Towards a physical interpretation of substituent effect: Quantum chemical interpretation of Hammett substituent constants

Abstract

Quantitative description of substituent effects is of a great importance especially in organic chemistry and QSAR-type treatments. The proposed approaches: substituent effect stabilization energy (SESE) and charge of the substituent active region (cSAR) provide substituent effect characteristics, physically independent of the Hammett's substituent constants, σ. To document abilities of these descriptors the B3LYP/6-311++G(d,p) method is employed to examine changes in properties of a reaction center Y (Y = COOH or COO− groups) and a transmitting moiety (benzene ring) due to substituent effects in a series of meta- and para-X-substituted benzoic acid and benzoate anion derivatives (X = NMe2, NH2, OH, OMe, CH3, H, F, Cl, CF3, CN, CHO, COMe, CONH2, COOH, NO2, NO). The transmitting moiety is described by aromaticity indices HOMA and NICS(1). Furthermore, an advantage of the cSAR characteristic is the ability to use it to describe both electron donating/accepting properties of a substituent as well as a reaction center. It allows demonstration of the reverse substituent effects of COOH and COO− groups on substituent X.