my first decarboxylation in DMSO

[element109]

Last night I had a strange dream:

15 gr of L-tryptophan were dissolved in hot water and mixed with a hot solution of 20 gr Cu(II)acetate.H2O ; the resulting blue precipitate filtered off and carefully dried in an oven on low heat. There was obtained 29 gr of TRP Cu-chelate.
 
This was mixed with DMSO in a RB flask with condensor and the resulting suspension heated at 175°C for 10 minutes. I was left with a darkbrown solution and a red precipitate which was assumed to be copper. It was allowed to cool to +-~50°C (it was still warm but i could hold the flask), and filtered.
Water was added to dilute the filtrate,
next, cold 10% NaOH solution was slowly added until pH=12 ,
the solution turned cloudy.
Petroleum ether was added resulting in a huge emulsion.
I wanted to saturate the aqueous layer with NaCl, but none was at hand so I added epsom salts (MgSO4.7H20)
The whole thing turned into a heavy sludge. Vacuum-filtered  this, was left with a large amount of greyblack crud.

From the filtrate i separated the pet.ether, dried it and sat'd it with HCl gas, it turned red and a teenie weenie bit precipitated. Apparantly tryptamine base is not soluble in most organic solvents.

I used an improvised vacuumfiltration apparatus and coffee filters, and an amount of white precipitate settled to the bottom aqueous layer after filtration that went through the ribbled bottom of the filters. This ppt. was filtered using normal gravity filtration, dried and weighed: 1.5grs of lightbrown crystals.

I washed the crud twice with boiling water (to remove by-product indole) and the crud was added to a beaker with water, and 2N HCl was slowly added until pH=3.

Filtered this, obtained a colorless filtrate and a black crud (which is assumed to be carbon?)

The filtrate was concentrated and it gave an (unweighed)amount of reddish-brown crystals.
This should contain the tryptamine.HCl, not? How should i proceed to clean this mess?


From the lightbrown crystals ppt. from the aqueous layer i still have to dream the mp.
This was my first dream with this procedure, i shouldn't have added the epsom salts i know..

e109

[foxy2]

"How should i proceed to clean this mess?"

Purification of Tryptamine

A good way to purify tryptamine without having to resort to distillation under strong vacuum is to dissolve the crude tryptamine hydrochloride in water, adjust the pH to between 7.6 and 8.2 and extract the solution with chloroform. The pH is then adjusted to 14 with NaOH and the pure tryptamine is filtered off with suction and air dried.

From

https://www.thevespiary.org/rhodium/Rhodium/chemistry/tryptophan.html

I hate my government, does this mean I'm a terrorist??

[Chromic]

That is a confusing purification writeup... anyone care to it explain what it's trying to say? Do they take aqueous solution of T.HCl, then basify to pH 7, then wash with chloroform (discard the chloroform), then basify the aqueous to pH 14 and filter to claim Tryptamine freebase?

[Antoncho]

It all looks good up to this point:

Petroleum ether was added resulting in a huge emulsion.

Pet ether is a very non-polar solvt and probably isn't very food for xtacting amines - i might bee wrong though.

You probably should try to use some other solvt, adjusting pH could help too, but you'll have a hard time figuring that unless you've got a pH meter.

I wanted to saturate the aqueous layer with NaCl, but none was at hand so I added epsom salts (MgSO4.7H20)
The whole thing turned into a heavy sludge.

Wrong! Always use NaCl. Probably unreacted tryptophane formed an insoluble w/Mg++ (By chance, you're certain it'a hydrate salt?)

From the filtrate i separated the pet.ether, dried it and sat'd it with HCl gas, it turned red and a teenie weenie bit precipitated. Apparantly tryptamine base is not soluble in most organic solvents.

Isn't tryptamine hcl soluble somewhat in non-polars? Well, not in pet. ether, i'd guess.

As for a way to purify it - recrystallize it, but ask someone else what solvent to use     . A good thing would bee to know if it's really tryptamine - that is actually of a primary concern

And - please, follow my advice - always record all the weights and volumes in the course of your experiment - otherwise it becomes worthless for both the future generations and further optimization.

Looking forward to hear the sequel of your dream ,

Antoncho

[hypo]

This was mixed with DMSO in a RB flask with condensor and the resulting suspension heated at 175°C for 10 minutes. I was left with a darkbrown solution and a red precipitate which was assumed to be copper. It was allowed to cool to +-~50°C (it was still warm but i could hold the flask), and filtered.
Water was added to dilute the filtrate,
next, cold 10% NaOH solution was slowly added until pH=12

i have heard a report about the same reaction and similar problems: 3gm of the copper chelate was decarboxylated in dmso. the darkbrown solution was filtered. water was added. and allready here lots of fine yellow precipitate formed. NaOH was added and the precipitate changed in consistency (much more clumpy and darker). after letting the precipitate settle for some hours, the liquid was decanted. the precipitate (which was now dark brown) was washed with NaOH solution (rationale: get rid of tryptophan and DMSO) and multiple times with water (rationale: get rid of NaOH) then dried on a 70°C hotplate. this gave a dark brown-black rocky powder. which dissolves very good in acetone and EtOH and nearly not at all in water, dcm and toluene.

so far all trys to isolate the HCl salt have failed. the reporter tried to acidify acetone and EtOH solutions with HCl, but only got really ugly black solutions. except once, when a spatula tip of the brown stuff was dissolved in 2ml acetone, a little water was added resulting in a bright yellow solution with black precipitate. the solution was decanted and 2 drops of conc HCl where added (to the solution) resulting in a bright yellow to white precipitate. unforunately all of it was lost in a blue ribbon filter and the reporter was never able to repeat this.  

also dissolving in dcm, washing with Na(CO3)2 and water, then evaporating the dcm failed: result was always a dark red not pretty oil or black tar. gassing the dcm resulted in a little black powder.

[Student]

Referring to:
As for a way to purify it - recrystallize it, but ask someone else what solvent to use. A good thing would bee to know if it's really tryptamine - that is actually of a primary concern

Tryptamine dissolves OK in ethyl acetate, but not in petroleum ether or xylene. The only recrystallization solvent I've tried is boiling xylene (300 mg/5 mL). If your solid dissolves completely in the boiling xylene, that's a good sign that it is tryptamine. Side products I've obtained using ketone catalyzed decarboxylation tend to be insoluble in boiling xylene. A melting point determination is much more convincing, though. I haven't worked with the hydrochloride, but recrystallization from 99-100% isopropanol is where I would start.

[hypo]

boiling toluene dissolved part of the precipitate and the rest "tarred out". toluene solution was yellow. adding HCl gave red brown precipitate described by e109. looks good.

[element109]

Well, the mess was dried with low heat and was all thrown into a beaker with conc Na2CO3 solution. A metallic grey precipitate was filtered off and dried.
The melting point from this, and the powder earlier isolated from the aq solution was taken, but both solids didn't melt at 250°C.  Probably unreacted tryptophan.(but if it is why didn't it dissolve into the basic solution?)

Well, yesterday i dreamed that i took 10 gr of L-tryptophan, added 75ml DMSO and 2ml acetone, and refluxed the resulting suspension for 4 hours. After cooling there was left a dark red solution to which was added 700 ml dH2O.
Yellow-orange crystals precipitated   , this was allowed to stand 30 min and they were vacuum-filtered off, washed with dH2O and spread open on filter paper to air-dry (then i woke up, so they are still drying, i couldn't weigh 'em yet)
A small bit of half-dry crystals were put in the oven pre-heated at 120°C and they melted immediately.
(if its completely dry i will dream the mp with a cappilary tube)


I don't think i will try the copper-chelate route again, seems like too much a mess to me.



e109

[Student]

In reply to:
Well, the mess was dried with low heat and was all thrown into a beaker with conc Na2CO3 solution. A metallic grey precipitate was filtered off and dried. The melting point from this, and the powder earlier isolated from the aq solution was taken, but both solids didn't melt at 250°C. Probably unreacted tryptophan.(but if it is why didn't it dissolve into the basic solution?)
If the solution was basic, then any tryptamine present would have precipitated as the base, not the hydrochloride, and would be expected to melt at 118°C, not 248°C. Also, I wouldn't count on tryptamine hydrochloride separating easily from aqueous solution. The base seems pretty stable as a solid at least, and is how I prefer to isolate the product.

In reply to:
A small bit of half-dry crystals were put in the oven pre-heated at 120°C and they melted immediately.
Really? I tried refluxing DMSO with butanone, and my solid melted around 200°C. If your product recrystallizes from xylene and melts sharply around 118°C, I would say Congratulations! Maybe I didn't reflux fast enough and oxygen got to the solution and destroyed the product. I've had varying results in other solvents which suggest this may happen.

[element109]

I refluxed it for 4 hours.
I didn't use boiling xylene, but maybe i should, because there's a red tar in there that's almost impossible to get out with EtOH or DCM

e109

[TranceMe]

Why don't just use this method

https://www.thevespiary.org/rhodium/Rhodium/chemistry/tryptophan.txt

by Drone 342? It's incredible simple, OTC AND cheap. And THEN further purify the goods by whatever mean at hand. (eg: as in foxy's post)
Chemically enhanced.

[hypo]

any success stories to share, trance?

Post 258219

(Student: "Re: my first decarboxylation in DMSO", Tryptamine Chemistry) suggests that simple refluxing in DMSO doesn't work.

[TranceMe]

Nope, not yet. And for you to draw a smile I'll tell you why. I was thinking about using xylol + MEK cause I live in this fucked up part of the world where MEK is otc and relatively cheap. No prob with xylol of course, BUT there´s not a single gram of Tryptophan (or L_ tryptophan) yes, go  ahead and laugh on me   . It has to be imported, and that's what I'm trying to do. As soon as I get it, I'll update.
Chemically enhanced.

[hypo]

cool, keep us posted. but don't expect too much:

Post 201916

(Stanley: "Tryptamine from DL-tryptophane", Tryptamine Chemistry) is the only report i found using xylene.

[element109]

As i said before i 've got a yellow precipitate after refluxing Trp in DMSO with acetone. I tried to recrystallise it from EtOH and EtOH/DCM, with little success. I know now that it was a dumb idea, and that i should have used boiling xylene or toluene.
Anyway, i tried to alkylate 1gr of this with NaOH & EtBr in EtOH for 24 hours stirring. It was filtered and I removed the DCM in vacuo and added some EtOH. A white precipitate was collected. Water was added to this and a dark-yellow ppt
was filtered off. Half the amount of this melted in the cappilary tube at around 90œC leaving again a red tar.

I don't suppose i have anything here, but the white precipitate got me assuming it was the quarternary salt.

Did Drone tried his synth's himself or was he just (very optimisticly) assuming things ?

e109

[hypo]

after reading tihkal i was under the impression that you need a sterically hindered organic base for the dialkyation to have reasonable yields. also i don't see no easy way to isolate the tertiary amine from the reaction mixture. could one use the fact that tertiary amines are more basic than primary or secondary ones?

edit: the other way would be using a PTC, of course...

[Lilienthal]

Use acetanhydride to trap the mono- and unsubstituted compound. Acid / base extraction will to the rest.

[hypo]

wow, your tryptamine chemistry knowledge is really impressing! i allready wondered what shulgin was trying to achieve with acetic anhydride...

[element109]

I don't have no DIPEA or Et3N at hand, so i used NaOH, because i have seen a lot of examples in the literature that use it. (Bi)Carbonate is insoluble, but maybe better?
I discussed this with a real chemist and he thought that maybe NaOH could react somewhat with the indole ring but that i should get some yield.
Well, 0.7 grams of yellowish powder from 1 gr assumed tryptamine. I could add ether and filter off the tryp , evap solvent, leaving a mix of NET and DET. Unfortunately i don't have any access to Ac2O unless synthing it from acetone. NET is completely inert, isn't it? What would the ratio of NET:DET be?
e109