Sciencemadness Discussion Board

oxidation of N-vinil-2-pirrolidone to N-ethanamide-2-pirrolidone, a little help please.

Dr.S.A.M. - 27-2-2008 at 06:14

Hi this is my first post, forgive me if its against the board rules to open a new topic before posting.

I'm trying to find a route to pirrolidone-N-ethanamide from povidone and so far i came up with this synthesis and i would like to know from some of you if its actually feasible in terms of simplicity and yield.

Ok so:
step 1) the povidone is dissolved in conc. H3PO4 and boiled at lets say 150-200c with activated carbon to give a primary alcohol.

(pirrolidone)-C=CH2 + H2O --(H3PO4)--> (pirrolidone)-C-C-OH

(I also read that it is possible to oxidise the alkane with sulphuric acid, would that be better?)

Step 2) the alcohol is oxidised to a carboxylic acid by heating it for a long time in a aqueous solution of potassium dichromate.

(pirrolidone)-C-C-OH + K2Cr2O7 ---[O]--> (pirrolidone)-C-(C=O)-OH

Step 3) the substace is turned into an amide by dissolving it with an excess of diluted ammonia to form an ammonum salt which becomes an amide upon dehydration.

(pirrolidone)-C-(C=O)-OH + NH3 ---(- H2O)--> (pirrolidone)-C-(C=O)-NH2

Would this work? Can anyone spot a mistake or suggest a better reaction? can the pirrolidone be damaged during these reactions?

Any help will be greatly apreciated

[Edited on 27-2-2008 by Dr.S.A.M.]

Nicodem - 27-2-2008 at 06:53

Well, a simple internet search would have told you that povidone is a polymer which I would tend to guess is pretty impossible to depolymerize to N-vinyl-pyrrolidone by any simple means. From your post it is pretty obvious you have mistaken the monomer with the polymer.

Besides that, the addition of H2O on N-vinyl-pyrrolidone can only yield the intermediate N-(1-hydroxyethyl)-pyrrolidone which decomposes either back to N-vinyl-pyrrolidone or to acetaldehyde and pyrrolidone (which in short means that heating N-vinyl-pyrrolidone with H3PO4 in presence of water gives pyrrolidone and the black tar resulting from acetaldehyde acidic decomposition). I will not go into details regarding the steps 2 and 3 but things are not so simple as you tend to believe.

PS: The end compound is actually available as a pharmaceutical product, a nootropic for preventing dementia in elderly and alcoholics. It's most known trade name is Piracetam. So instead of wasting time in trying to prepare your end compound you can just buy it if all you need is small quantity. It generally comes in 400 mg capsules/pills and can easily be purified. Patients usually take several grams per day and it is fairly cheap. See also http://en.wikipedia.org/wiki/Piracetam. It is also commercially available from chemical suppliers, though apparently at least twice more expensive than if bought in a pharmacy (unless you buy in bulk, of course). The synthesis of this compound was also already discussed here:
https://sciencemadness.org/talk/viewthread.php?tid=9288
https://sciencemadness.org/talk/viewthread.php?tid=4592

[Edited on 27/2/2008 by Nicodem]

Dr.S.A.M. - 27-2-2008 at 08:49

wops, i read again and i noticed that even the water dissolved form is in fact a polymer, sorry my mistake.

well nicodem, the reason why i am curious about this synthesis is because im not from america where everything can be bought in a k-mart.
where i'm from piracetam has to be prescribed (here where i am even 5-htp has to be prescribed, ridicuous) and the funny thing is that most doctors dont know what the heck that substance is since they sit around doing nothing all day thinking that what they studied 20 years before is enough to do their jobs. Many doctors ive talked to didnt even know what ritalin was....bwaha.

yes i did some reaserch on the compound, its a potent nootropic which besides preventing brain deterioration in elderly and alcoholics, enhances the neural connections between the two hemispheres of the brain, enhances cognition, concentration, memory, brain oxygenation, neurotransmitter efficency and neuroimmunity. it has been used extensively as a studying and working aid and in some countries it is used as a food supplement, im not an alcoholic and i highly doubt i have dementia, however im still interested in giving it a try.

ok, back to the synthesis: povidone is only found in its polymer form right? so the most logical route would be to hydrolize the pirrolidone from the polycarbom chain (maybe with the help of some H3PO4), extract it (acid base extraction should work fine i guess), and react it with 2-bromoethanol (maybe even chloroethanol?) instead of using the nasty ethyl-bromoacetate. then oxidise it to a carboxylic acid with a permanganate (that shouldn't attack the amine according to other similar reactions i've saw, correct me if im wrong), re-extract and react it with ammonia to form the ammonium salt, then according to what i've read on wikipedia, dehydration should give the amide.

any flaws?

not_important - 27-2-2008 at 08:57

Quote:
Originally posted by Dr.S.A.M.povidone is only found in its polymer form right? so the most logical route would be to hydrolize the pirrolidone from the polycarbom chain (maybe with the help of some H3PO4), ...
any flaws?



Look at http://en.wikipedia.org/wiki/Crospovidone

the backbone is the vinyl pyrrolidone, a vinyl amine. There's nothing there to hydrolise, except to open the pyrrolidone ring. You'd likely have more success starting with MSG to make the ring. See United States Patents 3235563 and 7022863, for example.


[Edited on 27-2-2008 by not_important]

Dr.S.A.M. - 27-2-2008 at 10:35

About the phosphoric acid, i was kind of referring to what nicodem said.

He said that reacting H3PO4 with the povidone monomer would yield pyrrolidone and a black tar from acetaldehyde decomposition. i thoguht it would be the same even in case of a vinyl polymer.

Thanks for the info about monosodium glutamate, i will research on that.

Do the rest of the steps work out? is there a chance that some unreacted carboxylic pyrrolidine could condensate with the final amide?

Chemrox i have a few difficulties understanding your post...
where you asking if it is hard to get piracetam here?

Yup unfortunately many substances that in the us can be bought in a common store are available only with prescription here.
Here in Italy as i said before even 5-HTP which is nothing more that a nutritional supplement (a hydroxylated version of an aminoacid commonly found in any mammals) can only be bought with prescription.....i find that ridiculous.

Klute - 27-2-2008 at 12:26

Concerning the amide formation, idealy you should transform your carboxylic acid to an acyl halide with SOCl2 or PCl3 for example, if the rest of the molecule can handle reflux with such a reagent (I think the cyclic amide wouldn't be harmed, but don't take lmy word on it.).
Otherwise, make an ester with the carboxylic acid and MeOH or EtOH and cat. acid, and react your ester with conc. NH4OH or even dry NH3. You should get better yields/fewer byproducts than heating the ammonium salt in general.

Nicodem - 27-2-2008 at 13:25

Dr.S.A.M., It is quite possible you are one of the last internet users who had the luck of never had heard of online pharmacies. You must have one hell of an effective spam filter on your email. ;)

Povidone is a polymer that can not be hydrolyzed to any simpler constituent. As not_important already said, the product of hydrolysis would still be a polymer (a poly amino acid). The only way to obtain some pyrrolidone from povidone would be to oxidize the polymer (this would result in a terrible mixture of products of which pyrrolidone would be only one). This would be completely pointless since pyrrolidone is a commercially available and unregulated chemical – you can simply buy it, especially in EU where buying from chemical suppliers is so easy. You can also buy piracetam directly as a chemical, since buying it this way you don't need any prescription, but then you would be found in a boring situation where there is no need to do any synthesis and you would learn no chemistry. With your current level of knowledge you would not be able to synthesize it even if you had all the starting materials, however if you hang around for a couple of years, read more about chemistry and laboratory practice, do some experiments and so on… then such a synthesis should be no problem.

It also appears to me that you have no actual experience with Piracetam. It has nearly no effects on healthy people (at least not on me – assuming that I could pass as healthy). It is only useful to ameliorate dementia symptoms in those who already are demented. Furthermore, it is not psychoactive and its use (by normal subjects) gives no improvements in cognition and memory that could be distinguished from a placebo (unless you actually are demented).

LSD25 - 28-2-2008 at 09:00

See, now I expect I qualify:P

I have actually reacted povidone with polyphosphoric/metaphosphoric acid (I actually did this with Povidone-Iodine*), giving a muddy-brown precipate and a clear solution when some water was added. Now, as the brown precipate did not appear to hold the iodine that was also in the mix, would this be the acetaldehyde-derived tar of which you speak?

In that case, both the iodine and the pyrrolidinone would be in the solution? I suspected at least the iodine was in there, there was a distinctive halide-type smell.

*This is the only quick & completely effective method by which I have managed to remove the remnants of the polyphosphoric/metaphosphoric acids from a vessel. Iodine is just too hard to come by now for me to use it for this so PVP-I2 will have to suffice.

not_important - 28-2-2008 at 09:16

Quote:
Originally posted by LSD25
See, now I expect I qualify:P

I have actually reacted povidone with polyphosphoric/metaphosphoric acid (I actually did this with Povidone-Iodine*), giving a muddy-brown precipate and a clear solution when some water was added. Now, as the brown precipate did not appear to hold the iodine that was also in the mix, would this be the acetaldehyde-derived tar of which you speak?
...


NO - povidone - iodine is a mix of iodine and poly-vinyl-pyrrolidone. Like most vinyl polymers, it does not readily depolymerise; those that do such as polystyrene and poly methylmethacrylate, do so when strongly heated.

Nicodem was talking about the monomer N-vinyl-pyrrolidone, before it is made into the plastic. The monomer is rather nasty stuff, toxic and carcinogenic. This is an alkene, a vinyl-amine, which can rearrange to an imine and the hydrolyse to the amine (actually an amide in this case) and acetaldehyde.

You are not going to be able to prepare your target compound from povidone, the polymer is not going to unzip in wet chemical reactions.

What you got was likely a complex and/or mixture of povidone, iodine, and phosphoric acids; the brown colour is a clew that the iodine is there in complexed form.

LSD25 - 28-2-2008 at 09:29

Good, I was wondering what it was

The reaction is the same every single time I have done it, quick as all fuck, the solid glass-like polyphosphoric acid is shifted in no time.

The reason I originally tried it is because PVP is said to be vulnerable to strong acids, undergoing hydrolysis to pyrrolidinone. I should now go and have another look to make sure the articles I took this information from were referring to the polymer, although I have a sinking feeling about it right at the moment.:(

Back soon

[EDIT]

Back again,

My memory is not serving me all that well at present. In the presence of protic acids PVP crosslinks to PVP-P under PH4.

http://www.patentstorm.us/patents/6660800-description.html

http://www.wipo.int/pctdb/en/wo.jsp?wo=2004035637&IA=WO2...

Although the patents generally use heat and a base, this would be my guess (it actually is/was my guess) as to what happens. The polyphosphoric/metaphosphoric acids seem to do some strange shit.

BTW the expected amount of iodine from the reactions seriously exceeds the amount of polymeric crud formed. I expect that there is some of it in the crud, I also feel that there is a lot of it in the clear solution remaining (the smell is sufficient to tell me that).

[Edited on 28-2-2008 by LSD25]