10-23-03 04:20
No 466220
Hi there; this is my first post here ;)
I tried looking this up, but nothing really came up.
I want to synthesize tryptamine from L-tryptophan using a zinc acetate catalyst. My problem is that I need to minimize the amount of zinc that will be in the tryptamine. The protocol calls for a chloroform extraction of the tryptamine formed afterwards, and I assume there shouldn't be a lot of zinc residues that will extract into the CHCl3 layer, but I need the amount of zinc to be less than 10^(-6)M, preferably. This is because an amount higher than this might interfere with the experiment. Is there a possibility that that much zinc might be extracted, if it's a good extraction? If so, might it be possible (given the freebase extraction) that EDTA could be added to chelate the zinc and reduce the amount of zinc extracted? EDTA is usually soluble in basic solutions, so is there a possibility of adding EDTA to chelate the zinc and then basifying and extracting the tryptamine? I would like to stay away from distillation if I can (I will if I have to, but I really, really, really would like it if I didn't.)
Also, in the protocol it says to basify and do a non-polar extraction.... I'm assuming I should pH to 8, or does it not matter????
Eidt: I just realized with the molarity of zinc you need the concentration of tryptamine. It'll be added about 1.6g/45mL = .18 M solution of tryptamine. In this solution, zinc should be < 10^(-6)M, if possible. Just to give a reference point. The reaction was at a 40% yeild in the paper, so we'll say 35%????
Thanks in advance,
--
Micro
(Chief Bee)
10-23-03 10:42
No 466259
Washing a solution of tryptamine freebase in ethyl acetate (or other np solvent) with aqueous Na2EDTA should chelate any zinc still bound to the tryptamine.
Also, in the protocol it says to basify and do a non-polar extraction.... I'm assuming I should pH to 8, or does it not matter?
A solution with pH 8 isn't really basic - aim for 11 or so. As long as distinctly basic, the exact pH isn't critical.
Also make a habit out of linking to the procedures/protocols you are referring to, as we aren't mind-readers.
(Moderator)
10-23-03 11:16
No 466266
The best way of purification would be distillation in a microdistillation bridge under oilpump-vacuum. The second best choice would be repeated extraction with dichloromethane or chloroform (which have a pretty low capacity for dissolving tryptamine) and subsequent multiple crystallizations. You don't want to chelate the zinc because it would make it more soluble in organic solvents. But with extractions you don't have any guaranty for such a low Zn2+ concentration.
(Hive Addict)
10-23-03 11:54
No 466272
excuse my ignorance,
is there a reference for this Zn(OAc)2 decarboxylation?
is it similar to the Cu chelate method?
(which produces lots of ugly shit)
n'importe quoi
(Stranger)
10-23-03 15:30
No 466295
Hey -- thanks a lot, people; I really appreciate it. Sorry for not posting the ref; I was pretty drunk last night. Yeah, the zinc acetate is being used in place of the copper acetate; the synth says it's ok:
../rhodium /tryptop
Thanks again,
--
Micro
(Chief Bee)
10-23-03 17:43
No 466314
You don't want to chelate the zinc because it would make it more soluble in organic solvents.
Lilienthal: Huh? Are you saying that EDTA chelates prefer organic solvents over water?
(Moderator)
10-23-03 18:53
No 466323
No, I just suggested that the complex could be more lipophilic than free Zn2+ ions
I still think it is
(Stranger)
10-23-03 19:01
No 466325
Interesting.... If they do might it be possible to dilute acetic acid extract the freebase and add concentrated acid to precipitate out the EDTA?
I really appreciate the help -- I'll ask a metallurgist I know tonight about the sol. of zinc chelates and I'll see what she says, if she knows. Oh, well, I'll be back....
--
Micro
(Stranger)
10-23-03 19:05
No 466326
You mean because of the organic chain on the EDTA? Would the zinc chelate be soluble in np solvents? I will be doing an acid/base extraction, but the wash was to further purify it afterward.
--
Micro
(Hive Addict)
10-23-03 19:40
No 466329
maybe you find something of interest in this thread:
(inbetween lots of ramblings by myself (how embarassing!))
Post 401891 (hypo: "trp decarboxylation with HCl/benzene?", Tryptamine Chemistry)
short version: EtOAc disolves it all, but on evaporation
the yellow sticky precipitate is turned into disgusting tar.
DCM disolves only very little. maybe try removing the
DMSO under vacuum and do a continuous extraction with DCM?
n'importe quoi
(Stranger)
10-23-03 19:58
No 466333
Thanks, hypo -- a lot of good info. I think I'm going to centrifuge it and pipette off just the organic layer and .2-micron filter if I have to....
It still leaves the question about ionic zinc, though. I might just have to test it with a spectrophotometer for the zinc to see if I can get it to chelate. I don't know how I'd do this to test for leftover zinc intermediates, though.
--
Micro
(Chief Bee)
10-23-03 22:38
No 466372
If you just need a small analytically pure sample to test, you can try vacuum sublimation in a test tube - But maybe you wanted to analyse the crude product to get an impurity profile?
What kind of analysis is that sensitive against zinc?
(Stranger)
10-24-03 02:56
No 466439
I was thinking just look up the peaks for Zn2+ and compare before and after the wash.... would this not work? The spectrophotemeter is really sensitive (used to calculate pmol concentrations of DNA, even though I realize DNA is a lot bigger....)
BTW -- the metallurgist I know said she thought the chelates should still carry a charge and should prefer the aq. solution.
Thanks,
--
Micro
(Hive Addict)
10-24-03 09:19
No 466485
facts:
*) CO2 evolves during this reaction
*) Cu precipitates
if we only look at electrons, not configuration:
we start with:
R-COO-Cu-COO-R (I)
minus CO2:
R-Cu-R (II)
now if metallic copper precipitates we end up with
R-R (III) (=dimeric, disgusting crap)
i'm pretty sure that precipitated copper means ugly side product,
what we really want is (II), which when hydrolised with H2O gives:
2R-H + Cu(OH)2
i have no idea what (II) looks like. i can imagine the beginning of
the reaction, which i think looks like this:
this would make sense, considering that all Ns and Os interact with
the empty d-orbitals of the Cu.
but what is the end product?
surely not this:
(yes i know, you can't write structures like this)
if nobody disagrees, i'll just continue believing that
the world is flat...
n'importe quoi
(Stranger)
10-24-03 15:19
No 466506
Hmmm.... interesting, hypo. You have a great mind, but the handwriting of a 2nd grader -- almost worse than me (but not quite.)
I don't know -- from what I see, in the beginning you lose a proton, and the electrons, I would guess, would go to the double bond in the carboxyl formed? I'm guessing the proton goes to the catalyst because it's used again in the end.... In the end, the CO2 simply breaks off with the catalyst, and the proton is reclaimed. Since it's a catalyst, though, I would think you should end up with zinc acetate, but the tryptamine should precipitate.
Tell me if I'm close at all....
Of course, this doesn't mean other crap doesn't form -- it probably does.... 2 washes with disodium EDTA should help.
--
Micro
(Stranger)
10-26-03 23:48
No 466913
I didn't get a precipitate (with a saturated Zn(OAc)2 solution) -- even tried heating up the reaction. I don't think there was anything I could have been missing....
Back to the drawing board I guess....
--
Micro
(Hive Addict)
10-27-03 14:50
No 467000
hi, micro
could you please elaborate on what you did? with amounts, colors etc.
tryptophan needs lots of water to dissolve, so i don't understand
what you mean with a "saturated Zn(OAc)2 solution".
with Cu(OAc)2, you need less than a half of Cu(OAc)2 by weight.
color change is immediate (from yellow to blue), the precipitate
with copper is bright blue. but with zinc it will probably not be
blue
n'importe quoi
(Stranger)
10-27-03 18:47
No 467044
Thanks, hypo. I didn't measure anything, just dissolved as much zinc acetate as would dissolve until there was a bit that wouldn't dissolve, at all, and I added this to a solution af L-tryptophan (all ACS reagent grade chemicals.) I didn't measure the solution of tryptophan, but it had a decent amount in it, however below the saturation level. When I added the sat. zinc acetate to the tryptophan solution nothing happened; it just dissolved. I got pissed. I couldn't think of why it didn't work, but I tried heating the reaction, and still nothing.
Anything else it could be (besides the zinc not working?)
Thanks.
--
Micro
(Moderator)
10-27-03 22:01
No 467078
Who said that the complex precipitates? Maybe you have to evaporate the water (and to use exactly calculated and measured amounts) to get a solid complex. Otherwise you might be able to precipitate the complex, e.g. with ethanol.
(Stranger)
10-27-03 22:43
No 467089
Thanks, L -- I was under the impression that because of the position of the carboxyl group and the position of the metal catalyst the zinc chelate complex should become completely insoluble in water. In the paper (referenced above) it says that a precipitate forms. Are you saying that the zinc itself might make enough of a charge to not precipitate? How would I be able to tell, by evaporating, if the chelation even ever took place? Thanks,
--
Micro
(Moderator)
10-27-03 23:37
No 467110
Could you give the Zn-procedure from that paper? Or is online somewhere or has been posted before?
(Stranger)
10-28-03 00:52
No 467132
Sorry -- the ref for the reaction is at:
../rhodium /tryptop
It seems, from the r(x) scheme, like Cu and Zn should be interchangable.... look at the picture w/t/ r(x) scheme.
--
Micro
(Chief Bee)
10-28-03 01:36
No 467152
The full reference - Synthesis 171 (1974) - can be retrieved for free, see Post 363228 (Rhodium: "Free Online Chemistry & Medicinal Journals", Novel Discourse)
10-28-03 01:52
(Rated as: get back when sober, all answers are here)
(Stranger)
10-29-03 03:16
No 467414
Sorry, damn Steel Reserves. I switched to Corona tonight.
I signed up for that 30-day thingy, but Synthesis 1971 vol 3 goes up to 153 and vol 4 starts at 175....
Honestly, I think I need a new approach. I think I can get cyclohexene; I need cyclohexanol and a ketone. Does this sound right (sorry, been a while:)
Cyclohexene + HCl / H2O -> cyclohexanol
Cyclohexanol + paracetic acid -> hexanone
Thanks,
--
Micro
(Moderator)
10-29-03 10:57
No 467486
Wasn't it cyclohexenone?
(Hive Addict)
10-29-03 11:39
No 467489
conclusion in older threads was that only cyclohexenone works.
imho the most appealing route seems to be ketone in tetraline.
tetraline is ass-cheap (if you can get it).
n'importe quoi