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

Abstract

A new synthesis strategy for the preparation of cellulose derivative-based chiral selectors and the subsequent mild immobilization onto pre-functionalized silica gel are introduced, utilizing Cu(I)-catalyzed alkyne-azide Huisgen cycloaddition (“click”) chemistry. A cellulose 3,5-dimethylphenyl carbamate derivative carrying propynyl carbamate groups was prepared by a combination of carbonate aminolysis and isocyanate chemistry. For immobilization, 3-azidopropyl-functionalized silica gel as an inert carrier was used, synthesized via a 3-chloropropyl intermediate. The chiral selector, as well as the inorganic/organic hybrid materials (silica gel/chiral selector), were comprehensively characterized by ATR-FTIR, solid-state 13C and 29Si NMR, liquid-state NMR, GPC, TGA, and elemental analysis. The enantioseparation performance of the immobilized-type chiral stationary phase was evaluated by HPLC with a set of representative chiral test analytes and different eluents and compared to a respective coated-type (=non-covalently bound) chiral stationary phase carrying the same selector quality and quantity on the same silica gel matrix. The immobilization did not adversely affect the chiral separation performance; on the contrary, in some chromatographic separations the immobilized-type chiral stationary phase surprisingly even surpassed the coated reference material. Graphical abstract

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.…”

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

“…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.…”

“…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…”