paraguay
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stork reaction amine alternatives?
Interested in creating an enamine, but have no reasonable access to the classic pyrrolidine, moprholine or piperidine.
I'm told that succinimide will not work because, while it has the N-H bond, the lone pair is too delocalized between the two carbonyl groups.
Hoewever, what if the localization was only between a single carbonyl and the amino function, say like a lactam (e.g. 2-pyrrolidone)?
I'd attempt synthesis of pyrrolidine from proline a'la Scr0t but that 20+ hour time frame of turpentine under reflux is simply not feasible for me
right now.
Proline by itself I've heard has a tendency to form parasitic oxazolidones.
Maybe i just have to break down and use the amine specifically but if anyone has any other ideas, I'd appreciate it!
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byko3y
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Diethanol cocamide is sold OTC, reaction with conc. H2SO4 leads to morpholine. For making enamine you need an amine, not an amide, not imide, not even
a triazole, neither carbamate.
You might consider using something like dimethylamine from DMF hydolysis. Alkylation of saccharine yields secondary amine. Anyway, you don't have a
ready-for-use amine, you need at least one reaction to make one.
For some weird reasone I realize there's no easy OTC options for secondary amine. I'm gonna cry a lot and then cut my wrist.
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CuReUS
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What are you trying to synthesise ? (CAS no please). Surely there must be better ways to alkylate ketones than the stork enamine route.
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paraguay
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Thank you so much, those definitely are some great ideas and the way you listed what cannot be used has made the mechanism obvious to me now. Correct
me if i'm wrong but it seems that in order for condensation to occur, the electrons have to exist as a lone pair in order to be nucleophilic. Because
imides, amides and carbamates have electrons stabilized in the carbonyl group(s), and I assume that triazoles are stabilized throughout, their
reactivity is low to nil even though they contain a secondary amino functional group? In regards to the synthesis let's just say I am exploring
enamine oxidation options when applied to various formyl substrates. u2u me. I did manage to find one or two online chem houses that have up to a
liter of morpholine for pretty cheap, ebay has small amounts of pyrrolidine and morpholine as well, but being hazardous materials apparently they can
only be shipped according to ORM-D regulations (ebay's restriction it seems). Cocamide DEA is definitely cheap and OTC. H2SO4 would hydrolize the
amide to the amine as it's an A/B reaction, and then complete ring closure? The second part looks pretty straightforward in this patent US2777846
using just DEA. They have it down to 1.5 hours albeit with fuming sulfuric acid not conc. but 7-8 hours seems reasonable.
[Edited on 25-11-2016 by paraguay]
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paraguay
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Not really a lot out there on lab technique for acid hydrolysis, although Chemplayer's vid on Piperine to Piperidine was really informative and seems
applicable, just vice-versa from what I want to accomplish. Their hydrolysis was base catalyzed to yield the salt of the acid and freebase whereas an
acid catalyst should yield the sulfate of the amine and the free acid. If applied to Cocamide DEA, would it probably just take a little more reflux
time to ensure conversion to morpholine?
Experimental:
Diethanolamide is added to an excess of sulfuric acid and held under reflux. Fatty acid is extracted from reaction with naptha.
Aqueous layer evaporated and residue taken up into dry methanol and titrated with conc. NaOH/methanol soln. to yield amine freebase.
or
Aqueous layer basified with NaOH soln. and treated with NaCl to separate the freebase.
thoughts/feedback greatly appreciated!
[Edited on 2-12-2016 by paraguay]
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Corrosive Joeseph
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SideArms Morpholine making....................
'To make morpholine from what you've got on hand, you have two ways to ethylene chlorohydrin, then two ways to morpholine from there. For making
Cl-CH2-CH2OH, you might produce ethylene by squirting ethanol on H2SO4 at 170c, then duct it in to (gradually) acidulated bleach. Or you could put HCl
into ethylene glycol antifreeze to distill ethylene chlorohydrin.
This latter you can treat with ammonia, dry or aqueous, but it will give you a mix of three amines to separate by distillation. Then you can obtain
morpholine from the diethanolamine by dehydration in acid. But a less complicated way to form its ether, dichlorodiethylether, by distilling a mix of
ethylene chlorohydrin and sulphuric acid. This chlorinated ether treated with ammonia will give the secondary amine, closing the ring to morpholine in
higher yields, since you don't need to worry about what to do with the little bottles of monoethanolamine and triethanolamine.'
Taken from 'New preparation of phenylacetic acid' thread in the Chem Discourse forum (on the recently reloaded ArcHive)
Its untried by myself but hey.................
Morpholine from antifreeze, sulphuric, HCl and ammonia is got to be worth a try.
Maybe someone else knows more or can add to this.
Hope it helps..................
/CJ
[Edited on 2-12-2016 by Corrosive Joeseph]
Being well adjusted to a sick society is no measure of one's mental health
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paraguay
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sorry to drag this back out, still working on this... so yeah i think the easiest way is gonna be the diethanolamine route.
In regards to acid-catalyzed dehydrations, can this be done using the same techniques for dioxane?
i.e. excess H2SO4 + DEA, heated in distillation apparatus at 180*c or thereabouts, collect azeotropic distillate, basify with KOH, decant crude
morpholine?
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wg48
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He is obviously not real chemist if that’s his best exit strategy LOL
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LearnedAmateur
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If you want to try this, I recommend that you still do the base hydrolysis. Instead of synthesising the amine salt in the same vessel, distill off the
amine into a separate flask with hydrochloric or sulphuric acid. It skips the step of needing to separate out the salt, inevitably contaminated with
some of the acid, and you can simply crystallise a fairly pure product ready to use.
[Edited on 26-9-2017 by LearnedAmateur]
In chemistry, sometimes the solution is the problem.
It’s been a while, but I’m not dead! Updated 7/1/2020. Shout out to Aga, we got along well.
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clearly_not_atara
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Piperazine is OTC as an antihelmintic, and acylation of piperazine with esters has the useful property that the first acetylation happens faster than
the second. So my recommendation is N-acetylpiperazine. In particular, phenyl esters react quickly with piperazine, so my specific recommendation is
acetylsalicylic acid (aspirin) as acylating agent. See attached paper.
Attachment: pappas2009.pdf (112kB)
This file has been downloaded 315 times
| Quote: | | I'd attempt synthesis of pyrrolidine from proline a'la Scr0t but that 20+ hour time frame of turpentine under reflux is simply not feasible for me
right now. |
I'm not sure why Melgar's results here:
https://www.sciencemadness.org/whisper/viewthread.php?tid=74...
wouldn't at least possibly generalize to proline. It's a secondary rather than primary amine, but the iminium can still form and it should
help to kick off the carboxylate. Reflux for 3 hours in propylene glycol sounds doable. However, I don't actually believe that proline is OTC, which I
see as the bigger problem.
EDIT: Another possibility if piperazine is not available is tetrahydroisoquinoline, derived from the Pictet-Spengler reaction of phenethylamine with
formaldehyde.
https://en.wikipedia.org/wiki/Pictet%E2%80%93Spengler_reacti...
I strongly recommend HBr or H2SO4 over HCl if taking this route as the combination of formaldehyde and hydrochloric acid results in the production of
extremely carcinogenic bis(chloromethyl)ether.
[Edited on 26-9-2017 by clearly_not_atara]
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Cryolite.
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Proline is sold at health food stores as a supplement (for some reason). It is also available on ebay. However, since gelatin contains significant
amounts of proline, it maybe possible to make proline from that too.
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paraguay
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I should have probably started a new thread lol.
I've checked out most options at this point and I already have a 500ml bottle of Diethanolamine (cas# 111-42-2). If this doesn't work I will try the
decarboxylation.
My question at hand however is:
Can I directly distill over an azeotropic mixture of morpholine in one pot as is done dioxane?
| Quote: |
i.e. excess H2SO4 + DEA, heated in distillation apparatus at 180*c or thereabouts, collect azeotropic distillate, basify with KOH, decant crude
morpholine?
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I don't mind a reflux + workup of complete reaction mixture either, I just wanted to know if the above would work properly.
[Edited on 28-9-2017 by paraguay]
[Edited on 28-9-2017 by paraguay]
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clearly_not_atara
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It won't; morpholine bisulfate will not decompose at 180 C. You'll need to liberate the freebase in situ. Dioxane unlike morpholine does not form a
salt with sulfuric acid. However H2SO4 works ok as a dehydrating agent.
[Edited on 28-9-2017 by clearly_not_atara]
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paraguay
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Yep because its an a/b, so basify first and then distill, makes sense now... dangit i knew i was missing something super easy, thank you!
[Edited on 29-9-2017 by paraguay]
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