Structural and electronic properties of anticonvulsant drugs: substituted 3-tertiary-amino-6-aryl-pyridazines, -1,2,4-triazines, and -pyrimidines

Crystal structures of three anticonvulsant compounds 1-[6-(4-chloro-2-methylphenyl)pyridazin-3-yl]piperidin-4-ol (1), 1-[6-(4-chlorophenyl)-1,2,4-triazin-3-yl]piperidin-4-ol (2), and 1-[5-(4-methoxyphenyl)pyrimidin-2-yl]piperidin-4-ol (3), have been solved by direct methods from single crystal X-ray diffraction data and refined by the full-matrix least-squares method. The X-ray diffraction results suggest a limited inclination of the phenyl ring, when ortho-substituted, with regard to the middle heterocycle, a marked delocalization of the piperidine nitrogen lone pair towards the middle heterocycle, and a critical orientation for the piperidine-like group due to this delocalization. Assumptions made on the basis of the experimental data are confirmed and quantified by ab initio molecular-orbital calculations.