Erwin Buncel

Alkali metal ion catalysis and inhibition in nucleophilic displacement reactions at phosphorus centers: ethyl and methyl paraoxon and ethyl and methyl parathion.

We report on the ethanolysis of the P=O and P=S compounds ethyl and methyl paraoxon (1a and 1b) and ethyl and methyl parathion (2a and 2b). Plots of spectrophotometrically measured rate constants, kobsd versus [MOEt], the alkali ethoxide concentration, show distinct upward and downward curvatures, pointing to the importance of ion-pairing phenomena and a differential reactivity of free ions and ion pairs. Three types of reactivity and selectivity patterns have been discerned: (1) For the P=O compounds 1a and 1b, LiOEt > NaOEt > KOEt > EtO-; (2) for the P=S compound 2a, KOEt > EtO- > NaOEt > LiOEt; (3) for P=S, 2b, 18C6-crown-complexed KOEt > KOEt = EtO(-) > NaOEt > LiOEt. These selectivity patterns are characteristic of both catalysis and inhibition by alkali-metal cations depending on the nature of the electrophilic center, P=O vs P=S, and the metal cation. Ground-state (GS) vs transition-state (TS) stabilization energies shed light on the catalytic and inhibitory tendencies. The unprecedented catalytic behavior of crowned-K(+) for the reaction of 2b is noteworthy. Modeling reveals an extreme steric interaction for the reaction of 2a with crowned-K(+), which is responsible for the absence of catalysis in this system. Overall, P=O exhibits greater reactivity than P=S, increasing from 50- to 60-fold with free EtO(-) and up to 2000-fold with LiOEt, reflecting an intrinsic P=O vs P=S reactivity difference (thio effect). The origin of reactivity and selectivity differences in these systems is discussed on the basis of competing electrostatic effects and solvational requirements as function of anionic electric field strength and cation size (Eisenmans theory).

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.

High Brønsted βnuc values in SNAr displacement. An indicator of the SET pathway

Nucleophilic substitutions of 4-chloro-7-nitrobenzofurazan (NBD-Cl) and 3-methyl-1-(4-nitrobenzofurazanyl)imidazolium ions (NBD-Im+) with a series of 4-X-substituted anilines have been kinetically investigated in 70–30 (v/v) and 20–80 (v/v) H2O–Me2SO mixtures. The rate-limiting step in these reactions is nucleophilic addition with formation of Meisenheimer-type σ-adducts followed by fast expulsion of the leaving group (Cl− or Im). The reactions are characterized by a notable sensitivity to basicity of the aniline nucleophiles, with Hammett ρ values of −2.68 and −3.82 in 30% and 80% Me2SO, respectively, for NBD-Cl and even more negative values, −3.43 and −5.27, respectively, for NBD-Im+. This is consistent with significant development of positive charge at the nitrogen atom of the zwitterionic σ-adduct. Unexpectedly, the Bronsted-type plots reveal abnormally high βnuc values, ca. 1.0 and 1.3–1.4, respectively. Satisfactory correlations between the rates of the reactions and the oxidation potentials of the respective anilines support a SET mechanism for this process, i.e. initial (fast) electron-transfer from the aniline donor to the nitrobenzofurazan acceptor moiety and subsequent (slow) coupling of the resulting cation and anion radicals within the solvent cage with formation of the σ-adduct. An alternative possible explanation of the high βnuc values being related to the strong −I effect exerted by the negatively charged 4-nitrobenzofurazanyl structure, which would induce a greater positive charge at the developing anilinium nitrogen atom in the σ-adduct-like transition state as compared with the situation in the reference protonation equilibria of anilines, is considered less probable. It is thus proposed that obtention of abnormal βnuc values may be an indicator of electron-transfer in nucleophilic aromatic substitution and highlights the transition from the polar (SNAr) to the single electron-transfer (SET) mechanism.

A kinetic study on nucleophilic displacement reactions of aryl benzenesulfonates with potassium ethoxide: role of K+ ion and reaction mechanism deduced from analyses of LFERs and activation parameters.

Pseudofirst-order rate constants (k(obsd)) have been measured spectrophotometrically for the nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzenesulfonates 4a-f and Y-substituted phenyl benzenesulfonates 5a-k with EtOK in anhydrous ethanol. Dissection of k(obsd) into k(EtO(-)) and k(EtOK) (i.e., the second-order rate constants for the reactions with the dissociated EtO(-) and ion-paired EtOK, respectively) shows that the ion-paired EtOK is more reactive than the dissociated EtO(-), indicating that K(+) ion catalyzes the reaction. The catalytic effect exerted by K(+) ion (e.g., the k(EtOK)/k(EtO(-)) ratio) decreases linearly as the substituent X in the benzenesulfonyl moiety changes from an electron-donating group (EDG) to an electron-withdrawing group (EWG), but it is independent of the electronic nature of the substituent Y in the leaving group. The reactions have been concluded to proceed through a concerted mechanism from analyses of the kinetic data through linear free energy relationships (e.g., the Brønsted-type, Hammett, and Yukawa-Tsuno plots). K(+) ion catalyzes the reactions by increasing the electrophilicity of the reaction center through a cyclic transition state (TS) rather than by increasing the nucleofugality of the leaving group. Activation parameters (e.g., ΔH(‡) and ΔS(‡)) determined from the reactions performed at five different temperatures further support the proposed mechanism and TS structures.

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.

Can ground-state destabilization of an α-nucleophile induce an α-effect?

Abstract The possible importance of ground-state destabilization as the origin of the enhanced reactivity of α-nucleophiles is critically examined and it is concluded that, in general, this factor will contribute only slightly, if at all, to the manifestation of α-effects.

Effects on the Reactivity by Changing the Electrophilic Center from CO to CS: Contrasting Reactivity of Hydroxide, p-Chlorophenoxide, and Butan-2,3-dione Monoximate in DMSO/H2O Mixtures

Second-order rate constants have been measured spectrophotometrically for the reactions of O-p-nitrophenyl thionobenzoate (1, PNPTB) with HO(-), butan-2,3-dione monoximate (Ox(-), alpha-nucleophile), and p-chlorophenoxide (p-ClPhO(-), normal nucleophile) in DMSO/H(2)O of varying mixtures at (25.0+/-0.1) degrees C. Reactivity of these nucleophiles significantly increases with increasing DMSO content. HO(-) is less reactive than p-ClPhO(-) toward 1 up to 70 mol % DMSO although HO(-) is over six pK(a) units more basic in these media. Ox(-) is more reactive than p-ClPhO(-) in all media studied, indicating that the alpha-effect is in effect. The magnitude of the alpha-effect (i.e., k(Ox(-) )/k(p) (-ClPhO(-) )) increases with the DMSO content up to 50 mol % DMSO and decreases beyond that point. However, the dependency of the alpha-effect profile on the solvent for reactions of 1 contrasts to that reported previously for the corresponding reactions of p-nitrophenyl benzoate (2, PNPB); reactions of 1 result in much smaller alpha-effects than those of 2. Breakdown of the alpha-effect into ground-state (GS) and transition-state (TS) effects shows that the GS effect is not responsible for the alpha-effect across the solvent mixtures. The role of the solvent has been discussed on the basis of the bell-shaped alpha-effect profiles found in the current study as well as in our previous studies, that is, a GS effect in the H(2)O-rich region through H-bonding interactions and a TS effect in the DMSO-rich media through mutual polarizability interactions.

Alkali‐Metal‐Ion Catalysis and Inhibition in the Nucleophilic Displacement Reaction of Y‐Substituted Phenyl Diphenylphosphinates and Diphenylphosphinothioates with Alkali‐Metal Ethoxides: Effect of Changing the Electrophilic Center from PO to PS

A kinetic study of the nucleophilic substitution reaction of Y-substituted phenyl diphenylphosphinothioates 2 a-g with alkali-metal ethoxides (MOEt; M = Li, Na, K) in anhydrous ethanol at (25.0±0.1) °C is reported. Plots of pseudo-first-order rate constants (k(obsd)) versus [MOEt], the alkali ethoxide concentration, show distinct upward (KOEt) and downward (LiOEt) curvatures, respectively, pointing to the importance of ion-pairing phenomena and a differential reactivity of dissociated EtO(-) and ion-paired MOEt. Based on ion-pairing treatment of the kinetic data, the k(obsd) values were dissected into k EtO - and k(MOEt), the second-order rate constants for the reaction with the dissociated EtO(-) and ion-paired MOEt, respectively. The reactivity of MOEt toward 2 b (Y = 4-NO(2)) increases in the order LiOEtNaOEt>KOEt>EtO(-). The current study based on Yukawa-Tsuno analysis has revealed that the reactions of 2 a-g (P=S) and Y-substituted phenyl diphenylphosphinates 1 a-g (P=O) with MOEt proceed through the same concerted mechanism, which indicates that the contrasting selectivity patterns are not due to a difference in reaction mechanism. The P=O compounds 1 a-g are approximately 80-fold more reactive than the P=S compounds 2 a-g toward the dissociated EtO(-) (regardless of the electronic nature of substituent Y) but are up to 3.1×10(3)-fold more reactive toward ion-paired LiOEt. The origin of the contrasting selectivity patterns is further discussed on the basis of competing electrostatic effects and solvational requirements as a function of anionic electric field strength and cation size (Eisenmans theory).

Metal ion-biomolecule interactions. XII. 1H and 13C NMR evidence for the preferred reaction of thymidine over guanosine in exchange and competition reactions with Mercury(II) and Methylmercury(II)

Abstract Mercury(II) bridge complexes of the type [Nuc-Hg-Nuc] (Nuc = thymidine or guanosine), and methylmercury(II) complexes of thymidine and guanosine of the type [CH 3 Hg(Nuc)], have been prepared under appropriate conditions of pH and reactants stochiometry in acqueous soluton. The various complexes have been characterized by 1 H and 13 C NMR and used as probes, in competition and exchange studies, to establish the relative affinities of Hg(II) and CH 3 Hg(II) towards the nucleosides guanosine and thymidine. These studies have confirmed that Hg(II) and CH 3 Hg(II) bind to N 3 of thymidine in preference to N 1 of guanosine. The studies further show that reactions of mercury(II) with the nucleosides are thermodynamically controlled; the preperential binding reflects the relative stabilities of the respective complexes.

Metal ion biomolecule interactions. VI: Synthesis and spectroscopic properties of methylmercury(II) complexes of xanthosine

Abstract The interaction of MeHg(II) with xanthosine (Xanth H2, 1) in aqueous medium has been found to lead to several methylmercurated complexes depending on the reactant stoichiometries and the pH. The N-bound complexes [(MeHg)(Xanth H)] (2), [(MeHg)2Xanth] (3), [(MeHg)3(Xanth)]NO3 (4), [(MeHg)(Xanth H2)]NO3 (5), and the N- and C-bound complex [(MeHg)4(Xanth)]NO3 (6) have thus been prepared. The complexes were characterized by means of 1H and 13C nuclear magnetic resonance and infrared as well as elemental analysis. Formation of the carbon-bound methylmercurated species 6 is in accord with our previous results obtained with inosine and imidazole derivatives, thus substantiating our proposal that activation through electrophilic coordination at N7 is a requirement for C8-H abstraction. Correlations are drawn between 2J(1H-119Hg) values and pKa as well as 13C chemical shifts.