An examination of the compounds possessing curariform activity reveals that a fused bicyclic ring system with nitrogen common to both rings is a structural feature present in many of the highly active compounds.4 For example, such a ring system is present, or thought to be present, in members of the erythrina, calabash curare, and canadine alkaloids as well as in certain active synthetic compounds.5 In view of this coincidence between curariform activity and the presence of a bicyclic, fused, nitrogen-containing ring system, model compounds based on the quinolizi-dine6 nucleus have been prepared and tested to determine whether this structural unit, by itself, is sufficient for curariform activity. The results

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The synthesis of citric acid labeled symmetrically in the 1and 5-positions Rith carbon-14 has been accomplished in rela-A new procedure for the extraction of citric acid from the reaction mixture simplifies the isolation of pure tively high yield. material; Recent interest in carbo;-14 labeled citric acid as a tool in the study of carbohydrate metabolism makes it desirable to present a well-defined synthesis of this compound. Early report^^,^^^ on the preparation of citric acid are vague as to the experimental details and yields, while a recent paper6 on the preparation of asymmetrically labeled citric acid reports too low a yield for a general synthetic approach to labeled citric acid.We have examined the method of Grimaux and Adam in detail and have succeeded in defining the conditions required for the preparation of citric acid-l,5-C14 in 35-40y0 yield by the reaction of labeled cyanide with potassium bis-chloromethylglycolate. The citric acid was isolated as trimethyl citrate prepared by addition of an excess of an ethereal solution of diazomethane to the dry hydrolysis mixture. This method of isolation is superior to the usual method which employs the calcium salt, inasmuch as trimethyl citrate is a crystalline solid with a sharp melting point and is easily purified prior to its conversion to citric acid.During the course of this work two new compounds were characterized, bis-chloromethylglycolamide (Ia) and methyl bis-chloromethylglycolate (Ib) (ClCH2)2C( 0H)CO-Ia = -NH2 Ib = -0CHa Experimental6Bis-chloromethylglycolic Acid.-A twofold excess of hydrogen cyanide was added rapidly to a slurry of 105 g. of symmetrical dichloroacetone in 10 ml. ethanol a t 0'. About 100 mg. of sodium cyanide was added and the mixture was stirred at 0 to 10" for two hours and then a t 60' for two hours. After cooling, 250 ml. of cold concd. hydrochloric acid was cautiously added with stirring. The solution was kept at 0' overnight and finally boiled under reflux for 24 hours. The hydrochloric acid was evaporated, water was (1) This research was carried out under Contract A7-(40-1)-279 with the U. S. Atomic Energy Commission. (2) E. Grimaux and P. Adam, Bull. SOC. chim. Froncc, [2] 86, 21 (1881). (3) H. von Pechman and M.