HPLC solvent miscibility- EthOAc in water!!

[Nish]

Hi All,

Thank you all for the comments on my earlier post.

I have a general question, which I would like to discuss in the forum. This is about miscibility of ethyl acetate in water. Strictly speaking EthOAc is slightly soluble in water with about 8% dissolving fairly readily following a short vigorous shaking (and will not separate out on standing, I believe Merck Index also says so).

The HPLC solvent miscibility chart shows that the 2 are immiscible. If one happens to use such a eluting condition (where EthOAc is more than 15-20%) we can see that water and EthOAc will phase-out and elute separately out of the column (as alternating water and EthOAc bands) and result in high column backpressure.

Still I have seen many published papers (peer-reviewed) and couple of technical bulletins from column manufacturers, where water and EthOAc has been used as eluting solvents and sometimes running from a gradient of 90-10 to 50-50 on a C18 column at room temperature (~25C) with uv detection.

I am perplexed here. Could anyone help me out? I would greatly appreciate it.

Thank you

Nish

[danko]

Maybe there was ACN or MeOH or isopropanol as well in one or both solvents, which of course would’ve facilitated the miscibility?

Best Regards

[rhaefe]

The terms "Solubility" and "Miscibility" have two different definitions:

Miscibility: Two or more (liquid) compounds can be mixed in all proportions and result in one phase.

Solubility: One compound is soluble (to a certain degree) in another.

So, in your case EtOAc is soluble in water (up to 8%?) but it is not miscible in water.

Not sure if this is an official definition but that's what I have been taught quite some time ago.

[tom jupille]

Still I have seen many published papers (peer-reviewed) and couple of technical bulletins from column manufacturers, where water and EthOAc has been used as eluting solvents and sometimes running from a gradient of 90-10 to 50-50 on a C18 column at room temperature (~25C) with uv detection.

Can you cite references for those? I really, really doubt that anyone ever ran up to 50/50 water/ethyl acetate. The only way that could happen is with the presence of a co-solvent as danko suggested.