Switching Conjugation Is the Predominant Factor Contributing to Complete Reversal of Amide cis–trans (Z-E) Preference through N-Methylation

N-Methylation strongly influences the cis–trans (Z-E) preference of amides, especially in benzanilide. While the trans (E) conformation is preferred in NH-benzanilide, N-methylation shifts the balance to favor the cis (Z) form. This switch, often attributed to steric hindrance, is frequently utilized in molecular design. However, our findings suggest an alternative mechanism. Through bond model analysis (BMA), we explored the structural preferences driven by bond orbital interactions and assessed the stability of cis–trans (Z-E) preferences in response to electronic perturbations via electron-donating or -withdrawing groups on the benzene rings. Our results reveal that N-methylation rebalances conjugation: NH-benzanilides prefer the trans (E) form due to phenyl-amine conjugation, while N-Me benzanilides favor the cis form due to phenyl-carbonyl conjugation.