Elyane Kizilian

Super acidifiers: the origin of the exceptional electron transmission capability of the SO2CF3 group in carbanion stabilization

As part of studies aimed at clarifying conflicting reports concerning the acidifying effects exerted by the SO2CF3 vs. NO2 moieties with respect to carbanion stabilities, we have investigated the ionization equilibria of an extended set of benzyltriflones and have determined both pKa values of the carbon acids and 1H and 13C NMR parameters of the resulting carbanions. Acidities determined in H2O-Me2SO mixtures and in pure Me2SO show a contrasting behaviour between 4-X-substituted benzyl triflones and related arylnitromethanes. While the latter exhibit a decreasing acidity on going from H2O to Me2SO media, the benzyltriflone analogues show in fact increasing acidity in Me2SO. This opposing trend suggests that the exocyclic alpha-SO2CF3 moiety is strongly stabilizing the negative charge of the carbanions through polarizability effects favored by the dipolar aprotic Me2SO solvent. As a result, inversions in the acidity sequences of alpha-NO2 and alpha-SO2CF3 activated carbon acids are observed on going from H2O to Me2SO. 1H and 13C NMR data are in full accord with the conclusion that only little negative charge is transferred to the 4-X-substituted phenyl ring upon ionization. Increasing further the ring substitution by electronegative groups to 2,4- and 2,4,6- patterns, enhances the charge transfer but this nevertheless remains moderate even with the most activated 2,4,6- trinitro or 2,6-dinitro-4-SO2CF3 sequences. Altogether, our results provide convincing evidence of the unusual electron transmission ability of the very strongly acidifying SO2CF3 group.

Electrophilic aromatic substitutions: reactions of hydroxy- and methoxy-substituted benzenes with 4,6-dinitrobenzofuroxan: kinetics and mechanism

Rate constants have been determined in aqueous Me2SO mixtures for the reaction of super-electrophilic 4,6-dinitrobenzofuroxan (DNBF) with a series of hydroxy- and methoxy-substituted benzenes whose pKa values range between -3 and -9. The study extends the reactivity range of weakly basic aromatics with DNBF, from the family of indoles previously studied with pKa values ranging from -1 to -6. The overall rate constants for the reactions of DNBF as the electrophile are at least one order of magnitude greater than for the reactions of H3O+ with the same series of aromatics. This lends further credence to the notion that DNBF possesses super-electrophilic properties. An LFER is observed between logk and pK with slope 0.54. In the case of 1,3,5-trimethoxybenzene a significant kinetic isotope effect (KIE) is observed (kH/kD = 3.71 in 50% Me2SO). This system hence affords one of the few instances in which a KIE has been observed in SEAr reactions. It follows from the observed KIE that the addition of DNBF to the aromatic is not rate-limiting and that reversion to reactants and proton loss from the arenonium intermediate occur at comparable rates. Structures of the products of electrophilic substitution have been confirmed by 1H NMR. In all cases the regiochemistry of the reactions was identical to that observed in protonation studies of the starting aromatics.

Non-linear Brønsted correlations: evidence for a levelling off in the reactivity of oximate ions in aqueous solution

A kinetic study of the reactivity of a series of pyridinium carbaldoximate ions (pKa= 7.13–9.02), which are all potential reactivators of acetylcholinesterase inhibited by organophosphorus poisons, towards p-nitrophenyl acetate in aqueous solution is reported. The corresponding Bronsted plot is non-linear, defining a plateau at pKa 8 which fits very well the data previously obtained for a number of structurally different oximate ions. This phenomenon appears to be typical for the behaviour of these bases since Bronsted plots for reactions of oximate ions with other electrophiles show a similar levelling off. These observations support an explanation in terms of a requirement for desolvation of the oximate ion prior to nucleophilic attack which becomes more difficult with increasing basicity. Possible implications of the rapid levelling off in reactivity of oximate ions on their chemical ability to act as efficient reactivators are discussed.

ELECTROPHILIC HETEROAROMATIC SUBSTITUTIONS : THE COUPLING OF 4,6-DINITROBENZOFUROXAN WITH 3-METHOXYTHIOPHENE IN H2O-ME2SO MIXTURES

Rate constants have been determined in three aqueous Me2SO mixtures for the SEAr substitution of 3-methoxythiophene (5) by super-electrophilic 4,6-dinitrobenzofuroxan (DNBF). The absence of a significant dependence of the rates of reactions on the hydrogen or deuterium labelling at Cα of the thiophene ring indicates that electrophilic addition (k1DNBF) of DNBF at this position is the rate-limiting step of the substitution process. A notable increase in the k1DNBF rate constant with increasing water content of the solvent mixtures is observed. This trend is consistent with the idea that the addition step proceeds through a highly dipolar transition state where the development of negative charge in the DNBF moiety is concomitant with that of a partial positive charge in the thiophene ring. Assuming that the behaviour of 5 fits the rate-equilibrium, Bronsted-type relationship previously established for the coupling of DNBF with nitrogen heterocycles, a pKa H2O value of –6.5 may be estimated for the protonation of 5 in aqueous solution. Interestingly, a similar estimate is obtained when the reactivity of 5 is compared with that of an homogeneous series of enol methyl ethers. Despite a low carbon basicity, comparable to that of a rather weakly basic enol ether, 5 appears to be one of the most reactive thiophene compounds toward electrophilic reagents.