SYNTHESIS OF 2,2-DIMETHYLSUCCINIC ACID

CAUTION: This preparation must be carried out in an efficient fume cupboard.

• Into a 500-ml round-bottomed flask, provided with a double surface condenser, place 50 g (63 ml, 0.86 mol) of pure, dry acetone, 50 g (47 ml, 0.44 mol) of ethyl cyanoacetate and 0.5 g of piperidine. 

• Allow to stand for 60 hours and heat on a water bath for 2 hours. 

• Treat the cold reaction mixture with 100 ml of ether, wash with dilute hydrochloric acid, then with water, and dry over anhydrous sodium sulphate. 

• Distil under diminished pressure and collect the ethyl isopropylidenecyanoacetate (ethyl 2-cyano-3,3-dimethylacrylate) at 114-1 16 °C/14mmHg (1). The yield is 39 g (58%). 

• Dissolve 20 g (0.13 mol) of the cyano ester in 100 ml of rectified spirit and add a solution of 19.2 g (0.295 mol) of pure potassium cyanide (CAUTION) in 40 ml of water. 

• Allow to stand for 48 hours, then distil off the alcohol on a water bath. 

• Add a large excess of concentrated hydrochloric acid and heat under reflux for 3 hours. (CAUTION: hydrogen cyanide evolved.) 

• Dilute with water, saturate the solution with ammonium sulphate and extract with four 75 ml portions of ether. 

• Dry the combined ethereal extracts with anhydrous sodium sulphate, and distil off the ether. 

• Recrystallise the residual acid from excess concentrated hydrochloric acid, and dry in the air. The yield of pure 2,2-dimethylsuccinic acid, m.p. 141-142 °C, is 12 g (63%). The p.m.r. spectrum is recorded in trifluoracetic acid and reveals signals at 5 1.48 (s, 6H, Me 2 ) and 2.92 (s, 2H, CH 2 ); the hydroxyl proton is not observed.

Notes to keep in mind:

1.  Higher (including cycloaliphatic) ketones may be condensed with ethyl cyanoacetate under the following conditions. Mix 0.50 mol of ethyl cyanoacetate, 0.55-0.70 mol of the ketone, 0.02 mol of piperidine and 50ml of dry benzene (CAUTION) and heat under reflux for 12-24 hours in an apparatus incorporating an automatic water separator. Piperidine may be replaced by a catalyst composed of 7.7 g (0.1 mol) of ammonium acetate and 24 g (0.4 mol) of glacial acetic acid. Wash the cold reaction mixture with three 25-ml portions of 10 per cent sodium chloride solution, and remove the benzene on a water bath under reduced pressure. Transfer the residue to a 1 -litre bottle containing a solution of 65 g of sodium metabi-sulphite in 250ml of water and shake mechanically for 2-6 hours. Dilute the turbid solution, which contains the sodium metabisulphite addition compound, with 400 ml of water, and extract the ethyl cyanoacetate with three 50 ml portions of benzene. Cool the bisulphite solution in ice, and add dropwise, with mechanical stirring, an ice-cold solution of 28 g of sodium hydroxide in 110 ml of water, Extract the regenerated unsaturated ester at once with four 25 ml portions of benzene, wash the extracts with 50 ml of 1 per cent hydrochloric acid and dry with anhydrous sodium sulphate. Filter and distil through a fractionating column under reduced pressure; the benzene may be conveniently removed by distilling at atmospheric pressure until the temperature rises to 90°C. Diethyl ketone yields ethyl 2-cyano-3,3-diethylacrylate, b.p. 123-125 °C/ 12mmHg or 96-97 °C/3 mmHg; dipropyl ketone gives ethyl 2-cyano-3,3-dipropyl-acrylate, b.p. 136-137 °C/11 mmHg or 1 16-1 17 °C/4 mmHg. The yield is 60-70 per cent.

The appropriate succinic acid can be prepared by condensation of the unsaturated cyano ester with alcoholic potassium cyanide and subsequent treatment with hydrochloric acid.