halogen - 20-5-2009 at 13:45
I know that reductive amination is entirely possible, but is it possible on a quaternary ammonium salt?
For example, if one had (C2H5)2N=C(CH3)2Br (or iodide) could this be reduced with H2 and a suitable catalyst to (C2H5)2N-CH(CH3)2 or its salt?
turd - 20-5-2009 at 15:15
http://lmgtfy.com/?q=reduction+of+iminium+ion
Arrhenius - 20-5-2009 at 18:19
Where's the quarternary ammonium salt in what you've written? You've got the diethyl iminium salt of acetone drawn. What you've drawn can be
reductively aminated to the amine. Lowering the pH with acetic acid may be necessary. If starting from an ammonium salt (primary or secondary amine.
tertiary or quaternary won't react) you may have problems running the reaction due to solubility issues. Generally a free amine is used and the
iminium ion carries a proton, but it is possible to do reductive amination with ammonium bromide and Pd/C.
[Edited on 21-5-2009 by Arrhenius]
Arrhenius - 21-5-2009 at 08:01
This is still technically not a 'quaternary' center. The nitrogen is tertiary in this imine (three things bonded to it), and SP2 hybridized.
Heinen AW, Peters JA, van Bekkum H. The reductive amination of benzaldehyde over Pd/C catalysts: Mechanism and effect of carbon modifications on the
selectivity. European journal of organic chemistry. 2000: 13;2501-06
"Unless otherwise stated, these experiments were performed at 90 °C and 40 bar H2."
Here's a decent review article:
Gomez S, Peters JA, Maschmeyer T. The reductive amination of aldehydes and ketones and the hydrogenation of nitriles: Mechanistic aspects and
selectivity control. Advanced synthesis & catalysis. 2002: 344;1037-57
"However, imine intermediates are not possible in the reductive amination with secondary amines. Formation of an enamine followed by its reduction to
the corresponding tertiary amine was proposed as an alternative for the mechanism (Scheme 4)."
So, I misspoke, the imine rearranges to an enamine in the case of a secondary amine nucleophile, and the enamine is hydrogenated.
Again, the reaction conditions used were 3bar H2, 50ºC to 80bar H2, 90ºC. You'll need a hydrogenation flask at the very least.