NaBH4 reduction of piperidones, use of ammonium salts
Planning on reducing triacetoneamine to the alcohol with NaBH4 shortly, I was considering using a salt of TAA during the reduction.
My reasoning was that in a number of reducive aminations, ammonium salts are present (triethylammonium chloride for example), and these do no appear
to be acidic enough to destroy the hydride.
obviously, i would no be suing the hydrosulfate, which must be too acidic in that case, but what about the hydrochloride?
Triethylamine's pka is of 10.78, tetramethylpiperidine 11.07, so I suppose triacetoneamine must have a pka pretty similar (hven't found a litt value),
which would the protonated ammonium musn't be much more acidic than triethylamine's.
I guess I could use aqueous conditions, basifying a suspension of the salt in methanol with NaOH, then adding NaBH4 as a solid, or as a aqueous
solution stabilized with a little NaOH.
The other solution would be to basify the salt seperatly, extract with AcOEt and saturate the aq with potassium carbonate to avoid looses from
thefreebases' solubility in water, and then add the dried solution dropwise to a suspension of NaBH4 in MeOH or EtOH..
EDIT:
Solo very kindly provided two revelant articles on the subject, discussing the influence of the ammonium ion and substituants on stereochemistry of
the reduction of susbtitued piperidones.
Two major things appeared: the hydobromide can be used for the NaBH4 reduction with slight change in epimeric composition (equatorial predominating,
irrevelant for 4-oxo-TEMPO, no stereochemical outcome as the moleculce is symetric)
The piperidones can be reduced in aqueous meduium, neutralizing the salts before introducing the hydride as an aqueous solution. The recation takes
two hours at RT, and the workup very easy:
| Quote: |
Method (f).
Potassium hydroxide (0.56 g) was added to a solution of 1.40 g of 3-methyl-4-piperidone hydrochloride
[9, 10] in 12 ml of water, and then with ice cooling,0.20 g of NaBH 4 in 5 ml of water was added. The
mixture was left at 20 ~ for two hours, acidified with 1.7 ml of concentrated hydrochloric acid, and evaporated
down to about 2 ml; the base was liberated by the action of K2CO a and extracted with chloroform. [Followed by the description of the methylation of
the amine with paarformaldehdye/hydrogenation] |
Solo saved my day, once again. I am forever in debt 
[Edited on 1-6-2008 by Klute]
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
-Alice Parr
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