Effect of medium on reactivity for alkaline hydrolysis of p-nitrophenyl acetate and S-p-nitrophenyl thioacetate in DMSO-H2O mixtures of varying compositions: ground state and transition state contributions

Second-order rate constants (kN) for reactions of p-nitrophenyl acetate (1) and S-p-nitrophenyl thioacetate (2) with OH– have been measured spectrophotometrically in DMSO–H2O mixtures of varying compositions at 25.0 ± 0.1 °C. The kN value increases from 11.6 to 32 800 M–1 s–1 for the reactions of 1 and from 5.90 to 190 000 M–1 s–1 for those of 2 as the reaction medium changes from H2O to 80 mol % DMSO, indicating that the effect of medium on reactivity is more remarkable for the reactions of 2 than for those of 1. Although 2 possesses a better leaving group than 1, the former is less reactive than the latter by a factor of 2 in H2O. This implies that expulsion of the leaving group is not advanced in the rate-determining transition state, i.e., the reactions of 1 and 2 with OH– proceed through a stepwise mechanism, in which expulsion of the leaving group from the addition intermediate occurs after the rate-determining step. Addition of DMSO to H2O would destabilize OH– through electronic repulsion between the anion and the negative-dipole end in DMSO. However, destabilization of OH– in the ground state is not solely responsible for the remarkably enhanced reactivity upon addition of DMSO to the medium. The effect of medium on reactivity has been dissected into the ground state and transition state contributions through combination of the kinetic data with the transfer enthalpies (ΔΔHtr) from H2O to DMSO–H2O mixtures for OH– ion.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Comparison of Aminolysis of 2‑Pyridyl and 4‑Pyridyl X‑Substituted Benzoates in Acetonitrile: Evidence for a Concerted Mechanism Involving a Cyclic Transition State

A kinetic study on reactions of 2-pyridyl X-substituted benzoates (<b>6a</b>–<b>i</b>) with a series of cyclic secondary amines in MeCN is reported. The Hammett plot for the reaction of <b>6a</b>–<b>i</b> with piperidine consists of two intersecting straight lines while the Yukawa–Tsuno plot exhibits an excellent linear correlation with ρ_X = 1.28 and <i>r</i> = 0.63, indicating that the nonlinear Hammett plot is not caused by a change in the rate-determining step but rather by resonance stabilization of substrates possessing an electron-donating group (EDG) in the benzoyl moiety. The Brønsted-type plots are linear with β_nuc = 0.59 ± 0.02, which is typical of reactions reported to proceed through a concerted mechanism. A cyclic transition state (TS), which forces the reaction to proceed through a concerted mechanism, is proposed. The deuterium kinetic isotope effect of 1.3 ± 0.1 is consistent with the proposed mechanism. Analysis of activation parameters reveals that Δ<i>H</i>^‡ increases linearly as the substituent X changes from an electron-withdrawing group (EWG) to an EDG, while <i>T</i>Δ<i>S</i>^‡ remains nearly constant with a large negative value. The constant <i>T</i>Δ<i>S</i>^‡ value further supports the proposal that the reaction proceeds through a concerted mechanism with a cyclic TS

Electronic Nature of Substituent X Governs Reaction Mechanism in Aminolysis of 4-Pyridyl X-Substituted-Benzoates in Acetonitrile

A kinetic study is reported for aminolysis of 4-pyridyl X-substituted-benzoates <b>5a</b>–<b>i</b>. Plots of pseudo-first-order rate constants (<i>k</i>_obsd) vs [amine] curve upward for the reactions of substrates possessing a strong electron-withdrawing group in the benzoyl moiety (<b>5a</b>–<b>d</b>) but are linear for the reactions of those bearing an electron-donating group (<b>5e</b>–<b>i</b>), indicating that the electronic nature of substituent X governs the reaction mechanism. The <i>k</i>₁<i>k</i>₂/<i>k</i>_–1 and <i>k</i>₁<i>k</i>₃/<i>k</i>_–1 values were calculated from the intercept and slope of the linear plots of <i>k</i>_obsd/[amine] vs [amine], respectively. The Hammett plot for <i>k</i>₁<i>k</i>₂/<i>k</i>_–1 consists of two intersecting straight lines, while the Yukawa–Tsuno plot exhibits an excellent linear correlation with ρ_X = 0.41 and <i>r</i> = 1.58, implying that the nonlinear Hammett plot is not due to a change in rate-determining step but is caused by stabilization of substrates possessing an electron-donating group through resonance interactions. The small ρ_X suggests that the <i>k</i>₂/<i>k</i>_–1 ratio is little influenced by the nature of substituent X. The Brønsted-type plots for aminolysis of 4-pyridyl 3,5-dinitrobenzoate 5a are linear with β_nuc = 0.98 and 0.79 for <i>k</i>₁<i>k</i>₂/<i>k</i>_–1 and <i>k</i>₁<i>k</i>₃/<i>k</i>_–1, respectively. The effect of amine basicity on the microscopic rate constants is also discussed

Medium Effect (H2O versus MeCN) on Reactivity and Reaction Pathways for SNAr Reaction of 1-Aryloxy-2,4-dinitrobenzenes with Cyclic Secondary Amines

A kinetic study on SNAr reactions of 1-aryloxy-2,4-dinitrobenzenes (1a-1h) with a series of cyclic secondary amines in 80 mol% H2O / 20 mol% DMSO at 25.0 ± 0.1 oC is reported. The plots of kobsd vs [amine] curve upward except for the reactions of substrates possessing a strong electron-withdrawing group in the leaving aryloxide with strongly basic piperidine. The curved plots indicate that the reactions proceed through both uncatalytic and catalytic routes. Linear Brønsted-type plots have been obtained for the uncatalyzed and catalyzed reactions of 1-(4-nitrophenoxy)-2,4-dinitrobenzene (1a) with βnuc = 0.84 and 0.78, respectively. The Yukawa-Tsuno plot for the uncatalyzed reactions of 1a-1h with piperidine results in an excellent linear correlation with ρ = 1.66 and r = 0.31. In contrast, rate constants for catalyzed reactions are independent of the electronic nature of the substituent in the leaving group. The current SNAr reactions have been proposed to proceed via a zwitterionic intermediate (MC±) that partitions to products through uncatalytic and catalytic routes. The catalyzed reaction from MC± has been concluded to proceed through a concerted mechanism with a six-membered cyclic transition state (TScycl) rather than via a stepwise pathway with a discrete anionic intermediate (MC‒): the traditionally accepted mechanism. Medium effects on reactivity and reaction mechanism are discussed. Particularly, hydrogen-bonding of the amines to water precludes formation of kinetically significant dimers found in some aprotic solvents; no explicit role for water in the catalytic transition state is required or proposed. The specific stabilization of the leaving aryloxides substituted with strong electron-withdrawing groups accounts for the lack of the catalytic pathway in these systems (1a-c) with piperidine nucleophile.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Alkali-Metal Ion Catalysis and Inhibition in Alkaline Ethanolysis of O-Y-Substituted-Phenyl O-Phenyl Thionocarbonates: Contrasting M+ Ion Effects upon Changing Electrophilic Center from C=O to C=S

Pseudo-first-order rate constants (kobsd) were measured for nucleophilic substitution reactions of O-Y-substituted-phenyl O-phenyl thionocarbonates (4a–4h) with alkali metal ethoxides (EtOM, M = Li, Na, or K) in anhydrous ethanol at 25.0 ± 0.1 °C. Plots of kobsd vs. [EtOM] exhibited upward curvature for the reaction of O-4-nitrophenyl O-phenyl thionocarbonate (4a) with EtOK in the presence of 18-crown-6-ether (18C6), but showed downward curvature for the reaction with EtOLi, indicating that the reaction is catalyzed by the 18C6-crowned K+ ion, but is inhibited by Li+ ion. The kobsd values were dissected into kEtO− and kEtOM, the second-order rate constant for the reaction with dissociated EtO− and ion-paired EtOM, respectively. The reactivity of EtOM toward 4a increases in the order EtOLi < EtONa < EtO− < EtOK < EtOK/18C6, which is in contrast to that reported previously for the corresponding reaction of 4-nitrophenyl phenyl carbonate (a C=O analogue of 4a), e.g., EtO− ≈ EtOK/18C6 < EtOLi < EtONa < EtOK. The reaction mechanism, including the transition-state model and the origin of the contrasting reactivity patterns found for the reactions of the C=O and C=S compounds, are discussedThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Medium Effect on the α-Effect for Nucleophilic Substitution Reactions of p-Nitrophenyl Acetate with Benzohydroxamates and m-Chlorophenoxide in DMSO-H2O Mixtures as Contrasts with MeCN-H2O Mixtures: Comparing Two Very Different Polar Aprotic Solvent Components

A kinetic study is reported on nucleophilic substitution reactions of p-nitrophenyl acetate (1a) with three α-effect nucleophiles, benzohydroxamate (BHA‒), p-methylbenzohydroxamate (MBHA‒) and p-methyl-N-methylbenzohydroxamate (M2BHA‒), and a reference nucleophile, m-chlorophenoxide (m-ClPhO‒) in DMSO-H2O mixtures of varying compositions at 25.0 ± 0.1 oC. Second-order rate constants for the reactions with BHA‒ and MBHA‒ decrease upon addition of DMSO to the reaction medium up to 60 mol % DMSO and then increase thereafter only a little. In contrast, M2BHA‒ and m-ClPhO‒ become much more reactive as the DMSO content in the medium increases. Such contrasting medium effects on reactivity are consistent with the report that hydroxamic acids behave as OH acids in H2O but as NH acids in dipolar aprotic solvents (e.g., DMSO and MeCN). It has been concluded that BHA‒ and MBHA‒ form an equilibrium of a reactive form I with less reactive species II in DMSO-H2O mixtures and the position of the equilibrium is dependent on solvent compositions. BHA‒ and MBHA‒ exhibit the α-effect in H2O but not in in 90 mol % DMSO. In contrast, the α-effect yielded by M2BHA‒ increases steeply up to 70 mol % DMSO and then levels off thereafter.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author