Microwave-Assisted, Metal- and Azide-Free Synthesis of Functionalized Heteroaryl-1,2,3-triazoles via Oxidative Cyclization of N-Tosylhydrazones and Anilines
Zachary Z. Gulledge, Damian P. Duda, David A. Dixon, Jesse D. Carrick
Abstract
As the search for competent soft-Lewis basic complexants for separations continues to evolve toward identification of a chemoselective moiety for speciation of the minor actinides from the electronically similar lanthanides, synthetic methods must congruently evolve. Synthetic options to convergently construct unsymmetric heteroaryl donor complexants incorporating a 1,2,3-triazole from accessible starting materials for evaluation in separation assays necessitated the development of the described methodology. In this report, metal- and azide-free synthesis of diversely functionalized pyridyl-1,2,3-triazole derivatives facilitated by microwave irradiation was leveraged to prepare a novel class of tridentate ligands. The described work negates the incorporation of thermally sensitive and toxic organoazides by using N-tosylhydrazones and anilines as viable synthetic equivalents in an efficient 12 min reaction time. Adaptation to alternative synthons useful for drug discovery was also realized. Method discovery, optimization, N-tosylhydrazone and aniline substrate scope, as well as a preliminary mechanistic hypotheses supported by DFT calculations are reported herein.