SYNTHESIS OF 1,2:5,6-DI-O-CYCLOHEXYLIDENE-𝛼-D-GLUCOFURANOSE

• Fit a 3-litre flange flask with a multiple socket head carrying a mechanical stirrer capable of effecting vigorous agitation, a calcium chloride guard-tube, a 100-ml dropping funnel and a stoppered opening wide enough to allow for the addition of solid. 

• Immerse the flask in a large plastic or metal container filled with an intimate mixture of ice and salt. 

• Add 1000 g (1050 ml, 10mol) of redistilled cyclohexanone to the flask and cool to °C. 

• Charge the separatory funnel with 62.5 ml of concentrated sulphuric acid and run the acid slowly into the vigorously stirred cyclohexanone; the final solution should be a light straw colour. 

• Add slowly and portionwise with continued vigorous stirring 450 g (2.5 mol) of finely powdered dried 𝛼-D-glucose (1). 

• Remove the cooling bath and allow the reaction mixture to reach ambient temperature with continual stirring; over a period of 8 hours the reaction mixture becomes progressively more viscous and finally sets into a solid off-white crystalline mass. 

• Some caution should be exercised to prevent the stirrer motor from being overstrained. 

• Allow the reaction mixture to stand at room temperature overnight, break up the crystalline mass, add 750 ml of heptane and a solution of 124 g of sodium carbonate in 375 ml of water, and heat on a boiling water bath with vigorous stirring. 

• Decant as much of the upper heptane layer as possible from undissolved solid. 

• Add a further 750 ml portion of heptane to the residue and heat under reflux until the remainder of the solid dissolves; decant the clear heptane layer and cool the combined heptane extracts in the refrigerator. 

• Filter off the crystalline material, m.p. 121-124 °C, and recrystallise from heptane (2) using decolourising charcoal to clear the hot solution of traces of dark oily droplets. 

• The purified l,2:5,6-di-0-cyclohexylidene-oe-D-glucofuranose has m.p. 131-132 °C, [𝛼]ᴅ²⁰-2.2° (cl.8 in EtOH); the yield is 380 g (47%).

Notes to keep in mind:

1.  If adequate cooling and stirring is not employed the final solution is dark yellow; furthermore the addition of glucose leads to an unacceptable local rise in temperature, and the final appearance of the reaction mixture is a dark red intractable oily mass. The powdered glucose should be dried in a vacuum desiccator over phosphorus pentoxide, not in an oven which apparently causes changes on the surface of the glucose particles which render them unreactive.

2.  Another solvent for recrystallisation is methylcyclohexane (0.17g/ml).

Cognate preparations: 1,2:4,5-Di-O-cyclohexylidene-D-fructopyranose

• Add 200 g (1.1 1 mol) of finely powdered dry D-fructose with vigorous stirring to 419 g (440 ml, 4.49 mol) of ice-cooled cyclohexanone containing 30 ml of concentrated sulphuric acid; the reaction mixture becomes solid within 30 minutes. 

• Leave the mixture overnight at room temperature, dissolve the product in 500 ml of chloroform and wash the solution with dilute aqueous sodium hydroxide, dilute hydrochloric acid and water and finally dry and evaporate. 

• Solidify the residue by m.p. 145-156 °C, [𝛼]ᴅ²⁰ - 133.5° (c 1 in CHCl₃). The yield is 142 g (37%).

1,2:5,6-Di-O-isopropylidene-𝛼-D-glucofuranose

• A suspension of 150g (0.83 mol) of dry D-glucose, 120 g (0.83 mol) of anhydrous zinc chloride and 7.5 g of phosphoric acid (88% v/v) in 1 litre of dry acetone is stirred at ambient temperature for 30 hours. 

• Unchanged glucose is removed by filtration, and inorganic salts are precipitated by the addition of a solution of 85 g of sodium hydroxide in 85 ml of water. 

• The resulting suspension is filtered, the residue washed with acetone and the acetone evaporated. The mass which remains is dissolved in 200 ml of water and extracted with five 100-ml portions of dichloromethane. 

• The organic phase is dried and evaporated on a rotary evaporator. 

• Recrystallisation from light petroleum (b.p. 80-100 °C) gives 70g of product, m.p. 109-110°C,[𝛼]ᴅ²⁰ -18.5° (c5 in H 2 0).

1,2:5,6-Di-O-isopropylidene-D-mannitol

• To a solution of 60 g of zinc chloride in 300 ml of acetone is added 10 g of finely powdered D-mannitol. 

• The mixture is stirred vigorously at 20°C until solution is complete (2-3 hours) and then allowed to stand for 16 hours. 

• The reaction mixture is then poured into a solution of 70 g of potassium carbonate in 70 ml of water which is covered with 300 ml of ether. 

• The mixture is stirred for half-an-hour when the organic layer is filtered from the agglomerated pellets of zinc carbonate. 

• The latter is washed with 100 ml of 1:1 acetone-ether solution, and the combined filtrates evaporated to dryness on a rotary evaporator. 

• The dry residue is successively extracted with five 250-ml portions of boiling light petroleum (b.p. 60-80°C) and the combined filtrates slowly cooled to give the product, 7.9 g (55%), having m.p. 119°C.