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TCI Practical Example: Regioselective Benzylidene Acetal Protection of the β-Glucoside

We are proud to present the regioselective benzylidene acetal protection at 4,6-hydroxy groups of glucose moiety in salicin by using benzaldehyde dimethyl acetal.

Used Chemicals

• Salicin [S0003]
• Benzaldehyde Dimethyl Acetal [B1197]
• p-Toluenesulfonic Acid Monohydrate (= p-TsOH·H₂O) [T0267]
• Triethylamine [T0424]
• DMF

Procedure

To a solution of salicin (200 mg, 0.7 mmol) in DMF (2 mL) was added benzaldehyde dimethyl acetal (125 µL, 0.8 mmol) and p-TsOH·H₂O (12 mg, 0.07 mmol) and the mixture was stirred at 80 °C for 2 hours. The reaction was quenched with triethylamine (19 µL, 0.14 mmol) and the solvent was removed under reduced pressure. The residue was purified by column chromatography (ethyl acetate:hexane = 10:90 - 85:15) to give 1 as a white solid (165 mg, 63%).

Experimenter’s Comments

The reaction mixture was monitored by UPLC.

Analytical Data

4,6-O-Phenylmethylidene-D-salicin (1)

¹H NMR (270 MHz, DMSO); δ 7.46-7.37 (m, 6H), 7.24-7.19 (m, 1H), 7.11 (d, J = 7.6 Hz, 1H), 7.02 (t, J = 7.6 Hz, 1H), 5.65-5.61 (m, 2H), 5.42 (d, J = 5.4 Hz, 1H), 5.05-4.98 (m, 2H), 4.65 (dd, J = 5.4, 14.0 Hz, 1H), 4.48 (dd, J = 6.2, 14.0 Hz, 1H), 4.23 (dd, J = 4.32, 9.45 Hz, 1H), 3.76-3.38 (m, 5H).

Lead Reference

• Water-Soluble Organometallic Catalysts from Carbohydrates. 2. A Strategy for the Preparation of Catalysts with Pendant Quaternary Ammonium Groups Using D-Salicin
• • Y.-Y. Yan, T. V. RajanBabu, J. Org. Chem. 2001, 66, 3277.