Aqua-regia1
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Preparation of piperidine from pyridine?
Hi
Does anyone know a good alternative with full particulars recipe for hydrogenations of pyridine to piperidine?
The following ways to piperidine are disinterrested (for me):
-from pepper via piperin
-pyrolise of cadaverine
-hydrogenisation with etOH + Na
Thx: Aqua
[Edited on 22-2-2008 by Aqua-regia1]
[Edited on 22-2-2008 by Aqua-regia1]
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Klute
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Try the search engine:
http://www.sciencemadness.org/talk/viewthread.php?tid=8339&a...
http://www.sciencemadness.org/talk/viewthread.php?tid=8158&a...
and countless others....
From a quick glance, electrolysis looks interesting if you can't perform hydrogenations safely.
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Aqua-regia1
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Ok, thx. It woluld seem, I'm stock-blind again  )
Otherwise, does it work the hidrogenisation with Sn + HCl, or too forceful?
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Fleaker
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Well if you can get pyridine, you can get piperidine, can't you?
But as our good chemist Klute has mentioned, the search engine should have all you need on it.
I seem to recall that it can be hydrogenated in ~90% yields with Pd/C or PtO2 at about 5 atm H2. I am fairly sure this is at room temperature. I've
never had to make it before, it is commercially available, but I would either try hydrogenation, or electroreduction.
Sn+HCl probably will not work for this.
Sodium and ethanol is extremely wasteful of sodium (six moles of Na required).
Lithium aluminum hydride and borohydride would probably work as well, but they are both expensive, and the former is a bothersome reagent to use
safely.
Doing some peptide coupling?
Oh, as a caveat, general we don't ask for recipes here.
Neither flask nor beaker.
"Kid, you don't even know just what you don't know. "
--The Dark Lord Sauron
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Sauron
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Sodium and ethanol are indeed the usual method for lab scale preops of piperidine from pyridine. The method does consume rather a lot of sodium.
But the alternative is catalytic nuclear hydrogenation in an autoclave. If you have a suitable pressure reactor, fine, but if you don't, you'd
certainly have to need piperidine rather badly to spend that sort of money for this purpose alone.
In my case, I have 6 Kg of Na metal at hand and I also have a 1 liter Parr stirred pressure apparatus, with mantle, thermostat, controller for mantle
and motor, etc. Paid a couple thousand dollars for it last year, and it is still sitting in USA awaiting shipment here along with some other goodies.
This system can handle 1900 PSI and has a working capacity of about 650 ml.
Eventually I will need some piperidine for Fmoc-strategy peptide coupling, a 5% soln of piperidine is usual deprotection reagent in this strategy. And
piperidine is proscribed here, for no good reason since AFAIK angel dust was never a problem street drug here. But, there you are.
I am unaware of any alternative methods of effecting this reduction.
You might be better off closing the ring from an acyclic precursor.
Sic gorgeamus a los subjectatus nunc.
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chemrox
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PCP has about disappeared but piperidine and cyclohexanone still bear the stigma.
"When you let the dumbasses vote you end up with populism followed by autocracy and getting back is a bitch." Plato (sort of)
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Sauron
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The drug enforcers will argue back that PCP has disappeared because of their interdiction of diversion of piperidine and cyclohexanone and
bromobenzene etc etc.
I disagree, but, no one listens to me anyway.
I think PCP has dropped off the radar because it was altogether an unsatisfatory experience even for polydrug abusers.
Sic gorgeamus a los subjectatus nunc.
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MagicJigPipe
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I know that (as of 2 years ago) PCP is virtually non-existent. Don't get me wrong, I never touched or wanted to touch the stuff but when you hang
around the kind of "losers" I did for long enough, you start to learn what is available and what isn't.
I agree with you Sauron in that PCP has disappeared not because of govt. intervention but because of it's stigma (angel dust), the fact that it's no
longer used on animals or humans (no diversion) and because of it's unpleasant effects.
In fact, I think ketamine would be equally non-existent if it wasn't able to be diverted from veteranary clinics.
I don't know many other legitimate uses for piperidine off the top of my head but I know there are many. I was interested in it at one point.
Does this belong in detritus?
[Edited on 23-2-2008 by MagicJigPipe]
"There must be no barriers to freedom of inquiry ... There is no place for dogma in science. The scientist is free, and must be free to ask any
question, to doubt any assertion, to seek for any evidence, to correct any errors. ... We know that the only way to avoid error is to detect it and
that the only way to detect it is to be free to inquire. And we know that as long as men are free to ask what they must, free to say what they think,
free to think what they will, freedom can never be lost, and science can never regress." -J. Robert Oppenheimer
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garage chemist
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There is a very easy electrolytic method for reduction of pyridine to piperidine.
It involves electrolysis of a solution of pyridine in dilute H2SO4 (with at least 4 mol H2SO4 per mol pyridine) with two lead electrodes. A diaphragm
is not necessary. The electrolysis is continued until only hydrogen continues to be evolved at the cathode.
Then basify, extract and distill, and form an amide (e.g. benzoylpiperidine) to separate it from pyridine residues, as pyridine and piperidine can't
be separated easily via distillation.
This was from a patent I once read, here is a similar one, but not the one I meant:
http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=GB395741&a...
As I said, a diaphragm isn't absolutely necessary.
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Aqua-regia1
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Have you ever tryed this patent? I have a bad experience with them. Occurs a strong hydrogenolysis, althoug I used diaphragm. The yield only 20% of
pure piperidine. My current was 0,1A/ cm2. I isolated high percentage of aliphatic amino coumpond. For example amylamine, propylamine. It is a proof,
that the ring has broken.
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Nicodem
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Here are two references, one a CTH reduction and the other a hydrogenation. Ru and Ni based catalysts work best. Pd an Pd only appear to work under
very harsh conditions, probably due to partial poisoning by piperidine and pyridine (maybe under acidic conditions… I don’t know since I did not
check the literature).
Reduction of aromatic rings by 2-propanol with Raney nickel catalysis.
Srivastava, S.; Minore, J.; Cheung, C. K.; Le Noble, W. J
Journal of Organic Chemistry, 50 (1985) 394-396.
Hydrogenation of derivatives of pyridine.
Adkins, Homer; Kuick, Leo F.; Farlow, Mark; Wojick, Bruno.
Journal of the American Chemical Society, 56 (1934), 2425-2428.
Piperazine hexahydrate is said to work just as well as piperidine for Fmoc deprotection.
To Sauron, Chemrox and MagicJigPipe: Do not pollute every thread with your drug discussions. Stick to the topic or I’ll remove your
posts. If you can’t help yourself from diverting the discussion, then rather chose to discuss these things through U2U system or in appropriate
threads. It is sad to see a thread being hijacked on every opportunity.
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solo
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Reference Information
Reduction of aromatic rings by 2-propanol with Raney nickel catalysis.
Srivastava, S.; Minore, J.; Cheung, C. K.; Le Noble, W. J
Journal of Organic Chemistry 50 (1985) 394-396.
[Edited on 23-2-2008 by solo]
Attachment: Reduction of aromatic rings by 2-propanol with Raney nickel catalysis.pdf (964kB)
This file has been downloaded 1360 times
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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solo
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Reference Information
Hydrogenation of derivatives of pyridine
Adkins, Homer; Kuick, Leo F.; Farlow, Mark; Wojick, Bruno.
Journal of the American Chemical Society 56 (1934), 2425-2428
Attachment: Hydrogenation of derivatives of pyridine..pdf (823kB)
This file has been downloaded 1495 times
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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Ramiel
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This may be of interest to you regarding your suggested source of piperine from <i>Piper nigrum</i>. Many moons ago I extracted piperine
in this manner and converted it to piperic acid with limited sucess.
<ul><b>Piperine isolation</b>
<li>30 g black pepper seeds (blended) was added to 250 mL of ethanol and refluxed for two hours, the brown liquid was filtered and concentrated
to a viscous brown oil at 40ºC under reduced pressure. </li>
<li>30 mL of 10% w/v (54 mmol) KOH(ethanol) was added to dissolve completely any acidic tannins and piperidine, 80 mL water was added and the
product was extracted with 3x100mL portions of ether. The ethereal layer was separated and dessicated with 50mL brine solution. The ethereal solution
was then brought to 5 mL of dark brown viscous oil under reduced pressure (crude piperine). </li>
<li>To the crude piperine was added 15 mL acetone, the solution was then boiled down to approximately 2 mL. 2mL petrol was added slowly in a
dropwise manner to effect precipitation, a black oil separated, no precipitate formed.</li>
<li>The point here is to effect a precipitation of crude piperine, it is possible the solution was too concentrated, need advice on this
one!</li>
<li>Addition of acetone, reduction and addition of petrol was repeated twice with same results; solution was boiled to near dryness and left to
cool, a brown crude precipitate was collected (0.86 g, crude).</li>
<b>Base Hydrolysis of piperine</b>
<li>0.73 g of crude piperine was added to about 7.5 mL of 10% w/v (13 mmol) KOH(ethanol) and refluxed for 90 minutes. </li>
<li>The reaction liquor was then evaporated to dryness under vacuum, the solution was acidified by dropwise addition of 10M HCl (positive litmus
test) to precipitate the weakly acidic piperic acid, and heated on a steam bath; a brown precipitate (crude piperic acid) was collected. </li>
<li>The crude piperic acid was dissolved in minimum hot ethanol, a brown oil came out with the pale yellow crystals of piperine, more hot
ethanol was added until the brown oil redissolved. The solution was filtered: remaining yellow crystals redissolved during filtration. The ethanol
solution was evaporated to dryness and the brown solid redissolved in minimum hot ethanol, the solution was left to cool and yellow needle-like
crystals were collected via vacuum filtration. The liquor flask was washed out with about 2 mL acidified cold ethanol, yellow crystals were washed
with this liquid and turned white (0.27 g, 0%*, mp > 300ºC).
<u>This is the point where I think I fucked up, somehow I lost all my beautiful needlelike yellow piperic acid and got a white cubic crystalline
mass which would not melt (probably salt).</u></li>
</ul>
Excuse the imperfect scientific writeup!  
Caveat Orator
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Sauron
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Everything I read about extraction of piperine from such sources, indicated that while piperine isolation was possible, piperidine isolation was not
worth the effort required.
To some extent that is a value judgement and becomes untrue if one is sufficiently motivated and without alternatives. However, it ought to be obvious
that any of the synthetic routes will be more productive.
Sic gorgeamus a los subjectatus nunc.
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