Study On Regioselective Construction Of Imidazole Derivatives From Alkynyl Aldehydes

As an important aromatic five-membered heterocyclic compound,imidazole derivatives are widely existed in many fields,such as natural products,drug molecules,material chemistry,organic chemistry,biochemistry and so on.Especially,imidazole derivatives have a wide range of pharmacological activities,and many of the drugs on the market have imidazole heterocyclic structure.Among the imidazole derivatives,sulfonylated imidazoles and hydroxylated imidazoles have better biological activity,so explore the methods of constructing these compounds with high efficiency and high regioselectivity has become an important in the field of chemical synthesis.On the other hand,alkyne aldehydes have alkynyl group and aldehyde group,which can be used for cyclization and addition reaction.Also,alkyne aldehyde as a basic raw material is involved in the synthesis of many important compounds.Based on these points above,it is great significance to develop the method to construct imidazole derivatives by using alkynyl aldehyde.In this context,we focused on the strategy of functionalization of alkynyl aldehydes to synthesize sulfonylated imidazoles and hydroxylated imidazoles via C-N,C-S and C-O bonds formation.The details in the following three chapters:In chapter one,The applications of imidazole derivatives in natural products,drug molecules,material chemistry,organic chemistry,biochemistry and other fields are summarized.Then,the recent progress in the synthesis of alkynyl aldehydes and imidazole derivatives were introduced.In chapter two,we have developed an highly regioselective pathways for constructing different of sulfonylated imidazoles via three-component reactions of amidines,ynals and sodium sulfonates.On the one hand,AcOH-promoted condition for affording the 4-sulfonylated imidazole.On the other hand,TBHP controlled for the synthesis of the5-sulfonylated imidazole.Nucleophilic addition and free radical formation are proposed as the key steps in these two processes.In addition,the selective construction of different imidazoles from the same starting materials by an additive selection has few reported before.In chapter three,we have reported an highly regioselective pathways for constructing 4-hydroxylated imidazoles and 5-hydroxylated imidazoles.H₂O¹⁸ labeling experiments showed that the oxygen of the hydroxyl group came from water.This method features simple operation,mild reaction conditions and high atomic economy,which have shown strong practical application potential.