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Preparation  of  Arsphenamine.     (Am  Tour.  Pharm. 
1  J  L  1       May,  1919. 
jections  to  methyl  alcohol  and  other  considerations  connected  there- 
with will  be  discussed  on  page  — .  In  order  to  eliminate  the  methyl 
alcohol  or  any  other  organic  solvents  in  the  process  of  prepara- 
tion, the  following  method  was  developed: 
II.  Method  of  Preparation. — Finding  that  the  dihydrochloride 
of  the  arsphenamine  base  was  insoluble  in  an  excess  of  chlorides,  as 
might  be  expected  from  the  Law  of  Mass  Action,9  an  excess  of 
hydrochloric  acid  was  tried  in  "  salting  "  out  the  drug.  When  first 
tried,  by  making  an  aqueous  solution  of  the  dihydrochloride  directly 
from  the  base,  by  dissolving  in  twice  normal  sodium  hydroxide  and 
adding  a  slight  excess  of  hydrochloric  acid  and  then  pouring  the 
solution  of  hydrochloride  into  a  strong  solution  of  hydrochloric  acid 
(1-1),  a  white  precipitate  was  formed  which,  however,  soon  turned 
to  a  dark-colored  gum.  This  transformation  of  the  white  pre- 
cipitate into  the  black  gum,  was  due  simply  to  the  coalescence  of  the 
particles.  This  coalescence  was  prevented  when  the  precipitation 
was  conducted,  (1)  at  a  low  temperature,  (2)  under  more  dilute 
conditions,  and  (3)  with  vigorous  stirring. 
As  the  purity  of  the  hydrochloride  depends  also  on  the  purity  of 
the  arsphenamine  base,  the  details  of  this  preparation  will  be  briefly 
given ;  in  other  words,  the  process  starting  with  the  nitro-oxyphenyl- 
arsonic  acid10  will  be  described. 
1.  Reduction  of  Nitro-0 xy phenyl- Arsonic  Acid. — Two  hundred 
and  twenty  (220)  grams  of  magnesium  chloride  are  dissolved  in 
5,500  Cc.  of  distilled  water  and  1,100  grams  of  sodium  hydrosul- 
phite  are  quickly  added,  while  stirring  or  shaking,  in  an  eight-liter 
bottle. 
To  this  solution  is  then  added,  with  stirring  or  shaking,  85  grams 
of  crude  nitro-oxyphenyl-arsonic  acid,  dissolved  in  290  Cc.  of  2.0  Ar 
sodium  hydroxide  and  diluted  with  1,700  Cc.  of  water.  The  mix- 
ture11 is  then  allowed  to  stand  at  room  temperature  or  it  is  slowly 
9  Nernst,  Z.  phys.  Chem.;  4,  372,  1889;  Noyes,  ibid.,  6,  241,  1890. 
10  Owing  to  the  ease  with  which  />-arsanillic  acid  can  now  be  made,  which 
is  described  in  a  separate  communication  (Journal  of  the  American  Chemical 
Society,  41,  300,  1919),  we  prefer  to  make  nitro-oxyphenyl-arsnic  acid  by 
nitrating  the  oxalic  acid  derivative  of  />-arsanillic  acid  (Bcr.,  44,  3095,-  191 1) 
and  saponifying  according  to  the  directions  of  Ehrlich  and  his  collaborators 
(Ber.,  44,  3451,  1911). 
11  These  amounts  of  material  and  solution  practically  fill  an  eight-liter 
bottle,  so  that  little,  if  any,  inert  gas  is  needed  nor  do  other  anaerobic  precau- 
tions have  to  be  taken. 
