Theoretical study of the global and local reactivity of a series of 3-aryl coumarins

Coumarins are bioactive derivatives of the 1-benzopyran-2-one family with biological properties, such as antioxidant, antiviral, anti-inflammatory, and antitumoral, among others. In this work, the theoretical study of global (η, μ −, μ +, ω −, ω +, and Δ\(\omega^{ \pm }\)) and local reactivity properties (f k +, f k −, f k 0, f k (2), Δρ k Elec, and Δρ k Nuc) of a series of 18 substituted 3-aryl coumarins is carried out through density functional theory methods including solvation effect. From the global reactivity point of view, the substituted compounds are better electron donors than the non-substituted 3-aryl coumarin. In contrast, from the local reactivity point of view, the C4 site of the pyrone ring shows the highest probability for a nucleophilic attack; radical attacks are also described within the pyrone ring, whereas electrophilic attacks are mainly described for the phenyl ring or in atoms of the substituent. In addition, a statistical analysis was carried out in order to validate the global reactivity results.