zed (Newbee)
04-20-02 07:46
No 299426
      Easy Route to DMT ?     

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
(Old P2P Cook)
04-20-02 08:05
No 299432
      Tryptophan oxidation.     

Indoleacetaldehyde is rather easily obtained by the oxidation of tryptophane by NaOCl.
Got any references for this?
 
 
 
 
    foxy2
(Distinctive Doe)
04-20-02 08:48
No 299445
      terb     

../rhodium/chemistry /indoleacetaldehyde.html
wink

Those who give up essential liberties for temporary safety deserve neither liberty nor safety
 
 
 
 
    PolytheneSam
(Master Searcher)
04-20-02 16:13
No 299513
      Holy grail?     

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. tongue



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
(Chief Bee)
04-20-02 17:23
No 299526
      Tri?     

Tricyclic? As in that it inevitably forms the pictet-spengler product?
 
 
 
 
    zed
(Newbee)
04-20-02 17:32
No 299529
      Thank you Sam.     

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
(Old P2P Cook)
04-20-02 17:41
No 299530
      Mimosa hostilis     

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 ../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
(Master Searcher)
04-20-02 18:08
No 299535
      indole-3-pyruvic acid     

This patent looks interesting. Patent US4808728

http://www.geocities.com/dritte123/PSPF.html
The hardest thing to explain is the obvious
 
 
 
 
    zed
(Newbee)
04-20-02 19:55
No 299546
      Thank you Sam!     

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
(Master Searcher)
04-20-02 20:25
No 299550
      transamination     

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
(Newbee)
04-20-02 22:01
No 299565
      Onward!     

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
(Hive Bee)
05-03-02 08:02
No 304498
      Indolepyruvic acid!     

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
(Hive Bee)
05-16-02 17:25
No 309394
      Indole-acetaldehyde     

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
(Stranger)
04-09-03 22:16
No 425180
      Improved method
(Rated as: excellent)
    

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 43-45C, 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 2:8) 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)

The candle that burns twice as bright burns half as long
 
 
 
 
    Lilienthal
(Moderator)
04-09-03 23:06
No 425195
      The correct reference is: J. Med. Chem.     

The correct reference is: J. Med. Chem. 33(1), 386-394 (1990) (it doesn't have a DOI yet).
 
 
 
 
    Rhodium
(Chief Bee)
07-09-03 18:02
No 445890
      Tryptophan to Indole-3-Acetaldehyde
(Rated as: good read)
    

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: 50C
Arch.Biochem.; 81; 1959; 480, 483. (../rhodium/chemistry /indoleacetaldehyde.html)

Tryptophan + NaOCl -> Indole-3-Acetaldehyde
Solvent: Water, Benzene Conditions: 35 min, 43-45C, pH 9-10, Yield 44%
J. Med. Chem. 33(1), 386-394 (1990) (../rhodium/pdf /indole-3-acetaldehyde.pdf)
 
 
 
 
    urushibara
(Hive Bee)
07-11-03 05:38
No 446338
      Tryptophol???     

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?

you can't keep peace with a gun
 
 
 
 
    bbell
(Newbee)
07-14-03 06:46
No 446978
      a simple prepn. of tryptamine     

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
(Chief Bee)
07-14-03 13:41
No 447049
      Old news     

That is an old procedure, that and several others are listed in ../rhodium/chemistry /tryptophan.html
 
 
 
 
    urushibara
(Hive Bee)
07-19-03 05:41
No 448374
      diphenylmethane???     

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?

we can't stop here, this is bat country
 
 
 
 
    Rhodium
(Chief Bee)
07-20-03 02:09
No 448516
      diphenylmethane and nabh4     

The merit of diphenylmethane lies just in its high boiling point, I guess...

As for alternatives to NaBH3CN, there has recently been posted a method using NaBH4 in this forum, using low temperature and slow simultaneous addition of the hydride and formaldehyde from two separate addition funnels to make it work.
 
 
 
 
    Rhodium
(Chief Bee)
11-21-03 20:35
No 472299
      More about Tryptophan -> 3-Indoleacetaldehyde
(Rated as: excellent)
    

Kinetics of Oxidation of Tryptophan by Sodium Hypochlorite
Thomas Rausch, Frieder Hofmann, and Willy Hilgenberg
Z. Naturforsch. 36B, 359-361 (1981) (../rhodium/pdf /tryptophan.strecker.kinetics.pdf)

Abstract
The oxidation of tryptophan to 3-indoleacetaldehyde with sodium hypochlorite was investigated with 14C labelled DL-tryptophan. The reaction was performed under pseudo first order conditions. From the pH dependence of the reaction it was concluded that only the unprotonated tryptophan is converted to the aldehyde. The activation energy is 352.2 (SE) kJ x mol-1 as derived from the Arrhenius plot. Varying the pH between 8.5 and 11.0 and the temperature in the range from 298 K to 318 K did not alter the selectivity of the reaction as confirmed by TLC of the product (purity > 90%). A possible reaction mechanism is proposed.
 
 
 
 
    Vitus_Verdegast
(Hive Addict)
06-16-04 00:09
No 513642
      failed attempts to prepare indole-3-acetaldehyde     

The route to indole-3-acetaldehyde by simple NaOCl oxidation of tryptophan has always intrigued me since it was posted here a couple of years ago. Granted, the dilution and amount of solvent used is huge, but in practice this takes only more time in the work-up, a price that is most willingly paid for what could be an OTC route to the dialkyltryptamine of choice. It is astounding that nobody has reported trials for what looks like a very straightforward route, even if indole-3-acetaldehyde is an unstable critter, it has worked for at least 2 different groups in the literature.


../rhodium/pdf /indole-3-acetaldehyde.pdf
Two trials were made (by a famous Hungarian actor who appeared to me in a vivid dream wink) using the above procedure, but substituting toluene for carcinogenic and thus restricted benzene.

From the first trial, after evaporating the red toluene extract in vacuo (fridge compressor, +- 50C), a thick red oil containing orange solid material was obtained, that failed to produce a bisulfite adduct. This was, however, chalked up to inefficient stirring.

In the second trial, heavy overhead stirring was used, so that an almost uniform emulsion was attained during the whole process. Again, the toluene layer was deep red in color, and after concentrating the organic layer in vacuo using the same fridge compressor, a dark red oily residue was obtained instead of a yellow one like described in the above article. This formed a greyish brown solid upon treatment with a saturated bisulfite solution, which was washed several times with water. This was added to a warm sodium carbonate solution, stirred for 20 minutes and extracted with DCM.

The solid should have been washed with alcohol too, but that was forgotten by mistake.

After evaporation of the DCM, about 2 grams of a red oily residue was again obtained. This was diluted with ethanol, an excess of aqueous dimethylamine solution (containing 2 grams Me2NH) was added and the mixture was stirred for an hour in a cold water bath. A gram of NaBH4 was added in small portions while cooling the mixture in a cold water bath, stirring was continued for an hour, and the mixture was acidified with acetic acid.

Standard A/B work-up, extraction of the basic mother-liquor with DCM and evaporation of the solvent yielded... nothing but an unknown red-coloured solid which was certainly not the desired compound frown.


Maybe it would help to add some kind of polymerization-inhibitor to the organic layer before adding the hypochlorite solution?

http://www.psychedelicrepublicans.com/
 
 
 
 
    Lilienthal
(Moderator)
06-16-04 00:49
No 513651
      Have you checked the pH?     

Have you checked the pH? Maybe you could even lower the pH to 8 or 9 in order to prevent polymerization?
 
 
 
 
    Vitus_Verdegast
(Hive Addict)
06-16-04 01:10
No 513659
      yes     

pH was 9 before addition of hypochlorite.

I was thinking maybe to dilute the hypochlorite solution even more, as it was stated that the dilution is necessary to avoid excessive coloring (polymerisation probably?) of the reaction mixture..

http://www.psychedelicrepublicans.com/
 
 
 
 
    Sunlight
(Pioneer Researcher)
06-18-04 00:51
No 514016
      Anhydrous dimethylamine     

May be the problem is the water in the imine formation ... Why the hell you didn't make a bit of anhydrous methylamine for that excelse moment ?
 
 
 
 
    Vitus_Verdegast
(Hive Addict)
06-18-04 21:15
No 514163
      because I doubted that I had the correct product     

1. The miserable red goo I got instead of what should have been yellow as stated in the most recent paper, and colorless in the first 1950's Ann. Chim. one.

2. Surely it can not be even when using aqueous dimethylamine that no enamine at all is formed? Lower yields maybe, yes, Barium proved in the past that 40% aqueous methylamine works fine for reductive amination with phenylacetones.

3. I am very busy lately, and I should refrain from chemistry completely instead of trying things in a hurry crazy.. Ahh, the call of the Sirens wink

I'll be back on top of this in a month or so, with anhydrous dimethylamine in alcohol, but meanwhile....

wink


http://www.psychedelicrepublicans.com/