Quantum-chemical modeling of the spatial and electronic structure of asphaltenes containing different numbers of electron-withdrawing substituents used the DFT/B3LYP-6-31G(d,p) method to predict the reactivity of petroleum asphaltenes upon their chemical modification. The change of torsion angle of the polycondensed aromatic asphaltene structure depending on the type of substituent was studied. The electronic structure and electron-density charge distribution over the aromatic carbon atoms were analyzed to determine the predominant direction of electrophilic substitution of the studied asphaltene model structures. A high degree of polycondensation of the asphaltenes and the presence of electron-donating aromatic heterocyclic fragments were shown not to affect significantly the direction of attack of an electrophilic reagent. Introduction of electron-withdrawing substituents decreased the rate of electrophilic substitution.