hypo (Hive Addict)
01-27-03 08:17
No 401891
      trp decarboxylation with HCl/benzene?  Bookmark   


anyone heard about this method or got this journal?


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

ok i'm stupid, probably HCl/benzene is only used for making tryptamine.HCl. could
this be the last method in http://rhodium.ws/chemistry/tryptophan.html where
the ref isn't given?
(Hive Bee)
01-29-03 06:00
No 402334
      Chem. Nat. Compd., "Chemistry of Natural...  Bookmark   

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.
(Hive Addict)
01-30-03 06:36
No 402660
      thanks for your reply :)  Bookmark   

> 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.
(Chief Bee)
01-30-03 09:47
No 402694
      EDTA  Bookmark   

Can't you chelate/extract the copper with an EDTA solution?
(Hive Addict)
01-30-03 10:03
No 402700
      EDTA?  Bookmark   

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)
(Chief Bee)
01-30-03 11:59
No 402737
      Anti-emulsion suggestions  Bookmark   

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.
(Hive Addict)
01-30-03 12:28
No 402742
      ah, ok  Bookmark   

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?)
(Chief Bee)
01-30-03 16:06
No 402802
      my idea  Bookmark   

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.
(Hive Addict)
01-31-03 05:03
No 402922
      now i get it  Bookmark   

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

where would one search for the solubility of tryptamine in various

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...
(Chief Bee)
01-31-03 08:41
No 402968
      Tryptamine solubility.  Bookmark   

Ethyl acetate shouldn't be too bad, I think (among the water-immiscibles, otherwise THF is really good).
(Hive Addict)
02-03-03 05:06
No 403951
      thanks (and another question :P)  Bookmark   

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

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

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


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)
(Chief Bee)
02-03-03 18:05
No 404184
      Tryptophan Copper Chelate  Bookmark   

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

(Hive Addict)
02-04-03 01:50
No 404326
      cool  Bookmark   

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... smile

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

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%. smile
(Chief Bee)
02-04-03 12:25
No 404446
      CuTrpOAc  Bookmark   

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?
(Hive Addict)
02-05-03 02:09
No 404677
      partial success!  Bookmark   

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

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. tongue unfortunately there are
no TLC-plates available, so it's pretty hard to tell what's happening in each

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 smile

ps: is it me or are tryptamines much more sensible than phenethylamines??
(Chief Bee)
02-05-03 11:29
No 404780
      tryptamines are oxidation-sensitive  Bookmark   

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?)


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?
(Hive Addict)
02-06-03 01:44
No 405026
      oh well...  Bookmark   

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?
(Chief Bee)
02-06-03 01:55
No 405033
      DMF is probably good  Bookmark   

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

../rhodium/pdf /tryptophan.cu-chelate.decarbox.pdf
(Hive Addict)
02-06-03 02:15
No 405048
      yes,  Bookmark   

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 smile))
(Chief Bee)
02-06-03 02:20
No 405050
      Water  Bookmark   

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)
(Hive Addict)
02-06-03 02:23
No 405051
      hmmm...  Bookmark   

but the water is added after the CuO is filtered of and the CO2
has gone away, isn't it?
(Hive Addict)
02-08-03 08:43
No 405634
      DMF "works" too.  Bookmark   

it just takes longer (about 1h-1.5h). same result as with DMSO.

the reason i put works in quotes is that for some reason on
extracting with EtOAc everything turns into tar.

basifying with Na2CO3, no basifying, extraction of the organic
phase with 0.5N H2SO4 has all been tried.

(sidenote: boiling the tar in toluene and cooling gives a green

plan for next week: wash with EDTA solution, try the charcoal / celite
trick and if this doesn't help file this method under "workup impossible
probably due to bad lab technique". frown
(Hive Addict)
03-01-03 13:41
No 412862
      reaction mechanism??  Bookmark   

(first of all, the 2 articles were retrieved by lugh (thaaankssmile)
and the chemists use the known diphenyl methane under N2 method.)

but rhodium (or other chem god): do you know how this reaction
is supposed to work? this time, i really gave some thought to it,
but i just don't get it!? i have no doubt that it does work (what
would the yellow precipitate on hydrolysis be?), i just can't understand how!

even without trying to come up with electron dances:

1) in the picture you posted, it's clear that the covalent O-Cu bond is
in reality an ionic bond, where the oxygen has a negative charge.

2) the CO2 evolution and the red inorganic precipitate happen in
aprotic medium.

CO2 is a neutral molecule, so where the heck does the negative
charge go? my first thought was that the red precipitate is copper
(CuO is black according to merck and where should the oxygen come
from?) and that the negative charge would reduce the ionic copper
to metalic copper, but that would leave us with a tryptamine radical!
i can't believe this. the other idea i had was that one ends up with
an organo copper compound. but what would then the red precipitate be?
and it sounds totally strange too.

so please, what am i missing?
(Hive Addict)
03-02-03 01:17
No 412996
      wild guesses...  Bookmark   

one theory i have (seeing the low yield), is that
the reaction gives partly the copper salt of the
tryptamine derivate which misses one proton on the
-NH2 group. (an amide?) and partly polimerised crap,
which happens when the copper is reduced (thus the
red precipitate).

but that sounds very unlikely too... frown