Dimethyltryptamine

[KrZ]

Tryptamine hydrochloride (10 g, 62.4 mmol) and sodium cyanoborohydride (6.28 g, 100 mmol) in a mixture of methanol (400 mL) and glacial acetic acid (11.76 g, 196 mmol) were cooled to 0C in an ice bath over a steady stream of nitrogen.  A solution of 4.20 g formaldehyde (140 mmol, 11.05 mL of 38% Aq. CH2O) in 125 mL of Methanol was added dropwise to the solution over a period of one hour with mild stirring.  The flask was stoppered, the reaction allowed to return to room temperature slowly, and allowed to proceed for the next 60 hours. Upon completion the pH was adjusted to 8.0 by the dropwise addition of an aqueous solution of sodium bicarbonate.  The mixture was then extracted 4x with 50 mL of ethyl acetate.  The combined extracts were washed once with 250mL of brine and dried over MgSO4 (15g) for 15 minutes.  The MgSO4 was washed clean with another 75 mL of ethyl acetate.  The solvent was reduced to 100 mL on the rotary evaporator.  The hot solution was added to a 200mL beaker and covered with plastic wrap which was sealed on with a rubber band.  Upon cooling in the freezer overnight, the precipitated dimethyltryptamine was removed by filtration, and dried in the dessicator.  Overall yield: 7.88g, 45 mmol, 67%.

[sunlight]

I'm afraid that this product could contain some n-methyl tryptamine too, there's no purification with acetic anhydride or chloride to separate primary and secondary amines, have you tested melting point or whatever ?

[KrZ]

The mp is solid, right around 64-67C.  I'm not sure about the solubilities or pKa's of the 3, but this was an 84x scaleup (ever so slightly modified) of a journal article which reported a clean product, 1H NMRs and all...

[Rhodium]

The melting point of pure DMT is about 67°C, and the HCl salt is reported to melt at 165-167°C. What is this compound melting at 138-140°C?

http://rhodium.lycaeum.org

[KrZ]

That's a good question rhodium.  I probably should ban myself from posting when I've been up for 36 hours cramming for a monstorous biochemistry II exam.  I went ahead and changed it to the right numbers (real).  I was looking at the reference when I typed that, trying to see how the workup could effect purity.  I knew the mp had been right around the lit. one and I spaced out and punched in the mp of the tryptamine in the article! What I found curious was this in tihkal "This was pressed on a porous plate and washed with petroleum ether to give N,N-dimethyltryptamine (DMT) as an off-white solid with a mp of 47 °C"  What's up with that?

----Momo- I can't wait to see you, I felt like you needed this.

[fanofshulgin]

DMT has notoriously been reported having a HUGE range of different melting points.  I would presume that this is due to various factors including differing average particle size. (differing physical forms cause large differences in physical properties - ask your average industrial plant chemist)

Peace, Love and Empathy

Fan of Shulgin

[STQ]

OK, so finally someone is doing N-alkylatipon the right way - formaldehyde and NaBH3CN is the only real decent way to go about this.  The methyl iodide approach ain't happening for DMT, IMHO.

One question KrZ - it seems like you might have the salt here?  The pKa of a tertiary amine is something on the order of 11, so bringing the solution to pH = 8 should still be the HCl or HOAc salt.  The other thing that makes me think that might be what you got is the easy crystallization that you get.  In my experience, DMT freebase is a waxy, low melting solid that is very difficult to get to really crystallize - that's the reason for the varying melting points that are reported.

OTOH, trying to make the acid salt of DMT leads to some rearrangements (I think - things certainly get very colorful when I've tried), and I assume that you've sampled the product, so take my comments worth a grain of salt (so to speak).  I assume that the chloride or acetate is not smokeable (smokable?).

I still like the indole to DMT route using oxalyl chloride/Me2NH followed by LiAlH4.  If you can get the chemicals, it's hard to beat, and indole is easy to get in large quantities.  The intermediate glyoxamide is very quick and easy to make and is very stable, so you can make a big batch of that and LAH small amounts as needed.  If you make a bunch of DMT (7 grams qualifies as a bunch in the DMT world ), you have to keep it in the freezer to keep it from turning red.

STQ...

I can take it or leave it, but, so far, I always seem to take it...

[2ndAmRevolution]

After reading many of the extraction posts of DMT from the Acacia species, I've got a question regarding something I have yet to see anyone mention: Acacia Senegal - more commonly known as Gum Arabic - contains all of the components of the plant - it is merely ground up and then sprayed and dried. Dr Duke's Phytochemical Database lists the DMT as one of the constituents of the plant, so how about just using the standard plant extraction on Gum Arabic? After all, this shit is so commonly available anywhere that sells arts and crafts stuff - who would ever think twice, even if you bought a truckload of it?

[superhybrid]

Hey, why do you think a haloalkane coupling reaction is out of the question. I seemed to have seen it a many times while researching other coupling reactions. Many a goofball many a problemo. You need Et3N to inhibit the coupling of the HX produced to the alkylamine. You will produce 2 moles HCl for every mole of DMT produced. The HX will inhibit this coupling. HX binds the Et3N better than the the tryptamine. I am also under the impression that you shouldn't just dump all the haloalkane in at once. Dropwise will be the key. Ain't you ever done a coupling reaction before?

[superhybrid]

SWIM found this interesting. Notice how you get the mono sub or tri sub. I bet if you have a 2:1 ratio of XCH3 to amine it will produce the di sub. SWIM acquired this from Beilstein. They ironically did not have the di sub amine rxn. Seems to SWIM like it would work. If you went to a 4:1 molar ratio you would probably find a methyl attatched to the N on the indole ring also although it is aromatic which inhibits this from taking place first. The journal entry is on the bottom, 1940 !!!!

http://www.maybenot.com

SWIM says now stay safe and don't do anything illegal.

[Lilienthal]

It seems to be impossible to get the dimethylamine derivative via alkylation with MeI. Please see

Post 126957

(Lilienthal: "Breath of Hoax? / PTC tryptamine alkylation on the test bench", Tryptamine Chemistry).
For indole-N alkylation you need very strong basic conditions like LiNH₂, NaH, BuLi, or PTC / NaOH.

[superhybrid]

The coupling reactions swim has done have been with di-alkylamines and have had no problems adding a third alkyl group. Swim has seen methyl goups added to phenylethylamines in the same way. Only thing was that they were added to the N,N-dimethyl configuration with CH3X. Why would not the tryptamine do the same also. Besides Et3N,imadazole works also for pulling out access HX from the reaction. The way that other coupling rxn was done seems way different than any coupling reaction swim has ever done.

This is how it could be done swim says , possibly.

CH3X dissolved in CHCl3 with the Et3N/or/imidazole also dissolved added dropwise to tryptamine dissolved in CHCl3. Dropwise means real slow say 1 drop every 10 seconds = 1mL every 3 mins. You could even go slower. A big stir bar would also be in order.

SWIM has decided also that it is indeed impossible. He says he is sorry for getting your hopes up

[psychokitty]

Paraformaldehyde, sodium borohydride, zinc chloride, tryptamine, in DCM solvent is probably and easier and more decent way to get dimethyltryptamine.

But what do I know.  I have a reference, though.

--PK

[psychokitty]

Sunlight:  I'll get the reference but I believe that it is mentioned somewhere on Rhodium's page.  It's an article written by that Bhattacharaya (or however the hell it's spelled) chick or guy who pioneered that sodium borohydride/titanium isopropoxide reductive amination proceedure that looks oh-so-promising but has yet to be experimented with by anyone here at the Hive-myself included.

--PK

[sunlight]

Oh, I think to remeber it's a general procedure, not pecifical for tryptamine, so it is not too much info. These one-pot reactions utilize only cheap and (more or less) non-toxic chemicals (no carcinogenic and expensive methyl iodide!). Because of the aprotic, non acidic reaction and work-up conditions no cyclization to beta-carbolines should occur. The yields after purification are good to excellent (phenylethylamine: 72%, diisopropylamine: 92%, holafébrine: 85%).

Synth. Comm. 25, 2061 1995. Sukanta Bhattacharyya

A mixture of prim. amine (5 mmol) or sec. amine (10 mmol), ZnCl2 (20 mmol) and paraformaldehyde (20 mmol) in 25 ml CH2Cl2 was stirred at RT for 1h under dry atmosphere. NaBH4 20 mmol was then added and the resulting mixture was stirred for 9 h (sec. amines) or 12h (prim. amines). The reaction mixture was then quenched by addition of aqueous ammonia (40 ml, 2 N), stirred for 10 min. and the organic layer was separated. The aqueous part was extracted with CH2Cl2 (1x25 ml) and the combined organic extracts were concentrated in vacuo after drying over anhydrous Na2CO3. Prim. amines were purified by distillation, crystallization or flash chromatography. The sec. amines afforded the pure tert amines without any chromatographic separation.

Tet. Lett. 3, 261 1973. B. L. Sondengam

Formaline (35%, 35 mmol) was added with stirring to a solution of holafébrine (prim. amine) 3 mmol in methanol (10 ml) and the solution was refluxed for 30 min. After cooling 400 mg NaBH4 was added slowly. After 1 h the reaction was evaporated and the mixture was extracted with CHCl2. Evaporation yields iréhine (dimethyl-holafébrine, 85%).

[KrZ]

If you're worried about NMT/T contaminating your product just do the workup this way;

Basify the aq. reaction mix to 13-14 with NaOH.  Extract repeatedly with DCM.  Rotovap off the DCM and add Petroleum Ether, heat to a boil and decant the Pet. Ether from any undissolved material.  Cool the Pet. Ether in the freezer and collect any precipitated solids.  This will remove any unreacted tryptamine.  To remove NMT you can react this mixture with acetic anhydride and seperate.  I know that's quite a hassle but it's a good way to cover all the bases as far as purity is concerned.

[kurupira]

Would Ti isopropoxide act as an imine generator on CH2O/NaCNBH3/Tryptamine and improve the yield?

K-boclo

[sunlight]

KrZ, I always thought that a single rxn with acetic anhydride should remove T and n-MT, forming the amides.

[jim]

Lilienthal,

Your link states that N, N, N, trimethyltryptamine is produced via Drone's receipe as the major product, right?

Therefore you state that the production of dimethyltryptamine is impossible via that route, I agree and disagree...

There are compounds which de-quaternize amines, like ethanolamine.

[psychokitty]

My view is that using titanium isopropoxide might make the sodium cyanoborohydride method obsolete.  It produces high yields of amines with NO BYPRODUCTS (no higher amines, in other words) using cheap, non-suspicious, and pretty easy to find reagents.  Also, if one hypothetically wanted to make just plain old MDA one would only need ammonium CHLORIDE (NOT acetate) to do so-that and some triethylamine, that is.

--PK