NMR spectra and conformational analysis of substituted 1,3,4,5‐tetrahydro‐2H‐1,5‐benzodiazepin‐2‐one derivatives

Abstract

An investigation of the molecular dynamics of substituted 1,3,4,5-tetrahydro-2H-l,Ibenzodiazepin-2-0ne derivatives revealed that these molecules adopt cycloheptadiene-like boat conformations. There is an equilibrium between the quasi-axial and the quasiequatorial conformer in which the quasi-axial conformer is predominant. The difference in their conformational energies is less than 1 kcal mol-'. The most important factor influencing the energy barrier between the conformers is the presence of a substituent other than hydrogen at N-1. Our findings disprove earlier reports by other workers.

Sex pheromone for the brownbanded cockroach is an unusual dialkyl-substituted alpha-pyrone.

“…The only other reported synthesis of 3,5-dimethyl-2H-pyran-2-one (18) involved a lowyield (=1%) photochemical decomposition. Careful analysis of the 'H NMR spectrum, the nuclear Overhauser effect difference spectrum (23), and the twodimensional correlation spectroscopy via long-range coupling (COLOC) spectrum (24) of 3,5-dimethyl-2H-pyran-2-one confirmed that our original assignment of the pheromone as an alkyl-substituted a-pyrone was correct. However, the ring methyl is located at the 3 position, which is contrary to what the long-range coupling data suggested.…”

Conformational Complexity in Seven-Membered Cyclic Triazepinone/Open Hydrazones. 2. Molecular Modeling and X-ray Study

“…Attempts at clarification have been made both experimentally (mainly NMR spectroscopy) and theoretically (mainly molecular mechanics calculations) for the most stable conformations and the interconversion mechanisms of cycloheptenes, benzocycloheptenes, 1a, seven-membered benzoheterocycles, and other related heterocyclic compounds . Most of these studies suggest that the chair form ( C ) has the lowest energy for both cycloheptenes and benzocycloheptenes, although some disagreement appears to exist as to the nature of the transition state conformation for the most likely interconversion pathway.…”

“…proposed five coplanar carbon atoms. Simple carbocyclic derivatives of cycloheptene have very low ΔG ⧧ values,1a and replacement of the ring carbons by heteroatoms causes such constraints that the barriers to interconversion become higher 3a…”

“…The idea that biological activity of the benzotriazepines (mainly as psychotherapeutic agents) 5 depends not only on the pharmacophoric grouping 4c but also on the conformation of the seven-membered ring in the biological fluids 3c makes the present potentially active and structurally related compounds attractive for a computational study. To our knowledge, no experimental and/or computational study on compounds related to our 1,3,4-benzotriazepin-5-ones exists, with the exception of the cis − trans isomerization at the annelation of the hetero ring of some 1,3,4-benzotriazepinones 3b 1 Compounds under Study …”

Circular Dichroism Studies on New Optically Active 1,5-Benzodiazepine Derivatives

“…In continuation of our studies on benzodiazep ine-based compounds, widely used as therapeutic agents for the treatm ent of anxiety and neuroses [1][2][3][4] and for reasons of studying structure-activity relationships, perform ed by pharmacologists [1][2][3][4][5][6][7][8], we described recently synthetic routes to optically active l,3,4,5-tetrahydro-2//-l,5-benzodiazepin-2-ones as analogs of Lofendazam [9], 1.3.4.5-tetrahydro-2//-benzodiazepines and 1.3.4.5-tetrahydro-2//-benzodiazepin-2-thiones [10]. For the Lofendazam analogs, 4-methyl-1.3.4.5-tetrahydro-2//-benzodiazepin-2-one with one chiral center at C-4 in the 7-membered ring was used as a starting m aterial which could be eas ily prepared by the reaction of o-phenylenediamine with crotonic acid in 5.5 N HC1 [11].…”