Progress Towards Electrophilic Cyclization of Heterocyclic Hydrazone Derivatives to Afford Unsymmetric, Functionalized, 5,6-Diphenyl-3-(Pyridin-2-yl)-1,2,4-Triazinyl Complexants

  • Zachary Gulledge


In continuation of this lab’s pursuit towards soft-Lewis basic complexant molecules for separating minor actinides from lanthanides contained within spent nuclear fuel, the feasibility of synthesizing unsymmetrical complexants bearing a 5,6-diphenyl-3(pyridine-2-yl)-1,2,4,-triazine core was explored and is reported herein. Oxidation pathways were screened for previously described Sonogashira coupling adducts to convert them to their corresponding ketones. Further derivatization to either a hydrazone or an oxime was then performed, affording the possibility to form a 1,2-pyrazole or 1,2-isoxazole, respectively, through an adapted iodine-mediated intramolecular electrocyclization procedure. The efficacy of this cyclization reaction was tested against a variety of substituted hydrazone examples. The possibility of utilizing Suzuki-Miyaura cross-coupling conditions on the resulting 4-iodo-3-phenyl-1,2-pyrazole (or 4-iodo-3-phenyl-1,2-isoxazole) for downstream functionalization was tested, and chromatographic purification protocols for the hydrazone derivatives and their successfully cyclized products were developed. Additionally, a copper-catalyzed cycloaddition pathway towards 1,2,3-triazoles was investigated. The current extent of method optimization relevant to production of starter materials and products will be discussed.