Reactions

 of  Amines:  Reductive  Amination  (Borch  Reaction)  

 
Reactions:  
 
 
  O
1) NH2 NH
  2) H2 / Pt (pressure), EtOH
 
 
 
  O 1) NH2 / NaBH3CN, HCl (1eq) NH
  CH3OHsolvent
  2) neutralization, NaOH
 
Mechanism:  
 
  H H N
2

  O CH 3
H
  O
H O

 
 
 
  H
H
HOCH3
H
  N N H

  O CH3

  OH OH
H
 
 
 
  H
H
  N
N H Na

  H B CN N

  OH 2
H H
H
 
 
  H
Neutralization
  O CH3
step, NaOH

  H

 
  N
NH

 
 
 
 
When  ketone  or  aldehydes  react  with  1°  amines  an  imine  is  formed.  
Enamines  are  the  product  of  2°  amines  and  an  aldehyde  or  a  ketone.    These  imines  
or  enamines  can  be  reduced  to  2°  or  3°  amines,  respectively.    One  way  is  hydrogen  
addition  using  a  metal  catalyst.      
  
The  mechanism  for  the  use  of  a  non-­‐metal-­‐hydride  as  the  reducing  agent  is  
shown  above.    This  synthesis  procedure  requires  the  formation  of  an  intermediate  
imine.    Because  the  formation  of  an  amine  from  the  imine  does  not  require  a  
nucleophilic  attack  of  the  nitrogen  there  is  no  concern  with  over-­‐alkylation.  
The  reaction  between  an  amine  and  formaldehyde  followed  by  reductive  
amination  can  produce  a  selectively  methylated  amine.    A  tertiary  amine  is  usually  
the  product  of  the  reaction  if  excess  formaldehyde  is  used.      The  mechanism  for  the  
synthesis  is  the  same  as  the  above.  
 
CH3
  O

  NH2 1) H H
(xs) / NaBH3CN, acetic acid
N
  CH3CN / H2Osolvent system CH3
  2) neutralization, NaOH