DlHYDROCHLORIDE OF DlAMINODIOXYARSENOBENZENE. 23 



16 (1391) 



A method of preparing pure dihydrochloride of 

 diaminodioxyarsenobenzene. 



By Philip Adolph Kober. 



[From the Division of Laboratories and Research, New York State 

 Department of Health, Albany, N. Y.] 



The synthesis of a pure arsphenamine or salvarsan, in spite of 

 the excellent published work of Ehrlich and Bertheim 1 and their 

 collaborators, is still a vital problem. It is known by those who 

 have given attention to the subject that the toxicity of arsphena- 

 mine varies and that batches from individual manufacturers vary 

 more than they can account for in their procedures. Further- 

 more, as it seems fairly well proven that even Ehrlich's own manu- 

 facturers are unable to keep up a uniformly high standard, 2 it is 

 evident there are some factors which are not understood or under 

 control. 



In studying this subject, I came to the idea that the toxicity 

 of arsphenamine is largely due to the use of methyl alcohol and 

 ether in the precipitation of the dihydrochloride and therefore 

 made experiments to prepare the arsphenamine in aqueous solu- 

 tions, free from any extraneous and objectionable substances: 



Finding that the dihydrochloride of the salvarsan base was 

 insoluble in excess of chlorides, as might be expected from the Law 

 of Mass Action, an excess of hydrochloride acid was tried in salt- 

 ing out the drug. When first tried by making an aqueous solu- 

 tion of the dihydrochloride directly from the base, by dissolving 

 in two normal sodium hydroxide and adding a slight excess of 

 hydrochloride acid, and pouring the solution of hydrochloride into 

 a strong solution of hydrochloric acid (1-1), a white precipitate 

 was formed which, however, turned to a dark-colored gum. This 

 transformation of the white precipitate into the black gum, as 

 will be shown later, was due simply to coalescence of the particles. 

 To prevent this coalescence three factors were changed: (1) The 

 precipitation was conducted at a low temperature and (2) under 

 more dilute conditions and (3) with vigorous stirring. 



1 Ber., 45, 756, 1912. 



* Roth, Hygienic Laboratory Bulletin, 113, p. 7, 1918. 



