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L6L
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L-tryptophan decarboxylation
to start off, i would like to tell you that i have no formal background or education in chemistry, aside from a basic high school chemistry course
(i'm in high school). so allow myself to apologize in advance if i post some bad chemistry. i'm committed to improving however.
OK, i am following a synthesis in which L-tryptophan is decarboxylated with a ketone catalyst to yield tryptamine. what i did was this: i put 35g of
L-tryptophan in a 500mL RBF with 130mL of xylene as solvent. i added about 4 grams of MEK. i then turned on the magnetic stirrer (hotplate/stirrer
combo), and held this mixture at reflux for 9 hours. the temperature of the oil bath was 135 - 145 the entire time. once the 9 hours had finished, i
left the temperature at what it was, but just removed the liebig condenser. during this time, i took out the spinbar and let the xylene evaporate. i
was now left with (hopefully) decarboxylated product.
this is where i am having trouble. i cannot seem to find much information about the tryptamine compound! the synthesis tells me to dissolve the
contents of the flask in DCM, followed by a wash with sodium bicarbonate solution and drying with MgSO4.
where can i find information on tryptamines solubility in DCM? or other similar, useful information?
it seems like the remaining flask contents will require at least a liter of DCM for it to be dissolved.
and yeah, i'm having my doubts on whether the reaction even went well. i couldn't tell if the bubbling was from the xylene evaporating or CO2 being
formed. any pointers you guys can give me would be great.
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Furch
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You should've somehow tried to measure the gas evolution using hoses, plugs, water baths and water filled upside-down beakers and some other cool
gadgets. That way you could at least tell for sure that the stuff has reacted.
I'm sorry to say I don't Merck at hand, but according to some site on the net it's "soluble in ethanol, acetone, insoluble in ether, benzene and
chloroform", and I'd say that if it's insoluble in chloroform, it's probably insoluble in DCM as well.
Good luck!
\"Those who say do not know, those who know do not say.\" -Lao Tzu
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Methyl.Magic
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Hey !!!
I've successfully decarboxylate tryptophan !
The first tests didnt works. I refluxed Tryptophan in NMP with MEK as catalyst, dont know about yield, but tryptamine is hard to isolate.
The problem is that T is insoluble in DCM, hexane,ether or other non-polar solvant and slightly soluble in water (you get a white cream impossible to
filtrate trhough a G4). Another problem is that acidic water destroy your T freebase... therefore you cant do the regular acid/base extraction.
I suggest you can add your T/tryptophan mixture into basic water (not too strong), tryptophan is (slightly) soluble into basic water. Than you must
find a nonmiscible solvent wich dissolves T. MEK is a ketone and you know that T is very soluble in acetone, right ? Perhaps pentanone or MIBK are
better because there are less soluble in water.
Boil your ketone to get pure T freebase.
The best methode I did is refluxing Tryptophan in a high-boiling point liquid ketone.
I refluxed 1g of T in a few ml of Acetophenone for 1 hour. Distilled the solvent off and get a >95% tryptamine freebase as cream colored solid.
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IPN
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Methyl.Magic what do you mean by acidic water destroying tryptamine freebase?
I think best results could be had from using cyclohexanol as a solvent and cyclohexanone as the catalyst. This was mentioned in some references at
rhodium. Then just add dry HCl in toluene to precipitate the tryptamine as the hydrochloride.
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L6L
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where did you get acetophenone from, or did you have to synthesize it yourself? that would be awesome if i had a high boiling point ketone like that.
but i'm a little confused on what you are saying about treating the tryptophan/tryptamine mix. if i were to add basic water to dissolve the
tryptophan, and then acetone to dissolve the tryptamine, acetone and water are miscible. do you mean i should first get rid of the basic water with
dissolved tryptophan?
i referred to the Merck index, and it only got as detailed as saying that tryptamine is soluble in acetone. does anyone have more specific information
so i know how much acetone i should use?
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Nicodem
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He just says to wash the organic phase, for example with 5% aqueous NaHCO3, in order to remove the unreacted tryptophan and other potential acidic
side products. You will still need to recrystallize tryptamine until proper mp is achieved. Ethyl acetate is appropriate for extracting tryptamine.
CH2Cl2 will also work if enough is used. But first you will need to properly decarboxylate tryptophan. Xylene is too low boiling for the
decarboxylation to finish in 9 hours.
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L6L
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thanks for all the help you guys are giving me.
so i guess i'll have to add some more xylene and MEK and let it react for longer... oh well, the weekend is coming up and i'll have time.
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jon
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I've read that mek, acetone whatever does'nt do a very good job or does'nt work at all.
In the original paper they specify the use of cyclohexeneones (not cyclohexanones) and in rhodium he uses spearmint oil which contains pulgelone an
isoprenylcyclohexenone and gets the goods. something to think about.
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Methyl.Magic
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| Quote: | Message original : IPN
Methyl.Magic what do you mean by acidic water destroying tryptamine freebase?
I think best results could be had from using cyclohexanol as a solvent and cyclohexanone as the catalyst. This was mentioned in some references at
rhodium. Then just add dry HCl in toluene to precipitate the tryptamine as the hydrochloride. |
yes, dry HCl is HCl in gas form because tryptamine is destroyed in aqueous HCl (processus of destruction preasent in the human body). Indole (?) is
formed, as far as I know...
I thing he dindn't use cyclohexanone but cyclohex-èn-one wich is harder to find that acetophenone.
L6L, you should buy acetophenone, or synthetise it if you can (grignard, friedel-craft, ... ). This is the best method of decarboxylation I ever done.
Xylène dont do the job... perhaps anethole but low bp.
Yes acetone is soluble in water, therefore you must use MEK or other non-soluble ketone (MIBK, pentanones, ... ), or insoluble esters like nicodem
said.
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jon
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yes cyclohexenone is hard to find but it's isoprenyl cousins are naturally occuring in spearmint oils and in others in excess of 50% and it does the
same job because the neccesary functional groups are there the double bond and the carbonyl function.
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L6L
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between work, school, work, work, work, school, and work, i squeezed in some time on sunday for chemistry! (more like sunday night - monday
morning...)
well, i let the solution reflux for another 11 hours, for a total of 20 hours refluxing.
however, in this time, i found a source of acetophenone. learning from methyl.man's experiences, i'll take his word that the acetophenone
decarboxylation was the best method he tried  since i want to run this reaction
properly, i figured i should stop messing around with the MEK and xylene and just do what will work best. Good thing for me too, because otherwise i
would have been forced doing a friedel-crafts reaction, which may have been beyond my current lab abilities 
also in the meantime, i purchased some DMSO. it has a significantly higher boiling point. would there be any reasons why i should not substitute DMSO
for the xylene?
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jon
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dmso and xylene are two totally different animals dmso has a higher dielectric constant and It might chage the dynamics of your reaction system, it's
possible this reaction is done in aromatic solvents for a reason but I can't say for sure.
It's cocievable that acetophenone would work I think there has to be some kind af electron pair conjugation between a double bond Pi system and the
carbonyl oxygen for the ketone to properly work and acetophenone fits the bill, benzophenone might work too but this is doubtful due to steric
factors.
[Edited on 5-6-2007 by jon]
[Edited on 5-6-2007 by jon]
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Methyl.Magic
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DMSO dont do the job !
Benzophenone works but this is a solid...
Go with acetophenone !
Perhaps other solvent are usable with a keto-catalyst : diphenylmethane, phenetole, benzylic alcool, diphenylether, pure cyclohexanone, ...
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Grimble_Gromble
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Distilling acetophenone off
| Quote: | Originally posted by Methyl.Magic
Hey !!!
I refluxed 1g of T in a few ml of Acetophenone for 1 hour. Distilled the solvent off and get a >95% tryptamine freebase as cream colored solid.
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Did you distill off acetophenone in a reduced pressure environment?
Acetophenone has a bp of about 120-150ºC, I´m not sure. My concern is to destroy the tryptamine with high temperatures.
Look at the sky... look at the river... isn´t it good?
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Misanthropy
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AFAIK, tryptamine is available without restrictions in the USA.
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beheada
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Why wouldn't the DMSO work? Perhaps because it is a slightly acidic solvent? It seems like it would work under anhydrous conditions with the
appropriate ketone added (MEK, acetone, etc).
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chemrox
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This is all re-inventing the wheel. Decarboxylation of tryptophan in various media with yields are discussed in the article at Rhodium published with
references. It looked like the best method was in diphenylmethane with a ketone catalyst. The refs are:
1. D. H. R. Barton, On the origin of the C-1 Fragment in Indole Alkaloids, J. Chem. Soc., 3990-3994 (1965)
2. T. Kametani, A Simple Preparation of Tryptamine, Synthesis 475 (1972)
3. T. Kametani, Synthesis 171 (1974)
4. S. Takano, Efficient Synthesis of Tryptamine, Heterocycles 6(8), 1167-1171 (1977)
5. M. Hashimoto, A Novel Decarboxylation of alpha-Amino Acids, Chem. Lett., 893-896 (1986)
6. E. J. John, Casein, Org. Syn. Coll. Vol. 2, 120-122 (1943)
7. G. J. Cox, L-Tryptophan, Org. Syn. Coll. Vol. 2, 612-616 (1943)
8. G. Laval, One-pot Sequence for the Decarboxylation of alpha-Amino Acids, Synlett 542-546 (2003)
Source: Synthesis of Tryptamine from Tryptophan
by Rhodium
Here's the purification from that article:
"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. "
impurities go with ChCl3?
"The pH is then adjusted to 14 with NaOH and the pure tryptamine is filtered off with suction and air dried."
simple!
[Edited on 7-10-2007 by chemrox]
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Sergei_Eisenstein
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No, it's not. Many people have experimented with the decarboxylation of tryptophane, and there usually are problems with the reproducibility of the
experiment. Sometimes there is little or no reaction, at other times transamination is a disturbing side-reaction.
damnant quod non intelligunt
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chemrox
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and as has been pointed out, the stuff isn't even watched in the US so why not buy it. I haven't checked but I'm guessing that tryptamine is less
expensive than tryptophan (US spelling).
Sergie makes a good point. I should not have said, 'simple.' I've had fits reproducing "simple" looking published procedures.
Decarboxylation of amino acids requires two things: heat and the right catalyst. Who knows what actually went into some of the published mxitures?
Recall the Cooper's Blue accident.
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Methyl.Magic
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| Quote: | Message original : Grimble_Gromble
| Quote: | Originally posted by Methyl.Magic
Hey !!!
I refluxed 1g of T in a few ml of Acetophenone for 1 hour. Distilled the solvent off and get a >95% tryptamine freebase as cream colored solid.
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Did you distill off acetophenone in a reduced pressure environment?
Acetophenone has a bp of about 120-150�C, I�m not sure. My concern is to destroy the tryptamine with high temperatures.
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haha !
tryptophan needs high temperature to be decarboxylated. More heat = faster decarboxylation ! I think less than min of acetophenone reflux is
sufficiant !
You can evaporated the PhCOMe under vacuum but it isnt necessairy, you can evaporated acetophenone at normal pressure to get the liquid tryptamine.
Tryptamine can probably be precipited without difficulty by passing dry HCl into the solution to get Tryptamine hydrochloride. Be careful because in
the presence of water, HCl destroy the T !
The tryptamine freebase can be crystalised from (perhaps) toluene.
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antibody
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You are right 2-Cyclohexen-1-one is a challenge to source. It isn't available locally and shipping it across a border means shipping costs which
triple its cost . . . sigh
But cyclohexanone is readily available. Any opinions on whether this would work as well in cyclohexanol? It is also a ketone and there is only one
double bond difference b/w the two. Based on this reference.
M. Hashimoto, A Novel Decarboxylation of alpha-Amino Acids, Chem. Lett., 893-896 (1986)
I was under the impression that it was a MAO that destroyed tryptamine in the body (perhaps mistakenly). I haven't been able to find any reference
that says tryptamine is unstable in acidic conditions, other than possible ring closure when reacted with formaldehyde. In fact the only prohibitive
condition I've seen is against oxidizers. Have I overlooked something?
Thanks in advance for any opinions/refs
Quote: Originally posted by Methyl.Magic  | | Quote: | Message original : IPN
because tryptamine is destroyed in aqueous HCl (processus of destruction preasent in the human body). Indole (?) is formed, as far as I know...
I thing he dindn't use cyclohexanone but cyclohex-èn-one wich is harder to find that acetophenone.
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[Edited on 8-2-2011 by antibody]
[Edited on 8-2-2011 by antibody] |
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turd
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Carvone is a cyclohexenone. It can be sourced by vacuum distillation of spearmint oil (up to 60% carvone content!).
Cyclohexanol might not be the best solvent, see: https://www.sciencemadness.org/whisper/viewthread.php?tid=99...
I like the idea of using acetophenone.
[Edited on 8-2-2011 by turd]
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madscientist
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The use of a ketone catalyst will result in the formation of beta-carbolines (Pictet-Spengler), which are difficult to separate from tryptamines. They
may or may not be potent neurotoxins, or toxic in other unforeseen ways, so be careful not to accidentally inhale any...
I weep at the sight of flaming acetic anhydride.
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antibody
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| Quote: Originally posted by madscientist | | The use of a ketone catalyst will result in the formation of beta-carbolines (Pictet-Spengler), which are difficult to separate from tryptamines. They
may or may not be potent neurotoxins, or toxic in other unforeseen ways, so be careful not to accidentally inhale any... |
No kidding, I was under the impression that an acid catalyst of some sort would be necessary to effect a PS ring closure? I suppose Tryptoline would
be the product that side reaction?
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madscientist
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Conditions don't have to be what we'd consider acidic in order for it to occur. I have a paper on this somewhere, I'll post it soon.
I weep at the sight of flaming acetic anhydride.
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