From: aankrom@nyx.cs.du.edu (Anthony Ankrom)
Subject: Mescaline from toluene
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Date: Thu, 7 Jan 93 17:26:27 GMT


  A while ago someone posted offhandedly remarked about someone that he
knew knew how to make mescaline from toluene. I must say that I scoffed
along with everyone else at first, but I thought about it for a bit and
decided that it could actually be done, althoguht through several stepd
and not very efficiently. But this line of thought led me to realise that
other analogues of mescaline can be had from toluene with slightly better
effiency. Keep in mind that these ideas or just thought games for me and I
doubt that I, myself could actually repaet the procedure in a lab, but a
will present here a rough idea:

 It should be well known to most chemists that aromatic nuclei can be
nitrated and the nitro group(s) be reduced, followed by conversion into
hydroxyl groups. (I won't go into synthetic detail. I thought about
cross-posting to sci.chem, but there are enough chemists here, I think.
Further, I doubt such a discussion would be welcome in sci.chem...) 
 Getting all of the nitro groups into a 3,4,5 configuration is no simple
task, however and probably can't be done. I would first nitrate the
toluene to para-nitro toluene. Then I would brominate this to
3-bromo-4-nitro-toluene. The bromine converted to hydroxyl via lithiation,
etc. (References I can dig up for the doubtful...) There are of course
several methods for going about this given the simple structure of toluene
in relation to mescaline, but I'll just proceed with what comes to mind. 
Personally, I would have started from catechol, a just as easilly
obtainable precursor with much more potential. What with Vilsmeier-Haack
formylations, the lack of the beginning of an alkyl side-chain is really
trivial, but I digress...
 At this point, I am stuck at choosing between several methods, most of
which I'm not sure would work. I could go ahead and reduce the nitro group
followed by conversion of the amino into hydroxyl, then I could attempt to
oxidise it to an orthoquinoid compound, perhaps even oxidising the methyl
group to carboxyl, which I'll be needing to do anyway. Choosing the
oxidising agent here is the tough part.Electroodxidation would be
specific, but persulfate would be simpler. I think before I reduce the
nitro I should go ahead and methylate the one hydroxl with MeI or Me2SO4,
perhaps making the oxidation to the orthoquinoid simpler. At this point, I
want to give up because there are much simpler ways to make mescaline.
Hell it can be made easilly enough from gallic acid. But I would _love_ to
see a reference describing the whole process from toluene! If one exists
that is. 
 However. TMA-6, (2,4,6-trimethoxyphenylisopropylamine), a creation of
Alexander Shulgin's, can be made from toluene via nitration to TNT,
followed by oxidation of the methyl to carboxyl, followed by
decarboxylation (a reaction specific to trinitro benzoic acid)
reduction to triaminobenzene, follwed by conversion to phloroglucinol,
methylated by MeI or Me2SO4, formylated via Vilsmeier-Haack, condensed
with nitroethane (Knoevanagel-Walter) to the nitropropene, followed by
redutction with LiAlH4. 
 TMA-6 is equipotent to TMA-2 (2,4,5-trimethoxyphenylisopropylamine.
Having a potency about 10 times that of mescaline.

St. Anthony


r

--
          / N \   O                   Mi vsi smo krizhani,
         |   \ |  || Ph               chlani izbrani
         |   | |_O-C-C-OH             mesarskega ceha...
BZ        \ / /      Ph                            aankrom@nyx.cs.du.edu
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