Conformational Properties of Aromatic Amides Bearing Imidazole Ring and Acid-Induced - Amide Switching.

Aromatic amides bearing secondary amide bond exist in trans conformation both in the crystal and in solution, whereas the conformation of the -methylated derivatives is cis in the crystal and predominantly cis in various solvents. The cis conformational preference of -alkylated benzanilide provides access to aromatic foldamers such as oligo(-alkyl--benzamide)s, which adopt dynamic helical structures. Here, the conformational properties of imidazole-substituted amide in the crystal and in solution were examined. Imidazole-substituted amides and existed mainly in the cis conformation in solution. The ratio of the cis conformer of -methyl--(1-methyl-1-imidazol-4-yl)benzamide () was smaller than that of ,1-dimethyl--phenyl-1-imidazole-2-carboxamide () or -methylbenzanilide, but the introduction of a substituent strongly affected the conformer ratio. Compounds and bearing an electron-withdrawing group on the imidazole ring existed predominantly in trans form. On the other hand, the introduction of an electron-withdrawing group on the phenyl ring or a bulky substituent on the amide nitrogen of increased the ratio of cis conformer. Further, the major conformer of -alkylated -imidazolylamides was switched from cis to trans by the addition of acid. These results suggest that imidazole-substituted amides might be applicable as conformational switches in aromatic foldamers to enable environment-dependent structural change.