New Method for the Benzylation of Hindered Sugar Hydroxyls
S. Czernecki, C. Georgoulis, C. Provelenghiou
*Laboratoire de Cinétique et Mécanismes de Réactions Organiques, CNRS ER 84 associée à l'Université Pierre et Marie Curie, 4 place Jussieu, 75230 Paris, Cedex 05 France
S. Czernecki, C. Georgoulis, C. Provelenghiou, Tetrahedron Lett., 1976, 17, 3535-3536.
see article for more examples
A fast, quantitative benzylation of hindered sugar hydroxyls with NaH/THF is possible in the presence of a catalytic amount of the quaternary ammonium salt IN(Bu)4. A sample procedure with catalyst produces quantitative yield after 10 - 165 min at r.t. versus 24 h at reflux with excess benzyl bromide and no catalyst.
To a solution of diacetone-D-glucose (39 g, 150 mmol) in 250 mL of anhydrous THF maintained under inert atmosphere was added slowly with stirring and cooling 7.3 g (152 mmol) of sodium hydride (50% dispersion in oil, Prolabo). The medium was homogenous when the addition was complete, so the alkoxide thus formed was soluble in THF at this concentration (0.6 M).
Next, 540 mg (1.5 mmol, 1 mol%) of IN(Bu)4 was added, followed by 18 mL (151 mmol) of benzyl bromide. From TLC monitoring of hydrolyzed aliquots (Merck silica H, ether:pentane 2:1 (v/v)), diacetone-D-glucose had completely disappeared after 2 h 45 min at 20 °C. [With 5.4 g (15 mmol, 10 mol%) of IN(Bu)4, the reaction was complete in 10 min, while 24 h at reflux with a 25% excess of benzyl bromide was necessary in the absence of IN(Bu)4.]
The reaction mixture was charged with 10 g of florisil (60/100 mesh, Prolabo), and the solvent was evaporated at reduced pressure.
Elution of the florisil with pentane and evaporation yielded 52.5 g (100%) of a product freed from all impurities, and for which the results of combustion analysis corresponded to the empirical formula of the benzyl ether.