Frontier Orbitals and Charge Approaches in Electrophilic Aromatic Substitution: The Cases of Anisole and Benzaldehyde

The study aimed to verify the possible use of DFT calculation in the prediction of the orien-tation in electrophilic aromatic substitution. An activated ortho/para orienting substrate, and a deactivated meta orienting substrate were used in DFT calculations using B3LYP, B3PW91, BPV86, CAM-B3LP, HCTH, HSEH1PBE, LSDA, MPW1PW91, PBEPBE, TPSSTPSS, and WB97XD functionals were performed. The results showed that the reactiv-ity of anisole can be adequately described considering charge control in reaction per-formed in hard conditions (nitration), while frontier orbital control can play a role in reac-tions performed in softer conditions (chlorination). Nitration of benzaldehyde can be ra-tionalized through Hirshfeld charges analysis. Neither the frontier orbital nor Mulliken charges approach adequately account for behavior observed in chlorination of benzalde-hyde. The effect of different basis sets was tested performing calculations with B3LYP functional and aug-cc-pVDZ, 6-311G+(d,p), aug-cc-pVQZ,, DGTZVP, and LanL2DZ basis sets. For anisole, all basis sets provided a HOMO electron density distribution consistent with experimental reactivity, Hirshfeld charges analysis consistently reproduced the ob-served reactivity of anisole across all tested basis sets. All the basis sets were able to ex-plain the observed reactivity of benzaldehyde in hard experimental condition, while they failed to give a correct description when a softer reagent was used.