Nuclear magnetic resonance spectra of psychotherapeutic agents. V*—conformational analysis of 1,3,4,5‐tetrahydro‐2 H ‐1,5‐benzodiazepin‐2‐ones

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 1 H 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 (85%) towards the conformer showing pseudoaxial H‐1 and 5‐Ph. The remarkable influence of steric requirements in 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‐tetraydro‐ 2H ‐1,5‐benzodiazepin‐2‐ones.