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NMR of some benzodiazepine drugs: Structure elucidation with lanthanide‐induced shifts of N‐1 substituted benzodiazepinones
Author(s) -
Cazaux Louis,
Vidal Christiane,
Pasdeloup Maurice
Publication year - 1983
Publication title -
organic magnetic resonance
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0030-4921
DOI - 10.1002/omr.1270210310
Subject(s) - chemistry , steric effects , lanthanide , moiety , ring (chemistry) , stereochemistry , solid state , side chain , crystallography , ion , organic chemistry , polymer
Two 1,4‐benzodiazepinones of psychopharmacological interest, pinazepam (2) and prazepam (3), were studied in solution by 13 C and 1 H NMR. 1 H variable‐temperature experiments showed that the seven‐membered ring exists in a simple pseudo‐boat form at room temperature, but the energy barrier is higher in 3 (Δ G 405°c = 82.8 kJ mol −1 ) than in diazepam (1). Moreover, upon addition of LSR, the boat conformation is retained in the lanthanide ion‐substrate complex, as with 1 in the solid state. Using a concentration‐dependent shift technique and a computer‐assisted LIS method, the conformations of the N ‐branched side‐chain were investigated. Two preferred orientations were found for the propargyl group of 2, while three unequally populated conformations of the cyclopropyl moiety of 3 are distributed preferentially in the sterically unhindered space around the complex.