Optimization of the regioselective synthesis of mixed cellulose 3,5-dimethylphenyl and α-phenylethyl carbamate selectors as separation phases for chiral HPLC

Abstract

Regioselective tritylation and carbonate aminolysis were employed in this work to synthesize cellulose 2,3-bis(3,5-dimethylphenyl carbamate)-6-(α-phenylethyl carbamate)-type chiral selectors. We evaluated and optimized the critical aspects of regioselective tritylation and detritylation at C6 of the glucopyranose units of the polysaccharide backbone. The advantage of using cellulose II in comparison to cellulose I for tritylation was analyzed and the detritylation time was determined by a fast and simple thin-layer chromatography method. Optimization of both tritylation and detritylation was accompanied by a combination of analytical techniques. Oxycarbonylation with phenyl chloroformate was used to introduce a reactive phenyl carbonate moiety at C6 of the intermediate cellulose 2,3-bis(3,5-dimethylphenyl carbamate), which was subsequently converted to the respective cellulose 6-(α-phenylethyl carbamate) derivative by aminolysis with enantiopure (R)- or (S)-α-phenylethylamine. The starting material, intermediates, and target cellulose derivatives were comprehensively analytically characterized by ATR-FTIR, solid- and liquid-state 13C NMR, GPC, and elemental analysis. With the optimized protocol, it became possible to obtain cellulose carbamate-type chiral selectors through carbonate aminolysis with simple and commercially available primary amines instead of reaction with isocyanate reagents. The enantioseparation performance of the obtained chiral selectors was evaluated against cellulose tris(3,5-dimethylphenyl carbamate) as a reference selector with a selection of chiral analytes. Graphical abstract: [Figure not available: see fulltext.].