Absolute configuration of 1,5-diazepin-2-ones: A critical test case for density functional theory

• Published in: Computational and theoretical chemistry Vol. 1044; pp. 15 - 23
• Main Authors: Jahangir, Sajid, Khan, Khalid Mohammed, Fabian, Walter M.F.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.09.2014
• Subjects: Benzodiazepinones; Electronic circular dichroism; LPNO-CEPA/1; Ring conformation; TDDFT; LPNO-CEPA/1; Benzodiazepinones; Ring conformation; Electronic circular dichroism; TDDFT
• ISSN: 2210-271X
• DOI: 10.1016/j.comptc.2014.06.003

[Display omitted] •Two nearly isoenergetic conformations of benzodiazepinones by CEPA/1 calculations.•Almost mirror image ECD curves of these conformations by TDDFT simulation.•Reversal of conformer stability and sign of the CD curves by N5 substitution.•Closest agreement with experiment with the B3PW91 functional except nitro derivatives. The absolute configuration of a series of 4(R)-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-ones is assigned by comparison of experimental and calculated CD spectra using time-dependent density functional theory (TDDFT) in combination with four different functionals (B3PW91, CAM-B3LYP, M06-2X, BMK). Closest agreement with experiment is obtained with B3PW91. All compounds except those bearing an acyl group at N5 exist in two nearly isoenergetic conformations of the seven-membered ring (G⩽0.5kcalmol−1 with the local pair natural orbital coupled-electron pair approximation LPNO-CEPA/1/def2-TZVPP//B3LYP/6-311G(d,p)). Agreement between simulated and experimental CD spectra was found to critically depend on a proper description of conformer population as well as the position of the calculated longest-wavelength transitions of the individual conformers.