La3+-catalyzed methanolysis of N-aryl-beta-lactams and nitrocefin

The kinetics of the La(3+)-catalyzed methanolysis of N-phenyl-beta-lactam (2) and N-p-nitrophenyl-beta-lactam (3) as well as that of nitrocefin (1) were studied at 25 degrees C under buffered conditions. In the case of 2 and 3, the observed second-order rate constants (k(2)(obs)) for catalysis plateau at pH 7.5-7.8, reaching values of 1 x 10(-)(2) and 35 x 10(-)(2) M(-)(1) s(-)(1) respectively. Potentiometric titrations of solutions of 2 x 10(-)(3) M La(OTf)(3) were analyzed in terms of a dimer model (La(3+)(2)((-)OCH(3))(n)()), where the number of methoxides varies from 1 to 5. The species responsible for catalysis in the pH range investigated contain 1-3 methoxides, the one having the highest catalytic activity being La(3+)(2)((-)OCH(3))(2), which comprises 80% of the total La(3+) forms present at its pH maximum of 8.9. The catalysis afforded by the La(3+) dimers at a neutral pH is impressive relative to the methoxide reactions: at pH 8.4 a 1 mM solution of catalyst (generated from 2 mM La(OTf)(3)) accelerated the methanolysis of 2 by approximately 2 x 10(7)-fold and 3 by approximately 5 x 10(5)-fold. As a function of metal ion concentration, the La(3+)-catalyzed methanolysis of 1 proceeds by pathways involving first one bound metal ion and then a second La(3+) leading to a plateau in the k(obs) vs [La(3+)](total) plots at all pH values. The k(max)(obs) pseudo-first-order rate constants at the plateaus, representing the spontaneous methanolysis of La(3+)(2)(1(-)) forms, has a linear dependence on [(-)OCH(3)] (slope = 0.84 +/- 0.05 if all pH values are used and 1.02 +/- 0.03 if all but the two highest pH values are used). The speciation of bound 1 at a La(3+) concentrations corresponding to that of the onset of the kinetic plateau region was approximated through potentiometric titration of the nonreactive 3,5-dinitrobenzoic acid in the presence of 2 equiv of La(OTf)(3). A total speciation diagram for all bound forms of La(3+)(2)(1(-))((-)OCH(3))(n)(), where n = 0-5, was constructed and used to determine their kinetic contributions to the overall pH vs k(max)(obs) plot under kinetic conditions. Two kinetically equivalent mechanisms were analyzed: methoxide attack on La(3+)(2)(1(-))((-)OCH(3))(n)(), n = 0-2; unimolecular decomposition of the forms La(3+)(2)(1(-))((-)OCH(3))(n)(), n = 1-3.     

La(3+)-Catalyzed methanolysis of hydroxypropyl-p-nitrophenyl phosphate as a model for the RNA transesterification reaction

The methanolysis of hydroxypropyl-p-nitrophenyl phosphate (HPNPP, 1) promoted by La(OTf)(3) under buffered conditions was studied in methanol as a function of pH at 25 degrees C. (31)P NMR studies at -90 degrees C indicate that there are at least three La/1 complexes formed at pH approximately 5.3 of 1:1, 2:2, and 1:2 stoichiometry. Kinetic studies of the observed pseudo-first-order rate constants for the methanolysis of 1 as a function of [La(3+)] at 4.5 < pH < 10.5 indicate there are two general pH regimes. In the low pH regime between 4.5 and 7.6, the plots of k(obs) versus [La(3+)] exhibit saturation behavior with very strong 1:1 binding, with a plateau rate constant that depends on [OCH(3)(-)]. The catalytically productive species is shown to be a 2:2 complex of La(3+) and 1, where the phosphate is proposed to be doubly activated, thereby promoting the methoxide reaction by some 4.6 x 10(10)-fold. In the high pH regime from 7.9 to 10.5, 1:1, 2:2, and 2:1 La(3+)/1 complexes are formed with the La(3+) coordinated in the form of [La(3+)(OCH(3)(-))](1,2). Throughout this pH regime at high [La(3+)], a saturation complex, (La(3+)OCH(3)(-))(2)/1, is formed that spontaneously decomposes with a rate constant of (5-10) x 10(-)(3) s(-)(1), leading to an acceleration of 10(9)-fold at pH 8.0.     

Europium ion catalyzed methanolysis of esters at neutral pH and ambient temperature. catalytic Involvement of Eu3+(CH3O-)(CH3OH)x

The Eu(3+)-promoted methanolysis of three esters, p-nitrophenyl acetate (1), phenyl acetate (2), and ethyl acetate (3) is reported, as well as the potentiometric titration of Eu(3+) in MeOH at various [Eu(SO(3)CF(3))(3)] (SO(3)CF(3) = OTf). The titration data are analyzed in terms of two ionizations corresponding to macroscopic and values, which are respectively defined as the values at which the [CH(3)O(-)]/[Eu(3+)] = 0.5 and 1.5. As a function of increasing [Eu(OTf)(3)], increases slightly due to a proposed Eu(3+)/(-)OTf ion pairing effect, which tends to reduce the acidity of the metal-coordinated CH(3)OH, while decreases due to the formation of Eu(3+) dimers and oligomers which stabilize the (Eu(3+)(CH(3)O(-))(2))(n)forms through bridging of the methoxides between two or more metal ions. For ester 1, a detailed kinetic analysis of the reaction rates as a function of both [Eu(OTf)(3)] and in buffered methanol reveals that the /second-order rate constant (k(2)) plot for the catalyzed reaction follows a bell-shaped profile, suggesting that the active form is a Eu(3+)(CH(3)O(-)) monomer with a kinetic of 6.33 +/- 0.06 for formation and a of 8.02 +/- 0.10 for its conversion into the inactive (Eu(3+)(CH(3)O(-))(2))(n)oligomeric form. At higher values, plots of k(obs) vs [Eu(OTf)(3)] are linear at low metal concentration and plateau at higher metal concentration due to the formation of inactive higher order aggregates. The Eu(3+)(CH(3)O(-)) catalysis of the methanolysis of esters 1, 2, and 3 is substantial. Solutions of 10(-2) M of the catalyst at 7.12 accelerate the reaction relative to the methoxide reaction at that by 8 530 000-, 195 000 000- and 7 813 000-fold, respectively.     

Zn2+-catalyzed methanolysis of phosphate triesters: a process for catalytic degradation of the organophosphorus pesticides paraoxon and fenitrothion

The methanolyses of two neutral phosphorus triesters, paraoxon (1) and fenitrothion (3), were investigated as a function of added Zn(OTf)(2) or Zn(ClO(4))(2) in methanol at 25 degrees C either alone or in the presence of equimolar concentrations of the ligands phenanthroline (4), 2,9-dimethylphenanthroline (5), and 1,5,9-triazacyclododecane (6). The catalysis requires the presence of methoxide, and when studied as a function of added NaOCH(3), the rate constants (k(obs)) for methanolysis of Zn(2+) alone or in the presence of equimolar 4 or 5 maximize at different [(-)OCH(3)]/[Zn(2+)](total) ratios of 0.3, 0.5, and 1.0, respectively. Plots of k(obs) vs [Zn(2+)](total) either alone or in the presence of equimolar ligands 4 and 5 at the [(-)OCH(3)]/[Zn(2+)](total) ratios corresponding to the rate maxima are curved and show a nonlinear dependence on [Zn(2+)](total). In the cases of 4 and 5, this is explained as resulting from formation of a nonactive dimer, formulated as a bis-mu-methoxide-bridged form (L:Zn(2+)((-)OCH(3))(2)Zn(2+):L) in equilibrium with an active monomeric form (L:Zn(2+)((-)OCH(3))). In the case of the Zn(2+):6 system, no dimeric forms are present as can be judged by the strict linearity of the plots of k(obs) vs [Zn(2+)](total) in the presence of equimolar 6 and (-)OCH(3). Analysis of the potentiometric titration curves for Zn(2+) alone and in the presence of the ligands allows calculation of the speciation of the various Zn(2+) forms and shows that the binding to ligands 4 and 6 is very strong, while the binding to ligand 5 is weaker. Overall the best catalytic system is provided by equimolar Zn(2+), 5, and (-)OCH(3), which exhibits excellent turnover of the methanolysis of paraoxon when the substrate is in excess. At a concentration of 2 mM in each of these components, which sets the pH of the solution at 9.5, the acceleration of the methanolysis of paraoxon and fenitrothion relative to the methoxide reaction is 1.8 x 10(6)-fold and 13 x 10(6)-fold, respectively. A mechanism for the catalyzed reactions is proposed which involves a dual role for the metal ion as a Lewis acid and source of nucleophilic Zn(2+)-bound (-)OCH(3).     

Cu(II)-Mediated decomposition of phosphorothionate P=S pesticides. Billion-fold acceleration of the methanolysis of fenitrothion promoted by a simple Cu(II)-ligand system

The kinetics of methanolysis of the title compound (3) were studied in the presence of Cu(2+), introduced as Cu(OTf), in the presence of 0.5-1.0 eq. of methoxide and in the presence of 1.0 eq. of a ligand such as bipyridyl (5), phenanthroline (6) or 1,5,9-triazacyclododecane (4). In all cases the active species involve Cu(2+)((-)OCH(3)). In the case of added strong-binding ligands 5 or 6, a plot of the observed rate constant for methanolysis of 3 vs. [Cu(2+)](total) gives a curved line modelled by a process having a [Cu(2+)](1/2) dependence consistent with an active monomeric species in equilibrium with an inactive dimer i.e.[LCu(2+)((-)OCH(3))](2) <==> 2LCu(2+)((-)OCH(3)). In the case of the added strong binding ligand 4, the plot of the observed rate constant for methanolysis of 3 vs.[Cu(2+)](total) gives a straight line consistent with the catalytically active species being Cu(2+)(OCH(3)) which shows no propensity to form inactive dimers. Turnover experiments where the [3] > [Cu(2+)](total) indicate that the systems are truly catalytic. In the optimum case a catalytic system comprising 1 mM of the complex 4Cu(2+)((-)OCH(3)) catalyzes the methanolysis of 3 with a t(1/2) of approximately 58 s accounting for a 1.7 x 10(9)-fold acceleration relative to the background reaction at near neutral (s)(s)pH (8.75).     

Palladacycle-promoted solvolytic cleavage of O,O-dimethyl O-aryl phosphorothioates. Converting a phosphorane-like transition state to an observable intermediate

The mechanism of cleavage of a series of seven O,O-dimethyl O-aryl phosphorothioates (6a-g) promoted by a C,N-palladacycle, (2-[N,N-dimethylamino(methyl)phenyl]-C(1),N)(pyridine) palladium(II) triflate (5:OTf) in methanol at 25 °C was investigated with the aim of identifying catalytically important intermediates. Complete (s)(s)pH/rate profiles (in methanol) were conducted for the cleavage of 6a-g in the presence of 0.08 mM 5. The log k(obs) for the catalyzed methanolysis of 6a increases linearly with (s)(s)pH with a plateau above the (s)(s)pK(a)(1) of 11.16 for formation of 5:(-)OCH3. The profiles for 6b-g are bell-shaped, depending on the apparent ionizations of two acidic groups, with the rate constant maximum of the bell and the (s)(s)pK(a)(1) values shifting to higher (s)(s)pH values as the (s)(s)pK(a)(HOAr) of the leaving group phenol increases. A Br?nsted plot of the log k(obs)(max) (the maximum rate constants for cleavage of 6a-g) vs (s)(s)pK(a)(HOAr) exhibits a downward break at ~ (s)(s)pK(a)(HOAr) 13, with the two wings having β(lg) values of 0.01 and -0.96. A model describing the kinetically important species involves a complex series of equilibria: 5:(HOCH(3)):pyr <=> 5:((-)OCH3):pyr + H(+) <=>(6) 5:((-)OCH3):6 + pyr <=> phosphorane 7 → product, where the rate limiting steps change from formation of 5:((-)OCH3):6 to formation of thiophosphorane 7 and then to product formation as the aryloxy leaving groups of 6 get progressively worse. Kinetic experiments indicate that the reaction of 5 with 6e, having a 4-chlorophenoxy leaving group, rapidly produces a transient intermediate, postulated to be the palladacycle-bound 5-coordinate thiophosphorane (7e) that exists long enough to obtain its UV/vis spectrum by stopped-flow spectrophotometry. Detailed analysis of the data sheds light on the origins of a previously reported anomalously large β(lg) of -1.93 for the descending wing of a Br?nsted plot (J. Am. Chem. Soc. 2010, 132, 16599). Finally, energetics analysis indicates that the binding of palladacycle to the transition state comprising attack of methoxide on 6e, [MeO(-) + 6e](++), stabilizes the latter by 34.9 kcal/mol, converting that transition state into an observable intermediate.     

A simple DNase model system comprising a dinuclear Zn(II) complex in methanol accelerates the cleavage of a series of methyl aryl phosphate diesters by 10(11)-10(13)

The di-Zn(II) complex of 1,3-bis[ N1, N1'-(1,5,9-triazacyclododecyl)]propane with an associated methoxide ( 3:Zn(II) 2: (-)OCH 3) was prepared and its catalysis of the methanolysis of a series of fourteen methyl aryl phosphate diesters ( 6) was studied at s (s)pH 9.8 in methanol at 25.0 +/- 0.1 degrees C. Plots of k obs vs [ 3:Zn(II) 2: (-)OCH 3] free for all members of 6 show saturation behavior from which K(M) and kcat (max) were determined. The second order rate constants for the catalyzed reactions (kcat (max)/K(M)) for each substrate are larger than the corresponding methoxide catalyzed reaction (k 2 (-OMe)) by 1.4 x 10(8) to 3 x 10 (9)-fold. The values of k cat (max) for all members of 6 are between 4 x 10(11) and 3 x 10(13) times larger than the solution reaction at s (s)pH 9.8, with the largest accelerations being given for substrates where the departing aryloxy unit contains ortho-NO 2 or C(O)OCH 3 groups. Based on the linear Br?nsted plots of k cat (max) vs s (s)pKa of the phenol, beta lg values of -0.57 and -0.34 are determined respectively for the catalyzed methanolysis of "regular" substrates that do not contain the ortho-NO 2 or C(O)OCH 3 groups, and those substrates that do. The data are consistent with a two step mechanism for the catalyzed reaction with rate limiting formation of a catalyst-coordinated phosphorane intermediate, followed by fast loss of the aryloxy leaving group. A detailed energetics calculation indicates that the catalyst binds the transition state comprising [CH 3O (-): 6], giving a hypothetical [ 3:Zn(II) 2:CH 3O (-): 6] complex, by -21.4 to -24.5 kcal/mol, with the strongest binding being for those substrates having the ortho-NO 2 or C(O)OCH 3 groups.     

La3+-catalyzed methanolysis of O,O-diethyl S-(p-nitrophenyl) phosphorothioate and O,O-diethyl S-phenyl phosphorothioate. Millions-fold acceleration of the destruction of V-agent simulants

The La3+-catalyzed methanolysis of two phosphorothioate derivatives, O,O-diethyl S-(p-nitrophenyl) phosphorothioate (4a) and O,O-diethyl S-phenyl phosphorothioate (4b) were studied as a function of [La3+] and pH in methanol solvent. In both cases the kinetics of catalyzed methanolysis maximize at pH 9.1 and a detailed analysis indicates that the dominant species responsible for catalysis are dimers formulated as La3+(2)(-OCH3)2 and La3+(2)(-OCH3)4. The catalysis is compared with that seen for the corresponding phosphate esters, namely paraoxon (3a) and O,O-diethyl phenyl phosphate (3b) for which La3+ catalysis is slightly better and markedly worse than for 4a and 4b respectively. Overall, at s(s)pH 9.1, a 2 mmol dm-3 solution of La(OTf)3 with equimolar NaOCH3 provides accelerations of 2.2x10(8)-fold, 9.7x10(6)-fold and 9.3x10(6)-fold for methanolysis of 3a, 4a and 4b, relative to the background reaction of methoxide reacting with the three substrates. In each case, the P-containing product of the reactions is exclusively diethyl methyl phosphate. Turnover experiments with 6-fold and 100-fold excesses of 4a and 4b respectively, methanolyzed in the presence of approximately 10 mmol dm-3 La3+ and equimolar NaOCH3, indicate that the reactions are essentially complete within 103 s and 70 min respectively. The latter turnover experiment with 4b corresponded to 100 turnovers in 70 min and an overall reaction t1/2 of 8 min. A common mechanism of reaction is postulated for each of the substrates which involves Lewis acid coordination of one of the La3+ to the P=O unit, followed by nucleophilic attack by the second La3+-(-)OCH3.     

Metal ion-catalyzed cycloaddition vs hydride transfer reactions of NADH analogues with p-benzoquinones

1-Benzyl-4-tert-butyl-1,4-dihydronicotinamide (t-BuBNAH) reacts efficiently with p-benzoquinone (Q) to yield a [2+3] cycloadduct (1) in the presence of Sc(OTf)(3) (OTf = OSO(2)CF(3)) in deaerated acetonitrile (MeCN) at room temperature, while no reaction occurs in the absence of Sc(3+). The crystal structure of 1 has been determined by the X-ray crystal analysis. When t-BuBNAH is replaced by 1-benzyl-1,4-dihydronicotinamide (BNAH), the Sc(3+)-catalyzed cycloaddition reaction of BNAH with Q also occurs to yield the [2+3] cycloadduct. Sc(3+) forms 1:4 complexes with t-BuBNAH and BNAH in MeCN, whereas there is no interaction between Sc(3+) and Q. The observed second-order rate constant (k(obs)) shows a first-order dependence on [Sc(3+)] at low concentrations and a second-order dependence at higher concentrations. The first-order and the second-order dependence of the rate constant (k(et)) on [Sc(3+)] was also observed for the Sc(3+)-promoted electron transfer from CoTPP (TPP = tetraphenylporphyrin dianion) to Q. Such dependence of k(et) on [Sc(3+)] is ascribed to formation of 1:1 and 1:2 complexes between Q(*)(-) and Sc(3+) at the low and high concentrations of Sc(3+), respectively, which results in acceleration of the rate of electron transfer. The formation constants for the 1:2 complex (K(2)) between the radical anions of a series of p-benzoquinone derivatives (X-Q(*)(-)) and Sc(3+) are determined from the dependence of k(et) on [Sc(3+)]. The K(2) values agree well with those determined from the dependence of k(obs) on [Sc(3+)] for the Sc(3+)-catalyzed addition reaction of t-BuBNAH and BNAH with X-Q. Such an agreement together with the absence of the deuterium kinetic isotope effects indicates that the addition proceeds via the Sc(3+)-promoted electron transfer from t-BuBNAH and BNAH to Q. When Sc(OTf)(3) is replaced by weaker Lewis acids such as Lu(OTf)(3), Y(OTf)(3), and Mg(ClO(4))(2), the hydride transfer reaction from BNAH to Q also occurs besides the cycloaddition reaction and the k(obs) value decreases with decreasing the Lewis acidity of the metal ion. Such a change in the type of reaction from a cycloaddition to a hydride transfer depending on the Lewis acidity of metal ions employed as a catalyst is well accommodated by the common reaction mechanism featuring the metal-ion promoted electron transfer from BNAH to Q.     

Ligand-modification effects on the reactivity, solubility, and stability of organometallic tantalum complexes in water

Tantalum complexes [TaCp*Me{κ(4)-C,N,O,O-(OCH(2))(OCHC(CH(2)NMe(2))=CH)py}] (4) and [TaCp*Me{κ(4)-C,N,O,O-(OCH(2))(OCHC(CH(2)NH(2))=CH)py}] (5), which contain modified alkoxide pincer ligands, were synthesized from the reactions of [TaCp*Me{κ(3)-N,O,O-(OCH(2))(OCH)py}] (Cp* = η(5)-C(5)Me(5)) with HC≡CCH(2)NMe(2) and HC≡CCH(2)NH(2), respectively. The reactions of [TaCp*Me{κ(4)-C,N,O,O-(OCH(2))(OCHC(Ph)=CH)py}] (2) and [TaCp*Me{κ(4)-C,N,O,O-(OCH(2))(OCHC(SiMe(3))=CH)py}] (3) with triflic acid (1:2 molar ratio) rendered the corresponding bis-triflate derivatives [TaCp*(OTf)(2){κ(3)-N,O,O-(OCH(2))(OCHC(Ph)=CH(2))py}] (6) and [TaCp*(OTf)(2){κ(3)-N,O,O-(OCH(2))(OCHC(SiMe(3))=CH(2))py}] (7), respectively. Complex 4 reacted with triflic acid in a 1:2 molar ratio to selectively yield the water-soluble cationic complex [TaCp*(OTf){κ(4)-C,N,O,O-(OCH(2))(OCHC(CH(2)NHMe(2))=CH)py}]OTf (8). Compound 8 reacted with water to afford the hydrolyzed complex [TaCp*(OH)(H(2)O){κ(3)-N,O,O-(OCH(2))(OCHC(CH(2)NHMe(2))=CH(2))py}](OTf)(2) (9). Protonation of compound 8 with triflic acid gave the new tantalum compound [TaCp*(OTf){κ(4)-C,N,O,O-(OCH(2))(HOCHC(CH(2)NHMe(2))=CH)py}](OTf)(2) (10), which afforded the corresponding protonolysis derivative [TaCp*(OTf)(2){κ(3)-N,O,O-(OCH(2))(HOCHC(CH(2)NHMe(2))=CH(2))py}](OTf) (11) in solution. Complex 8 reacted with CNtBu and potassium 2-isocyanoacetate to give the corresponding iminoacyl derivatives 12 and 13, respectively. The molecular structures of complexes 5, 7, and 10 were established by single-crystal X-ray diffraction studies.     

The mechanism of the hydroalkoxycarbonylation of ethene and alkene-CO copolymerization catalyzed by Pd(II)-diphosphine cations

All the intermediates in the "carboalkoxy" pathway, and their interconversions giving complete catalytic cycles, for palladium-diphosphine-catalyzed hydroalkoxycarbonylation of alkenes, and for alkene-CO copolymerization, have been demonstrated using (31)P{(1)H} and (13)C{(1)H} NMR spectroscopy. The propagation and termination steps of the "hydride" cycles and the crossover between the hydride and carboalkoxy cycles have also been demonstrated, providing the first examples of both cycles, and of chain crossover, being delineated for the same catalyst. Comparison of the propagation and termination steps in the pathways affords new insight into the selectivity-determining steps. Thus, reaction of [Pd(dibpp)(CH(3)CN)(2)](OTf)(2) (dibpp = 1,3-(iBu(2)P)(2)C(3)H(6)) with Et(3)N and CH(3)OH affords [Pd(dibpp)(OCH(3))(CH(3)CN)]OTf, which, on exposure to CO, gives [Pd(dibpp){C(O)OCH(3)}(CH(3)CN)]OTf immediately. Labeling studies show the reaction to be readily reversible. However, the back reaction is strongly inhibited by PPh(3), indicating an insertion/deinsertion pathway. Ethene reacts with [Pd(dibpp){C(O)OCH(3)}(CH(3)CN)]OTf at 243 K to give [Pd(dibpp){CH(2)CH(2)C(O)OCH(3)}]OTf, that is, there is no intrinsic barrier to alkene insertion into the Pd--C(O)OMe bond, as had been proposed. Instead, termination is proposed to be selectivity determining. Methanolysis of the acyl intermediate [Pd(dibpp){C(O)CH(3)}L]X (L = CO, CH(3)OH; X = CF(3)SO(3) (-) (OTf(-)), CH(3)C(6)H(4)SO(3) (-) (OTs(-))) is required in the hydride cycle to give an ester and occurs at 243 K on the timescale of minutes, whereas methanolysis of the beta chelate, required to give an ester from the carbomethoxy cycle, is slow on a timescale of days, at 298 K. These results suggest that slow methanolysis of the beta chelate, rather than slow insertion of an alkene into the Pd--carboalkoxy bond, as had previously been proposed, is responsible for the dominance of the hydride mechanism in hydroalkoxycarbonylation.     

Study on the transesterification of methyl aryl phosphorothioates in methanol promoted by Cd(II), Mn(II), and a synthetic Pd(II) complex

Methanol solutions containing Cd(II), Mn(II), and a palladacycle, (dimethanol bis(N,N-dimethylbenzylamine-2C,N)palladium(II) (3), are shown to promote the methanolytic transesterification of O-methyl O-4-nitrophenyl phosphorothioate (2b) at 25 °C with impressive rate accelerations of 10(6)-10(11) over the background methoxide promoted reaction. A detailed mechanistic investigation of the methanolytic cleavage of 2a-d having various leaving group aryl substitutions, and particularly the 4-nitrophenyl derivative (2b), catalyzed by Pd-complex 3 is presented. Plots of k(obs) versus palladacycle [3] demonstrate strong saturation binding to form 2b:3. Numerical fits of the kinetic data to a universal binding equation provide binding constants, K(b), and first order catalytic rate constants for the methanolysis reaction of the 2b:3 complex (k(cat)) which, when corrected for buffer effects, give corrected (k(cat)(corr)) rate constants. A sigmoidal shaped plot of log(k(cat)(corr)) versus (s)(s)pH (in methanol) for the cleavage of 2b displays a broad (s)(s)pH independent region from 5.6 ≤ (s)(s)pH ≤ 10 with a k(minimum) = (1.45 ± 0.24) × 10(-2) s(-1) and a [lyoxide] dependent wing plateauing above a kinetically determined (s)(s)pK(a) of 12.71 ± 0.17 to give a k(maximum) = 7.1 ± 1.7 s(-1). Br?nsted plots were constructed for reaction of 2a-d at (s)(s)pH 8.7 and 14.1, corresponding to reaction in the midpoints of the low and high (s)(s)pH plateaus. The Br?nsted coefficients (β(LG)) are computed as -0.01 ± 0.03 and -0.86 ± 0.004 at low and high (s)(s)pH, respectively. In the low (s)(s)pH plateau, and under conditions of saturating 3, a solvent deuterium kinetic isotope effect of k(H)/k(D) = 1.17 ± 0.08 is observed; activation parameters (ΔH(Pd)(++) = 14.0 ± 0.6 kcal/mol and ΔS(Pd)(++)= -20 ± 2 cal/mol·K) were obtained for the 3-catalyzed cleavage reaction of 2b. Possible mechanisms are discussed for the reactions catalyzed by 3 at low and high sspH. This catalytic system is shown to promote the methanolytic cleavage of O,O-dimethyl phosphorothioate in CD3OD, producing (CD3O)2P═O(S(-)) with a half time for reaction of 34 min.     

Conversion of bis(trichloromethyl) carbonate to phosgene and reactivity of triphosgene, diphosgene, and phosgene with methanol(1)

Triphosgene was decomposed quantitatively to phosgene by chloride ion. The reaction course was monitored by IR spectroscopy (React-IR), showing that diphosgene was an intermediate. The methanolysis of triphosgene in deuterated chloroform, monitored by proton NMR spectroscopy, gave methyl chloroformate and methyl 1,1, 1-trichloromethyl carbonate in about a 1:1 ratio, as primary products. The reaction carried out in the presence of large excess of methanol (0.3 M, 30 equiv) was a pseudo-first-order process with a k(obs) of 1.0 x 10(-)(4) s(-)(1). Under the same conditions, values of k(obs) of 0.9 x 10(-)(3) s(-)(1) and 1.7 x 10(-)(2) s(-)(1) for the methanolysis of diphosgene and phosgene, respectively, were determined. The experimental data suggest that, under these conditions, the maximum concentration of phosgene during the methanolysis of triphosgene and diphosgene was lower than 1 x 10(-)(5) M. Methyl 1,1,1-trichloromethyl carbonate was synthesized and characterized also by the APCI-MS technique.     

Catalytic oxidation of 3,5-Di-tert-butylcatechol by a series of mononuclear manganese complexes: synthesis, structure, and kinetic investigation

The manganese compounds [Mn(bpia)(OAc)(OCH(3))](PF(6)) (1), [Mn(bipa)(OAc)(OCH(3))](PF(6)) (2), [Mn(bpia)(Cl)(2)](ClO(4)) (3), [Mn(bipa)(Cl)(2)](ClO(4)) (4), [Mn(Hmimppa)(Cl)(2)] x CH(3)OH (5), and [Mn(mimppa)(TCC)] x 2CHCl(3) (6) (bpia = bis(picolyl)(N-methylimidazole-2-yl)amine; bipa = bis(N-methylimidazole-2-yl)(picolyl)amine; Hmimppa = ((1-methylimidazole-2-yl)methyl)((2-pyridyl)methyl)(2-hydroxyphenyl)amine; TCC = tetrachlorocatechol) were synthesized and characterized by various techniques such as X-ray crystallography, mass spectrometry, IR, EPR, and UV/vis spectroscopy, cyclic voltammetry, and elemental analysis. 1 and 2 crystallize in the triclinic space group Ponemacr; (No. 2), 4 and 6 crystallize in the monoclinic space group P2(1)/n (No. 14), and 5 crystallizes in the orthorhombic space group Pna2(1). Complexes 1-4 are structurally related to the proposed active site of the manganese-dependent extradiol-cleaving catechol dioxygenase exhibiting an N(4)O(2) donor set (1 and 2) or N(4)Cl(2) donor set (3 and 4). Cyclic voltammetric data show that the substitution of oxygen donor atoms with chloride causes a shift of redox potentials to more positive values. These compounds show high catalytic activity regarding the oxidation of 3,5-di-tert-butylcatechol to 3,5-di-tert-butylquinone exhibiting saturation kinetics at high substrate concentrations. The turnover numbers k(cat) = (86 +/- 7) h(-1) (1), k(cat) = (101 +/- 4) h(-1) (2), k(cat) = (230 +/- 4) h(-1) (3), and k(cat) = (130 +/- 4) h(-1) (4) were determined from the double reciprocal Lineweaver-Burk plot. Compounds 5 and 6 can be regarded as structural and electronic Mn analogues for substituted forms of Fe-containing intradiol-cleaving catechol dioxygenases. To our knowledge 5 is the first mononuclear Mn(II) compound featuring an N(3)OCl(2) donor set.     

Rapid three-step cleavage of RNA and DNA model systems promoted by a dinuclear Cu(II) complex in methanol. energetic origins of the catalytic efficacy

A dinuclear Cu(II) complex of 1,3-bis-N(1)-(1,5,9-triazacyclododecyl)propane with an associated methoxide (2-Cu(II)(2):(-OCH(3))) was prepared, and its kinetics of reaction with an RNA model (2-hydroxypropyl-p-nitrophenyl phosphate (1, HPNPP)) and two DNA models (methyl p-nitrophenyl phosphate (3) and iso-butyl p-chlorophenyl phosphate (4)) were studied in methanol solution at (s)(s)pH 7.2 +/- 0.2. X-ray diffraction structures of 2-Cu(II)(2):(-OH)(H(2)O)(CF(3)SO(3)-)(3):0.5CH(3)CH(2)OCH(2)CH(3) and 2-Cu(II)(2):(-OH)((C(6)H(5)CH(2)O)(2)PO(2)-)(CF(3)SO(3)-)2 show the mode of coordination of the bridging -OH and H(2)O between the two Cu(II) ions in the first complex and bridging -OH and phosphate groups in the second. The kinetic studies with 1 and 3 reveal some common preliminary steps prior to the chemical one of the catalyzed formation of p-nitrophenol. With 3, and also with the far less reactive substrate (4), two relatively fast events are cleanly observed via stopped-flow kinetics. The first of these is interpreted as a binding step which is linearly dependent on [catalyst] while the second is a unimolecular step independent of [catalyst] proposed to be a rearrangement that forms a doubly Cu(II)-coordinated phosphate. The catalysis of the cleavage of 1 and 3 is very strong, the first-order rate constants for formation of p-nitrophenol from the complex being approximately 0.7 s(-1) and 2.4 x 10(-3) s(-1), respectively. With substrate 3, 2-Cu(II)(2):(-OCH(3)) exhibits Michaelis-Mentin kinetics with a k(cat)/K(M) value of 30 M(-1) s(-1) which is 3.8 x 10(7)-fold greater than the methoxide promoted reaction of 3 (7.9 x 10(-7) M(-1) s(-1)). A free energy calculation indicates that the binding of 2-Cu(II)(2):(-OCH(3)) to the transition states for 1 and 3 cleavage stabilizes them by -21 and -24 kcal/mol, respectively, relative to that of the methoxide promoted reactions. The results are compared with a literature example where the cleavage of 1 in water is promoted by a dinuclear Zn(II) catalyst, and the energetic origins of the exalted catalysis of the 2-Cu(II)(2) and 2-Zn(II)(2) methanol systems are discussed.     

Scandium ion-promoted reduction of heterocyclic N=N double bond. Hydride transfer vs electron transfer

Hydride transfer from 10-methyl-9,10-dihydroacridine (AcrH(2)) to 3,6-diphenyl-1,2,4,5-tetrazine (Ph(2)Tz), which contains a N=N double bond, occurs efficiently in the presence of Sc(OTf)(3) (OTf = OSO(2)CF(3)) in deaerated acetonitrile (MeCN) at 298 K, whereas no reaction occurs in the absence of Sc(3+). The observed second-order rate constant (k(obs)) increases with increasing Sc(3+) concentration to approach a limited value. When AcrH(2) is replaced by the dideuterated compound (AcrD(2)), the rate of Sc(3+)-promoted hydride transfer exhibits the same primary kinetic isotope effect (k(H)/k(D) = 5.2+/-0.2), irrespective of Sc(3+) concentration. Scandium ion also promotes an electron transfer from CoTPP (TPP(2)(-) = tetraphenylporphyrin dianion) and 10,10'-dimethyl-9,9'-biacridine [(AcrH)(2)] to Ph(2)Tz, whereas no electron transfer from CoTPP or (AcrH)(2) to Ph(2)Tz occurs in the absence of Sc(3+). In each case, the observed second-order rate constant of electron transfer (k(et)) shows a first-order dependence on [Sc(3+)] at low concentrations and a second-order dependence at higher concentrations. Such dependence of k(et) on [Sc(3+)] is ascribed to formation of 1:1 and 1:2 complexes between Ph(2)Tz(*)(-) and Sc(3+) at the low and high concentrations of Sc(3+), respectively, which results in acceleration of the rate of electron transfer. The formation of 1:2 complex has been confirmed by the ESR spectrum in which the hyperfine structure is different from that of free Ph(2)Tz(*)(-). The 1:2 complex formation results in the saturated kinetic dependence of k(obs) on [Sc(3+)] for the Sc(3+)-promoted hydride transfer, which proceeds via Sc(3+)-promoted electron transfer from AcrH(2) to Ph(2)Tz, followed by proton transfer from AcrH(2)(*)(+) to the 1:1 Ph(2)Tz(*)(-)-Sc(3+) complex and the subsequent facile electron transfer from AcrH(*) to Ph(2)TzH(*). The effects of counteranions on the Sc(3+)-promoted electron transfer and hydride transfer reactions are also reported.     

Kinetic resolution of esters via metal catalyzed methanolysis reactions

Some chiral lanthanide complexes of the Schiff base adducts of: a) bis(2-pyridylcarboxaldehyde) and (1R),(2R)-trans-1,2-diaminocyclohexane (Pyr-R,R'-chxn: 3); b) 6-methyl-2-pyridylcarboxaldehyde and (1R),(2R)-trans 1,2-diaminocyclohexane (MePyr-chxn, 4); and c) 2,6-pyridyldicarboxaldehyde and (1R),(2R)-trans-1,2-diaminocyclohexane ((Pyr-R,R'-chxn)(2), 5) have been screened for their utility to promote kinetic resolution via metal catalyzed alcoholyses of the p-nitrophenyl esters of chiral D- and L-Boc-protected glutamine and phenylalanine. Solvents were varied to optimize the kinetic selectivity values, defined as k(2)(L)/k(2)(D) or k(2)(D)/k(2)(L), for the methanolysis and in some cases, ethanolysis of these substrates. At ambient temperature the greatest selectivity was found for the ethanolysis of Boc-Gln-OPNP, catalyzed by 3:Yb(3+):((-)OEt) (k(2)(L)/k(2)(D) = 7.2). The greatest selectivity for Boc-Phe-OPNP is k(2)(D)/k(2)(L) = 3.9 for its methanolysis promoted by 5:La(3+):((-)OMe). A kinetic method is introduced for the determination of both d and l rate constants for catalyzed alcoholysis from a single kinetic experiment. The activation parameters DeltaH(double dagger) and DeltaS(double dagger) were determined for the metal catalyzed methanolysis and ethanolysis of the Boc-Gln-OPNP substrates, and selectivity factors were found to increase at lower temperatures. A low temperature time course for the ethanolysis of racemic Boc-Gln-OPNP catalyzed by 3:Yb(3+):((-)OEt) at -15 degrees C indicated that after 3 hours 60% residual d-enantiomer was observed having an enantiomeric excess of >95% ee. The activation parameters for the ethanolysis of the same substrate catalyzed by (Pyr-R,R'-chxn)(2):La(3+):((-)OEt) predict a k(2)(D)/k(2)(L) = 40.4 at -40 degrees C with a large ee of >99% with approximately 80% of l isomer remaining at that temperature which has been experimentally confirmed.     

Catalysis of the methanolysis of activated amides by divalent and trivalent metal ions. The effect of Zn(2+), Co(2+), and La(3+) on the methanolysis of acetylimidazole and its (NH(3))(5)Co(III) complex.

The metal ions Zn(2+), Co(2+), and La(3+) strongly catalyze the methanolysis of the activated amides acetylimidazole (1) and its ligand-exchange-inert Co(III) complex, (NH(3))(5)Co(III)-AcIm (2). Studies of the kinetics of methanolysis are performed with pH measurement and control, and the metal ions are soluble in the medium throughout the pH regions where ionization of the M(x+)(CH(3)OH)(y) occurs. Zn(2+) and Co(2+) act as Lewis acids toward 1, catalyzing attack of external methoxide on a 1:M(2+) complex at values only 100-fold lower than the diffusion limit, the k(OR) values being 5.6 x 10(7) M(-1) s(-1) and 2.5 x 10(7) M(-1) s(-1), while that for CH(3)O(-) attack on 2 is 4.69 x 10(7) M(-1) s(-1). Since neither Zn(2+) nor Co(2+) promotes the methanolysis of 2, these metals appear to be acting through transient binding to the distal N of 1, which activates the C=O of the complex to external CH(3)O(-) attack. La(3+) catalyzes the methanolysis of both 1 and 2, which occurs by a mechanism that is fundamentally different from that exhibited by Zn(2+) and Co(2+) in that the active species appears to be a bis-methoxy-bridged dimer (La(3+))(2)(CH(3)O(-))(2)(CH(3)OH)(x)() that interacts directly with the C=O unit of the substrate.     

Oxidation of di- and tripeptides of tyrosine and valine mediated by singlet molecular oxygen, phosphate radicals and sulfate radicals.

Kinetics and mechanism of the oxidation of tyrosine (Tyr) and valine (Val) di- and tripeptides (Tyr-Val, Val-Tyr and Val-Tyr-Val) mediated by singlet molecular oxygen [O(2)((1)Delta(g))], phosphate (HPO(4)(*-) and PO(4)(*2-)) and sulfate (SO(4)(*-)) radicals was studied, employing time-resolved O(2)((1)Delta(g)) phosphorescence detection, polarographic determination of dissolved oxygen and flash photolysis. All the substrates were highly photooxidizable through a O(2)((1)Delta(g))-mediated mechanism. Calculated quotients between the overall and reactive rate constants for the quenching of O(2)((1)Delta(g)) by Tyr-derivatives (k(t)/k(r) values, accounting for the efficiency of the effective photooxidation) were 1.3 for Tyr, 1 for Tyr-Val, 2.8 for Val-Tyr and 1.5 for Val-Tyr-Val. The effect of pH on the kinetics of the photooxidative process confirms that the presence of the dissociated phenolate group of Tyr clearly dominates the O(2)((1)Delta(g)) quenching process. Products analysis by LC-MS indicates that the photooxidation of Tyr di- and tripeptides proceeds with the breakage of peptide bonds. The information obtained from the evolution of primary amino groups upon photosensitized irradiation is in concordance with these results. Absolute rate constants for the reactions of phosphate radicals (HPO(4)(*-) and PO(4)(*2-), generated by photolysis of the P(2)O(8)(4-) at different pH) and sulfate radicals (SO(4)(*-), produced by photolysis of the S(2)O(8)(2-)) with Tyr peptides indicate that for all the substrates, the observed tendency in the rate constants is: SO(4)(*-) > or = HPO(4)(*-) > or = PO(4)(*2-). Formation of the phenoxyl radical of tyrosine was detected as an intermediate involved in the oxidation of tyrosine by HPO(4)(*-).     

Scandium ion-promoted photoinduced electron transfer from electron donors to acridine and pyrene. Essential role of scandium ion in photocatalytic oxygenation of hexamethylbenzene

Photoinduced electron transfer from a variety of electron donors including alkylbenzenes to the singlet excited state of acridine and pyrene is accelerated significantly by the presence of scandium triflate [Sc(OTf)(3)] in acetonitrile, whereas no photoinduced electron transfer from alkylbenzenes to the singlet excited state of acridine or pyrene takes place in the absence of Sc(OTf)(3). The rate constants of the Sc(OTf)(3)-promoted photoinduced electron-transfer reactions (k(et)) of acridine to afford the complex between acridine radical anion and Sc(OTf)(3) remain constant under the conditions such that all the acridine molecules form the complex with Sc(OTf)(3). In contrast to the case of acridine, the k(et) value of the Sc(OTf)(3)-promoted photoinduced electron transfer of pyrene increases with an increase in concentration of Sc(OTf)(3) to exhibit first-order dependence on [Sc(OTf)(3)] at low concentrations, changing to second-order dependence at high concentrations. The first-order and second-order dependence of k(et) on [Sc(OTf)(3)] is ascribed to the 1:1 and 1:2 complexes formation between pyrene radical anion and Sc(OTf)(3). The positive shifts of the one-electron redox potentials for the couple between the singlet excited state and the ground-state radical anion of acridine and pyrene in the presence of Sc(OTf)(3) as compared to those in the absence of Sc(OTf)(3) have been determined by adapting the free energy relationship for the photoinduced electron-transfer reactions. The Sc(OTf)(3)-promoted photoinduced electron transfer from hexamethylbenzene to the singlet excited state of acridine or pyrene leads to efficient oxygenation of hexamethylbenzene to produce pentamethylbenzyl alcohol which is further oxygenated under prolonged photoirradiation of an O(2)-saturated acetonitrile solution of hexamethylbenzene in the presence of acridine or pyrene which acts as a photocatalyst together with Sc(OTf)(3). The photocatalytic oxygenation mechanism has been proposed based on the studies on the quantum yields, the fluorescence quenching, and direct detection of the reaction intermediates by ESR and laser flash photolysis.