SYNTHESIS OF METHYL 4,6-O-BENZYLIDENE-𝛼-D-GLUCOPYRANOSIDE

• Shake vigorously a mixture of 105g (1.0 mol) of purified benzaldehyde, 38.8g (0.2 mol) of methyl 𝛼-D-glucopyranoside(1) and 29.5g of freshly fused and powdered anhydrous zinc chloride (0.22 mol) in a conical flask in a mechanical shaker for about 10 hours, until a clear solution is obtained.

• Allow the solution to stand at room temperature for a further period of 18 hours and then pour it into 700 ml of iced water (2). 

• Stir the mixture vigorously, filter off the solid which separates and wash the compressed filter cake with light petroleum (b.p. 40-60 °C) to remove as much of the unreacted benzaldehyde as possible. 

• Remove the solid from the Buchner funnel, stir or shake it vigorously with a solution of 12g of sodium metabisulphite in 120 ml of water, filter and wash the filter cake with water. 

• Crystallise the solid from hot water, or after drying in a vacuum desiccator, from a mixture of chloroform and ether. 

• The pure product has m.p. 165°C, [a]o° +112° (c0.5 in CHC1 3 ), the yield is 29 g (52%).

Notes to keep in mind:

1.  Methyl 𝛼-D-glucopyranoside is available commercially and it is not usually economic to prepare it in the laboratory; should, however, its preparation be necessary the method, may be employed. The crude product (containing a mixture of anomeric glucosides) which is obtained after removal of methanol is stirred with cold (10 °C) methanol (0.6ml/g), and the crude a-anomer removed by filtration. The pure compound, obtained after recrystallisation from ethanol (l0ml/g), has m.p. 167-169 °C, [𝛼]ᴅ²º + 157° (c2 in H₂O). The yield is in the region of 30-40 per cent.

2.  An alternative isolation procedure is to extract the clear solution by shaking it with three successive 100 ml portions of light petroleum (b.p. 40-60 °C), which removes the unreacted benzaldehyde more effectively, and then to stir the viscous residue with ice-water until solidification occurs.

Cognate preparations: Methyl 4,6-O-benzylidene-𝛼-D-galactopyranoside 

• [recrystallised from ethanol/light petroleum (b.p. 60-80 °C)], m.p. 169-170°C, [𝛼]ᴅ²º +168.2 (cl.4 in CHCl₃), methyl 4,6-O-benzylidene-𝛽-D-gluco-pyranoside (recrystallised from methanol), m.p. 194-196 °C, [𝛼]ᴅ²º —74° (c1 in EtOH), and methyl 4,6-O-benzylidene-𝛽-D-galactopyranoside (recrystallised from methanol), m.p. 198-200 °C, [𝛼]ᴅ²º -35.5° (c2 in CHCl₃), may all be prepared similarly in yields of around 68 per cent.