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.