DMT a la KrZ

[notJedZed]

Does anyone remember a post KrZ made about DMT from T and formaldehyde?  Presumably it was done with Pd/C.  I have Used The Fucking Search Engine! on both the UBB and this new board but to no avail.
     ...Anybody remember this?  nJZ

[halfapint]

I have been gleaning the wealth of the old Hive in a thoroughly unsystematic fashion, just grabbing handfuls of synths and refs like a monkey in a plum tree, grabbing the juiciest stuff that's closest. I have what I think you mean, but I don't know how to quickly find it again.

Tryptophan (454g) was suspended in tetralin (1150 ml) containing acetone (12.9 g) and the mixture was heated to reflux for 12 hours with vigorous stirring until no more carbon dioxide was evolved and the reaction mixture became clear. The solvent was removed under vacuum, and the residue was distilled under reduced pressure to give a yellow crystalline solid. (from rhodium). Next 30g of formaldehyde and 120 g tryptamine were disolved in 1800ml of MeOH, to this was slowly added dropwise 50g of NaCNBH3 disolved in 550ml MeOH. Then 14g Glacial Acetic Acid was added dropwise with stirring. The mixture was then stirred for 60 hours. The majority of the MeOH was distilled off (2L collected) to the distillation flask was added 1L of 5% Aq. Ammonia which was extracted with 3x 250ml of DCM. The DCM was washed with a salt solution (not saturated but still pretty strong) then the DCM seperated and dried with a large portion of MgSO4 made by dehydrating epsom salts overnight in the oven at 450C (the rock-solid mass had to be pounded into a powder with a hammer and the small remaining clumps ground in a pestal, quickly so as not to allow H2O uptake from the atmosphere). The DCM was distilled off at atmospheric and then the distillation was continued (~1 torr now) until the dimethyltryptamine was collected. Which was recrystalized from boiling hexane with a few mls of Ethyl Acetate added (these were the 2 hardest things to get!) This afforded 48.8g of DMT, a 35% yield. Not high but it was still a fun adventure. The DMT was immediately mailed 3500 miles away.

Was that it? I also picked up a mention of zinc borohydride,somewhere.

The n-methylation I found fascinating was with phase-transfer catalysis. (Off yr topic tho):

N-alkylation is done properly at ambient temperature by disolving PTC in CH2Cl2, and adding finely-ground NaOH or KOH. This is stirred for a half an hour or so, then your amine is added (in this case, tryptamine). After another 0.5 h, add your alkyl halide, and let stir overnight. The next day, filter the solution, wash the filtrate, then combine the washing with the rest of the solution, wash with H2O, then dry with MgSO4, then evaporate off the solvent. Yields are in the high 90's.

The Hive was where I first learned about PTC's, microwave mediated chemistry, and a bunch of other neat stuff too.
Makes me wanna run to Goodwill and grab a nuke, to drill a hole in the top for a reflux tube, just to see how some of these highly optimized reactions will work in the readers' digest condensed instant versions. With extract of Bounce unscented fabric softener for PTC, on activated kitty-litter clay, under UV irradiation. Whee!
Half-a-Pint

Half a pint's a half a pound, a half the world around, around.

[sunlight]

The last news about PTC method is that it does not work, is it true Lilienthal ?

[Lilienthal]

At least it looks like as if the PTC methylation it is not working everytime or for everybody.
See the thread at the old board:

Breath of Hoax? / PTC tryptamine alkylation on the test bench

(http://hive.lycaeum.org/ubb_board/Forum12/HTML/000016.html).

[yellium]

The tryptophan decarboxylation is also a bit troublesome, at least for me. I've never gotten it to work. Always ended up with less than half of the tryptophan converted. I found the synth using indole & oxalyl chloride lots easier. Of course, indole isn't exactly OTC..

[halfapint]

Whoa! Corn shuckin's! I have been intimidated for (lots of) years, at the prospect of working with oxalyl chloride, and LAH. Yellium, indole is derived so easily from natural products, it might as well be OTC. The oldest example I found was by "fusing ovalbumin with potash"; the costliest is extracting it from oil of lavender. I can vouch for both of these. Indole distills with steam. Somehow, I could never bring myself to try the extraction from human excrement, though we all shit out several grams daily.

Indole is absolutely no problem. It is the primary breakdown product of tryptophan, so is found absolutely everywhere in nature. The same cannot be said of lithium aluminum hydride. Oxalyl chloride is, in theory, obtained by the standard prep's of organic acid chlorides, though its extreme toxicity is discouraging. The real hold-up is still in the reduction. For decades LAH has been practically unavailable, except through institutional connections.

I have vaguely considered the use of two-stage reductions, to mitigate the need for LAH, but haven't found the exact combination I considered reliable enough to really study. Something like Clemmenson reduction (Zn/Hg/HCl) would for sure tear every bit of your product to shreds.

Lil: that thread you referred to on the old board, where you tore Drone to shreds. What did you mean, by doubting the ethanolamine rectification of the quaternary amine?
------------- quote ------------
Teo: I would say you can't be sure if the right alkyl group will be split off using ethanolamine - you have four possible groups.
--------------------------------
I can see the problem, if you ripped off the "alkyl" group containing the indole group, leaving indole-3-ethanol and trimethylamine. But surely, at least 75% of the time you are pulling off the excess methyl group, and surely they are all interchangeable?

Could you, by chance, be able to point me to an acceptable two-stage reduction, of the indole glyoxyl dialkylamine? Or perhaps any other reduction technique which is productive, even at some cost in yield? Just say I'm superstititious about LAH.

Half-a-Pint

Half a pint's a half a pound, a half the world around, around.

[halfapint]

Yellium:

For the decarboxylation of tryptophan, have you tried the antique "classical" reagent for decarboxylating amino acids, namely soda lime? This is an equimolar mixture of CaO and NaOH, and as far as I know is completely general for the decarb of amino acids. For the solvent, I don't have tetralin on hand, so I would consider ethylene glycol, a.k.a. Prestone (distilled).

No, bad idea to use glycol (dummy). All those tempting hydroxides would saponify, yuck. That was just the first high b.p. solvent lying around the house I thought of, but it wasn't a good choice, was it?

Half-a-Pint

Half a pint's a half a pound, a half the world around, around.

[Rhodium]

When treating a quaternary salt with ethanolamine, the shortest alkyl group go first (methyl). The indolealkyl group won't leave.

http://rhodium.lycaeum.org

[yellium]

  I have been intimidated for (lots of) years, at the prospect of working with oxalyl chloride, and LAH.

In my experience, it wasn't *that* dangerous. You better don't spill it. And use dry solvents etc. Of course, this isn't exactly kitchen chemistry, but IMO the performic is synth-wise trickier than these reactions.

I've tried the decarboxylation a few times in cyclohexanol with acetone or cyclohexanone as catalyst. Reaction starts a bit in the beginning, but after a few hours nothing happens, and a large quantitity of trp remains. Adding more catalyst didn't help.

(BTW: the red-al procedure as described by shulgin in tihkal #33 seems to work. Bioassay needs to be performed yet, but the end product is a compound which behaves as expected in an acid/base workup.  )

Indole is absolutely no problem

:
And how about 5-MeO-indole?

[KrZ]

You do need to add more catalyst, especially if you're using acetone, just setup an addition funnel and add some every few hours.  Unless you are using a 600mm high-ass surface area condensor with ice, the acetone will come off easily.  PS I used a 600mm high-ass surface area condensor with ice.  And how long did you run the thing for?  You know nothing is going to be hurt by running it longer, and if you got your tryptophan back there is not much to complain about, you're good to go for another decarboxylation when you need it!

I do not see how you can think the indole route is easier, to each his own, but I can't see where you're coming from.

[yellium]

Running time varied from 4 to 8 hours, with a relatively inefficient condensor. But if all the acetone was evaporated, running it much longer would't have helped. Using cylohexanone (bp 154'c) wasn't much of a success either. If I had to do it again, I would try soda lime.

Then again, I got the goodies using the indole route, so I don't really feel like checking out what went wrong with the decarboxylation..

[notJedZed]

So to get the thread back on topic, not even KrZ remembers this?  Maybe I'm just confused in my mind...  Well, let SWInJZ build a hydrogenator & he'll get back to the hive 'ssoon as he's got something to share.

[thoughtcrime23]

This is my first post here.  But I've been following this procedure a little and am quite pleased to see this dug up from possible permanent deletion.  The journal ref. for KrZ's method is as follows:

    Journal of Medical Chemistry, 1994, vol. 37, No. 19 pg.3029
    "Gen. for the preparation of n,n-dimethyltryptamines"

     To a cooled (-2 C) and stirred sol. of (substituted amine)(7.0mmol), NaCNBH3(14.0mmol), and GAA(35.0mmol) in MeOH was added dropwise, over 17min., a sol. of CH2O(38% w/v aq. sol.) in MeOH. After 20min. of stirring at 0Celsius and 2.5hrs. at roon temp., sat. aq. k2co3 was added and the MeOH was removed under vac.. The residue was diluted w/ H2O and the product was extracted with EtOAc twice, washed with salt sol. twice, dried, and concentrated. Yield of sub. trypt= 83%.

   It is ironic that this is actually quite similar to a DMT proposed synth. back at DMT world that was also "lost and forgotten" (ref. Tet. Letters 3, 261.  1973 B.L. Sondengam e. a.) with the only major difference being the catalyst NaBH4 vs. the more selective NaCNBH3.  I recall it actually being discarded, without much trial, as producing quarternary tryptamines (betacarbolines) rather than the desired n,n-dimethyl because of a cerntian mechanism in the reaction (Pickett-Spengler?).
   However, to my knowledge when our revolutionary bee KrZ first posted the procedure of this thread's topic, Rhodium somewhat concluded that the combo of a gentler catalyst AND the use ose GAA to regulate the pH of the reaction that quarternary product formation would be reduced and/or eliminated!! WOW!

    I feel that if KrZ's method is what it seems to be, that this could be potentially the most accessible hypothetical route to DMT thus present so far. Sodium Cyano, albeit be no means OTC, is less hazadous than LAH or Red Al (not to mention its varied applications in other realms)... and everthing else in the process's 2nd half (from T to DMT) CAN be had in some relative OTC form, save Ethyl Acetate.  I've always dreamed of open the Pandora's box of dimethyltryptamine accessability via revolutionary synthesis, and I have to be cautious in my enthusiasm so as to remain rational and wary of hard evidence.
    Which brings me to this... as of now, KrZ is the only bee who has dreamt this, and ultimately the test will be our own dreaming. Let's not let this one lie in the limbo of misinformation, speculation, and the nebula of abstact debate.

[halfapint]

Ahh... didn't spot that despite many more hours browsing the old Hive...

Half a pint's a half a pound, a half the world around, around.

[gnrm23]

wasn't there talk of a NaBH4 reduction using CuSO4 or other metal salts as a catalyst?

don't you folks ever sleep?

[Rhodium]

Copper sulfate or acetate together with NaBH4 has been used to reduce nitrostyrenes. I don't think it would be useful for reductive amination.

http://rhodium.lycaeum.org

[foxy2]

I like the new title Rhodium.
I tried one Decarboxylation reaction in mineral oil, it sucked ass.  Next go is with plain old turpentine, since tetralin is turpentine substitute and the bp is about right im going to go for it.

What have bee's used as ratios of tryptophan to solvent, i have not checked its solubility in turpentine yet but i doubt its super high(at least until after decarboxylation).
Will i be ok if its not all dissolved?

[Student]

Did turpentine work? If I remember correctly the boiling point is around 175C, or about 30 degrees below tetralin, making the reaction rate about eight times slower - a few days. So far I've had no luck with xylene, DMSO or glycerine using catalytic butanone. Even though l-Trp dissolves great in the latter two at high temp., something other than tryptamine quickly forms.

[Ritter]

Hey foxy,

I'm guessing that you are looking for an OTC decarboxylation by indicating you tried mineral oil.  Make the Cu(II) chelate with equimolar portions of Cu Acetate and aminoacid in H2O then heat in boiling DMSO for 5 minutes---50% yield for tryptophan.  The ref is here in this forum somewhere.

[hypo]

Post 211603

(Rhodium: "Another tryptophan decarboxylation", Tryptamine Chemistry)

btw: i dont think you need equimolar amounts of Cu++ and Trp.