JJay
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Phenylacetaldehyde from Phenylalanine
In the thread on preparing phenylacetaldehyde from styrene, SM2 mentioned that it is possible to react bleach with phenylalanine to produce phenylacetaldehyde.
I attempted this today by dissolving 10 grams of phenylalanine in 500 mL of water and adding 14.5 mL of 8% bleach. The smell of flowers was almost
immediately apparent. I let the solution sit for a few minutes and then extracted 3x with 10 mL DCM and then attempted to create the bisulfite adduct
(I assumed 70% yield). My lab still smells like a rose garden but I got no product....
Questions:
1. How many equivalents of hypochlorite are necessary to do Strecker degradation of phenylanine?
2. Does the bleach really need to be concentrated?
3. How long does the reaction take? For that matter, does anyone know what reaction conditions to use? If I use a stoichiometric amount of bleach, I
could do iodometric tests to see if the reaction is complete, but it would save a lot of time if someone has done this before....
4. Am I correct in assuming that I can extract phenylacetaldehyde with DCM and create the bisulfite adduct? That seems a lot easier than distillation
from an aqueous mixture.
5. Is there any danger of accidentally overoxidizing the phenylacetaldehyde to phenylacetic acid? This is something I would actually like to avoid.
I'm certainly going to attempt this again soon, but I'd like to get a weighable product this time. If anyone has successfully degraded phenylalanine
to phenylacetaldehyde before, your input is appreciated.
[Edited on 24-5-2016 by JJay]
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DraconicAcid
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Hmmm....it melts at 33 oC and is only slightly soluble in water. I wonder- if you do the reaction at low temperatures, will the solid precipitate
out?
Merck Index says 33-34 oC, as does the 70th CRC.
[Edited on 24-5-2016 by DraconicAcid]
Please remember: "Filtrate" is not a verb.
Write up your lab reports the way your instructor wants them, not the way your ex-instructor wants them.
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zed
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The problem with oxidations, is putting on the brakes. Phenylacetaldehyde could be further oxidized to PhenylAcetic acid, and then Benzaldehyde or
Benzoic acid. In fact, I think you can bet on it.
Sometimes, this tendency is combated, by using a two-phase solvent system. An aqueous-phase, and a non-polar phase. The Amino-Acid reacts with
hypochlorite in the aqueous phase to produce Phenylacetaldehyde. The Phenylacetaldhyde, is much more soluble in the non-polar Phase, and it migrates
there, where it is protected from further oxidation.
It works, but yer dancin' with the devil. Temperature control, speed of agitation, and working with massive volumes of dilute solutions, all come
into play. Yields are often....meh.
Experimental details applied to tryptophane/indole-acetaldehyde, should be around.
https://www.erowid.org/archive/rhodium/chemistry/indoleaceta...
[Edited on 24-5-2016 by zed]
[Edited on 24-5-2016 by zed]
[Edited on 24-5-2016 by zed]
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clearly_not_atara
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IIRC, dehydroascorbic acid, the oxidized version of vitamin C, is an active oxidant for the concerted Strecker (as is any vicinal tricarbonyl).
However, it tends to undergo anannulation to a hexahydrodifuran, so it has to be produced in situ.
I'm not aware of any reports using DHA as a Strecker reagent in vitro, but it has been suggested that Strecker reactions could mediate DHA toxicity in
vivo.
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Crowfjord
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JJay: Did you see my post in that same thread? In order to isolate aldehyde in any decent yield, dilute conditions and pH control (buffer) are
important. I can post the entire article later, if desired. I thought I had already posted it somewhere, but I can't find it.
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JJay
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From https://www.erowid.org/archive/rhodium/chemistry/indoleaceta...
| Quote: |
Preparation of 3-Indoleacetaldehyde from Tryptophan
To 100 ml. of distilled water were added 15 ml. of 10% NaOH solution and 3.0 g. of DL-tryptophan. After the tryptophan was completely dissolved, 4 N
HCl was added until tryptophan crystals just started to separate at a pH near 8.5. The solution was diluted immediately with 1200 ml. of distilled
water in a 4000-ml. Erlenmeyer flask. To this solution was added 700 ml. benzene followed by 200 ml. of 0.52% sodium hypochlorite solution made by
mixing 1 part Chlorox with 9 parts water. The flask and contents were shaken with a swirling motion immediately after the addition of the hypochlorite
and during the entire duration of the experiment so that the aldehyde was taken up in the benzene as soon as it was produced. Care was taken to avoid
an excess of hypochlorite which produced brown-colored products. This also happened if dilute solutions were not used. The flask was immersed in a hot
water bath, and the temperature of the contents was raised to 50 degrees C. over a period of 20 min. The temperature was held between 50 and 51
degrees C. for 15 min. more. The benzene layer became yellow in color and later turned orange. The benzene was separated from the aqueous phase with a
separatory funnel while still warm.
The benzene solution was concentrated to 65 ml. in a large evaporating dish placed in a swift current of air in a fume hood. Slight heat was supplied
with a warm water bath at 40-50 degrees C. The resulting benzene solution was shaken with 50 ml. of saturated sodium bisulfate solution in a closed
wide-mouth bottle. Crystals of the IAc.NaHSO3 formed immediately and were filtered almost dry by suction.. The product was resuspended twice and
shaken vigorously in 95% ethanol and filtered each time. The crystals were washed again with absolute alcohol and finally with ether. After drying at
room temperature, the yield was 4.06 g. of white crystalline material. The yield was 90% of theoretical based on the amount of tryptophan used. Most
of the IAc.NaHSO3 was dissolved in a small amount of water making a saturated solution. The solution was filtered, and the IAc.NaHSO3 was
recrystallized by adding absolute ethanol to a final concentration of 90% ethanol, yielding 2.5 g. of recrystallized product.
To obtain the free aldehyde, 200 mg. of the IAc.NaHSO3 was dissolved in 8 ml. water. A few drops of a saturated solution of Na2CO3 was added until the
solution turned slightly turbid. After standing a few minutes, the free aldehyde was extracted by shaking the solution with three portions of
peroxide-free ether. After evaporation of the ether and drying at reduced pressure, 82 mg. IAc was obtained as a colorless sirupy liquid.
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I suspect that the major step I left out was the heating step. It also looks as if I should have used twice as much hypochlorite.
That seems like an awful waste of benzene... with such a dilute aqueous solution, it may be required to ensure that two layers form, but wouldn't the
nitrogen in the amino acid be considerably more nucleophilic than the carbonyl in the aldehyde? And the hypochlorite oxidation is SN2, right?
I'm not that concerned about forming a little tar.
[Edited on 25-5-2016 by JJay]
[Edited on 25-5-2016 by JJay]
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JJay
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Quote: Originally posted by Crowfjord  | | JJay: Did you see my post in that same thread? In order to isolate aldehyde in any decent yield, dilute conditions and pH control (buffer) are
important. I can post the entire article later, if desired. I thought I had already posted it somewhere, but I can't find it. |
Found it: https://www.sciencemadness.org/whisper/viewthread.php?tid=22...
Those are indeed extremely dilute reaction conditions. I don't see how a phosphate buffer would be beneficial under those conditions, but maybe I'm
missing something... I think pH could matter, but I'm trying to wrap my head around exactly why.
[Edited on 25-5-2016 by JJay]
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Crowfjord
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Here's the paper and supplemental materials.
Facile one-pot synthesis of tetrahydroisoquinolines from
amino acids via hypochlorite-mediated decarboxylation
and Pictet–Spengler condensation
Maresh, J. et. al.
Tetrahedron Letters 55 (2014) 5047–5051
Attachment: Facile one-pot synthesis of tetrahydroisoquinolines from amino acids via hypochlorite-mediated decarboxylation and Picte (815kB)
This file has been downloaded 1031 times
Attachment: Facile one-pot synthesis of tetrahydroisoquinolines from amino acids via hypochlorite-mediated decarboxylation and Picte (2.7MB)
This file has been downloaded 1228 times
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JJay
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I can't seem to find Figure S2, referenced in the PDF. The other file appears to be a Microsoft Word file and has a caption for it, but I don't see
the figure.
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Crowfjord
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I converted the supplementary materials to a PDF. Maybe that will help.
Attachment: Supplementary Info.pdf (3.4MB)
This file has been downloaded 941 times
[Edited on 25-5-2016 by Crowfjord]
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Cryolite
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Another potential route to phenylacetaldehyde from phenylalanine would be oxidation to phenylacetonitrile with TCCA (DOI: 10.1055/s-0029-1218827),
followed by reduction of the nitrile to the aldehyde, via a great many possible methods: SnCl2/HCl is the classical Stephen aldehyde synthesis,
Helvetica Chemica Acta 243, pg 2560 claims that zinc/AcOH/cobalamin works, but the reference is in German, and http://www.scielo.org.za/pdf/sajc/v61/27.pdf discusses several methods using Raney nickel.
This is two steps as opposed to one, and phenylacetonitrile is a DEA listed precursor (really, what isn't when talking about ethylbenzene
derivatives?), but both reactions can proceed in fairly concentrated conditions and are high yielding and well documented-- the yield of
phenylacetonitrile in DOI: 10.1081/SCC-200030958 by TCCA oxidation is 77% after purification.
[Edited on 25-5-2016 by Cryolite]
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DraconicAcid
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My computer doesn't recognize that as a pdf....
Please remember: "Filtrate" is not a verb.
Write up your lab reports the way your instructor wants them, not the way your ex-instructor wants them.
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careysub
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Try editing the very long file name to include ".pdf" on the end after it is dowloaded.
Generally it is a bad idea to try to make an abstract into a file name.
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JJay
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I can see the figure in that PDF. Upon giving this further thought, I suppose that I should be thinking about the intermediates when considering side
reactions and the effects of differing reaction conditions... I really need to find a better description of the mechanism than a short Wikipedia
article....
It looks as though they think that 5 mmol is the optimum concentration (for tyrosine oxidation). I have to wonder about the concentrations of these
byproducts....
I found this old paper on hypochlorite oxidations of amino acids... Langheld claimed to have obtained 2.5 grams of isoveraldehyde from 5 grams of
leucine, which he first made into a sodium salt and then reacted (in strong concentration--I'm not completely sure I'm understanding this, but it
looks like 50 mL of water was used) with 0.1 M hypochlorite. That works out to a 76% yield. I don't speak German, but it looks to me as though he
removed the product by steam distillation (isoveraldehyde forms an azeotrope with water at 70 C).
I'm still not seeing why removing the product as it forms would be terribly necessary, though it would improve yields... of course, phenylacetaldehyde
would be harder to remove by distillation.... I might give this a try later today with phenylalanine and isolate the product with nonpolar extraction
/ bisulfite adduct formation and see if I get anything.
Attachment: Uber den Abbau der alpha-Aminosauren zu fetten Aldehyden mittels Natriumhypochlorit.pdf (101kB)
This file has been downloaded 708 times
[Edited on 25-5-2016 by JJay]
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Crowfjord
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| Quote: Originally posted by careysub |
Try editing the very long file name to include ".pdf" on the end after it is dowloaded.
Generally it is a bad idea to try to make an abstract into a file name. |
Sorry about that. I edited the post and file for everyone's convenience.
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zed
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Ummm. Theoretically, trans-amination would do the trick.
Formation of Phenyl-pyruvic acid, followed by decarboxylation.
That being said. Regarding hypochlorite.... I would carefully follow a known procedure, first. Before, trying to tweak reaction conditions. Guys
have reported dismal results, even when they towed the line.
I am reminded of a passage from SNL. There is a little bit of Eve in all of us.
http://www.hulu.com/watch/606107
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JJay
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Reading over that German paper again... at high magnification, it looks like Langheld used 4/10 N (??) hypochlorite. The numbers in the concentration
of sodium hydroxide are obscured, but I can't see how they could be anything other than 1/4 N. That's consistent with others who have cited the paper
who have said that the reaction was carried out in alkali (I'm referring in particular to Schonberg and Maubacher's "The Strecker Degradation of
α-Amino Acids"). So his initial experiment translates something like: "The amino acid (about 0.1 g) was dissolved in .25 M sodium hydroxide (1-2 mL)
and then combined with 2 mL of 0.4 M sodium hypochlorite." This works out to a stoichiometric amount of hypochlorite.... Langheld believed that sodium
hypochlorite chlorinated the amino acid at the nitrogen, and that the product hydrolized to an imine - giving off hydrochloric acid and carbon
dioxide, and that the imine hydrolized in the presence of water to the aldehyde.
I'm not sure what the role of alkali is here... I'm actually wondering why this isn't done in glacial acetic acid... there is water in the
hypochlorite solution....
[Edited on 27-5-2016 by JJay]
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Refinery
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The Phenylalanine definitely produces phenylacetaldehyde in such amounts that it is clearly detectable.
I dissolved 1g of L-Phen in 50mL of water and added 3mL of bleach and heated it at water bath. The aldehyde smell of flowers hit the air immediately
after first drop, and soon after my whole apartment smells like flowers. I kinda like the smell, but it gets sort of annoying after a while. My
flatmate turned right after 2 minutes to ask what is that smell. The solution turned yellowish after a while, and when the flask was moved to salt ice
bath, it turned cloudy. After an hour a few particles have settled to the bottom, but mostly it is just colloidal solution if anything. Note, this is
not balanced reaction, just a proof of concept that something actually happens. Having a bag of L-Phen hanging around, could consider running an
actual balanced reaction to find out if anything can be extracted.
I detect this smell from previous test where styrene was oxidized and then isomerized.
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JJay
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As it turns out, monochlorination of phenylalanine leads to a degradation that produces phenylacetaldehyde, and dichlorination produces
phenylacetonitrile, which is responsible for most of the odor: https://www.sciencedirect.com/science/article/abs/pii/S00431...
I will be checking this forum infrequently for the next few months, but I will be back for a short time in August and hopefully shoot some colorimetry
demonstrations.
[Edited on 10-5-2020 by JJay]
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arkoma
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| Quote: Originally posted by JJay | As it turns out, monochlorination of phenylalanine leads to a degradation that produces phenylacetaldehyde, and dichlorination produces
phenylacetonitrile, which is responsible for most of the odor: https://www.sciencedirect.com/science/article/abs/pii/S00431...
I will be checking this forum infrequently for the next few months, but I will be back for a short time in August and hopefully shoot some colorimetry
demonstrations.
[Edited on 10-5-2020 by JJay] |
Your back.......Yay
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