The Direct Construction Of Fused Heterocyclic Structures Via The Dimroth Rearrangement Of Isatins And Aryl Isothiocyanates

Isatin,also known as indoline-2,3-dione,is a well known natural product with simple structures and a wide range of sources.Isatin was first found in 1841 by Erdman and Laurent in the oxidation product of indigo.Due to the gamma-lactam group and the active carbonyl group in the C-3 position,isatins have become a kind of widely used substrates in organic chemistry for more than a century.Indolinones are one of the most common alkaloids found in nature.Because of their similarity to isatin,chemists often choose isatin or its derivatives as starting materials for the synthesis of these alkaloids.Also,the active carbonyl group of the C-3 could also serve as a potential chiral center.On the other hand,studies on the oxidation reaction and ring expansion reaction of isatins are not common.In this thesis,the oxidation reaction and ring-expansion reaction of isatins were combined which was achieved by capturing with isothiocyanates under an oxidizing weak alkaline environment.During this process,we tried to change the reaction temperature,the substituents of the reactants and other conditions to explore the novel and effective method for the construction of 12H-benzo[4,5]thiazolo[2,3-b]quina-zolin-12-ones,2-amino-4H-benzo[d][1,3]thiazin-4-ones and 2-thioxo-2,3-dihydro-quinazolin-4(1H)-ones.The main contents of this thesis include the following three parts:In the first chapter,the synthetic methods of the isatins were summarized first.Then its applications in the synthesis of natural products and fused heterocycles were described.According to previous literatures and our experiments,we proposed our research topic.In the second chapter,based on our previous studies for the oxidative ring expansion of isatins,the ring expansion reaction of isatins and o-haloarylisothiocyanates was studied.Ring expansion reactions of isatins such as Pfizinger reactions,were important methods for the synthesis of heterocyclic compounds.In this type of reaction,isatins were generally hydrolyzed to o-aminobenzoylformates under strong alkaline conditions(such as sodium hydroxide).Then,ring expansion with another component took place and would give the corresponding product,while other types of reactions were relatively rarely reported.We used isatins and o-haloarylisothiocyanates as substrates to carry out the decarboxylative cyclization of isatins under the oxidizing weak base environment to give 12H-benzo[4,5]thiazolo[2,3-b]quinazolin-12-ones.Preliminary mechanistic studies have shown that isatins first underwent Baeyer-Villiger-type oxidation,and then decarboxylation and cyclization took place under weak alkaline conditions.During the process of ring opening,Dimroth rearrangement was interrupted by intramolecular amidation,thereby forming 12H-benzo[4,5]thiazolo[2,3-b]quinazolin-12-ones.In the third chapter,based on the control experiments in Chapter 2,we found that the reaction of isatins with arylisothiocyanates produced a stable,separable intermediate 2-amino-4H-benzo[d][1,3]thiazin-4-one.We then studied the temperature-controlled oxidative decarboxylation and cyclization of isatin and isothiocyanate under oxidative weak alkaline conditions,which could give kinetically stable product 2-amino-4H-benzo[d][1,3]thiazin-4-one at room temperature.When the temperature rose,Dimroth rearrangement of the 2-amino-4H-benzo[d][1,3]thiazin-4-one occurred,thus giving thermodynamically stable product 2-thio-2,3-dihydroquinazolin-4(1H)-one.