Easy Route to DMT ?

[zed]

Bees, please enlighten me! Has no one been successful, at synthesising DMT, Via the Indoleacetaldehyde? I can find no information on this. Indoleacetaldehyde is rather easily obtained by the oxidation of tryptophane by NaOCl.

Theoretically, this aldehyde can be reductively aminated with H2/Pt and Dimethylamine, or Diethylamine, to produce respectively, either DMT or DET. Has this been done? Has this been found impossible?

I have seen a number of proceedures for producing tryptamine and then alkylating it. Thus far, none of these, has me shouting for joy, and doing cartwheels.

If this is obvious, please excuse me. The search engine and I haven't developed a good working relationship yet.

So how about it? Does anyone know if the route, Indoleactaldehyde to DMT works?

[terbium]

Indoleacetaldehyde is rather easily obtained by the oxidation of tryptophane by NaOCl.
Got any references for this?

[foxy2]

https://www.thevespiary.org/rhodium/Rhodium/chemistry/indoleacetaldehyde.html

Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[PolytheneSam]

I found this in

The Chemistry of Heterocyclic Compounds 25th volume
Indoles part 2
W.J. Houlihan (editor)
John Wiley & Sons

and you probably would have found it too if you went to the library like I told all of you to do.  

https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_docs/000299426-file_t3pi.jpg" title="View this image">

References given are:

102 J.W. Daly & B. Witkop, J. Org. Chem. 27, 4104 (1962)
602 H. Wieland & Th. Wieland Justus Liebig's Ann. Chem. 528, 324
348a F. Marki, et al J. Amer. Chem. Soc. 83, 3341 (1961)
432a B. Robinson, et al. Proc. Chem. Soc. 1961, 310

http://www.geocities.com/dritte123/PSPF.html
The hardest thing to explain is the obvious

[Rhodium]

Tricyclic? As in that it inevitably forms the pictet-spengler product?

[zed]

So, now the question is: "Have any of you Bees, produced DMT from Indoleacetaldehyde and Dimethylamine, via ANY type of reduction, LAlH4, NaBH4, Al/Hg, Etc.?

Does this reaction work well enough to be used?

It would be especially sweet if Al/Hg works. You all know why.

Thank you again Sam, you really are the master.

So, does anyone have more insight? Please Post!

[terbium]

Does this reaction work well enough to be used?

Well, I thought you said that indoleacetaldehyde was easily prepared from tryptophan. Unless you know of a beter preparation of indoleacetaldehyde than this

https://www.thevespiary.org/rhodium/Rhodium/chemistry/indoleacetaldehyde.html

then I would have to say that extraction of Mimosa hostilis rootbark is more practical, cost effective and amenable to large scale production.

[PolytheneSam]

This patent looks interesting.

Patent US4808728

http://www.geocities.com/dritte123/PSPF.html
The hardest thing to explain is the obvious

[zed]

Thank you Sam for your Excellent reference.

The NaOCl reference in rhodium, does use a lot of solvent, which is a pain. However, most of solvent is water, and as such, the reaction, with some tweeking, might be scaled up, say to Alhambra water bottle size. If the reduction can be performed. Rest assured, some of the Bees will try NaOCl.

There are a few ways to make Indoleacetaldehyde that may be better. Sam's excellent reference. Looks very promising!

Basically, it is a high yield transamination, where in a Rival carbonyl group, steals Tryptophane's amino function, Converting The Tryptophane to a Keto-acid. Ketoacids love to decarboxylate to form aldehydes. In this case, to Indoleacetaldehyde. This decarboxylation could be considered analogous to that used to produce Tryptamine. Only the Keto function itself =O, is present, rather than the imino =N-R.

I don't have details for this decarboxylation, heat is surely one way, enzymatic decarboxylation another.

Thank you again Sam, I've been away a long time, I don't have your modern research skills. You, really are the Master Researcher.

[PolytheneSam]

Speaking of transamination see

Post 281536

(PolytheneSam: "Transamination idea", Tryptamine Chemistry) .
Maybe someone can tell us how something like that works out.
http://www.geocities.com/dritte123/PSPF.html
The hardest thing to explain is the obvious

[zed]

Thank you Sam, I don't know if I will be able to continue posting on this thread. It is not impossible that my obnoxious person will be required to take a vacation. I'm really enjoying how this is going however. And, I hope people will follow through on this.

So, how about it Bees? Has any one produced DMT via The reductive Amination of Indoleacetaldehyde?

Has anyone produced Indoleacetaldehyde?

Does any one have a decarboxylation, for that Indole Keto-acid?

Thank you all for your kind attention, you have been great!

Please Post..........I wish you all the best.....All for One, And One for All.....zed 

[zed]

Sam, Thank you for your serendipitous Indolepyruvic acid reference. I studied the full patent carefully, and determined that the reagents involved might make the synthesis impractical. There were however, some later patents, using enzymes, that looked promising.

As it turns out, Indolepyruvic acid itself, may be psychoactive. It increases serotonin levels in the brain, and might be useful as an antidepressent. Further, many theraputic uses are projected for this material. It is useful for treating certain degenerative neurological disorders, and a wide variety of other diseases. It even has uses in sunscreens and cosmetics. I expect, it may become commercially available at reasonable prices.

Since I have a dear friend, that is currently suffering from an otherwise untreatable disorder, I must investigate further. For the moment, my interest in indoleacetaldehyde, and its usefullness for DMT synthesis, must wait.

For those that are not aware, U.S. Patents are fully viewable now....via IE 6 and a free Tiff plug in. Research that formerly might have taken months or years, can now be accomplished in hours or days.

Thanks again .......................................zed

[zed]

Oxidations that produce aldehydes are touchy, hard to stop before they go too far. Think Reduction.

1. Indole to Indole-3-carboxaldehyde.......Pretty easy!

2. Indole-3-carboxaldehyde + Nitromethane to.... Nitrostyrene Analog........Pretty easy!

3. Nitrostyrene analog via Reduction......To Oxime.

4. This Oxime of course, is the the oxime of Indole- Acetaldehyde. Do with it what you will.

True, Indole isn't always an easy get nowadays. And there could be a snafu somewhere. But, the sequence might be pretty scalable, and most of us know the chemistry.

Sam, any opinion?

[Lego]

Journal of Medicinal Chemistry, 1990, Vol. 33, No. 1, page 392


Indole-3-acetaldehyde (1) was prepared by a modification¹⁵ of the published procedure:¹⁶
A solution of 3.052 g (14.9 mmol) of DL-tryptophan in 100 ml water and 15 ml of 10% NaOH (aq) was prepared in a 2-L beaker.
This solution was stirred mildly at room temperature with a mechanical stirrer, and 10 ml of 4 N HCl (aq) was added to bring the pH to 9-10 after tryptophan has dissolved.
The solution was diluted with 350 ml of water, 250 ml of brine, and 400 ml of benzene. The mixture was stirred and heated to 43-45°C, and 200 ml of a 0.52% NaOCl (aq) solution (10% solution of commercial Chlorox) was added dropwise over a period of 30 min.
Following the addition, another 100 ml of benzene was added 5 min before the end of the stirring.
The warm solution was transferred to a separatory funnel, and the layers were seperated. The aqueous phase was extracted with 200 ml, 150 ml, and 100 ml of benzene. The combined benzene extracts were extracted with 75 ml of brine, dried (Na₂SO₄), and concentrated to give 1.765 g (74%) of crude 1 as a viscous yellow oil.
This was purified by flash chromatography (44 g of silica, acetone/pentane, from 1:9 to 2: to yield 1.0548 g (44%) of the known¹⁶ 1 as viscous yellow oil.


(15) Tsarouthis, D. B.S., Thesis, Polytechnic University, 1968
(16) Arch. Biochem. Biophys. 1959, 81, 480 [see above]; J. Labelled Compd. Radiopharm. 1981, 18, 1491



Comment by Lego:
Benzene is carcinogenic, perhaps toluene or xylene should work too.
This method should also work with NaOCl on clay. See

Post 422851

(Lego: "Oxidation of Amines to Aldehydes on Clay with...", Novel Discourse)

[Lilienthal]

The correct reference is: J. Med. Chem. 33(1), 386-394 (1990) (it doesn't have a DOI yet).

[Rhodium]

Literature search on the conversion of Tryptophan to Indole-3-Acetaldehyde (scarce, I know). Other synthesis of this aldehyde include Swern oxidation of Tryptophol (cumbersome, smelly), oxidation of tryptamine (redundant) and DIBAL-H reduction of Indoleacetic acid and its amide/nitrile/ester derivatives (not cost-effective), so I believe that this is the best literature method of its preparation available.

Tryptophan + peroxomonophosphoric acid(aq) -> Indole-3-Acetaldehyde 
Conditions: Varying reaction temperatures, times and pH, addition of NaClO₄; mechanism; oxidation rate vs. pH at different temperatures
Panigrahi, Ganesh P.; Paichha, Ramesh C.; Indian J.Chem.Sect.A.; 29; 3; 1990; 272-273.

Tryptophan + NaOCl -> Indole-3-Acetaldehyde
Solvent: Water, Benzene Conditions: 50°C

Arch.Biochem.; 81; 1959; 480, 483.

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/indoleacetaldehyde.html)

Tryptophan + NaOCl -> Indole-3-Acetaldehyde
Solvent: Water, Benzene Conditions: 35 min, 43-45°C, pH 9-10, Yield 44%

J. Med. Chem. 33(1), 386-394 (1990)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/indole-3-acetaldehyde.pdf)

[urushibara]

I have found a number of references here on the hive regarding the use of tryptophol as the precursor for a dmt synth, which can be made by brewing tryptophan in brewers yeast. Since DMF can be turned into DiMeAm, with a simple acid reflux isomerisation, here we have two easy sources of the amine and an alcohol, all that is needed is the right reduction mechanism. Nickel catalyst was mentioned in one reference - has anyone got more information on this route?

[bbell]

Direct quote from 'Synthesis'page 475(1972)by:Tetsuji Kametani et al.,
We wish to report an inexpensive one-step prepn. of tryptamine from L-tryptophan.
A suspension of L-tryptophan(250mg)in warm diphenylmethane(10g was gently refluxed in a stream of nitrogen for 5-20 min. until no more evolution of CO2 was observed.  After cooling, the clear pale yellow reaction mixture was treated with a benzene solution (20ml) saturated with dry hydrogen chloride.  The resulting precipitate was collected by filtration, washed with n-hexane and dried to afford crude tryptamine HCL (233mg. 93%) which was recrystallized from ethanol/ethyl acetate to yield tryptamine HCL (151mg. 63%) as colourless needles, m.p.248-249 degrees.
From this to DMT should be easy.The manufacturing of drugs is illegal, and can put you in jail a long time.

[Rhodium]

That is an old procedure, that and several others are listed in

https://www.thevespiary.org/rhodium/Rhodium/chemistry/tryptophan.html

[urushibara]

that sounds rather easy. is that diphenylmethane as in:

(R)-CH2-(R) where R=benzene

so it is a solvent and reagent in one in this situation?

and it's cheap - for the price of a decent meal in a restaurant, enough to treat 2.5g of tryptophan.

how does that reaction work? I mean, what is it about diphenylmethane that makes it able to be used this way?

also, since CO2 is the main product of the reaction, couldn't the diphenylmethane be distilled and reused?

still, is there a worthwhile dimethylation process, yieldwise, sans cyanoborohydride?