Enrique A. Castro

Kinetics and mechanism of the aminolysis of thioesters and thiocarbonates in solution

The aminolysis reactions of thioesters and thiocarbonates, in either aqueous solution or in 44 wt % aqueous ethanol at 25 °C, are subjected to a kinetic investigation. The Brønsted-type plots (lg kN vs. amine pKa, where kN is the nucleophilic rate constant) obtained for these reactions can be grouped in three categories: linear plots with slopes 0.8-1, biphasic plots (two linear portions and a curve in between), and linear plots with slopes 0.4-0.6. The two former plots are attributed to stepwise reactions through a zwitterionic tetrahedral intermediate. The latter plots are associated with a concerted mechanism. The fact that some reactions are stepwise and others concerted depends on the stability of the zwitterionic tetrahedral intermediate. This work shows how the experimental data allows one to assess the mechanism of these reactions. Also discussed are the factors that affect the stability of this intermediate, which in turn determines the pathway followed by the reaction. The factors analyzed in this work are (i) the leaving group of the substrate, (ii) the nature of the amine, (iii) the non-leaving group of the substrate, (iv) the electrophilic group of the substrate (CS vs. CO), and (v) the solvent.

Experimental and theoretical studies on the nucleofugality patterns in the aminolysis and phenolysis of S-aryl O-aryl thiocarbonates.

The reactions of S-phenyl, S-(4-chlorophenyl), and S-(2,3,4,5,6-pentafluorophenyl) 4-nitrophenyl thiocarbonates (9, 11, and 16, respectively) with a series of secondary alicyclic (SA) amines and those of S-(4-methylphenyl) 4-nitrophenyl thiocarbonate (8) and compounds 9 and 11 with a series of phenols are subjected to a kinetic investigation in 44 wt % ethanol-water, at 25.0 degrees C and an ionic strength of 0.2 M. The reactions were followed spectrophotometrically. Under nucleophile excess, pseudo-first-order rate coefficients (k(obsd)) were found. For all these reactions, plots of k(obsd) vs. free amine or phenoxide anion 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 nucleophiles) for the aminolysis of 9, 11, and 16 are linear with slopes beta = 0.85, 0.90, and 0.67, respectively. The two former slopes are consistent with a stepwise mechanism, through a zwitterionic tetrahedral intermediate, which breaking to products is rate determining. The latter beta value is consistent with a concerted mechanism. The Brønsted-type plots for the phenolysis of thiocarbonates 8, 9, and 11 are linear with slopes beta = 0.62, 0.70, and 0.69, respectively. These beta values and the absence of curvature at pK(a) = 7.5 confirm a concerted mechanism. In all these reactions, except those of 16, the main nucleofuge is 4-nitrophenoxide, being the thio benzenethiolate the minor nucleofuge. For the reactions of thiocarbonate 16 the main nucleofuge is pentafluorobenzenethiolate whereas little 4-nitrophenoxide was found. The reactions of two SA amines with S-(3-chlorophenyl) 4-nitrophenyl thiocarbonate (10) were subjected to product analysis, showing 60% 4-nitrophenoxide and 40% 3-chlorobenzenethiolate. The study is completed with a theoretical analysis based on the group electrophilicity index, a reactivity descriptor that may be taken as a measure of the ability of a group or fragment to depart from a molecule with the bonding electron pair. The theoretical analysis is in accordance with the experimental results obtained and predicts relative nucleofugalities of O-aryl vs. S-aryl groups in a series of diaryl thiocarbonates not experimentally evaluated to date.

Concerted Pyridinolysis of Aryl 2,4,6-Trinitrophenyl Carbonates

The Brønsted plots for the title reactions are linear with slopes of 0.53-0.56. The magnitude of the slopes and the fact that there are no breaks at the predicted pK(a) for stepwise mechanisms indicate that these reactions are concerted. This finding is in great contrast to the stepwise mechanisms found for the pyridinolysis of other carbonates. The concerted mechanism is attributed to the fact that the title carbonates possess two O-aryl groups, one of them being an exceptionally good nucleofuge.

Kinetics and mechanisms of reactions of thiol, thiono and dithio analogues of carboxylic esters with nucleophiles. An update

The objective of this review is to update a previous one (published in 1999) on the kinetics and mechanism of the reactions of thioesters, thiocarbonates and analogous thiocarbonyl derivatives with different nucleophiles in solution. There has been abundant literature on this topic since 1999 and it is of interest to chemists and biochemists to have a comprehensive view on the recent developments on the title reactions. Most of these occur through a tetrahedral intermediate, usually in steady state condition, whose breakdown generally leads to the final products (stepwise reactions). Nevertheless, depending on the stability of the tetrahedral intermediate, some reactions take place in one step (concerted mechanism). This review also discusses the factors that affect the stability of this intermediate, which in turn determines the pathway followed by the reaction.

Mechanisms of Degradation of Paraoxon in Different Ionic Liquids

Herein, the reactivity and selectivity of the reaction of O,O-diethyl 4-nitrophenyl phosphate triester (Paraxon, 1) with piperidine in ionic liquids (ILs), three conventional organic solvents (COS), and water is studied by (31)P NMR, UV-vis, and GC/MS. Three phosphorylated products are identified as follows: O,O-diethyl piperidinophosphate diester (2), O,O-diethyl phosphate (3), and O-ethyl 4-nitrophenyl phosphate diester (4). Compound 4 also reacts with piperidine to yield O-ethyl piperidinophosphate monoester (5). The results show that both the rate and products distribution of this reaction depend on peculiar features of ILs as reaction media and the polarity of COS.

Concerted mechanisms of the reactions of methyl aryl carbonates with substituted phenoxide ions.

The reactions of 4-nitrophenyl, 2,4-dinitrophenyl, and 2,4,6-trinitrophenyl methyl carbonates (NPC, DNPC, and TNPC, respectively) with substituted phenoxide ions are subjected to a kinetic study in water at 25.0 degrees C, ionic strength 0.2 M (KCl). Production of the leaving groups (the nitro derivatives) is followed spectrophotometrically. Under excess of the phenoxide ions pseudo-first-order rate coefficients (k(obsd)) are found throughout. Plots of k(obsd) vs substituted phenoxide concentration at constant pH are linear, with the slope (k(N)) independent of pH. The Brönsted-type plots (log k(N) vs pK(a) of the phenols) are linear with slopes beta = 0.67, 0.48, and 0.52 for the phenolysis of NPC, DNPC, and TNPC, respectively. The magnitudes of these Brönsted slopes are consistent with a concerted mechanism. In the particular case of the phenolysis of NPC the expected hypothetical curvature center of the Brönsted plot for a stepwise mechanism should be pK(a)(0) = 7.1 (the pK(a) of 4-nitrophenol). This curvature does not appear within the pK(a) range of the substituted phenols studied (5.3--10.3), indicating that these reactions are concerted. The phenolysis of DNPC and TNPC should also be concerted in view of the even more unstable tetrahedral intermediates that would be formed if the reactions were stepwise. The reactions of the same substrates with pyridines are stepwise, which means that substitution of a pyridine moiety in a tetrahedral intermediate by a phenoxy group destabilizes the intermediate perhaps to the point of nonexistence. The k(N) values for the title reactions are larger than those for the concerted phenolysis of the corresponding ethyl S-aryl thiolcarbonates. The k(N) values found in the present reactions are subjected to a dual regression analysis as a function of the pK(a), of both the nucleophile and leaving group, the coefficients being beta(N) = 0.5 and beta(lg) = -0.3, respectively. These coefficients are consistent with a concerted mechanism.

Hydrogen Bond Contribution to Preferential Solvation in SNAr Reactions

Preferential solvation in aromatic nucleophilic substitution reactions is discussed using a kinetic study complemented with quantum chemical calculations. The model system is the reaction of a series of secondary alicyclic amines toward phenyl 2,4,6-trinitrophenyl ether in aqueous ethanol mixtures of different compositions. From solvent effect studies, it is found that only piperidine is sensitive to solvation effects, a result that may be traced to the polarity of the solvent composition in the ethanol/water mixture, which points to a specific electrophilic solvation in the aqueous phase.

Concerted mechanism of the reactions of 2,4-dinitrophenyl 4-cyanobenzoate with secondary alicyclic amines in aqueous ethanol

The title reactions are subjected to a kinetic analysis in 44 wt% ethanol-water, at 25.0°C, ionic strength 0.2 (KCl). With a large excess of amine over the substrate, pseudo-first-order rate coefficients (kobs) are obtained, which are linearly dependent on the amine concentration. The nucleophilic rate constants (kN) are determined from plots of kobs vs. amine concentration. The Bronsted-type plot obtained with the kN values is linear, with slope β=0.63. The magnitude of this slope suggests that the mechanism is concerted, as opposed to a stepwise process with rate-determining breakdown of a zwitterionic tetrahedral intermediate (T±), in which the value of β is usually 0.8–1.0. The pyridinolysis of the same substrate in the same solvent is stepwise with the breakdown of T± as the rate-determining step. The change to a concerted mechanism for the title reactions is attributed to the superior nucleofugality of the alicyclic amines, compared to the isobasic pyridines, which destabilizes kinetically the “intermediate” T± in such a way that it does not exist, and the mechanism becomes enforced concerted.

The kinetics of hydrolysis of methyl and phenyl lsocyanates

The hydrolysis of phenyl isocyanate is subject to general base catalysis by tertiary amines and the point for water falls on the Bronsted plot, which indicates that the uncatalysed reaction involves two molecules of water, one acting as a nucleophile and the other as a general base. The rather small solvent isotope effect, kwH2O/kwD2O= 1.65, and the proton inventory, are discussed. The hydrolysis of methyl isocyanate (unlike phenyl isocyanate) is acid- catalysed, probably proceeding with pre-equilibrium protonation. Methyl isocyanate reacts with hydrogenphosphate dianion and with hydrogensulphate ion, forming mixed anhydride species. The formal reaction with hydrogensulphate ion may proceed by pre-equilibrium protonation followed by nucleophilic attack by sulphate ion.

Kinetics of reaction of substituted pyridines and oxygen anions with methyl chloroformate in aqueous solution

The rate constants for nucleophilic reaction of nine substituted pyridines with methyl chloroformate gives a sharply curved Bronsted plot, the slope changing from β 0.93 to 0.15 with increasing reactivity. This contrasts with the straight line (β 0.93) observed with p-nitrophenyl acetate, and is shown to be quantitatively consistent with a change in rate-determining step. It is argued that this is from breakdown to formation of a zwitterionic tetrahedral intermediate which is only just stable enough to exist. The hydrolytic stabilities of some of the methoxycarbonylpyridinium ions produced by this reaction, and the nucleophilic reactivities towards methyl cloroformate of imidazole, of phenolate, p-nitrophenolate, and acetate anions, and of phosphate dianion are reported and discussed.