Synthesis
Under argon protection, m-chloroperbenzoic acid (containing about 30% water, purity >65%, 41.7 g, about 157 mmol) was added batchwise to a solution of 3,4-dibenzyloxybenzaldehyde (25.3 g, 105 mmol) in dichloromethane (160 mL). The reaction mixture was stirred at room temperature for 7.5 hours before the reaction was quenched with saturated aqueous NaHCO3 solution. The mixture was diluted with water and the organic layer was separated. The aqueous layer was further extracted with dichloromethane. The combined organic extracts were washed sequentially with saturated aqueous NaHCO3, water and brine, followed by drying and concentration with Na2SO4. The residue was dissolved in methanol (300 mL), K2CO3 (72.3 g, 523 mmol) was added in batches and stirred at room temperature for 1 h. The solvent was evaporated under reduced pressure. Water was added to the residue and the product was extracted with ether. The organic extract was washed sequentially with water and brine, dried over Na2SO4 and concentrated. The residue was recrystallized by diethyl ether-hexane to give 3,4-bis(benzyloxy)phenol (14.7 g, 61% yield) in light yellow granular form. The recrystallized mother liquor was concentrated and the residue was purified by silica gel column chromatography (hexane-ethyl acetate=3:1) to afford additional 3,4-bis(benzyloxy)phenol in the form of light yellow solid (3.14 g, 13% yield). In total, 17.8 g of 3,4-bis(benzyloxy)phenol was obtained in 74% overall yield.
References
[1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1993, # 11, p. 2165 - 2170
[2] Journal of Organic Chemistry, 2003, vol. 68, # 22, p. 8500 - 8504
[3] Heterocycles, 2014, vol. 89, # 1, p. 59 - 68
[4] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 24, p. 6563 - 6580
[5] Tetrahedron, 2005, vol. 61, # 34, p. 8101 - 8108
