Enantioseparation of 3-substituted isoindolin-1-ones by HPLC

The enantioseparation of 3-alkyl-isoindolin-1-ones (1-9) and 3-alkyl-3-hydroxy-isoindolin-lones (10-14) (R = Me, Et, n-Pr, n-Bu, n-C5H11, n-C7H15, i-Bu, Ph and Bn), as well as 3-n-heptyl-2[2-hydroxy-1-phenylethyl]-isoindolin-1-one(15) by HPLC using (S)-tert-leucine and (S)-1-alpha-NEA as a chiral stationary phase, and 1%-6% (volume fraction) 2-propanol. or ethanol in hexane as the mobile phase was studied. The effect of content of polar solvent in mobile phase on the enantioseparation was discussed. The effects of 3-substituents on retention factor and chiral recognition were studied.. For the majority of racemates (1-14) a baseline separation could be obtained. For racemate(15), the elution orders are (3R,1'R)/(3S,1'S) then (3R,1'S)/(3S,1'R) with n-hexane/2-propanol (volume ratio 99:1) as a mobile phase and the resolutions are 1.44 and 5.58, respectively.