Synthesis and Conformational Analysis of N‑Aromatic Acetamides Bearing Thiophene: Effect of Intramolecular Chalcogen–Chalcogen Interaction on Amide Conformational Stability

The conformations of aromatic amides bearing an N-(2-thienyl) or N-(3-thienyl) group were investigated in solution and in the crystal state. NMR spectral data indicate that the conformational preferences of these amides in solution are dependent not only on the relative π-electron densities of the N-aromatic moieties, but also on the three-dimensional relationship between carbonyl oxygen and the N-aromatic moieties. A comparison of the conformational preferences of N-(2-thienyl)­amides and N-(3-thienyl)­amides revealed that the Z-conformers of N-(2-thienyl)­acetamides are stabilized by 1,5-type intramolecular S···OC interactions between amide carbonyl and thiophene sulfur. The crystal structures of these compounds were similar to the solution structures. The stabilization energy due to 1,5-type intramolecular S···OC interaction in N-aryl-N-(2-thienyl)­acetamides and N-methyl-N-(2-thienyl)­acetamide was estimated to be ca. 0.74 and 0.93 kcal/mol, respectively.