Nuclear magnetic resonance spectra of psychotherapeutic agents. V*—conformational analysis of 1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-ones |
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Authors: | M. C. Aversa P. Giannetto G. Romeo P. Ficarra M. G. Vigorita |
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Abstract: | 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 (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. |
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