Browsing by Author "Contreras, Renato"
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Item Activation of Electrophile/Nucleophile Pair by a Nucleophilic and Electrophilic Solvation in a SNAr Reaction(2018) Sánchez, Bruno; Calderon, Cristian; Tapia, Ricardo A.; Contreras, Renato; Campodónico, PaolaNucleophilic aromatic substitution reactions of 4-chloroquinazoline toward aniline and hydrazine were used as a model system to experimentally show that a substrate bearing heteroatoms on the aromatic ring as substituent is able to establish intramolecular hydrogen bond which may be activated by the reaction media and/or the nature of the nucleophile.Item Are Electrophilicity and Electrofugality Related Concepts? A Density Functional Theory Study(2011) Ormazábal-Toledo, Rodrigo; Campodónico, Paola; Contreras, RenatoIt is proposed that the electrofugality of a fragment within a molecule is determined by its group nucleophilicity. The variation of electrofugality should be tightly related to the electron releasing ability of the substituent attached to the electrofuge moiety. This contribution closes the set of relationships between philicity and fugality quantities: while nucleofugality appears related to the group electrophilicity of the leaving group, electrofugality is related to the group nucleophilicity of the permanent group.Item Changes in the SNAr reaction mechanism brought about by preferential solvation(Royal Society of Chemistry, 2015) Alarcón-Espósito, Jazmín; Tapia, Ricardo; Contreras, Renato; Campodónico, PaolaWe herein report an experimental and theoretical study on preferential solvation effects for the reactions of 1-fluoro and 1-chloro-2,4-dinitrobenzene towards morpholine in acetonitrile, water and mixtures of them of varying compositions. A detailed kinetic study opens the possibility of analyzing preferential solvation and reaction rates. The kinetic study was complemented with an exploration of the potential energy surface in order to analyze the nature of the molecular interactions. For the fluorine derivative, this analysis reveals that the solvation of the TS in the mode TS1F-water/MeCN clearly outweighs the solvation of TS1F-MeCN/water, thereby suggesting that there is preferential solvation in favor of the aqueous phase.Item Effect of the nature of the nucleophile and solvent on an SNAr reaction(2018) Gazitúa, Marcela; Tapia, Ricardo A.; Contreras, Renato; Campodónico, PaolaThe reaction of 2,4-dinitrobenzenesulfonyl chloride toward propylamine was kinetically evaluated in 19 organic solvents and 10 ionic liquids as reaction media. This study was compared with a previous study to experimentally show that solvent effects and the nature of the reacting pair drastically affect the reaction rate and the reaction mechanism. While the reaction of the reference electrophile 2,4-dinitrobenzenesulfonyl chloride with piperidine is favored in polar solvents with the ability to donate or accept hydrogen bonds, the reaction with propylamine is favored in solvents with the ability to accept hydrogen bonds.Item Gutmann's Donor Numbers Correctly Assess the Effect of the Solvent on the Kinetics of SN Ar Reactions in Ionic Liquids(2016) Alarcón-Espósito, Jazmín; Contreras, Renato; Tapia, Ricardo A; Campodónico, PaolaWe report an experimental study on the effect of solvents on the model SN Ar reaction between 1-chloro-2,4-dinitrobenzene and morpholine in a series of pure ionic liquids (IL). A significant catalytic effect is observed with reference to the same reaction run in water, acetonitrile, and other conventional solvents. The series of IL considered include the anions, NTf2 (-) , DCN(-) , SCN(-) , CF3 SO3 (-) , PF6 (-) , and FAP(-) with the series of cations 1-butyl-3-methyl-imidazolium ([BMIM](+) ), 1-ethyl-3-methyl-imidazolium ([EMIM](+) ), 1-butyl-2,3-dimethyl-imidazolium ([BM2 IM](+) ), and 1-butyl-1-methyl-pyrrolidinium ([BMPyr](+) ). The observed solvent effects can be attributed to an "anion effect". The anion effect appears related to the anion size (polarizability) and their hydrogen-bonding (HB) abilities to the substrate. These results have been confirmed by performing a comparison of the rate constants with Gutmann's donicity numbers (DNs). The good correlation between rate constants and DN emphasizes the major role of charge transfer from the anion to the substrate.Item Gutmann´s Donor and Acceptor Numbers for ionic liquids and deep eutectic solvents(2022) Sánchez, Bruno; Campodónico, Paola; Contreras, RenatoAn experimental and computational methodology for the analysis of the Lewis acid/base responses of ionic liquids (IL) and deep eutectic solvents (DES) is proposed. It is based on the donor and acceptor of electronic charge ability of Lewis acid and bases concepts (donicity and acceptor numbers, DN and AN, respectively) proposed by Viktor Gutmann. The enthalpy of interaction between the IL/DES with the probe antimony pentachloride (SbCl5) in dichloroethane displays good correlations with experimental data. This approach could serve as a first approximation to predict the responses to H-Bonding abilities of new IL or DES. Although useful, the problems encountered to model the electron AN of these solvents limit the usefulness of the approach to completely describe their polarity properties. The experimental data were recorded using UV-Vis spectroscopy for a wide range of IL and a couple of DES. Two reactions were used as benchmarks to test the reliability of the DN model to discuss the reactivity of real systems in these neoteric solvents.Item Hydrogen bond contribution to preferential solvation in SNAr reactions(ACS Publications, 2013) Ormazábal-Toledo, Rodrigo; Santos, Jose; Ríos, Paulina; Castro, Enrique; Campodónico, Paola; Contreras, RenatoPreferential 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.Item Iso-solvation effects in mixtures of ionic liquids on the kinetics of a model SNAr reaction(2017) Alarcón-Espósito, Jazmín; Contreras, Renato; Campodónico, PaolaThe SNAr reaction between 1-chloro-2,4-dinitrobenzene and morpholine was used as a model system to study solvation effects in a series of mixtures involving imidazolium based ionic liquids. Iso-solvation regimes (i.e. a solvent composition regime where the solute is being solvated by approximately the same number of different solvent molecules in the mixture) are reported for the first time in ionic liquid mixtures, for 4 mixtures including [EMIM][SCN][DCN], [BMIM][DCN][BF4], [BMIM][BF4][PF6] and [BMIM][PF6][FAP]. The results show that for significant changes in composition, the rate coefficients remain approximately constant. An additional interesting result is that the mixture [BMIM][BF4][PF6] (in the proportion of 0.9 for the molar fraction of BMIMBF4) shows a slightly better kinetic performance as compared to pure BMIMBF4 and BMIMPF6. Finally, for the [EMIM][SCN][DCN] mixture, an increasing proportion of EMIMSCN with respect to EMIMDCN results in a decrease in the rate coefficient within the range of {0.1–0.75} for the molar fraction of EMIMSCN. This result may be traced to competition between the anions [SCN] and [DCN] towards the reaction center driven by the basicity of the reaction medium.Item Kinetic and theoretical study on nucleofugality in the phenolysis of 3-nitrophenyl and 4-nitrophenyl 4-cyanophenyl thionocarbonates(Elsevier, 2013) Castro, Enrique; Cañete, Alvaro; Campodónico, Paola; Cepeda, Marjorie; Pavez, Paulina; Contreras, Renato; Santos, JoseThe phenolysis of 3-nitrophenyl 4-cyanophenyl thionocarbonate (1) and 4-nitrophenyl 4-cyanophenyl thionocarbonate (2) are subjected to a kinetic investigation in order to evaluate the nucleofugality of the corresponding leaving groups. For the reaction of 2 only 4-nitrophenoxide is obtained as leaving group. For the reaction of 1 the nucleofugality ratio 3-nitrophenoxide/4-cyanophenoxide is 1/3 from the corresponding T− intermediate. Theoretical calculations confirm the experimental results. From these results it can be concluded that the non-leaving group affects the nucleofugality ratio.Item Lewis Acidity/Basicity Changes in Imidazolium Based Ionic Liquids Brought About by Impurities(American Chemical Society, 2015) Gazitúa, Marcela; Fuentealba, Patricio; Contreras, Renato; Ormazábal-Toledo, RodrigoWe herein report on the effect that water molecules, present as impurities, in the vicinity of an ionic liquid model structure, may induce on the Lewis acidity/basicity patterns normally observed in these materials. Depending on the position and orientation of water, the Lewis acidity/basicity pattern changes from “normal distribution” (i.e., the basicity located at the anion moiety and the acidity located at the cation fragment) to “bifunctional distribution” (i.e., the acidity and basicity located at the cation moiety). In some specific cases, there appears a third Lewis acidity/basicity distribution, where water may bind both the cation and the anion of the ion pair; a response we tentatively call “amphoteric”. These effects are clearly traced to the hydrogen bond formation ability of water to coordinate different regions of pure ionic liquids taken as references.Item Mechanism for the SNAr reaction of atrazine with endogenous thiols: experimental and theoretical study(Royal Society of Chemistry, 2017) Calfuman, Karla; Gallardo, Sebastian; Contreras, Renato; Tapia, Ricardo; Campodónico, PaolaReaction mechanism in aromatic nucleophilic substitution reactions is discussed using kinetic study complemented with quantum chemical calculations. The model system is the reaction of a series of biothiols toward atrazine (ATZ) in aqueous media. The proposed reaction mechanism discloses a non-catalyzed pathway and the presence of a deprotonated (thiolate) nucleophile in water suggests that the reaction mechanism is borderline between a stepwise route and a concerted process. The full analysis of the potential energy surface reinforces the addition/elimination mechanism. Despite of numerous attempts to locate transition structures associated with the leaving group departure were unsuccessful, presumably because this step is extremely fast.Item Mechanistic pathways of aromatic nucleophilic substitution in conventional solvents and ionic liquids(Royal Society of Chemistry, 2014) Gazitúa, Marcela; Tapia, Ricardo; Contreras, Renato; Campodónico, PaolaSolvation effects on the reaction mechanism of the title reactions have been kinetically evaluated in 21 conventional solvents and 17 ionic liquids. Solvent polarity affects the catalyzed and non-catalyzed SNAr pathways differently. The ambiphilic character of water and formamide, which act as a hydrogen bond donor/acceptor, induces nucleophilic activation at the nitrogen center of the nucleophile. The ionic liquid EMIMDCN appears to be the best solvent for the SNAr route probably due to the high polarizability of the dicyanamide anion.Item Permanent group effect on nucleofugality in aryl benzoates(2010) Campodónico, Paola; Ormazábal-Toledo, Rodrigo; Aizman, Arie; Contreras, RenatoWe herein report on the group electrophilicity of molecular fragments present in the title compounds to describe leaving group abilities in reactions of aryl benzoates toward CN. It is found that the presence of electron-withdrawing substituents in the permanent group enhances its electrophilicity, thereby contributing to the stabilization of the tetrahedral intermediate involved in the stepwise pathway. On the other hand electron-releasing substituents attached to the permanent group enhance the nucleofugality of the leaving groups in these systems. Substituent effects are used to rationalize the activation/deactivation patterns induced by electron-withdrawing and electron-releasing groups at the aromatic rings.Item Predicting the reaction mechanism of nucleophilic substitutions at carbonyl and thiocarbonyl centres of esters and thioesters(John Wiley & Sons, 2012) Ormazábal-Toledo, Rodrigo; Castro, Enrique; Santos, Jose; Millan, Daniela; Cañete, Alvaro; Contreras, Renato; Campodónico, PaolaIn nucleophilic substitution reactions at carbonyl centres, there are two possible channels. The first one occurs when the attack of nucleophilic agents takes place simultaneously with the departure of the nucleofuge. This process is named as concerted. The second possibility is the formation of a reaction intermediate, typically a tetrahedral intermediate from which the nucleofuge departs after passing through a second transition state. This second mechanism is defined as stepwise. Whether a concerted or stepwise mechanism is to be expected for a given reaction depends on several factors. Among these determinants are the nucleophilicity of the attacking group, the leaving group ability of the nucleofuge, and the solvent, which affects both the stability of the intermediate or the transition states involved. The role of the electrophilic centre can however become an important factor that can determine the reaction mechanism. In this work we show that the group nucleophilic Fukui function model may be used to rationalize and to predict the reaction mechanism of the title compounds towards alicyclic amines. In general, when the electrophilic carbon centre is attached to the soft sulfur atom, the reaction mechanism is predicted to follow a stepwise route. When the electrophilic carbon atom is attached to a harder oxygen centre, the reaction mechanism is determined by chemical substitution at the nucleofuge moiety. Experimental verification for a set of four substrates is presented.Item Reactivity indices profile: a companion tool of the potential energy surface for the analysis of reaction mechanisms. Nucleophilic aromatic substitution reactions as test case(American Chemical Society, 2013) Ormazábal-Toledo, Rodrigo; Contreras, Renato; Campodónico, PaolaWe herein report on the usefulness of the reactivity indices profiles along a reaction coordinate. The model is tested to fully describe the reaction mechanism of the title reactions. Group nucleophilicity and electrophilicity profiles help describe the bond-breaking/bond-formation processes and the intramolecular electron density reorganization. The reactivity indices’ profile analysis is consistently complemented with hydrogen bonding (HB) effects along the reaction coordinate: the final outcome of the reaction is determined by the stage at which the HB complex can be formed. Transition-state structures located for six reactions studied, including the charged nucleophile thiocyanate, show that the main stabilizing interaction is that formed between the hydrogen atom of the nucleophile and the o-NO2 group. This result discards the role of HB interaction between the nucleophile and the leaving group previously proposed in the literature.Item Reactivity of benzohydrazide derivatives towards acetylation reaction. Experimental and theoretical studies(2010) Campodónico, Paola; Aliaga, Margarita E.; Santos, José G.; Castro, Enrique A.; Contreras, RenatoWe herein report an experimental and theoretical study on the acetylation reaction of benzohydrazide derivatives towards p-nitrophenyl acetate (NPA). The kinetic data are consistent with a stepwise mechanism with the nucleophilic attack as the rate determining step. From the theoretical analysis it is found that benzohydrazide derivatives establish intramolecular proton rearrangement. The enol form appears as the active species for nucleophilic attack. A reaction mechanism incorporating keto-enol pre-equilibria is proposed. The study is completed with a local reactivity analysis describing the most reactive centers for nucleophilic attack together with a site activation analysis describing inductive substituent effectItem Site activation effects promoted by intramolecular hydrogen bond interactions in SNAr reactions(Royal Society of Chemistry, 2014) Gallardo-Fuentes, Sebastián; Tapia, Ricardo; Campodónico, Paola; Contreras, RenatoThe nucleophilic aromatic substitution reaction of benzohydrazide derivatives towards 2-chloro-5-nitropyrimidine is used as model system to experimentally and theoretically show that intramolecular hydrogen-bond formation operates as a perturbation that elicits a dual response at the reaction center of the transition state (TS) structure, by enhancing the electrophilicity of the pyrimidine moiety and the nucleophilicity of the nitrogen atom of the benzohydrazide fragment. The electronic mechanism can therefore be described as a (non-local) site activation problem.Item Specific nucleophile–electrophile interactions in nucleophilic aromatic substitutions(Royal Society of Chemistry, 2013) Ormazábal-Toledo, Rodrigo; Contreras, Renato; Tapia, Ricardo; Campodónico, PaolaWe herein report results obtained from an integrated experimental and theoretical study on aromatic nucleophilic substitution (S(N)Ar) reactions of a series of amines towards 1-fluoro-2,4-dinitrobenzene in water. Specific nucleophile-electrophile interactions in the title reactions have been kinetically evaluated. The whole series undergoes S(N)Ar reactions where the formation of the Meisenheimer complex is rate determining. Theoretical studies concerning specific interactions are discussed in detail. It is found that H-bonding effects along the intrinsic reaction coordinate profile promote the activation of both the electrophile and the nucleophile. Using these results, it is possible to establish a hierarchy of reactivity that is in agreement with the experimental data. Second order energy perturbation energy analysis highlights the strong interaction between the ortho-nitro group and the acidic hydrogen atom of the amine. The present study strongly suggests that any theoretical analysis must be performed at the activated transition state structure, because the static model developed around the reactant states hides most of the relevant specific interactions that characterize the aromatic substitution process.Item Surfactant-mediated enzymatic superactivity in water/ionic liquid mixtures, evaluated on a model hydrolytic reaction catalyzed by α-chymotrypsin(Elsevier B.V., 2019-06) Calderón, Cristian; Contreras, Renato; Campodónico, PaolaIn this work, the influence of the C12-, C14-, and C16-alkyl chain derivatives of 1-alkyl-3-methyl-imidazole tetrafluoroborate over the hydrolisis of p-nitrophenyl trimethylacetate catalyzed by α-chymotrypsin was studied in water and water - ionic liquids mixtures. The ionic liquid used is 1-butyl-3-methyl-imidazole tetrafluoroborate (BMIMBF4). 1-alkyl-3-methylimidazole tetrafluoroborate derived surfactants can increase the catalytic efficiency of α-chymotrypsin on the hydrolysis of p-nitrophenyl trimethylacetate. This effect is negatively affected by the decrease on the surfactant's critical micelle concentration (CMC) and the partition of the substrate between the micelles and the external media observed above the critical miscellar concentration (CMC). In water/BMIMBF4 mixtures, the presence of the ionic liquid (IL), render the C14 and C16 surfactants insoluble, and overrides the effect elicited by the C12 alkyl chain surfactant on the activity of α-chymotrypsin. The loss of the surfactants influence on the enzymatic activity due to the presence of BMIMBF4 seems to be a complex process, controlled by a decreased affinity between α-chymotrypsin and the surfactant molecules and, to a larger extent, the appearance of an “acquired resistance” of the enzyme to the influence of the surfactants, related to a more compact and resilient conformation of the protein in the presence of BMIMBF4. The influence of BMIMBF4 is not only limited to the surfactant/enzyme interaction, but also it does modifies the partition of the substrate between the aqueous media and the micellar environment.