8io 
Preparation  of  Piperazine. 
Am.  Jour.  Pharm. 
Nov.,  19 18. 
However,  nitrous  acid  reacts  with  dyphenyl  piperazine,  and  this 
derivative  can  be  hydrolyzed.  According  to  German  patent  No. 
60,547,  boiling  with  alkalies  accomplishes  the  desired  result. 
The  conversion  of  dyphenyl  piperazine  into  its  dinitroso  deriva- 
tive involves  difficulties  which  are  not  disclosed  in  this  or  other 
patents.  The  addition  of  sodium  nitrite  to  a  suspension  of  diphenyl 
piperazine  in  acidulated  cold  water  results  in  the  formation  of  sticky, 
green  tars  which  give  no  traces  of  piperazine  on  boiling  with  aqueous 
or  alcoholic  alkali.  Many  fruitless  attempts  to  carry  out  this  step  in 
such  a  way  as  to  avoid  decomposition  of  the  desired  product  were 
made.  It  was  eventually  found  possible  to  obtain  good  yields  of 
the  dinitroso  derivative  by  suspending  finely  ground  diphenyl  piper- 
azine in  ice-cold  cone,  hydrochloric  acid  and  adding  slowly  a  satu- 
rated aqueous  solution  of  sodium  nitrite.  The  suspension  should 
be  stirred  vigorously  throughout,  and  the  nitrite  solution  should  be 
added  by  means  of  a  tube  reaching  to  the  bottom  of  the  container. 
The  solution  turns  red  immediately  and  insoluble  diphenyl  pipera- 
zine is  rapidly  converted  into  the  hydrochloride  of  dinitrosodiphenyl 
piperazine  which  remains  in  suspension  as  a  golden-orange  precipi- 
tate, quite  stable  while  moist. 
It  may  be  removed  by  filtration  and  washed  with  cold  water 
without  undergoing  serious  decomposition.  The  amount  of  nitrite 
necessary  is  only  slightly  greater  than  theoretical,  and  yields  are  ex- 
cellent. The  use  of  cone,  hydrochloric  acid  instead  of  dil.  acid  is 
vital.  Before  this  factor  was  determined,  all  attempts  to  prepare  the 
desired  base  were  failures. 
Dinitrosodiphenyl  piperazine  may  be  hydrolyzed  by  boiling  with 
alcoholic  potash  to  give  free  piperazine  and  nitrosophenol.3  If  this 
method  is  employed,  the  alcohol  is  removed  and  piperazine  obtained 
by  distillation  with  superheated  steam.  We  have  found  low  yields 
rather  general,  and  considerable  difficulty  in  avoiding  volatile  col- 
ored by-products. 
Aromatic  nitroso  amines  combine  with  sodium  bisulphite4  to  give 
sulphonic  acid  derivatives  which  readily  rearrange  with  loss  of  the 
amine  group  and  hydrolysis.  This  reaction  has  been  applied5  to 
dinitrosodiphenyl  piperazine.  When  these  specifications  are  carried 
out  as  outlined,  one  obtains  considerable  amounts  of  ammonia,  rep- 
3  D.  R.  P.  60547. 
*Ibid.,  65236. 
5  Ibid.,  74628. 
