Synthesis Of Nitrogen-containing Heterocyclic Compounds Via Multi-component1,4-dipolar Cycloaddition Reactions

Synthesis of nitrogen-containing heterocyclic compounds currently have drawed much attention in organic chemistry. Multicomponent reactions (MCRs) are powerful tools for the synthesis of complex and diverse molecules, which is due to their simple procedures, without separation of intermediates, high atom economy, and formation of several new covalent bonds in one pot manner. In this thesis, multi-component1,4-dipolar cycloaddition reactions were developed to construct novel nitrogen-containing heterocyclic compounds. The results and details are as fel lowing:1. The methodology of substituted trifluoromethyl-1,3-oxazine derivatives via a continuous flow microreactor has been developed. The products were obtained in moderate to good yields via1,4-dipolar cycloaddition cascade nucleophilic approach of acetylenedicarboxylate, substituted isoquinoline and trifluoromethyl acetophenone, and the structures of products were determined by1H NMR、13C NMR、HRMS and IR, and the possible reaction mechanism was proposed as well. The fast mass/heat transferring and perfect mixing of regents associated with the flow technique eliminated the formation of the six-member byproduct. Compared with the corresponding batch operation, microreactor exhibted fast reaction rate, high selectivity and better yields.2. A simple and facial approach to highly functionalized pyrimidone derivatives and indole fused pyrimidones has been developed. The synthesis of substituted pyrimidone derivatives in moderate to good yields involves [4+2] cycloaddition of1,4-dipoles generated from α,β-unsarurated imines and dimethyl acetylenedicarboxylate (DMAD) with isocyanates as a dipolarophile. This procedure was simple and efficient. The reaction conditions were mild and the substrates were well tolerated. Moreover, the pyrimidones resulted from2-bromine phenyl isocyanate could be transformed into various indole fused pyrimidones via intramolecular palladium-catalyzed Heck reaction under different conditions. The decarboxylation products were detected, which provide a new method for decarboxylation. The structures were confirmed by single crystal X-ray analysis,1H NMR,13C NMR, HRMS and IR. Also, the possible mechanism was proposed.