Author Topic: Sensible routes to stimulants.  (Read 595 times)

Naf1

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Sensible routes to stimulants.
« on: March 02, 2010, 02:13:11 AM »
Route 1 [Nitroethane Bypass];

Benzaldehyde or substituted benzaldehyde with nitromethane in a Henry reaction producing beta-nitrostyrene[1]. b-Nitrostyrene can be selectively reduced with NaBH4 to 2-nitroethylbenzene[1], which upon treatment with DMSO, Sodium Nitrite and Acetic Acid affords phenylacetic acid[3]. Dry distillation with Lead (II)Acetate to give P2P[4], metyhylamine to the aldimine....


Route 2 [OTC Method];

There was a method that was being experimented with at WD, I dont know what happened to it but I remember Java had a PDF of some WD posts regarding oxidizing phenylalanine with TCA and base to produce the nitrile. I dont know if they knew how close they actually were? But it is definitely worth revisiting this if anyone is looking for experiments to do.[5]
Phenylalanine can be oxidized with trichloroisocyanuric acid and base to produce benzyl cyanide in 98% yield[6], which can be be treated with ethyl acetate and lithium ethoxide to produce P2P[7]. Ethyl acetate can be made from ethanol and acetic acid via Fischer esterification, lithium ethoxide is produced by opening a lithium battery and dissolving the lithium out of it in ethanol. Decarboxylation of phenylalanine produces phenethylamine, which can be oxidized with easily prepared nickel peroxide and potassium persulfate to the nitrile (Benzyl Cyanide)[8].

notes: Cyanide will be produced in the reaction above, but P2P is completely insoluble in water so should be thoroughly washed with water many times after being prepared. You really dont want any residual cyanide hanging about obviously, so make sure to really wash it well after preparing, then it would be very sensible to test the P2P with any of the methods contained here, with preference for the simple prussian blue test;
http://en.wikipedia.org/wiki/Cyanide#Chemical_tests_for_cyanide

[1]http://www.erowid.org/archive/rhodium/chemistry/345-meo-ns.html
[3]http://www.filefactory.com/file/b4a1b2e/n/000539103-nitropropene_nitrite.pdf

[4]http://www.lycaeum.org/rhodium/chemistry/p2p.paa-pb.html
[5]http://www.sciencemadness.org/talk/files.php?pid=110598&aid=4207
[6]http://www.sciencemadness.org/talk/files.php?pid=69963&aid=1539
[7]http://www.lycaeum.org/rhodium/chemistry/phenylacetone.html#benzylcyanide
[8]http://www.journalarchive.jst.go.jp/english/jnlabstract_en.php?cdjournal=bcsj1926&cdvol=63&noissue=1&startpage=301

Run number                   Substrate                             NiSO4 mol%             Reaction time                          Product                                    Yield            
« Last Edit: March 02, 2010, 03:33:38 AM by Naf1 »

Wizard X

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Re: Sensible routes to stimulants.
« Reply #1 on: March 02, 2010, 11:13:58 AM »
Route 1 [Nitroethane Bypass];

Benzaldehyde or substituted benzaldehyde with nitromethane in a Henry reaction producing beta-nitrostyrene[1]. b-Nitrostyrene can be selectively reduced with NaBH4 to 2-nitroethylbenzene[1], which upon treatment with DMSO, Sodium Nitrite and Acetic Acid affords phenylacetic acid[3]. Dry distillation with Lead (II)Acetate to give P2P[4], metyhylamine to the aldimine....

I wouldn't waste the Benzaldehyde.
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SOMA

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Re: Sensible routes to stimulants.
« Reply #2 on: March 02, 2010, 08:18:08 PM »
You can make shitloads of PAA with styrene monomer so, why bother? The Phenylalanine is the only one interesting, for small schale without too stinky chems.

Naf1

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Re: Sensible routes to stimulants.
« Reply #3 on: March 02, 2010, 09:29:24 PM »
@SOMA, are you talking about the Willgerodt reaction? To produce PAA from styrene?

Anyway, I thought I would document those techniques as they dont appear anywhere else.

no1uno

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Re: Sensible routes to stimulants.
« Reply #4 on: March 02, 2010, 10:21:30 PM »
There is always the a-bromopropiophenone route, often overlooked, but relatively easily acquired chemicals (Benzoic acid, (about the easiest thing in the world to make from Toluene, just try making BnO ;D), propionic acid (look around, you'll find it, if not the haloform rxn on MEK will give it), iron salts, bromine, dichloromethane, NMP (Paint stripper - got to work out an easier way to get it out) or ethanol and methylamine).

That'll give methcathinone, reducing that is up to the individual (hypothetically speaking). The picture below is the yield of propiophenone from benzoic acid and propionic acids with iron salts....

The best yields I've yet seen on the bromination are in the last paper (the one pot), using Br2/DCM with the propiophenone, carefully removing the excess DCM & Bromine by distillation and then adding the bromoketone to the NMP solution of the amine... I suspect it would work way better if we could get NMP purified, but ethanol will work (just not that well). As to whether or not NMP would be a useful solvent for the N-Methylaminoketone - check out this from the Wellbutrin synthesis (the step-by-step 1 pot, student note 2)

Note 2. The displacement of a bromine atom by an amine is usually an SN2 process. Why would you expect that the reaction you are carrying out, using t-BuNH2, might be much slower than the same reaction using methyl amine?

It really couldn't be much more blatant a hint could it?
« Last Edit: March 02, 2010, 10:27:42 PM by no1uno »
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Enkidu

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Re: Sensible routes to stimulants.
« Reply #5 on: March 03, 2010, 07:23:33 AM »
^ Those aryl ketone synthesis papers are interesting. Do you think the reaction would work with alpha-bromo carboxylates?
« Last Edit: March 03, 2010, 07:39:45 AM by Enkidu »

Goldmember

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Re: Sensible routes to stimulants.
« Reply #6 on: March 03, 2010, 07:28:35 AM »
"The Phenylalanine is the only one interesting, for small schale without too stinky chems."

Imho The phenylalanine/Tcca thing stinks as bad as any PAA route.Not that that is of any major imprortance.

Vesp

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Re: Sensible routes to stimulants.
« Reply #7 on: March 03, 2010, 09:30:35 PM »
Route 1 [Nitroethane Bypass];

Benzaldehyde or substituted benzaldehyde with nitromethane in a Henry reaction producing beta-nitrostyrene[1]. b-Nitrostyrene can be selectively reduced with NaBH4 to 2-nitroethylbenzene[1], which upon treatment with DMSO, Sodium Nitrite and Acetic Acid affords phenylacetic acid[3]. Dry distillation with Lead (II)Acetate to give P2P[4], metyhylamine to the aldimine....

I wouldn't waste the Benzaldehyde.

Would you like to elaborate on why? A simple comment like that doesn't do anyone any good. Are you saying this wouldn't work? If not, why not?
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Naf1

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Re: Sensible routes to stimulants.
« Reply #8 on: March 03, 2010, 10:10:07 PM »
Also there where little things that were meant to be added to that synth, like decarboxylating phenylalanine with any of the known methods (easy) then treating the phenethylamine produced with nitrous acid (sodium nitrite + HCl) as stated previously produces 2-phenylethanol which can be reacted as in the Disposable Stirbar thread with bleach and nickel chloride to produce phenylacetic acid or that 2-phenylethanol upon treatment with a hydrogen halide (preferentially HBr) produces (2-bromoethyl)benzene which can then be analogously treated with sodium nitrite, DMSO and acetic acid to also produce phenylacetic acid in 85% yield.

NiCL2 NaOCl oxidation of primary alcohol
http://127.0.0.1/talk/index.php/topic,822.0.html

As to it working you would just check the link that I originally put up;

Synthesis of 3,4,5-Trimethoxy-beta-nitrostyrene and 3,4,5-Trimethoxyphenyl-2-nitroethane
Text & Photos by Vaaugh, HTML by Rhodium
http://www.erowid.org/archive/rhodium/chemistry/345-meo-ns.html

As you can see from that pictorial above it is not a great yielding procedure, but it is a straightforward synth does not require an inert atmosphere and proceeds in a standard way. If you can get the sodium borohydride it is very feasible. Decarboxylation then diazotization with nitrous acid on phenylalanine is also a good cheap OTC way to produce 2-phenylethanol which can be oxidized to phenylacetic acid or the bromo compound that can be treated the same as (2-nitroethyl)benzene can be prepared.

I would still be very interested in WizardX's response as to why this is not good enough (or what is).
« Last Edit: March 03, 2010, 10:12:47 PM by Naf1 »

Enkidu

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Re: Sensible routes to stimulants.
« Reply #9 on: March 04, 2010, 12:15:08 AM »
I wouldn't waste the Benzaldehyde.

Would you like to elaborate on why? A simple comment like that doesn't do anyone any good. Are you saying this wouldn't work? If not, why not?

He's just saying that there are better routes, if you're just looking for phenylacetic acid... no need to waste the benzaldehyde.

lugh

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Re: Sensible routes to stimulants.
« Reply #10 on: March 04, 2010, 04:09:51 AM »
The Darzens condensation is a better way from benzaldehyde  8)
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shroomedalice

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Re: Sensible routes to stimulants.
« Reply #11 on: March 04, 2010, 05:50:51 AM »
yes a darzen is on the books for my old friend but still I must say nothing beats the smell of the aldol :).

Wizard X

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Re: Sensible routes to stimulants.
« Reply #12 on: March 04, 2010, 10:25:46 AM »
Route 1 [Nitroethane Bypass];

Benzaldehyde or substituted benzaldehyde with nitromethane in a Henry reaction producing beta-nitrostyrene[1]. b-Nitrostyrene can be selectively reduced with NaBH4 to 2-nitroethylbenzene[1], which upon treatment with DMSO, Sodium Nitrite and Acetic Acid affords phenylacetic acid[3]. Dry distillation with Lead (II)Acetate to give P2P[4], metyhylamine to the aldimine....

I wouldn't waste the Benzaldehyde.


Quote
Would you like to elaborate on why? A simple comment like that doesn't do anyone any good. Are you saying this wouldn't work? If not, why not?

2-nitroethanol, HOCH2CH2NO2 (taut: HO-NO=CH-CH2OH)

2-Nitroethanol is particularly valuable as a synthetic intermediate for the preparation of nitroethylene. Nitroethylene is conveniently prepared by heating 2-nitroethanol with phthalic anhydride and allowing the nitroethylene to distil under reduced pressure.

2-nitroethanol => nitroethylene => nitroethane

Synonyms for nitroethylene: nitroethene.


I would synthesize 2-nitroethanol HOCH2CH2NO2 from nitromethane using http://www.orgsyn.org/orgsyn/pdfs/CV5P0833.pdf

Then condense benzaldehyde with 2-nitroethanol using part B. http://www.orgsyn.org/orgsyn/pdfs/V78P0014.pdf
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no1uno

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Re: Sensible routes to stimulants.
« Reply #13 on: March 04, 2010, 10:39:03 AM »
^ Those aryl ketone synthesis papers are interesting. Do you think the reaction would work with alpha-bromo carboxylates?

???

Noone even going to try and work out how to purify NMP from the OTC (as all fuck - it is the new-age replacement for THF/GBL/DCM), low-odour (dead giveaway) paint remover/strippers?

Whatever the fuck they gel it with is a biatch to get out, especially given the solubility of this shit in water - how to get it out (BP is over 200' so distillation would be slooooooowwwww and it certainly ain't gonna dry it, plus heating jelled solvents over 200'C is terribly hard on glassware - wait till it comes time to get the shit out the flask & you'll see what I mean).

It would appear to be a must-have for fast alkylation of monoalkylamines, it is OTC and ALL I WANT is a nice, quiet, low-tech route to get the bitch out :'(

Anyone think salting it out would work? It's gonna need a shitload of something hella soluble, it is miscible with water...
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SOMA

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Re: Sensible routes to stimulants.
« Reply #14 on: March 04, 2010, 12:14:17 PM »
@ Naf1 check the work of Manimal at WetDreams, look for PAA from Styrene at the org chem forum. Of course your proposals are always interesting ;)

"The Phenylalanine is the only one interesting, for small schale without too stinky chems."

Imho The phenylalanine/Tcca thing stinks as bad as any PAA route.Not that that is of any major imprortance.

Ok it is too stinky, but I was comparing the method with the Willgerodt, in withch not only you work with PAA, but Phenylacetamide (that's the impurity that makes PAA stink like cat piss) a sultions of sulfides witch generate small ammounts of H2S, yes the thing that makes farts smell like they smell :)

no1uno

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Re: Sensible routes to stimulants.
« Reply #15 on: March 27, 2010, 06:07:38 AM »
Phenylacetonitrile is stinky enough, the phenylacetamide that is the intermediate in the hydrolysis of it to phenylacetic acid, stinks just as bad as phenylacetamide made any other way...
"...     "A little learning is a dang'rous thing;
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McTeeth

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Re: Sensible routes to stimulants.
« Reply #16 on: August 08, 2010, 02:40:18 PM »
Would the 'substituted benzaldehydes' mentioned in route 1 include the methylenedioxy variety? I have read as much as I've found but I've come across little in the way of nitroethane bypasses for that synthesis which could result in the p2p.

Naf1

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Re: Sensible routes to stimulants.
« Reply #17 on: August 09, 2010, 12:50:57 AM »
It was not intended too, the method to the phenylacetic acid would work for piperonal.

I also looked and I gave a reference for reduction of nitrostyrenes to alkylamines which is a general procedure. If you want to selectively reduce to the nitroalkane with NaBH4 you need this reference;

Selective Reduction of Nitroalkenes with Methanolic Sodium Borohydride: A Facile Route To Nitroalkanes
Rajender S. Varma and George W. Kabalka
Synthetic Communications, 15(2), 151-155 (1985)

http://www.erowid.org/archive/rhodium/chemistry/nitroalkene2nitroalkane.v-k.nabh4.html

Vanadium

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Re: Sensible routes to stimulants.
« Reply #18 on: August 09, 2010, 03:41:29 AM »
^This reduction can also be performed by yeast for the borohydride-poor among us.

Naf1

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Re: Sensible routes to stimulants.
« Reply #19 on: August 09, 2010, 05:29:40 AM »
^^Good point!^^^

Actually excellent point, even if you are NaBH4 rich. You would be better saving it for a more worthy cause, I do remember ziggy was working with the yeast reductions. The only drawback IIRC was making a huge mess, and having to work up said huge mess at the end. Would be great to get some experimental details on that reduction.