Conformational analysis of substituted perhydro‐1,2‐oxazolo[3,2‐c] [1,4]oxazines by NMR spectroscopy

Abstract

AbstractThe 13C NMR spectra of most of the substituted perhydro‐1,2‐oxazolo[3,2‐c] [1,4]oxazines (3) at low temperature showed the presence of two isomers of unequal populations. The major isomer is shown to be the cis isomer {except in 2‐hydroxymethyl‐2‐methylperhydro‐1,2‐oxazolo[3,2‐c] [1,4] oxazine (3e)}, which is in equilibrium with the minor isomer (trans conformer) by a relatively slow nitrogen inversion. Intramolecular hydrogen bonding in oxazines, having 2‐hydroxymethyl substituents, is shown to be an important factor in determining the population ratio of the two isomers. The barrier to nitrogen inversion was determined by detailed band‐shape analysis of proton and carbon NMR spectra and were in the range 66·3–72·9 kJ mol−1. The chair inversion had been slowed down, in one case, trans‐dimethylperhydro‐1,2‐oxazol[3,2‐c] [1,4]oxazine‐2,3‐dicarboxylate (3j), to show the presence of the two forms of the cis isomers. The barrier to chair inversion is 41·5 kJ mol−1 as determined by proton NMR band‐shape analysis of 3j.