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

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 P2(1)/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. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

In this study, a novel pyridazine and triazolopyridazine compound was successfully synthesized through a multi-step organic synthesis approach. The synthesized compound was characterized and analyzed using various spectroscopic techniques to investigate its intermolecular interactions.