itsmetheuglykid
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Chlorination of tertiary amino alcohol
I'm theoretically looking for a method other than thionyl chloride; something easily synthed or obtained in chlorinating this amino alcohol. Any
ideas? 
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Darkstar
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You could try anhydrous ZnCl2 with conc. HCl (Lucas' reagent). I don't know how good the yields would be, though.
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itsmetheuglykid
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Ah thats interesting, I will check that out! Thank you
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DJF90
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What makes you think you won't get aziridine formation? You should protect the amine first (possibly just as HCl salt) and then use (almost) whatever
methodology you like.
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Chemosynthesis
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Good responses.
Theoretically, huh? itsmetheuglykidYou need to post references here or post in Beginnings next time.
This is pretty obviously the source you are/should be working from: https://www.erowid.org/archive/rhodium/chemistry/methadone.h...
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Nicodem
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Thread Moved
26-11-2014 at 08:07 |
itsmetheuglykid
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Ah, i apologize, i'm new to this forum.
https://www.erowid.org/archive/rhodium/chemistry/methadone.h...
Chemosynthesis you are correct, unfortunately Rhodium uses thionyl chloride in this step and as I am sure you probably know
SOCl2 is not the easiest substance to come by. I was having trouble finding a scholarly article or patent on ZnCl2 use in this
reaction. Thanks for the responses!
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zed
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Dunno. Research the references in Organic Synthesis. The article of interest pertains to the production of Dimethylaminoethyl Chloride
Hydrochloride, from Dimethylaminoethyl Alcohol via Thionyl Chloride. No doubt, there will be references to alternate synthesis.
HI might be an alternative. As a similar situation exists at one stage in the reduction of Ephedrine via I2/P. Though the benzyl group present,
because of it's unusual stability, may lend itself to substitution and reduction.
Ummm. Organic Synthesis suggests HBR might do the trick. Apparently it requires quite a bit of HBR.
Before embarking on such a journey, consider the possible consequences.
Just because it is possible to climb Mt. Everest, doesn't mean it is a great idea.
Check local ordinances before preceding.
[Edited on 30-11-2014 by zed]
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Chemosynthesis
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Reactivity of the halogenation is obviously going to be solvent dependent if you try less synthetically-traditional halogenation routes
(protic/aprotic).
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forgottenpassword
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There is some similar discussion in this thread:
http://www.sciencemadness.org/talk/viewthread.php?tid=10358
I link to it only because of the warnings given for handling these type of compounds -- especially in their freebase form.
[Edited on 30-11-2014 by forgottenpassword]
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itsmetheuglykid
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Alot of great insight, thank you everyone who commented.
@ zed Thank you for your concern. I am a first year Med student and have always been somewhat interested in addiction and opiate withdrawal therapy.
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AvBaeyer
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One alternative you might consider is making the p-toluenesulfonate ester rather than the chloride. If you are going to do a displacement of the
chloride in a subsequent reaction, then the tosylate should work equally well if not better. (p-Toluenesulfonyl chloride is available from Elemental
Scientific). If you run the tosylation reaction using the amino alcohol free base in a polar solvent like DMF you should get directly the tosylate
ester hydrochloride. You might also find some of the desired chloro compound as the tosylate salt. For this latter possibility , there is an older
reference which I do not have at hand from A.I. Meyers et al in J Org Chem in the late 1970's (?) regarding tosylations in DMF which give the chloro
compounds directly.
AvB
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itsmetheuglykid
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Ya I found the article you are referring to.
Facile and specific conversion of allylic alcohols to allylic chlorides without rearrangement
E. W. Collington, and A. I. Meyers, J. Org. Chem., 36, 3044 (1971).
Unfortunately for some unknown reason my school is not allowing me access to this article :/ and i'm not about to pay 22 quid to browse a publication
that should be open access for anyone trying to further their understanding of (whatever). Damn you ACS!
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itsmetheuglykid
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This is interesting
Acetyl chloride–ethanol brings about a remarkably efficient conversion of allyl acetates into allyl chlorides
http://www.sciencedirect.com/science/article/pii/S0040402003...
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CuReUS
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what about PCl5 or PCl3 ?
http://en.wikipedia.org/wiki/Phosphorus_pentachloride#Reacti...
http://en.wikipedia.org/wiki/Phosphorus_trichloride#PCl3_as_...
for PCl3 ,it says that in the presence of base ,it reacts with alcohols to give alkyl phosphites ,but in the absence of base ,it gives
alkyl chlorides from alcohols
since there is a tertiary amine in the molecule ,there may be a chance that the amine may itself act as a base and form phosphites instead of alkyl
chlorides
so PCl5 is the best bet
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chemrox
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If you protect the amine with HCl you might limit your solvent choices. It might be an opportunity to develop a green method with either a solid setup
or an aqueous solvent sys. It depends on the alcohol of course. I might like to assist you perhaps using cyclohexanol. What do you think?
"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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forgottenpassword
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You could do something like this, to get the hydrobromide:
http://www.orgsyn.org/demo.aspx?prep=CV2P0091
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chemrox
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Same issues as with HCl. (Personally I prefer bubbling gas.) However a vinyl carbamate can be made with vinyl chloride and MgO in water and dioxane.
It is broken with HCl in dioxane. Please see Greene, Protective groups in organic synthesis, ...also the amide can be made by any method that won't
preferably react with the alcohols. I believe the vinyl chloride, under the cited conditions, will immediately move to the amino locus. I haven't
tried it and I sometimes wish people wouldn't suggest methods they haven't tried.
"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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itsmetheuglykid
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Any comments are welcome To generate ideas and discussion.
@ Chemrox I have to leave town for a week or so for a family emergency; my Mum is ill, but i will indeed get back to you as soon as i can! Thank you
all for your input.
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forgottenpassword
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I've given you a procedure which is pretty-much as easy as they come. Why do you want more discussion/ideas? If you actually intend to make the thing
then just make it. Add concentrated HBr and boil it off, essentially. Precipitate and wash the hydrobromide with acetone. It will work with your
substrate without a doubt. They make dimethylaminoethanol in the paper I linked to. Do you think that your extra alkyl group will prevent the
bromination?! No! It will make it EASIER!
What's the need for an eternal conversation? Do you insist on generating the chloride rather than the bromide?! If you don't have HBr then look up how
to make it. It will be a simple distillation or two and you'll have a new reagent to play with! Perhaps I've removed too many barriers for you and
actually made it possible?! Now you'll have to think about doing it, rather than just talking about it. Sorry about that! 
[Edited on 2-12-2014 by forgottenpassword]
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itsmetheuglykid
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no worries...ya i insist on generating the chloride, sorry for the delay
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