stoichiometric_steve
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Scaleup woes - Reduction of Nitrostyrenes to Nitroalkanes
Hey guys, what's currently the best/cleanest/most scalable reaction for the Reduction of Nitrostyrenes to Nitroalkanes? The ones i am familiar with
diminish in yields very drastically upon scaling up beyond a few grams of substrate.
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solo
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Quote: Originally posted by stoichiometric_steve  | Hey guys, what's currently the best/cleanest/most scalable reaction for the Reduction of Nitrostyrenes to Nitroalkanes? The ones i am familiar with
diminish in yields very drastically upon scaling up beyond a few grams of substrate.
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One-pot Reduction of Nitrostyrenes to Phenethylamines using Sodium Borohydride and Copper(II) chloride
[Edited on 4-7-2024 by solo]
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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stoichiometric_steve
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Hey Solo, that's among the ones i know that don't scale, also wrong target product sadly!
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solo
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Aust. J. Chem., 1996, 49, 1257-1260
The Yeast-Mediated Reduction of Nitrostyrenes
in Organic Solvent Systems
Attachment: Aust. J. Chem., 1996, 49, 1257-1260 The Yeast-Mediated Reduction of Nitrostyrenes in Organic Solvent Systems.pdf (292kB)
This file has been downloaded 37 times
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zed
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Reduction of Nitrostyrenes?
Catalytic Hydrogenation, via Platinum Black, in an Acetic environment. Glacial Acetic Acid, with a molar equivalent of Sulfuric Acid, makes a nice
solvent mix. Without a strong mineral acid present, extensive polymerization may take place.
Yields vary, but it isn't a difficult process.
Strike, discusses the reduction in one of his writings. Uses HCl, as I recall. Produces Mescaline.
Back in the 1900s, a German chap, used Glacial Acetic acid and Sulfuric acid, also to produce Mescaline.
Check the literature. Once upon a time, I translated the paper.... It wasn't easy!
Yields are in the 65% range (for Mescaline). The reduction is very exothermic, and as such, stirring your hydrogenation is much superior to shaking
it. Easier to control the heat in a stationary flask. Just cool your flask.
Not so easily done in the case of a shaken flask. Yields are highly dependent on the substituents attached to the Benzene Ring.
As far as I know, Hydrogenation is futile if you are attempting to reduce Nitropropenyl Benzenes, directly to the Amine. Keto-Oximes are more
difficult to reduce than Aldehyde Oximes. In the case of Nitropropenyl Benzenes, the reduction stops at the Oxime stage.
In the past, some forum members have suggested that, Amalgamated Aluminum can reduce Nitropropenyl Benzenes directly to Phenylisopropylamines, but I
have no direct knowledge of this matter.
Oh yes! I forgot to mention. This hydrogenation proceeds nicely at STP.
[Edited on 6-7-2024 by zed]
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Mateo_swe
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There are different methods used depending of the target nitroalkane, maybe you can be little more specific?
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stoichiometric_steve
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I meant 2-Nitroethenylbenzenes, possibly with substituents at the ring,reduced to the corresponding Nitroalkane.
I did find a paper that uses a 2 step, one pot sequence to the Amine, albeit with an expensive homogenous Rh based catalyst for the Alkene reduction,
and only ~40% total yield of the Amine. Might be worth it if the Rh catalyst can be bound on a resin support and thus made into a flow chemistry
cartridge
Paper
[Edited on 8-7-2024 by stoichiometric_steve]
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Dope Amine
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Hey Steve,
I know someone with the same issue. They'd like to reduce ~300 g of 2,5-DMNS to the phenethylamine.
Likely going to reduce to the nitroalkane with NaBH4 in DCM. Then reduce to the amine with 10% Pd/C + KOOCH in Methanol with ~5% water.
If you have access to Me3SiCl then you could do both reductions with LiBH4/NaBH4 https://doi.org/10.1002/anie.198902181
[Edited on 9-7-2024 by Dope Amine]
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stoichiometric_steve
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Hey Dope Amine, thank you for your input. I have previously used BF3*Et2O with NaBH4 (which should mechanistically be the same, as BH3 is the actual
reducing agent) for this kind of reduction and have found it to be rather inconvenient even at small scale. Not that this would definitively exclude
it but i am an extremely lazy fucker and thus am always looking for more practical methods.
What's most limiting for me is not access to reagents or equipment but rather the aspect of working all alone on things that most people really have
no interest in or simply don't understand.
I wish reduction of the double bond of Nitrostyrenes was as easy as the aqueous NaBH4/PTC reduction of 2-nitropropenylbenzenes. The yields are
stellar, conditions are so, so tame and workup is a breeze.
So yeah, if anyone has a proven method that works reliably at a scale of several hundred grams, that would be awesome!
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solo
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...why not the old stand by wth amalgamated aluminum...it will remove double bonds and convert nitrates to amines.....solo
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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stoichiometric_steve
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| Quote: Originally posted by solo | | ...why not the old stand by wth amalgamated aluminum...it will remove double bonds and convert nitrates to amines.....solo |
Hey Solo, not the worst idea actually. Have you run this on a scale of several hundred grams?
I've persobally never touched Al/Hg, my shtick is NaBH4 and Pd/C if i want amines. So any input on how to run an Al/Hg safely on this scale would be
welcome!
[Edited on 12-7-2024 by stoichiometric_steve]
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