Author Topic: N-Hydroxy-Amphetamines from Amphetamines  (Read 2423 times)

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Rhodium

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N-Hydroxy-Amphetamines from Amphetamines
« on: September 16, 2004, 06:58:00 PM »
Synthesis of N-Alkyl-N-Hydroxyamphetamines and Related Nitrones
A. H. Beckett, R. T. Coutts and F. A. Ogunbona

Tetrahedron 29, 4189-4193 (1973)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/n-oh-amphetamines-1.pdf)

Abstract
The action of m-chloroperbenzoic acid on various amphetamines and on dibenzylamine is shown to yield N-hydroxy derivatives and related nitrones.
____ ___ __ _

Synthetic Routes to Optical Isomers of Primary and Secondary Hydroxylamines of 1-Arylisopropylamines
A. H. Beckett, K. Haya, G. R. Jones and P. H. Morgan

Tetrahedron 31, 1531-1535 (1975)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/n-oh-amphetamines-2.pdf)

Abstract
A number of optically pure primary 1-arylisopropylamines were converted to 3-phenyl-2-(1'-arylisopropyl)oxaziridines by the oxidation of the corresponding benzylamines with m-chloroperbenzoic acid. Subsequent acid hydrolysis of the 3-phenyloxaziridines yielded optically pure N-hydroxy-1-arylisopropylamines. The action of m-chloroperbenzoic acid on optically pure secondary 1-arylisopropylamines gave optically pure N-hydroxy derivatives. The optical purity of the hydroxylamines were analysed by GLC utilizing N-trifluoroacetyl-L-prolyl chloride as a reagent.


cattleprodder

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research chemical loopholes
« Reply #1 on: September 17, 2004, 06:32:00 PM »
That is an interesting article, Rhodium.

Now the few remaining RC companies could give us
N-hydroxymethamphetamine with ease, I suppose.  It's not that much different than supplying methylone or 4-fluoroamphetamine, right?

Captain_America

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$
« Reply #2 on: September 17, 2004, 06:46:00 PM »
Now the few remaining RC companies could give us
N-hydroxymethamphetamine with ease, I suppose.  It's not that much different than supplying methylone or 4-fluoroamphetamine, right?


Not quiet. In order to make the N-OH-amphetamines following this method at least they'd have to pass the illegal ampetamines. Situation like this is also probably the major reason you haven't seen DOI pushed by them, as they need to go via illegal 2,5-DMA, alternatively another route which would upon reduction give some 2,5-DMA. But there is an easy way around that, luckily, they are blind to see it...

cattleprodder

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2,5-DMA
« Reply #3 on: September 17, 2004, 06:48:00 PM »
There is a prescription drug in the US called methoxamine (which is chemically 2,5-dimethoxyphenylproponalamine) which could be reduced ala one of the (pseudo)ephedrine to methamphetamine methods to 2,5-DMA. (I think.) 

Is this what trick you are alluding to?  I kind of doubt it.  You have just piqued my interest, though.  Do tell.

Rhodium

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Methoxamine is no good precursor.
« Reply #4 on: September 18, 2004, 09:56:00 AM »
methoxamine (which is chemically 2,5-dimethoxyphenylproponalamine) which could be reduced ala one of the (pseudo)ephedrine to methamphetamine methods to 2,5-DMA. (I think.)

Nope, any HI based reductive protocol will demethylate the methoxy groups with more ease than the alcohol being reduced.

The way around 2,5-DMA is to make 4-Iodo-P2P and reductively aminate that.

latest addition (09-20-04): Edit: Naturally I meant 4-Iodo-2,5-dimethoxy-P2P.
You would have to research/experiment to find a procedure which did not effect dehalogenation of the ring though, but there are several mild methods available out there.


Captain_America

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The way around 2,5-DMA is to make 4-Iodo-P2P...
« Reply #5 on: September 18, 2004, 02:49:00 PM »
The way around 2,5-DMA is to make 4-Iodo-P2P and reductively aminate that.

Sounds like the first thing that comes to mind, but, what about dehalogenation of the fragile iodine during reduction(s)? Even the minimal dehalogenation would render the route useless law-wise.

obia

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many ways to skin this particular cat, for...
« Reply #6 on: September 19, 2004, 04:05:00 PM »
many ways to skin this particular cat, for example diazotising 4 amino DMA, itself produced by reducing 4nitro 25 dimeo alpha methyl nitrostyrene, first with LAH and then with hydrogen over palladium (or even old fashioned Sn/HCl)  The aliphatic amine is unaffected by diazotisation provided the pH is controlled and kept strongly acidic the protonated amine is unaffected.  
i shall now slink back off to my cave

cattleprodder

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Sorry Rhodium, I guess I should have known...
« Reply #7 on: September 19, 2004, 05:53:00 PM »

cattleprodder

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Oh yes, I do confess.
« Reply #8 on: September 20, 2004, 01:03:00 AM »
O Rhodium,

Oh yes, I do confess, I did digress, at length, at best.  With pseudoscientific ramblings better suited to a diary than to this game, this game, our game of chess. 

But how on Earth you plan to get 2,5-DMA or DOI from reductively aminating 4-iodo-P2P is well beyond me.  I thought that the synthesis would at least involve 2 methoxyphenyl groups somewhere and at some point, no?

Captain_America,

To avoid dehalogenation such as de-iodination of the benzene ring, one must be careful to keep the temperature cold and to use only 1 equivalent of LAH.  Using this method usually does not strip away the aromatic halogen.

obia, How do you plan to obtain the 4-nitro-2,5-dimethoxyphenyl-2-nitropropene itself, make it from scratch (meaning, starting from 1,4-dimethoxybenzene and then formylating)?  Is this not an uncommon chemical which you mention, or am I missing something?

However, synthetically speaking, I find your proposed synthetic outline to be factually correct if not a tad bit too laborious, or perhaps as the case may be, just laborious enough to work as you might reply.

Rhodium

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Excuse my typo, I have added a correction to...
« Reply #9 on: September 20, 2004, 03:24:00 AM »
Excuse my typo, I have added a correction to

Post 532000

(Rhodium: "Methoxamine is no good precursor.", Novel Discourse)



Captain_America

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cattlepoder
« Reply #10 on: September 20, 2004, 04:06:00 AM »
Even if the ephedrine-DMA route you propose worked w/ RP/HI, it wouldn't bee cool to bee ripped-off by pharmaceutical companies and extract the precursor from thier shitty tablets for this synthesis...

But, if you really like that route read:

Post 504623

(Kinetic: "Another way to methaephetamine", Novel Discourse)

Captain_America

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To avoid dehalogenation such as de-iodination...
« Reply #11 on: September 20, 2004, 10:54:00 AM »
To avoid dehalogenation such as de-iodination of the benzene ring, one must be careful to keep the temperature cold and to use only 1 equivalent of LAH.  Using this method usually does not strip away the aromatic halogen.

This would not work while the iodine is on, period. Temperature has little significance, nor does stochiometry, the hydride ion (theoretical) is a very powerful nucleophile, it would replace the iodine on the ring to some extent.