[Dan]

Hi all.

I'm having an issue with an mCPBA epoxidation. The reaction works perfectly but the excess mCPBA is coeluting with my epoxide during chomatography. It is the peracid, not the benzoic acid (which was removed by bicarb washing and/or chromatography), that is the problem.

I need to fiddle with the eluents to see if I can get separation on silica, but my question to you is: does anyone know of a good, gentle destructive workup for mCPBA? I was thinking of adding a sacrificial alkene, maybe cyclohexene.

The product is fairly advanced and delicate, so I really want to avoid pH extremes or strongly reducing reagents.

Thoughts appreciated.

[discodermolide]

The sacrificial alkene is probably the best way to go.

[sjb]

Hi all.

I'm having an issue with an mCPBA epoxidation. The reaction works perfectly but the excess mCPBA is coeluting with my epoxide during chomatography. It is the peracid, not the benzoic acid (which was removed by bicarb washing and/or chromatography), that is the problem.

I need to fiddle with the eluents to see if I can get separation on silica, but my question to you is: does anyone know of a good, gentle destructive workup for mCPBA? I was thinking of adding a sacrificial alkene, maybe cyclohexene.

The product is fairly advanced and delicate, so I really want to avoid pH extremes or strongly reducing reagents.

Thoughts appreciated.

Anything useful in http://www.chemicalforums.com/index.php?topic=33754.0 ? Or of course different stationary phases ? What would the next step(s) be, would the mCPBA affect them?

[Dan]

What would the next step(s) be, would the mCPBA affect them?

This had occurred to me as well. Next step is a silyl deprotection.

I'd rather start with a clean compound, at least the first time through, because the deprotection will probably not be straightforward ("oh no, TBAF shredded my compound..."). I would much prefer to eliminate residual peracid as a possible factor when troubleshooting the next step...

[clarkstill]

Would a thiosulfate wash prior to the bicarb work? You use it to reduce residual halogens (I2, Br2), but I don't see why you couldn't use it here to reduce the O-O, then wash out the resulting benzoic acid...

[Dan]

Thiosulfate could work, yeah.

I decided to submit the contaminated material for silyl deprotection because I have plenty more material coming through, but I think I will test thiosulfate on an aliquot the next run as well as cyclohexene.

I am also investigating the reverse sequence (silyl deprotection - epoxidation), but my gut feeling is that epoxidation first will be more efficient.

[Corribus]

Not too long ago*, I published a paper on m-CPBA epoxidation of a conjugated polymer. After the oxidation was completed, we quenched residual m-CPBA with saturate aqueous sodium thiosulfate, then poured the reaction mixture into a 10% (w/w) solution of sodium carbonate. The organic layer was then washed 3x with more sodium carbonate solution. Followed with washes with water. Organic layer was isolated, dried over sodium solufate, decanted into a clean vial and evaporated to dryness. We then performed an extraction of the solid with ethanol to remove residual m-CPBA or derivatives. This was repeated until the ethanol no longer fluoresced blue from m-CPBA under UV-illumination. Analysis of the material at that point showed no residual m-CPBA in the sample. (Whether you can do this will depend on the solubilty of your product in ethanol.)

* Geez, 2009. Holy crap, time flies!

[Dan]

Wow, sounds like you had fun with that one. Hopefully thiosulfate and bicarb washes will do the trick. I should have mentioned my product is an oil and very likely soluble in EtOH, I don't think trituration is a viable option for me.

[wildfyr]

thiosulfate wash is just the ticket, give it a shot. If that doesnt work then try harder, more irritating methods. Worked like a charm last time I needed it.

[Dan]

For future reference, I repeated the reaction today and as a workup washed with 1:1 NaHCO₃/Na₂S₂O₃ three times. [n.b. the first time I only washed with bicarb]

Columned as before and this time it is spotless, 80% yield.

Thanks to all for your helpful comments.