SYNTHESIS OF 2.3.4.6-TETRA-O-ACETYL-𝛼-D-GLUCOPYRANOSYL BROMIDE (𝛼-Acetobromoglucose)

• Fit a 1 -litre three-necked flask located in the fume cupboard with a mechanical stirrer unit using a Kyrides seal, a dropping funnel and a thermometer to read the temperature of the reaction mixture. 

• Immerse the flask in an ice-salt bath supported on a laboratory jack so that it may be easily removed if the reaction conditions so demand. 

• Place 432 g (400 ml, 4.24 mol) of acetic anhydride in the flask, cool to 4 °C and add dropwise and with stirring 2.4 ml of 60 per cent perchloric acid. 

• Remove the cooling bath and allow the reaction mixture to warm to room temperature; then add 100g (0.56 mol) of dry powdered 𝛼-D-glucose in portions with stirring so that the temperature of the reaction mixture is maintained at between 30 and 40 °C. 

• Cool to about 20°C and add 31 g (1 mol) of red phosphorus followed by 181 g (58ml, 2.26 mol) of bromine (CAUTION) dropwise at a rate that the temperature does not exceed 20 °C. 

• Then add 36 ml of water over a period of about half an hour, the stirring and cooling being continued and the temperature being maintained below 20 °C. 

• Allow the reaction mixture to stand for 2 hours at room temperature, transfer to a fume cupboard and dilute with 300 ml of dichloromethane, and filter through a large 60° glass funnel having a glass wool plug inserted not too tightly into the outlet (1). 

• Finally rinse the reaction flask and funnel with small portions of dichloromethane, transfer the filtrate and washings to a 3-litre separatory funnel and wash it rapidly by shaking vigorously with two 800 ml portions of iced water (2). 

• Run the lower dichloromethane layer from the second washing into 500 ml of a stirred saturated solution of aqueous sodium hydrogen carbonate to which has also been added some crushed ice. 

• When the vigorous evolution of carbon dioxide has subsided transfer the mixture to a separatory funnel, run the dichloromethane layer into a large flask containing 10 g of powdered activated silica gel and filter after about 10 minutes (the bulk of the solution may be decanted from the silica gel and the remainder filtered under reduced pressure using a sintered glass funnel). 

• Remove the solvent under reduced pressure using a rotary evaporator on a water bath maintained at 60 °C. 

• Towards the conclusion of this operation the syrupy mass crystallises as a thick layer around the inside of the flask. 

• At this stage remove the flask from the evaporator, break the crystalline cake away from the sides of the flask and remove the remaining solvent under reduced pressure without heating further. 

• Transfer portions of the solid to a mortar and grind with a 2:1 mixture of light petroleum (b.p. 40-60 °C) and dry ether. 

• Filter the combined slurry and wash the filter cake first with a light petroleum-ether solvent mixture and then with 50 ml of previously chilled (0°C) dry ether. 

• The crude product is obtained in a yield of 210 g (92%), and when recrystallised from ether-light petroleum (b.p. 40-60 °C) has m.p. 88-89 °C, [𝛼]ᴅ²⁰ + 197.5° (c2 in CHC1₃). 

• The glucosyl halide should be stored in a desiccator over sodium hydroxide pellets; whenever possible it should be used without delay.

Notes to keep in mind:

1.  If care is used most of the solution may be decanted from the solid deposit so that the glass wool does not become blocked with material and hence slow down the filtration process. This filtration is best conducted in a fume cupboard.

2.  All the isolation operations must be conducted with the minimum of delay and under conditions which reduce the contact of the solutions of unstable glucosyl halide with moisture. Solutions to be used for washing the organic layer should have been previously prepared and contain sufficient ice to ensure that the temperature of the liquid is approximately 4 °C. To obtain good yields and to ensure that vessels do not become unduly 'sticky' as the result of residual carbohydrate deposits, the separatory funnels, receiver vessels and aqueous extracts before being discarded should be rinsed with dichloromethane at each stage and these washings combined with the main

organic solution.

Cognate preparations: 2,3,4,6- Tetra-O-acetyl-𝛼-D-galactopyranosyl bromide

• Use 100 g (0.56 mol) of dry D-galactose under precisely the same conditions; the product is obtained in a yield of 202 g (88%). When recrystallised from ether-light petroleum (b.p. 40-60 °C) it has m.p. 84-85 °C, [𝛼]ᴅ²⁰ + 214° (c 1.2 in CHC1 3 ).

2,3,4-Tri-O-acetyl-𝛽-L-arabinopyranosyl bromide

• For this preparation use 10 g (0.067 mol) of l-( + )-arabinose, 40 ml (0.424 mol) of acetic anhydride, 0.24 ml of 60 per cent perchloric acid, 30 g (0.1 mol) of red phosphorus, 18.1 g (5.8 ml, 0.226 mol) of bromine and 3.6 ml of water. 

• The yellow syrup which is obtained after the appropriate isolation procedure gives 21 g of crude crystalline product. 

• Recrystallisation is effected by dissolving it in a mixture of benzene/ether (5:95) warming and adding light petroleum (b.p. 40-60 °C) until a slight cloudiness is apparent, and then allowing the solution to cool. The pure product is obtained in a yield of 11 g (48%), m.p. 136-138 °C, [𝛼]ᴅ²² +280° (c3.13 in CHC1 3 ).