The_Davster
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Aromatic halogen exchange: chloro to bromo
I am in need of a certain bromo aromatic compound, which is unavailable commercially. However the chloro version is available, I was wondering if
this reaction ( http://www.organic-chemistry.org/abstracts/literature/090.sh... ) could be modified to produce the bromo from the chloro? The only other
functional group present is a sulfone para to the chloro.
If this would not work, can someone recommend another which may work?
Thanks
(Apologies for the vagueness, part of unpublished work)
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sonogashira
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It just so happens that I have been looking at this reaction recently and have requested a review article in references (which has not yet been
provided) so keep an eye out if/when it is found. Have a look in Larock (p671) also for more references.
Edit: It seems that large ---> smaller halogen is more common (at least for the references given in Larock), though there are some references for
Cl--->I eg. with NaI in DMF: JOC 23 305 (1958). Perhaps NaBr could be used simillarly?
[Edited on 18-5-2008 by sonogashira]
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The_Davster
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Thanks, I am currently away from my scifinder so I could not search the literature that way, but I do have access from home to journals so check the
attachment.
Attachment: review halogen substitution.pdf (2MB)
This file has been downloaded 2575 times
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ziqquratu
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As far as I can remember, the Cl --> I exchange was fairly poor yielding, and Cl --> Br exchange is likely to be worse. You could try it on a
model compound, but my suspicion is you'll need to try something different.
An idea that occurs to me (and I don't know how compatible this would be with the sulfone!) would be to make the aryl lithium with BuLi and treat that
with bromine, CBr4 or 1,2-dibromoethane. The yields should be quite good - I've attached a paper where they do this with the latter two compounds.
If the sulfone would react with the lithium reagent (I know little about them, but suspect it would), is the sulfide available? Sulfides are easily
oxidised to sulfones.
Attachment: BrominationArylLi.pdf (418kB)
This file has been downloaded 1300 times
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The_Davster
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While the sulfide is available, it's cost is prohibitive (>700$/g), and the chloro sulfone is dirt cheap, even for a hundred grams, and I expect
the use of a significant portion of that.
I do like the lithiation idea very much, and I am not finding any issues with reaction of the sulfone(according to my precursory googling), so I hope
to give it a shot soon! Thanks!
Does dibromoethane react with the lithium salt producing acetylene(EDIT: oops, typo, meant ethylene) as a byproduct? Hello easy workup
[Edited on 19-5-2008 by The_Davster]
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Nicodem
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Sulfones, as far as I know are not compatible with BuLi. The side product from ArLi + BrCH2-CH2Br is LiBr and ethene along ArBr.
If the sulfone group is para toward the chloro, you could try with the nucleophilic aromatic substitution - that is heating the substrate with KBr in
NMP to above 150°C. You should however use a large excess of the bromide is unfortunately the chloride is a better nucleophile in aprotic polar
solvents than bromide. I have doubts this would works, except maybe if you could use CsBr instead of KBr.
The Ullmann reaction (the SRN1 reaction) like the example you linked generally does not work well with aryl chlorides (actually usually it does not
work at all). It does work nicely in the other direction though (ArBr->ArCl) under the same conditions.
In short, it is all about try and see.
…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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millerxia
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in my opinion, to get bromo aromatic compound, you can get form amino aromatic compound , diazotizated , then bromine is dropped to it. it is more
possible.
last time, i get 2-methyl-5-iodinpyridine from 2-methyl-5-aminopyridine,not from 2-methyl-5-chloropyridine or 2-methyl-5-bromopyridine.
if there is still any other problem, you can contact me . send the message to me
immediately
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sonogashira
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Does anyone know how generally applicable the Cu(I) catalyzed halide interconversion is (say for Ar-Br to Ar-Cl) in the presence of side-chain
substituents, OH and NH2 for instance.
Would they perhaps need protecting?
[Edited on 21-5-2008 by sonogashira]
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franklyn
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http://pubs.acs.org/spotlight/april2003/ja028865v.pdf?sessid...
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