Selective Secondary Face Modification of Cyclodextrins by Mechanosynthesis

Abstract

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 (1)H 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.

Greener Paal–Knorr Pyrrole Synthesis by Mechanical Activation

“…The best result (96 % conversion) was obtained with 10 mol‐% citric acid at 30 Hz. Independent of the catalyst amount, these results corroborate previous studies regarding the crucial role of the ball‐mill frequency on the reaction yield 32,33. Actually, increasing the frequency of the milling resulted in an increase in the kinetic energy, which resulted in a transfer of more effective energy to the reactants.…”

Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins

“…While the mechanochemical manipulation of covalent bonds is hardly a brand new concept, its diffusion into carbohydrate chemistry, and particularly into CD derivatization, has been rather slow [22–23]. The ability of HEBM to favour the nucleophilic substitution reaction of 6 I -monotosyl-β-CD has been demonstrated in a previous article [22].…”

Hydroformylation of Alkenes in a Planetary Ball Mill: From Additive‐Controlled Reactivity to Supramolecular Control of Regioselectivity

“…Concurrently with works of Cravotto et al., we showed that regioselective mono‐2‐ O ‐tosylation of the secondary face of CDs proceeds quantitatively upon grinding on very short reaction times (ca. 1 min) via supramolecular means, the reactant (tosylimidazole) being included into the CD cavity . Similarly, highly selective processes were identified in the mechanically‐activated Au‐catalyzed reduction of nitroarenes in the presence of CDs .…”