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stimo-roll
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HCl? Ya i read some russ patents, in first unsaturated ketone - divinyl keton react with MeAm to afford piperidone, and second patent with improved
procedure were chloromethyl vinyl ketone react with MeAm, yelds are adout80-90%. May be HCl added to double bond of divnyl ketone.
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tr41414
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i think you are confusing two different reactions. one is the known-to-work divinyl ketone + MeAm, which by the way is very similiar to the acrylate
method, just that here the ring is already in its position... The second one is mannich rxn, which usualy employs usage of hcl...
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stimo-roll
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Sorry, youre right this not a mannich, but some interesting:
patent RU2123495
ketone structure CH2C(CH3)COCH2CHClCH3 (obtained with Friedel-Crafts reaction chloroanhydryde metacrylic acid and propylene AlCl3 in CH2Cl2) react
with 30% aqua MeAm to 1,2,5-trimethylpiperidone-4.
For F-C reaction see US2105792 and J.Chem.Soc. 1970, p2401 I.R.Owen.
too complicated for such shit like fent.
[Edited on 29-5-2007 by stimo-roll]
[Edited on 29-5-2007 by stimo-roll]
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dr. nick
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well, seems the ning is all around here somehow :)
got some pm's from him long, long ago, too, and always wanted to give it a try - at least the NPP thing, but never had all ingredients at hand. Now
they are available so i'd start a little experiment, but i'm still not sure about the right mannich variation - should it be done with Formalin (i
think so) or Paraformaldehyd? Does anyone have some relevant hints maybe on performing this? Of course i'd share any results :)
As far as i can remember ning said, PEA, Formaldehyd and MEK would yeild some 3-Methyl-Piperidon ... but not sure, got to look it up.
of course you can well i couldn\'t before
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jon
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well if you want this to condense to the intermediate formalin is used paraformaldehyde won't condense on it.
yes it seems mek would give 3-methyl piperidones which are 5X better.
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dr. nick
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thanks!
| Quote: | well if you want this to condense to the intermediate formalin is used paraformaldehyde won't condense on it.
yes it seems mek would give 3-methyl piperidones which are 5X better. |
In how far do you mean "5X better"?
could you explain a little, please?
thanks again!
of course you can well i couldn\'t before
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jon
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well the end product would be 400 X morphine depending on what your synthing.
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john_do
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Dr Nick: Do this board a favour and pretend not to be excited about what you have just learnt. Considering you claim to have spoken with Ning about
this very subject, I find it hard to believe that you still need clarification from others. Find out the hard way like everybody else around here,
spoonfeeding is so 90's.
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dr. nick
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@jon: thanks! i've read some somehow contradictory statements on 3-methyl-fentanyl - not so much about the strength, even if they differ there also,
but on the time of action.
maybe you have some more definite information about this point?
oh dear, forgive me, great master chemist j_do - and if you want to do me a favour stop talkin silly stuff - i haven't been asking to be spoon fed
here, especially not by you and i really don't care if someone like you believes me or not.
--edit: sorry if(?) being a bit harsh, i am no chemist, i'm just interested in some rather specific experiments out of privat reasons, so i really
have no interest in any ego-fights, boss honcho contests or such stuff. don't take it personal.
[Edited on 1-6-2007 by dr. nick]
of course you can well i couldn\'t before
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chemrox
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I had another thought on 4-piperidone synthesis and dug up this old thread via the SE. My thought was this:
4-Br-pyridine + alcohol/Na --> 4-Br-piperidine + NaOH --> 4-hydroxypiperidine ---(chromic oxidation) --> 4-piperidone? This basic procedure
is known for 4-pyridone .. I added the alcohol reduction at the beginning.
[Edited on 29-1-2009 by chemrox]
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not_important
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Would the bromine survive the Na/alcohol reduction?
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Ebao-lu
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i assume it would not, Na/alcohol is oftenly used for reduction of alkylhalides..
But, if you first change Br to OH(hopefully, this reaction will easily proceed), and then you can feel free to use any method of reduction. Probably,
in bit more harsh conditions, the bromine could be replaced with NH-R( )
directly, and even you can try to alkylate the N atom of pyridine with b-phenylethylhalide(provided you protect the NHR group by acylation ), and then reduction(acyl may go off, but you can once again attach it)... (:surprized that mu-opioids discussion is allowed
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sparkgap
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"But, if you first change Br to OH(hopefully, this reaction will easily proceed)"
So you're saying γ-pyridone (which is the more stable tautomer) can be reduced to 4-hydroxypiperidine with that reagent?
sparky (~_~)
[Edited on 30-1-2009 by sparkgap]
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Ebao-lu
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Well(sorry, forgot about tautomers).. not sure about sodium/EtOH, but there should be many reagents that can reduce it like this(or are there any
potential problems with it? i dont see any, except the nucleophile addition in b-position of pyridone and amine elimination, causing cycle breaking))
besides chemrock written | Quote: | | This basic procedure is known for 4-pyridone .. |
I think that was said about reduction of 4-pyridone
[Edited on 30-1-2009 by Ebao-lu]
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Tunnels
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Nothing conclusive on the Mannich? Missed the ref but from what I gather the procedure might look something like...?
Experimental.
12.1 g of phenethylamine is dissolved in 8.9 ml 37% aq formaldehyde and 7.3 ml of acetone. Glacial acetic acid is then slowly added and solution is
brought to reflux. NPP should be slightly yellow solid with a mp between 57-60 degrees.
That'd be not much to work with. How long is this reaction thought to take? If it takes at all, that is.
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Ebao-lu
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Are you sure treatment with Na gives ketal, not a-carbmethoxy-NPP? that should be a usual Claisen condensation.
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chemrox
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key ref for the method
The method for making NPP via PEA is in Beckett, Casy & Kirk on a&b Prodines. Here it is.
Attachment: 4-piperidones, a & b prods.pdf (1MB)
This file has been downloaded 1760 times
"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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Nicodem
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| Quote: | Originally posted by Ebao-lu
Are you sure treatment with Na gives ketal, not a-carbmethoxy-NPP? that should be a usual Claisen condensation. |
It is, it's just that Chemrox does not know the difference between a Claisen condensation and a reduction, or between a beta-ketoester or ketal... You
should not take other members claims too seriously. Most people here are amateurs.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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chemrox
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oh there goes Nicodem being mean again.. anyway I posted the article for you and yeah I either didn't know or didn't remember sue me call me an
amateur abuse me if this is the kind of thing that makes you feel like a bigshot professional ..
"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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Ebao-lu
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| Quote: |
12.1 g of phenethylamine is dissolved in 8.9 ml 37% aq formaldehyde and 7.3 ml of acetone. Glacial acetic acid is then slowly added and solution is
brought to reflux. NPP should be slightly yellow solid with a mp between 57-60 degrees.
That'd be not much to work with. How long is this reaction thought to take? If it takes at all, that is. |
If you're not sure the reaction would give NPP, you can try to do a set of small-scale experiments in test-tubes, with TLC control(you only need to
identify the NPP by its Rf, and to find proper eluent, UV light ). Instead of reflux, you can keep temperature in test-tubes experiment a bit elevated
in a water bath(less then boiling point). And then, if you succeed, do it in a large scale
As for Claisen condensation, i've written that only for clarification, not for abusing. It should be much easier for a one to study new information
directly in the thread, instead of annoying books reading. Now chemrox probably knows, what is claisen condensation and what product is formed in the
reaction And it could take another n months for him to come accross an
article in a book.
Ok, next time a will not take it too serious, less patronizing.
[Edited on 9-2-2009 by Ebao-lu]
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chemrox
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@Ebau-Lu thanks for the comment. The article I cited came from JACS btw, not a book. Where does the above experiment with formaldehyde and acetone
come from?
"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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Ebao-lu
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That's Tunnels had written above, i quoted his post. From his words "the procedure might look something like...?" i can conclude this procedure is a
proposal. But he said about some ref, so maybe the original procedure was there, ask Tunnels better. As for experiment, i think small-scale
experiments(several ml) in organic chemistry are feasible, to find the proper conditions (reagents and their ratio, pH, tempereture, time) for the
reaction. I've never heared of such kind of carrying out a research in professional organic chemistry, but for amateur chemists with their shortage of
chemicals, it should be a good option
| Quote: | | The article I cited came from JACS btw, not a book. |
yes, but i mean not that article, i mean the article(a paragraph) about ester and claisen condensation in a theory book
[Edited on 9-2-2009 by Ebao-lu]
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chemrox
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So the article is rather longish but reading again (last time was over a year ago) the short story was: the amine and ester are combined yielding the
amine diester which undergoes internal condensation, cyclization to the ethyl ketal which is relased to the amine/ketone with acid. So wouldn't this
be a Dieckmann rather than a Claisen?
"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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chemrox
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Some piperidines by the Mannich Reax
A member asked about this ref and I happened to have it. I also posted the Russian patent that was mentioned earlier in Refs hoping for a
translation.
[Edited on 9-2-2009 by chemrox]
Attachment: piperidines by Mannich reax.pdf (349kB)
This file has been downloaded 3572 times
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Nicodem
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| Quote: | Originally posted by Ebao-lu
As for experiment, i think small-scale experiments(several ml) in organic chemistry are feasible, to find the proper conditions (reagents and their
ratio, pH, tempereture, time) for the reaction. I've never heared of such kind of carrying out a research in professional organic chemistry, but for
amateur chemists with their shortage of chemicals, it should be a good option
|
In an organic synthesis research lab it is highly unusual to do any reaction above the 10 mmol scale (this has to do with avoiding dumb accidents, not
wasting very expensive materials, enabling a multistep synthesis, but most importantly because the most common method of isolation is chromatography).
The exception is when following a published procedure or when repeating a successful synthesis in order to prepare enough starting material for a
multistep synthesis. So, I would say it is just the opposite of what you seem to believe. It is the synthesis on a scale larger than 10 mmol that is
highly unusual in "professional organic chemistry". On the other hand it often seems to me that amateur chemists, understandably being more
irresponsible (as well as more naive about the experiment outcome and less stingy about the chemicals they have), have this tendency to do experiments
on irrationally large scales.
| Quote: | Originally posted by chemrox
So the article is rather longish but reading again (last time was over a year ago) the short story was: the amine and ester are combined yielding the
amine diester which undergoes internal condensation, cyclization to the ethyl ketal which is relased to the amine/ketone with acid. So wouldn't this
be a Dieckmann rather than a Claisen? |
Chemrox, please check what a ketal is (and what not). The expression you were seeking for "the amine and ester are combined" is Michael addition, a common reaction which uses the 1,4-conjugative addition for alkylating various nucleophiles. The Dieckmann condensation is intramolecular Claisen condensation. This is a bit confusing since it means that the Dieckmann condensation is a Claisen condensation, but a Claisen condensation
is not necessarily a Dieckmann condensation. I have noticed that many chemists prefer to only call the intramolecular condensation of
alpha,omega-dinitriles as Dieckmann condensation (probably just to avoid such confusion).
Anyway, I was not trying to be mean. I was only taking defence on your mistakes.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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