Nitrosation of dialkylhydroxylamines, and computational and NMR investigations of the interconversion of conformational isomers of N -nitroso-dimethylhydroxylamine

Abstract

The effect of acidity upon the rate of nitrosation of N-benzyl,O-methylhydroxylamine (3) in 1:1 (v/v) H2O/MeOH at 25 °C has been investigated. The pseudo-first-order rate constant (kobs) for loss of HNO2 as the limiting reagent decreases as [H3O+] increases. This is compatible with two parallel reaction channels (Scheme 2). One involves the direct reaction of the free hydroxylamine with HNO2 (k1 = 1.4 × 102 dm3 mol−1 s−1, 25 °C) and the other involves the reaction of the free hydroxylamine with NO+ (k2 = 5.9 × 109 dm3 mol−1 s−1). In contrast, there is only a very slight increase in kobs with increasing [H3O+] for nitrosation of N,O-dimethylhydroxylamine (4) in dilute aqueous solution at 25 °C to give N-nitroso-dimethylhydroxylamine, 5. This also fits a two-channel mechanism (Scheme 3). Again, one involves the nitrosation of the free base by NO+ (k2 = 8 × 109 dm3 mol−1 s−1, 25 °C) but the other channel now involves catalysis by chloride (k3 = 1.3 × 108 dm3 mol−1 s−1). Arising from these results, we propose an estimate of pKa ∼ −5 for protonated nitrous acid, (O = NOH), which is appreciably different from the literature value of +1.7. The interconversion of cis and trans conformational isomers of 5 has been investigated by temperature-dependent NMR spectroscopy in CDCl3, methanol-d4, toluene-d8 and dimethyl sulfoxide-d6. Enthalpies and entropies of reaction and of activation have been determined and compared with computational values obtained at the B3LYP/6-31G* level of theory. The cis form is slightly more stable at normal temperatures and no solvent effects upon the thermodynamics or kinetics of the conformational equilibrium were predicted computationally or detected experimentally. In addition, key geometric parameters and dipole moments have been calculated for the cis and trans forms, and for the lowest energy transition structure for their interconversion, in the gas phase and in chloroform. These results indicate electronic delocalisation in the ground states of 5 which is lost in the transition structure for their interconversion. Copyright © 2010 John Wiley & Sons, Ltd.