332 
Developments  in  Organic  Compounds. 
f  Am.  Jour.  Pharm. 
I        July,  1901. 
The  investigations  of  Schmiedeberg  demonstrated  that  anilin  was 
altered  and  rendered  less  toxic  in  the  organism  through  oxidation 
in  the  para  position  yielding  para-amido-phenol. 
OH 
Anilin 
(amido-benzol) 
Para-amido-phenol 
NH, 
NH, 
With  this  in  view,  also  that  para  amido  phenol  was  less  toxic 
than  anilin,  an  acetyl  radical  was  introduced  with  the  hope  of 
obtaining  an  ideal  antipyretic.  The  resulting  acetyl  para  amido 
phenol  still  possessed  toxic  antipyretic  symptoms,  hence  it  was  found 
necessary  to  close  or  protect  the  free  hydroxyl  group  through  the 
introduction  of  an  alkyl  radical.  If  a  methyl  group  is  employed, 
methacetin  results;  an  ethyl,  phenacetin;  other  alkyls,  as  propionyl, 
butyryl,  etc.,  have  been  employed  in  place  of  the-  ethyl,  but  the 
resulting  compounds,  because  of  their  great  insolubility,  react  too 
slowly  in  the  system. 
/OCH, 
C  H  / 
Anisidin 
7OC2H5 
XNH2 
Phenetidin 
CH 
OCH3 
"xNHCH3CO 
Methacetin 
OC2H5 
CH  / 
4xNHCH3CO 
Phenacetin 
The  maximum  of  antipyretic  and  antineuralgic  action  is  found  in 
the  methyl  derivative  (methacetin),  while  the  least  toxicity  is  pos- 
sessed by  the  ethyl  derivative  (phenacetin).  The  readiness  with 
which  the  acid  secretions  of  the  stomach  split  off  the  acid  rest  pre. 
paratory  to  the  decomposition  of  the  resulting  phenetidin  nucleus 
depends  largely  upon  the  nature  of  the  acid  employed.  Among  these 
derivatives  in  which  the  acetic  acid  rest  of  phenacetin  is  replaced 
by  other  acid  rests  are  lactic  (Lactophenin),  valeric  (Sedatin), 
salicylic  (Saliphen),  phenyl  glycolic  (Amygdophenin),  vanillic 
(Vanillin-p-phenetidin),  etc. 
