O-Alkylation of N-Phenylhydroxylamine in Dimethyl Sulfoxide with Methylarenesulfonates

Abstract

The methylation of N-phenylhydroxylamine (NPHA) with methylarenesulfonates in DMSO gives alkylation of the O atom in contrast to methylation in methanol where N alkylation occurs. The Hammett ρ values indicate that alkylations with N-methylanilines and NPHAs both involve the N atom. The NPHAs show “nominal α-effects” but involve comparison of N atoms with O atoms. The reactivity of the principle component, the zwitterion I, is examined with leaving group studies and comparison with benzyl alkoxide reactivity.

Pitfalls in Assessing the α-Effect: Reactions of Substituted Phenyl Methanesulfonates with HOO−, OH−, and Substituted Phenoxides in H2O

“…The origin of the enhanced reactivity that is generally observed for nucleophiles possessing an atom with an unshared electron pair adjacent to the nucleophilic center, described originally by Edwards and Pearson as the α-effect, continues to be controversial. − Prevalent theories on the α-effect phenomenon include ground-state (GS) destabilization, transition-state (TS) stabilization, thermodynamic stabilization of products. and solvent effects. − Impetus for these studies has recently come from two fronts: (1) development of new mass spectrometric techniques, which have provided insight into gas-phase reactivity, and (2) rapid advances in calculational methods. − …”

Dissection of Activation Parameters in the Bell-Shaped α-Effect Following Solvent Modulation (DMSO–H2O Media)

“…Because of this enhancement they have been used effectively for nucleophilic breakdown of neurotoxins, antidotes for nerve gases, cleanup of contaminated sites, etc. − In analysis of the α-effect it has been pointed out that the effect must be carefully defined; as previously suggested here the ratio of the rate constant for reaction of α-nucleophile to the rate constant for a normal reference nucleophile of the same or similar pK a defines the α-effect . Numerous studies have been performed to assess the factors that govern α-nucleophilicity so as to design better decontaminants, for example. − …”

“…The most common theories suggested to account for the α-effect phenomenon are ground-state (GS) destabilization, transition-state (TS) stabilization, thermodynamic stabilization of products, and solvent effects, while other possible specific origins include a TS having aromatic or radicaloid character. − However, none of these theories can decisively explain the α-effect phenomenon. Particularly controversial has been the solvent effect on the α-effect. ,− …”

Solvent Effect on the α-Effect for the Reactions of Aryl Acetates with Butane-2,3-dione Monoximate and p-Chlorophenoxide in MeCN−H2O Mixtures

“…Numerous studies have been performed to account for the α-effect phenomenon − However, none of these factors alone can fully account for the α-effect phenomenon. Particularly, the effect of solvent on the α-effect has been controversial. − While the effect of solvent on the α-effect has been suggested to be unimportant on the basis of the similar magnitude of the α-effect for reactions performed in H 2 O and in neat organic solvents, gas-phase studies and theoretical calculations indicate a significant solvent effect on the α-effect …”