Studies On The [3+2] Cyclization Of N,S-acetals With Active Methylene Isocyanides

Poly-substituted imidazole and its derivatives are important nitrogen-containing heterocyclic compounds.Because of their good pharmacological and biological activities,they are widely used in the fields of organic synthesis,medicine,agricultural products and so on.In addition,it plays an important role in the field of dyes and polymer materials.Therefore,the development of simple and efficient synthetic methods for imidazole derivatives has always been a hot topic in organic synthetic chemistry.Ketene N,S-ketal is an easily-available organic intermediate with multiple reaction sites.The push and pull effects of electron donors and acceptors connected to the double bond allows ketene N,S-ketal to have polarity.Thus,ketene N,S-ketal showed excellent reactivity toward a variety of chemical reactions,such as nucleophilic addition,cyclization,etc.It has played important roles in the synthesis of heterocyclic compounds.Recently,our group developed an efficient synthesis of a series of4-aminoquinoline derivative from ketene N,S-ketal.Based on this work,and combined with the chemistry of active methylene isocyanide in the construction of nitrogen-containing heterocycles,the[3+2]cyclization of ketene N,S-ketal and active methylene isocyanide was studied,and a series of 1,4,5-trisubstituted imidazole derivatives were synthesized.This method has the advantages such as mild reaction conditions,simple operation and high yield.It provides a new way for the synthesis of poly-substituted imidazoles.Such a high regioselective synthesis may proceed via a ketene imine intermediate.The C=N double bond in the in-situ generated ketene imine intermediate showed high reactivity toward the active methylene isocyanide,leading to an efficient[3+2]cyclization reaction for the formation of1,4,5-trisubstituted imidazole.In this thesis,21 new 1,4,5-trisubstituted imidazole derivatives were synthesized.The structure of the products was confirmed by s ¹H-NMR,¹³C-NMR,high-resolution mass spectrometry and single crystal ray diffraction experiment etc.The reaction mechanism was also analyzed.