Posted by This article presents an environmentally friendly approach to modifying β-cyclodextrin (β-CD), a bio-based and biodegradable oligosaccharide derived from starch. This study presents a sustainable two-step method for synthesizing ethylated β-cyclodextrin (RE-β-CD) without using toxic alkylation agents. The first step involved a previously reported protocol for vinyl acetate-based transesterification, which achieved a “greener” acetylation pathway with a notably low environmental factor (E-factor) of 2.83 through catalytic dosage of DBU (1,8-Diazabicyclo(5.4.0)undec-7-ene) and high recycling rates for the employed solvents, acetonitrile (96%) and isopropanol (94%). In the second step, the acetylated β-CDs were efficiently reduced to RE-β-CDs under mild conditions, reaching high conversions by employing close to stoichiometric amount of TMDS and 4 mol% GaBr3 per ester group. The authors reported the novel use of anisole , a non-toxic, bio-available solvent alternative to its conventional hazardous and carcinogenic counterparts. These carefully optimized parameters, monitored by ATR-IR spectroscopy, ensured efficient reaction progress while minimizing waste generation. The synthesized RE-β-CDs exhibited physicochemical properties comparable to methylated CDs, including solubility in both protic (H2O, MeOH, or EtOH) and aprotic solvents (DMSO) and thermal stability as characterized by TGA and DSC analyses. Additionally, their host–guest properties with the non-polar guest molecule anisole was characterized through DOSY and ROESY NMR methods, to verify the formation of inclusion complexes.
In conclusion, this work showcased a more benign synthetic alternative for etherification of β-CD. It was demonstrated that RE-β-CDs obtained via the developed approach retain their characteristic performance without compromise, offering a more sustainable alternative to the conventionally synthesized β-CD derivatives.
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Leon J. Bartlewski, Peter Conen, Qianyu Cai, Maximilian Bürk, Dominique Armspach and Michael A. R. Meier (2025) A more sustainable two-step synthesis of alkylated β-cyclodextrin via acetylation and GaBr3-catalyzed reduction. RSC Sustainability, 3, 4126-4136. https://doi.org/10.1039/D5SU00590F