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         Synthesis of DMT and other dialkyltryptamines via Tryptophol
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Octahedrical
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Side Step 1:

Reflux dimethylformamide (DMF) in 6M HCl for at least 6 hours-->
dimethylamine + CO2H and other stuff. Use an acid-base extraction to isolate the
amine product.

Main Step 1:

Indole acetic acid (IAA) + B2H6 (diborane) in THF (tetrahydrofuran) or diglyme
at room temperature--> 3-(2-hydroxyethyl)-indole.

Main Step 2:

3-(2-hydroxyethyl)-indole + PBr3 (phosphorus tribromide)--> 3-(2-bromoethyl)-indole.
Add water. Use a sep funnel and discard the water layer.

Final Step:

3-(2-bromoethyl)-indole + dimethylamine--> dimethyltryptamine (DMT)


Yields will be better than anything else out there. Main Step 1 happens very
quickly at room temperature. Step 2 I've heard is really a breeze (again no
reflux required I don't think). Step three takes a couple of days, but it is at
room temp I think. I'll read up on this some more. No one has ever done this, to
my knowlegde. (Unless they want to come forward.)

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Teonanacatl
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Synthesis of tryptophols (indole-3-ethanols):

a) Sodium-Alcohol reduction: first chem. synth of tryptophol by Bouveault-Blanc
reduction (Na/EtOH) of methyl or ethyl esters of IAA...yields up to 81%
reported...46% yield from another source [could you react IAA w/
methanol/ethanol (excess, distilling of H2O) to produce the methyl or ethyl
ester and then use a Bouveault-Blanc procedure?... even easier to get hold of
reagents!...if you've got the proper supplies, you could even do a reductive
halogenation with LAH, followed by HBr, ie. IAA-->3-(2-bromoethyl)indole]

b) LAH reduction: first reported 65% yield of tryptophol from IAA...methyl and
ethyl esters of IAA giving over 90% yields...for large scale procedures, it has
been reported that the glyoxyl chloride of indole can be converted to the
glyoxylic acid ester and then reduced w/ LAH to tryptophol...over 85% yield
claimed.

This definately seems a possibility...same ref goes on to say:

Reactions of tryptophols:..."usually used as intermediates for one of the
earliest yet most convenient tryptamine syntheses: phosphorous tribromide in
ether or benzene converts tryptophols into 3-(2-bromoethyl)indoles in good yield
and subsequent reaction with ammonia or amines makes available a wide array of
tryptamines."

The only flaw I see with your procedure is the diborane bit...I've never seen
this used for reduction of carboxylic acids or esters...

ref: "Hydroxyindoles, Indole Alcohols, and Indolethiols" Spande, Thomas F. in:
The Chemistry of Heterocyclic Compounds: A Series of Monographs Vol. 25, Part
III: Indoles, Part III, 1979.

Just found another ref:

"N-disubstituted tryptamines are obtained in high yield on boiling a solution of
tryptophols in benzene or xylene with secondary amines and a nickel catalyst."

V.I. Shvedov, L.B. Altukhova, L.A. Chernyshkova, and A.N. Grinev, J. Org. Chem.
USSR, 5, 2158 (1969).

Anyone want to look this one up?

P.S. Do you think 4-chloro-IAA would survive this same rxn?.. it's another
reasonably common plant hormone... 4-Cl-DMT?

-Teo

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Know Conscience
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Main Step One:

Diborane is a newer (than LAH), more selective reducing agent specific for
carboxylic acids. It reduces them to primary alcohols quickly and in high yield
at room temperature in an ether solvent such as diglyme or tetrahydrofuran.

LAH will also get the job done, but it is notoriously difficult to work with and
apparently only gives a 65% yield in this instance.

Main Step 2:

Once you've got the 3-(2-hydroxyethyl)-indole made, PBr3 is a better way to
brominate it than HBr. This is because HBr is a stronger acid than PBr3 and will
therefore tend to favor an unwanted dehyration side reaction on this primary
alcohol.

That is,

3-(2-hydroxyethyl)-indole + HBr--> 3-(2-bromoethyl)-indole + 3-styrene-indole.

Also, every one PBr3 molecule has the potential to brominate three
3-(2-hydroxyethyl)-indole molecules to form three 3-(2-bromoethyl)-indole
molecules plus one H3P04 (phosphorus acid) molecule. So if you have X moles of
3-(2-hydroxyethyl)-indole, you will only need to use X/3 moles PBr3.

Phosphorus acid is water soluble and has a high boiling point, so it can
therefore be separated from the brominated indole product by means of an
oil-water separation or by simple distillation.

* * *

The 1969 USSR reference you mention sounds very promising as well, especially
since it would negate the necessity of having a third step in the first place.

4-Cl-IAA can also be used. Since the chlorine of 4-Cl-IAA is attached to an
aromatic portion of the molecule, it is much harder to remove than the bromine
of 3-(2-bromoethyl)-indole--especially if you use the very mild B2H6 followed by
PBr3 followed by dimethylamine (an Sn1 reaction).

In this case you will get, 4-chloro-DMT. 4-Cl-DMT looks pretty damn psychoactive
to me, and could also be converted to psilocin or even 4-methoxy-psilocin!

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Rhodium:
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This is the article from J Org Chem USSR, 5, 2158 (1969) mentioned above

General procedure for the preparation of dialkyltryptamines:

Into a flask fitted with a Dean-Stark recieving trap were placed 0.1 moles of 
tryptophol [2-(3-indolyl)-ethanol], 0.1 moles of a secondary amine [dimethylamine 
for DMT], 4ml of skeletal nickel suspension in water and 100ml of benzene or 
xylene [I assume toluene is good too]. The reaction mixture was refluxed, and 
the condensed water collected for four hours, the hot solution filtered and the 
catalyst washed repeatedly with benzene or xylene [or toluene] and the mother-
liquor concentrated under vacuum. The product was either distilled in vacuo or 
isolated as the hydrochloride by acidifying with an equivalent of hydrogen 
chloride solution [they are probably referring to a non-aqueous HCl solution here]. 
The yields were in the 82-98% range. 

Preparation of skeletal nickle: http://water-cooler.com/WC/patentviewer/patent-4086264.html
Perhaps one could use Raney Ni or just powdered/precipitated nickle?

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Lilienthal:

J. Am. Chem. Soc. 61,3499 1939 gives the mechanism: the alcohol is catalytically 
dehydrogenated to the aldehyde, which reacts with the amine to an imine, which 
is subsequently hydrogenated to the amine. Usually this gives moderate yields 
and needs high temperatures (very uncool for the low-boiling dimethylamine...).

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