chemrox
International Hazard
Posts: 2961
Registered: 18-1-2007
Location: UTM
Member Is Offline
Mood: LaGrangian
|
|
TLC monitoring progress of STAB reductive am
I'm running an STAB mediated reductive amination of an aniline and a saturated cyclic ketone. I'm using: 10:2:1, DCM: AcOEt:MeOH + drop or two Et3N.
It's going slowly.
There's been a bit of smearing and spot overlap but the major constituents are well separated and distinct. Only oddity is the aniline spot which as
a core and halo... bizarre (at least to me).. any explanation of the latter phenonmenon or suggestions for improvement much appreciated.
CRX
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
|
|
|
grind
Hazard to Others
Posts: 120
Registered: 13-1-2007
Member Is Offline
Mood: No Mood
|
|
Your solvent mixture is not suitable for STAB reductions! Methanol destroys STAB quickly and you must not use it!
Usual solvents are toluene, acetonitrile, 1,2-dichloroethane and THF, occassionally DCM and ethyl acetate. Addition of acetic acid accelerates the
reaction.
I think the unknown spot is the alcohol, derived from your cyclic ketone. The methanol in your solvent mixture promotes this side reaction.
|
|
|
Nerro
National Hazard
Posts: 596
Registered: 29-9-2004
Location: Netherlands
Member Is Offline
Mood: Whatever...
|
|
What's a STAB reduction? Google was useless, only gave me info on how not to get stabbed...
#261501 +(11351)- [X]
the \"bishop\" came to our church today
he was a fucken impostor
never once moved diagonally
courtesy of bash
|
|
|
Klute
International Hazard
Posts: 1378
Registered: 18-10-2006
Location: France
Member Is Offline
Mood: No Mood
|
|
Nerro: STAB: Sodium Triacetoxyborohydride, see related thread.
Grind: No, no, he is using the above system as TLC eluant, not reaction solvent.
Chemrox: Sometimes TLC does some weird things.. Some stains do strange patterns, one compound can make two different forms on the same plate, etc...
I should worry too much, it can simply be because of the solvent system when it reacts the aniline, elutin g it side ways at different rayes. It's
hard to give a valid explanation. Maybe you could try doing a spot of aniline with the same eluant but withut any other compounds and see if it acts
the same.
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
-Alice Parr
|
|
|
chemrox
International Hazard
Posts: 2961
Registered: 18-1-2007
Location: UTM
Member Is Offline
Mood: LaGrangian
|
|
I think I caused a misunderstanding. The solvent system is for TLC plate development. For the reax I'm using DCE.
@Klute: the aniline reference spot didn't do that so it might be a reaction phenomenon...(?) and thanks for helping clear up the solvent
misunderstanding.
[Edited on 21-11-2008 by chemrox]
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
|
|
|
grind
Hazard to Others
Posts: 120
Registered: 13-1-2007
Member Is Offline
Mood: No Mood
|
|
Oh I see I was wrong with the solvent mixture. Sorry....
May be the reaction product is still complexed with the boron compound, that could interfere with the TLC. The safe way is to take an aliquot of the
reaction suspension (solution AND solid particles!) and to treat it in the following way (mini workup):
Add diluted HCl, shake until you have 2 clear phases and 5 minutes longer, then basify with NaOH-solution, separate the DCE-Phase, dry the organic
phase with Na2SO4 (or omit the drying step). Now you can run your TLC.
Note: DCE is able to react with amines to form 2-chlorethylamines, especially at elevated temperatures! So you can expect (tiny amounts of) products
of this side reaction. On the other side, DCE usually gives the highest yields in STAB reductions, compared with toluene, THF and acetonitrile.
|
|
|
chemrox
International Hazard
Posts: 2961
Registered: 18-1-2007
Location: UTM
Member Is Offline
Mood: LaGrangian
|
|
"DCE usually gives the highest yields in STAB reductions, compared with toluene, THF and acetonitrile.." I've also read this. Does anyone know why?
Why not DCM for example?
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
|
|
|
stoichiometric_steve
National Hazard
Posts: 819
Registered: 14-12-2005
Member Is Offline
Mood: satyric
|
|
Even though 1,2-Dichloroethane gives the highest yield, i would still avoid it being pretty carcinogenic.
|
|
|
12AX7
Post Harlot
Posts: 4803
Registered: 8-3-2005
Location: oscillating
Member Is Offline
Mood: informative
|
|
Different components can spread at different rates in the reaction solvent when you apply the drop to the TLC plate. So if you're getting a halo,
that would be from whatever moves the fastest in that solvent. It shouldn't be possible to get a "core and halo" from the same compound...
Tim
|
|
|
chemrox
International Hazard
Posts: 2961
Registered: 18-1-2007
Location: UTM
Member Is Offline
Mood: LaGrangian
|
|
@steve I'm not drinking it..anyway, I'll do an NaOH workup on a small aliquot and extract with ether. Maybe the aniline halo will disappear then.
It's been running a long time anyway. Time to quench and obtain product. I edited this to add a thought I had.. I looked at the reference aniline
spot and it has a sort of broad halo as well. I wonder if the Et3N in the development solution is making this? I'll try an Et3N reference spot and
see where it ends up.
[Edited on 23-11-2008 by chemrox]
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
|
|
|
chemrox
International Hazard
Posts: 2961
Registered: 18-1-2007
Location: UTM
Member Is Offline
Mood: LaGrangian
|
|
STAB gen proc: HELP wanted
Anyone using STAB for red. ams. please weigh in here. My general procedure calls for "quenching with 1N NaOH, then extract with ether..." after the
reax is done. It doesn't provide any guidance on how much solution to use or what to look for. I added 1N NaOH until it looked like no more white
solids were being generated. I added ether. I've got an ethereal solution with white solids and a lot of globular looking emulsion. What should I
do? What's the recovery?
[Edited on 25-11-2008 by chemrox]
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
|
|
|
grind
Hazard to Others
Posts: 120
Registered: 13-1-2007
Member Is Offline
Mood: No Mood
|
|
When your reaction mixture is strongly (!) alkaline, you can extract the amine. The NaOH solution destroys residual STAB and acetic acid salts of your
amine. You need the free amine to extract it with ether. My suggestion is to test the pH of your mixture and then you add an excess of NaOH-solution.
If you can´t get rid of a solid - don´t worry. Separate the solid by filtration and extract the filtrate with ether.
The solid is probably the acetamide of your amine (it´s a secondary amine - right?), arising from a side reaction. Boil the solid with 6N HCl for
some hours, make alkaline and extract with ether. That should increase the yield of your amine.
|
|
|
Klute
International Hazard
Posts: 1378
Registered: 18-10-2006
Location: France
Member Is Offline
Mood: No Mood
|
|
In my experience with STAB, fine white solids that are a pain to work with/filter are formed when quenching with acids, and then dissolve by addition
of strong NaOH. Maybe you haven't added enough base, don't be afraid to go to pH 14, they should dissolve. Wash well the organic extract with your
amine, otherwise when you add dilute acid some solids reappear and seem to form emulsions very easily.
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
-Alice Parr
|
|
|
chemrox
International Hazard
Posts: 2961
Registered: 18-1-2007
Location: UTM
Member Is Offline
Mood: LaGrangian
|
|
Thanks! Both of you!
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
|
|
|
stoichiometric_steve
National Hazard
Posts: 819
Registered: 14-12-2005
Member Is Offline
Mood: satyric
|
|
The solid is H3BO3 (borates with basic quench), no acetamide or anything!!
[Edited on 26-11-2008 by stoichiometric_steve]
|
|
|
grind
Hazard to Others
Posts: 120
Registered: 13-1-2007
Member Is Offline
Mood: No Mood
|
|
| Quote: | Originally posted by stoichiometric_steve
The solid is H3BO3 (borates with basic quench), no acetamide or anything!!
[Edited on 26-11-2008 by stoichiometric_steve] |
If the solution pH is < 7, that´s correct. But normally you add NaOH until the solution is strongly alkaline, then soluble sodium borate is
formed.
In one of my reductive aminations with STAB I´ve also got a solid which wasn´t soluble even in an excess of dilute NaOH solution.
Analysis of this solid showed it was the acetamide of the product amine. Saponification of the amide yielded a further crop of product amine.
So I assume it´s very similar in chemrox´case.
|
|
|
chemrox
International Hazard
Posts: 2961
Registered: 18-1-2007
Location: UTM
Member Is Offline
Mood: LaGrangian
|
|
I'll run an IR on the stuff. It's all going to keep until Monday. I'm going out of state for the hollidays. Which reminds me how grateful I am for
this forum/website/whatever we are.
Peace,
CRX
[Edited on 26-11-2008 by chemrox]
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
|
|
|
chemrox
International Hazard
Posts: 2961
Registered: 18-1-2007
Location: UTM
Member Is Offline
Mood: LaGrangian
|
|
I did check the aqueous layer and found the pH to be ~7 so i added enough base to get it up to ~ 12-14. I re-extracted with the first ether portion
and got a gawdawful emulsion that is sitting in the fridge overnight
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
|
|
|
chemrox
International Hazard
Posts: 2961
Registered: 18-1-2007
Location: UTM
Member Is Offline
Mood: LaGrangian
|
|
So does anyone know a coarse filtration medium to reduce the solids and make this mess a little more manageable? I tried glass wool... not very
effective....clogged quickly
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
|
|
|
stoichiometric_steve
National Hazard
Posts: 819
Registered: 14-12-2005
Member Is Offline
Mood: satyric
|
|
That was fucking triple posting
use Celite
|
|
|
grind
Hazard to Others
Posts: 120
Registered: 13-1-2007
Member Is Offline
Mood: No Mood
|
|
I filtered my reduction mixture through a simple small glass filter frit (so called G4 frit), that was satisfactory. Or like steve said - you can use
a celite pad of approx. 1-2 cm thickness in the frit.
|
|
|
![[*]](images/xpblue/default_icon.gif){kind=icon}
