This study investigates the reactivity of the electrophilic nitroso group towards nucleophilic aniline derivatives from various nitrosating agents. A relationship between the rate of nitrosation and Edwards' nucleophilic parameter (En) is disclosed, indicative of a transition state that is mostly product-like in nature with respect to cleavage of the nitroso bond in the nitrosating agent. A similar relationship based on the work of Marcus provides a considerably better explanation of the data. Through application of the Marcus equation, the free energy change of reaction is calculated for the nitrosation reactions studied, which in turn is applied to develop an equation linking the free energy of formation of a nitrosamine and its corresponding protonated amine. This equation accounts for the often-observed Brønsted relationships in nitrosation reactions. The intrinsic barrier to reaction is estimated to be 10 kJ mol⁻¹, indicating that the main impedance to nitrosation arises from the unfavourable reaction thermodynamics. However, for the nitrosation of aniline derivatives substituted with π-electron withdrawing groups, an unbalancing of the transition state results in an increased intrinsic barrier, of the order of 19 kJ mol⁻¹. For electronic-effect aniline derivatives, a More O'Ferrall-Jencks diagram shows the nitrosation transition state to be synchronously well balanced between reactants and products. This diagram also confirms that the reaction follows a concerted mechanism. The nitrosation of resonance-stabilised aniline derivatives is somewhat less synchronous, however, due to delocalisation of the lone electron pair on the amino group, induced by π electron withdrawing substituents. Transition states were located according to the theory of harmonic parabolic wells. The results of these calculations agreed with transition state locations predicted using linear free energy relationship techniques. A method is developed which approximates free energy profiles by treating the product and reactant free energy wells as harmonic parabola, while the free energy profile around the transition state is taken as the parabolic barrier to the product and reactant energy wells. Applying this technique, free energy profiles for electronic-effect and resonance-stabilised aniline nitrosation are predicted, utilising measured kinetic values and predicted thermodynamic properties. We couple the simulated free energy profiles with their corresponding More O'Ferrall-Jencks diagrams in order to elucidate the three-dimensional reaction path traversed between reactants and products, in terms of both structure and energy. We also demonstrate that the nitrosonium ion behaves as a soft acid, and should therefore undergo covalent frontier-orbital controlled bonding.
Journal of Physical Organic Chemistry Vol. 20, Issue 3, p. 167-179