A broadly applicable quantitative relative reactivity model for nucleophilic aromatic substitution (SNAr) using simple descriptors† † Electronic supplementary information (ESI) available: detailed experimental and computational procedures, statistical modeling information, supplementary figures, tables of molecular descriptors, and coordinate files for calculated structures. See DOI: https://doi.org/10.1039/d2sc04041g

ABSTRACT: We report a multivariate linear regression model able to make accurate predictions for the relative rate and regioselectivity of nucleophilic aromatic substitution (SNAr) reactions based on the electrophile structure. This model uses a diverse training/test set from experimentally-determined relative SNAr rates between benzyl alcohol and 74 unique electrophiles, including heterocycles with multiple substitution patterns. There is a robust linear relationship between the experimental SNAr free energies of activation and three molecular descriptors that can be obtained computationally: the electron affinity (EA) of the electrophile; the average molecular electrostatic potential (ESP) at the carbon undergoing substitution; and the sum of average ESP values for the ortho and para atoms relativ

SUBMITTER: Lu J 

PROVIDER: S-EPMC9645419 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature