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

Aromatic amides bearing secondary amide bond exist in trans conformation both in the crystal and in solution, whereas the conformation of the N -methylated derivatives is cis in the crystal and predominantly cis in various solvents. The cis conformational preference of N -alkylated benzanilide provides access to aromatic foldamers such as oligo( N -alkyl- p -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 2a and 4a existed mainly in the cis conformation in solution. The ratio of the cis conformer of N -methyl- N -(1-methyl-1 H -imidazol-4-yl)benzamide ( 4a ) was smaller than that of N ,1-dimethyl- N -phenyl-1 H -imidazole-2-carboxamide ( 2a ) or N -methylbenzanilide, but the introduction of a substituent strongly affected the conformer ratio. Compounds 6a and 7a 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 4a increased the ratio of cis conformer. Further, the major conformer of N -alkylated N -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.