Hohenheim
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Benzodioxole Acetonylation
First post. Enjoy?
My theory is this: free radical Acetonylation promoted by manganese (III) acetate onto benzodioxole (1,3-methylenedioxybenzene) is possible with
(regio)isomerization favoring the production of 2,3-methylenedioxy-phenylpropan-2-one. 3,4-MDP-2-P is produced in lesser yields.
The basis of my theory is based on the citation below. Given that the mechanism seems to favor positions -ortho to an electron withdrawing functional
group, as suggested by yields of ketone from anisole being the highest and with excess favoring -ortho positioning, I propose a similar result with
benzodioxole. I seek the opinion of chemists far more experienced than myself (my name would suggest otherwise, as pompous as he was).
Stigma carried by the compound is duly noted; let's keep it scientific, and I'll be ecstatic with any and all feedback.
Here is the paper, for those of you with access to the Journal of Organic Chemistry (ACS):
J. Org. Chem., 1984, vol. 49 (1603-1607) "Aromatic Acetonylation Promoted by Manganese (III) and Cerium (IV) Salts"
Let no man belong to another that can belong to himself.
-Paracelsus Von Hohenheim
Quote from Turd:
"And what is Stugartt supposed to be? Are you sure you don't mean Stuttgart, or is this supposed to be a transcription of some crazy high German
dialect?"
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turd
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If this is the thing Mn(III) thing posted on the rhodium site: Attention, yields are given relative to the Mn-salt with the aromatic used as solvent.
This may be fine for benzene or anisole, but for benzodioxole it is quite terrible! To make it viable you would need to find a way to do this in an
inert solvent - good luck.
And what is Stugartt supposed to be? Are you sure you don't mean Stuttgart, or is this supposed to be a transcription of some crazy high German
dialect?
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Hohenheim
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You caught me; idiocy that's subtle is the worst...
Definitely Stuttgart...
As for your response, what do you mean 'as a solvent?'
I thought the conversion was to ketone by Acetonylation, and that acetic acid was solvent enough. Mn(III) Acetate should be soluble in glacial acetic
acid, yes? (EDIT 2: Glacial acetic acid is a good solvent for both aromatics and polar salts; it is polar itself, but has the ability to dissolve
non-polar oils and aromatics)
Also, I thought benzene was terrible in comparison (40% conversion) to anisole (over 70%)... if you have a reference, or other reasoning, please do
share.
I'm all ears.
(thanks, by the way, for not makin' fun of me!)
I'm also aware of the Rhodium post, but I have found nothing in terms of benzodioxole...
[Edited on 23-2-2012 by Hohenheim]
[Edited on 24-2-2012 by Hohenheim]
Let no man belong to another that can belong to himself.
-Paracelsus Von Hohenheim
Quote from Turd:
"And what is Stugartt supposed to be? Are you sure you don't mean Stuttgart, or is this supposed to be a transcription of some crazy high German
dialect?"
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turd
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My point was that they use a whopping excess of aromatic, probably to avoid polycondensation. This is fine for benzene and anisole, which are dirt
cheap, but not so nice for benzodioxole. The yields are given relative to the Mn(III)-acetate, which under normal circumstances is the limiting
reagent if using benzene (though some people here seem to have problems acquiring benzene), but not in the case of benzodioxole. Calculate the yield
based on the aromatic and things look quite sad.
Rhodium has some speculation on reducing the excess of aromatic:
https://www.erowid.org/archive/rhodium/chemistry/p2p.mangane...
(Also note the point on bad regioselectivity)
I wouldn't put all my eggs in that particular basket - looks annoying.
And yes, by analogy I would also think that the 2,3-MeO-P2P is the major product, but I never understood this +M/+I thing. Might be some chelating
with the Mn ion in this case?
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Hohenheim
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Yeah, tough one...
Thanks for your input.
I realize that the yields are relative to the Mn salt, and that distillation can recover reactant benzodioxole... Although the method is rather
annoying, and the regioselectivity is weak, the ability to proceed with such relative ease in synthesis makes it attractive.
As for the mechanism, Mn III Acetate tends to buddy up with methoxy groups (basically anything that creates a slightly positive charge by attracting
an electron from the ring) and bind to the site para to the functional group.
On a side note, the conversion of the resultant ketone to amine would provide 2,3-MDMA, which is active, according to some tedious Irish scientists
(below). If one did not want such and wanted to reduce this to the amino alcohol after a tidy nitrosation (I don't know what to call it, I just know
that the ketone can be easily converted to the ketoxime), it would provide a rather useful means of obtaining both regioisomers for potency analysis.
Whatever the use, this information should be available for all.
If one should consider that benzodioxole is actually really cheap to produce from catechol and DCM, one might not think much of excess benzodioxole.
Well, this was just a curiosity, as I have better reactions to consider anyway. Thanks!
British Journal of Pharmacology (2007) 152, 1121–1130
[Edited on 2-3-2012 by Hohenheim]
Let no man belong to another that can belong to himself.
-Paracelsus Von Hohenheim
Quote from Turd:
"And what is Stugartt supposed to be? Are you sure you don't mean Stuttgart, or is this supposed to be a transcription of some crazy high German
dialect?"
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