Structure‐activity relationship in the case of intramolecular ortho ‐cyclization of aromatic nitroso oxides: Inverted steric effect of substituent in the 2‐R‐C 6 H 4 NOO transformation

A systematic theoretical study at the M06L/6‐311+G(d, p) level of theory was carried out to calculate the activation barriers Δ H ≠ for the intramolecular ortho ‐cyclization of aromatic nitroso oxides 2‐R‐C 6 H 4 NOO and to reveal the effect of substituent nature and position in the benzene ring on the nitroso oxides reactivity. A set of 24 substituents with widely differing spatial and electronic properties (inductive, resonant, steric effects of R) was studied. The para ‐substituent was shown to have little effect on the Δ H ≠ value. The full set of effects of the R substituent contributes to the reactivity of ArNOO for 3‐substituted aromatic nitroso oxides. In the case of 5‐substituted ArNOO the Hammett‐type relationship was obtain to describe inductive and resonant effects of R on the ortho ‐cyclization reactivity. The ortho ‐cyclization for 2‐substituted nitroso oxides is a nontrivial example of the existence of an “inverted” steric effect, when an increase in substituent size accelerates intramolecular transformation. The substituent in position 6 also exhibits an “inverted” steric effect, but it is noticeably weaker than that for 2‐R‐C 6 H 4 NOO.