Multivariate Characterization and Modelling of the Chemical Reactivity of Epoxides. Part II: Extension to Di‐ and Trisubstitution

Abstract

AbstractThe chemical reactivity toward 4‐nitrobenzylpyridine (4‐NBP) of a series of twelve mono‐, di‐ and trisubstituted epoxides has been modelled by means of multivariate quantitative structure‐property relationships (QSPRs). The models were established using theoretical descriptor variables and partial least squares (PLS) analysis. It was found that a multivariate set of eleven descriptor variables was sufficient to adequately model the chemical reactivity. Furthermore, there existed a non‐linear relationship between the theoretical descriptors and the chemical reactivity. Two‐component PLS models were generally required, using the second component to compensate for non‐linearity in the first. The nature of the non‐linearity suggests that different physico‐chemical factors are regulating the chemical reactivity among two observed subgroups of epoxides. The reactivity of one group of five epoxides with one non‐substituted ring carbon is regulated by the electronegative properties of the substituent on the other ring carbon, whereas the reactivity of seven di‐ and trisubstituted epoxides depends on a combination of the substitution pattern around the epoxide ring and the size of these substituents. Two additional points of general relevance for QSPR modelling are also addressed, namely predictor variable selection and appropriate transformation of the dependent variable.