C–ON bond homolysis of alkoxyamines: when too high polarity is detrimental

Abstract

Throughout the last decade, the effect of electron withdrawing groups (EWGs) has been known to play a role - minor or moderate depending on the nitroxyl fragment RRNO - in the change in the homolysis rate constant (k) for C-ON bond homolysis in alkoxyamines (RRNOR). It has been shown that the effect of EWGs on k is described by a linear relationship with the electrical Hammett constant σ. Since then, linear multi-parameter relationships f(σ,ν,σ) have been developed to account for the effects involved in the changes in k, which are the stabilization of the released radical (σ) and the bulkiness (ν) and polarity (σ) of the alkyl fragment. Since a decade ago, new results have been published highlighting the limits of such correlations. In this article, previous multi-parameter linear relationships are amended using a parabolic model, i.e. (σ - σ), to describe the effect of EWGs in the alkyl fragment on k. In contrast to previous studies, these improved linear multi-parameter relationships f(σ,ν,Δσ) are able to account for the presence of several EWGs on the alkyl fragment, R. An unexpectedly strong solvent effect - a ca. 1500-fold increase in k - from tert-butylbenzene to the water/methanol mixture is also observed for 3-((2,2,6,6-tetramethylpiperidin-1-yl)oxyl)pentane-2,4-dione 1b in comparison to a ca. 5-fold increase in k that is generally observed.

How intramolecular hydrogen bonding (IHB) controls the C–ON bond homolysis in alkoxyamines

“…21,22 However, in our view, activation processes based on physicochemical events cannot be disregarded. Indeed, very recently, 23 a dramatic solvent effect on the C-ON bond homolysis rate constant k d (Scheme 1) has been reported for 1 (Fig. 3).…”

2-Butyl-2-tert-butyl-5,5-diethylpyrrolidine-1-oxyls: Synthesis and Properties

“…An increase in solvent polarity accelerates the rates of reactions where a charge develops in the activated complex, starting from a neutral or slightly charged reactant. The solvent effect is well known in the chemistry of reversible homolyses of alkoxyamines, where one of the reaction partners is a nitroxide radical [38]. Table 1.…”

Alkoxyamines Designed as Potential Drugs against Plasmodium and Schistosoma Parasites

“…Among more than a hundred of prepared alkoxyamines (see Figure S1 ), the derivatives whose synthesis, reactivity and biological activity will be discussed in detail are depicted in Figure 2 . Most of the alkoxyamines were prepared as previously reported [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. The syntheses of new compounds are depicted in Scheme 1 (compound 6F ), Scheme 2 (compound 2F and 4F ), and Scheme 3 (compound 8F ).…”

“…LC-MS: t R [( RR / SS )- 2F or ( RS/SR )- 2F ] = 13.4 min, m/z = 571.3 (M + H + ); t R [ 22 ] = 4.7 min, m/z = 262.3 (M + H + ), 284.3 (M + Na + ); t R [ 24 ] = 8.0 and 10.0 min, m/z = 521.4 (M + H + ), 543.4 (M + Na + ); t R [ 25 ] = 5.8 min, m/z = 276.3 (M + H + ), 298.3 (M + Na + ).…”