Rearrangements of 2-Nitrobenzyl Compounds. 2. Substituent Effects on the Reactions of the Quinonoid Intermediates

Photoinduced tautomerization of 2-nitrobenzyl derivatives (1) gives rise to quinonoid intermediates (2), which
may undergo further reactions competing with the retautomerization to 1. Rearrangements of 2 with different
α substituents were studied with methods based on the density functional theory. The B3LYP functional with
three different basis sets was used to optimize geometries of the minimum-energy and transition structures.
The single-point energies were computed at these geometries by using the 6-311+G(2d,p) basis set in
combination with four different hybrid functionals. Bulk solvent effects were estimated from the B3LYP/6-311+G(2d,p) free energies computed at the gas-phase geometries with the self-consistent reaction field polarized
continuum model method. A common reaction pathway for the E isomers of substituted 2 was identified as
the exothermic cyclization leading to 2,1-benzoxazoline derivatives (3). The cyclization was predicted to be
highly stereoselective, two distinct modes of the reaction were found for two stereoisomers differing in the
position of the α substituent relative to the nitronic moiety. The activation barrier for the cyclization appeared
to be reasonably well correlated with the electron-donating ability of the substituent that was characterized
by the Hammett-type σp+ constants. The effective barrier height for the tautomerization 2 → 1 showed an
opposite trend. The isomerization 2 → 3 was predicted to compete efficiently with retautomerization for all
compounds except for the parent compound and those with strong electron-withdrawing susbstituents. The
cyclization of 2 in the gas phase and water was predicted to encounter a much smaller activation barrier than
the analogous isomerization reaction of the deprotonated species (2-). Very high activation energies for the
reaction 2- → 3- were linked to profound structural changes predicted for deprotonation of 3. The computational
results were discussed in respect to mechanism(s) of the photoinduced isomerization of 1 and to development
of more efficient photolabile protecting groups.