The Vespiary

The Hive => Tryptamine Chemistry => Topic started by: freakyDMT on May 23, 2003, 02:14:00 PM

Title: KrZ DMT syntheses experience
Post by: freakyDMT on May 23, 2003, 02:14:00 PM
I would like to know what the experiences are with the KrZ
NaCNBH3syntheses,how is the yield,i see that there are a lot of disinformation about this DMT route.
Title: DMT from Tryptamine/NaBH3CN/37% HCHO
Post by: Rhodium on May 23, 2003, 04:57:00 PM
If you UTFSE in this forum for "nabh3cn or cyanoborohydride", you will find almost exclusively posted procedures which involve reductive amination of various tryptamines with formaldehyde and NaBH3CN - all of them have yields of 60% or more.

KrZ's synthesis in particular is not optimized, he runs the reaction for a far longer time than necessary, and in the first procedure he posted he used far too little formaldehyde for the reaction to go to completion. Try the procedure below instead, if you don't have any silica gel for chromatography, then you can try repeated recrystallization instead to purify the product, either from hexane (petroleum ether), ethyl acetate (EtOAc) or am mixture of both.

DMT by reductive methylation of Tryptamine with 37% Formaldehyde and NaBH3CN in Methanol
Synthesis according to a general procedure in

J. Med. Chem. 37(19), 3029 (1994) (https://www.thevespiary.org/rhodium/Rhodium/pdf/reductive.tryptamination-2.pdf)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/reductive.tryptamination-2.pdf)


Tryptamine (1.12g, 7 mmol), Sodium Cyanoborohydride (0.88g, 14 mmol) and Glacial Acetic Acid (2ml, 35 mmol) was dissolved in 110ml Methanol at 0°C, and a solution of 37% Formaldehyde (1.4 mL, 18.5 mmol) in 15ml Methanol was added dropwise over 20 min, and the resulting solution was allowed to stir for 20 min at 0°C and 2.5h at room temp. The methanol was evaporated under reduced pressure, and 80ml 25% aqueous potassium carbonate was added and the solution extracted with 2x125ml EtOAc, the extracts washed with 2x40ml brine, dried over MgSO4 and the solvent evaporated under reduced pressure to give an amber oil, which was purified by flash chromatography on 30g silica gel using a gradient of EtOAc:MeOH to give an oil, which was crystallized from boiling hexane to give N,N-Dimethyltryptamine as colorless waxy crystals, weighing 0.9g (69%).
Title: Thank you,RHODIUM,you realy helpt me ...
Post by: freakyDMT on May 23, 2003, 08:34:00 PM
Thank you,RHODIUM,you realy helpt me out,thanks!!
by the way,what about the use of sodiummethoxide,what is the use of that and does it give it a higher yield?
a second question what is the exact purpuse of the acetic acid,does it control the pH or is it to make the tryptamine/DMT solvable?
Title: acetic acid & sodium methoxide
Post by: Rhodium on May 24, 2003, 02:55:00 PM
The acetic acid will probably change the pH to an optimum level, but may also contribute to form some acetoxycyanoborohydride species in solution, which probably has other reducing properties than plain cyanoborohydride. I don't know which of these two effects is the most important here.

I don't see any sodium methoxide in this procedure?
Title: What i mean is see post 285474 03-20-02 were...
Post by: freakyDMT on May 25, 2003, 03:12:00 AM
What i mean  is see

Post 285474 (https://www.thevespiary.org/talk/index.php?topic=12713.msg28547400#msg28547400)

(Rhodium: "Tryptamine -> DMT w/ formaldehyde/NaBH3CN", Tryptamine Chemistry)
were they also use sodiummethoxide in the synthese.
Title: Cyanoborohydride required?
Post by: ClearLight on May 25, 2003, 08:43:00 AM
Is the Cyanoborohydride required for this reduction or could NaBH4 be substituted?  If it is a yields question I can live/ that.

Title: Reductive methylation of tryptamine
Post by: Rhodium on May 25, 2003, 09:10:00 AM
I'm not sure about the reason for the sodium methoxide in that procedure, maybe another pH is desired when working with a cyano-substituted tryptamine. This procedure uses tryptamine/cyanoborohydride/acetic acid/formaldehyde in a 1/2/5/2.5 ratio while the other one uses a 1/2/3/2.5 ratio (plus one equivalent of sodium acetate, which forms from 1 eq of acetic acid and 1 eq of sodium methoxide). There is no real difference but the final pH of the solution. The yields are erssentially the same anyway (even though the method with NaOMe hasn't been tried on DMT yet).

No, sodium borohydride cannot be used in this case, the formaldehyde will be reduced to methanol by it before it has had a chance to form an imine with the tryptamine.

Here is some more reading on acetoxyborohydrides and tryptamine:

Post 243844 (https://www.thevespiary.org/talk/index.php?topic=12768.msg24384400#msg24384400)

(Rhodium: "Tryptamine reductive alkylation with NaBH(OAc)3", Tryptamine Chemistry)
Title: tryptamine v. tryptamine HcL
Post by: freakyDMT on May 25, 2003, 11:29:00 AM
Rodium is there a diverence between tryptamine and the HcL form in use in the synthese,and what i read is it so hard to get cyanoborohydride,is it a controlled substance,were i live you can order it whitout any questions.
Title: Methoxide Mystery Solved
Post by: Rhodium on May 25, 2003, 12:19:00 PM
You have a good eye for details! Then of course the sodium methoxide is added to deprotonate the 5-CN-Tryptamine HCl to its freebase, and there is only the 4 vs. 5 equivalents of acetic acid that differs. I really wonder if the active reducing species is a cyanoacetoxyborohydride or id it is free cyanoborohydride which does the job. NaBH3CN is stable down to around pH 3, so if the final reaction mixture isn't more acidic than that, then we can be pretty sure that it is free cyanoborohydride.

NaBH3CN is easy to aquire in many parts of the world, it is only in the US it is watched closely.
Title: Rodium,i think the sodiumcyanoborohydride is...
Post by: freakyDMT on May 25, 2003, 01:48:00 PM
Rodium,i think the sodiumcyanoborohydride is in its free form,because i always messure the pH at the end of the reaction and the pH is normally around pH 5-5.5.
by the way what does the word bookmark mean?
Title: pH & bookmarks
Post by: Rhodium on May 25, 2003, 03:42:00 PM
During a NaBH3CN reduction, the pH of the solution becomes progressively more basic, so you should rather measure the pH when you initiate the reaction to be able to tell for sure, but I agree with you that it is probably above 3 in the beginning too.

Bookmarking a post will add it to you personal list of favorite posts at

https://www.the-hive.ws/forum/favorites.pl?Cat (https://www.the-hive.ws/forum/favorites.pl?Cat)

= (accessible by clicking "Show bookmarks" in your private area) so that you easily can go back to certain posts you want to read again without having to UTFSE for them every single time.
Title: Great DMT synth
Post by: Chimimanie on May 25, 2003, 03:54:00 PM
Rhodium I like this DMT synthesis, it is great!

So simple and yet effective!

DMT easy way...
Title: Acetic acid and trioxy?
Post by: ClearLight on May 27, 2003, 07:22:00 PM
Hmm, Rhodium,  this post indicates addition of acetic acid in the reaction, and in the post you linked to above using triacetoxyborohydride, they indicate that acetic acid would cause things to go bad quickly...

  Is there a modification of this method that would enable triacetoxyborohydride  to be substituted for the NaCNBH4 and not require acetic acid?  I really like the idea of using triacetoxyborohydride  since it seems to be easily made...

Title: 2 mL HOAc is ok...
Post by: Rhodium on May 27, 2003, 07:43:00 PM
The thing which made things go bad was when they used acetic acid as the solvent. There is a big difference between that and only 2 mL HOAc in 125 mL methanol... And don't worry about it, this procedure is used in almost a dozen articles on dimethyltryptamines over the last decade. It will not produce the indoline.
Title: Please UTFSE
Post by: Lego on May 28, 2003, 02:59:00 AM

Is the Cyanoborohydride required for this reduction or could NaBH4 be substituted?  If it is a yields question I can live/ that




No, cyanoborohydride is not required, plain sodium borohydride can bee used, too.

A quick search with TFSE will tell you this  ;)

The search string is almost in your post, perhaps you have to try an abbreviation but the hit will lead you to the right post.

Hint: The post you are looking for is quite new........



Title: cyanoboro is way too expensive to play with.
Post by: raffike on May 28, 2003, 11:59:00 AM
cyanoboro is way too expensive to play with.

Post 431982 (https://www.thevespiary.org/talk/index.php?topic=12949.msg43198200#msg43198200)

(Lego: "Article on DMT derivate synths", Tryptamine Chemistry)


Title: thx
Post by: ClearLight on May 28, 2003, 12:02:00 PM
For that indirect reference to the article you posted  :) !

  I downloaded the article and read your synopsis.   I'm afraid my theoretical understanding does not make the leap from the journal article to a practical synth from what was described. (Rhod let me know if you want the pdf of the tetrahedron original). I don't want compount 11b i would like the NN DMT variant.  A little clearer explanation of how YOU would adapt this procedure to produce elf spice would be appreciated!

Title: think moles not grams
Post by: raffike on May 28, 2003, 12:16:00 PM
think moles not grams
PS you want 9b without that sulfonylmethyl group

Title: right raffike
Post by: ClearLight on May 28, 2003, 10:06:00 PM
but when i read that synth i can't see HOW that sulfonylmethyl group got in there in the first place, since none of the reagents listed carry a sulfur atom..?  So this is where I go "What am I not seeing here???!!!"

Title: What am I not seeing here?
Post by: Lego on May 29, 2003, 03:17:00 AM

but when i read that synth i can't see HOW that sulfonylmethyl group got in there in the first place, since none of the reagents listed carry a sulfur atom..?  So this is where I go "What am I not seeing here???!!!"



Check Scheme 2 of the article. They use a 4-sulfonyl derivate of aniline. So the sulfur is in the molecule since the beginning of the synthesis.





The procedure for DMT would go like this:


A solution of 35% formaldehyde (35 mL, 416 mmol) in MeOH (35 mL) and a solution of NaBH4 (5 g, 132 mmol) in H2O (70 mL) were added dropwise, simultaneously, at 15°C to a well-stirred solution of tryptamine (4.166 g, 26 mmol) in MeOH (150 mL). The mixture was stirred at 15°C for 0.5 h, 2N aqueous HCl was cautiously added to bring the pH to 3, and the resulting mixture was stirred for 10 min. Then, the pH was adjusted to 6.5-7 with saturated aqueous NaHCO3, MeOH was evaporated, and H2O (50 mL) was added. The mixture was washed with EtOAc (2x150 mL), basified with K2CO3, and extracted with EtOAc (2x130 mL). The organic extracts were dried, filtered, and concentrated to give DMT.




All italic words are modifications of the original procedure.
The modification of the original procedure is quite simple, calculate the molar weight of tryptamine (either by hand or Merck Index or with a computer programm) multiply it with the molar amount and you get the weight of tryptamine you have to use. That's all, now try it yourself..........


Yields should be similiar to the original procedure (88%, about 4.3 g) but expect rather 2-3 g than 4 g if you do it the first time.

Good luck!  8)



Title: NaBH4 in H2O?
Post by: freakyDMT on May 29, 2003, 08:09:00 AM
you say in the synthese to drip simultaneously a solution of formaline in MeOH and a solution of NaBH4 in H2O (70 ml),is this correct or do you mean MeOH instead of H2O?
Title: No i think it meant H2O.H2O doesn't hurt ...
Post by: raffike on May 29, 2003, 10:28:00 AM
No i think it meant H2O.H2O doesn't hurt NaBH4.Formalin used also contains water so process isn't anhydrous anyway,why should it be?MeOH could/should be substituted with EtOH or IPA imo cuz NaBH4 reacts with MeOH

Title: Right out of the abstract.
Post by: ClearLight on May 29, 2003, 11:02:00 AM
That NaBH4 in H20 is right out of the article.. raffike is right about MeOH as well...  That is not an error.

Title: But all that makes synth of DMT out of ...
Post by: raffike on May 29, 2003, 11:15:00 AM
But all that makes synth of DMT out of tryptophan worth considering.Whole process doesn't even need vacuum distillation apparatus.Tryptophan,which is bought for pennies,is easily decarboxylated to tryptamine.Sodium borohydride might be bitch to get but raf could get it quite easily as it's not watched over here.Other chemicals are cheap and available also.This just might become raf's next project.

Title: Reductive Methylation
Post by: Rhodium on May 29, 2003, 06:02:00 PM
If you prepare an aqueous solution of NaBH4 immediately before putting it into an addition funnel and use it in this reaction, then it will keep long enough - just not several hours.

The article, which now can be read in its entirety at

Tetrahedron 57(6), 1041-1048 (2001) (https://www.thevespiary.org/rhodium/Rhodium/pdf/tryptamine.nabh4.methylation.pdf)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/tryptamine.nabh4.methylation.pdf), references the sodium borohydride reductive methylation of tryptamines from

Patent ES2084560 (http://l2.espacenet.com/dips/viewer?PN=ES2084560&CY=gb&LG=en&DB=EPD)

, where the procedure is largely the same.

Why can the authors of this article now succeed where so many have failed, and use the lowly and unselective reducing agent NaBH4 for the reductive methylation of tryptamine, and in addition to that even get yields of 80-90%? The answer lies in their use of low temperatures (-15°C, attainable with a cooling bath filled with sodium chloride/crushed ice in a 1:3 ratio), as well as the fact that they are adding the formaldehyde and NaBH4 solutions slowly, simulataneously and separately.

By performing the reaction cold, they are weakening the reducing power of NaBH4 so that it might reduce imines slightly faster than aldehydes, and by introducing both the aldehyde and NaBH4 slowly and in parallell they are insuring that as much as possible of the added formaldehyde manages to react with the tryptamine (and/or the intermediate N-methyl-tryptamine, NMT) to form an imine before the NaBH4 reduces the formaldehyde to methanol. All this is logical, but I couldn't imagine that it was possible to make it work that good by playing with the reaction conditions...
Title: Amazing...
Post by: ClearLight on May 30, 2003, 01:05:00 AM
Chemistry is truely amazing!!! thx! rhodium for the goodies..

Title: Strange
Post by: Barium on May 30, 2003, 02:46:00 AM
What I find peculiar is that the imine formation is so much faster than the aldehyde reduction at that low temp. Since the yield of the N,N-dimethylated tryptamine is in the 80-90% range the imine must be formed immediately. When for example methylamine and benzaldehyde is reacted one is still recommended to let them react for an hour or so to allow the reaction to go to completion. Here the reducing agent is added simultanously with the carbonyl compound and the yield is sky-high.

Title: +15 or -15 ?
Post by: freakyDMT on May 30, 2003, 05:06:00 AM
it has to be -15°C instead of 15°C,doesn't it? there is is a major difference between those to, see

Post 436291 (https://www.thevespiary.org/talk/index.php?topic=13164.msg43629100#msg43629100)

(Lego: "What am I not seeing here?", Tryptamine Chemistry)
Title: Actually the article says 15 C not -15 ...
Post by: raffike on May 30, 2003, 05:10:00 AM
Actually the article says 15 C not -15 C.Anyways wouldn't it be better to add formaldehyde first and then NaBH4?Probably no,even though raf's non-chemist brain says it might as it would leave imine some time to form.

Title: Someone plz test this...
Post by: ClearLight on May 30, 2003, 01:19:00 PM
It's SUCH a no brainer w/ these simple chems could someone please test and report?  ( I can't get to it immediately or I would  :( )

Title: It would take at least a month to get all...
Post by: raffike on May 30, 2003, 11:03:00 PM
It would take at least a month to get all needed chemicals if raf had money,but at the moment he's nearly broke.But raf hopes to check this out in near future.

Title: Shiff base shite
Post by: L42L on September 09, 2003, 12:11:00 PM
Building from Raffike's 'non-chemist' thoughts and what Barium finds 'piculiar', would it be wize to promote imine formation before the reduction? If so, maybe we could microwave the tryptamine/formaldehyde over clay to form the imine first before moving on to the reduction? Would formaldehyde behave in the microwave(B.P.?)?

See the microwave chem section at rhodium, the sodium borohydride on wet clay (tetrahedron 54 6293-8) for the imine formation i'm yakin about.

Lurk
Title: NaBH4 in water?
Post by: koalaa on February 26, 2004, 09:24:00 AM
The opportunity to try the tryptamine/formaldehyde/NaBH4 DMT synthesis has presented itself.  The procedure is (from Lego, 5/29/03):

A solution of 35% formaldehyde (35 mL, 416 mmol) in MeOH (35 mL) and a solution of NaBH4 (5 g, 132 mmol) in H2O (70 mL) were added dropwise, simultaneously, at 15°C to a well-stirred solution of tryptamine (4.166 g, 26 mmol) in MeOH (150 mL). The mixture was stirred at 15°C for 0.5 h, 2N aqueous HCl was cautiously added to bring the pH to 3, and the resulting mixture was stirred for 10 min. Then, the pH was adjusted to 6.5-7 with saturated aqueous NaHCO3, MeOH was evaporated, and H2O (50 mL) was added. The mixture was washed with EtOAc (2x150 mL), basified with K2CO3, and extracted with EtOAc (2x130 mL). The organic extracts were dried, filtered, and concentrated to give DMT.

There are a series of concerns with this, however.  First, formaldehyde reacts with methanol, and the only available formaldehyde is in water solution.  So the procedure will be attempted with 37% formaldehyde in water, rather than methanol.  The second concern is with the NaBH4 in water.  NaBH4 reacts explosively with water, so how can a solution of 5 g in 70 mL be safely made?  Instead of making a water solution, an IPA solution is being considered.  Would there be an undesirable difference between the two solvents?  The last question concerns the statement 'The mixture was washed with EtOAc (2x150 mL), basified with K2CO3, and extracted with EtOAc (2x130 mL).'  The pKa DMT is something like 8.86, so to what extent is the basification with K2CO3 taken?  pH 9, 10, 11?  Also, should concentration of the organic extracts be conducted with rotovap?

These two modifications, if valid, don't really change the reaction extensively.  Using water/formaldehyde and NaBH4/IPA would be essentially the same, upon mixing with the tryptamine/MeOH, as MeOH/formaldehyde and NaBH4/H2O, the only difference being presence of IPA.

Some comments on these ideas would be welcomed.  Especially before the procedure is eXecuted, circa 1 week from the present.
Title: The link to Lego's post is Post 436291 :-P...
Post by: Lilienthal on February 26, 2004, 09:33:00 AM
The link to Lego's post above in this thread is

Post 436291 (https://www.thevespiary.org/talk/index.php?topic=13164.msg43629100#msg43629100)

(Lego: "What am I not seeing here?", Tryptamine Chemistry)
 :P

This is a hypothetical procedure and I'm very very sure that it doesn't work because of cyclization (UTFSE). At least it's nothing for a beginner without adequate analytical methods to determine the products of this synthesis.
Title: NaBH4 doesn't react explosively with plain...
Post by: Lilienthal on February 26, 2004, 09:37:00 AM
NaBH4 doesn't react explosively with plain water (without a strong acid), it's a pretty slow reaction.  Formaldehyde in methanol shouldn't be a problem because the reaction is reversible.
Title: Successful synthesis, reduced yields.
Post by: koalaa on April 14, 2004, 09:30:00 PM
Title: pretended
Post by: elfspice on April 15, 2004, 04:51:00 AM
one went to all that effort to write a nice atemporal apersonal report and sticks just one (although i was a little cursory in my perusal) personal attribution of activity and intent (mind you, it was a little to broad in the scope that it introduced to be pretending really) it just ruins everything... the info in there is good, please repost with more careful editing.
Title: please repost SWIY's experiance edited, SWIM...
Post by: Madog on June 01, 2004, 06:32:00 PM