Optimizing a separation on TLC is important but it is not the only thing that matters when translating into flash chromatography.

The first step is to obtain a TLC separation with the aim of keeping the retention factor (Rf) values as low as possible.

Solvent Solvent Strength Methanol 0.95 Ethanol 0.88 2-Propanol 0.82 Acetonitrile 0.65 Ethyl Acetate 0.58 Tetrahydrofuran 0.57 Acetone 0.56 Dichloromethane 0.42 Chloroform 0.40 Diethyl Ether 0.38 Toluene 0.29 Hexane 0.01

Hexane:EtOAc Hexane:CH2Cl2 1:1 1:2

Optimizing a separation using TLC does not necessarily translate to optimum column chromatography.

Using a ‘slower’ solvent system can greatly improve the degree of separation.