Chromatography Forum

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

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

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.

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.