Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins

Abstract

A number of per-6-substituted cyclodextrin derivative syntheses have been effectively carried out in a planetary ball mill under solvent-free conditions. The preparation of Bridion® and important per-6-amino/thiocyclodextrin intermediates without polar aprotic solvents, a source of byproducts and persistent impurities, could be performed. Isolation and purification processes could also be simplified. Considerably lower alkylthiol/halide ratio were necessary to reach the complete reaction in comparison with thiourea or azide reactions. While the presented mechanochemical syntheses were carried out on the millimolar scale, they are easily scalable.

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

“…Recently, focus has been in controlling selectivity of organic reactions under solventless ball‐milling conditions . 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 .…”

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

“…[9][10][11][12][13] However,t he substrate preorganization in hydroformylation reactions could also be achieved through hydrophobic effects.F or example,w es howed that bidentate ligands and cyclodextrins (CDs,c yclic oligosaccharides consisting of glucopyranose units) supramolecularly interact to compel terminal alkenes to react preferentially by their terminal carbon, leading to very high regioselectivity toward linear aldehyde. [15] Concurrently with works of Cravotto et al, [16,17] we showed that regioselective mono-2-O-tosylation of the secondary face of CDs proceeds quantitatively upon grinding on very short reaction times (ca. [15] Concurrently with works of Cravotto et al, [16,17] we showed that regioselective mono-2-O-tosylation of the secondary face of CDs proceeds quantitatively upon grinding on very short reaction times (ca.…”

New Lipidyl-Cyclodextrins Obtained by Ring Opening of Methyl Oleate Epoxide Using Ball Milling

“…The NMR experiments were carried out on 2 Bruker AVANCE spectrometers (400 and 600 MHz). They were therefore performed respectively at 400 MHz for 1 H and 101 MHz for 13 C, or 600 MHz for 1 H and 151 MHz for 13 C. The deuterated solvents used were pyridine, chloroform, water, or methanol.…”

“…1 H NMR (400 MHz, CDCl 3 ) δ (ppm): 3.65 (s, 3H, OCH 3 ), 2.96-2.82 (m, 2H, H 9 and H 10 ), 2.31-2.27 (t, 2H, J = 7.5 Hz, CH 2 COOCH3), 1.71-1.55 (m, 2H, CH 2 ), 1.55-0.96 (m, 24H, CH 2 ), 0.87 (t, 3H, J = 6.9 Hz, CH 3 ). 13 C NMR (101 MHz, CDCl 3 ) δ (ppm): 174.4 (C=O), 57.4, 57.3 (C-9 and C-10), 51.6 (C-…”

“…Indeed, activation modes such as ultrasound [8,9], microwaves [10,11], or mechanochemistry [12] are considered as useful green tools for the chemical modification of cyclodextrins. Cravotto et al reported some works where ball milling is used to obtain well-known CD derivatives but under green and solventless conditions and with better yields [13,14]. Very few examples of more specific regioselectivity induced by mechanochemistry are reported.…”