8l2 
Preparation  of  Piperazine. 
Am.  Jour.  Pharm. 
Nov.,  19 18. 
stirring  to  about  8o°.  The  reaction  proceeds  smoothly,  giving  a 
deep  reddish  orange  solution  and  considerable  suspended  matter  that 
was  removed  by  nitration,  and  discarded.  At  this  point  D.  R.  P. 
74,628  specifies  the  addition  of  a  large  excess  of  hydrochloric  acid 
and  heating  to  the  boiling  point  before  making  alkaline  with  caustic 
soda.  This  results  in  the  formation  of  ammonia  due  to  decomposi- 
tion, and  of  sodium  chloride  in  large  amounts. 
We  have  omitted  the  treatment  entirely  without  sacrificing  the 
yield  of  piperazine.  The  reddish  orange  solution  obtained  above 
was  made  strongly  alkaline  with  caustic  soda  and  concentrated  by 
distillation.  Some  ammonia  was  liberated  at  first,  but  the  amount 
appeared  negligible.  The  distillation  was  continued  with  super- 
heated steam,  the  flask  being  immersed  in  an  oil  bath  at  1600.  Piper- 
azine distilled  over  rapidly  with  the  steam,  and  was  caught  in  hydro- 
chloric acid. 
Micro  tests  were  found  convenient  for  determining  when  to  stop 
the  distillation.  Traces  of  piperazine  give  very  characteristic  light 
yellow  crystals  with  platinum  chloride  solution.  These  vary  ac- 
cording to  concentration,  but  in  general  are  square  or  rectangular. 
A  drop  of  the  condensate  on  a  microscopic  slide  was  run  into  a  drop 
of  platinum  chloride  solution.  The  formation  of  a  precipitate  at 
once  indicates  that  the  distillation  should  be  continued.  Picric  acid 
may  be  substituted  for  platinum  chloride,  but  the  resulting  crystals 
are  not  so  characteristic.  When  no  precipitate  formed  at  once, 
examination  under  the  microscope  readily  revealed  whether  more 
than  mere  traces  of  piperazine  were  coming  over. 
Another  reagent  giving  characteristic  crystals  with  piperazine  is 
bismuth  potassium  iodide.  The  reagent  is  made  by  adding  enough 
nitric  acid  to  dissolve  suspended  bismuth  nitrate  and  sufficient  potas- 
sium iodide  to  give  a  clear  red  solution.  Slight  traces  of  piperazine 
salt  in  faintly  acid  solution  give  very  brilliantly  colored  garnet  crys- 
tals with  a  drop  of  this  reagent.  The  form  of  the  crystals  varies 
from  compact  prisms  to  the  more  usual  clusters  of  feathery  needles. 
The  double  salt  is  very  insoluble  and  it  is  hoped  that  it  will  offer  a 
means  of  determining  piperazine  quantitatively. 
A  less  delicate,  but  very  definite,  micro  test  for  piperazine  is  the 
formation  of  dinitroso  piperazine.  A  drop  containing  piperazine  is 
acidified  with  hydrochloric  acid  in  excess  and  flowed  into  a  drop  of 
saturated  sodium  nitrate  solution.  Slight  warming  gives  character- 
istic, thin,  rhombic,  colorless  plates. 
