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

Cellulose carbamates via transcarbamoylation/transurethanization of methyl carbamates in superbase–acid conjugate ionic liquids

“…[66][67][68] In effort to limit this, we lower the reaction temperature to 65 °C, but the experiment did not provide any clear trend (Table 5 entries 9 vs. 7). The reactions with butyl isocyanate proceed similarly to phenyl isocyanate for up to 3 equivalents of reagent (Table 5 entries [14][15][16][17][18][19]. However, the reaction with butyl isocyanate seems to proceed better with larger excess of the reagent yielding rather highly substituted cellulose (Table 5 entry 20).…”

“…Among them, the most popular derivative is the cellulose 3,5-dimethylphenyl carbamate, commonly known as Chiralcel® OD. [15][16][17][18] Other potential areas of application for CCDs can include food packaging and wound treatment due to the materials good biodegradability and excellent antimicrobial properties. [19][20][21] In addition, some CCDs are capable of pHresponsiveness, effective extraction of dyes, or removal of chlorinated phenols.…”

“…However, the modification of cellulose with isocyanates requires rather harsh conditions (elevated temperature, catalysis, or both), thus jeopardizing the stability of the isocyanate reagent. 18,20,29,38,39…”

“…However, the modi-cation of cellulose with isocyanates requires rather harsh conditions (elevated temperature, catalysis, or both), thus jeopardizing the stability of the isocyanate reagent. 18,20,29,38,39 The two-step indirect approach towards CCDs (Scheme 1a carbonate pathway) includes the preparation and isolation of an active cellulose intermediate. 5,22,23,30,33,40 In the rst step cellulose carbonate is prepared.…”

Structure design of polysaccharides by selective conversion: Old hat or topical?

“…Bui and Rosenau used a 6-O-protected cellulose derivative for the preparation of novel chiral selectors for the separation of enantiomers by high performance liquid chromatography (HPLC) (Bui et al 2023a). The resulting cellulose 2,3-bis(3,5dimethylphenyl carbamate) was further reacted with phenyl chloroformate, which underwent aminolysis with enantiopure -methylbenzylamine affording cellulose 2,3bis(3,5-dimethylphenyl carbamate)-6-(R/S-α-phenylethyl carbamate).…”