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Nuclear magnetic resonance spectra of psychotherapeutic agents. III . . Stereochemistry of 1‐methyl‐5‐phenyl‐2,3,4,5‐tetrahydro‐1 H ‐1,5‐benzodiazepine‐2,4‐diones
Author(s) -
Aversa Maria C.,
Giannetto Placido,
Romeo Giovanni,
Ficarra Paola,
Vigorita Maria G.
Publication year - 1980
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570170326
Subject(s) - chemistry , substituent , cycloheptatriene , atropisomer , ring (chemistry) , conformational isomerism , stereochemistry , steric effects , europium , computational chemistry , molecule , organic chemistry , ion
The stereochemistry of some 1‐methyl‐5‐phenyl‐2,3,4,5‐tetrahydro‐1 H ‐1,5‐benzodiazepine‐2,4‐diones was determined by proton magnetic resonance using the paramagnetic shift reagent tris (6,6,7,7,8,8,8‐heptafluoro‐2,2‐dimethyl‐3,5‐octanedionato)europium [Eu(fod) 3 ] two of these compounds, clobazam and triflubazam, are clinically used as psychotherapeutic agents. Several model structures, with intermediate stereochemistry in the range of the possible limit situations of benzocycloheptene, ‐cycloheptadiene or ‐cycloheptatriene type, are considered; LIS (3) are computer simulated on the basis of proton geometric parameters. It was found that at room temperature, these derivatives exist in only one pseudo‐boat cycloheptadiene‐like conformation, showing the 5‐phenyl group directed pseudo‐axially. This conformational preference is interpreted in terms of a balance between the steric requirements of the bulky substituent and electronic repulsion in the ring π‐system.