Synthesis of cellulose carbamates bearing regioselective substituents at 2,3- and 6-positions for efficient chromatographic enantioseparation

Abstract

Nine cellulose derivatives bearing two different carbamate substituents at 2,3- and 6-positions of a glucose unit were synthesized by a sequential process based on the regioselective protection at 6-position. Their chiral recognition abilities were then evaluated as the chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) after coating them onto the macroporous silica gel. The introduction of two different phenylcarbamates at 2,3- and 6-positions of glucose unit was comparatively more attractive than that of one phenylcarbamate and one cyclohexylcarbamate to enhance the chiral recognition ability of these cellulose derivatives. Different combination of carbamate substituents of cellulose derivatives seems to offer superior resolution of different racemic compounds. The chiral recognition ability of these derivatives is apparently dependent on the nature, position and number of the substituents on the aromatic moieties. Many derivatives exhibit good enantioselectivity for the racemates in this study, and those based on cellulose 2,3-(3,5-dimethylphenylcarbamate) showed relatively better chiral recognition than others. Some racemates could be even more efficiently resolved on the cellulose derivatives with different carbamate groups at 2,3- and 6-positions than on the cellulose tris(3,5-dimethylphenylcarbamate), which is commercially available as one of the most popular chiral columns, Chiralcel OD. The structures of the obtained cellulose derivatives were also investigated by circular dichroism spectroscopy.