SYNTHESIS OF 3-BROMO-l,4-DIOXASPIRO [4.5] DECANE

2-Hydroxymethyl-l,4-dioxaspiro[4.5]decane (1  ,2-O-cyclohexylidenegly-cerol) 

• Concentrated sulphuric acid (15 ml) is added to an ice-cooled solution of glycerol (184g, 2.0 mol) and cyclohexanone (196g, 2.0 mol) in light petroleum (b.p. 60-80 °C, 400ml). 

• The mixture is shaken for 18 hours when the petroleum layer is separated and dried (anhydrous potassium carbonate). 

• Distillation of the residue after solvent evaporation yields a clear liquid (193 g, 56%), b.p. 108-109 °C/2.2 mmHg, t R 18.8 minutes on a Carbowax 20M (10% on Chromosorb W) 1.5-m column held at 150 °C with a nitrogen carrier gas flow rate of 40 ml/minute. The p.m.r. spectrum (CDC1 3 , TMS) shows signals at 31.55 (m, 10H, cyclohexylidene) and 3.30-4.40 (m, 6H, — CH 2 -CH-CH 2 OH).

2-Methanesulphonyloxymethyl-l,4-dioxaspiro[4.5]decane

• The foregoing 1,2- O-cyclohexylideneglycerol (88 g, 0.5 mol) and dry pyridine (220 ml) (CAUTION) are placed in a 500-ml three-necked flask fitted with a stirrer, a pressure-equalising funnel and a calcium chloride guard-tube, and cooled to °C. Methanesulphonyl chloride (68 g, 0.5 mol) (CAUTION) (1) is placed in the addition funnel and added dropwise with vigorous stirring over a period of 30 minutes. 

• The reaction mixture is allowed to stand for 3 hours at °C (2) before the addition of sufficient water to dissolve the precipitated pyridine hydrochloride. 

• The reaction mixture is then poured into excess water and the oil which separates is washed repeatedly with fresh aliquots of water before being extracted into dichloromethane (300 ml). 

• The organic layer is washed with dilute hydrochloric acid (3 x 50 ml) and then repeatedly with water until the washings are neutral. 

• The organic layer is dried over magnesium sulphate, the solvent evaporated and the residue distilled to give the product as a yellow/orange oil (109 g, 88%), b.p. 130-136 °C/2 x 10 _2 mmHg; the p.m.r. spectrum (CDC1 3 , TMS) shows signals at 5 1.60 (m, 10H, cyclohexylidene), 3.08 (s, 3H, MeS0 2 — ) and 3.50-4.50 (m, 5H, — CH 2 -CH-CH 2 — ).

2-Bromomethyl-l,4-dioxaspiro[4.5]decane

• In a 50-ml two-necked flask fitted with a stirrer unit and a reflux condenser are placed the foregoing meth-anesulphonate (7.5 g, 0.03 mol), hexadecyltributylphosphonium bromide (0.75 g, 0.001 5 mol), potassium bromide (10.7 g, 0.09 mol), toluene (10 ml) and water (3 ml). 

• The reaction mixture is stirred vigorously and heated under reflux until t.l.c. analysis shows the reaction to be complete (2). 

• Dichloro-methane (15 ml) is added, the organic layer separated and the residue extracted with a further portion of dichloromethane (15 ml). 

• The combined organic extracts are dried with magnesium sulphate and the solvent evaporated. 

• The residue is distilled under reduced pressure to give the product (4.9 g, 70%), b.p. 87-88 °C/1. 5 mmHg, t R 3.8 minutes using the g.l.c. system noted above at a temperature of 180 °C.

Notes to keep in mind:

1. The handling of methanesulphonyl chloride, which is highly toxic and corrosive, must be carried out in a fume cupboard and protective gloves must be worn. The reaction should also be conducted in a fume cupboard.

2. These reactions may be monitored by t.l.c. analysis on Silica gel G plates using toluene: methanol, 9:1, as solvent; the components may be located by iodine vapour.