3,5-Dinitrobenzoyl-9-amino-9-deoxy-9-epiquinine as Pirkle-Anion Exchange Hybrid-Type Chiral Selector in High-Performance Liquid Chromatography

Abstract

A new chiral stationary phase was designed by introducing 9-amino-9-deoxy-9-epiquinine, one of the most versatile organocatalysts in asymmetric synthesis, as chiral scaffold. The derivatization of its amino group with the 3,5-dinitrobenzoyl (DNB) fragment provided hydrogen bonding and π–π donor/acceptor systems in addition to the quinoline and quinuclidine moieties having two nitrogen atoms with different basicities. The selector offers multiple interaction sites in both typical of the Pirkle-type phases and classical of weak-anion-exchanger phases. The immobilization step took place through thiol-ene addition onto 3-mercaptopropyl-silica gel and gave a grafting density of 180 µmol of chiral selector per gram of silica. A silica with reduced particle size (Daisogel silica, pore size 120 A, particle size 2.5 µm, and specific surface area 343 m2 g−1) has been employed to improve the efficiency and the speed of separations. The chiral stationary phase was packed in a small format column (50 × 4.6 mm) that allowed, by van Deemter analysis, 180,000 plates/m and approximately 5.1 µm of plate height. The ability of chiral discrimination was then studied with more than 30 test compounds using both polar-organic and normal phase conditions. In polar-organic mode, N-protected amino acids, α-aryloxy carboxylic acids, as well the non-steroidal anti-inflammatory profens were analyzed. Interesting results were obtained in normal phase elution, where the chiral selector behaves like a Pirkle-type stationary phase. Aryl amides, esterified DNB-amino acids, benzodiazepines, and binaphthol were well resolved with a very good peak symmetry and in short analysis time (mainly in less than 5 min).