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Benignium
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Decarboxylation of L-tryptophan in DMSO
This is a write up of my third attempt at decarboxylating tryptophan to yield tryptamine. Please note that so far I haven't been able to confirm
whether or not the product of this preparation is actually tryptamine.
(The first attempt was made by heating a copper chelate prepared by combining aqueous solutions of copper(II) acetate and L-tryptophan. Work up was an
absolute dumpster fire and the approach was quickly abandoned. For the second attempt I prepared acetophenone to act as a catalyst and got promising
results. This second attempt was then reproduced and documented more thoroughly.)
20 grams of commercial L-tryptophan, 175 grams of DMSO and 5 grams of acetophenone were placed in a 1000 mL Erlenmeyer. The vessel was purged with
argon and gradual heating was commenced with strong stirring. Vigorous effervescence was observed starting at 110 deg. C that died down in minutes as
all of the tryptophan eventually dissolved and the mixture became completely clear. The mixture was further heated at a steady pace to 175 deg. C over
40 minutes with no apparent reaction taking place. The mixture had a mild unpleasant odor reminiscent of boiled brussels sprout.
     
The solution was cooled to room temperature and treated with 60 grams of acetic acid and roughly 300 mL in total of water. The aqueous phase
thoroughly washed with 7x25 mL portions of DCM and treated with 54 grams of sodium bicarbonate. The aqueous phase was twice more washed with 25 mL
portions of DCM and finally basified with 40 grams of NaOH. The mixture was extracted with 3x50 mL DCM and combined extracts were stripped of solvent.
The residue was washed twice with 50 grams of boiling acetonitrile. The product is separated by filtration as 10.0 grams (63.7%) of cream colored
crystalline powder and using a steel spatula shaped into the form of poor housing.
        
However, as mentioned in the beginning of this post I haven't confirmed that what I have is indeed tryptamine. My melting point tests utilizing a test
tube and a hotplate have been a failure, but it seems that in a beaker the product seems to melt starting at about 110 deg. C and shortly starts to
decompose and sublime depositing as a tan dusting with some tiny crystals of same color. If anyone can advise me on how to better and more reliably
find melting point ranges on the cheap or ways to identify tryptamine I would be very grateful.
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Antigua
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Wow, these are some really good results. You can buy capillary tubes for no more than 10USD per 200 on AliExpress, they work great as a way of melting
point determination. Just seal them on one side, load some product in, seal on the end side and chuck into a thin layer of mineral oil that is being
stirred and heated alongside an electrical thermocouple. Does your product smell of acetophenone? Did you cool down the solution before basyfing? Was
there any oil formed? You could try the purification via oxalate method mentioned in one of the millions posted threads about tryptamine. That, or the
fumarate, both are reported to work well.
Great work.
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Benignium
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Thank you Antigua! I've been meaning to get capillary tubes for a long time now but I thought I might get by using a small test tube. No such luck, it
seems.
The product does not smell at all like acetophenone (the reaction mixture does, though). There is a subtle but distinct smell somewhat reminiscent of
N,N-dimethyltryptamine, which I've had the good fortune to smell before. The mixture was only ever cooled down to room temperature before adding
something to it. Never really any oil to speak of, save for the product "oiling out" as a thick red gel once DCM was removed prior to washing with
MeCN.
I've been reading through the other threads and will be trying the oxalate method next! 
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mackolol
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If you did it in plain acetophenone without any solvent, the yield would be higher.
But anyways, great reaction. 
[Edited on 5-11-2020 by mackolol]
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Benignium
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Thank you mackolol!
Right now I do not view using acetophenone as the solvent as worthwhile; acetophenone is something I have to make whereas DMSO I can still easily
order online (knock on wood!). I am also going to need acetophenone for other experiments such as the Willgerodt-Kindler. Anything over 50% would be
plenty for me, all things considered.
I dried some oxalic acid dihydrate in the oven at 100 deg. C for a couple of hours and dissolved 5 grams of my product as well as 5 grams of the dried
acid (technical grade, turned grey from blackened impurity) in ~37 grams of methanol. White crystals started forming immediately after filtering the
hot solution. I will give the test tube melting point thing one more shot once I've got the base again.
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mr_bovinejony
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How many times did you extract the post reaction mixture with acetic acid? You had mentioned using 60 grams of acetic acid and 300 mls of water, but I
dont think the water would be any good if it's not acidic
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ArbuzToWoda
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Interesting. I tried to follow your procedure as closely as possible, but had to tweak a couple of things.
1. My largest sep funnel is 250ml so I washed all of the solution in 2 batches using total of over 250ml DCM (around 5x25ml each time). Right now I'm
after the addition of bicarbonate, extraction with DCM (actually no brown or gooey stuff came out after adding all of the bicarbonate, so I'm not sure
if the washing is neccessary) and basification. After adding 40g of NaOH in 100ml of water this is what I'm left with (attachement 1). The rest of
attachements are:
The clear, yellow solution is what I obtained after all of the DCM washings, before the addition of bicarb
The dark solution is the reaction mixture after adding it to 60g of GAA in 300g water.
What do you guys suggest I do with this red/opaque mixture? I'm also a bit confused, many many sources claim that tryptamine is very weakly soluble in
DCM, so how were you able to extract it using it? What's the opaque stuff? Tryptamine chemistry leaves me so dumbfounded every time, yet I've done it
a couple of times already.
Also I was a little confused, you were left with oil after evaporating the DCM that you used to extract the tryptamine after basification? It suddenly
turned into a nice solid after washing with acetonitrile? What's the photo with precipitate? Thanks in advance to y'all.
  
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mackolol
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Maybe try to heat it up when adding NaOH. Always, when after addition of NaOH solution the whole thing doesn't crash out nicely, I add more NaOH in
solid form to it. At first, I have thought, that it just needs more NaOH to break the buffer, so I just added straightly NaOH as I was too lazy to
dissolve it once again. But it turns out that it's the heat of exothermic dissolution that helps the reaction, as probably it breaks the
tryptamine-acetophenone ketimine leaving tryptamine crystals, contaminated with just the same coloured oil as in your 1st attachment. After filtering
the whole thing, the oil just goes with liquids.
So don't cool your NaOH solution before adding.
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ArbuzToWoda
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Quote: Originally posted by mackolol  | Maybe try to heat it up when adding NaOH. Always, when after addition of NaOH solution the whole thing doesn't crash out nicely, I add more NaOH in
solid form to it. At first, I have thought, that it just needs more NaOH to break the buffer, so I just added straightly NaOH as I was too lazy to
dissolve it once again. But it turns out that it's the heat of exothermic dissolution that helps the reaction, as probably it breaks the
tryptamine-acetophenone ketimine leaving tryptamine crystals, contaminated with just the same coloured oil as in your 1st attachment. After filtering
the whole thing, the oil just goes with liquids.
So don't cool your NaOH solution before adding. |
Wouldn't it be plausible to think that heating or refluxing this solution for a bit would lead to the same effect? Unless the imine can only be broken
at the same moment as adding the NaOH, but I would call such claim a very brave one.
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mackolol
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It's just about the heat evolved so, yes. But why would you have to reflux it, if the heat from NaOH addition is just enough and you have to add the
NaOH anyways...
This is just slight modification of the procedure, instead of adding dilute and cooled NaOH solution, add hot NaOH solution or solid NaOH.
I mean... it's obvious isn't it?
[Edited on 7-11-2020 by mackolol]
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ArbuzToWoda
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| Quote: Originally posted by mackolol | It's just about the heat evolved so, yes. But why would you have to reflux it, if the heat from NaOH addition is just enough and you have to add the
NaOH anyways...
This is just slight modification of the procedure, instead of adding dilute and cooled NaOH solution, add hot NaOH solution or solid NaOH
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I'm considering what to do now, after I've already added the hydroxide. I wouldn't like to add more, as the solution is already really concentrated in
salts, DMSO and leftover hydroxide. I might try what you suggest tomorrow. Just heat it up, huh? Interesting.
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mackolol
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Yeah, do it, as far as I remember, you heated the mixture once when doing the oxalate thing and it also resulted in some oil formation.
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Benignium
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| Quote: Originally posted by ArbuzToWoda | | ...actually no brown or gooey stuff came out after adding all of the bicarbonate, so I'm not sure if the washing is neccessary...
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No brown or gooey stuff for me either! I do not actually know if it's absolutely necessary to wash with DCM after adding the bicarbonate, but seeing
as the pKa of tryptamine is 10.2 I figured it wouldn't hurt. Some tryptamine definitely gets washed but I suspect the amount is not significant.
| Quote: Originally posted by ArbuzToWoda | | What do you guys suggest I do with this red/opaque mixture? I'm also a bit confused, many many sources claim that tryptamine is very weakly soluble in
DCM, so how were you able to extract it using it? |
I'm fairly certain you could just go ahead and do the DCM extractions now that you've added the NaOH. I, too, found conflicting information on the
solubility of the base in DCM but found that it's actually quite good. I haven't tried it, but I have read that tryptamine is "insoluble" in
chloroform, which originally led me to believe the same applies for DCM.
| Quote: Originally posted by ArbuzToWoda | | Also I was a little confused, you were left with oil after evaporating the DCM that you used to extract the tryptamine after basification? It suddenly
turned into a nice solid after washing with acetonitrile? What's the photo with precipitate? Thanks in advance to y'all. |
Yes, that's pretty much how it happened. Once practically all of the DCM had evacuated the oil started to solidify into a tan, vaguely crystalline but
waxy-looking mass. I didn't take a picture of it, unfortunately, but the picture with the precipitate under a layer of red MeCN was taken immediately
after adding MeCN and stirring for some seconds. Outright crystals formed the moment MeCN touched the oil.
I'm away from home right now but I will carry out the rest of the oxalate purification and see if that helps me confirm that the product contains
tryptamine. Be weird if it didn't, right?
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ArbuzToWoda
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Are you going to perform or give it to someone to perform the dimethylation? That would be an okay way to test the identity of your product. Do you
think the acetonitrile could be substituted with anything else? Or whether it's needed at all? Maybe the residue could be just dissolved in a tiny
quantity of methanol and then fumaric-acid-saturated acetone or oxalic acid acetone solution could be added?
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ArbuzToWoda
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Extracted the red goop with 120ml DCM. I figured more wouldn't be neccessary, as pretty much all of the color was in the DCM washing after the first
50ml. Evaporated it and I'm left with a red goopy gel that refuses to crystallize. I don't think that there's much DCM left there, even when heated up
to 100C there wasn't any boiling you'd see if there was CH2Cl2 left. Maybe the acetonitrile really saves the day? No idea.
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mackolol
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The acetonitrile is very good idea. I didn't know that way, thanks benignium, it surely comes in handy, when performing this reaction.
The fact that it isn't soluble in chloroform but is in DCM is also interesting, if true...
This would explain why, I would experience some losses when washing acidic tryptamine solution with DCM, but not with chloroform
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ArbuzToWoda
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| Quote: Originally posted by mackolol | The acetonitrile is very good idea. I didn't know that way, thanks benignium, it surely comes in handy, when performing this reaction.
The fact that it isn't soluble in chloroform but is in DCM is also interesting, if true...
This would explain why, I would experience some losses when washing acidic tryptamine solution with DCM, but not with chloroform
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No, that still doesn't make any sense. Tryptamine in it's salted form is protonated and therefore cannot be possibly soluble in DCM in amounts greater
than miniscule.
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mackolol
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| Quote: Originally posted by ArbuzToWoda |
No, that still doesn't make any sense. Tryptamine in it's salted form is protonated and therefore cannot be possibly soluble in DCM in amounts greater
than miniscule. |
But the salt is acetate, so it's organic, maybe that's the reason, organic salts should be more soluble in organic solvents than inorganic ones.
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ArbuzToWoda
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| Quote: Originally posted by mackolol | | Quote: Originally posted by ArbuzToWoda |
No, that still doesn't make any sense. Tryptamine in it's salted form is protonated and therefore cannot be possibly soluble in DCM in amounts greater
than miniscule. |
But the salt is acetate, so it's organic, maybe that's the reason, organic salts should be more soluble in organic solvents than inorganic ones.
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If that were the case then I would be inclined to believe that salts such as sodium acetate would be even a bit soluble in organic solvents. The thing
is, it doesn't even dissolve in such a MORE polar solvent as acetone. Therefore it cannot possibly dissolve in something even less polar. It's not a
matter of being organic or inorganic, but of having a negative or positive charge. Tryptamine exists only as a molecule with
R-NH3+ in the acetate form and therefore there's just no way for it to migrate into a layer that does not at all encourage
electrolytic dissociation. How possibly could charges move around in a solvent that is as non-polar as DCM?
I might be wrong, but so far I'm pretty confident in these speculations.
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mackolol
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Sodium acetate does dissolve in acetone, its solubility is low, but it does 0,5g/kg. And sodium acetate includes metal ion, which won't dissolve so
likely in oganic solvents. Tryptamine acetate is fully organic.
I'm not sure either, if it is soluble in DCM, but I don't deny it. Maybe someone who knows better can tell if tryptamine acetate could be soluble in
DCM.
Maybe tryptamine reacts with DCM as DMT does and although it reacts extremely slowly, in form of ion it may react faster .
If not, then it might be its solubility in DCM/water solution when freebased.
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mr_bovinejony
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Tryptamine acetate is not soluble in dcm. I do my pulls from the post decarb mixture with store bought vinegar and then do a few dcm washes. A uv
light on the dcm washes shows no glow like the aqueous solution of tryptamine acetate does.
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mackolol
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| Quote: Originally posted by mr_bovinejony | | Tryptamine acetate is not soluble in dcm. I do my pulls from the post decarb mixture with store bought vinegar and then do a few dcm washes. A uv
light on the dcm washes shows no glow like the aqueous solution of tryptamine acetate does. |
Oh that's good. So it seems that for me it was some technical problem with DCM, although I have done it few times, it may be some sort of accident.
[Edited on 10-11-2020 by mackolol]
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Benignium
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| Quote: Originally posted by mr_bovinejony | | How many times did you extract the post reaction mixture with acetic acid? You had mentioned using 60 grams of acetic acid and 300 mls of water, but I
dont think the water would be any good if it's not acidic |
What I meant to say was that to the reaction mixture was straight added 60 grams of acetic acid in some 300 milliliters of water. The point is to
indeed make the mixture acidic so that impurities can be washed off using DCM.
| Quote: Originally posted by ArbuzToWoda | | Are you going to perform or give it to someone to perform the dimethylation? That would be an okay way to test the identity of your product. Do you
think the acetonitrile could be substituted with anything else? Or whether it's needed at all? Maybe the residue could be just dissolved in a tiny
quantity of methanol and then fumaric-acid-saturated acetone or oxalic acid acetone solution could be added? |
I am planning to react the product with iodomethane (need to prepare some first, but that shouldn't take too long as I already have everything I need)
and go from there. I quite dislike the uncertainty going into it but that's what I get for lacking prowess, I guess.
I'm sure the acetonitrile isn't strictly necessary, in fact I think one could just skip it and go on to do the oxalic acid thing. It just seems to be
an efficient way to get rid of most of the remaining impurity.
After trying out the oxalic acid method twice, it does seem to produce very clean material. It can be a bit annoying and time consuming to do, though.
Here's some 6 grams of the oxalate salt:
And here is some freebase:
Although the base looks almost yellow they're both the same off-white color. The automatic white balance of my phone camera just sucks sometimes.
I once more tried to melt the purified base in a beaker as well as by immersing it in oil in a sort of diving bell made from a glass pasteur pipette.
Unfortunately it behaves exactly the same. Will not melt, eventually starts to sublime (>130 deg. C) and with stronger heating decomposes (>150
deg. C). One of the salts might work better.
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mr_bovinejony
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Well that's a new one, I've always seen it extracted with portions of acid, never seen the whole mixture acidified that way! But it looks like it
worked fine for you. Maybe since your solvent is dmso is ends up cleaner. I mostly use straight acetophenone which is a disaster every time.
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ArbuzToWoda
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There's no use trying to extract such a mixture using acid, as DMSO is miscible with water. What I wonder is - I'm still left with a red goo after
evaporating the DCM and letting it sit in the freezer for a couple of days. I measured it to weigh around 15g and added 60ml of methanol and 5g of
dried oxalic acid, as I didn't have any more. I'll dry and add some more tomorrow. @Benignium, how exactly did you do the oxalic acid purification?
Just dumped it all into the methanol and heated up? And then it started crystallizing?
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