Column Chromatography ketone/silica

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SUMMARY

The discussion centers on the unexpected transformation of a carbonyl group to a hydroxyl group during column chromatography using silica gel after a Baylis-Hillman reaction involving 2-nitrobenzaldehyde and acrylonitrile with DABCO as a catalyst. The silica gel's acidity, influenced by its purity, can lead to protonation of the carbonyl, resulting in the formation of a beta-hydroxy compound. To achieve the desired ketone product, a mild oxidizing workup is recommended, utilizing Dicyclohexyl-carbodiimide (DCC) and triethylamine for effective transformation without product degradation.

PREREQUISITES
  • Understanding of Baylis-Hillman reactions
  • Knowledge of column chromatography techniques
  • Familiarity with NMR spectroscopy for product analysis
  • Basic organic chemistry concepts, particularly carbonyl chemistry
NEXT STEPS
  • Research the effects of silica gel acidity on organic reactions
  • Learn about the use of Dicyclohexyl-carbodiimide (DCC) in organic synthesis
  • Study the mechanisms of carbonyl reduction and oxidation reactions
  • Explore one-pot reaction strategies in organic synthesis
USEFUL FOR

Organic chemists, synthetic chemists, and researchers involved in reaction optimization and product purification will benefit from this discussion.

emmy
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I recently ran a baylis-hillman reaction of 2nitrobenzaldehyde and acrylonitrile (DABCO catalyst) and after my reaction had gone to completion (determined by tlc) i extracted with chloroform/washed with brine, dried, filtered, rotovaped etc etc

I ran a crude NMR and determined I did have my desired product.

I ran a silica pipette column with %anhydrous diethyl ether/hexanes and took HNMR again, it indicated that my carbonyl had become a hydroxyl group.

The only thing I can figure is that the silica gel in the column protonated my carbonyl. I know that silica gel is somewhat acidic...does anyone know if this would likely occur or what else could have occurred? )':

NewPicture-1.png


MBH product on left, my product after column on right
 
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The acidity of silica depends on the purity of the silica gel. Silica contaminated with heavy metals end up with the metal atoms integrated into the silica molecule and this causes the silanol (Si-OH) groups to be deprotonated far easier. Pure silica isn't very acidic at all. Even if there were protons present to protonate the carbonyl oxygen, there would have to be a nucleophile present to reduce the carbonyl group. That reaction scheme you posted, the nucleophile would have to be a hydride ion. My organic chem knowledge isn't very advanced though, that's the only reaction I know of for reducing carbonyl groups.
 
I would expect the beta hydroxy compound you indicated during silica gel workup. The ketone you wanted (?) would need a mild oxidizing workup of the beta hydroxy compound.

Remember that the DABCO forms an active nucleophilic C from the acrylonitrile, alpha to the CN (a Michael 1,4- adduct)... This then attacks the aromatic carbonyl (like an Aldol reaction), to form an alkoxy anion, that is easily protonated during workup to the hydroxyl.

If your desire is the ketone, a mild oxidant that won't tear up the product (the methylene is doubly activated as a Michael acceptor with an alpha CN and an alpha' CO- the multiple conjugation will also make it prone to polymerization) and a mild workup would be necessary. Dicyclohexyl-carbodiimide (DCC) and stoichiometric base (triethyl amine) could work without isolation of the DABCO reaction mixture as a one pot reaction.

If you have other transformations to perform on the active compound you may want to strategize a bit and see if they can also be done in the same pot with minimal workup-

Good luck!
 

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