Liquid chromatographic resolution of 3‐amino‐1,4‐benzodiazepin‐2‐ones on crown ether‐based chiral stationary phases

3‐Amino‐5‐phenyl (or 5‐methyl)‐1,4‐benzodiazepin‐2‐ones, which are chiral precursors of anti‐respiratory syncytial virus active agents, were resolved on three different chiral stationary phases (CSPs) based on (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid or (3,3′‐diphenyl‐1,1′‐binaphthyl)‐20‐crown‐6. Among the three CSPs, the CSP that is based on (3,3′‐diphenyl‐1,1′‐binaphthyl)‐20‐crown‐6 and containing residual silanol group‐protecting n ‐octyl groups on the silica surface was found to be most effective with the use of 80% ethanol in water containing perchloric acid (10 mM) and ammonium acetate (1.0 mM) as a mobile phase. The separation factors (α) and resolutions (R S ) were in the range of 1.90–3.21 and 2.79–5.96, respectively. From the relationship between the analyte structure and the chromatographic resolution behavior, the chiral recognition mechanism on the CSP based on (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid was proposed to be different from that on the CSP based on (3,3′‐diphenyl‐1,1′‐binaphthyl)‐20‐crown‐6. In addition, the chromatographic resolution behavior of the most effective CSP was investigated as a function of the composition of aqueous mobile phase containing organic and acidic modifier and ammonium acetate. Chirality 24:427‐431, 2012 . © 2012 Wiley Periodicals, Inc.