Chapter 3: Structure and Reactivity

Potential energy diagrams reveal critical information about activation energy barriers, intermediate species, and the energetic landscape governing reaction pathways. Students learn to distinguish between thermodynamic control, where reaction outcomes reflect the relative stability of products, and kinetic control, where reaction rates determine which product predominates. The chapter integrates free energy thermodynamics by exploring how enthalpy and entropy contributions combine to influence whether reactions proceed spontaneously. Hammond's postulate is presented as a conceptual tool for predicting transition state structure based on product resemblance, while the Curtin-Hammett principle explains how competing pathways are governed by activation energy differences rather than intermediate stability. Kinetic isotope effects are analyzed as experimental evidence for mechanistic understanding, revealing how isotopic substitution affects reaction rates when bonds to that isotope are broken in the rate-limiting step. Molecular orbital theory connects structure to reactivity through frontier orbital analysis, particularly HOMO-LUMO interactions that rationalize electrophilic and nucleophilic attack patterns. The chapter emphasizes frontier molecular orbital theory as a predictive framework, demonstrating how orbital symmetry, energy levels, and spatial overlap dictate reactivity and selectivity. By synthesizing quantum mechanical principles, thermodynamic reasoning, and kinetic analysis, this chapter equips students with conceptual tools to predict, rationalize, and design organic transformations.