A Computational Investigation of the Stereoisomerism in Heteroatom-Substituted Amides

Equilibrium and transition structures for conformational interconversions in formamide ( 8 ), N -chloroformamide ( 9 ), N -methoxyformamide ( 10 ), N -chloro- N -methoxyformamide ( 11 ), N, N -dimethoxyformamide ( 12 ), and N -chloro- N -(dimethylamino)formamide ( 13 ) were determined at the Becke3LYP/6-31G(D) hybrid Hartree−Fock−density functional theoretical level. The structure and rotational barrier of formamide 8 agree well with experimental values. The computations suggest that in 9 and 10 the acyl nitrogen atom is planar after vibrational motion is considered. The barriers to acyl C−N rotation are lowered by 1−2 kcal/mol relative to normal amide barriers to about 16 kcal/mol and N−O rotation barriers in 10 are 5.6 and 7.4 kcal/mol, lower by 4−5 kcal/mol compared to those in simple hydroxylamines. The equilibrium and transition structures of the bisheteroatom-substituted formamides, 11, 12, and 13, are influenced by inductive effects, repulsive lone pair−lone pair interactions, and anomeric effects. The consequences of the anomeric interactions are the following: N−Cl bonds longer than normal by 0.05−0.35 Å in the equilibrium structures of 11 and 13; the N−O and N−N bonds are shortened by 0.04−0.14 Å in 11 and 13, the larger deviations occurring in 13; in each of the equilibrium and transition structures, except the transition structures to N−O and N−N bond rotation, the donor (X) and acceptor (N−Y) groups are always oriented so as to place the donor n X orbital in an approximate anti-coplanar arrangement relative to the acceptor N−Y bond. The anomeric interaction does not appear to have a specific contribution to lowering of acyl−C−N rotation barriers which are in the range 8−10 kcal/mol for all three bisheteroatom-substituted systems, nor to the magnitude of the inversion barriers which are constant at about 2−3 kcal/mol. However it significantly increases the magnitude of barriers to rotation about N−O and N−N bonds, bringing the N−O barriers in 11 back to normal values for hydroxylamines, thereby countering the effect of acyl substitution and raising the N−N rotation barrier in 13 to almost 20 kcal/mol.