[Babcock_Hall]

We recently made a 3-carbon, one-carboxylic acid vinyl sulfone using an excess of sodium phenylsulfinate as one of the reactants.  The procedure we followed called for extraction between ethyl acetate and water prior to silica gel chromatography.  We would like to perform a similar reaction to produce a 4-carbon, two-carboxylic acid vinylsulfone (see attached drawing).  I am concerned that our product will partition significantly into water.  So far my ideas to minimize this are a) increase the relative proportion of ethyl acetate, b) try 7:3 chloroform/isopropanol (a suggestion from a colleague), or c) try extracting versus saturated potassium chloride or other salt.  Tactic (c) is based on the idea that we might be able to increase the partitioning of our desired product into ethyl acetate by making the aqueous phase more polar.  We should have enough crude product to try more than one purification method if we need to.  Any thoughts on which is most likely to succeed? 

[TheUnassuming]

I would guess that a combination of saturating your aqueous layer with salt and doing many extractions with EtoAc will be your best bet for getting the most of your compound out of the aqueous layer.

What are you trying to get your material away from that requires the extraction?

[Babcock_Hall]

Sodium phenylsulfinate is used in 1.5 molar excess in this reaction.

[TheUnassuming]

Fun extraction . So in the aqueous layer you are trying to straddle the pka of the sulfinic acid and the carboxylic acids when you extract? 

Are the rf's of the two so close on silica that you can't load the whole lot?

[Babcock_Hall]

Fun extraction . So in the aqueous layer you are trying to straddle the pka of the sulfinic acid and the carboxylic acids when you extract? 

Are the rf's of the two so close on silica that you can't load the whole lot?

I was not thinking about the possibility of proton transfer until you brought it up.  I found a pK_a value of about 2.7 for the sulfinic acid, but I am not sure about the pK_a values of the product.  The pK_a values of fumaric acid are 3.0 and 4.4.  I think that the R_f of the sodium salt is quite low, but we did not examine the R_f of the free acid.

[TheUnassuming]

Dang, then I'm guessing any of the ideas to push the product into the organic are going to push the excess SM there as well. 

The good news is that your product looks far more polar than your excess SM, so the separation on the column shouldn't be too bad, especially if you dope the mobile phase with the right acid to keep them from streaking into each other.

[TheUnassuming]

Whats the next step in the synthesis?

[Babcock_Hall]

The good news is that we would have our product once we purify it (it is a proposed enzyme inactivator).

[TheUnassuming]

Oh, nice!  If the reaction is relatively clean (and you have enough material) you might try crystalizing the sodium salt of your compound.  The di-sodium salt I'd imagine will make some nice crystals for running your assays.

[Babcock_Hall]

That's also a good idea.  Occasionally, IEX using triethylammonium bicarbonate can be useful as well.

[wildfyr]

What about trying to fully oxidize whatever sulfinate is left over? I think Ive seen hydrogen peroxide used. Itll be the sulfonic acid which will be deprotonated in anything but very concentrated acid. The carboxylic acid can be protonated with a weak acid solution, and then you can do a normal extraction in say, chloroform/1M HCl.

[wildfyr]

If you try mine you gotta let me know. I'm proud of that one, its subtle.

[Babcock_Hall]

Will do.  We have been slowed down with inclement weather, but we will pick it back up.  We are interested in making other compounds in this series.