phenylacetic acid from phenylalanine

stratosphere · Tue Jun 14, 2005 7:03 pm

while phenylalanine might sound like a pricey (~2$/g) precursor to phenylacetic acid it seems in theory that the ease of conversion might make suitable for those interested in creating small amounts of phenylacetic acid.

i was wondering how well oxidative deamination with nitrous acid would work for producing 2-hydroxy-3-phenyl-propanoic acid?
the other possibile and unwanted outcome being that the diazonium would decompose by eliminating a proton from the benzyl carbon and givie cinnamic acid before water could nucleophilicly add to the 2 carbon.

if this succeded in giving the 2 hydroxy species, is there any convient and perhaps more mild way to oxidize it besides permanganate?
im not very familiar with the chemistry of alpha-hydroxy acids and google seems to just want to give skin care products or complex biochemistry when anything invlving alpha-hydroxy acids is searched.

Elementary · Tue Jun 14, 2005 7:31 pm

You're diving a bit to deep into chemistry here for me, but I can add that phenylalanine has been succesfully converted into phenylacetaldehyde using a hypochlorite, I remember contributing to a hive thread about the topic.

java · Consumer

This was donated to me by a member at WD (psuedonymph)......................java
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Aurelius
(Hive Bee)
12-01-01 23:37
No 243107
Re: PPA from benzaldehyde & nitromethane

on the topic of Phenylacetaldehyde, does anybody have the reaction conditions and workup for P. Alanine to phenylacetaldehyde with bleach?

Aurelius
(Hive Bee)
12-01-01 23:40
No 243108
Re: PPA from benzaldehyde & nitromethane

there shouldn't be a problem using Ca(OCl)2, correct?

(assuming 1/2 the molar ratio or same number of OCl- equivalences)

Rhodium
(Chief Bee)
12-02-01 03:12
No 243144
Re: PPA from benzaldehyde & nitromethane

References on the Strecker degradation of amino acids to aldehydes:

http://www.geocities.com/chempen_software/reactions/RXN375.htm

Here is the procedure for tryptophan to indoleacetaldehyde. I don't think too many variables has to be changed for it to work with phenylalanine:

http://www.rhodium.ws/chemistry/indoleacetaldehyde.html

- - - - - -

Here are two old a.d.c posts on the subject:

I suppose my original post was a little glib when I claimed simply that phenylalanine in dilute sulfuric acid would turn ino phenylacetaldehyde,with portionwise additions of NaNO@ or lazy. Since I got some bad mail suggesting I' a spook and since the post has dissappeared, I guess i"ll try again providing contions and a little homework:

Standard organic chemistry texts that I have read give nitrosification in acetic aqueous media as a means of deamination of aromatic amines ( the product being the corresponding alcohol). The same texts stane that the reaction is of LITTLE or no utility with aliphatic amines in general, giving mixtures of alkenes and alcohols. Again, another reaction I want to point out is that of DECARBONYLATION OF ALPHA HYDROXY AMINES. Such elementary texts describe, and I quote from Noller: CHEMISTRY OF ORGANIC COMPOUNDS, Saunders, p 857, " When alpha hydroxy acids are boiled with dilute sulfuric acid, carbon monoxide and water are lost with the formation of an aldehyde, a behavior called decarbonylation. Now, dilute acid (aqueous albeit chilled with additions of NaNO2 are just the mixtures used to deaminate aromatic amines) and I am claiming that the deamination of phenylalanine that subsequently proceedes to decarbonylation to produce phenylacetaldehyde is of very good utility indeed under rather simple conditions, and if you follow my steps this claim will be born out:

TO a saturated aqueous solution of phenylalaine and some sufuric acid ( not so concentrated that the evolution of NO2 gas is too vigorous or abrupt) I added portions of NaNO2 (noxious brown gas comes off - a fume hood or other good ventilation is necessary although carbon monoxide evolution is not so vigorous as to be dangerous) it is desired that the mixture be stirred to a gentle effervescence by adding portions of NaNO2 with gentle loving care, then gradually heating to boiling as gas (NO2) evolution gets weaker,then cool and repeat. After about 20 minutes a light brownish oily residue of drops begin to separate ourt having a sweet and candy-like smell somwhat reminiscent of cinnamaldehyde. I continue adding NaNO2, stirring and heating this way untill phenylalanine is spent or I add more phenylalanineand continue as a process. If necessary add HCl to keep acidic when NaNO2 gas is no longer emitted. I have by no means perfected the process, maybe it would get better milage from the NaNO2 if I started it chilled, but the phenylacetaldehyde is fine and easily extracted from this mommie liquor with trichloroethane (god have mercy on the enviornment).

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Conceivably conditions could be found that would allow in-situ hydrolysis of the imine formed from phenylalanine to give phenylacetaldehyde would would then be further oxidized to phenylacetic acid which can then be converted to P2P and then to ---- by any of the usual methods. Of course, this oxidation would stink to high heaven (phenylacetaldehyde smells even stronger than phenylacetic acid, which really smells), but it uses readily available materials. I haven't had a chance to try it out so if anyone else would like to I'd love to hear of your results (see H. L. Slates et al, J. Org. Chem., 29, p. 1424 (1964) for a starting point).

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blondie
(Hive Bee)
10-22-02 14:50
No 371231
phenylacetaldehyde

another route to phenylacetaldehyde -

benzaldehyde + nitromethane --> b-nitrostyrene
b-nitrostyrene (Cr(ii)Cl catalysed nef reaction) --> phenylacetaldehyde (80%) foxy2: "Re: P2P - 100% OTC !?!" (Chemistry Discourse)

Wouter
(Stranger)
12-14-02 17:55
No 389461
Henry (Kamlet) reaction with ethylamine

Does anyone know of this is possible; Henry reaction* with EtNH2 instead EtNO2? If it works it's possible to make PPA with one-reaction from BzH!!smile Please let me know...

*http://themerckindex.chemfinder.com/TheMerckIndex/NameReactions/onr182.htm

Rhodium
(Chief Bee)
12-14-02 21:38
No 389514
No, the henry reaction only works with ...

No, the henry reaction only works with nitroalkanes.

stratosphere · Fri Jun 17, 2005 3:36 pm

well thanks for the input, it appears the hypochlorite method might be the way to go.
bleach, borax for ph buffer and p-alanine, doesn't get much more otc then that.

i found this reference for it http://designer-drugs.com/pte/12.162.180.114/dcd/chemistry/p2p.strecker.html

stratosphere · Sat Jun 18, 2005 5:35 pm

indeed a quick and dirty experiment seems to confirm the bleach route.

a 400mg PA capule was emptied into about 50ml of warm water and dissolved to the extent possible, 25ml of 6% bleach was added and after a minute or 2 of stirring a strong lilac odor began permeating the room.(if youve ever stood next to a blooming lilac bush this is dead on what it smells like) this indeed matches the description of the oder of phenylacetealdyhde.