Keto-enol tautomerism

[Philip]

Hi all,

If you had a compound that underwent keto-enol tautomerism in solution, what would you do to improve selectivity?

Additionally, there is a change in conformation of a substituent in solution, resultant in positions that change between planar and non-planar. How would you improve selectivity?

Stationary phase packing?

Also, one of the molecules has an absorbance around 200 nm. How do you deal with this utilizing UV-HPLC or PDA-HPLC...?

Look forward as always to your feedback. Thank you in advance for your help!

Best Regards,

Philip

[westlake]

I saw similar problem too. Did you try adjust MP pH?

[Uwe Neue]

What are you trying to do? Get a single peak from the tautomerism, or two well defined separate peaks? In the first case, increasing the temperature will help, in the second case, a decrease in temperature might be able to get you two clean peaks.

If you can separate something by chromatography depends on the speed of change between the configurations. I do not recall a case, where a planar form of a molecule can be separated from a non-planar form of the same molecule.

How does your chromatography look like at this point?

[Philip]

Yes, I can see how the temp change may help, thank you.

Would like to separate them, but haven't yet a clue on how the chromatography looks (yet to experiment).

Plus, vague on absorbance. The only absorbance possible is around 200 nm.

What type of system would you suggest starting from?

Thanks!

Regards,

Phil

[HW Mueller]

Normally, especially in acidic or basic aqu. solution (catalysis), the tautomerism should be too fast for chromatographic separation. You seem to have a ring system with some constraints, nevertheless, I would certainly like to see the structure of this substance if you are able to separate something (at low temp. as mentioned, also possibly neutral pH).
This is again a matter of kinetics and thermodynamics. The thermodynamics may be such that you have detectable amounts of both forms at equilibrium, but this equilibrium may be attained so fast (kinetics) that chromatography will "see" one substance.

[JM]

Tautomers are always a problem in HPLC separation, I am also dealing with some anomeric separation. Suggest follwing,

1. See the pH/tempeffect , this can affect the conversion.
2. Try using normal phase column ( Si or CN with haxane/IPA).most of the time non-aqueous solvents give better steric selectivity than RP.
3. Use columns that has got some steric selectivity.
4. Use additive that binds to the labile group to provide some steric hindrance like TFA

Though i got anomeric separation on HPLC but could not isolate each anomer due to their conversion as soon as they come out of prep column.

JM