Globey
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Finkelstein Swap?
Hi,
I'm making a request for an actual practicle procedure, partly because of time constraints (only had time to browse Vogels). So please don't be
snotty! J/K So thanks in advance =)
What I want to do, is start from cinnamyl chloride, and do a Finkelstein type swap with bromine. The alkene might already have the reactivity I want,
but bromine will leave quicker. Assuming the alkene in DMSO and add some NaBr? If someone could post the actual procedure, it would be most
appreciated. Every time I looked it up here, I just saw ref. going from bromide to iodide, but in theory, chloride to bromide would work as well (not
as well, but in addition too). Many thanks
[Edited on 4-4-2009 by Globey]
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solo
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......chlorine to Iodine can be seen here, hence similar approach can probably be used for Chlorine to Bromine......solo
http://designer-drugs.com/pte/12.162.180.114/dcd/chemistry/d...
...also something here about it,
http://www.psychonaut.com/index.php?option=com_forum&pag...
[Edited on 4-4-2009 by solo]
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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Arrhenius
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In theory chloride to bromide wouldn't work very well. The reaction is entropically driven because sodium iodide is soluble in acetone, whereas
sodium bromide (product) is not.
Typical procedure is to reflux in acetone with excess NaI, followed by aqueous workup.
[Edited on 4-4-2009 by Arrhenius]
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Ebao-lu
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I've seen several mentions that in acetone this swap works fine only for NaI, and NaBr does not work (prob. due to poor solubility). Maybe in other
solvents it will. What is the problem with using NaI?
Another possible method (take into consideration) is with PTC and HBr. J. Chem. Soc. Perkin Trans. 1, 1992, p. 2309, "Finkelstein reaction with
aqueous hydrogen halides efficiently catalyzed by lipophilic quarternary onium salts" Unfortunately, i dont have access there, but the procedure
should definitely be given there
[Edited on 4-4-2009 by Ebao-lu]
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DJF90
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You could theoretically use NaI in acetone with your substrate, seeing as you only want to increase the reactivity... I suppose the only prevention is
the high cost of the NaI.
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Globey
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Thanks all for the advice. I'll look up perhaps KBR is more soluble in DMK than Na? It's either spa salts or Kodak photography grade. The original
procedure calls for using the alkeyl bromide, so was just trying to follow it as closely as possible. Wonder if substituting chloride (when bromide
is called for) would work. Perhaps just increased rxn time? Wonder if iodide would present some unanticipated problems and be too reactive.
Sometimes it's not so simple as just halogen order of reactivity. Am compensating for increased (or decreased) molar mass, but really would prefer to
use the bromide. Maybe MEK instead of acetone? Don't have the phase transfer catalyst, but do have silica gel and some polyquat-7 I think. How about
acetone/DMSO as the solvent system? Again, thanks to everyone for the help.
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Globey
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Quote: Originally posted by Arrhenius  | In theory chloride to bromide wouldn't work very well. The reaction is entropically driven because sodium iodide is soluble in acetone, whereas
sodium bromide (product) is not.
Typical procedure is to reflux in acetone with excess NaI, followed by aqueous workup.
[Edited on 4-4-2009 by Arrhenius] |
Wouldn't the halide react with the hydroxyl during aq. workup, or do I need a strong base to deprotenate? There is no acid or base involved (just
Na/KI & acetone), so workup means just successively diluting out the excess iodide with several DI water washes?
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Globey
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Another question. Would it be OK to use a saturated brine of NaI in acetone? Worried that maybe by salting out the cinnamyl chloride, it won't
dissolve so easily in the acetone, and that would hinder rxn? Was thinking of quick and dirty, having saturated acetone with even excess NaI at the
bottom of the flask. It could help to make the boiling more even. If this sounds remiss, please someone shout. Thanks.
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DJF90
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Ok Globey, do you want the bromide or the iodide?? Here is information on the finkelstein reaction:
http://www.organic-chemistry.org/namedreactions/finkelstein-...
It clearly states that KCl and KBr are insoluble in acetone, and so this is no way to go if you want the bromide. However if you want the iodide you
can get very good yeilds by using an excess of KI. Being an allylic chloride, cinnamyl chloride is a very good substrate for an Sn2 reaction which
this is, and the acetone will aid the Sn2 reaction as it is a polar aprotic solvent, meaning that the iodide ion is unsolvated and thus very reactive.
I would use a 1.5 molar equilvalent of KI and enough acetone to just dissolve everything. Make the solutions of the KI and the cinnamyl chloride
separately and then add them together, and reflux with heat. I would leave the reaction for about an hour, and precipitate of KCl will be a rough
guide to reaction progress. If in doubt follow the reaction with TLC.
For workup I would filter out the KCl, then distill out most of the acetone. This is to facilitate solvent extraction as acetone is miscible with
water and orther common organic solvents, meaning that you wont get two phases when you try extraction. Add Water and a suitable solvent (perhaps
DCM?) and this should take the excess KI into the aqueous layer and your cinnamyl iodide into the organic layer. Separate out the aqueous layer and
wash the organic layer with perhaps a dilute thiosulfate solution and then a water wash. Finally dry over anhydrous magnesium sulfate or sodium
carbonate (I would expect these to be suitable), filter, and then distill off the solvent.
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Globey
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Thanks DJF90. Realize KI will always be better, but is NaI fine on this one?
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not_important
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Compare the solubility of KI and NaI in organic solvents, the sodium salt is more soluble than the potassium salt in most common solvents ( Seidell's
solubilities of inorganic and organic compounds is your friend, the 1919 2nd edition is available at the Internet Archives).
KBr is slightly soluble in acetone, but the ratio compared to KCl is fairly low, a clean reaction is doubtful and an excessive amount of acetone or
alcohol would be needed.
When I performed this, after filtering out the NaCl, I would concentrate it until crystals started forming, then add several volumes of toluene or
xylene and filter out the NaI precipitated, followed by a small quick ice water wash and drying with MgSO4.
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Globey
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not_important, perfect...am now prepared. My intuition would have told me KI the more soluble, so M=many tnx
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DJF90
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Sorry, I knew NaI is more soluble but suggested KI because of the link I posted. Either salt should work fine but NaI is preferable due to its higher
solubility in acetone.
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Nicodem
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Cinnamyl chloride is an allyl halide and as such it is highly electrophilic. Transforming it into cinnamyl bromide does not make much sense since
there practicaly are no polar reactions where such a change would be considered rational (except for alkylations of carboanions at -78°C and similar
low energy conditions). This is not like the difference in electrophilicity between alkyl chlorides and alkyl bromides, allyl and benzyl halides do
not have such large gaps in reactivities.
The solubility of alkali salts in acetone (as well as in ethers) follows some simple rules to some extent: the more acidic the cation the more soluble
the salt, also higher polarizability or hydrophobicity of the anion also immensily helps in increasing the solubility. Hence if you want to dissolve a
chloride, you need an acidic cation like Li<sup>+</sup>. However, with such a large cation as the Cs<sup>+</sup> things get
more complicated, because even though this cation is essentially nonacidic its salts are nevertheless generally more soluble in organic solvents than
potassium salts.
Anyway, since the chloride/bromide exchange with iodide in acetone does not follow SN2 rules of reactivities (Cl<sup>-</sup> in acetone is
actually even slightly more nucleophilic than I<sup>-</sup>!), but is instead driven by solubility differences, it can not be efficiently
used for alkyl chloride to alkyl bromide echange.
…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)
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Globey
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Nicodem,
Let me see if I follow. If it were between benzyl bromide vs/ benzyl chloride, then YES, it might make a difference, but the double bond (- wd'ing)
here increases reactivity, so under normal alkylation conditions to typical substrates (OH in this case), cinnamyl chloride/bromide should pretty much
be interchangeable? The end result will be a cinnamyl ether, with the rxn taking place in acetone/potassium carbonate at reflux. Many thanks
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Ebao-lu
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I am afraid, there can be a side reaction of alkylation of acetone because alcoholates are enough basic to form some equilibrium amount of acetonyl
anion. But if is a literature procedure, then its fine.
[Edited on 6-4-2009 by Ebao-lu]
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Nicodem
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| Quote: Originally posted by Globey | Nicodem,
Let me see if I follow. If it were between benzyl bromide vs/ benzyl chloride, then YES, it might make a difference, but the double bond (- wd'ing)
here increases reactivity, so under normal alkylation conditions to typical substrates (OH in this case), cinnamyl chloride/bromide should pretty much
be interchangeable? The end result will be a cinnamyl ether, with the rxn taking place in acetone/potassium carbonate at reflux. Many thanks |
Not exactly. I said in my previous post that the reactivity difference between benzyl chlorides/bromides (like BnCl vs. BnBr), as well as between
allyl chlorides/bromides (like in your case, PhCH=CHCH2Cl vs. PhCH=CHCH2Br) is no such big deal as with the difference between the reactivity of alkyl
chloride/bromide reagents (such as, for example butyl chloride/bromid pair). Anyway, the point was the same - you can use cinnamyl chloride and get
the same results, just follow the reaction progress.
Actually, even with alkyl chlorides it is often worthless to first transform them into alkyl iodides or bromides if they are primary and to be used in
SN2 reactions. For example, if you would want to alkylate a phenol with butyl chloride it would not be rational to first transform it into butyl
iodide even though this is much more reactive. A comparable yield can be attained by simply changing the reaction conditions, for example increasing
the reaction temperature and using DMF as solvent, and eventually Cs2CO3 instead of K2CO3. Things are different if you have secondary alkyl halides
which are already quite unreactive by themselves, then if you have a chloride instead of a iodide or tosylate, you are in troubles.
Also, as you were warned above, you can not use acetone if you are alkylating alkoxides. This type of reaction, the Williamson ether synthesis, is
done in the solution of the parent alcohol.
…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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Globey
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Thank you all for the help...without it, I surely would be lost.
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