Seven couples of position isomers on the aromatic ring of benzodioxinic compounds had to be separated. The tries made on classical systems in gas chromatography or liquid chromatography did not allow the separation. We have studied the structures of solutes by molecular modeling. Many molecular descriptors (lipophilic, electronic and steric) were calculated. Our objective was to compare the relative difference between the isomers in term of lipophilicity, electronic and steric properties and design the chromatographic system where these interactions are dominant. From these results, the porous graphitic carbon stationary phase was chosen and allowed a good separation of all the products.