X-RAY, NMR AND THEORETICAL-STUDIES OF THE STRUCTURE AND CONFORMATION OF THE NOOTROPIC AGENT TENILSETAM

The conformational properties of the nootropic agent Tenilsetam (3-(2-thienyl)-2-piperazinone) have been assessed in the solid, liquid and isolated state by X-ray diffraction, NMR spectroscopy (H-1, C-13) and quantum chemical calculations (MO semiquantitative PM-3 method), respectively. The thienyl and 2-piperazinone rings are nearly perpendicular in the crystal. The 6-membered ring adopts a very distorted chair conformation with the thienyl at C(6) in equatorial position. Bond angles and distances agree with their standard values. The high-field H-1 and C-13 NMR spectra were run in CDCl3 solution. The results of the spectral analysis indicate that the 2-piperazinone ring in solution undergoes fast interconversion between the half-chair and the twist-boat forms. Theoretical calculations produced 2 almost equi-energetic conformational minima, both corresponding to the 2 relative possible perpendicular arrangements of the rings. The relative minimum is in fairly good agreement with the conformation in the crystal.