Differentiation of substituent effects from hydrogen bonding and protonation effects in carbon-13 NMR spectra of pyridine N-oxides

Abstract

Aromatic ¹³C chemical shifts are reported for 4-substituted and 3-substituted pyridine N-oxides measured in deuteriochloroform, deuterium oxide, perchloric acid (60% in D₂O) and dichloroacetic acid (80% in CDCl₃), and also for O-alkylated derivatives in (CD₃)SO and D₂O. The substituent chemical shift (SCS) data show systematic non-additivity in comparison with monosubstituted benzenes. Data for the position para to the variable substituent were analysed by means of the dual substituent parameter equation. For this position multiple substituent interactions are responsible for the non-additive shifts; interactions have both an inductive (polar) and a resonance component. Hydrogen bonding and protonation effects were differentiated from the substituent effect. It is shown that the relative ¹³C chemical-shift difference [(Δ₃–Δ₄)/Δ₃] is a measure of the hydrogen bond and protonation effects and is not subject to substituent effects. 3-Dimethylaminopyridine N-oxide is protonated at the dimethylamino group, but 4-dimethylaminopyridine N-oxide at the oxygen.