Sciencemadness Discussion Board

nutra sweet ---> Phenylacetic acid

ewok_poacher - 20-11-2007 at 21:52

Nutra Sweet and equal are mostly Aspartme wich is phenylalanine aspartic amide methyl ester.
The amide group and the methyl ester on the carbonyl group are both hydrolized by boiling HCl acid mixtures to give methyl chloride, aspartic acid, and phenylalanine.
Treat phenylalanine with household bleach (strecker degredation) to make phenylacetaldehyde.
Then add H2SO4 --sulfuric acid--and a dichromate salt to make chromic acid to oxidise the aldehyde to the acid via reflux.
Phenylacetic acid is purified from the mix by steam distillation.

is this possible? It is just a theory of mine.

ewok_poacher - 20-11-2007 at 21:55

Here is aspartme to benzaldehyde

Benzaldehyde Formation from Aspartame in the Presence of Ascorbic Acid and Transition Metal Catalyst

Glen D. Lawrence* and Dongmei Yuan

Chemistry Department, Long Island University, Brooklyn, New York 11201

Received for review February 2, 1996. Revised manuscript received August 2, 1996. Accepted August 20, 1996.

Abstract:

Benzaldehyde was produced from aspartame in aqueous acidic solutions containing ascorbic acid and Cu(II) or Fe(III) ion. Benzaldehyde was identified in the system by GC-MS. The yield of benzaldehyde decreases dramatically as the pH of the medium increases above 2.0. EDTA and DTPA completely inhibited benzaldehyde production, while desferrioxamine inhibited only the Fe(III)-catalyzed reaction. Benzaldehyde is not produced under anaerobic conditions unless H2O2 is added to reaction mixtures. H2O2 is produced by reduction of atmospheric oxygen under aerobic conditions. Benzaldehyde production was dependent on ascorbic acid concentration, but the yield of benzaldehyde decreased as the concentration of ascorbic acid exceeded that of aspartame. Addition of ethanol to the reaction mixture had little or no effect on benzaldehyde production, suggesting a mechanism that may not involve free hydroxyl radical. A mechanism is proposed for the reaction.

Keywords: Aspartame; benzaldehyde; ascorbic acid; free radical degradation products; copper(II)

evil_lurker - 20-11-2007 at 22:45

IIRC phenylacetaldehyde is not easy to oxidize to the corresponding caboxylic acid.

Most oxidizing agents are simply too harsh, and the end product is benzoic acid.

[Edited on 21-11-2007 by evil_lurker]

chemrox - 20-11-2007 at 22:55

This seems a rediculously expensive way to get PAA. How about Ph-Br + CuCN -> Ph-CN thence to the acid by hydrolysis?

Sauron - 20-11-2007 at 22:55

Most people who are interested in these products by this route just proceed from phenylalanine and decarboxylate that. Hydrolyzing the dipeptide methyl ester Phe-Asp-Me (i.e., Aspartame) is rather wasteful.

not_important - 20-11-2007 at 23:08

What the others have said. And also
Quote:
The amide group and the methyl ester on the carbonyl group are both hydrolized by boiling HCl acid mixtures to give methyl chloride...


Uh, no, not methyl chloride. Do some reading on esters.

MagicJigPipe - 20-11-2007 at 23:45

Is there any use for phenylacetic acid other than the preperation of phenylacetone?

not_important - 21-11-2007 at 00:13

Some of its esters are used in perfumery and the like, often having a honey-like scent with floral hints. And it's used in making penicillin G.

solo - 21-11-2007 at 07:15

There is a thread at WD called Phenylalanine + TCCA revisited there you might find what you seek......solo


.................here it is ,

Attachment: phenylalanine +TCCA - thread from WD.pdf (131kB)
This file has been downloaded 8218 times

Sauron - 21-11-2007 at 07:31

chemrox my friend, I think you mean benzyl bromide not bromobenzene.

PhCN is one carbon short to hydrolyze to phenylacetic acid.

The precursor is phehylacetonitrile (benzyl cyanide.) The preparation from any benztl halide is described in Org.Syn.

MagicJigPipe - 21-11-2007 at 10:00

I always wondered why benzyl cyanide was a list 1. I knew it had to do with methamphetamine. I just didn't connect it with phenylacetone... makes perfect since now though...

solo - 17-10-2008 at 07:01

Quote:

PhCN is one carbon short to hydrolyze to phenylacetic acid.


.........not so,

......Phenylacetic acid from Benzyl Cyanide [2]




In a silica basin of about 35 cm. diameter, a mixture of 2.5 kilos of benzyl cyanide [3] and 7.5 kilos of 70% sulfuric acid is warmed until a few bubbles of gas appear. The heating is at once stopped, since a very vigorous action now ensues. As the vapors evolved are injurious to health, the basin is covered when the reaction begins with a sliding cover from which the vapors can be led into water. As soon as the reaction ceases, the product is poured upon crushed ice in a large, earthenware vessel. Crude phenyl acetic acid, contaminated on the surface with phenyl acetamide, is precipitated on cooling. In order to remove the amide, the acid is dissolved in lukewarm dilute soda solution. The amide remains undissolved and can be filtered off, while the phenyl acetic acid goes into solution as sodium salt and is reprecipitated in a sufficiently pure state by the addition of dilute mineral acid. After drying it is acceptably pure.

Ref
[2] Perfumery Essent. Oil Record 14, 336 (1924)
-----------------------------------------------------------------------

Note: I guess nomenclature can be difficult, and so i stand corrected in my comment...but will leave the nice reaction....solo

[Edited on 17-10-2008 by solo]

sparkgap - 17-10-2008 at 07:26

Friend solo,

That indeed is a nice prep; Sauron's remark still stands, unfortunately. That which you posted started from benzyl cyanide (phenylacetonitrile). PhCN (damn abbreviations, I always said) is benzonitrile, C<sub>6</sub>H<sub>5</sub>CN, indeed one carbon short from being phenylacetonitrile.

sparky (~_~)

Sauron - 18-10-2008 at 05:39

Ph is certainly phenyl, not benzyl.

Benzyl cyanice (phenylacetonitrile) is made by reacting benzyl chloride or bromide with alkili cyanide. And those benzyl halides by halogenating toluene, not benzene.

Benzyl cyanide like PAA has 8 carbons.

Benzonitrile has only 7 carbons.

It's named as a derivative of benzoic acid via benzamide, while phenylacetonitrile is a derivative of phenylacetic acid via phenylacetamide.

The benzyl nomenclature is an extension of the halogenated toluenes, regarding -CN as a pseudohalogen, fair enough.

Phenyylacetonitrile = phenyl methyl cyanide.

Well, people do get mixed up about acetophenone and methyl benzyl ketone, as well, even though they shouldn't.

Ephoton - 18-10-2008 at 12:24

I take back everything I have said about my dark lord

[Edited on 18-10-2008 by Ephoton]

Sauron - 18-10-2008 at 16:47

Well, taken out of thread context, that post appears to be a litany of the obvious, but people do seem to stumble over these nomenclatural nuances from time to time. Benzonitrile isn't "benzyl nitrile" even though they sound alike. Which is probably the source of the confusion.

At least in the instance of phenylacetonitrile, thinking phenyl + acetonitrile will get you where you want to go.

But the prefixes are not always logical OR consistent. Benzo- in benzonitrile is not quite the same as benzo-in benzotrichloride is it? Or for that matter in benzophenone?

I guess that's why there's an IUPAC Nomenclature Committee.

The abbreviations are even murkier.

I would have thought Ph was unambiguous.

But, I always have problems with Bz which I took to be nenzyl, but I am informed by len1 it is actually benzoyl, while Bn is benzyl.

And don't get me started about protecting-group abbreviations from peptide chemistry because it is utterly upgefucked. I mean Z- is for the chemist Zervas who was Max Bergmann's student who came up with benzyl chlorofotmate as a protecting reagent. No one else got a named PG.


[Edited on 19-10-2008 by Sauron]

zed - 19-10-2008 at 01:13

Interesting reaction....You can easily Produce Phenylacetonitrile from Phenylalanine....... Using simple stuff you can probably buy at K-Mart.

I didn't know that.

I know this though. Nitriles are a lot more toxic than many people imagine, and if you want to continue to wake up in the morning, you will treat them with respect.

Tee, hee....."Wake up in the morning". That was a clever reference to how nitriles often kill people. They are overexposed to a nitrile, perhaps Acetonitrile, they go home, go to sleep, and then they never wake up in the morning.

There were a rash of such deaths in the late 70s, and I received a barrage of warnings by post. Acetonitrile, which had formerly been used in "Closed" systems, as an industrial solvent......Was starting to be used as a common lab solvent, and some folks had died thereby.

Turns out, that as Nitriles go, Acetonitrile actually isn't very toxic. Play as free and easy with some of its analogs, and you may come due for a rude "Non-Awakening".

http://en.wikipedia.org/wiki/Acetonitrile

Sauron - 19-10-2008 at 02:08

As a generalization organic nitriles are less toxic than inorganic cyanides. I can think of one exception, which is 1,4-tetramethylene dinitrile. I never looked into why this is so.

Phenylacetonitrile is also not very toxic. That does not mean you should take a bath in it or deliberately overexpose yourself to its vapors. Would you do those things with methanol or benzene?

A lot of reactions involving nitriles as precursors or products can release HCN to some extent and that IS toxic. On the other hand unless you have a deathwish you will always work IN A GOOD FUME HOOD which cannot be stressed enough.

HCN intoxication is rather easily countered with bottled O2, a breather and a Fischer kit. The trick is not to work alone.

But compare this to H2S intoxication, for which there isn't any antidote I know of. In the petrochemical industry H2S is the 2nd major cause of industrial fatalities, after fire.

Making PAA out of Phe or D-Phe is a waste of a perfectly good amino acid. And as a reminder, we do not spoonfeed the drug cooks on this forum. They have their own forums for that, may thgeir bandwidth vanish.

[Edited on 19-10-2008 by Sauron]

jarynth - 19-10-2008 at 04:41

Quote:
Originally posted by Sauron
As a generalization organic nitriles are less toxic than inorganic cyanides.


I used to think so too, but apparently, the brain toxicity of higher alkyl cyanides is comparable with that of inorganic cyanides.

Sauron - 19-10-2008 at 06:20

Higher alkyl? Like C-what? It does not appear to apply to aryls or arylalkyls or heterocyclics.

And "brain toxicity"? Inorganic cyanides block oxygen takeup by hemoglobin in blood. That's why O2 inhalation is immediate aid, and methylene blue and thiosulfate antidortes. Inorganic cyanides are ionic and water soluble. Highert alkyls nitriles are going to be covalent, hydrophobic and insoluble. So what route of administration are we talking?

There are -CN containing OP CW agents but that is not what we are talking about.

Alkili cyanides were used in clandestine (illegal) PCP labs and some of those hapless cooks were not up to handline them, while others left them in the angel dust and killed their customers. When I was at school the department used to get calls from the local narcs, asking "Hey this lab has piperidine, bromobenzene, and NaCN (or KCN) what are they marking?) "PCP" I'd yell to the prof from my lab bench. "Tell your boys to watch out for the ether." And of course a lot of those labs got spotted after ether fires. The firemen would rat them out.

Klute - 19-10-2008 at 06:27

Sauron, sodium nitrite is an antidote to H2S poisoning. Nitrite esters can also retard the effect as long as they are inhaled (optionw hen waiting for proper treatment).

Sauron - 19-10-2008 at 06:35

That's reassuring to learn.

tapira1 - 19-10-2008 at 07:31

Where you wrote pH you meant Bn,i.e,
BnBr + NaCN --> Ph-CH2-CN
Ph-CH2-CN + H+ --> Ph-CH2-CO2H + NH4+
Better: Ph-CH2-CN + NaOH --> pH-CH2-CO2-
Quote:
Originally posted by chemrox
This seems a rediculously expensive way to get PAA. How about Ph-Br + CuCN -> Ph-CN thence to the acid by hydrolysis?

Sauron - 19-10-2008 at 08:55

Damn those abbreviation!

If you want to use Bn use it, if you want to use PhCH2- use that. Please do not jumble them up, it's heaache-making!

BnBr + CuCN (or NaCN) -> BnCN + inorg. bromide

or

PhCH2Br + (pick your cyanide) -> PhCH2CN -> PhCH2COOH

Isn't that less painful?

This is the classical Ortg.Syn. blessed route from benzyl halide to PAA

starman - 19-10-2008 at 15:27

Quote:

Benzaldehyde was produced from aspartame in aqueous acidic solutions containing ascorbic acid and Cu(II) or Fe(III) ion. Benzaldehyde was identified in the system by GC-MS. The yield of benzaldehyde decreases dramatically as the pH of the medium increases above 2.0. EDTA and DTPA completely inhibited benzaldehyde production, while desferrioxamine inhibited only the Fe(III)-catalyzed reaction. Benzaldehyde is not produced under anaerobic conditions unless H2O2 is added to reaction mixtures. H2O2 is produced by reduction of atmospheric oxygen under aerobic conditions. Benzaldehyde production was dependent on ascorbic acid concentration, but the yield of benzaldehyde decreased as the concentration of ascorbic acid exceeded that of aspartame. Addition of ethanol to the reaction mixture had little or no effect on benzaldehyde production, suggesting a mechanism that may not involve free hydroxyl radical. A mechanism is proposed for the reaction.

This looks like classic Fenton/Udenfriend hydoxylation.I would doubt the authors claim about the production of no free radicals.I haven't seen ethanol used as a determining scavenger before.

Ephoton - 19-10-2008 at 20:44

if pan is toxic then im a ghost

a nice easy way although it doesn't abuse a other
scheduable compound would be loomins too benzyl chloride. lead tartrate reduction of cyanates too cyanide and the rest as stated here.

lead acetate and disolved cream of tartar will percipitate lead tartrate.

this is all very smooth and easy as well as otc.
just do your home work and fear that lead ;)

at least with cyanide you know if your poisoned.

[Edited on 20-10-2008 by Ephoton]

[Edited on 10-20-2008 by Polverone]

Ephoton - 22-10-2008 at 02:41

a note pure paa is almost sentless. slight acidic honey smell. cat piss in the morning is sloppy ;).
the amide stinks though and the mix of the two in any quantity gives that horrid smell.

[Edited on 22-10-2008 by Ephoton]

Ephoton - 23-10-2008 at 06:11

please lock this thread