A Theoretical Analysis of Enantiomerization in Aromatic Amides

The mechanisms for enantiomerization in benzamide (B), N,N-dimethylbenzamide (DB), 1-naphthamide (N), and N,N-dimethyl-1-naphthamide (DN) were investigated both in the gas phase and in solution at the MP2-FC/6-311+G(d,p)//B3LYP/6-31+G(d,p) theory level. The effect of solvent (DMSO, chloroform) was taken into account by using the polarizable continuum model-united atom Hartree-Fock (PCM-UAHF) model. Two different kinds of mechanisms were found. The first kind proceeds through rotation about the Ar-CO bond and inversion at the nitrogen atom, while the second one consists of concerted Ar-CO and C-N rotations. Solvent effect destabilizes mostly the transition states (TSs) with concerted rotations owing to the loss of amide conjugation in these structures. According to our results using DMSO and chloroform as solvents, for benzamide, the mechanism through inversion is, respectively, 14.1 and 13.2 kcal mol^-1 more favorable than that through concerted rotations. This difference diminishes when a second ring is introduced (11.3 and 10.7 kcal mol^-1, respectively, for N) and even more when the hydrogen atoms on N are substituted by methyl groups so that for DB the route through inversion is, respectively, 5.5 and 4.8 kcal mol^-1 more favorable than that through concerted Ar-CO and C-N rotations and for DN this difference reduces to 1.1 and 0.6 kcal mol^-1, respectively, rendering both mechanisms practically competitive in this case.