SYNTHESIS OF CIS-CYCLOHEXANE-l,2-DIOL

CAUTION: This preparation involving the toxic osmium tetroxide must be carried out in a fume cupboard. For the precautions to be followed when using 30 per cent hydrogen peroxide.

• Prepare the reagent as follows. 

• To a mixture of 100 ml of pure t-butyl alcohol (2-methylpropan-2-ol) and 25 ml of 30 per cent hydrogen peroxide, add anhydrous sodium sulphate or magnesium sulphate in small portions; two layers separate out.

• Remove the alcohol layer which contains most of the hydrogen peroxide, and dry it with magnesium sulphate, followed by anhydrous calcium sulphate.

• The resulting liquid is a stable solution of 6.3 per cent hydrogen peroxide in t-butyl alcohol.

• Free cyclohexene from peroxides by treating it with a saturated solution of sodium metabisulphite, separate, dry and distil; collect the fraction having b.p. 81-83 °C. Mix 8.2 g (0.1 mol) of cyclohexene with 55 ml of the reagent (0.1 mol), add 3 ml of a 0.5 per cent solution of osmium tetroxide [CAUTION: (1)] in anhydrous t-butyl alcohol and cool the mixture to 0°C. 

• Allow to stand overnight, by which time the initial orange coloration will have disappeared. 

• Remove the solvent and unreacted cyclohexene by distilla- tion at atmospheric pressure and fractionate the residue under reduced pres- sure using an air condenser. 

• Collect the fraction of b.p. 120-140 °C/15 mmHg; this solidifies almost immediately. 

• Recrystallise from ethyl acetate. 

• The yield of pure ds-cyclohexane- 1,2-diol, m.p. 96 °C, is 5.0 g (45%).

Notes to keep in mind:

1. Osmium tetroxide is extremely irritating and toxic and constitutes a severe eye injury hazard. It may be purchased in sealed ampoules, e.g. 100 mg; the solution in t-butyl alcohol must be prepared and dispensed in an efficient fume cupboard, with the added protection of gloves and goggles. This solution is reasonably stable (e.g. the decomposition after one month is about 20%), provided that no 2-methylprop-l-ene arising from the t-butyl alcohol is present as impurity. In the latter case formation of black colloidal osmium, which can catalyse the decomposition of hydrogen peroxide, is rapid.

Cognate preparations: Hydroxylation using cetyhrimethylammonium permanganate (CTAP). 74 

• The reagent is prepared as follows. 

• To a stirred solution of potassium permanganate (3.168 g, 20mmol) in water (100ml) at 20°C is added dropwise over 20 minutes a solution of cetyltrimethylammonium bromide (8.02 g, 22mol) in water (100ml). 

• A fine violet precipitate forms immediately. Stirring is continued for 30 minutes, the product isolated by suction, washed thoroughly with water, and dried in a desiccator over phosphorus pentoxide in vacuo for 3 hours at room temperature to give a fluffy violet solid; yield 6.5 g (80%). 

• The reagent is stored in a brown bottle in a refrigerator.

Method A: 

• A solution of CTAP (2.02 g, 5 mmol) in dichloromethane (30 ml) is added dropwise to a stirred solution of the alkene (5 mmol) in dichloromethane (15 ml) at 20 °C. Stirring is continued for 1-5 hours and the mixture then concentrated to half its volume under reduced pressure. 

• The residual solution is diluted with ether (50 ml) and filtered through a pad of Celite and magnesium sulphate. The filtrate is evaporated under reduced pressure and the remaining uic-diol purified by recrystallisation from ethyl acetate/light petroleum.

Method B: 

• A solution of CTAP (2.02 g, 5 mmol) in t-butyl alcohol (20 ml) and water (5 ml) is added dropwise to a stirred solution of the alkene (5 mmol) in t-butyl alcohol (4 ml) at 20 °C, and stirring continued for 1-5 hours. 

• Chloroform (50 ml) and 5 per cent aqueous sodium hydroxide solution (15 ml) are added, the mixture stirred for 30 minutes and the organic layer separated. 

• The aqueous phase is extracted with chloroform (3 x 50 ml). 

• The combined organic extracts are dried with magnesium sulphate, filtered, and evaporated to leave the w'c-diol which is purified as in Method A.

• The following alkenes have been hydroxylated by these methods (method, stirring time, yield %): dicyclopentadiene (A, 4 hours, 86%); oct-1-ene (A, 2 hours, 85%) (1); cyclohexene (B, 1 hour, 86%); cyclooctene (B, 1 hour, 73%).

Notes to keep in mind:

1. In the case of the hydroxylation of oct-1-ene, the product was purified by column chromatography using ether: light petroleum 2:5 as eluate.