Nuclear Magnetic Resonance Spectra of Psychotherapeutic Agents. V*-Conformational Analysis of 1,3,4,5-Tetrahydro-2H-1,5-benzodiazepin-2-ones

Article abstract of DOI:10.1002/mrc.1270150414

The conformational analysis of biologically active lofendazam (7-chloro-5-phenyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one) is carried out by means of lanthanide shift reagent assisted 1H NMR spectroscopy: the lanthanide induced shift computer simulation suggests that in deuteriochloroform the heterocyclic ring of lofendazam assumes a cycloheptene-like chair conformation, where 1-N moves away from trigonal stereochemistry to a very flattened pyramidal structure.At room temperature the conformational equilibrium is markedly shifted (85percent) towards the conformer showing pseudoaxial H-1 and 5-Ph.The remarkable influence of steric requirements is controlling conformation, and the importance of 3- and/or 4-methyl groups in hindering the ring inversion at room temperature, have been verified by conformational analysis of suitable analogous 1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-ones.