Stereochemistry of benzanilides and N-methylbenzanilides

Abstract

Conformations of benzanilide (1), N-methylbenzanilide (2) and those with a methyl group(s) ortho to the amide bond (11-16, 21-26) in solution and in the crystal have been studied. N-Methylbenzanilide (2) exists in cis-amide (E) form in the crystal. In CDCl3 solution, cis-amide form is also predominant (99%), while benzanilide (1) exists in trans-amide (Z) form in the crystal and in solution. In the crystal, all the methyl-substituted benzanilides (11-16) exist in trans-amide conformation and the introduction of an ortho-methyl group(s) makes the interplanar angles of the aromatic rings and the amide group (Aramide) larger. N-Methylbenzanilides (21-25) exist in cis form in the crystal except the compound (26) which has four methyl groups ortho to the amide bond. For the N-methylbenzanilides, the effects of introduction of one or two ortho-methyl groups on dihedral angles of Ar-amide are smaller than that for the secondary benzanilides. In solution, benzanilides (11-16) exist exclusively in trans conformation except for the compound 12 which has a minor cis conformer (3%) in CDCl3, whereas N-methylbenzanilides (21-25) exist in equilibrium between the major cis-form and the minor trans-form. The tetramethyl derivative (26) exists in trans conformation in solution as observed in the crystal. For N-methylbenzanilides, an introduction of a methyl group(s) ortho to the amide bond seems to destabilize the cis-amide conformation in solution, resulting in an increased ratio of the trans-amide conformation.