Hello everybody,

I need some advice on chiral separation of a carboxilic acid (MW around 150-200).
I have already tested a Daicel AD-H with a wide gradient 90/10 Isohexan/EtOH and some Astec chirabiotics column in reversed phase(CH3CN/H2O).
I dont have any resolution between both enantiomers.
I have a method on a Daicel AD for the corresponding ester that works perfectly.
Maybe i have to add some buffer or try another phase ?
Thanks for your advices,

Laurent

try SFC

Since this is an acidic compound you probably need some acid in your mobile phase. I would recommend 0.1% v/v TFA. 90/10 isohexane/EtOH is a "intermediate strength" mobile phase on Chiralpak AD-H. If the peak(s) are poorly retained (i.e., k of <2), then I would recommend using 95/5/0.1 alkane/EtOH/TFA, if they are still poorly retained then try 98/2/0.1.

If the compound is well retained you can use "stronger" mobile phase such as 85/15/0.1 alkane/EtOH/TFA or even straight EtOH/TFA 0.1% (or MeOH/TFA 0.1% - note MeOH is not miscible with isohexane, so you need to go through a switch with EtOH first). If you use staight EtOH the back pressure will be high, so use 0.5 mL/min.

Further, chrial separations can be very dependent on solvent. I would recommend that you also try alkane/2-PrOH/TFA. Sometimes there is a dramatic difference in the separation, sometimes there is almost no effect.

As far as analogs go, the fact that the ester worked under one set of conditions is almost irrelevant. Since the separation is based upon steric recognition, small changes in the structure of the molecule can have a large affect on the separation. I would try the alkane/alcohol conditions on the OD that were given above for AD-H.

I would also look at as many different columns as possible. The ASTEC website (www.astecusa.com) also contains examples of acid separations on their columns.

If you wish to discuss this further, my email address is william.champion@us.rhodia.com.