Kinetics and mechanism of the reactions of aryl chlorodithioformates with pyridines and secondary alicyclic amines

The reactions of pyridines and secondary alicyclic (SA) amines with phenyl and 4‐nitrophenyl chlorodithioformates (PClDTF and NPClDTF, respectively) are subjected to a kinetic study in aqueous ethanol (44 wt% ethanol) solution, at 25.0 °C, and an ionic strength of 0.2 M (KCl). The reactions are studied spectrophotometrically. Under amine excess, pseudo‐first‐order rate coefficients (k_obs) are found. Plots of k_obs versus [amine] are linear and pH independent, with slope k_N. The Brønsted‐type plots (log k_N vs. pK_a of aminium ions) are linear for the reactions of PClDTF with SA amines (slope β of 0.3) and pyridines (β = 0.26) and those of NPClDTF with pyridines (β = 0.30). For the reaction of NPClDTF with SA amines the Brønsted‐type plot is biphasic, with slopes β₁ = 0.2 (at high pKa) and β₂ = 1.1 (at low pKa). The pK_a value at the center of curvature (pK) is 7.7. The magnitude of the slopes indicates that the mechanisms of these reactions are stepwise, with the formation of a zwitterionic tetrahedral intermediate as the rate‐determining step, except for the reaction of NPClDTF with SA amines where there is a change in the rate‐determining step, from formation to breakdown of the tetrahedral intermediate, as the amine basicity decreases. Copyright © 2009 John Wiley & Sons, Ltd.     

Kinetics and mechanism of the anilinolysis of aryl 4‐nitrophenyl thionocarbonates in aqueous ethanol

The reactions of bis(4‐nitrophenyl), 3‐chlorophenyl 4‐nitrophenyl, and 3‐methoxyphenyl 4‐nitrophenyl thionocarbonates ( 1 , 2 , and 3 , respectively) with a series of anilines are subjected to a kinetic investigation in 44 wt.% ethanol–water, at 25.0 °C and an ionic strength of 0.2 M. Under aniline excess, pseudo‐first‐order rate coefficients (k_obs) are found. Plots of k_obs versus aniline concentration are linear, with the slopes (k_N) pH independent, k_N being the rate coefficient for the anilinolysis of the thionocarbonates. The Brønsted plot (log k_N vs. pK_a of anilinium ions) for thionocarbonate 1 is linear, with slope (β) 0.62, which is consistent with a concerted mechanism. The Brønsted plots for thionocarbonates 2 and 3 are curved, with slopes 0.1 at high pK_a for both reaction series and slopes 0.84 and 0.79 at low pK_a for the reactions of 2 and 3 , respectively. The latter plots are in accordance to stepwise mechanisms, through a zwitterionic tetrahedral intermediate (T^±) and its anionic analogue (T^?), the latter being formed by deprotonation of T^± by the basic form of the buffer (HPO). The Brønsted curves are explained by a change in the rate‐limiting step, from deprotonation of T^± at low pK_a, to its formation at high pK_a. The influence of the amine nature and the non‐leaving and electrophilic groups of the substrate on the kinetics and mechanism is also discussed. Copyright © 2010 John Wiley & Sons, Ltd.     

Kinetics and mechanism of the pyridinolysis of diaryl carbonates

The reactions of 4‐methylphenyl and 4‐chlorophenyl 4‐nitrophenyl carbonates ( 1 and 2 , respectively), phenyl, 4‐methylphenyl, 4‐chlorophenyl, and 4‐nitrophenyl 2,4‐dinitrophenyl carbonates ( 3 , 4 , 5 , and 6 , respectively), and bis(2,4‐dinitrophenyl) carbonate ( 7 ) with a series of pyridines are studied kinetically at 25.0 °C in 44 wt% ethanol–water and an ionic strength of 0.2 M (KCl). The reactions are followed spectrophotometrically and under excess amine pseudo‐first‐order rate coefficients (k_obs) are found. For all these reactions, plots of k_obs versus free amine concentration at constant pH are linear, the slope (k_N) being independent of pH. The Brønsted‐type plots (log k_N vs. pK_a of the conjugate acids of the pyridines) are all biphasic (linear portions at high and low pK_a and a curvature in between). These plots are in accordance with a stepwise mechanism, through a zwitterionic tetrahedral intermediate (T^±), and a change in the rate‐determining step from formation of T^± to its breakdown to products, as the pyridine basicity decreases. Also studied are the effects of the leaving, non‐leaving, and electrophilic groups of the substrate, and of the amine nature, on the value (value at the center of curvature of the Brønsted‐type plots). Copyright © 2008 John Wiley & Sons, Ltd.     

Reactions of O‐aryl S‐aryl dithiocarbonates with pyridines in aqueous ethanol: kinetics and mechanism

The reactions of O‐(4‐methylphenyl) S‐(4‐nitrophenyl) dithiocarbonate ( 1 ), O‐(4‐chlorophenyl) S‐(4‐nitrophenyl) dithiocarbonate ( 2 ), and O‐(4‐chlorophenyl) S‐phenyl) dithiocarbonate ( 3 ) with a series of pyridines were subjected to a kinetic investigation in 44 wt% ethanol–water, at 25.0 °C and an ionic strength of 0.2 M. The reactions were followed spectrophotometrically. Under amine excess, pseudo‐first‐order rate coefficients (k_obs) were determined. For the studied reactions, plots of k_obs versus free pyridine concentration at constant pH were linear, with the slope (k_N) independent of pH. The Brønsted‐type plots for ( 1 ) and ( 2 ) were biphasic, suggesting a stepwise mechanism with a change in the rate‐determining step, from breakdown to the formation of a tetrahedral intermediate (T^±), as the basicity of the pyridines increases. For the reactions of ( 3 ), at the pK_a range of the pyridines studied, only the breakdown to products of T^± was observed. Copyright © 2009 John Wiley & Sons, Ltd.     

Reactions of O‐aryl S‐aryl dithiocarbonates with secondary alicyclic amines in aqueous ethanol. Kinetics and mechanism

The reactions of O‐(4‐methylphenyl) S‐(4‐nitrophenyl), O‐(4‐chlorophenyl) (4‐nitrophenyl), O‐(4‐chlorophenyl) S‐phenyl, and O‐(4‐methylphenyl) S‐phenyl dithiocarbonates ( 1 , 2 , 3 , and 4 , respectively) with a series of secondary alicyclic (SA) amines are subjected to a kinetic investigation in 44 wt% ethanol‐water, at 25.0 °C and an ionic strength of 0.2 M. The reactions are followed spectrophotometrically. Under amine excess, pseudo‐first‐order rate coefficients (k_obs) are found. For some of the reactions, plots of k_obs vs. free amine concentration at constant pH are linear but others are nonlinear upwards. This kinetic behavior is in accordance with a stepwise mechanism with two tetrahedral intermediates, one zwitterionic (T^±) and the other anionic (T^?). In some cases, there is a kinetically significant proton transfer from T^± to an amine to yield T^?. Values of the rate micro constants k₁ (amine attack to form T^±), k_?1 (its back step), k₂ (nucleofuge expulsion from T^±), and k₃ (proton transfer from T^± to the amine) are determined for some reactions. The Brønsted plots for k₁ are linear with slopes β₁ = 0.2–0.4 in accordance with the slope values found when T^± formation is the rate‐determining step. The sensitivity of log k₁ and log k_?1 to the pK_a of the amine, leaving and non‐leaving groups are determined by a multiparametric equation. For the reactions of 1 – 4 with 1‐formylpiperazine and those of 3 and 4 with morpholine the k₂ and k₃ steps are rate determining. Copyright © 2010 John Wiley & Sons, Ltd.     

Kinetics and mechanism of the reactions of O‐aryl S‐(4‐nitrophenyl) dithiocarbonates with anilines in aqueous ethanol

The reactions of O‐(4‐methylphenyl) S‐(4‐nitrophenyl) dithiocarbonate and O‐(4‐chlorophenyl) S‐(4‐nitrophenyl) dithiocarbonate with a series of anilines are subjected to a kinetic investigation in 44 wt% ethanol–water, at 25.0 °C and an ionic strength of 0.2 M. The reactions are followed spectrophotometrically at 420 nm (appearance of 4‐nitrobenzenethiolate anion). Under excess amine, pseudo‐first‐order rate coefficients (k_obs) are found. For the reactions of both substrates with anilines, plots of k_obs versus free amine concentration at constant pH are nonlinear upwards, according to a second‐order polynomial equation. This kinetic behavior is in agreement with a stepwise mechanism consisting of two tetrahedral intermediates, one zwitterionic (T^±) and the other anionic (T^?), with a kinetically significant proton transfer from T^± to an aniline to yield T^?. The rate equation was derived from the proposed mechanism. By nonlinear least‐squares fitting of the rate equation to the experimental data, values of the rate micro‐coefficients involved in both steps were determined. Copyright © 2009 John Wiley & Sons, Ltd.     

Kinetic investigation on carbamate formation from the reaction of carbon dioxide with amino acids in homogeneous aqueous solution

The kinetics of carbamate formation from the reaction of carbon dioxide with α‐amino acids in D₂O was first investigated by means of nuclear magnetic resonance spectroscopy. Potassium carbonate was used as the CO₂ source. For each amino acid, the maximum carbamate yield, the apparent rate constant for the carbamate formation k_app, and the rate constants for the formation k₁ and the breakdown k_?1 of the carbamate were estimated. Plots of log k₁ or log k_?1 versus pK_a of amino acids indicated that the formation rate k₁ increased with the basicity (pK_a) of amino acid, while the decomposition rate k_?1 decreased. A Br?nsted β value of 0.39 was obtained from the former plot, being in good agreement with the previously reported ones (0.26–0.43). The observed negative pK_a dependence of log k_?1 (Br?nsted α = 0.34) is reasonable, because the carbamate decomposition is acid‐catalyzed and the steady‐state concentration of H⁺ should be higher for weaker basic amines. The charge (σ) and the lone‐pair energy (E_N) at the nitrogen atom of the amino group were calculated. Although log k₁ correlated with σ and E_N, log k_?1 was unrelated with both of these parameters. Considering that the carbamate formation (k₁) is not only base‐catalyzed but should also be promoted by the nucleophilicity of the amino nitrogen, its correlation with σ and E_N in addition to pK_a is rational. The irrelevance of log k_?1 to σ and E_N is not surprising, because σ and E_N are not a direct measure of [H⁺] of the solution. Copyright © 2011 John Wiley & Sons, Ltd.     

Kinetics and mechanism of the reaction of alkoxymethylidene malonate and malononitrile with hydrazines and anilines

The kinetics and mechanism of the nucleophilic vinylic substitution of dialkyl (alkoxymethylidene)malonates (alkyl: methyl, ethyl) and (ethoxymethylidene)malononitrile with substituted hydrazines and anilines R¹–NH₂ (R¹: (CH₃)₂N, CH₃NH, NH₂, C₆H₅NH, CH₃CONH, 4‐CH₃C₆H₄SO₂NH, 3‐ and 4‐X‐C₆H₄; X: H, 4‐Br, 4‐CH₃, 4‐CH₃O, 3‐Cl) were studied at 25 °C in methanol. It was found that the reactions with all hydrazines (the only exception was the reaction of (ethoxymethylidene)malononitrile with N,N‐dimethylhydrazine) showed overall second‐order kinetics and k_obs were linearly dependent on the hydrazine concentration which is consistent with the rate‐limiting attack of the hydrazine on the double bond of the substrate. Corresponding Brønsted plots are linear (without deviating N‐methyl and N,N‐dimethylhydrazine), and their slopes (β_Nuc) gradually increase from 0.59 to 0.71 which reflects gradually increasing order of the C–N bond formed in the transition state. The deviation of both methylated hydrazines is probably caused by the different site of nucleophilicity/basicity in these compounds (tertiary/secondary vs. primary nitrogen). A somewhat different situation was observed with the anilines (and once with N,N‐dimethylhydrazine) where parabolic dependences of the kinetics gradually changing to linear dependences as the concentration of nucleophile/base increases. The second‐order term in the nucleophile indicates the presence of a steady‐state intermediate ‐ most probably T^±. Brønsted and Hammett plots gave β_Nuc = 1.08 and ρ = ?3.7 which is consistent with a late transition state whose structure resembles T^±. Copyright © 2013 John Wiley & Sons, Ltd.     

Nitrosation of dialkylhydroxylamines,and computational and NMR investigations of the interconversion of conformational isomers of N‐nitroso‐dimethylhydroxylamine

The effect of acidity upon the rate of nitrosation of N‐benzyl,O‐methylhydroxylamine ( 3 ) in 1:1 (v/v) H₂O/MeOH at 25 °C has been investigated. The pseudo‐first‐order rate constant (k_obs) for loss of HNO₂ as the limiting reagent decreases as [H₃O⁺] increases. This is compatible with two parallel reaction channels (Scheme 2 ). One involves the direct reaction of the free hydroxylamine with HNO₂ (k₁ = 1.4 × 10² dm³ mol^?1 s^?1, 25 °C) and the other involves the reaction of the free hydroxylamine with NO⁺ (k₂ = 5.9 × 10⁹ dm³ mol^?1 s^?1). In contrast, there is only a very slight increase in k_obs with increasing [H₃O⁺] for nitrosation of N,O‐dimethylhydroxylamine ( 4 ) in dilute aqueous solution at 25 °C to give N‐nitroso‐dimethylhydroxylamine, 5 . This also fits a two‐channel mechanism (Scheme 3 ). Again, one involves the nitrosation of the free base by NO⁺ (k₂ = 8 × 10⁹ dm³ mol^?1 s^?1, 25 °C) but the other channel now involves catalysis by chloride (k₃ = 1.3 × 10⁸ dm³ mol^?1 s^?1). Arising from these results, we propose an estimate of pK_a ～ ?5 for protonated nitrous acid, (O = N? OH), which is appreciably different from the literature value of +1.7. The interconversion of cis and trans conformational isomers of 5 has been investigated by temperature‐dependent NMR spectroscopy in CDCl₃, methanol‐d₄, toluene‐d₈ and dimethyl sulfoxide‐d₆. Enthalpies and entropies of reaction and of activation have been determined and compared with computational values obtained at the B3LYP/6‐31G* level of theory. The cis form is slightly more stable at normal temperatures and no solvent effects upon the thermodynamics or kinetics of the conformational equilibrium were predicted computationally or detected experimentally. In addition, key geometric parameters and dipole moments have been calculated for the cis and trans forms, and for the lowest energy transition structure for their interconversion, in the gas phase and in chloroform. These results indicate electronic delocalisation in the ground states of 5 which is lost in the transition structure for their interconversion. Copyright © 2010 John Wiley & Sons, Ltd.     

Higher reactivity of 3‐pyridinium boronic acid compared with 3‐pyridinium boronate ion toward 4‐isopropyltropolone in acidic aqueous solution: fundamental reaction analyses for an effective organoboron‐based chemosensor

The pK_as of 3‐pyridylboronic acid and its derivatives were determined spectrophotometrically. Most of them had two pK_as assignable to the boron center and pyridine moiety. The pK_a assignment performed by ¹¹B nuclear magnetic resonance spectroscopy revealed that both boron centers in 3‐pyridylboronic acid [3‐PyB(OH)₂] and the N‐methylated derivative [3‐(N‐Me)Py⁺B(OH)₂] have strong acidities (pK_a = 4.4 for both). It was found that introduction of a substituent to pyridine‐C atom in 3‐pyridylboronic acid drastically increased the acidity of the pyridinium moiety, but decreased the acidity of the boron center, whereas the introduction to pyridine‐N atom had no influence on the acidity of the boron center. Kinetic studies on the complexation reactions of 3‐pyridinium boronic acid [3‐HPy⁺B(OH)₂] with 4‐isopropyltropolone (Hipt) carried out in strongly acidic aqueous solution indicated that the positive charge on the boronic acid influenced little on its reactivity; 3‐HPy⁺B(OH)₂ reacts with Hipt and protonated H₂ipt⁺, and its reactivity was in line with those of a series of boronic acids. Kinetics in weakly acidic aqueous solution revealed that 3‐HPy⁺B(OH)₂ reacts with Hipt faster than its conjugate boronate [3‐HPy⁺B(OH)₃^–], which is consistent with our recent results. The reactivity of 3‐(N‐Me)Py⁺B(OH)₂ towards Hipt was also examined kinetically; the reactivities of 3‐(N‐Me)Py⁺B(OH)₂ and 3‐(N‐Me)Py⁺B(OH)₃^– are almost the same as those of their original 3‐HPy⁺B(OH)₂ and 3‐HPy⁺B(OH)₃^–, respectively. Copyright © 2012 John Wiley & Sons, Ltd.     

Electrostatic interactions effect in the aminolysis of some β‐lactams in the presence of poly(ethyleneimine):structure‐reactivity

The aminolysis reaction of a series of β‐lactams in the presence of poly(ethyleneimine) (PEI) at 30°C and pH = 8.40 has been studied. The substrates investigated follow a pseudo first order rate, except two β‐lactams which show a two step consecutive reaction. Increasing the polyelectrolyte concentration, Michaelis–Menten type kinetics are been observed and for four substrates a more complex rate behaviour was verified owing to the polyelectrolyte inhibition effect. Both the binding constant K₁ between polyelelectrolyte and β‐lactam and the first order rate constant of the reactive complex decomposition k_cat were calculated. The substituent effect at C‐6′ or C‐7′ position of β‐lactam on the aminolysis rate does not correlate with the σ_I value (Taft plot). Most probably, steric and electronic effects are important, but the electrostatic ones are determining factors for the relevant acceleration attributable to both the binding phenomena and the increased reactivity of the substrate–polyelectrolyte complex. The comparison between poly(ethyleneimine) and Human Serum Albumin (HSA) is also discussed. Copyright © 2007 John Wiley & Sons, Ltd.     

Rapid and controlled transformation of nitrate in water and brine by stabilized iron nanoparticles

Highly reactive zero-valent iron (ZVI) nanoparticles stabilized with carboxymethyl cellulose (CMC) were tested for reduction of nitrate in fresh water and brine. Batch kinetic tests showed that the pseudo first-order rate constant (k _obs) with the stabilized nanoparticles was five times greater than that for non-stabilized counterparts. The stabilizer not only increased the specific surface area of the nanoparticles, but also increased the reactive particle surface. The allocation between the two reduction products, NH₄ ⁺ and N₂, can be manipulated by varying the ZVI-to-nitrate molar ratio and/or applying a Cu–Pd bimetallic catalyst. Greater CMC-to-ZVI ratios lead to faster nitrate reduction. Application of a 0.05 M HEPES buffer increased the k _obs value by 15 times compared to that without pH control. Although the presence of 6% NaCl decreased k _obs by 30%, 100% nitrate was transformed within 2 h in the saline water. The technology provides a powerful alternative for treating water with concentrated nitrate such as ion exchange brine.     

Chemistry of aryl N‐(2‐pyridyl) thionocarbamates in basic media

Three aryl N‐pyridylthionocarbamates were synthesized by thioacylation of 2‐aminopyridine and 2‐methylaminopyridine with the respective chlorothionoformates. Their hydrolysis mechanism was studied in aqueous basic media. The aryl N‐(2‐pyridyl)thionocarbamates are considerably less reactive than their oxo analogues, the aryl N‐(2‐pyridyl) carbamates, especially the N‐monosubstituted ones ( 1a ‐ b ). Absence of significant buffer catalysis, isolation of the product resulting from trapping of the unsaturated intermediate with piperidine and the entropy of activation observed for the hydrolysis of compound 1b clearly indicate an E1cB mechanism for the N‐monosubstituted aryl N‐(2‐pyridyl)thionocarbamates. The experimental data suggest that the N,N‐disubstituted substrate ( 2 ) undergoes basic hydrolysis by a general base catalysed B_AC2 mechanism. Copyright © 2008 John Wiley & Sons, Ltd.     

Kinetics study of a Diels‐Alder reaction in mixtures of an ionic liquid with molecular solvents

The second‐order rate constants for cycloaddition reaction of cyclopentadiene with naphthoquinone were determined spectrophotometrically in various compositions of 1‐(1‐butyl)‐3‐methylimidazolium terafluoroborate ([bmim]BF₄) with water and methanol at 25 °C. Rate constants of the reaction in pure solvents are in the order of water > [bmim]BF₄ > methanol. Rate constants of the reaction decrease sharply with mole fraction of the ionic liquid in aqueous solutions and increase slightly to a maximum in alcoholic mixtures. Multi‐parameter correlation of logk₂ versus solute–solvent interaction parameters demonstrated that solvophobicity parameter (Sp), hydrogen‐bond donor acidity (α) and hydrogen‐bond acceptor basicity (β) of media are the main factors influencing the reaction rate constant. The proposed three‐parameter model shows that the reaction rate constant increases with Sp, α and β parameters. Copyright © 2008 John Wiley & Sons, Ltd.     

Anilinolysis of O‐butyl phenyl phosphonochloridothioate in acetonitrile: Synthesis,characterization, kinetic study,and reaction mechanism

This paper describes a simple optimized method for the synthesis of O‐butyl phenyl phosphonochloridothioate ( 4 ) under mild conditions. The target compounds were characterized by ¹H‐nuclear magnetic resonance (NMR), ¹³C‐NMR, and ³¹P‐NMR spectroscopy, as well as mass spectroscopy. The apparent structure of 4 was confirmed by optimization using the B3LYP/6‐311 + G(d,p) level in the Gaussian 09 program in acetonitrile. The nucleophilic substitution reactions of 4 with X‐anilines (XC₆H₄NH₂) and deuterated X‐anilines (XC₆H₄ND₂) were investigated kinetically in acetonitrile at 55.0°C. The free energy relationship with X in the anilines looked biphasic concave upwards with a break region between X = H and X = 3‐MeO, giving large negative ρ_X and small positive β_X values. The deuterium kinetic isotope effects were secondary inverse (k_H/k_D < 1: 0.789‐0.995) and the magnitudes, (k_H/k_D), increased when the nucleophiles were changed from weakly basic to strongly basic anilines. A concerted S_N2 mechanism is proposed on the basis of the selectivity parameters and the variation trend of the deuterium kinetic isotope effects with X.     

Inclusion complexes of estrone and estradiol with β‐cyclodextrin: Voltammetric and HPLC studies

The interaction of estrone and estradiol with β‐cyclodextrins (βCD) was investigated by differential pulse voltammetry (DPV) and high‐performance liquid chromatography (HPLC) in mixed media. The co‐solvent influence on the tendency of these estrogens to form inclusion complexes with βCD was examined. Thus, acetonitrile (MeCN) and ethanol (EtOH) were used in a mixed aqueous medium containing phosphate buffer. The association constant of the inclusion complexes (K_a) of estrone and estradiol with βCD were determined in two different media by using both voltammetric and chromatographic techniques. Estradiol was found to bind to βCD with higher affinities than estrone, irrespective of the medium. We have also found a clear influence of the co‐solvent on the K_a value, which means a competition of co‐solvent molecules with estrogens for binding to the cavity of βCD. Consequently, interaction between βCD and the steroids is weakened when acetonitrile is used. Copyright © 2007 John Wiley & Sons, Ltd.     

Kinetic study of the formation of N‐chloro compounds using N‐chlorosuccinimide

Second‐order rate constants were determined for the chlorination reaction of 2,2,2‐trifluoethylamine and benzylamine with N‐chlorosuccinimide at 25 °C and an ionic strength of 0.5 M. These reactions were found to be of first order in both reagents. According to the experimental results, a mechanism reaction was proposed in which a chlorine atom is transferred between both nitrogenous compounds. Kinetics studies demonstrate that the hydrolysis process of the chlorinating agent does not interfere in the chlorination process, under the experimental conditions used in the present work. Free‐energy relationships were established using the results obtained in the present work and others available in the literature for chlorination reactions with N‐chlorosuccinimide, being the pK_a range included between 5.7 and 11.22. Copyright © 2014 John Wiley & Sons, Ltd.     

Transition from concerted to stepwise processes as a function of leaving group ability: density functional theory and experimental study of lyoxide‐promoted cleavages of phosphorothioate and phosphate triesters in water and methanol

The base‐promoted solvolysis of a series of O,O‐dimethyl O‐aryl and O,O‐dimethyl O‐alkyl phosphorothioates (1) as well as O,O‐dimethyl O‐aryl and O,O‐dimethyl O‐alkyl phosphates (2) was studied computationally by density functional theory methods in methanol and water continuum media to determine the transition between concerted and stepwise processes. In addition, an experimental study was undertaken on the solvolysis of these series in basic methanol and water. The computations indicate that the solvolytic mechanism for series 1 involves lyoxide attack anti to the leaving group in a concerted manner with good leaving groups having pK_a^Lg values < 12.3 in methanol and in a stepwise fashion with the formation of a 5‐coordinate thiophosphorane intermediate when the pK_a^Lg > 12.3. A similar transition from concerted to stepwise mechanism occurs with series 2 in methanol as well as with series 1 and 2 in water, although for the aqueous solvolyses with hydroxide nucleophile, the transitions between concerted and stepwise mechanisms occur with better leaving groups than in the case in methanol. The computational data allow the construction of Brønsted plots of log k₂^?OS versus pK_a^Lg in methanol and water, which are compared with the experimental Brønsted plots determined with these series previously and with new data determined in this work. Both the computational and experimental Brønsted data reveal discontinuities in the plots between substrates bearing O‐aryl and O‐alkyl leaving groups, with the gradients of the plots being far steeper than, and non‐collinear with, the O‐aryl leaving groups for solvolysis of the O‐alkyl‐containing substrates. These discontinuities signify that care should be exercised in interpreting breaks in Brønsted plots in terms of changes in rate‐limiting steps that signify the formation of an intermediate during a solvolytic process. Copyright © 2011 John Wiley & Sons, Ltd.     

Nucleophilic substitution reactions promoted by oligoethylene glycols: a mechanistic study of ion‐pair SN2 processes facilitated by Lewis base

We present a mechanistic study for nucleophilic substitution (S_N2) reactions facilitated by multifunctional n‐oligoethylene glycols (n‐oligoEGs) using alkali metal salts MX (M⁺ = Cs⁺, K⁺, X^– = F^–, Br^–, I^–, CN^–) as nucleophilic agents. Density functional theory method is employed to elucidate the underlying mechanism of the S_N2 reaction. We found that the nucleophiles react as ion pairs, whose metal cation is ‘coordinated’ by the oxygen atoms in oligoEGs acting as Lewis base to reduce the unfavorable electrostatic effects of M⁺ on X^–. The two terminal hydroxyl (?OH) function as ‘anchors’ to collect the nucleophile and the substrate in an ideal configuration for the reaction. Calculated barriers of the reactions are in excellent agreement with all experimentally observed trends of S_N2 yields obtained by using various metal cations, nucleophiles and oligoEGs. The reaction barriers are calculated to decrease from triEG to pentaEG, in agreement with the experimentally observed order of efficiency (triEG < tetraEG < pentaEG). The observed relative efficiency of the metal cations Cs⁺ versus K⁺ is also nicely demonstrated (larger [better] barrier [efficiency] for Cs⁺ than for K⁺). We also examine the effects of the nucleophiles (F^–, Br^–, I^–, CN^–), finding that the magnitudes of reaction barriers are F^– > CN^– > Br^– > I^–, elucidating the observation that the yield was lowest for F^–. It is suggested that the role of oxygen atoms in the promoters is equivalent to that of –OH group in bulky alcohols (tert‐butyl or amyl‐alcohol) for S_N2 fluorination reactions previously studied in our lab. Copyright © 2012 John Wiley & Sons, Ltd.     

A deep insight into the mechanism of the acid‐catalyzed rearrangement of the Z‐phenylhydrazone of 5‐amino‐3‐benzoyl‐1,2,4‐oxadiazole in a non‐polar solvent

The conversion of the Z‐phenylhydrazone of 5‐amino‐3‐benzoyl‐1,2,4‐oxadiazole ( 1a ) into the relevant 1,2,3‐triazole ( 2a) has been quantitatively studied in toluene in the presence of several halogenoacetic acids ( HAA s, 3a – h ). Again, the occurrence of two reaction pathways has been pointed out: they require one or two moles of acid, respectively, thus repeating the situation previously observed in the presence of trichloroacetic acid. The observed rate constant ratios (k_III/k_II) are only slightly affected by the nature of the acid used. To gain a deeper insight into the action of the acids used we have measured the association constants of the HAA s ( 3a – h) with 4‐nitroaniline ( 4 ) in toluene. Also in this case, the formation of two complexes requiring one (K₂) or two (K₃) moles of acid has been evidenced, but now the K₃/K₂ ratios are significantly affected by the strength of the acid examined. The variation of the K₃/K₂ ratios larger than those concerning the k_III/k_II ratios appears useful to enlighten the very nature of the acid‐catalyzed pathways in toluene, which has been elucidated also carrying out the rearrangement in the presence of mixtures of tribromo‐ and trichloro‐acetic acids at different concentrations. Copyright © 2010 John Wiley & Sons, Ltd.