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Author: Subject: Solvant-free Decarboxylation of Amino-acid
Methyl.Magic
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[*] posted on 7-2-2008 at 12:52
Solvant-free Decarboxylation of Amino-acid


The standard decarboxylation method are not very good for L-tryptophan.

Refluxing in a high bp solvent with a ketone as catalyst give not really good yield and the reaction is long.

I never tried the chelate method but it seem to be not very interesting.

The best method I used is refluxing L-tryptophan in acetophenone (for 30 min to give 100% yield, no tryptophan formation) but the acetophenone is a problem : 1. formation of water dues to condensation of the amine/ketone imine formation. 2. Acetophenone is not easy to remove out from tryptamine.

But today, I had a new idea. I tried to heat 100mg of L-tryptophan on an aluminium paper in the same manner I did with lysine to form cadaverine when I was at school :P lol !
The CO2 is quickly envolved and it result a beautiful amber colored tryptamine crystal. The problem comes from the burner : the heat isn't steady and too high, this is the reason for black tar formation of some trial.

I'm thinking about a adjustable heater for gently decarboxylate the amino acid and easily collect the product as its liquid form.

Do you think is it possible to perform it to bigger amount of product ?
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roamingnome
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[*] posted on 7-2-2008 at 19:56


If by “aluminum paper” you mean foil… then Alumina could be acting as an effective catalyst for decarboxylation

http://pubs.acs.org/cgi-bin/abstract.cgi/langd5/2007/23/i20/...

in my own endeavors I think to mix alumina graphite and alanine ( what form though? zwitterion, acidic, or basic) with benzaldehyde in the proper mix for a true microwave akabori reaction


anyway… in the theme of this thread

ive priced X-Ray machines at a solid $20,000 and even considered buying 500,000 thousand smoke detectors for the .2 micrograms each of Am231 ( alpha/gamma source)

but alas, playing with those wavelengths is out of the question for the home lab.

I say this because some interesting chemistry is happening at those wavelengths…

http://www.fys.uio.no/biofysikk/eee/pdf_reprints/aa_rev.pdf
The Solid-State Radiation Chemistry of Simple Amino Acids, Revisited


http://www.springerlink.com/content/j284r84m34231659/
Stereoselective decarboxylation of amino acids in the solid state,……
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chemrox
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[*] posted on 7-2-2008 at 23:17


let's go back to his aluminum foil method for a second.. why not use a hot plate or electric frying pan and try again? let us know please!

Here's what I'm thinking of trying:
get an Al plate about 1/4" thick as a heat spreader, place the foil on top and the amino acid on that. The above onto the burner of an electric stove. A steel wire hoop might be incorporated to lift the foil during heat adjustments.

[Edited on 7-2-2008 by chemrox]




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tr41414
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[*] posted on 8-2-2008 at 07:43


How about using paint remover gun for uniform heating of foil?
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not_important
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[*] posted on 8-2-2008 at 08:06


If you can assay the reaction mix for its tryptamine and tryptophan percentages you should be able to optimise the process. Run a series of the reaction, varying the temperature and heating interval. Plot time on X axis, temperature on Y, and yield on the Z axis to see the most desirable conditions. If the peak yields are along an edge, run more trials to extend the chart until yelds drop off.

A heat gun is not at all optimal for uniform heating. Chemrox's idea of using a think plate to get a uniform temperature and reduce fluctuations from the heater cycling is much better. Drill a hole in the block to hold a thermometer so you know the actual temperature.
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[*] posted on 8-2-2008 at 08:35


Quote:
Originally posted by not_importantDrill a hole in the block to hold a thermometer so you know the actual temperature.


Non-mercury would be best, as glass thermometers have a high risk of breaking when in heating blocks.
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Methyl.Magic
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[*] posted on 8-2-2008 at 09:46


I 've just done the first trial. I used a hotplate equipped with a Pt-100.

Decarboxylation starts at almost 240°C. But it results brown pasta, not beautiful amber crytals !

[Edite le 8-2-2008 par Methyl.Magic]
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[*] posted on 8-2-2008 at 10:00


Maybe you can try immersion of your aluminum plate into an oil bath, or sand bath.

[Edited on 8-2-2008 by jokull]
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chemrox
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[*] posted on 8-2-2008 at 18:38


"Maybe you can try immersion of your aluminum plate into an oil bath, or sand bath."

That would get the oil or sand mixed up with the reactant/product unless you have a sequestration method, you didn't state, in mind (?)

What is a Pt-100? I suspect the apparatus got some oil or other contaminant mixed in. Clean everything real well and try it again, maybe with a slower heat up time..

(I can't seem to get the quote thing right)

[Edited on 8-2-2008 by chemrox]




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[*] posted on 8-2-2008 at 21:49


Missing from the original report is how fast it was heated. Metal foil heats very quickly, and it sounds as if it was heated by a flame. Contrast this with heating something from room temperature to 250 C using a hotplate.

This is why I suggested researching time/temperature combinations, perheat the hot plate, place a small amount of the amino acid into a foil or other low mass container and pop that onto the hotplate for a measured interval.
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[*] posted on 18-5-2008 at 21:23


Methyl.Magic,

Could you please give details of the procedure, heat source, etc. Also do you have a reference for the production of cadaverine using lysine/Al foil? Do that and I will try it with l-Phe the same day.




Whhhoooppps, that sure didn't work
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[*] posted on 12-6-2008 at 11:56


The reference has probably been posted before, but it case it hasn't (I didn't find it):
Journal of Pharmaceutical and Biomedical Analysis 41 (2006) 872–882
has a nice overview on impurities obtained by tryptamine decarboxylation in high boiling solvents with ketone catalysts.
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[*] posted on 14-6-2008 at 05:50


Quote:
Originally posted by turd
Journal of Pharmaceutical and Biomedical Analysis 41 (2006) 872–882


Attachment: Analytical characterisation - thermolytic decarboxylation from tryptophan to tryptamine.pdf (596kB)
This file has been downloaded 2659 times

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manimal
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thumbup.gif posted on 29-6-2008 at 15:06


There is an old procedure in my book "Organic Preparations" by Conrad Weygand on how to decarboxylate alpha-amino acids:

"The decarboxylation of a-amino acids can be carried out advantageously, according to Wada, through the hydantoins formed by reaction with urea. The hydantoins are hydrolyzed by concentrated alkalies or acids to form carbon dioxide and ammonia; thus, the basic primary amines are obtained in good yields according to the reaction:
R*CH(NH2)*COOH + H2N*CO*NH2 --> H2N*CO*NH*CHR*COOH ---> R[ring](CH-NH-CO-NH-CO] + H2O ---> R*CH2*NH2 + 2CO2 + NH3

10 g of phenylalanine are boiled under a reflux for 35 minutes with an excess of urea (5 g) in 150 ml of water. The uramido acid thus formed is converted to the hydantoin by evaporation to dryness with hydrochloric acid and the dry residue is dessolved in ether. The hydantoin crystallizes from the ether upon concentration. The product (4.9 g) is refluxed for 10 hours with 70 ml of water and 20 ml of concentrated sulfuric acid. The solution is then made alkaline and extracted with ether. There are thus obtained 2.5 g of phenethylamine (80% of the theoretical amount) boiling at 189C.

In place of urea, urethane, potassium cyanate, or phenyl isocyanate in neutral or alkaline solution may be used. Uramido acids or their salts are formed and these with dilute acids yield the hydantoins. Wada describes the decarboxylation of glycine, leucine, lysine, tyrosine, proline, tryptophan, arginine, cystine, aspartic acid and glutamic acid."

A more efficient method of preparing the amino acid hydantoin would be useful, if anybody knows of such.




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[*] posted on 30-6-2008 at 03:41


Quote:
Originally posted by manimal

The uramido acid thus formed is converted to the hydantoin by evaporation to dryness with hydrochloric acid and the dry residue is dessolved in ether. The hydantoin crystallizes from the ether upon concentration.
.......
A more efficient method of preparing the amino acid hydantoin would be useful, if anybody knows of such.


What do you suppose 'evaporation to dryness with HCl' means? One would assume its requires simply evaporating from an acidic medium of HCl?




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[*] posted on 30-6-2008 at 14:32


I guess it mean add some HCl and then let it evaporate.



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[*] posted on 17-6-2010 at 04:27


Quote: Originally posted by manimal  
There is an old procedure in my book "Organic Preparations" by Conrad Weygand on how to decarboxylate alpha-amino acids:

"The decarboxylation of a-amino acids can be carried out advantageously, according to Wada, through the hydantoins formed by reaction with urea. The hydantoins are hydrolyzed by concentrated alkalies or acids to form carbon dioxide and ammonia; thus, the basic primary amines are obtained in good yields according to the reaction:
R*CH(NH2)*COOH + H2N*CO*NH2 --> H2N*CO*NH*CHR*COOH ---> R[ring](CH-NH-CO-NH-CO] + H2O ---> R*CH2*NH2 + 2CO2 + NH3

10 g of phenylalanine are boiled under a reflux for 35 minutes with an excess of urea (5 g) in 150 ml of water. The uramido acid thus formed is converted to the hydantoin by evaporation to dryness with hydrochloric acid and the dry residue is dessolved in ether. The hydantoin crystallizes from the ether upon concentration. The product (4.9 g) is refluxed for 10 hours with 70 ml of water and 20 ml of concentrated sulfuric acid. The solution is then made alkaline and extracted with ether. There are thus obtained 2.5 g of phenethylamine (80% of the theoretical amount) boiling at 189C.

In place of urea, urethane, potassium cyanate, or phenyl isocyanate in neutral or alkaline solution may be used. Uramido acids or their salts are formed and these with dilute acids yield the hydantoins. Wada describes the decarboxylation of glycine, leucine, lysine, tyrosine, proline, tryptophan, arginine, cystine, aspartic acid and glutamic acid."

A more efficient method of preparing the amino acid hydantoin would be useful, if anybody knows of such.


Manimal, could you please print the relevant pages (everything pertaining to the hydantoin route) out using primoPDF (or whatever) and then post the whole thing up here? I'd love to go through the basis of why he chose to do that and work out from there what exactly is going on.:cool:

Some of the old, particularly German (also Japanese) papers, dealing with decarboxylation, etc. to get interesting natural products are quite good reading... Have to keep brushing up on my German anyway (Rammstein is great for it:P)
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[*] posted on 17-6-2010 at 21:26


The problems with high temp/ solvent free aminoacid decarboxylations, may be caused by a major side reaction.......polymerization.

In the ketone catalyzed reaction, the species decarboxylated is the imine produced by the reaction of the amino function and the ketone. Upon re-hydration, the resultant amine, and the solvent ketone are regenerated.

I would imagine the major competing reaction, would be the creation of complex polymeric amides. Peptide-ization. The reaction of the carboxylic acid and amino functions on adjacent molecules, may form amino-carboxylate salts. Heat then causes these salts to be dehydrated to amides. And on, and on, and on. In other words, it produces glop. Probably glop, that cannot be regenerated. Especially so, if it is well charred, because the hot reaction mixture, has not been protected from atmospheric oxygen.

Acetophenone works well. Why not use it? If you have trouble buying it......It's cheap and easy to make.

If you really must proceed with heat only, consider using a system that helps to prevent polymerization. Try to keep the individual molecules of aminoacid away from each other. Sometimes, heating very finely powdered material, well dispersed in white sand, will do the trick. Vacuum distillation from the hot reaction mass may be in order. Don't be surprised if you obtain solids or semisolids, when you were expecting liquid amines. Remember, the side products of this reaction will be H20 and CO2.....and THEY may combine to produce carbonic acid. Carbonic acid may then combine with your amines, to produce analogs of ammonium carbonate.

[Edited on 18-6-2010 by zed]

[Edited on 18-6-2010 by zed]
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[*] posted on 18-6-2010 at 02:09


Regarding the workup with acetophenone, does it form a bisulphite adduct?
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[*] posted on 20-6-2010 at 13:40


Quote: Originally posted by un0me2  
Quote: Originally posted by manimal  
There is an old procedure in my book "Organic Preparations" by Conrad Weygand on how to decarboxylate alpha-amino acids:...


Manimal, could you please print the relevant pages (everything pertaining to the hydantoin route) out using primoPDF (or whatever) and then post the whole thing up here? I'd love to go through the basis of why he chose to do that and work out from there what exactly is going on.:cool:

The hydrolysis of the alpha-amino acid derived hydantoins gives back the starting amino acid. Due to the weirdness of the claims, a group of researchers actually went so far as to repeat Wada's work and confirmed no decarboxylation occurs. I don't remember in which paper I read about this (and don't really have the time and will to again do a literature search), but it was when doing a literature search for the post here.




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[*] posted on 29-11-2010 at 14:34


Here is Wada's publication (obviously in German).

I am quite interested in the work of the researchers who attempted to reproduce the decarboxylation. This would be an easy method of preparing valuable amines, if it works. Can anyone provide a reference for the more modern attempt?


Eine neue Methode zur Darstellung von Aminen aus Aminosäuren
Wada, M
Biochemische Zeitschrift 1933 pp. 47-51

Attachment: decarboxylation amino acid.pdf (1000kB)
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[*] posted on 29-11-2010 at 19:33


In fact, I have looked up this reference in scifinder, and it shows no citing articles.
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[*] posted on 29-11-2010 at 19:48


Very cool, Methyl.

Have you confirmed the identity/purity of your product? This could be a fairly big deal which would explain quite a bit about the anomalous color formation (e.g. Maillard reaction) which occurs in bulk raw-sugar processing.

I will, when I have time (God help me), give this a shot, and i'll run it on the MS. A source of (relatively) highly reactive amine would help to explain a good deal.

Cheers,

O3

[Edited on 30-11-2010 by Ozone]




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[*] posted on 29-11-2010 at 20:00


On the reference that Bolt attached would any of our
German speaking bretheran care to translate Example 8 on page 4 title: Indolathylamin aus tryptophan. Perhaps theres something missing in modern reproductions or translations.





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[*] posted on 30-11-2010 at 01:32


The following is a table of "easily" decarboxylated acids from March's Adv. O. Chem., 6th ed., p. 836.



The decarboxylation mechanism requires alpha atom to draw electron density from the carboxylate group. If the alpha atom is not electronegative enough on "its own," as is the nitrogen in the case of [carbamic] acids (R-N-C(=O)-OH), the beta atoms should be electronegative or at least electrophilic, as in the cases of the trihaloacetate example from the table and beta keto acid decarboxylation, respectively. The beta - gamma bond is often of an order greater than one (even if it is not a full two). See the beta,gamma-unsaturated acid example from the table. That example illustrates that inductive effects are only part of the mechanistic explanation, and the labile electron density in the pi bonds must have a similar result (decarboxylation). Note that the imino species that decarboxylates in the ketone catalyzed amino acid decarboxylations is not mentioned as an "easy" acid to decarboxylate.

In light of these observations, an acid of the structure R1-C(=O)-N-CH2-C(=O)-OH is also likely to be able to be decarboxylated due to the electronegative nature of the nitrogen atom as well as the partial double bond character of the beta - gamma bond. This molecule probably does not decarboxylate as easily as a molecule with a beta - gamma bond of two, as in the imino species. I wonder if that is the intermediate through which an "uncatalyzed" alpha-amino acid decarboxylation occurs - condensation with one of its own kind and then decarboxylation.

[Edited on 1-12-2010 by Bolt]
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