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