QUININE ESTERS OF PHENYLARSINIC ACID DERIVATIVES. 25 



acid group. Phosphorus oxychloride readily combines with quinine. 

 When the oxychloride is distilled in vacuo after the above reaction and 

 a chloroform-quinine solution is then added and the whole warmed, 

 reaction takes place very incompletely because of the insolubility of the 

 different products, KPO3, HPO3, AsOa • CoH, ■ COCl in chloroform, 

 the half-liquid phosphorous acid protecting obstinately most of the acid 

 chloride against quinine. The result was still more unsatisfactory when 

 the salt was suspended in chloroform or benzene and the phosphorus 

 oxychloride was then added. 



Although the above method made it possible to isolate a product which 

 doubtless contained both quinine and arsenic in combination, nevertheless 

 it was abandoned for the following, by which benzoylchloride arsenic 

 tetrachloride (COCl • CgH^ ■ ASCI4) or benzoylchloride arsenic dichloride 

 (COCl • CgH^ • AsClj) were obtained, and which gave satisfactory results 

 by the final method described below. 



Phosphorus pen ta chloride (4-gram molecules) were added to benzarsinic acid 

 { 1-gram molecule) dried at 120° and suspended in chloroform, 



CO,H . G,H, . As03H,-|-4PCl5==4POCl3-|-COCl ■ CeH, • AsCl.-f-SHCl. 



A spontaneous reaction took place, which ' was completed by boiling in a flask 

 fitted with a reflux condenser until no more hydrochloric gas was given off and 

 a clear solution resulted. Most of the phosphorus oxychloride was then removed 

 by distilling the solution to dryness in vacuo on a water bath. The residue 

 dissolves readily in chloroform and a chloroform solution of quinine ( 1-gram 

 molecule) was then added. The precipitate which first formed again disappeared. 

 After boiling for one-half hour the clear solution was distilled to dryness in vacuo. 

 The residue consisted of the quinine ester-hydrochloride of carboxyphenyl-arsenic- 

 tetrachloride, phosphorus oxychloride and a small quantity of chloroform. 

 AsClj • CeH^ . CO2 • CsoHojNjOjHCl. The chloroform prevents the ready solution of 

 the reaction product in water or hydrochloric acid even on heating; on the other 

 hand, alkali saponifies it; and dissolving in alcohol, diluting with water and 

 neutralizing with alkali gives a sticky precipitate of the quinine derivative. In 

 view of these diSiculties the best way was found to be the following: 



On standing with cold water most of the phosphorus oxychloride decom- 

 posed; the solution was then heated on a water bath and by using a vacuum 

 the chloroform was boiled off at a low temperature and solution thereupon 

 readily took place. The resulting dilute solution was neutralized with sodium 

 hydroxide until a precipitate began to form, and then precipitated by sodium 

 carbonate solution. Excess of alkali is to be avoided, since the ester, stable as 

 is its acid solution even on boiling with a considerable excess of acid, saponifies 

 readily in presence of sodiiun hydroxide and slowly in sodium carbonate solution. 



The free ester formed a dense precipitate; after standing for several hours 

 it was filtered, washed and dried, first on a porous plate and subsequently at 

 110.° It still contained a certain amoimt of quinine, because the latter as a 

 rule was used in slight excess over phosphorus pentachloride, but the quinine 

 easily separated by dissolving the reaction product in a small quantity of absolute 

 alcohol and precipitating with ether. The quinine dissolves, its benzarsinic ester 

 forms a heavy white powder which is washed with ether and dried. 



No free, uncombined benzarsinic acid can be present, because the ester was 

 completely precipitated with sodium carbonate from its aqueous solution to a 



