I've been trying to evaluate different reductive methylation methods to find the ones which would be the most OTC.  My particular interest is in N,N-methylation of tryptamine to DMT.

Most of the original syntheses use sodium cyanoborohydride as the reducing agent, but this isn't remotely OTC anymore to my knowledge.

http://www.erowid.org/archive/rhodium/chemistry/tryptamine2dmt.html


Other possible agents listed are sodium borohydride, dimethylamine borane, and pyridine borane.  None of these sounds too practical either.

http://books.google.com/books?id=TsO2949cDpQC&pg=PA29&lpg=PA29&dq=reductive+methylation&source=bl&ots=idttCAJ6Fg&sig=yLgst9quQZcJiJPloPx4iESnr6c&hl=en&ei=tnKHSuGmHcWntgeohtjnDA&sa=X&oi=book_result&ct=result&resnum=9#v=onepage&q=reductive%20methylation&f=false


Some article and patent review gives alternative methods using Pt or Raney nickel catalysts, which may be somewhat more practical.   Reduction of P2P and MDP2P using catalysts has been documented pretty well and could maybe be adapted for this process.

http://www.patentstorm.us/patents/5105013/description.html
http://pubs.acs.org/doi/abs/10.1021/ja01146a522


Apparently dissolving metal reductions may work as well.  Here I believe it is done with zinc..

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6THS-4PJCY7T-6&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=981409121&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=0498d9ca813dacfbafc6a139ffc510ec
(Unfortunately I don't have access to the full article.)


So would a mercury aluminum amalgam be strong enough to perform the reduction?  Are there some other methods I'm overlooking?

This particular area of chemistry is a bit outside of my familiarity zone, so I could be completely off-base.  Any suggestions or further references are extremely appreciated.

Yep it does. One thing I'd like to point out though that was mentioned in the decarboxylation thread that pertains to DMT is..

N,N-Dimethylation of the commonly available tryptophan with paraformaldehyde and oxalic acid, followed by the above treatment with cyclohexanol would afford pure DMT in high yields.

-- http://127.0.0.1/talk/index.php/topic,321.0.html

Thank you guys.  Vesp I read that line the first time I looked at that post but I guess my eyes glazed over or something so I spent half an hour researching something that was right in front of me.

And thanks for the link Naf1, it's exactly what I needed.


I hope the links I posted are able to help someone else out though.

I don't know, there is some big thread on this forum about just that. I think the threads name is melatonin to 5-MeO-DMT or something.

^ You'll probably get cyclization.

that's true there atara you can do all kinds of n-alkylations backwards and forwards with n,n,n, n tetra alkyl ammonium halides .

Yep it does. One thing I'd like to point out though that was mentioned in the decarboxylation thread that pertains to DMT is..

Quote

N,N-Dimethylation of the commonly available tryptophan with paraformaldehyde and oxalic acid, followed by the above treatment with cyclohexanol would afford pure DMT in high yields.

-- http://127.0.0.1/talk/index.php/topic,321.0.html

Very interesting.

I'm going to try this soon, as soon as I can source a few reagents. Does anybody else have any relevant experience or writeups?

baldwin's rules of cyclization read all about, it in short no you can't reduce aldimes of tryptamines.

http://en.wikipedia.org/wiki/Baldwin's_rules

no shit? so what does the acid do does it protonate the ring?

so the nabh4 method would work then.