Empirical energy-density relationships for the analysis of substituent effects in chemical reactivity

Electronic substituent effects may be rationalized in terms of Hammett-like linear relationships between global energy-dependent quantities and local electronic descriptors of reactivity. These linear relationships are framed on a local hard and soft acids and bases (HSAB) principle in accord with p revious results reported by Li and Evens [J. Am. Chem Sec. 1995, 117, 7756] . Chemical substitution is indirectly assessed as local responses at the ac tive center of the substrate, with the Fukui function and local softness as the key quantities within the present approach. This model of chemical sub stitution has a potential advantage with respect to models based on group p roperties using the electronegativity equalization principle (EEP), since t he transferability of group properties is not required. The formalism is il lustrated for the gas-phase basicity of alkylamines, and the gas-phase acid ity of alkyl alcohols and alkyl thioalcohols. Our results based on the loca l HSAB rule agree a ell with those obtained from group properties analysis based on the EEP, suggesting that bath empirical rules consistently complem ent each other.