Synthetic Access to Unsymmetric, Tridentate, Pyridyl-1,3,4-oxadiazole Complexants via Intramolecular Oxidative Annulation of Arylhydrazides with Heteroaryl Carbaldehydes

Abstract

Over the last four decades, an ideal complexant for the chemoselective liquid−liquid separation of the minor actinides from the lanthanides contained within spent nuclear fuel has yet to be realized. As strategic performance objectives continue to evolve as a function of time, solubility in process-relevant diluents, fast complexation kinetics, as well as robustness to hydro-and radiolytic degradation remain at the forefront of this grand challenge. While the vast majority of soft-N-donors are symmetric in nature, this laboratory has focused on defining synthetic methods to afford unsymmetric complexants for further study to explore the impact subtle changes to the molecular topography of the complexant moiety have on performance, in addition to working toward the definition of structure−activity relationships. The development of an intramolecular iodine-mediated oxidative annulation of heteroaryl-aryl-hydrazones for the production of functionalized, tridentate, and unsymmetric 1,3,4-oxadiazole-based complexants is reported. Optimization of reaction conditions afforded numerous products in high isolated yield over two linear steps in one pot in one hour of reaction time. The cleanliness of the optimized conditions negated the need for the chromatographic purification of 32 of 44 examples attempted. Method development, optimization, substrate scope, application to related heteroarenes, and a scale-up reaction are described herein.

Synthesis of Fused [1,2,3]-Triazoloheteroarenes via Intramolecular Azo Annulation of N-Tosylhydrazones Catalyzed by 1,8-Diaza-bicyclo[5.4.0]undec-7-ene

“…The successful substrate necessitated the use of quinoline derivatives, as the three pyridine examples attempted were, ultimately, unsuccessful with the developed conditions. In 2021, our lab reported a Kornblum-type reaction to afford oxidized precursors, which lead to the construction of heteroaryl-1,3,4-oxadiazoles, although combining oxidation, condensation, and cyclization in one pot was unsuccessful in this work.…”