Separation of 1,2-dialkylcyclohexanes

[tony_herlt]

We are trying to separate the cis & trans isomers of 1,2-dialkylcyclohexanes by HPLC, the aim ultimately being to obtain 100 milligrams or so of each isomer. Our most successful conditions to date have been with a Cronusil Triple-E C18 4um 250mm x 4.6mm column eluted with acetonitrile and detection by refractive index, however the separation is still insufficient to attempt this preparatively. The compounds are not retained on unmodified silica eluted with hexanes due to their lack of polarity. Preparative GC would be a possibility but we no longer have an instrument capable of doing this. Any suggestions for alternative HPLC phases and condtions are very welcome. Thanks in advance.[/b]

[HW Mueller]

Since there are no "practical" answers (based on experience), I am risking a theoretical/academic skirmish.
If the alkyl side chain are short, especially methyl, it would be surprising that you have a problem at all, unless your rt is way too low. With long chain alkyl groups the geometrical differences might become obliterated. If you have various side chains than GC should be the only possibility, but prep work would be laborious.

[tony_herlt]

Thank you for your reply. One alkyl group is methyl but the other is n-C27H55, so the cyclhexane moiety is quite shielded

[mbicking]

There are some shape selective phases out there, but I don't know much about them. Search for a C30 phase (can't remember supplier, but could be Mac-Mod). Or maybe a liquid crystal phase?

It's evening and I'm just precipitating ideas all over, so if none of this makes sense, just ignore it.

[tony_herlt]

Thank you for your helpful reply - it makes good sense I will see if I can buy a Bischoff ProntoSil C30 column from Mac-Mod.

[Kelly Johnson]

The ZirChrom-CARB phase and the Diamondbond-C18 phase are very shape selective. They have a orthogonal selectivity when compared to a typical C-18 phase. Please feel free to contact me directly for additional information.

Kelly
support @zirchrom.com

[tony_herlt]

Thank you for your helpful reply. I am pretty sure we have a DiamomdBond C18 column in the lab somewhere so will give it a try.

[HW Mueller]

There is also the Hypercarb column or maybe a phenyl column. A cyclohexane ring is supposed to have a very small hint of aromaticity, so maybe the mentioned columns can "peel out" the cyclohexane from the n-alkyl "cloud", and thus see a difference??
Anyway, if you get anywhere it would be quite interesting to find out about it.

[tony_herlt]

Thank you for your reply. The phenyl column is definitely worth trying. I did some molecular modelling of the two isomers earlier this evening and the cyclohexane ring does have some accessibility. If I have success I will post to the forum.