chemrox
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washes and extractions
I have a final workup that goes like this:
dilute with DCM (reactions were in DCE)
wash with 5%NaOH followed by water
Shake the organic layer with 2N HCl
extract the aqueous fractions with DCM and combine organic layers, evaporate in vac
Assuming the mixture prior to dilution is ~ 500 ml, what are the correct amounts of the above washes and how many times for each (3x for all?)
I'm convinced I'm screwing up this part and have a lot of aqueous reserved for future re-workup.
I'm either not doing enough volume in the washes or not enough times.
[as an aside-One of the priocedures is a borohydride reduction so when the mixture isn't right there is a terrible emulsion that takes days of
freezing and vibrating to break up or extract.]
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Nicodem
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There is something terribly illogical in your extraction procedure.
Your substance is obviously pretty insoluble in neutral and basic aqueous media, yet when you extract it in 2N HCl - in which it is therefore more
soluble than CH2Cl2 - you then back extract it in CH2Cl2 without any change in between. It seems impossible to me that anything would be extracted in
the organic layer. Are you sure the procedure at that point does not call for a neutralization or basification?
Or perhaps does that "Shake the organic layer with 2N HCl" actually means that you need only to wash the CH2Cl2 solution with diluted HCl? Because, as
it is written now (not particularly meticulously), I read it like you need to extract it in to that HCl solution, but am not sure of it ("shake" does
not mean exactly neither "wash" nor "extract").
…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
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chemrox
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First, let me try to clean up the language a bit to make sure I'm telling you exactly what i read. I'm thinkig we can do this without my imposing on
you too much more; by sending you the article for example.
This is verbatim:
The reaction mixture is then diluted with dichloromethane and washed with 4% aqueous (woops but probably no biggy) sodium hydroxide solution followed
by water. The organic phase was then shaken with 2N HCl. The organic layer was separated and the aqueous layer was extracted with DCM. Combined
organic phase was dried over sodium sulfate and concentrated to yield the crude HCl salt.
Two notes:
the product is soluble in DCM and the "shake with 2N HCl" is an acidification to make the HCl salt.
why Na2SO4 instead of MgSO4? isn't the latter a lot quicker? certainly cheap and available anywhere.. just heat Epsom salts.
Your insights are greatly appreciated and sought after.
[Edited on 1-4-2007 by chemrox]
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Sandmeyer
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| Quote: | Originally posted by chemrox
The reaction mixture is then diluted with dichloromethane and washed with 4% aqueous (woops but probably no biggy) sodium hydroxide solution followed
by water. The organic phase was then shaken with 2N HCl. The organic layer was separated and the aqueous layer was extracted with DCM. Combined
organic phase was dried over sodium sulfate and concentrated to yield the crude HCl salt.
Two notes:
the product is soluble in DCM and the "shake with 2N HCl" is an acidification to make the HCl salt.
why Na2SO4 instead of MgSO4? isn't the latter a lot quicker? certainly cheap and available anywhere.. just heat Epsom salts.
Your insights are greatly appreciated and sought after.
[Edited on 1-4-2007 by chemrox] |
"Shaking" the organic phase with HCl, assuming that the product is an amine, will extract it over to the aq phase. "Extracting" the aq phase with DCM
is merely a wash to remove non-polar contaminants. At this point org phase contains no amine, so the rest of the protocol makes no sense (i.e drying,
concentrating...)
What would make more sense is:
1. Wash the DCM phase with NaOH, water
2. Extract DCM phase with dilute HCl
3. Wash the aq phase with DCM
4. Evaporate aq phase to get the HCl salt...
edit: generally you can use MgSO4 to dry org phases...
[Edited on 1-4-2007 by Sandmeyer]
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Nicodem
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I agree with Sandmeyer, but have to add a note of cautiousness that there are lots (well, relatively a lot given the general prejudice) of exceptions
where amine hydrochlorides are partitioned very well into the CH2Cl2 phase. I have extracted some amine hydrochlorides into CH2Cl2 from their aqueous
solutions, usually acidified with excess HCl, more than once (needless to say that I was always surprised by this paradoxical property). Admittedly it
is a rare thing that hydrochlorides are well soluble in CH2Cl2, but there are cases. But since I have no idea what hydrochloride we are talking, if of
an amine at all, I can not say anything whether it might possibly be soluble in CH2Cl2 or not. Certainly the additional extraction by a fresh portion
of the solvent is in consistency with this (it makes things look much more logical).
Na2SO4 or MgSO4 makes no difference. I prefer Na2SO4, but that is just because it is the nearest on the shelf.
…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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jon
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I think the amine he's refering to is teriary so it's salts would be somewhat soluble in a chlorinated hydrocarbon.
yet it would be prudent not to discard the Aqueous phase.
some people prefer MgSO4 because of it's surface area properties.
and, it's a fact 9 out of ten thugs prefer to wear blue jeans and white t-shirts.
that was rhetorical.
[Edited on 1-4-2007 by jon]
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chemrox
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| Quote: | | [... that there are lots (well, relatively a lot given the general prejudice) of exceptions where amine hydrochlorides are partitioned very well into
the CH2Cl2 phase. |
I hear you both but have determined that this is one of these cases (it partions into the CH2Cl2).. so given that this is the case:
1) does the process now make sense?
2) if so and given that the pot will contain about 500 ml, how to best apply, optimize the workup?
I really appreciate your thoughts .. its been giving me fits
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Nicodem
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1.) Yes it now makes sense.
2.) Just follow the instructions, the workup as it is, is just fine.
To jon: An amine being tertiary has not much of a consequences in its hydrochloride being soluble in CH2Cl2. All the amine hydrochlorides that I found
to be soluble in CH2Cl2 were of primary type while most tertiary amine hydrochlorides that I worked with were insoluble in CH2Cl2 (though even
Et3N*HCl is somewhat soluble in CH2Cl2, not as much as Et3N*HBr which is surprisingly well soluble). In general, I think being a primary, secondary or
tertiary amine salt bears no or little importance in this property.
…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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OK
so given the finished volume before dilution what would be the conventions viv a vis
the volume of dilution?
the volumes of the washes?
would it make as much sense to bubble HCl through the ch2Cl2 phase after the washes? or drop in con HCl?
(also sent by u2u)
with thanks for your replies so far,
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Nicodem
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Volumes? That is up to you. I can not answer you that.
No, bubbling HCl through the CH2Cl2 phase makes no sense. What would be the purpouse?
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chemrox
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to saturate the oganic layer with HCl so that on evaporation the HCl salt comes out .. same as shaking with 2N but possibly more reliable ..? seems
likme one might do it that way .. or drop con HCl into the organic layer as an alternative ..probably shouldn't .. probably should follow the
published ..
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Sandmeyer
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If sulfuric acid is available, a dilute alcohol/H2SO4 soln can be made and dripped to org phase untill pH 4, then filter crystals and wash... In order
to avoid the above-mentioned solubility problems, use ether instead of DCM, it should be even easier to obtain since it is not a chlorinated solvent.
When I did experiments in the kitchen I could obtain ether but not DCM, this may vary from place to place of course..
[Edited on 2-4-2007 by Sandmeyer]
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chemrox
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You're assuming the sulfate is insoluble aren't you? I have a little ether .. a lot more THF ..aren't they more or less comparable?
what is the SOP for washing 1000 ml of oganic? 3X50 ml? 3X 25 ml? 3x100 ml?
isn't there any wisdom on this or is it totally hit and miss?
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Nicodem
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No, diethyl ether is anything but comparable to THF by its solvating properties.
Amine sulfates are practically all insoluble in diethyl ether, but not all amines form crystalline sulfates (though even more amines don't form
crystalline hydrochlorides). So, unless you know from literature that your amine crystallizes as sulfate, do not even bother. Also, the amine
hydrochlorides that are soluble in CH2Cl2 are generally not soluble in diethyl ether. I would stick to the literature procedure if I were you.
| Quote: | what is the SOP for washing 1000 ml of oganic? 3X50 ml? 3X 25 ml? 3x100 ml?
isn't there any wisdom on this or is it totally hit and miss? |
Come on! Have you not been in school? Think about it a bit. Or just read any book about laboratory practice.
…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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well yeah there's that .. and I should have before now .. and I shouldn't have taken any shortcuts.. let me ask you this though, if the organic
solution is dried over one of the drying agents .. is it 'dry' enough for salt formation when the solution is clear? I was going to dry overnight on
about a 100 g of Na2SO4 or MgSO4 and if clear continue with the solvent stripping.
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Nicodem
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But at the stage of drying with Na2SO4, the hydrochloride salt is already formed and in solution? All it takes to remove the solvent. Unless the salt
is very hygroscopic the last traces of dissolved water get removed with the azeotrope. Or are you talking about some other procedure?
Anyway, if stirred a bit from time to time, even 15 min of drying is enough for most purposes. If passively standing, it of course takes longer.
…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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Furch
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Chemrox, I just have to add that a nice way to lower the necessary amount of drying agent (100 g per 1000 ml of solution sounds like a humongous
excess by the way), which is good because your product tends to get trapped on the surface of the drying agent... Pre-dry the organic phase with a
fair amount of brine (saturated sodium chloride-water solution). If you do this, you will need no more than a couple of grams of Na2SO4*H2O at the
most to dry 1000 ml of organic phase.
Also, to make sure you're not using a too big an excess of drying agent, add it in small portions with stirring till the solution becomes clear.
[Edited on 4-4-2007 by Furch]
\"Those who say do not know, those who know do not say.\" -Lao Tzu
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chemrox
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Thanks to you both for the above!
I'm having fits over the quanitities of washes because the product stays in the organic layer so what I'm doing with the washes is taking out
unreacted materials and side reaction products. So is 33 + 33 + 33 ml per 100 ml organic valid or way over the top? Seems like a shitload of base,
water and finally acid. On the other hand I tried using a lot less before and ended up with nada. (I've still got the water for later processing).
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bio2
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.......So is 33 + 33 + 33 ml per 100 ml organic valid or way over the top? .........
Seems right. Sometimes even half volume is used as needed.
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chemrox
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| Quote: | | In order to avoid the above-mentioned solubility problems, use ether instead of DCM |
why would someone run the reax in DCE and then dilute with DCM?
to make emulsions more likley just to keep everybody on his toes?
if I use it again I will carefully swirl the sep funnel with the base the first time or two .. I had a hell of an emulsion and alcohol wouldn't break
it, vibrators barely helped, freezing helped some.. I pretty much ended up extracting the emulsion until all the color was gone from both phases and
the emulsion .. sunny beach!
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Nicodem
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Heating the emulsion up to the boiling point of CH2Cl2 often efficiently breaks it (not always though). When possible, adding a couple of drops of HCl
also completely breaks any emulsion. Adding some brine also helps in certain cases.
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bio2
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Sprinkling powdered NaCl on the surface of the emulsion
will usually break it.
Granulated salt tends to fall through the emulsion layer.
As already mentioned swirling helps and turning the sep funnel
end to end rather than shaking will often prevent this
tendency to form emulsions in the first place.
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jon
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In general has anyone noticed what kind of structual moieties cause an amine hydrochloride to partition into CH2Cl2?
like the prescence of multiple aromatic rings for example?
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chemrox
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Thanks for the breakup suggestions. I will try them when I need to again. The solution this time was filtration through glass wool. I like the salt
crystals and HCl ideas.
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