The simplest Methamphetamine synthesis from Amphetamine

[redsm]

@G.Patton I believe one of the drawn intermediates on this synthesis (and from the original rhodium article) is incorrect.

(3), the representation of the amphetamine-formaldehyde imine intermediate possesses the same structure as the phenylacetone-methylamine imine that can be seen elsewhere

this does not seem correct to me for two reasons: first, drawing the standard mechanism for imine formation on the substrate produces an imine wherein the double bond is between N and the would-be methyl group on the methamphetamine, and NOT between N and the alpha-carbon as in the listed structure. and think about it: the double bond is generated when the lone pair of the amine kicks off the water formed on the formaldehyde oxygen as a leaving group, which must be done on the side of the formaldehyde (the would-be methyl group)

second, the synthesis is reported as stereospecific based on the starting substrate. that is, the reduction of d-amph will yield d-meth and the same for the l-isomer. structure as is shown (3) possesses no chiral centers, and its reduction is equivalent to the standard reductive amination of phenylacetone which yields a racemic product. the proposed structure I've given for the intermediate possesses a chiral center, which would be the same as the starting material's and therefore match the observed stereospecificity of the reaction.

if i am correct, this would clear up the issues regarding the stereospecificity of the reaction earlier in the thread. if i have made a mistake somewhere, i apologize, but i was curious as to why the reduction of the non-chiral (3) leads to a non-racemic mixture of products when a non-racemic amphetamine starting material is used.

 

[G.Patton]

Hi. Firstly, a-carbon has more electron density than methyl carbon. Typical mechanism lead to such intermediate (hidden under Breaking Bad watermark, sry):

Secondly, do you have any reliable data about stereo-specific result of this synthesis?

 

[NexusPrime]

rhodium is a mistake, the double bond is not there, see the example with benzaldehyde below

 

[NexusPrime]

rhodium is a mistake, the double bond is not there, see the example with benzaldehyde below

 

[ruen]

Hello chemists, cooks, law enforcement officers, and all other people with interest in clandestine drug synthesis,
Did anyone successfully manage to finish this monomethylation and could share his/her tips and yields?
I have tried on several occasions, but never sucessfully. Last time i tried, i took crude amphetamine freebase from synthesis, aded a huuge excess of paraformaldehyde aq solution and molar amount nabh4, then ive put it on stirring for several hours. Monomethylation via nabh4 is not described among the several ways on Erowid, but after studying monomethylations in scientific literature i figured out it should work and ill just yolo try it. The result was a fail of course, i did not manage to monomethylate the amphetamine into methamphetamine
After acidification i was left with a mix of white crystaline solids, mostly not soluble in isopropylalcohol. I assume this was either the excess paraformaldehyde, unreacted amphetamine or an intermidiate (tlc was not performed so i cannot confirm). Nevertheless, a small amout was soluble in alcohol, and after recrystalization and putting it into my friends crack pipe (lol im not ruining my own) BEHOLD! Its her! The queen of all stimulants!
The conclusion to my experiment is following:
1/ 10g crude amph freebase and other chemicals lost
2/ approximately one hit of racemic meth from the pipe
Does anybody have tips for my next trial or comments to my precious?
My ideas are: Excess nabh4? Less paraformaldehyde? Heat? More time? Purify crude amph freebase first? Or maybe it went well but the yields are shit? Also, id like to try one of the methods exactly as described on Erowid.

Looking forward to your insights!

 

[gnbarsh3463_11]

Why did you use paraformaldehyde? IMO it was hydrolysed and immidiately reduced by NaBH4. Or NaBH4 was hydrolysed in aqueous solution before it had chance to reduce anything other than hydrogen.
Try forming imine from formaldehyde solution (not paraformaldehyde) and amph. freebase in alcoholic solution beforehand, at least for few hours, only then reducing it? Or try using triacetoxyborohydride formed in situ to reduce imine? Find some preparative methods online where Na(AcO)3BH is used to selectivellyy reduce imines to better understand what to do.
Does amph and formaldehyde form any polymers similar to "phenol-formaldehyde resins"? If not then this reaction should be quite easy - I think.

 

[G.Patton]

NaBH4 reacts with water, I assume that it's the reason of your fail. Try with Al/Hg.

 

[amphmnamii]

Ohh I was thinking about that, and after I have thinked nahh this is bullshit but you posted here exact recipe describe! Wow
Respect belongs to you!
And respect also for other stuff you already posted here