Computational mechanistic study of thionation of carbonyl compounds with Lawesson's reagent

The thionation reaction of carbonyl compounds with Lawesson's reagent (LR) has been studied using density functional theory methods and topological analyses. After dissociation of LR, the reaction takes place through a two-step mechanism involving (i) a concerted cycloaddition between one monomer and the carbonyl compound to form a four-membered intermediate and (ii) a cycloreversion leading to the thiocarbonyl derivative and phenyl(thioxo)phosphine oxide. Topological analyses confirmed the concertedness and asynchronicity of the process. The second step is the rate-limiting one, and the whole process resembles the currently accepted mechanism for the lithium salt-free Wittig reaction. No zwitterionic intermediates are formed during the reaction, although stabilizing electrostatic interactions are present in initial stages. Phenyl(thioxo)phosphine oxide formed in the thionation reaction is capable of performing a second thionation, although with energy barriers higher than the first one. The driving force of the thionation reactions is the formation of trimers from the resulting monomers. In agreement with experimental observations, the amides are the most reactive when compared with esters, aldehydes, and ketones and the reaction is slightly influenced by the polarity of the solvent. Whereas for amides and esters substituents have little effect, aldehydes and ketones are influenced by both steric and electronic effects.This work was supported by the Spanish Ministerio de Economia y Competitividad (MINECO) (Project CTQ2013-44367-C2-1-P), by the Fondos Europeos para el Desarrollo Regional (FEDER), and by the Gobierno de Aragon (Zaragoza, Spain, Bioorganic Chemistry Group, E-10). M.A.C. thanks the University of Catania for partial financial support.Peer Reviewe

BET & ELF Quantum Topological Analysis of Neutral 2-Aza-Cope Rearrangement of γ-Alkenyl Nitrones

The 2-Aza-Cope rearrangement of γ-alkenyl nitrones is a rare example of the neutral thermal 2-aza-Cope process that usually takes place with cationic species. During the rearrangement, a redistribution of bonds and electronic density occurs in one kinetic step. However, the introduction of substituents with different steric requirements and electronic features might alter the activation energies and the synchronicity of the reaction. The electron localization function (ELF) analysis and its application to Bonding Evolution Theory (BET) analysis within the context of Molecular Electron Density Theory (MEDT) is an excellent tool to monitor the electron density along the reaction coordinate and thus investigate in detail bond breaking and formation and the corresponding energy barriers. By analyzing topological ELF calculations of seventeen 2-aza-Cope nitrone rearrangements with selected substituents, the main factors influencing the synchronicity of the process were investigated. This MEDT study results revealed that the rearrangement is a non-polar process mostly influenced by steric factors rather than by electronic ones, and confirms the pseudoradical character of the process rather than any pericyclic electron-reorganization

Pivotal neighboring-group participation in substitution versus elimination reactions – computational evidence for ion pairs in the thionation of alcohols with Lawesson's reagent

The mechanism of the thionation of alcohols with Lawesson's reagent was explored through quantum chemical DFT methods. Evidence that carbocations are involved was found. The mechanism is completely different to that established recently for the thionation of carbonyls. The presence of a phenyl ring at the alcoholic carbon atom exerts a pivotal role in the stability of the carbocation and enables a S–π interaction, which is crucial for favoring thionation instead of undesired elimination. The influence of the solvent was also studied, and elimination is preferred in toluene, whereas substitution leading to thionation is favored in acetonitrile. A clear correlation between solvent polarity and elimination was observed. The study is in complete agreement with the different behavior observed experimentally for primary, secondary, and tertiary alcohols (bearing a phenyl ring or not), and the best conditions for minimizing undesired elimination can be predicted.This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO) (project number CTQ2016-76155-R), the Fondos Europeos para el Desarrollo Regional (FEDER), and the Gobierno de Aragón (Zaragoza, Spain, Bioorganic Chemistry Group, E-10). M.-A. C. thanks the University of Catania for partial financial support. L. L. thanks the University of Pavia for partial financial support.Peer Reviewe

Revealing carbocations in highly asynchronous concerted reactions: The ene-type reaction between dithiocarboxylic acids and alkenes

The ene-type reaction between (dithio)carboxylic acids and alkenes has been studied computationally by DFT and topological (analysis of the electron localization function, ELF) methods. The reaction proceeds under kinetic control and the observed differences in regioselectivity are well-explained by the relative stability of the different transition structures. In agreement with experimental observations, electron-rich alkenes lead to Markownikoff adducts while electron-poor alkenes lead to Michael adducts. In all cases the reaction proceeds through an only transition structure (one kinetic step) although a different synchronicity was observed depending on the alkene electronics. The ELF analysis of the reactions corroborates the existence of a transient carbocation (hidden intermediate) in the reactions with electron-rich alkenes. On the other hand, electron-poor alkenes proceed through a more synchronous concerted mechanism. It can be predicted that with electron-rich alkenes bearing highly donating the transient carbocations might be captured by a nucleophile.This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO) (project number CTQ2016-76155-R), by the Fondos Europeos para el Desarrollo Regional (FEDER) and the Gobierno de Aragón (Zaragoza, Spain, Groups E34-R17). M.-A. C. and L. L. thank Universities of Catania and Pavia for partial financial support.Peer reviewe

Design of New Schiff Bases and Their Heavy Metal Ion Complexes for Environmental Applications: A Molecular Dynamics and Density Function Theory Study

Schiff bases (SBs) are important ligands in coordination chemistry due to their unique structural properties. Their ability to form complexes with metal ions has been exploited for the environmental detection of emerging water contaminants. In this work, we evaluated the complexation ability of three newly proposed SBs, 1–3, by complete conformational analysis, using a combination of Molecular Dynamics and Density Functional Theory studies, to understand their ability to coordinate toxic heavy metal (HMs) ions. From this study, it emerges that all the ligands present geometries that make them suitable to complex HMs through the N-imino moieties or, in the case of 3, with the support of the oxygen atoms of the ethylene diether chain. In particular, this ligand shows the most promising coordination behavior, particularly with Pb2+

Introducing topology to assess the synchronicity of organic reactions. Dual reactivity of oximes with alkenes as a case study

The synchronicity of organic reactions not always can be determined by only the analysis of transition structures. We present a case study that illustrates that topological analyses provide information regarding synchronicity that, often, is not reflected in the geometry of transition structures. We have chosen the competitive reactions of oximes with alkenes, (3 + 2) dipolar cycloaddition and ene-like reaction, which have been computationally studied to determine the parameters favoring each process. The competition between the two reactions is particularly evidenced in alkenyl oximes leading to intramolecular processes. Up to 26 examples of intramolecular reactions have been calculated and the results predicted the favored process.This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO) (project number CTQ2016-76155-R), the Fondos Europeos para el Desarrollo Regional (FEDER) and the Gobierno de Aragón (Zaragoza, Spain, Bioorganic Chemistry Group, E-10). The authors acknowledge the Institute of Biocomputation and Physics of Complex Systems (BIFI) at the University of Zaragoza for computer time at the clusters Terminus and Memento. M.-A. C. and L. L. thank the University of Catania and University of Pavia for partial financial support.Peer reviewe

Multiple-source Data Collection and Processing into a Graph Database Supporting Cultural Heritage Applications

The continuous growth of available resources on the web, both in the form of Linked Open Data and on Social Networks, provides an important opportunity to gather information concerning specific kinds of touristic activities like, for example, cultural tourism, eco-tourism, bike-tourism, and so on. Both decision makers and tourists can take advantage from these data, as demonstrated by previous works, with institutional actors foreseeing an increase in the use of this data to substitute other time-consuming and expensive approaches. However, managing multiple sources built with different goals and structures is not straightforward, so specific design choices must be made when assembling this kind of information. Graph databases represent an ideal way to combine multiple-source data but, to be successful, strategies accounting for inconsistencies and format differences have to be defined to support coherent analysis. Also, the continuously changing nature of crowd-sourced data makes it difficult, for the research community, to compare technological approaches to the different tasks that are linked to cultural heritage, from recommendation to management. To support the research effort in this direction, we describe the data ingestion and enrichment procedure we followed to organise knowledge coming from three different sources, namely Wikidata, Wikipedia, and Flickr, into a single, application-oriented, resource organised as a graph database. We present the potential use of this resource to perform multiple source analyses targeting the specific case of cultural tourism on a nationwide scale, and we propose its use as a shared benchmark for technological applications designed to support optimal management of cultural resources

Transient and intermediate carbocations in ruthenium tetroxide oxidation of saturated rings

The ruthenium tetroxide-mediated oxidation of cyclopentane, tetrahydrofuran, tetrahydrothiophene and N-substituted pyrrolidines has been studied computationally by DFT and topological (analysis of the electron localization function, ELF) methods. In agreement with experimental observations and previous DFT calculations, the rate-limiting step of the reaction takes place through a highly asynchronous (3 + 2) concerted cycloaddition through a single transition structure (one kinetic step). The ELF analysis identifies the reaction as a typical one-step-two-stages process and corroborates the existence of a transient carbocation. In the case of pyrrolidines, the carbocation is completely stabilized as an energy minimum in the form of an iminium ion and the reaction takes place in two steps.This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO) (project number CTQ2016-76155-R), by the Fondos Europeos para el Desarrollo Regional (FEDER) and the Gobierno de Aragon (Zaragoza, Spain, Groups E34-R17). The authors acknowledge the Institute of Biocomputation and Physics of Complex Systems (BIFI) at the University of Zaragoza for computer time at clusters Terminus and Memento. St. Francis-Prof. Thyagarajan Foundation (San Antonio, TX, USA) is gratefully acknowledged for a donation for software acquisition. M.-A. C. and L. L. thank Universities of Catania and Pavia for partial financial support.Peer reviewe

Chemoselective Oxidation of Isoxazolidines with Ruthenium Tetroxide: A Successful Intertwining of Combined Theoretical and Experimental Data

The direct oxidation reaction of isoxazolidines plays an important role in organic chemistry, leading to the synthesis of biologically active compounds. In this paper, we report a computational mechanistic study of RuO4-catalyzed oxidation of differently N-substituted isoxazolidines 1a–c. Attention was focused on the endo/exo oxidation selectivity. For all the investigated compounds, the exo attack is preferred to the endo one, showing exo percentages growing in parallel with the stability order of transient carbocations found along the reaction pathway. The study has been supported by experimental data that nicely confirm the modeling results