Torsional angles in N-substituted benzamides and related compounds by carbon-13 N.M.R. chemical shifts

Abstract

The torsional angles in 30 N-substituted benzamides and related compounds have been estimated by the use of the 13C substituent chemical shifts of the meta and para carbon atoms. Steric interaction between the N-substituted groups and the ortho hydrogen atoms of the benzene ring is the major determinant of non-planarity in these systems. A linear relationship between steric substituent constants of the N-substituted groups of some benzamides and the torsional angles is proposed. Dynamic processes involving rotation about the C-N bond, nitrogen inversion and ring inversion contribute a dynamic steric effect to the overall steric interaction. The preferred conformations of some N-substituted groups is also discussed.

Captides: rigid junctions between beta sheets and small molecules

“…Aromatic carboxylic acids follow a more complex set of conformational rules; even the simplest case, a benzoyl group, adopts two near‐equivalent conformers. Benzamide bond conjugation competes with steric repulsion between amide and ortho ‐phenyl protons, such that the lowest energy conformations are plus and minus approximately 26° between the amide and benzene planes . See Figure .…”

“…Ortho substituent(s) can tune the ring‐plane to amide‐plane angle and thus the orientation of the aromatic small molecule adduct relative to the peptide chain. Hydrophobic ortho groups force benzamide bond angles higher . For example, 2,4,6‐trimethylbenzoic acid is oriented nearly antiplanar.…”

Inhibition of Human Neutrophil Elastase. 4. Design, Synthesis, X-ray Crystallographic Analysis, and Structure−Activity Relationships for a Series of P2-Modified, Orally Active Peptidyl Pentafluoroethyl Ketones

“…The energy profile for this dihedral as measured by the semiempirical AM1 Hamiltonian in MOPAC 6.0 is 4-fold, with the minimum at about 45° and barriers of 0.6 and 1.1 kcal/mol to bring the amide group in-plane and perpendicular to the aromatic ring, respectively and are in accordance with NMR data . Adjustments to the parameters ( V 2 = 7.0 kcal/mol and V 4 = 0.1 kcal/mol) for the C−C−C−N torsion were made in order to reproduce the semiempirical curve.…”

Chiral‐at‐Metal Octahedral Iridium Catalyst for the Asymmetric Construction of an All‐Carbon Quaternary Stereocenter

“…Furthermore, the amide catalysts Λ‐ Ir2 and Λ‐ Ir3 are significantly more active and provide the addition product ( S )‐ 2 a with higher enantioselectivity compared to Λ‐ Ir1 (Table 1), thus demonstrating the superiority of the N , N ‐diethylcarboxamide over the hydroxymethyl group as a hydrogen‐bond acceptor in this catalysis. This result can be rationalized with a superior hydrogen‐bond affinity of the carboxamide over the hydroxy group,16 in combination with a preferred conformation of the amide group rotated out of conjugation with the benzoxazole moiety because of steric reasons,21 thereby placing the amide oxygen atom in an ideal position for hydrogen bonding with the indole nucleophile. It is intriguing that the reaction 1 a →( S )‐ 2 a still provides high enantioselectivities (93 % ee ) with just 0.5 mol % Λ‐ Ir3 (Table 2, entry 13).…”