Selective Secondary Face Modification of Cyclodextrins by Mechanosynthesis

• Published in: Journal of organic chemistry 2015-06, Vol.80 (12), p.6259-6266
• Main Authors: Menuel, Stéphane, Doumert, Bertrand, Saitzek, Sébastien, Ponchel, Anne, Delevoye, Laurent, Monflier, Eric, Hapiot, Frédéric
• Format: Article
• Language: English
• Subjects: Catalysis; Chemical Sciences
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.5b00697

α-, β-, and γ-cyclodextrins (CDs) were modified on their secondary face by mechanosynthesis at room temperature using a laboratory-scale ball-mill. Mono-2-tosylated α-, β-, and γ-CDs were obtained in good yield from mixtures of native α-, β-, and γ-CDs, respectively, N-tosylimidazole, and an inorganic base, with each of them being in the solid state. The yields appeared to be dependent upon the nature of the base and the reaction time. A kinetic monitoring by 1H NMR spectroscopy demonstrated that the highest yields in mono-2-tosyl-CDs were measured using KOH as a base in very short reaction times (up to 65% in 80 s). Mono-(2,3-manno-epoxide) α-, β-, and γ-CDs were subsequently synthesized by ball-milling a mixture of monotosylated α-, β-, and γ-CDs, respectively, and KOH. The characterization of the modified CDs was carried out by X-ray diffraction, mass spectrometry, solid-state NMR, and diffuse reflectance UV–vis (DR UV–vis) spectroscopies. Clues to the supramolecular arrangement of the molecules in the solid state provide information on the reaction mechanism.