Premium
Ring inversion barrier of diazepam and derivatives: An ab Initio study
Author(s) -
Paizs Béla,
Simonyi Miklós
Publication year - 1999
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1999)11:8<651::aid-chir7>3.0.co;2-5
Subject(s) - chemistry , conformational isomerism , diazepine , computational chemistry , ring flip , ab initio , ring (chemistry) , diazepam , inversion (geology) , molecule , organic chemistry , medicine , paleontology , structural basin , pharmacology , biology
Systematic ab initio calculations were performed to investigate the ring inversion process of various 1,4‐diazepines including diazepam, N 1 ‐desmethyldiazepam, and 3‐methyl‐ N 1 ‐desmethyldiazepam. The diazepine ring adopts a shape of a boat; owing to asymmetric substitution two such boats are possible in mirror image relation to each other. In the present study both structural and solvent effects were investigated on the energetics of ring inversion of nine diazepine derivatives. The calculated ring inversion barriers for diazepam (17.6 kcal/mol) and N 1 ‐desmethyldiazepam (10.9 kcal/mol) are in good agreement with the corresponding experimental data. In the cases of diazepam and N 1 ‐desmethyldiazepam, the calculated minimum energy path of the ring inversion is asymmetric contrary to the fact that the terminals (M and P conformers) are equienergetic. Chirality 11:651–658, 1999. © 1999 Wiley‐Liss, Inc.