clearly_not_atara
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Ligands derived from niacin?
A recurring topic is niacin decarboxylation, which requires high temperatures and controlled conditions and often yields poorly if at all; this
suggests that we would be better off if we could avoid it, and the first alternative in my mind would be to make a similar ligand that isn't *exactly*
pyridine but which is mostly the same.
There are a couple of options:
3-ethylpyridine:
Niacin undergoes acetodecarboxylation with Ac2O/NaOAc to 3-acetylpyridine which is reduced by Clemmensen or Wolff-Kishner reduction to
3-ethylpyridine.
Pros: almost certainly works just like pyridine, OTC if you can make Ac2O/N2H4
Cons: long synthesis, longer OTC, hydrazine, mercury
Ethyl nicotinate:
Actually happens to be used in some syntheses.
Pros: very easy to synthesize, possibly even available.
Cons: less basic than pyridine, susceptible to hydrolysis. It's not obvious where and when this can be substituted for pyridine.
2-(3-pyridyl)-4-methyl-5-acetyloxazole:
The product of a condensation between nicotinamide and acetylacetone catalyzed by PdCl2/CuBr2 with K2S2O8. Acetylacetone may be made from
NaOEt/EtOAc/Me2CO as described on orgsyn.
Synthesis attached (actually, the similar product derived from benzene is synthesized in the paper, so we are generalizing a little).
Pros: one-step synthesis, reactivity likely very similar to pyridine, may be a bidentate ligand
Cons: uses palladium, has a ketone. Making acetylacetone is tricky. Original paper has DCE as solvent.
2-(3-pyridyl)-4-methyl-5-ethoxycarbonyloxazole:
Pros: Same as above, plus ethyl acetoacetate substitutes for acetylacetone, making the synthesis easier.
Cons: Same as above, except no ketone, but may be susceptible to hydrolysis.
Something else:
Pros: Might be better.
Cons: Synthesis and properties unknown.
Attachment: zheng2014.pdf (337kB)
This file has been downloaded 542 times
[Edited on 27-8-2016 by clearly_not_atara]
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CuReUS
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IMHO, the best bet would be using alkyl pyridines such as picoline , as adding a methyl group hardly changes the molecule( this law does not apply for
rocket propellants  )
picoline , I think ,could be made easily enough - http://www.sciencemadness.org/talk/viewthread.php?tid=28198
another idea would be to come up with a better method to make pyridine.I wonder what would happen if lysine was strecker degraded, cyclised to form
the imine and then dehydrogenated using Se to form pyridinehttps://en.wikipedia.org/wiki/Dehydrogenation
also can TEA or hunig's base be substituted for pyridine ?
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UC235
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I'm confused as to what the difficulty in decarboxylating niacin is? Nicotinic acid is cheap enough to buy in bulk as a supplement. I got high yields
using a simple distillation setup, it's amenable to scaleup and uses a tiny amount of catalyst (that can likely be substituted by a somewhat larger
amount of CuO or copper metal powder). There's no requirement for inert gas or elaborate purification or any solvents at all.
The simplest of the alternatives requires more than a full equivalent of sulfuric acid, a large volume of methanol to run the esterification in and
workup involves a distillation to get a product susceptible to acidic and basic hydrolysis and attack by other nucleophiles.
[Edited on 28-8-2016 by UC235]
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DraconicAcid
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Quote: Originally posted by CuReUS  | IMHO, the best bet would be using alkyl pyridines such as picoline , as adding a methyl group hardly changes the molecule( this law does not apply for
rocket propellants )
picoline , I think ,could be made easily enough - |
How easy is it to convert picoline into picolinic acid? Picolinate is a good ligand.
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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Alice
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Oxidation of picoline by KMnO4:
http://orgsyn.org/demo.aspx?prep=CV3P0740
Oxidation of picoline by MnO2/H2SO4:
https://www.google.com/patents/US2109954
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halogen
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Cyclopropane is combined by radical reaction with nitrogen dioxide to form 1,3-dinitro n-propane. 1,3-DNP is reacted with a base to form the bis
nitrostyrene, which is then allowed to condense with ammonia, to form the cyclic 3,5-dinitro piperidine, which undergoes pyrolysis to form pyridine.
(NO2 is a good leaving group)
[Edited on 28-8-2016 by halogen]
[Edited on 28-8-2016 by halogen]
F. de Lalande and M. Prud'homme showed that a mixture of boric oxide and sodium chloride is decomposed in a stream of dry air or oxygen at a red heat
with the evolution of chlorine.
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PHILOU Zrealone
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| Quote: Originally posted by halogen | Cyclopropane is combined by radical reaction with nitrogen dioxide to form 1,3-dinitro n-propane. 1,3-DNP is reacted with a base to form the bis
nitrostyrene, which is then allowed to condense with ammonia, to form the cyclic 3,5-dinitro piperidine, which undergoes pyrolysis to form pyridine.
(NO2 is a good leaving group)
[Edited on 28-8-2016 by halogen]
[Edited on 28-8-2016 by halogen] |
Do you have one (or more) reference(s) for that beautiful sequence of reactions?
I'm interested in all intermediary molecules aswel as the final one  .
PH Z (PHILOU Zrealone)
"Physic is all what never works; Chemistry is all what stinks and explodes!"-"Life that deadly disease, sexually transmitted."(W.Allen)
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clearly_not_atara
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| Quote: Originally posted by UC235 | | I'm confused as to what the difficulty in decarboxylating niacin is? Nicotinic acid is cheap enough to buy in bulk as a supplement. I got high yields
using a simple distillation setup, it's amenable to scaleup and uses a tiny amount of catalyst (that can likely be substituted by a somewhat larger
amount of CuO or copper metal powder). There's no requirement for inert gas or elaborate purification or any solvents at all. |
If you are referring to copper chromite then I would like to hear more details as I have heard conflicting reports on this method. Maybe I
overestimated the difficulty involved?
| Quote: | | another idea would be to come up with a better method to make pyridine.I wonder what would happen if lysine was strecker degraded, cyclised to form
the imine and then dehydrogenated using Se to form pyridinehttps://en.wikipedia.org/wiki/Dehydrogenation |
If you are willing to do multiple steps I think it is possible to make phenanthroline (starting from benzene/toluene, nitrate, sulfuric acid,
glycerol):
nitrobenzene (or p-nitrotoluene) + [H] >> aniline
(famous, many routes)
aniline + potassium persulfate >> 2-hydroxyaniline
https://en.wikipedia.org/wiki/Boyland%E2%80%93Sims_oxidation
2-hydroxyaniline + glycerol + nitrobenzene + H2SO4 >> 8-quinol
http://en.wikipedia.org/wiki/Schlenk_reaction
http://en.wikipedia.org/wiki/8-hydroxyquinoline
8-quinol + NH3 + NaHSO3 >> 8-aminoquinoline
http://en.wikipedia.org/wiki/Bucherer_reaction
(A little research will confirm this in fact proceeds rapidly and cleanly on quinol)
8-aminoquinoline + glycerol + nitrobenzene + H2SO4 >> 1,10-phenanthroline
It's actually shocking how parsimonious the sequence is. I considered it for that five-materials challenge, but I think it requires six or seven.
Mononitrotoluenes can be substituted for all of the nitrobenzenes, making this extremely OTC.
[Edited on 28-8-2016 by clearly_not_atara]
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halogen
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no
F. de Lalande and M. Prud'homme showed that a mixture of boric oxide and sodium chloride is decomposed in a stream of dry air or oxygen at a red heat
with the evolution of chlorine.
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UC235
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| Quote: Originally posted by clearly_not_atara |
If you are referring to copper chromite then I would like to hear more details as I have heard conflicting reports on this method. Maybe I
overestimated the difficulty involved? |
I provided a full illustrated writeup in prepublication as an add-on to magpie's thread. The original method presented is hugely wasteful of catalyst
in a manner that is wholly unnecessary.
I would rate it as one of the easier preps I have done.
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DDTea
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8-aminoquinoline (8-AQ) is a remarkably useful ligand. It can temporarily mask a carboxylic acid as the corresponding 8-AQ amide. The 8-AQ moiety
then serves as a directing group for a metal center, allowing reaction selectivity (often transformations of C-H bonds) at the beta position of the
carboxylic acid. Picolinic acid acid enables similar directed catalysis for amides. In essence, directing groups are tethers that allow an
otherwise unselective catalyst to react at only specific positions on a molecule.
The examples I'm most familiar with involve Pd(OAc)2 as catalyst. But the strategy has been applied to rhodium and copper as well for alkylation,
carbonylation, and sulfenylation.
For more on this, these are good references to start.
http://onlinelibrary.wiley.com/doi/10.1002/047084289X.rn0183...
http://onlinelibrary.wiley.com/doi/10.1002/anie.201301451/ab...
http://dx.doi.org/10.1016/j.tet.2015.03.085
"In the end the proud scientist or philosopher who cannot be bothered to make his thought accessible has no choice but to retire to the heights in
which dwell the Great Misunderstood and the Great Ignored, there to rail in Olympic superiority at the folly of mankind." - Reginald Kapp.
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NitratedKittens
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What, no to the multi step complex synth for a substitute for something that can be made in one go as outlined in this video: https://youtu.be/FNsqYwzm40M
Or just no in general
Basket of kittens for you ........BOOM
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Boffis
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I have recently come across an interesting ligand related to pyridine, 1,5-diazanapthalene. This is prepared by subjecting niacin to hoffmann's
degradation to produce 3-aminopyridine and then Skraup's quinoline synthesis on this. I'll try and dig out the papers again.
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PHILOU Zrealone
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| Quote: Originally posted by Boffis | | I have recently come across an interesting ligand related to pyridine, 1,5-diazanapthalene. This is prepared by subjecting niacin to hoffmann's
degradation to produce 3-aminopyridine and then Skraup's quinoline synthesis on this. I'll try and dig out the papers again. |
Interesting molecule!
Doesn't the Skraup's step also makes 1,7-diazanaphtalene (1,7-naphtyridine)?
PH Z (PHILOU Zrealone)
"Physic is all what never works; Chemistry is all what stinks and explodes!"-"Life that deadly disease, sexually transmitted."(W.Allen)
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Boffis
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Hi Philou, I don't have the original paper to hand but I would expect so. I mean to check this procedure out sometime as I am interested in this
compound but as usual its the time problem 
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Eddygp
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(possibly N-substituted) nicotinamide? More stable and much less reactive than acids or esters under most conditions, you don't need too much hassle
to prepare it and allows inner sphere electron transfer, potentially.
there may be bugs in gfind
[ˌɛdidʒiˈpiː] IPA pronunciation for my Username |
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Boffis
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Hi Philou, I have dug out some of my references on naphthyridines and it appears that 3-aminopyridine give almost exclusively the 1,5-naphthyridine in
a standard Skraup reaction but yields can vary from 25 to 90% depending on conditions, see the attached papers. There do appear to be modifications
that yield the 1,7 isomer.
Attachment: Preparation of 1,X-naphthyridines JCS A Albert 1960.pdf (90kB)
This file has been downloaded 429 times
Attachment: Synthesis of Naphthyridines by a one step process ChemPharmBull Hamada et al 1971.pdf (613kB)
This file has been downloaded 378 times
The Hoffmann degradation of nicotinamide to 3-aminopyridine is discribed in a European or worldwide patent referred to, but not posted, by Nicodem in
an old thread. I managed to track down the US patent equivalent.
Attachment: Manufacture of 2,3-dichloropyridine, 3-chloro and 3-aminopyridine from nicotinamide US 20070161797.pdf (850kB)
This file has been downloaded 418 times
This last ref. also contains some interesting pyridine chemistry including the preparation of 3-chloro and 2,3-dichloro pyridine from nicotinamide.
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PHILOU Zrealone
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@Boffis,
Thank you.
Very much appreciated.
PH Z (PHILOU Zrealone)
"Physic is all what never works; Chemistry is all what stinks and explodes!"-"Life that deadly disease, sexually transmitted."(W.Allen)
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UC235
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The video that runs my procedure posted on this forum in prepub?
Starts halfway down the page: https://www.sciencemadness.org/whisper/viewthread.php?tid=13...
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