MOLECULAR-STRUCTURES AND CONFORMATIONS OF 1-BENZENESULFONYL-2-OXO-5-ALKOXYPYRROLIDINES WITH ANTIAMNESIC ACTIVITY - X-RAY, H-1-NMR AND QUANTUM-MECHANICAL (PM3) STUDIES

The crystal and molecular structures of the nootropic agents RU-47001 ((±) 1-(4-nitrobenzenesulphonyl)-2-oxo-5-ethoxypyrrolidine) and RU-47064 ((±) 1-(4-nitrobenzenesulphonyl)-2-oxo-5-isopropyloxypyrrolidine) have been determined by X-ray analysis and their solution conformation has been investigated using 1H NMR spectroscopy. The conformations of these molecules together with those of their analogues RU-35929 ((±) 1-benzenesulphonyl-2-oxo-5-ethoxypyrrolidine), RU-47010 ((±) 1-(3-pyridinylsulphonyl)-2-oxo-5-ethoxypyrrolidine) and RU-35965 ((±) 1-benzenesulphonyl-2-oxo-5-isopropyloxypyrrolidine) have been deduced from semi-quantitative PM3 type theoretical calculations. The main feature of all compounds consists of a common envelope conformation with C (4) at the flap of the pyrrolidinone ring in the solid, that in solution changes into the analogous, but opposite, possible puckered conformational isomer. The 5-alkoxy groups were found rather flexible in solution. Theoretical preferred conformations about N-S and S-C bonds were in acceptable agreement with those of the solid state. The calculated torsional energetics suggested that 1–5 do not undergo conformational interconversion.