Author Topic: Will this route to TMA-2 work ok?  (Read 3902 times)

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sponsan

  • Guest
Will this route to TMA-2 work ok?
« on: July 22, 2003, 02:45:00 AM »
Hello everyone!

Is the following route to TMA-2 feasable?

 Calamus root oil ->
 Asarone -> Sodium Nitrite/H2SO4 ->
 Asarone pseudonitrosite -> Alcoholic KOH ->
 Asarone nitropropene -> Fe/HCl ->
 Asarone ketone -> (NH2OH)2.H2SO4/NaOAc.3H2O ->
 Asarone ketoxime -> Al/Hg reduction in Acidic EtOH ->
 TMA-2


Thanks,
Sponsan.

sYnThOmAtIc

  • Guest
A duuh
« Reply #1 on: July 22, 2003, 03:31:00 AM »
Yea I believe everything there is covered on rhodiums too...I'm positive about that up to the ketoxime formation part


El_Zorro

  • Guest
The only thing that would really hinder any...
« Reply #2 on: July 22, 2003, 03:48:00 AM »
The only thing that would really hinder any route taken from asarone, if I remember correctly, is that the methoxy groups on the molecule are exceptionally acid sensitive.  That's what makes it hard to put asarone through a peracid oxidation.  I'd bet a faster route would be just to use the oxone method on asarone, then rearrange the epoxide with LiI, or ZnI, or one of either bromides.


Rhodium

  • Guest
From asarone/calamus to TMA-2
« Reply #3 on: July 22, 2003, 04:10:00 AM »
At my site, you can find the following descriptions of some of the transformations you mention:

Calamus oil -> Asarone -> Pseudonitrosite -> Nitropropene -> Asarone ketone

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/tma2.html)

Calamus oil -> Asarone -> Pseudonitrosite

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/asarone.html)

Asarone -> Pseudonitrosite -> Nitropropene

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/pseudonitrosite.html)

The only part I'm a bit unsure of is the acidic Al/Hg reduction of the oxime, as I don't find that described in my notes on TMA-2 chemistry (but it might be posted somewhere at the Hive, can someone help finding it?). The oxime has been made in good yield using either

Sonson's method

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/mdaoxime.html)

Chromic's modification

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/alhg.oxime.html). The ketoxime is purified according to

Post 365007

(Barium: "IPA is a good solvent for asarone ketoxime ...", Methods Discourse)


A more common way is probably

reduce the nitropropene to TMA-2, directly or stepwise

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/tmp2np-red.html), as you don't have to proceed through the ketone and ketoxime, which probably gives notably lower yields. In this document there is also a good procedure for the iron reduction of the nitropropene to asarone ketone, if you should decide to use that route in the end.

Anyhow, I suggest that you UTFSE for posts written by Antibody2, Dr_Sister, Chromic and Uemura to find good asarone chemistry discussions. I think that the pros and cons of all the methods you mention has been discussed here at the hive at one time or another during the years.

sponsan

  • Guest
Thanks Rhodium! That direct nitropropeneš...
« Reply #4 on: July 22, 2003, 04:35:00 AM »
Thanks Rhodium!

That direct nitropropene reduction documented by Antibody2 looks much more straight forward than going via the oxime route.  Will give it a go and see what comes out!

Thanks again,
Sponsan.

starlight

  • Guest
experience
« Reply #5 on: July 22, 2003, 12:29:00 PM »
The pseudonitrosite works well on asarone. make sure you don't use too much H2SO4, or leave it too long or you will end up with red goo/tar and a ring nitrated product if I remember correctly. Little difference has been noted between dripping the acid into the top or bottom layers.

Stepwise reduction of the nitropropene also works well. A good route is reduction of the double bond with borohydride, followed by redution to the amine with Zn/NH4COOH in methanol.

have a look at

Post 352269

(Barium: "Wow", Chemistry Discourse)

GC_MS

  • Guest
nitrated impurity
« Reply #6 on: July 22, 2003, 01:17:00 PM »
make sure you don't use too much H2SO4, or leave it too long or you will end up with red goo/tar and a ring nitrated product if I remember correctly.

You remember correctly  ;) . Bruckner states that 2,4,5-trimethoxy-nitrobenzene is formed as impurity.

[...] Unterwirft man Asaron [...] in ätherischer oder ligroinischer Lösung der Einwirkung von nitrosen Gasen, so ist keine Ausscheidung eines Additionsproduktes zu bemerken. Auch im Falle sehr energischer Außenkühlung findet nur Oxydation oder Nitrierung statt, die zur Bildung von 2,4,5-trimethoxy-nitrobenzol führt und stets von starker Verharzung begleited wird. Diese merkwürdige Reaktion findet ihre Erklärung in der besonderen Sensibilität des Asarons, die wahrscheinlich mit der Stellung der Methoxylgruppen zur Propenylkette in Zusammenhange steht3.[...]

3. Eine ähnliche Erscheinung trafen beim Nitrierungsversuch der Asaronsäure (2,4,5-trimethoxy-benzoesäure) R Fabinyi und T Széki, Ber Deutsch chem Ges 39 (1906) 3681) an, indem in Eisessiglösung auf Einwirkung van 81 prozent. Salpetersäure die Carboxygruppe abspaltete und ebenfalls 2,4,5-trimethoxy-nitrobenzol entstand.

Bruckner also finds the nitrated impurity when he prepared the pseudonitrosite the traditional way. As Fabinyi and Széki found that 2,4,5-trimethoxybenzoic acid is converted to the same 2,4,5-trimethoxy-nitrobenzene when treated with HNO3, my guess is that asarone is partially oxidized to 2,4,5-trimethoxybenzoic acid (as a side reaction; atmospheric oxygen and an acidic environment can cause this cleavage), which in turn is nitrated.
For those interested in chemical history: Fabinyi and Széki have done quite some research in the asarone-field; for instance

Post 431532

(GC_MS: "Characterization of asaraldehyde", Chemistry Discourse)
.

Reference of the Bruckner text: V Bruckner. Über das Pseudonitrosit des Asarons. J prakt Chem 138 (1933) 268-274. Also found on Rh's site.


randolph_carter

  • Guest
well hold the phone ethyl......
« Reply #7 on: July 23, 2003, 11:08:00 PM »
it looks like we have another acorus explorer!!!
yer synth route sounds well....sound...
read the post at rhod's site.....
it has been dreamed as posted by none other than this stumbling questor ......
and the high yields are in fact doable.....

i STRONGLY suggest that you hone yer org synth skills with some more simple quest prior to embarking on this adventure though......

it is infinitely more demanding than a rp/i bubble in the ice house........

but good luck and let us all know what YOU find in your adventures fellow questor.....

i hope ya have some open minded friends.....
the sexual potential is QUITE interesting!!!!


sponsan

  • Guest
Hello Mr Carter :) I have read your previous...
« Reply #8 on: July 24, 2003, 01:28:00 AM »
Hello Mr Carter :)

I have read your previous adventures documented in Rhodium's archives - well done!  The only part i was unsure about was your final reduction.  Is the high yeild you reported really possible with leuckart on tma-2 ketone?

Rhodium pointed me at the alternative reduction with NaBH4 + Al/Hg, with ~ 55% yield, which i am tending to lean towards as it seems very simple.  But, the oxime route claims ~80% yield for MDA, and if the asarone ketoxime reduces in such yield also, i am going to probably go via oxime route to get the extra 30%.

So far i've sucessfully completed mdma, mda and 2c-b synths, in decent yields.  The organic synth skills have taken a big make-over over the last few sessions and seem to be improving. :)

Will keep you all posted!

Take care,
Sponsan.

gruns

  • Guest
urushibara catalyst
« Reply #9 on: July 26, 2003, 10:11:00 AM »
In antibody2's urushibara catalyst reduction of tmp2np,
should the ethanol added be dry?  Does anybody have
any caveats for this reaction?


madprosr

  • Guest
nitropropene -> ketone
« Reply #10 on: August 19, 2003, 07:56:00 AM »
why not use Al/AcOH to form the ketone from the nitropropene?
Rhodium posted an equivalent writeup for mdp2p giving 75% yeild...

gruns

  • Guest
I like the idea of performing only two ...
« Reply #11 on: September 07, 2003, 08:50:00 AM »
I like the idea of performing only two reactions rather
than three, especially such relatively simple ones.