Abstract:
The Hammett substituent parameter (σp) is fundamental to physical organic chemistry but often suffers from inconsistencies in experimental determination across diverse substituents. This study presents a quantum chemical approach for estimating σp values using 1H NMR chemical shift differences (Δδ) in hydrogen-bonded 2-pyridone heterodimers. Using density functional theory (M06L/6-311++G(d,p)), we examined four dimer topologies─da, db, dc, and dd─and found that the Δδ values in the db configuration, where the substituent is spatially remote from the hydrogen-bonding region, exhibit the strongest correlation with σp. This aligns with the sterically free nature of σp. Additional correlations are observed between σp and structural (Δr), energetic (ΔE), and electronic descriptors (MESP, QTAIM) of CO···HN hydrogen bonds. Among the topologies, db and dc systems provide the most reliable correlations, while deviations in da and dd dimers arise due to proximity-induced secondary interactions. The NMR-derived substituent constant, σp(NMR), was computed for a diverse set of 99 substituents, offering a unified, reliable, and computationally efficient framework for predicting and refining the Hammett constants. These findings underscore the potential of NMR chemical shifts as a powerful experimental and computational tool for quantifying substituent effects and enhance the theoretical foundation for structure–reactivity relationships in organic chemistry.
