I have performed a Sonogashira coupling, and I would ask if anyone knows an easy method to remove triphenylphosphine from the product (the product is pure after aqueous workup and only triphenylphosphine is there). The product decomposes on silica gel.
Will this maybe work for you?
http://pubs.acs.org/doi/abs/10.1021/ol0159219
Hello Vicente,
just a short question: what's the nature of your product so that it decomposes on silica gel? Is it unstable against slightly acidic conditions - then you might buffer the silica gel using, e.g., triethylamine together with the solvent. Otherwise you could use other stationary phases, such as basic aluminium oxide.
Regards
Simon
First of all, are you sure that your impurity is triphenylphosphine (TPP), and not triphenylphosphine oxide (TPPO) ? Usually TPP is easy to remove, while TPPO is not.
If your impurity is TPPO, its solubility in diethyl ether is not good, and you will need large amount of ether if you want to extract all TPPO; in this case most likely you will loose a lot of your product as well.
From my experience, in most cases TPPO happens to be more polar than the product and washing the crude mixture with non-polar solvent (like hexane or hexane-ether mixture) allows to extract the product from insoluble TPPO.
If nothing else, you may consider using polymer-supported TPP - relatively expensive, but no problems with either TPP or TPPO.
The product seems to be unstable in silica but on alumina it seems to be stable. This afternoon y managed to remove triphenylphosphine from the product by washing with hexane, but some product also dissolved.
Following article might help you:
Org. Lett., 2001, 3 (12), pp 1869–1871
Check the solubility of your product and non soluble nature of triphenylphosphine with different solvent. .Or
use column chromatography with change of polarity of solvent
Just ad some methyl iodide. The excess is volatile and your triphenylphosphine will be instantaneously converted into the phosphonium salt, insoluble in many solvents. It will also be retained if you filter through a short plug of neutral alumina. Anyway I doubt you have triphenylphosphine after aqueous workup. Check 31P NMR. You might have triphenylphosphine oxide, which will be quite difficult to get rid of. Good luck!
Sublimation in oil-pump vacuum ( PPh3 pressure ~0.01mmHg at 100oC ) for lab quantities (gram-scale) ;
extraction of product by mixtures of H2O with hydrophilic solvents (DMF, acetonitrile, methanol, ethanol, isopropanol...)
PPh3 and O=PPh3 can be sequestered simultaneously by readily available dichlorotriazine derivative :
http://pubs.acs.org/doi/abs/10.1021/ol0002222
@Javier Vicario
"Just ad some methyl iodide...."
At 20oC reaction of MeI with PPh3 needed ~12hrs.
Not sure about "SHORT plug of NEUTRAL alumina" , acidic alumina will work http://repository.tudelft.nl/assets/uuid:ce2b5c68-8a3c-4919-9e7f-0ac3689e4817/TR-diss-0001424(1).pdf.
If you will face the problem with TPP in the future you can try to add CuCl to the solution of your crude product in acetone. CuClxTPP complex is insoluble in this solvent....
Right now I'm doing a wittig reaction with the same biproduct. I Can't seem to find my source and I don't know if your product is reactive to this but Florisil might be option for an adsorbent, but if you can't I usually recrystallize in a water bath using hexane as the recrystallization solvent; sometimes 7:1 Hexane:Ethyl Acetate if the solubility is off. TPPO isn't soluble in hexane is stated above and it's not soluble in 7:1 Hexane: Ethyl Acetate either.
non polar solvent slurry or trituration is a very simple process used to remove TPP/TPPO impurities from a solid material. It is carried out by vigorously stirring a solid in a large volume of a given solvent in which the main component is insoluble and the impurities are soluble. The vigorous stirring facilitates the grinding of the solid to a fine powder thereby making it easier to extract (wash out) the soluble impurities from the solid.
I am facing the same difficulty now. Only that, I used a different method. Can you separate TPP or TPPO by GCC instead?
As you mentioned your product is adsorbed on silica, so it has basic character. I suggest to try silica column then elute first with ethyl acetate : hexane 1:1 at which phosphine can be eluted then with chloroform : methanol 3:7 this polar eluent will elute your material.
I would suggest to contact Dr Ross Denton (associate professor of organic chemistry / School of chemistry - The University of Nottingham) as he is very interested in developing new catalytic reactions using organophosphorus compounds.
Recent publication: http://pubs.rsc.org/en/content/articlepdf/2014/CC/C6CC00556J?page=search
TPP and TPPoxide could be separated from reaction mixtures according to the link below with a chloromethylated crosslinked polystyrene resin which is in situ activated with NaI (formation of iodomethylated resin). This resin should scavenge TPP by formation of phosphonium salt. This seams to be a reasonable method for this problem which irritated several generations of chemists.
https://www.ncbi.nlm.nih.gov/pubmed/11405732
Triphenylphosphine can be precipitated in ether, you can use ether to wash it.
Here is a JOC paper that describes removing TPPO with ZnCl2. J. Org. Chem. 2017, 82, 9931−9936. Thanks
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