A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1937, 17, 40
DOI: 10.15227/orgsyn.017.0040
Submitted by E. Raymond Riegel and F. Zwilgmeyer.
Checked by Reynold C. Fuson and William E. Ross.
1. Procedure
In a 1-l. round-bottomed flask, fitted with a reflux condenser protected by a calcium chloride tube, 46 g. (2 gram atoms) of sodium is dissolved in 600 cc. of absolute alcohol (Note 1). About one hour is required for the addition of the sodium, and another hour for its complete solution. Toward the end of the reaction the flask may be heated with a small smoky flame. While the sodium is being dissolved, the following materials are weighed in dry, stoppered containers: 58 g. (1 mole) of dry acetone (Note 2), 150 g. (1.03 moles) of freshly distilled ethyl oxalate (Org. Syn. Coll. Vol. I, 1941, 261), and 160 g. (1.1 moles) of ethyl oxalate.
About half of the sodium ethoxide solution is poured into a 3-l. round-bottomed, three-necked flask provided with a liquid-sealed stirrer and a reflux condenser; the other half is kept warm by a small flame. The first half of the solution is allowed to cool until a solid begins to appear, then 58 g. of dry acetone mixed with 150 g. of ethyl oxalate is added at once and the stirrer is set in motion. Heat is evolved, and the liquid turns brown but remains clear. As soon as any turbidity appears, the other half of the hot sodium ethoxide solution is poured into the mixture together with 160 g. of ethyl oxalate, the two streams being allowed to mix as they flow into the flask. The liquid initially is clear and of a deep brown color, but after stirring for about thirty minutes the mixture becomes practically solid. The flask is then connected with a condenser for distillation and heated in an oil bath at 110° until 150 cc. of alcohol has distilled. The flask is protected by a calcium chloride tube and the reaction mixture is cooled to 20°. The sodium derivative is removed to a 3-l. beaker by means of a glass rod and treated with a mixture of 300 cc. of concentrated hydrochloric acid (sp. gr. 1.19) and 800 g. of cracked ice (Note 3). All lumps are carefully crushed, and the creamy yellow suspension of acetonedioxalic ester is collected on a 15-cm. Büchner funnel. The ester is removed from the filter, stirred with about 100 cc. of ice water, and again collected (Note 4). For hydrolysis the crude material is heated with 300 cc. of concentrated hydrochloric acid in a 5-l. flask (Note 5) on the steam bath for twenty hours. After cooling to 20° the solid hydrated acid is collected on a 10-cm. Büchner funnel, washed with two 50-cc. portions of ice water, and dried, first at 100° for two hours, and then at 160° to constant weight to remove the water of crystallization. The yield of product decomposing at 257° (corr.) is 140–145 g. (76–79 per cent of the theoretical amount).
2. Notes
1. A good grade of absolute alcohol should be used (Org. Syn. Coll. Vol. I, 1941, 259).
2. The acetone is dried for several days over calcium chloride, filtered, and distilled. Some acetone is lost in this operation by combination with the calcium chloride.1
3. The temperature must be kept as low as possible during the neutralization, for any undue rise in temperature results in a darkening of the product.
4. The crude ester, after a further washing and after drying in a vacuum desiccator over sulfuric acid, melts at 98–100° and weighs 220 g. (85 per cent of the theoretical amount).
5. A large flask is used because the mixture froths seriously at first. If the frothing becomes troublesome it may be stopped by adding a little ether.
3. Discussion
Natural chelidonic acid is obtained from the herb celandine (Chelidonium majus). The synthesis from ethyl oxalate and acetone was first described by Claisen;2 the process was simplified by Willstätter and Pummerer3 and further improved by Ruzicka and Fornasir.4 The present procedure is modeled after that of the last-mentioned investigators.

References and Notes
  1. Bagster, J. Chem. Soc. 111, 494 (1917).
  2. Claisen, Ber. 24, 111 (1891).
  3. Willstätter and Pummerer, ibid. 37, 3744 (1904).
  4. Ruzicka and Fornasir, Helv. Chim. Acta 3, 811 (1920).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

alcohol (64-17-5)

calcium chloride (10043-52-4)

sulfuric acid (7664-93-9)

hydrochloric acid (7647-01-0)

ether (60-29-7)

acetone (67-64-1)

sodium (13966-32-0)

sodium ethoxide (141-52-6)

Ethyl oxalate

Chelidonic acid (99-32-1)