title: Conformational analysis, part 43. A theoretical and LIS/NMR investigation of the conformations of substituted benzamides.
abstract: A refined Lanthanide-Induced-Shift Analysis (LISA) is used with molecular mechanics and ab initio calculations to investigate the conformations of benzamide (1), N-methylbenzamide (2), N,N-dimethylbenzamide (3) and the conformational equilibria of 2-fluoro (4), 2-chloro (5) and N-methyl-2-methoxy benzamide (6). The amino group in 1 is planar in the crystal but is calculated to be pyramidal with the CO/phenyl torsional angle (ω) of 20-25°. The LISA analysis gave acceptable agreement factors (Rcryst ≤ 1%) for the ab initio geometries when ω was decreased to 0°, the other geometries were not as good. In 2, the N-methyl is coplanar with the carbonyl group in all the geometries. Good agreement was obtained for the RHF geometries, with ω 25°, the other geometries were only acceptable with increased values of ω. In 3, good agreement for the RHF and PCModel geometries was found when ω was changed from the calculated values of 40° (RHF) and 90° (PCModel) to ca. 60°, the X-ray and B3LYP geometries were not as good. The two substituted compounds 4, 5 and 6 are interconverting between the cis (O,X) and trans (O,X) conformers. The more stable trans conformer is planar in 4 and 6 but the cis form non-planar. Both the cis and trans conformers of 5 are non-planar. There is an additional degree of freedom in 6 due to the 2-methoxy group, which can be either planar or orthogonal to the phenyl ring in both conformers. The conformer ratios were obtained from the LISA analysis to give Ecis-Etrans in 4 > 2.3 kcal/mol (CDCl3 ) and 1.7 kcal/mol (CD3 CN), in 5 0.0 kcal/mol (CD3 CN) and in 6 > 2.5 kcal/mol (CDCl3 ) and 2.0 kcal/mol (CD3 CN). These values were used with the observed versus calculated (1) H shifts to determine the conformer ratios and energies in DMSO solvent to give Ecis-Etrans 1.1, -0.1 and 1.8 kcal/mol for (4), (5) and (6). Comparison of the observed versus calculated conformer energies show that both the MM and ab initio calculations overestimate the NH..F hydrogen bond in (4) by ca. 2 kcal/mol.
authors.affiliation: The Chemistry Department, University of Liverpool, Crown St., Liverpool, L69 7ZD, UK.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Abraham
authors.affiliation: The Chemistry Department, University of Liverpool, Crown St., Liverpool, L69 7ZD, UK.
authors.forename: Nuria
authors.initials: N
authors.lastname: Aboitiz
authors.affiliation: Dipartimento di Chimica e Chimica Industriale, Università degli Studi di Genova, Genova, I-16146, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Filippi
authors.affiliation: Dipartimento di Chimica e Chimica Industriale, Università degli Studi di Genova, Genova, I-16146, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Genesio
authors.affiliation: Dipartimento di Chimica e Chimica Industriale, Università degli Studi di Genova, Genova, I-16146, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Piaggio
authors.affiliation: Dipartimento di Chimica e Chimica Industriale, Università degli Studi di Genova, Genova, I-16146, Italy.
authors.forename: Fernando
authors.initials: F
authors.lastname: Sancassan
mesh_terms: D001549:Benzamides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D011789:Quantum Theory
chemical_list: D001549:Benzamides
keywords: 13C; 1H; LIS; NH.F H-bond; NMR; benzamide conformations; solvation