Synthesis, structure analysis, DFT calculations, Hirshfeld surface studies, and energy frameworks of 6-Chloro-3-[(4-chloro-3-methylphenoxy)methyl][1,2,4]triazolo[4,3-b]pyridazine

Abstract

In medicinal chemistry, heterocyclic compounds like pyridazine analogs has shown significant pharmaceutical importance. In this view, the compound 6-chloro-3-[(4-chloro-3-methylphenoxy) methyl][1,2,4]triazolo[4,3-b]pyridazine (4) was synthesized treating 2-(4-chloro-3 methylphenoxy) acetic acid (1) with 3-chloro-6-hydrazinylpyridazine (2) in dry dichloromethane (DCM) followed by the addition of lutidine, and O-(benzotriazole-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU) in cold condition to achieve 2-(4-chloro-3-methylphenoxy)-N'-(4-chloropyridazin-3-yl)acetohydrazide (3). Then the compound (3) was heated with chloroamine T in the presence of ethanol to furnish the desired compound (4). The synthesized compound was elucidated by spectroscopic techniques (IR, NMR and LC-MS), and finally the structure was confirmed by XRD technique. The compound (4) has crystallized in the monoclinic crystal system with the space group P21/c. Density functional theory calculations were carried out to find the extent of harmony between the theoretical and experimental values. HOMO-LUMO energy gap and the global reactivity descriptor values of the compound (4) have been determined. In the structure C-H...N intermolecular hydrogen bond and the scarce C-Cl...cg interaction are observed. Hirshfeld surface analysis is also performed. Energy frameworks were constructed to understand the packing of molecules by studying the different intermolecular interaction energies.