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Published on: January 3, 2018
Synthesis of 1,2,4-Triazole Derivatives Via Three-Component Tandem Cyclization Reactions Based on N-N Bond Formation
Shasha Wang1, Haoxian Wu1, Yaqi Zhan1
1School of Environmental and Chemical Engineering, Wuyi University, Jiangmen, 529020, China.
None:
We report a three-component tandem cyclization protocol that efficiently synthesizes 1,2,4-triazole derivatives from readily available primary amines, aldehydes, and amidines. The proposed mechanism proceeds through a multistep sequence involving initial condensation of an aldehyde and amine to form an imine intermediate, subsequent nucleophilic attack of an amidine on the imine-type intermediate, and final copper-catalyzed aerobic oxidative intramolecular N-N bond formation to yield the target product. Mechanistic insights are further elucidated through comprehensive density functional theory calculation studies. This protocol is operationally simple, uses low-cost starting materials, and exhibits broad functional group compatibility and high atom economy; these features highlight its strong potential for applications in pharmaceutical synthesis.
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