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Preparation Of 1,3-oxazine/oxazole Derivatives Based On Intramolecular Redox Cdc Reaction

Posted on:2021-03-05Degree:MasterType:Thesis
Country:ChinaCandidate:T T WangFull Text:PDF
GTID:2381330620976766Subject:Pharmaceutical engineering
Abstract/Summary:PDF Full Text Request
As a kind of important compound skeleton,nitrogen-oxygen heterocyclic compounds have important applications in many aspects.Oxazine/oxazole derivatives are widely used in natural products and medicines.They have a lot of pharmacological activities,such as antibacterial,anti-tumor,anti-tuberculosis,hypolipidemic,and hypoglycemic.1,3-Oxazine derivatives are also widely used in the field of total synthesis of natural product enantiomer alkaloids and materials.In 2016,the research group developed Zn(II)catalyzed intramolecular aromatic hydrogenation cross dehydrocoupling(Intramolecular Hydroarylation-Redox CDC)reaction,which realized the construction of C-C bond between N-propargyl compounds and different hybrid types of carbon nucleophilic reagents include nitromethane,indole and phenylacetylene.2-Substituted tetrahydroquinolines were synthesized efficiently.Based on this research,the nucleophilic group was changed to hydroxyl group with stronger nucleophilic property.At the same time,the nucleophilic group was connected to the nitrogen atom through carbon chain,and C-O bond was formed by cross dehydrogenation coupling to realize the efficient synthesis of 1,3-oxazine/oxazole derivatives.The innovation of this reaction is to realize the cross-dehydrocoupling of intramolecular C-O bonds,and a tricyclic product is constructed through one-step reaction using easily synthesized substrates.The work of this paper is divided into two parts: the first part is to optimize the conditions of catalyst,temperature,reaction time,reaction concentration,solvent and catalyst equivalent with N-(3-hydroxypropyl)-N-(2-propynyl)aniline as substrate.The optimum reaction conditions were as follows: CuI as catalyst,substrate concentration of 0.33 mol/L,reaction time of 10 h under the protection of nitrogen at 120 °C,in which condition the yield reach90%;The second part of the work is to expand the application scope of the reaction substrate,and 20 kinds of final products were obtained by replacing aromatic ring,alkynyl group and alkyl side chain with different substituents,and the yields ranged from 40% to 90%.The substrates have good applicability.
Keywords/Search Tags:1,3-Oxazine compounds, Cross-Dehydrocoupling Reaction, C-O bond formation reaction, Continuous cyclization, Green Synthesis
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