Solid-state studies of phthalazinylhydrazones and triazolophthalazines: the role of the nitro group

Abstract

Hydralazine is an antihypertensive drug, which is metabolized to hydrazone and fused triazole. A series of its derivatives: phthalazinylhydrazones, their chloride salts and triazolophthalazines possessing a nitro group has been synthesized and structurally characterized. A facile air promoted oxidative cyclization was proposed for the synthesis of triazolophthalazines from phthalazinylhydrazones. In contrast to the traditional synthetic methods, the reaction proceeds under mild conditions in the absence of additional transition metal catalysts or oxidants. Examination of the family of crystal structures of the compounds possessing a nitro group at different positions and without this group has allowed the determination of the steric and geometrical preferences for the occurrence of hydrogen and non-hydrogen bonding intermolecular interactions formed by nitro groups, and their effect on the molecular self-assembly of the solid state. The changes in the crystal packing caused by the change in the nitro group position and the presence of an additional linker group have been discussed. The description of intermolecular interactions has been combined with the analysis of the calculated interaction maps, and the differences in molecular packing have been correlated with the differences in the physical properties for the two polymorphic forms of one of the phthalazinylhydrazones.