Chemical Reactivity

Abstract

Expanding on the concepts outlined in the first chapter, the general reactivity of the carbonyl group is presented, now including the presence of substituents on the carbon. Nucleophilic addition may compete with hydrogen abstraction from the alpha carbon and addition may take place under thermodynamic or kinetic control, and may require acid catalysis. The Klopman–Salem equation is presented and its components are discussed qualitatively, stressing the importance of the frontier orbitals in nucleophilic additions. The approach of the nucleophile to the carbonyl is predicted to be close to the Bürgi–Dunitz trajectory, but will be sensitive to steric effects from carbonyl substituents. Electrophilic and basic properties of the carbonyl group are compared to imines and nitriles. LUMO energies can be used to predict that the relative electrophilic activities and acidities of the functional groups are aldehydes > ketones > imines > nitriles. Intrinsic basicities are correlated to the HOMO energies: imines > aldehydes ∼ ketones > nitriles. Carbon nucleophiles generally add to the carbonyl group, while oxygen or nitrogen nucleophiles can also react as bases. The abstraction of an alpha hydrogen requires alignment of the C–H bond with the HOMO of the carbonyl, imine, or nitrile. Prochirality, enantiotopic, and diastereotopic terms are introduced.