Amide N-oxides: an ab initio molecular orbital study

Abstract There are no known examples of amide N -oxides. The present study employs ab initio molecular orbital calculations at the 6-3G ∗ level to explore potential target molecules in this class. Bridgehead bicyclic lactams appear to be attractive targets for oxidation to form the corresponding N -oxides because they have reduced (or zero) amide resonance energy. The amide N -oxide linkage is predicted to have a ca. 9–10 kcal/mol rotational barrier due to eclipsing of nonbonded oxygen atoms in the transition state. The linkage has a nearly flat conformational ( Φ ON–CO ) profile in the range 120–240° and this suggests that a very sterically hindered acyclic amide N -oxide may be a practical synthetic target. The oxidation of strained amides is calculated to be highly exothermic if dimethyldioxirane is employed. This reagent is predicted to react appreciably exothermically with normal, stable amides such as N , N -dimethylacetamide, thus offering the potential for generating and studying such relatively unstable amide N -oxides at low temperatures.