Stereochemistry of nitrogen‐containing heterocycles. IV—1H and 13C NMR spectra, ASIS effects, nitrogen inversion, configuration and conformations of substituted tetrahydro‐1,3‐oxazines

Abstract

AbstractThe 1H and 13C NMR spectra of 50 methyl‐ and phenyl‐substituted tetrahydro‐1,3‐oxazines are presented and discussed. Conformational analysis based on the model of atom‐atom interactions in 3,5‐dimethyltetra‐hydro‐1,3‐oxazine shows that the free energy difference between the chair and twist forms is 21 kJ mol−1. The distortion of the ring, which adopts a chair conformation, is analysed by the R value method and by the ASIS effect. The use of geminal 2J(HH′) values in the heteroatomic moieties as a criterion of the ring conformation has been demonstrated. The equilibrium and activation parameters of the heterocycle and nitrogen inversion have been determined. A good correlation between the predicted and experimental chemical shift values, δc, has been obtained, and this is shown to depend on the spatial structure of the substituted tetrahydro‐1,3‐oxazine molecule; moreover, the influence of intermolecular associations on δc has been demonstrated. Conformational preferences and some peculiarities in the chemical shifts are explained in terms of interactions with the endocyclic β‐oxygen atom and the N‐methyl group.