trp decarboxylation with HCl/benzene?

[hypo]

Chem.Nat.Compd;17;1981
Chem.Nat.Compd;21;1985;502-509

anyone heard about this method or got this journal?

thx.

ps: i think i could get the russian original (Chimija prirodnych soedinenij)
but i don't speak a word russian   .

edit:
ok i'm stupid, probably HCl/benzene is only used for making tryptamine.HCl. could
this be the last method in

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

where
the ref isn't given?

[bottleneck]

Chem. Nat. Compd., "Chemistry of Natural Compounds"? Why would that be a russian journal?

Decarboxylation of 2-carboxylic indoles by hydrochloric acid seems to be a fairly common procedure. See for example Frederick Uhle in JACS 77, 3334-3337 (1955). He just uses concentrated acid in ethanol. This 2-group seemingly is fairly easy to get rid of, sometimes just heat is used.

But the carboxylic group of tryptophan is not so labile. However, just search for "tryptamine from tryptophan" on google, and a reference for thermal decarboxylation of tryptophan is given as one of the first links. However, this is not likely to produce very good yields. 30% maybe?

http://www.erowid.org/chemicals/dmt/dmt_info3.shtml

gives a lot of references to "tryptamine from tryptophan", so maybe there could be some good suggestions in one of those articles. Edit: Okay, I was wrong, it lists just one article, and it's the same as the above I need some sleep.

By the way, USP grade (>99%) tryptophan is about $130/kg. Animal feed quality (>98%) is about $30 per kilogram.

[hypo]

> Chem. Nat. Compd., "Chemistry of Natural Compounds"?
> Why would that be a russian journal?

well, strange question, because it is. actually "Chem. Nat. Compd."
is the english translation of a russian journal. but the library i
have access to only has the russian original.

> However, just search for "tryptamine from tryptophan" on google, and a reference
> for thermal decarboxylation of tryptophan is given as one of the first links.

do you talk about the Cu-chelate method? a friend of mine tried it (about 1 year ago)
and it seems to work ok, until the dilution with water and basification with NaOH,
where a very fine precipitate forms, which goes through filter paper and which can't
be extracted with DCM, PhMe or Et2O, because one ends up with ugly emulsions.

if the Chem.Nat.Compd. is not appealing, investigation into the Cu-Chelate method
will continue... for example one idea i have is too vac evaporate the DMSO, dissolve
the residue in HCl, and then try an A/B. i can't remember if that has been tried. IIRC,
the problem with tryptamine is it's general bad solubility in NPs.

[Rhodium]

Can't you chelate/extract the copper with an EDTA solution?

[hypo]

sorry rhodium, i think i wasn't clear enough

what i was talking about is this method:

Post 211603

(Rhodium: "Another tryptophan decarboxylation", Tryptamine Chemistry)

the preparation of the copper-chelate compound works perfectly well.
one obtains a marvellous blue powder and the yield is very consistent.

when heating the blue powder in DMSO, after a short while, there's
quite some gas evolution, which dies of after a few seconds, and the
reaction turns dark red. it can then be easily filtered giving
a dark red powder and a dark red solution. now when the filtrate is
diluted with water and basified with NaOH, the above described thing
happens: unfilterable yellow precipitate and monster emulsions.

another idea i have is to dry the DMSO. (although it _should_ bee good)

[Rhodium]

Yes, I understand what you are saying. Additon of EDTA to the basified solution should complex the remaining Cu²⁺ ions so that they don't create such a terrible emuslsion. Filtering of it all through a centimeter of Celite should also do wonders.

[hypo]

thanks alot for the tip, EDTA should be available.

> Filtering of it all through a centimeter of Celite should also do wonders.

you mean the filtration of the DMSO before the dilution/basification or
filtration of the tryptamine (that's what the yellow precipitate is, isnt it?)
after basification?

(or filtration of the emultion crap and washing the celite with hot NP?)

[Rhodium]

I thought that after basification, you add enough EDTA to complex with all Cu²⁺ (add 1 eq), and then shake with a relatively large portion of chloroform. Now everything you want should either be dissolved in the chloroform layer or the aqueous layer, so filtering everything through celite at this point should not cause any losses.

However, washing the filter cake with hot chloroform probably wouldn't hurt, but you will notice if that is necessary or not.

[hypo]

ok, thanks, i understand now. (sorry for me being so slow)

where would one search for the solubility of tryptamine in various
solvents?

unfortunately chloroform is not available and making bigger quantities
from acetone and Ca(OCl)2 is so painful! i fear that DCM may not be
a good enough solvent and i'm playing with the thought of building an
improvised liquid / liquid continuous extractor for heavy solvents...

[Rhodium]

Ethyl acetate shouldn't be too bad, I think (among the water-immiscibles, otherwise THF is really good).

[hypo]

thank you everybody for your replies (also via pm   ).
you have reawakened my interest in this method  

water immiscible is a must, since the goal is to extract
from basic H2O(+DMSO). ethyl acetate seems to be a good
guess, i've found a journal article giving some partition
values of tryptamine for some solvent/water systems. ethyl
acetate comes very close to chloroform. still the low values
somewhat scare me. iirc the log(P) for ethylacetate is 1.47
that gives a value in the range of 25 for P.

i have another question(s):

the blue copper chelate compound, how many molecules are there
per Cu? i guess it's 3. the anion is still acetate, right?

if it's really 3 mols Trp per Cu, and one uses an excess of
CuAc2, wouldn't one end up with a wild mixture of mono-, di-,
and tri-, conjugated (associated?) molecules?

the reason i want to know this is so that i can do correct yield
calculations.

also, the yield of 45% in the original article is that starting from
Trp or from the copper compound?

thx.

edit: thinking about this, the anion is probably tryptophan itself.
and there are probably 2 ligands. still i have no idea how this
compound really looks like.

edit #2:

here are the log(P) values of tryptamine in water/solvent systems:
source: J.Chem.Soc.,Perkin Trans. 2, 2002, 470-477
octanol: 2.147 (measured in this work)
octanol: 1.35 (MedChem 2001 Database)
chloroform: 1.526 (measured in this work)
cyclohexanone: -0.599 (measured in this work)
toluene: 0.268 (measured in this work)
benzene: 1.07 (MedChem 2001 Database, ion correction was applied)
ethyl acetate: 1.41 (MedChem 2001 Database)

[Rhodium]

The chelate looks like in the picture below (and it was formed in quantitative yield, so the overall yield of tryptamine is 45%):

[hypo]

i still somewhat wonder, why, when using an excess of CuAc2,
one doesn't end up with half complexed copper (CuTrpAc), but
i'll just accept it...  

i can't confirm the quantitative yield. using the values in the reference,
starting with 50g, one should obtain 57.29g of chelate, but they only
get 52g, or 91%. i don't think 9% can be attributed to losses during
filtering.

in a little experiment performed yesterday, a friend obtained (after thorough
washing with hot water and drying overnight at 70°) 10.75g chelate from 10g Trp
or 94%

anyway i'm happy with everything > 90%.  

[Rhodium]

I still somewhat wonder, why, when using an excess of CuAc2, one doesn't end up with half complexed copper (CuTrpAc)

Probably because the chelate is insoluble enough for the equilibrium

Cu(OAc)₂ + 2 Trp CuTrpOAc + Trp + HOAc Cu(Trp)₂ + 2 HOAc

to be shifted completely to the right? If mixing Pb(OAc)₂ with KI, there is hardly any "PbIOAc" left in solution, all of it becomes PbI₂ because of its insolubility.

What was the purity of the Tryptophan you used? If it was impure, then there wasn't enough actual tryptophan in it to make a quantitative yield?

[hypo]

yeah, solubility products of course, that  came to me after i posted  

the tryptamine used was tech grade. larger scale will show if the yield stays
the same or it's just constant losses. i wonder more about the meager 91% of
the paper...

anyways, ethyl acetate and EDTA was a great idea! not the slightest of emulsion!
very sharp separation. (well, there was a very small amount of inorganic crap,
but that happens with every extraction, doesn't it?)

still my retarded friend managed to fuck up.    unfortunately there are
no TLC-plates available, so it's pretty hard to tell what's happening in each
phase.

a suspension of 2g chelate in DMSO was strongly heated with stirring. after some
time the reaction turned red and there was a short burst of gas evolution, leaving
a red reaction mixture with a dark red precipitate. the precipitate was filtered
of, the filtrate diluted with water, giving a yellow precipitate. on basification
with dil. NaOH, the color of the precipitate turned from yellow to dark brown. (!)
a spatula di-sodium-EDTA was dissolved in water and added. the resulting solution
was extracted 3x with EtOAc, giving a very dark blue / magenta organic phase. the
organic phase was washed 3x with water and then extracted 3x with 10% HCl. this is
where things seem to have gone wrong: the organic phase has not decolorized, the
aq. phase was dark yellow, but there was pieces of disgusting sticky black tar.
the aq. phase was basified with dil. NaOH, the color changed from dark yellow to
clear with a small amount of brown (not pretty) precipitate. (10mg at most)

next steps: filter the dark organic phase, gas half of it with HCl, evaporate
the other half to see what's inside. evaporate the aqueous aq. to see if there's
anything besides NaCl / NaOH in it.

not perfect, but i'm still very happy that the whole mess goes into the organic
layer without emulsion, that's a big step forward  

ps: is it me or are tryptamines much more sensible than phenethylamines??

[Rhodium]

anyways, ethyl acetate and EDTA was a great idea! not the slightest of emulsion! very sharp separation.

I have no idea why EDTA is next to never mentioned in the literature to deal with metal ion induced emulsions... I have seen it used in one of the copper-catalyzed 5-bromovanillin methoxylations, but that was after I had invented it myself... It's probably because so many chemists work at millimole scale and either calculate GC yield (rather than isolated yield) or they spin their little test tube in a centrifuge to compress anything in suspension into ha hard little pellet and decant.

(well, there was a very small amount of inorganic crap, but that happens with every extraction, doesn't it?)

Yup.

ps: is it me or are tryptamines much more sensible than phenethylamines??

No kidding! Many tryptamine freebases turns visibly tan in weeks at RT, even if stored in a sealed bottle. Try to avoid extreme pH's, lewis acids and anything oxidizing (including prolonged air exposure) throughout your synthetic work.

To clean up your colored tryptamine solution, preferably vacuum filter it through a 1cm deep/3cm diam silica gel bed in a narrow fritted glass funnel (or column) and after sucking all of it through, elute with another 100ml EtOAc. Next best cleanup is to boil it with a gram of finely powdered activated carbon, which is subsequently removed by filtering through a cm of celite and washing the filter cake with EtOAc. Either method should make your solution light brown instead of black.

How are you planning to continue after isolating your tryptamine?

[hypo]

evaporation of the EtOAc gave a stinking disgusting tar. heh.
any tryptamine must have been destroyed during either basification
or acidification. i guess shulgin knows why he extracts his tryptamines
with 0.5N H2SO4.

if time permits, the experiment will be repeated today with less (and
a weighed amount) of NaOH, 0.5N H2SO4 instead of 10% HCl and evaporation
of small parts of the organic phase after each step, to check the tar content.

what then? should sufficiently pure tryptamine crystals be obtained, of which
i am no too sure, the first try will be at shulgin style dialkylation for
DxT, x > M. i realise that even shulgin with his 0.05torr pump had problems
with the purity of his dialkylation products. let's see. as long as tryptophan
is available it would be a shame not to try! btw: the limiting reagent will
probably be DMSO, will the decarboxylation work in DMF too?

[Rhodium]

Yes, that is very likely, see the original article below, they also use HMPA (toxic!) with good results, so why not DMF too?

https://www.thevespiary.org/rhodium/Rhodium/pdf/tryptophan.cu-chelate.decarbox.pdf

[hypo]

why not? thanks for putting the article online!

(btw: note how in the decarboxylation formula a H+ comes out of
nowhere in aprotic solvent? (ok with me as long as it works   ))

[Rhodium]

It's from the water added in the workup. Cu(Trp)₂ + H₂O 2 Tryptamine + 2 CO₂ + CuO

(But you took this further to Na₂EDTA + H₂O + CuO CuEDTA + 2 NaOH instead)