SYNTHESIS OF ETHYL 2,2,4-TRIMETHYL-3-OXOPENTANOATE (Ethyl isobutyrylbutyrate)

Triphenylmethyl sodium

Prepare a 1.5 per cent sodium amalgam from 15 g (0.65 mol) of sodium and 985 g of mercury (Section 4.2.70, p. 464). Place a mixture of 1000 g of the amalgam and 74 g (0.265 mol) of triphenylchloro-methane (Section 4.2.79, p. 466) in a 2-litre Pyrex glass-stoppered bottle and add 1 500 ml of sodium-dried ether. Grease the glass stopper with a little Silicone grease, insert it firmly, clamp the bottle in a mechanical shaker and shake. CAUTION: the reaction is strongly exothermic; cool the bottle with wet rags and stop the shaking from time to time, if necessary. A characteristic red colour appears after about 10 minutes' shaking. After shaking for 4 to 6 hours, cool the bottle to room temperature, remove it from the shaker, wire the stopper down and allow the mixture to stand undisturbed; sodium chloride and particles of mercury settle to the bottom.

Separate the ether solution of triphenylmethyl sodium as follows. Remove the glass stopper and replace it immediately by a tightly fitting two-holed bung carrying a short glass tube that protrudes about 1 cm into the bottle, and a long glass tube bent into an inverted U -shape. Connect the bottle

through a drying train to a cylinder of nitrogen. Lead the other arm of the U-tube into a 2-litre, two-necked round-bottomed flask (which has been previously filled with nitrogen) via a suitable screw-capped adapter and fit a dropping funnel into the other neck. Open the stopcock of the dropping

funnel slightly and force the ether solution of triphenylmethyl sodium slowly and steadily into the nitrogen-filled flask by means of a small pressure of nitrogen from the cylinder. By carefully adjusting the depth of the siphon tube in the bottle, all but 50-75 ml of the clear ether solution may be removed. If pure triphenylchloromethane and freshly prepared sodium amalgam are used, the yield of triphenylmethyl sodium should be almost quantitative and the concentration is usually 0.15 mol per litre (1). The reagent should be used as soon as possible after its preparation.

Ethyl 2,2,4-trimethyl-3-oxopentanoate. Add 24 g (28 ml, 0.21 mol) of ethyl 2-methylpropanoate b.p. 1 10-1 1 1 °C, to the solution of c. 0.21 mol of triphenyl-methyl sodium in approximately 1 400 ml of ether contained in the 2-litre two-necked flask. Stopper the flask, shake well to effect complete mixing and keep at room temperature for 60 hours. Acidify the reaction mixture by adding,

with shaking, 15 ml of glacial acetic acid, and then extract with 100 ml of water. Wash the ethereal solution with 50 ml portions of 10 per cent sodium carbonate solution until free from excess acid, dry over anhydrous sodium sulphate; remove the ether under reduced pressure with a rotary evaporator. Distil the residue under reduced pressure through a short fractionating column. Collect the ethyl 2,2,4-trimethyl-3-oxopentanoate at 95-96 °C/ 18mmHg; the yield is 14.5 g (74%). The b.p. at atmospheric pressure is 201-202 °C.

Note. (1) The solution may be analysed approximately as follows. Remove 25 ml of ether solution, run it into 25 ml of water contained in a small separatory funnel and shake. Run off the aqueous layer into a 250-ml conical flask and extract the ether layer with two 25 ml portions of water. Titrate the combined aqueous extracts with 0.95 m-sulphuric acid, using methyl red as indicator.

Ketonic hydrolysis to di-isopropyl ketone. Mix 1 4 g (0.75 mol) of the ester with 30 ml of glacial acetic acid, 10 ml of water and 10 ml of concentrated sulphuric acid, and boil under reflux until evolution of carbon dioxide ceases. Dilute the cooled solution with 180 ml of water, add 100 ml of ether and render alkaline to phenolphthalein with 20 per cent sodium hydroxide solution. Separate the ether layer, extract the aqueous layer with two 50 ml portions of ether, dry the combined ether layer and extracts with anhydrous sodium sulphate, distil off the ether and fractionate the residue. The yield of di-isopropyl ketone (2,4-dimethylpentan-3-one), b.p. 123-1 24 °C, is 6.5 g (76%).