Nucleophilic displacements in substituted pyridine N-oxides. Part I. Kinetics of the reactions between sodium ethoxide and 2- and 4-bromo-, 4-chloro-, 2-, 3-, and 4-nitro-, 4-chloro-3,5-dimethyl-, and 3,5-dimethyl-4-nitro-pyridine 1-oxide in anhydrous ethanol

Abstract

Rates of reaction of halogeno- and nitro-pyridine N-oxides with sodium ethoxide in anhydrous ethanol have been measured and the Arrhenius parameters calculated and discussed.

The reaction rates, entropies, and energies of activation for nitro-group displacements all decrease in the order 2 > 4 > 3. With the bromopyridine N-oxides both the entropy and energy of activation decrease in the order 4 > 2, but the positional reactivity is 2 > 4. Two methyl groups adjacent to the leaving group retard the reactions of 4-bromo- and 4-nitro-3,5-dimethylpyridine 1-oxides. Low activation energies are attributed to hindrance of nitro-group conjugation in the ground state, either by N-oxide oxygen dipolar repulsion (for 2-nitropyridine 1-oxide) or steric inhibition (in 3,5-dimethyl-4-nitropyridine 1-oxide).

Small negative (or small positive) values obtained for activation entropies are attributed to extensive desolvation in forming the transition state. The very high entropy of activation for the reaction of 2-nitropyridine 1-oxide is attributed to the increased freedom of rotation of the nitro-group in the transition state compared to the restriction imposed by the N-oxide oxygen in the ground state.