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				DMT from indoleacetic acid (IAA)
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Everybody who ever tried knows that synthesizing tryptamines is a real pain and
needs lots of know-how and experience. Especially dmt itself is notorious for
being very tough to obtain in pure form. The classical oxalylchloride route is
only for tough guys, imho, and the final reduction step needs to be so drastic
that the final product is extremely hard to purify. Blessed are those who have a
neat sublimation apparatus at hand, all others are pretty much lost.

That's why I looked into alternative methods, and re-found the old route by Fish
(JACS in the 50's, sorry, I haven't my notes here) starting from indoleacetic
acid (IAA). According to my still unconfirmed information IAA is used in
agriculture/horticulture as a plant grow hormone, which would make it an
affordable and obtainable precursor.

[Note: The actual reagent is IAA methyl ester, not the free acid]

In the first step the acid is converted to the amine, Fish uses glycol as a
solvent for the direct transformation. In my own trials, this works also very
well in the usual 40% aqueous solution of dimethylamine, using 0.5-1% conc.
H2SO4 as a catalyst. The reaction takes place at room temperature, but is slow,
allow 48h for completion. It is easily monitored by TLC, using ethylacetate with
a hint of MeOH or something polar like this. After completion an acid base
extraction is necessary the remove the catalyst, and the crude product is
evaporated to give a reddish thick oil. This can be recrystallized from ethyl
acetate, but though Fish states very good yields, I could never obtain more than
50% from this crystallization. The strange but true thing is, that the amide
breaks down while crystallizing! This is evident by TLC, two spots appears, one
above and one below the amide, none of them is the starting material (IAA). When
too much junk is in the solution, no crystallization occurs anymore. This is
strange, cause the raw-product of the substitution is quite pure. But not pure
enough to reduce it directly in the next step, recrystallization is essential.

Other strange things: IAA has been totally inert towards dipropylamine under
otherwise identical conditions. The junky mother liquor can be chromatographed
to obtain pure amide, again. Trying to crystallize this stuff again leads to the
same 50% yield in solid material.

The reduction of this amide is performed with LiAlH4, or better with NaAlH4.
I know the sodium stuff is much less common, and available usually only in tech
(90% pure) grade, but the workup is much easier, as it aggregates much better
during workup. As with ALL hydride reductions, an overhead mechanical stirrer is
very much preferred over a magnetic stirrer. It just works better. (And yes, it
gently to dramatically increases the yield in nitrostyrene reductions, too).
The organic solution can easily be decanted. Reduction is performed in THF
during 4 or so hours see Fish again, though he used ether. Use no more than
1.5 ml water per g hydride to hydrolize the cooled solution. The decanted or
filtered solution is remarkable colorless (but only if you listened earlier and
used only crystalline amide in the reduction step.) It is important that the
next steps are performed fast. Not in a hurry, not with haste, but fast. If you
used THF add enough ether to get a good separation of phases, and do an acid
base extraction, so that you end up with the base (trpytamine) in ether solution.
During the extraction the solution will turn more and more reddish, and it's sad
to watch this happen.  When you find a method to avoid this please let me know.
After evaporation the crude tryptamine is dissolved in boiling hexane. (I heard
cyclo-hexane would be better, but I haven't tried)

This is very difficult, and after a while you may add ethylacetate dropwise to
get all in solution, but not too much. I don't remember the correct amounts,
must be around 30ml hexane per gram of tryptamine. Keep it boiling! On cooling
down, usually an oil will separate. This is ok, as this oil is deeply colored,
leaving a much less colored solution. After a while decant from the oil, which
either collects at the bottom or sticks to the walls in to a clean flask. This
flask is cold, so a lot more oils out, reheat to reflux until all is in
solution, and clean the first flask while the second cools down. Decant from
oils again. Repeat as often as you feel it is needed. One can end up with a
perfectly clear solution this way, and be careful with the ethylacetate. Not too
much. If the solution is clean enough, seed it with a crystal and set it in the
freezer. Without a seed the task is kind of hopeless, sorry. If you really don't
have one, dissolve the oil you decanted from earlier and let it evaporate in a
petri dish or so. This can yield a semisolid material which may be good enough
for seeding, but doesn't match my demands on the final product. If the seed
dissolves the solution you made is way to dilute, evaporate a bit and try again.
With this method dmt crystalls that are only slightly yellowish can be obtained.
The real clear stuff is only obtainable by sublimation.

What I offer is no breakthrough, but obviously I spend some time in the
purification process. Although I read about it a lot in the literature, in MY
hands the material does not survive a column chromatography. In my experience
it's really important to work quick and to know what you are doing, fooling
around with tryptamines is not a good idea, they are unforgiving. Trying to
purify a dirty product makes things only worse, and that's why it is important
to start with a pretty pure product to begin with.  The gentler conditions of
reducing a simple amide instead of a glyoxylamide provides a much cleaner crude
product. 

Perhaps most importantly, IAA is probably available to those that are willing to
spend some effort, and the first step is as easy as it gets in organic
chemistry. TLC is essential during the whole process to know how things are
going. If you don't know exactly what I was describing in the procedure above,
don't even think about trying to reproduce it.

- - - - -

Drone:

Fish in his article described reaction between IAA methyl ester and soln of 
anhydrous dimethylamine in ethylene glycol. Interested? routine follows...

JACS 78, 3670 (1956)

N,N-dimethylindole-acetamide 

A mixture of 16.0 g of methyl-3-indoleacetate, 100 ml of ethylene glycol and 19.4 
of anhydrous dimethylamine was stirred at RT for 40 hrs. The mixture was poured 
into 100 ml of water and extracted with 5 100ml-portions of ethylacetate:ether 
(1:1). The extract was washed with a little water, dried and evaporated to give 
a red oil. This was taken up in warm EtOAc and on chilling, three crops of 
colorless cryst weighting a total of 12.5 g (70%) were obtained, mp 126-128°C.

N,N-Dimethyltryptamine (DMT) 

A suspension of finally-divided amide (2.1 g) in 100 ml of ether was added to a 
slurry of 0.8 g of LiAlH4 in 50 ml of ether, and the mixt refluxed for 4 hrs. 
The mixt. was treated in the usual way, and the final org. extract of amine gave 
after recryst. from hexane 1.6 g (85%) of material mp 47-49°C.

Take a note, only recrystalized amide acceptable for reduction step; reaction 
with crude amide gives a complex not-active mixture.

And IAA (twice recryst from hot water, white plates with mp 168°C) has a very 
slight smell, resembling strongly diluted phenylacetic acid. The amide has no 
smell at all.

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DMT from Indole-3-acetic acid

Take indole acetic acid (1 equivalent) and disslove it in dichloromethane. Add 
1.5 eq. of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimde and a tiny bit of 
dimethylaminopyridine (color change). Let this stir briefly. Prepare a seperate 
solution of dimethylamine HCL (2 eq) and Et3N (2.5 eq) in DCM... dont worry 
about the salt that crashes out. Mix the solutions and stir overnight (or until 
starting acid gone by TLC). Remove DCM, add EtOAc. Wash with 1N, sat NaHCO3, sat 
NaCl and dry over MgSO4.  Remove solvent and dry, rextal if you want. Reduce 
with LAH in THF at reflux overnight... work-up in the standard way- with an acid 
base extration. Rextal product from boiling hexane and a tiny bit of EtOAc (let 
it set in freezer a few days).

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