Studies On The Tandem Reactions Of N,N-Acetals And Orthoformates

The tandem reaction can efficiently construct complex compounds from simple raw materials,by two or more consecutive steps.It has many advantages such as environmental friendly,less energy consumption,simple operation,and so on.Therefore,the design of simple and efficient tandem reaction is an important task of organic synthetic methodology.N,N-ketene acetals is an important organic synthon with multiple reaction sites.It is also an important material for the synthesis of nitrogen-containing heterocyclic compounds and widely used in organic synthesis chemistry and pharmaceutical chemistry.N,N-ketene acetals can be synthesized by the nucleophilic substitution reaction of S,S-ketene acetals or S,N-ketene acetals with amine.This synthetic method has the advantages of simple operating,easy post-processing,high yield and environmental-friendly.Our group has been devoted to the study on synthesis methodology based on the chemistry of S,S-ketene acetals.We are good at the reaction of S,S-ketene acetals and S,N-aketene acetals.Therefore,on the basis of previous works,the new applications of N,N-ketene acetals in organic synthesis were studied to develop novel and practical strategies for the synthesis of nitrogen-containing heterocyclic compounds.Pyrimidine dihydroimidazole derivatives are heterocyclic compounds with high biological activities.They are the main components of anticoagulants,hypnotics,antimicrobials and insecticides.These compounds are widely used in biology,agriculture and pharmaceuticals.However,the traditional synthetic method usually needs multi-steps,and there are many problems,such as complex reaction procedures,the need to pre-modify the reactants and so on.The development of novel and practical synthetic methods of pyrimidine dihydroimidazole derivatives has good application is prospected.In this thesis,a series of pyrimidine dihydroimidazoles were designed and synthesized from easily available N,N-ketene acetals.A six-membered heterocycle was constructed by the convergence of N,N-ketene acetals,ammonium hexafluorophosphate and orthoformate in multicomponent reactions.Three C-N bonds and one C-C bond were also constructed.This is a 40 minutes'reaction without expensive transition metal catalysis,which has the advantages of simplicity and high efficiency.Ammonium hexafluorophosphate is used as not only a catalyst but also a reactant in the reaction.The orthoformate also play a dual role as reactants and solvents,making the reactionenvironmental-friendly.This synthetic strategy provides a simple and efficient way for the synthesis of nitrogen-containing heterocyclic compounds.In this paper,a series of new N,N-ketals were synthesized from dithioketals by a simple method.A series of imidazopyrimidines were synthesized from the synthesized N,N-ketals.The structures of all compounds were confirmed by ¹H-NMR,¹³C-NMR and HRMS.The structure of some compounds has also been confirmed by single crystal diffraction experiments.The reaction mechanism was also tested.