Evidence for a catalytic six-membered cyclic transition state in aminolysis of 4-nitrophenyl 3,5-dinitrobenzoate in acetonitrile: comparative brønsted-type plot, entropy of activation, and deuterium kinetic isotope effects.

A kinetic study for reactions of 4-nitrophenyl 3,5-dinitrobenzoate (1a) with a series of cyclic secondary amines in acetonitrile is reported. Plots of the pseudo-first-order rate constant (kobsd) vs [amine] curve upward, while those of kobsd /[amine] vs [amine] exhibit excellent linear correlations with positive intercepts, indicating that the reaction proceeds through both uncatalyzed and catalyzed routes. Brønsted-type plots for uncatalyzed and catalyzed reactions are linear with ßnuc = 1.03 and 0.69, respectively. The ΔH(⧧) and ΔS(⧧) values measured for the catalytic reaction with morpholine are -0.80 kcal/mol and -61.7 cal/(mol K), respectively. The negative ΔH(⧧) with a large negative ΔS(⧧) suggests that the reaction proceeds through a highly ordered transition state (i.e., a six-membered cyclic transition state, which includes a second amine molecule that accepts a proton from the aminium moiety of the zwitterionic tetrahedral intermediate and simultaneously donates a proton to the aryloxyl oxygen of the nucleofuge with concomitant C-OAr bond scission). This proposal is consistent with the smaller ßnuc value for the catalyzed reaction as compared to the uncatalyzed reaction. An inverse deuterium kinetic isotope effect (DKIE) value of 0.93 and a contrasting normal primary DKIE value of 3.23 for the uncatalyzed and catalyzed routes, respectively, also support the proposed cyclic transition state.

Alkali-metal ion catalysis and inhibition in SNAr displacement: relative stabilization of ground state and transition state determines catalysis and inhibition in SNAr reactivity.

We report here the first observation of alkali-metal ion catalysis and inhibition in SNAr reactions. The plot of kobsd versus [alkali-metal ethoxide] exhibits downward curvature for the reactions of 1-(4-nitrophenoxy)-2,4-dinitrobenzene with EtOLi, EtONa, and EtOK, but upward curvature for the corresponding reaction with EtOK in the presence of 18-crown-6-ether (18C6). Dissection of kobsd into the second-order rate constants for the reactions with the dissociated EtO(-) and the ion-paired EtOM (i.e., k EtO - and kEtOM , respectively) has revealed that the reactivity increases in the order EtOLi

Kinetic study on SNAr reaction of 1-(y-substituted-phenoxy)-2,4-dinitrobenzenes with cyclic secondary amines in acetonitrile: evidence for cyclic transition-state structure.

A kinetic study is reported for SNAr reactions of 1-(Y-substituted-phenoxy)-2,4-dinitrobenzenes (1a-1h) with amines in MeCN. The plots of pseudo-first-order rate constant versus amine concentration curve upward, indicating that the reactions are catalyzed by a second amine molecule. The Brønsted-type plots for the reaction of 1-(4-nitrophenyl)-2,4-dinitrobenzene (1a) with secondary amines are linear with ßnuc = 1.10 and 0.85 for the uncatalyzed and catalyzed reactions, respectively, while the Yukawa-Tsuno plots for the reactions of 1a-1h with piperidine result in excellent linear correlations with ρY = 1.85 and r = 0.27 for the uncatalyzed reaction and ρY = 0.73 and r = 0.23 for the catalyzed reaction. The catalytic effect decreases with increasing amine basicity or electron-withdrawing ability of the substituent Y in the leaving group. Activation parameters calculated from the rate constants measured at five different temperatures for the catalyzed reaction of 1a with piperidine are ΔH(‡) = 0.38 kcal/mol and ΔS(‡) = -55.4 cal/(mol K). The catalyzed reaction from a Meisenheimer complex (MC(±)) is proposed to proceed through a concerted mechanism with a cyclic transition-state rather than via a stepwise pathway with an anionic intermediate, MC(-). Deuterium kinetic isotope effects provide further insight into the nature of the concerted transition state.

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 (6a-i) with a series of cyclic secondary amines in MeCN is reported. The Hammett plot for the reaction of 6a-i with piperidine consists of two intersecting straight lines while the Yukawa-Tsuno plot exhibits an excellent linear correlation with ρX = 1.28 and r = 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 ßnuc = 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 ΔH(‡) increases linearly as the substituent X changes from an electron-withdrawing group (EWG) to an EDG, while TΔS(‡) remains nearly constant with a large negative value. The constant TΔS(‡) value further supports the proposal that the reaction proceeds through a concerted mechanism with a cyclic TS.

Dissection of activation parameters in the bell-shaped α-effect following solvent modulation (DMSO-H2O media).

This paper comprises results of our investigation of the α-effect phenomenon for the reaction of O-p-nitrophenyl thionobenzoate (PNPTB) with butane-2,3-dione monoximate (Ox(-), α-nucleophile) and p-chlorophenoxide (p-ClPhO(-), normal-nucleophile) in DMSO-H2O mixtures of varying compositions at 15.0 °C, 25.0 °C, and 35.0 °C. The reactivity of Ox(-) and p-ClPhO(-) increases significantly as the DMSO content in the medium increases, although the effects of medium on reactivity are not the same for the reactions with Ox(-) and p-ClPhO(-). Ox(-) exhibits the α-effect in all solvent compositions and temperatures. The α-effect increases up to 50 mol % DMSO and then decreases thereafter, resulting in a bell-shaped α-effect profile. Dissection of the activation parameters (i.e., ΔH(‡) and TΔS(‡)) has revealed that the bell-shaped α-effect behavior is due to entropy of activation differences rather than enthalpy terms, although the enthalpy term controls almost entirely the solvent dependence of the reaction rate. Differences in the transition-state (TS) structures for the reactions with Ox(-) (a six-membered cyclic TS) and p-ClPhO(-) (an acyclic TS) are consistent with the entropy-dependent α-effect behavior.

Kinetic study on Michael-type reactions of ß-nitrostyrenes with cyclic secondary amines in acetonitrile: transition-state structures and reaction mechanism deduced from negative enthalpy of activation and analyses of LFERs.

A kinetic study is reported for the Michael-type reactions of X-substituted ß-nitrostyrenes (1a-j) with a series of cyclic secondary amines in MeCN. The plots of pseudo-first-order rate constant k(obsd) vs [amine] curve upward, indicating that the reactions proceed through catalyzed and uncatalyzed routes. The dissection of k(obsd) into Kk2 and Kk3 (i.e., the rate constants for the uncatalyzed and catalyzed routes, respectively) revealed that Kk3 is much larger than Kk2, implying that the reactions proceed mainly through the catalyzed route when [amine] > 0.01 M. Strikingly, the reactivity of ß-nitrostyrene (1g) toward piperidine decreases as the reaction temperature increases. Consequently, a negative enthalpy of activation is obtained, indicating that the reaction proceeds through a relatively stable intermediate. The Brønsted-type plots for the reactions of 1g are linear with ß(nuc) = 0.51 and 0.61, and the Hammett plots for the reactions of 1a-j are also linear with ρX = 0.84 and 2.10 for the uncatalyzed and catalyzed routes, respectively. The reactions are concluded to proceed through six-membered cyclic transition states for both the catalyzed and uncatalyzed routes. The effects of the substituent X on reactivity and factors influencing ß(nuc) and ρX obtained in this study are discussed.

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.

Mechanistic assessment of S(N)Ar displacement of halides from 1-halo-2,4-dinitrobenzenes by selected primary and secondary amines: Brønsted and Mayr analyses.

Pseudo-first-order rate constants (k(obsd)) have been measured spectrophotometrically for nucleophilic substitution reactions of 1-X-2,4-dinitrobenzenes (1a-d, X = F, Cl, Br, I) with various primary and secondary amines in MeCN and H(2)O at 25.0 ± 0.1 °C. The plots of k(obsd) vs [amine] curve upward for reactions of 1a (X = F) with secondary amines in MeCN. In contrast, the corresponding plots for the other reactions of 1b-d with primary and secondary amines in MeCN and H(2)O are linear. The Brønsted-type plots for reactions of 1a-d with a series of secondary amines are linear with ß(nuc) = 1.00 for the reaction of 1a and 0.52 ± 0.01 for those of 1b-d. Factors governing reaction mechanisms (e.g., solvent, halogen atoms, H-bonding interactions, amine types) have been discussed. Kinetic data were also analyzed in terms of the Mayr nucleophilicity parameter for the amines with each aromatic substrate. Provisional Mayr electrophilicity parameter (E) values for 1-X-2,4-dinitrobenzenes have been determined: E = -14.1 for X = F, E = -17.6 for X = Cl and Br, and E = -18.3 for X = I. These values are consistent with the range and order of E values for heteroaromatic superelectrophiles and normal 6-π aromatic electrophiles.

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 5a-i. Plots of pseudo-first-order rate constants (k(obsd)) vs [amine] curve upward for the reactions of substrates possessing a strong electron-withdrawing group in the benzoyl moiety (5a-d) but are linear for the reactions of those bearing an electron-donating group (5e-i), indicating that the electronic nature of substituent X governs the reaction mechanism. The k(1)k(2)/k(-1) and k(1)k(3)/k(-1) values were calculated from the intercept and slope of the linear plots of k(obsd)/[amine] vs [amine], respectively. The Hammett plot for k(1)k(2)/k(-1) consists of two intersecting straight lines, while the Yukawa-Tsuno plot exhibits an excellent linear correlation with ρ(X) = 0.41 and r = 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 k(2)/k(-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 ß(nuc) = 0.98 and 0.79 for k(1)k(2)/k(-1) and k(1)k(3)/k(-1), respectively. The effect of amine basicity on the microscopic rate constants is also discussed.

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 P=O to P=S.

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 (Eisenman's theory).

Hydrolysis of 1-(X-substituted-benzoyl)-4-aminopyridinium ions: effect of substituent X on reactivity and reaction mechanism.

A kinetic study is reported for hydrolysis of 1-(X-substituted-benzoyl)-4-aminopyridinium ions 2a-i, which were generated in situ from the nucleophilic substitution reaction of 2,4-dinitrophenyl X-substituted-benzoates 1a-i with 4-aminopyridine in 80 mol% H(2)O/20 mol% DMSO at 25.0 ± 0.1 °C. The plots of pseudo-first-order rate constants k(obsd) vs. pyridine concentration are linear with a large positive intercept, indicating that the hydrolysis of 2a-i proceeds through pyridine-catalyzed and uncatalyzed pathways with the rate constant k(cat) and k(o), respectively. The Hammett plots for k(cat) and k(o) consist of two intersecting straight lines, which might be taken as evidence for a change in the rate-determining step (RDS). However, it has been proposed that the nonlinear Hammett plots are not due to a change in the RDS but are caused by stabilization of 2a-i in the ground state through a resonance interaction between the π-electron-donor substituent X and the carbonyl functionality. This is because the corresponding Yukawa-Tsuno plots exhibit excellent linear correlations with ρ(X) = 1.45 and r = 0.76 for k(cat) while ρ(X) = 1.39 and r = 0.72 for k(o). A possibility that the hydrolysis of 2a-i proceeds through a concerted mechanism has been ruled out on the basis of the large ρ(X) values. Thus, the reaction has been concluded to proceed through a stepwise mechanism in which the leaving group departs after the RDS since OH(-) is more basic and a poorer nucleofuge than 4-aminopyridine.

Aminolysis of Y-substituted-phenyl 2-methoxybenzoates in acetonitrile: effect of the o-methoxy group on reactivity and reaction mechanism.

Second-order rate constants (k(N)) were measured for aminolyses of Y-substituted-phenyl 2-methoxybenzoates 2a-i and 4-nitrophenyl X-substituted-benzoates 3a-j in MeCN at 25.0 °C. The Brønsted-type plot for the reactions of 2a-i with piperidine curves downward, indicating that a change in rate-determining step (RDS) occurs. The Hammett plot for the reactions of 3a-j with piperidine consists of two intersecting straight lines, which might be taken as evidence for a change in RDS. However, the nonlinear Hammett plot has been suggested not to be due to a change in RDS but rather to the stabilization of the ground state of substrates possessing an electron-donating group (EDG) (e.g., 3a-c) through a resonance interaction, since the corresponding Yukawa-Tsuno plot exhibits an excellent linear correlation with ρ = 0.54 and r = 1.54. The ρ value found for the reactions of 3a-j in MeCN is much smaller than that reported previously for the corresponding reactions in H(2)O (i.e., ρ = 0.75). It is proposed that the reactions of 3a-j in MeCN proceed through a forced concerted mechanism due to instability of T(±) in the aprotic solvent, while the reactions of 2a-i proceed through a stepwise pathway with a stabilized T(±) through an intramolecular H-bonding interaction.

Kinetic and theoretical studies on alkaline ethanolysis of 4-nitrophenyl salicylate: effect of alkali metal ions on reactivity and mechanism.

Pseudo-first-order rate constants (k(obsd)) for reactions of 4-nitrophenyl salicylate (7) with alkali metal ethoxides (EtOM, M = K, Na, and Li) in anhydrous ethanol have been measured spectrophotometrically. Interestingly, the k(obsd) value decreases significantly as the concentration of EtOM increases. Because the phenolic moiety of substrate 7 would be deprotonated and exist as an anionic form (i.e., 7(-)) under kinetic conditions, the ground-state stabilization of 7(-) through formation of a six-membered cyclic complex with M(+) (i.e., 8) is proposed to be responsible for the decreasing k(obsd) trend. The k(obsd) value at a given concentration of EtOK increases steeply upon addition of [18]crown-6 ether (18C6) up to [18C6]/[EtOK] = 1 in the reaction mixture and then remains relatively constant thereafter. In contrast, k(obsd) decreases upon addition of salts (e.g., LiClO(4) or KSCN) to the reaction mixture, which indicates that M(+) ions inhibit the reaction. However, in the presence of 18C6, the k(obsd) value is independent of the concentration of EtOK but remains constant, which indicates that the reaction proceeds through a unimolecular mechanism in the presence of the complexing agent. Although two conceivable unimolecular pathways (formation of ketene 9 and lactone 10) can account for the kinetic results, the reaction has been concluded to proceed via formation of ketene 9 as the reactive intermediate on the basis of theoretical calculations.

Pitfalls in assessing the α-effect: reactions of substituted phenyl methanesulfonates with HOO(-), OH(-), and substituted phenoxides in H(2)O.

Toward resolving the current controversy regarding the validity of the α-effect, we have examined the reactions of Y-substituted phenyl methanesulfonates 1a-1l with HOO(-), OH(-), and Z-substituted phenoxides in the gas phase versus solution (H(2)O). Criteria examined in this work are the following: (1) Brønsted-type and Hammett plots for reactions with HOO(-)and OH(-), (2) comparison of ß(lg) values reported previously for the reactions of Y-substituted phenyl benzenesulfonates 2a-2k with HOO(-) (ß(lg) = -0.73) and OH(-) (ß(lg) = -0.55), and for those of 1a-1l with HOO(-) (ß(lg) = -0.69) and OH(-) (ß(lg) = -1.35), and (3) Brønsted-type plot showing extreme deviation of OH(-) for reactions of 2,4-dintrophenyl methanesulfonate 1a with aryloxides, HOO(-), and OH(-), signifying extreme solvation vs different mechanisms. The results reveal significant pitfalls in assessing the validity of current interpretations of the α-effect. The extreme negative deviation by OH(-) must be due, in part, to the difference in their reaction mechanisms. Thus, the apparent dependence of the α-effect on leaving-group basicity found in this study has no significant meaning due to the difference in operating mechanisms. The current results argue in favor of a further criterion, i.e., a consistency in mechanism for the α-nucleophiles and normal nucleophiles.

Nonlinear Hammett plots in pyridinolysis of 2,4-dinitrophenyl X-substituted benzoates: change in RDS versus resonance contribution.

Second-order rate constants (k(OH)-) have been measured for nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzoates (1a-j) with Z-substituted pyridines in 80 mol% H(2)O/20 mol% DMSO at 25.0 +/- 0.1 degrees C. The Hammett plots for the reactions of 1a-j with pyridines consist of two intersecting straight lines, i.e., a large rho value for the reactions of substrates (1a-c) possessing an electron-donating group (EDG) in the benzoyl moiety and a small one for substrates (1e-j) bearing an electron-withdrawing group (EWG). The nonlinear Hammett plots have been attributed to stabilization of the ground state of substrates 1a-c through resonance interactions between the electron-donating substituent and the carbonyl functionality, since the corresponding Yukawa-Tsuno plots exhibit excellent linear correlations with large r values. It has been shown that substrates are not unusually more reactive than would be expected from the Hammett substituent constants, but rather, substrates 1a-c exhibit lower reactivity than would be predicted. The Brønsted-type plots for pyridinolysis of 1a-j are linear with beta(nuc) = 0.74-0.98, indicating that the reaction proceeds through a stepwise mechanism in which the second step is the RDS. It has been concluded that the electronic nature of the substituent X in the benzoyl moiety does not influence the RDS, but the degree of bond formation (or the effective charge on the nucleophilic site) in the transition state becomes more significant as the substituent X changes from a strong EDG to a strong EWG.

Aminolysis of X-substituted phenyl diphenylphosphinates: effect of amine nature on reactivity and transition-state structure.

A kinetic study is reported for aminolysis of X-substituted phenyl diphenylphosphinates (1a-i) in 80 mol % H(2)O/20 mol % dimethyl sulfoxide at 25.0 +/- 0.1 degrees C. The Brønsted-type plot for the reactions of 2,4-dinitrophenyl diphenylphosphinate (1a) with primary amines is linear with beta(nuc) = 0.53. The reactions of 1a-i with ethylamine also result in a linear Brønsted-type plot with beta(lg) = -0.81. These beta(nuc) and beta(lg) values are slightly larger than those reported previously for the reactions of 1a with secondary amines (beta(nuc) = 0.38) and for those of 1a-i with piperidine (beta(lg) = -0.66) but typical for reactions that proceed through a concerted mechanism. It has been concluded that aminolysis of 1a-i proceed through a concerted mechanism and the nature of amines does not affect the reaction mechanism. However, the reactions with primary amines have been suggested to proceed through a later transition state (i.e., more bond formation and bond rupture in the transition state) on the basis of the larger beta(nuc) and beta(lg) values. The concerted mechanism has been further supported from the fact that the Yukawa-Tsuno plot for the reactions of 1a-i with ethylamine exhibits an excellent linear correlation with rho = 2.24 and r = 0.22. Weakly basic primary amines are less reactive than secondary amines of similar basicity. However, strongly basic ethylamine is ca. 2-fold more reactive than piperidine toward 1a, although the former is 0.35 pK(a) units less basic than the latter.

Kinetic studies on nucleophilic substitution reactions of O-aryl thionobenzoates with azide, cyanide, and hydroxide: contrasting reactivity and mechanism.

A kinetic study is reported for nucleophilic substitution reactions of O-Y-substituted phenyl thionobenzoates (1a-h) and O-4-nitrophenyl X-substituted thionobenzoates (2a-f) with N(3)(-) and CN(-) in 80 mol % H(2)O-20 mol % DMSO at 25.0 +/- 0.1 degrees C. The Brønsted-type plot for the reactions of 1a-h with N(3)(-) exhibits a downward curvature, i.e., the slope (beta(lg)) changes from -1.10 to -0.33 as the leaving group basicity decreases, indicating that the reactions proceed through a stepwise mechanism with a change in rate-determining step (RDS). In contrast, the Brønsted-type plot for the corresponding reactions with CN(-) is linear with a beta(lg) value of -0.33. This value is similar to that found previously for the reactions of 1a-h with OH(-) (-0.35). Besides, sigma(o) constants result in much better Hammett correlation than sigma(-) constants. Thus, the reactions with CN(-) and OH(-) have been concluded to proceed through a stepwise mechanism in which departure of the leaving group occurs after RDS. Reactions of 2a-f with N(3)(-) and CN(-) result in nonlinear Hammett plots. However, the Yukawa-Tsuno plots for the same reactions exhibit excellent linearity with r = 0.5 +/- 0.1, indicating that the nonlinear Hammett plots are not due to a change in RDS but are caused by ground state stabilization through resonance interactions between the electron-donating substituent and the thio carbonyl functionality. Calculation of the k(1) values (nucleophile attack as RDS) for the reactions of 1a-h with N(3)(-) indicates that azide ion is more reactive than OH(-) toward the thione esters, although the former is over 11 pK(a) units less basic than the latter. The high polarizability of N(3)(-) has been suggested to be responsible for its great affinity for the polarizable thione esters 1a-h and 2a-f.

Effects on the reactivity by changing the electrophilic center from C==O to C==S: 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.

Aminolysis of O-aryl thionobenzoates: amine basicity combines with modulation of the nature of substituents in the leaving group and thionobenzoate moiety to control the reaction mechanism.

A kinetic study is reported for aminolysis of O-Y-substituted phenyl thionobenzoates (1a-f) and O-4-nitrophenyl X-substituted thionobenzoates (2a-f) in 80 mol % H2O/20 mol % DMSO at 25.0 +/- 0.1 degrees C. The reaction proceeds through one or two intermediates (i.e., a zwitterionic tetrahedral intermediate T(+/-) and its deprotonated form T(-)) depending on the basicity difference between the nucleophile and nucleofuge, that is, the reaction proceeds through T(+/-) when the leaving aryloxide is less basic than the attacking amine, but through T(+/-) and T(-) when the leaving group is more basic than the amine. However, the reaction mechanism is not influenced by the electronic nature of the substituent X in the nonleaving group. The Hammett plot for the reactions of 2a-f with benzylamine is consisted of two intersecting straight lines, which might be interpreted as a change in the rate-determining step (RDS). However, the Yukawa-Tsuno plot for the same reactions exhibits an excellent linear correlation, indicating that the nonlinear Hammett plot is not due to a change in the RDS but caused by stabilization of the ground-state of the substrate through resonance interaction between the electron-donating substituent X and the thionocarbonyl moiety.

Analysis of linear free-energy relationships combined with activation parameters assigns a concerted mechanism to alkaline hydrolysis of x-substituted phenyl diphenylphosphinates.

A kinetic study is reported for alkaline hydrolysis of X-substituted phenyl diphenylphosphinates (1 a-i). The Brønsted-type plot for the reactions of 1 a-i is linear over 4.5 pK(a) units with beta(lg)=-0.49, a typical beta(lg) value for reactions which proceed through a concerted mechanism. The Hammett plots correlated with sigma(o) and sigma(-) constants are linear but exhibit many scattered points, while the corresponding Yukawa-Tsuno plot results in excellent linear correlation with rho=1.42 and r=0.35. The r value of 0.35 implies that leaving-group departure is partially advanced at the rate-determining step (RDS). A stepwise mechanism, in which departure of the leaving group from an addition intermediate occurs in the RDS, is excluded since the incoming HO(-) ion is much more basic and a poorer nucleofuge than the leaving aryloxide. A dissociative (D(N) + A(N)) mechanism is also ruled out on the basis of the small beta(lg) value. As the substituent X in the leaving group changes from H to 4-NO(2) and 3,4-(NO(2))(2), DeltaH++ decreases from 11.3 kcal mol(-1) to 9.7 and 8.7 kcal mol(-1), respectively, while DeltaS++ varies from -22.6 cal mol(-1) K(-1) to -21.4 and -20.2 cal mol(-1) K(-1), respectively. Analysis of LFERs combined with the activation parameters assigns a concerted mechanism to the current alkaline hydrolysis of 1 a-i.