For the reduction of tertiary amides to to tertiary amines, I was wondering which reductant(s) in what reaction environments (solvent, reactant
concentrations, temperature, catalysts, agitation, etc.) work best in your guys's experience, as well as the exact reaction mechanisms and, more
importantly, all products yielded by the reactions (i.e., not just the target amine, but also byproducts that might, for instance, react with the
amine, or interfere with its work-up). Equipment, setups, and procedures are also good to know.
Reductants:
The main reagents I would think to use are the tetrahydridoborates, tetrahydridoaluminates, and triethylhydridoborates of alkali metals, mainly
lithium, sodium, and potassium (nine possible compounds, and I can imagine the prices going up from lithium to potassium). I would also like to know
how suitable alkali hydrides might be. For this specific reaction, how effective are each of the aforementioned anions in relation to one another, and
how does the effectiveness of each of them vary according to the identity of their alkali metal countercation?
"Effectiveness", in this case, refers to
1) the reductant's selectivity for the amide in the presence of conjugated double bonds and aromatic secondary amines,
2) how closely it can get to achieving quantitative yields,
3) its ability to avoid reducing the amide into an alcohol or alkane; and, somewhat less importantly,
4) how quickly it achieves maximum yield (I am aware that this is also affected by solvent and temperature).
Any other reductants worth considering?
Solvents
From what I've read so far, it seems that ethers (oxolane, ethoxyethane and dioxane) are most commonly used as solvents for amide reductions. None of
these are hard to get, but what about amines? For instance, how might dimethylamine fare?
Trimethylamine?
Ethane-1,2-diamine?
N,N,N',N'-tetramethylethane-1,2-diamine?
(Obviously, the thing to worry about with DMA and EDA is the potential for deprotonation of the nitrogen atoms, but are methyl groups liable to be
reductively removed by hydride donors?).
Is there anything else I'm missing?CuReUS - 21-3-2015 at 00:44
amalgamated Zn in conc HCl(clemmeson's reduction) will reduce amides to amines.Maybe even Al/Hg instead of Zn can do the job
[Edited on 21-3-2015 by CuReUS]Nicodem - 21-3-2015 at 12:39
amalgamated Zn in conc HCl(clemmeson's reduction) will reduce amides to amines.Maybe even Al/Hg instead of Zn can do the job
Seriously? Do you mind giving providing the references?
By the way, you are obviously not talking about a Clemmensen reduction, since we are not talking about deoxygenating ketones.zed - 25-3-2015 at 11:51
Such reductions are difficult to achieve. LiAlH4 can be effective, as can NaBH4-AlCl3.
Sadly, in the past, those procedures that used NaBH4-AlCl3 seemed to produce limited yields and may have required elevated temperatures and unusual
solvents.
Some have suggested that LiAlH4-AlCl3 works well. Personally, I am a little behind in this area, and I don't know what progress has been achieved
in recent years.
