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Author: Subject: Grignard reagent compatibility
Magpie
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[*] posted on 22-1-2016 at 16:59
Grignard reagent compatibility


I have this wild idea of building primary alcohols, one -CH2- at a time, using trioxane. A Lewis acid, eg, is needed to catalyze the decomposition of the trioxane to formadehyde. Ideally this would all be done in situ.

Will a Grignard reagent, eg, alkyl-MgBr, react with a Lewis acid, say ZnCl2 or FeCl3?

[Edited on 23-1-2016 by Magpie]




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UC235
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[*] posted on 22-1-2016 at 17:37


Yes, they will react. That is called transmetallation and is a common strategy to preparing metal alkyls. If you add ZnX2 to a grignard, expect it to catch on fire when you open it to atmosphere.

Sometimes the metal alkyls do chemistry that is modified from the original grignard which can be in your favor. For example, see http://www.orgsyn.org/Content/pdfs/procedures/v81p0033.pdf or Lithium dialkylcuprates.

Unfortuntely I have not found much to do with my large stock of trioxane either. It works well for Blanc Chloromethylation and probably will work in the Prins Reaction.
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PlatinumLab
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[*] posted on 22-1-2016 at 18:01


Magpie, have you tried to to see if Trioxane would directly react with your grignard reagent? While it is stable, it still has the full components of 3-formaldehyde, and I suspect there is a possibility for it to react as formaldehyde in-situ, especially in the presence of something as reactive as a grignard agent.

As far as I'm aware, the formation of Trioxane is naturally reversible, in spite of its stability. A lewis acid would probably just serve to speed up the reverse reaction and shift the equilibrium left. Your grignard reagent could serve the same purpose by gradually reacting with small amounts of formaldehyde that get freed up.

Just a hypothesis. You may have already tried this.

There are of course other things you could try.... such as pouring a solution of Trioxane down a column of a solid acid , causing it to convert to formaldehyde solution before it lands in your reaction, thus not contaminating the grignard.

[Edited on 23-1-2016 by PlatinumLab]
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Magpie
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[*] posted on 22-1-2016 at 18:08


UC235:

Thank you - I can throw out that idea. I had seen a hint of this transmetallation in the Wiki for ZnCl2.

I think the trioxane can still be used, however. It will just have to be decomposed to formaldehyde in a separate vessel that would then feed the vessel containing the Grignard reagent.

Paraformaldehyde could possibly also be used but it contains around 4% water. Trioxane has none. I bought my trioxane as camp stove fuel. Where did you get yours?

Platinum:

No, I have not tried using my trioxane yet. And I don't have any paraformaldehyde. I tried to recover some from an RV toilet disinfectant (Thetford) but this was a disaster. I reported on this some time ago.

[Edited on 23-1-2016 by Magpie]

[Edited on 23-1-2016 by Magpie]

[Edited on 23-1-2016 by Magpie]




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[*] posted on 22-1-2016 at 19:27


Magpie,

See: Organic Syntheses, Coll. Vol 1, p 188.

You have to depolymerize paraformaldehyde at high temperature and direct the formaldehyde gas into the Grignard reagent. Not easy but doable if you really want to go this route.

See reference 5 at the end. Maybe there is some procedure for direct reaction with paraformaldehyde in one of the journal refs there.

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PlatinumLab
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[*] posted on 22-1-2016 at 19:38


Why bother working with the pure formaldehyde gas? I would just dissolve it in an inert solvent and add it in that form. Perhaps reacting a trioxane solution with aluminua beads, or some other form of solid acid, and then filtering directly into the reaction could do the trick.

I'm not sure on the solubility of trioxane in organics, but I don't see it being problematic.
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DJF90
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[*] posted on 23-1-2016 at 01:10


You may find that the Lewis acidity of the grignard reagent is sufficient to effect the reaction with trioxane. Alternatively, you can form a monomeric formaldehyde solution by distillation of paraformaldehyde and acid catalyst (e.g. TsOH, Amberlyst 15) in THF. There is a Synthesis or SynLett paper detailing it but unfortunately it's saved to my desktop at work so you'll have to wait until Monday for the reference.
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Dr.Bob
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[*] posted on 23-1-2016 at 16:36


Not sure if it would work in Grignards, but I have successfully used paraformaldehyde directly in place of formaldehyde in many cases. But mostly for reactions in water or methanol, where there is likely an equilibrium between them. In the anhydrous conditions needed for a Grignard reaction, that might not be as simple, but it might still work. The Org Syn link below shows the depolymerization, but some other references do say that paraformaldehyde does work directly as well, just can't see them from home.

http://www.orgsyn.org/demo.aspx?prep=CV1P0188
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[*] posted on 23-1-2016 at 22:55


Quote: Originally posted by Magpie  

Paraformaldehyde could possibly also be used but it contains around 4% water. Trioxane has none. I bought my trioxane as camp stove fuel. Where did you get yours?


I purchased a significant number of army surplus trioxane fuel tablets from which the trioxane can be readily distilled (b.p. 115C).

Unfortunately, based on this paper (www.sciencemadness.org/talk/files.php?pid=165071&aid=892...), the depolymerization seems pretty non-trivial.

It could probably undergo transacetalization is an alcohol catalyzed by acid pretty readily but dialkoxymethanes are also resistant to attack by grignard.
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CuReUS
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[*] posted on 24-1-2016 at 05:55


Quote: Originally posted by Magpie  
I have this wild idea of building primary alcohols, one -CH2- at a time, using trioxane. A Lewis acid, eg, is needed to catalyze the decomposition of the trioxane to formadehyde. Ideally this would all be done in situ.

I don't understand,do you mean you will react an alkyl-MgBr with trioxane to get the alcohol,then convert that alcohol to halide and make a grignard reagent and then repeat the process till you get the alcohol of desired length ?

Quote:
Will a Grignard reagent, eg, alkyl-MgBr, react with a Lewis acid, say ZnCl2 or FeCl3?


see this paper,they use an Fe(+3) catalyst with their grignard reagent in their synthesis of juvabione
N. Soldermann, J. Velker, O. Vallat, H. Stoeckli-Evans and R. Neier, Helv. Chim. Acta, 2000, 83, 2266.
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Magpie
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[*] posted on 24-1-2016 at 16:00


Quote: Originally posted by CuReUS  

I don't understand,do you mean you will react an alkyl-MgBr with trioxane to get the alcohol,then convert that alcohol to halide and make a grignard reagent and then repeat the process till you get the alcohol of desired length ?


Yes, that's the idea. You stop when you have the alcohol you want. If you wanted iso-amyl alcohol react trioxane (decomposed to formaldehyde) with iso-butylMgBr.

If you had access to ethylene oxide you could add -(CH2)2- each time.




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DJF90
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[*] posted on 25-1-2016 at 04:21


Homologations play an important role in synthesis and what you describe is one way of achieving chain elongation. This approach is particularly important for preparing labelled compounds where the homologation reaction is performed with a labelled reagent, e.g. 13C or 2H-paraformaldehyde in this example. There was something similar recently in Chem. Eur. J. using an alkyne-aldehyde sequence (http://onlinelibrary.wiley.com/doi/10.1002/chem.201504248/ab...) also amenable to labelling.

Quote: Originally posted by DJF90  
Alternatively, you can form a monomeric formaldehyde solution by distillation of paraformaldehyde and acid catalyst (e.g. TsOH, Amberlyst 15) in THF. There is a Synthesis or SynLett paper detailing it but unfortunately it's saved to my desktop at work so you'll have to wait until Monday for the reference.


Please find the reference attached.

Attachment: Monomeric formaldehyde in ethereal solution.pdf (85kB)
This file has been downloaded 703 times

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