Hive Tryptamine Chemistry

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	Tryptamine Chemistry

All 38 posts Subject: KrZ DMT syntheses experience Please login to post New Down

freakyDMT
(Stranger)
05-23-03 21:14
No 435022
      KrZ DMT syntheses experience

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.

Rhodium
(Chief Bee)
05-23-03 23:57
No 435056
User Picture       DMT from Tryptamine/NaBH3CN/37% HCHO
(Rated as: excellent)

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.rhodium.ws/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%).

freakyDMT
(Stranger)
05-24-03 03:34
No 435084
      Thank you,RHODIUM,you realy helpt me ...

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?

Rhodium
(Chief Bee)
05-24-03 21:55
No 435246
User Picture       acetic acid & sodium methoxide

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?

freakyDMT
(Stranger)
05-25-03 10:12
No 435368
      What i mean is see post 285474 03-20-02 were...

What i mean is see Post 285474 (Rhodium: "Tryptamine -> DMT w/ formaldehyde/NaBH3CN", Tryptamine Chemistry) were they also use sodiummethoxide in the synthese.

ClearLight
(Hive Addict)
05-25-03 15:43
No 435414
      Cyanoborohydride required?

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

Infinite Radiant Light - THKRA

Rhodium
(Chief Bee)
05-25-03 16:10
No 435423
User Picture       Reductive methylation of tryptamine

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 (Rhodium: "Tryptamine reductive alkylation with NaBH(OAc)3", Tryptamine Chemistry)

freakyDMT
(Stranger)
05-25-03 18:29
No 435456
      tryptamine v. tryptamine HcL

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.

Rhodium
(Chief Bee)
05-25-03 19:19
No 435463
User Picture       Methoxide Mystery Solved

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.

freakyDMT
(Stranger)
05-25-03 20:48
No 435471
      Rodium,i think the sodiumcyanoborohydride is...

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?

Rhodium
(Chief Bee)
05-25-03 22:42
No 435494
User Picture       pH & bookmarks

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= (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.

Chimimanie
(Hive Bee)
05-25-03 22:54
No 435495
User Picture       Great DMT synth

Rhodium I like this DMT synthesis, it is great!

So simple and yet effective!

DMT easy way...

ClearLight
(Hive Addict)
05-28-03 02:22
No 435976
      Acetic acid and trioxy?

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...

Infinite Radiant Light - THKRA

Rhodium
(Chief Bee)
05-28-03 02:43
No 435988
User Picture       2 mL HOAc is ok...

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.

Lego
(Newbee)
05-28-03 09:59
No 436057
User Picture       Please UTFSE

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 wink

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........

The candle that burns twice as bright burns half as long

raffike
(Hive Addict)
05-28-03 18:59
No 436129
User Picture       cyanoboro is way too expensive to play with.

cyanoboro is way too expensive to play with.
Post 431982 (Lego: "Article on DMT derivate synths", Tryptamine Chemistry)

For those about to synth,we salute you

ClearLight
(Hive Addict)
05-28-03 19:02
No 436131
      thx

For that indirect reference to the article you posted smile !

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!

Infinite Radiant Light - THKRA

raffike
(Hive Addict)
05-28-03 19:16
No 436136
User Picture       think moles not grams

think moles not grams
PS you want 9b without that sulfonylmethyl group

For those about to synth,we salute you

ClearLight
(Hive Addict)
05-29-03 05:06
No 436251
      right raffike

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???!!!"

Infinite Radiant Light - THKRA

Lego
(Newbee)
05-29-03 10:17
No 436291
User Picture       What am I not seeing here?
(Rated as: excellent)

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! cool

The candle that burns twice as bright burns half as long

freakyDMT
(Stranger)
05-29-03 15:09
No 436342
      NaBH4 in H2O?

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?

raffike
(Hive Addict)
05-29-03 17:28
No 436363
User Picture       No i think it meant H2O.H2O doesn't hurt ...

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

For those about to synth,we salute you

ClearLight
(Hive Addict)
05-29-03 18:02
No 436369
      Right out of the abstract.

That NaBH₄ in H₂0 is right out of the article.. raffike is right about MeOH as well... That is not an error.

Infinite Radiant Light - THKRA

raffike
(Hive Addict)
05-29-03 18:15
No 436374
User Picture       But all that makes synth of DMT out of ...

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.

For those about to synth,we salute you

Rhodium
(Chief Bee)
05-30-03 01:02
No 436431
User Picture       Reductive Methylation

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.rhodium.ws/pdf/tryptamine.nabh4.methylation.pdf), references the sodium borohydride reductive methylation of tryptamines from Patent ES2084560, 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...

ClearLight
(Hive Addict)
05-30-03 08:05
No 436518
      Amazing...

Chemistry is truely amazing!!! thx! rhodium for the goodies..

Infinite Radiant Light - THKRA

Barium
(Hive Addict)
05-30-03 09:46
No 436542
      Strange

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.

Freaky

freakyDMT
(Stranger)
05-30-03 12:06
No 436561
      +15 or -15 ?

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

raffike
(Hive Addict)
05-30-03 12:10
No 436562
User Picture       Actually the article says 15 C not -15 ...

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.

For those about to synth,we salute you

ClearLight
(Hive Addict)
05-30-03 20:19
No 436646
      Someone plz test this...

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 frown )

Infinite Radiant Light - THKRA

raffike
(Hive Addict)
05-31-03 06:03
No 436728
User Picture       It would take at least a month to get all...

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.

For those about to synth,we salute you

L42L
(Stranger)
09-09-03 19:11
No 457947
      Shiff base shite

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

koalaa
(Stranger)
02-26-04 17:24
No 491255
      NaBH4 in water?

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.

Lilienthal
(Moderator)
02-26-04 17:33
No 491256
User Picture       The link to Lego's post is Post 436291 :-P...

The link to Lego's post above in this thread is Post 436291 (Lego: "What am I not seeing here?", Tryptamine Chemistry) tongue

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.

Lilienthal
(Moderator)
02-26-04 17:37
No 491257
User Picture       NaBH4 doesn't react explosively with plain...

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.

New: Posts 1 - 36 of 38 Subject: KrZ DMT syntheses experience Top Down

koalaa
(Stranger)
04-15-04 04:30
No 500899
      Successful synthesis, reduced yields.
(Rated as: pretending illegal activity)

The synthesis outlined in the message 'NaBH4 in water' was attempted as follows (1/4 scale):

A solution of 37% formaldehyde in H2O (8.6 mL, 104 mmol) in MeOH (9.5 mL) and a solution of NaBH4 (1.25 g, 33 mmol) in H2O (17.5 mL) were added dropwise, simultaneously, at 15°C to a well-stirred solution of tryptamine (1.06 g, 6.5 mmol) in MeOH (37.5 mL). The mixture was stirred at 15°C for 0.5 h, 6N aqueous HCl was cautiously added to bring the pH to 3.02, 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 on the rotovap, and H2O (12 mL) was added. The mixture was washed with EtOAc (2x37.5 mL), basified to pH 10.4 with K2CO3, and extracted with EtOAc (2x32.5 mL). The organic extracts were dried, over K2CO3, vacuum filtered, and EtOAc evaporated to give DMT. Products were obtained in (1) 0.46 g (2.44 mmol 37.6 % yield) and (2) 0.58 g (3 mmol, 46% yield).

Results: The entire process was completed twice, T1 and T2. Two differences existed between these trials. In T1 the simultaneous addition of NaBH4 and formaldehyde was rapid (ca. 2 minutes), whereas in T2 the addition took at least 7 minutes. In T1 the rotovap step was minimised to 45 minutes, whereas in T2 it was 1.5 hours.
The T1 product was crystalline, whereas the T2 product was an oil that solidified upon freezing and repeated collection with a razor in the evaporating dish. Both products were analyzed with GC-MS. Positive identification of the N,N-DMT product was established by comparing the spectrum with a reference from http://spectra.galactic.com/. Molecular ion peak is present at 188 m/z, with the largest peak at 58 m/z. The T1 product was 99.0% pure (by integration), whereas the T2 product was 91.6% pure. The T2 sumultaneous addition of reagents was executed with more precision than the T1, so it is probable that the longer rotovap time was responsible for the lower purity.
The T1 product was, in addition, analyzed with 1H NMR, in d-acetone, 300 MHz. The indole region from 7-9 ppm was unchanged from the tryptamine starting material. However, the production of N,N-DMT was supported by appearance of two triplets between 2 and 3 ppm (corresponding to the CH2) and a singlet at slightly under 2 ppm (corresponding to the double methylation). Integration of the singlet was 6 units, and each triplet 2 units.
This procedure shows promise...good yield can be obtained (46%) even in sub-optimal conditions. Furthermore, reagents are easy to obtain, and are inexpensive.
Some developments might include finding a way to avoid the rotovap step, since this appears to have an adverse effect on product purity. Instead of dissolving the tryptamine in MeOH, H2O will be used as solvent in a future trial. It is interesting to note that the original paper

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

reports yields of 80-90%. The difference between that procedure and this present one is a large sulfur-containing group at the 4-position on the benzene ring. Could this have activating effects that are not seen when the ring is unsubstituted?

Maybe the best conclusion to make from this venture is that individuals could do well to give up the difficult and time-consuming bromination/methylation/reduction procedures (eg. NaBH4 reduction of Keto-DMT thread), if the goal is production and not chemistry games. This procedure takes a total of 3.5 hours, does not depend on dry solvents, uses only one nasty reagent (formaldehyde), and costs very little. If the trial with water as solvent instead of methanol is successful, then 45 minutes will be taken off preparation time, and the rotovap step will be avoided. Product purity is generally high. But even when compromised (91.6%), the contaminants were identfied as N-methyltryptamine and unreacted tryptamine, so there is low potential for toxic byproducts or retention of formaldehyde.

elfspice
(Hive Bee)
04-15-04 11:51
No 500948
User Picture       pretended

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.

Madog
(Stranger)
06-02-04 01:32
No 510806
      please repost SWIY's experiance edited, SWIM...
(Rated as: Read the FAQ)

please repost SWIY's experiance edited, SWIM is very interested smile

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