SYNTHESIS OF METHYL 2,3-DI-O-METHYL-𝛼-D-GLUCOPYRANOSIDE

Methyl 4,6-O-benzylidene-2,3-di-O-methyl-𝛼-D-glucopyranoside

• Owing to the hazards in the use of dimethyl sulphate this experiment must be carried out in an efficient fume cupboard. 

• Mount a 500-ml, three-necked round-bottomed flask in an electrically-heated water bath and fit an efficient stirrer unit in the central neck. 

• Attach two 100-ml dropping funnels to the side-necks; one containing 38 g (29 ml, 0.30 mol) of purified dimethyl sulphate and the other containing 60 ml (0.6 mol) of 40 per cent aqueous sodium hydroxide solution. 

• Place 14.1 g (0.05 mol) of methyl 4,6-O-benzylidene-𝛼-D-glucopyranoside and 150 ml of acetone in the flask, run in 15 ml of sodium hydroxide solution, commence fairly rapid stirring and raise the temperature of the water bath to about 50 °C. 

• Add dropwise and simultaneously the remainder of the sodium hydroxide solution and the dimethyl sulphate over a period of about 1.5 hours. 

• Continue stirring at 50 °C for a further half an hour. 

• Remove the dropping funnels, fit a condenser set for downward distillation into one of the side-necks and a nitrogen inlet tube into the other. 

• Remove the acetone by distillation during 1 hour while maintaining a steady nitrogen flow. 

• Pour the contents of the flask into 1500 ml of ice-cold water and collect the solid produced by filtration. 

• Wash the product with cold water until the washings are neutral to litmus, dry overnight at 50 °C and recrystallise twice from light petroleum (b.p. 60-80°C), to give 12.5g (81%) of product having m.p. 122-123°C, [𝛼]ᴅ²⁰ +94° (c2 in CHC1₃), or [𝛼]ᴅ²⁰ +97° (c4 in Me₂CO).

Methyl 2,3-O-di-O-methyI-𝛼-D-glucopyranoside

• Dissolve 6.2 g (0.02 mol) of the foregoing derivative in 100 ml of acetone containing 0.3 per cent of concentrated sulphuric acid in a 250-ml round-bottomed flask fitted with a reflux condenser. 

• Boil the solution under gentle reflux on a steam bath. 

• Periodically remove the flask, cool to room temperature in a stream of cold water, remove an aliquot of suitable size and follow the progress of the hydrolysis by measuring the optical rotation, which changes from about 6.12 to about 5.74° for a 1-dm cell. 

• When the reaction is complete (under 1 hour), add 100 ml of water and neutralise the solution with solid barium carbonate. 

• Filter the reaction mixture and evaporate the filtrate on a rotary evaporator. 

• If an odour of benzaldehyde remains, add 100 ml of water and repeat the evaporation. 

• Distil the crude syrupy product under reduced pressure to give a colourless glass of b.p. 130-135 °C/0.1 mmHg which may be crystallised by trituration with dry benzene.

• Two recrystallisations from the same solvent give 3.2 g (72%) of methyl 2,3-di-O-methyl-𝛼-D-glucopyranoside, m.p. 85 °C, [𝛼]ᴅ²⁰ + 146° (c4 in Me₂CO).