Synthesis by carbonate aminolysis and chiral recognition ability of cellulose 2,3-bis(3,5-dimethylphenyl carbamate)-6-(α-phenylethyl carbamate) selectors

Abstract

Novel chiral selectors based on cellulose 2,3-bis(3,5-dimethylphenyl carbamate)-6-(α-phenylethyl carbamate) were regioselectively synthesized by carbonate aminolysis and isocyanate chemistry. By oxycarbonylation with phenyl chloroformate, carbamoylation with 3,5-dimethylphenyl isocyanate, and subsequent aminolysis of the previously introduced reactive carbonate moiety at C6 with enantiopure (R)-or (S)-α-phenylethylamine, chiral selectors have been obtained, which regioselectively carry two different phenyl carbamate substituents. The cellulose derivatives were comprehensively characterized by ATR-FTIR, solid-state NMR, GPC, and elemental analysis. In parallel, 3-aminopropyl-functionalized silica gel as an inert carrier material for the chiral selectors was prepared and the obtained coated-type chiral stationary phases were characterized by both solid-state 29Si NMR, 13C NMR, and elemental analysis. The enantioseparation performance of the chiral selectors was studied and compared to cellulose tris(3,5-dimethylphenyl carbamate) as a reference. With this protocol in hand, certain shortcomings of conventional approaches towards the regioselective synthesis of polysaccharide-based chiral selectors were overcome, such as the limitation to standard isocyanate reagents, being able to apply now the whole wealth of commercially available (chiral) primary and also secondary alkylamines instead. Graphical abstract

Immobilization of a cellulose carbamate-type chiral selector onto silica gel by alkyne-azide click chemistry for the preparation of chiral stationary chromatography phases

“…Further studies with smaller silica particles and higher surface areas, allowing higher efficiencies and consequently higher selector loadings with higher retention and selectivity, are ongoing. A previous comparison from our work (Bui et al 2022b) with coated materials carrying 20 wt% of selector has shown that the overall performance matched that of commercial reference materials. However, with the present silica dimensions (i.e., relatively low surface area), it was not possible to achieve such high selector loadings (vide supra).…”

“…The higher reactivity and selectivity of phenyl chloroformate towards C6-OH versus C2-OH and C3-OH have already been reported (Elschner et al 2014;Ganske and Heinze 2018). In a previous study, we have optimized the protocol towards quantitative oxycarbonylation of C6-OH (Bui et al 2022b) and also reported on the optimization and successful aminolysis reaction between the polysaccharidic carbonates (Bui et al 2022a). The obtained phenyl carbonate served as a reactive intermediate for subsequent aminolysis with propargylamine yielding a propynyl carbamate moiety as an alkyne donor for immobilization of the CS onto 3-azidopropyl-functionalized silica gel (Fig.…”

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

“…2, the EA results of all reported cellulose derivatives are summarized in Table 1. The FTIR and solid-state 13 C NMR spectra of cellulose derivative 1 were in full agreement with literature data (Liu et al 2013;Wei et al 2019;Bui et al 2022a;Bui et al 2022b). Cellulose derivative 1 is a well-known CS in chiral HPLC column materials and has been commercialized by several companies.…”

“…Previously published procedures were adapted to synthesize 3-aminopropyl-functionalized silica gel (APS) as an inert carrier for the CSs (Engelhardt and Orth 1987;Yashima et al 1996;Okada et al 2016;Bui et al 2022a). Silica gel (10 g) was immersed in toluene (200 mL) during mechanical stirring, and the mixture was dried by azeotropic distillation in a dry nitrogen atmosphere.…”

“…The coating amount of each CS (1, 6R, and 6S) on APS was 20 wt% (Zhang and Francotte 1995). The coating was performed according to a previously published protocol (Bui et al 2022a). Column packing was carried out as described in Bui et al (2022a, b).…”