Klute
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Registered: 18-10-2006
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Removal of excess acetoacetic ester
I'm currently preparing various tertiary amides by aminolysis of ethyl acetoacetate and secondary amines.
The reaction is done at high temp (>150°C), catalyzed by NaH, with removal of the formed ethanol by distn.
The mixture is then neutralized with NH4Cl, and in the procedure, excess AcAcOEt is removed by distn (20torr), followed by distn of the residu (0.4
torr).
The first time i tried this procedure, I obtained a viscous black residu after removal of excess ester, which I cannot fractionnate (too weak of a
vacuum). Column chroamtography was very tedious, and it was impossible to obtain a decent seperation of the complex mixture (>10 staisn by TLC).
After doing another columns on the major fraction, the product was still impur. I'm planning on removing most impurirtes after reducing the amide
function, but impurities in = impurites out, and I don't want to have them following through out the several subsequent steps...
So, I was thinking of a way of removing excess acetoacetic ester by chemical means, without affecting the acetoacetic amide. I can remove most of the
ester by distn, but I would like to avoid charring at the end.
My first though was hydrolsyis of the ester, at room temp. I'm not sure if acidic or basic is the best option. I think this shouldn't affect the
amide.
The ester is aslo slightly soluble in water (3g / 100mL), so maybe a few washes with the organics in a solvent could remove some. But I cannot find
any info the solubility of the amide.
Acetoacetic amides of aromatic amines are said to be soluble in basic media, but insoluble in neutral/acidic.
So, I guess my bets option would be to stir the residu obtained afetr removal of most of the ester with slight excess 10% NaOH for an hour or two, add
solvent neutralize to pH=7, and extarct the organics, or stir with dil. HCl for an hour or two, possibly with a cosolvent, and extarct.
I will try this with a sample, but I have no way on determining who is the amide and the ester (if visible under UV) by TLC...
Any comments or suggestions are welcome. Anybody familair with how easily AcACoEt is hydrolyzed?
\"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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Klute
International Hazard
Posts: 1378
Registered: 18-10-2006
Location: France
Member Is Offline
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Well, finally my hydrolysis proposal worked out fine.
The b-ketoester and b-ketoamide mixture was treated with 1N NaOH, amounting to the maximum amount of ester left, and stirred at Rt for 30min, with a
little methanol.
The mixture was then acidified to neutral with GAA, and extracted with DCM. TLC (10% AcOEt/Pet ether, or DCM as eleuant) showed there was a little
ester left, so another treatment in DCM solution was performed, with the same amount of NaOH (more concentrate dthough, about 2.5N) . After
neutralizing with GAA and extraction of the aqueous, the b-ketoamide was recovered freed from any acetoacetic ester in a 96% yield!
Compared to the first product, where the ester was removed under vacuum, this product displayed only 3 stains by TLC:
the only impurities was the enamine (kinetic product of the aminolysis), and a very slight amount of high MW compounds (thermal decomposition I
suppose).
Note: such b-ketoamides are said to be soluble in acids. Neutralization of the solution enables recovery by extraction. Apaprently the sodium salts
hardly form with somewhat dilute NaOH solution, as extarction of the basic mixture after RT hydrolsyis seemed to recover all the amide (test-tube
scale). The aq. was neutralized for safety though. On test tube scale, the addition of the acid caused vigorous CO2 evolution from the decomposition
of the acetoacetic acid. I guess it's because the mixture was much more concentrated. CO2 evolution was not seen on a preparative scale. Maybe more
concentrated NaOH solution should be used to get all the ester hydrolyzed in one go.
Hope this can be usefull to anyone.
\"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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