt catalyzed domino reaction to construct 3, 8a-disubstituted indolizinone derivatives was founded efficiently. The reaction started from readily available pyridyl ketones and terminal alkynes, avoiding of the separation alkynyl pyridine alcohol intermediates. The influence of catalysts, solvents and bases on the yields was studied. The optimized conditions was found to be: Cu(OAc)2 as catalyst, NEt3 as the base, 1, 4-dioxane as solvent. The substrate scope, and possible reaction mechanism was investigated next. It is proved that the di-pyridyl ketone with copper ion complexing enhanced the nucleophilicity of carbonyl group, so the intermediate alkynyl pyridine alcohol easily formed in the reaction system; alkynyl pyridine alcohol further undergoes migration and cyclization to afford the target product, and sometimes can be realized quantitatively.