24 OECHSLIN. 



first attempt was to combine phenylarsinic acid derivatives with that 

 alkaloid. ■ 



The molecule of quinine has necessaril}' to be altered as little as possible 

 during the synthetic reaction, since it was shown by experiments on try- 

 panosomata that slight changes in the structure diminish the desirable 

 properties of the alkaloid. The following are the types of compounds 

 the preparation of which was attempted: 



1. Quinine combined in an ester with an aromatic derivative of 

 arsenic acid; for instance, with benzarsinic acid, COOH • Cgll^ • AsOgHg, 

 dibenzarsinic acid (COOH • CoH^)2 • AsO^H, phenylglycinarsinic acid 

 (COgH • CH, • HN • CgH^ • ASO3H2), etc., to compounds corresponding 

 to quininebenzoyl derivatives. 



2. Quinine combined with oxy- or amidophenylarsinic acids by means 

 of quinine-carbonic acid chloride, etc., to carbonates or urethane 

 derivatives. 



3. Direct combination of quinine with arsenic through direct substi- 

 tution by means of arsenic trichloride. 



4. A fourth type is produced by the combination of chitenin or a 

 corresponding acid, with hydroxy- or amido-phenylarsenic derivatives. 

 However, this type is under a disadvantage because the quinine enters 

 into the compound in a form considerably less active in destroying 

 trypanosomata than is the case with quinine. 



I. BENZAESINIC ACID QUININE ESTER. 



Benzarsinic acid was prepared from ^amidophenylarsinic acid by 

 Sandmeyeris reaction.^ 



A number of experiments were carried out in chloroform 

 and benzene for the purpose of combining the potassium salt 

 of benzarsinic acid * with quinine by means of phosphorus oxy- 

 chloride as follows: 2ASO3H2 • CgH, ■ COaK+SC^oH^^N^O^-f POClg^ 

 AsOjH^-CeH^-CO^-CaoHsgNsO+gKCl+KPOg. This method seems 

 preferable since it avoids the application of phosphorus pentachloride. 

 The latter, when in excess, reacts on quinine, forming chlorquinine, and 

 reacts on both acid groups of benzarsinic acid to produce the benzoyl chlo- 

 ride substitution product of arsenic pentachloride, AsCl^^ • CgH^ • COCl, 

 and the group AsCl^ would give the possibility of substituting hydrogen 

 in quinine by chlorine. 



The following reactions of this class were carried out with variations : 



Phosphorus oxychloride was added in large excess to dry potassium 

 benzarsinic acid, AsOgH, • CgH^ • COjK- A reaction sets in upon slight 

 warming and hydrochloric acid is evolved. This proves that the reagent 

 reacts not only with the salt, biit at the same time with the free arsinic 



'A. Berskinn, Ber. d. deutschen chem. Ges. (1908), 41, 1852. 

 ^La Coste, Ann. d. Chem. (Liebig) (1881), 208, 6. 



