Probing Chiral Recognition on Amylose Tris(3,5-Dimethylphenylcarbamate) Using Cinnamyl 2-Aminoanilides: The Subtle Impact of Aliphatic Substituents.

This study investigates the chiral recognition behavior of the polysaccharide‑based chiral stationary phase amylose tris(3,5‑dimethylphenylcarbamate) (Chiralpak AD‑3) under polar organic conditions, using a series of racemic cinnamyl 2‑aminoanilides differing only in the nature of their aliphatic substituents. Remarkably large differences in enantioselectivity were observed among closely related compounds, with enantioseparation factors reaching exceptionally high values (α up to 37) when neat 2‑propanol was employed as the mobile phase. In contrast, replacement of 2‑propanol with 1‑propanol led to a dramatic reduction or complete loss of chiral discrimination, highlighting the crucial role of solvent structure in modulating analyte-selector interactions. Analysis of retention and selectivity trends suggests that chiral recognition primarily arises from hydrogen bonding involving the anilide NH2 group, combined with other interactions modulated by the aliphatic side chains. These findings emphasize how subtle structural modifications, together with mobile phase composition, can profoundly affect enantioselectivity on polysaccharide‑based chiral stationary phases.