scholarly journals A Molecular Electron Density Theory Study of the Synthesis of Spirobipyrazolines through the Domino Reaction of Nitrilimines with Allenoates

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4159
Author(s):  
Luis R. Domingo ◽  
Fatemeh Ghodsi ◽  
Mar Ríos-Gutiérrez
Keyword(s):  
Electron Density ◽  
Energy Cost ◽  
Reaction Path ◽  
Bond Formation ◽  
Domino Reaction ◽  
Formation Processes ◽  
Free Energies ◽  
Molecular Electron ◽  
Molecular Electron Density Theory ◽  
Computational Level

The reaction of diphenyl nitrilimine (NI) with methyl 1-methyl-allenoate yielding a spirobipyrazoline has been studied within molecular electron density theory (MEDT) at the MPWB1K/6-311G(d) computational level in dichloromethane. This reaction is a domino process that comprises two consecutive 32CA reactions with the formation of a pyrazoline intermediate. Analysis of the relative Gibbs free energies indicates that both 32CA reactions are highly regioselective, the first one being also completely chemoselective, in agreement with the experimental outcomes. The geometries of the TSs indicate that they are associated to asynchronous bond formation processes in which the shorter distance involves the C1 carbon of diphenyl NI. Despite the zwitterionic structure of diphenyl NI, the appearance of a pseudoradical structure at the beginning of the reaction path, with a very low energy cost, suggests that the 32CA reaction between diphenyl NI, a strong nucleophile, and the allenoate, a moderate electrophile, should be mechanistically considered on the borderline between pmr-type and cb-type 32CA reactions, somewhat closer to the latter.

Unveiling the Synthesis of Spirocyclic, Tricyclic and Bicyclic Triazolooxazines From Intramolecular [3+2] Azide-alkyne Cycloadditions With a Molecular Electron Density Theory Perspective

2021 ◽  
Author(s):  
Nivedita Acharjee ◽  
Haydar A Mohammad-Salim ◽  
Mrinmoy Chakraborty
Keyword(s):  
Electron Density ◽  
Reaction Path ◽  
Function Analysis ◽  
Kinetic Control ◽  
Free Energies ◽  
Covalent Interaction ◽  
Species Analysis ◽  
Molecular Electron ◽  
Oxazine Ring ◽  
Molecular Electron Density Theory

Abstract The intramolecular [3+2] cycloaddition (32CA) reactions of azido alkynes leading to spirocyclic, tricyclic and bicyclic triazolooxazines has been studied within the molecular electron density theory (MEDT) at the MPWB1K/6-311G(d,p) level. The Electron localization function (ELF) characterizes the azido alkynes as zwitterionic species. Analysis of the Conceptual DFT indices allows classifying the azide moiety as the electrophilic counterpart and the alkyne as the nucleophilic one. These 32CA reactions are under kinetic control with the activation free energies of 23.4 - 26.7 kcal mol-1. Along the reaction path, the pseudoradical center is created initially at C4, consistent with the Parr function analysis, however the sequence of bond formation is controlled by the energetically feasible formation of the six membered oxazine ring. The intermolecular interactions at the TSs were characterized from the Quantum Theory of Atoms in Molecules (QTAIM) study and the Non covalent interaction (NCI) gradient isosurfaces.

scholarly journals Unveiling the Unexpected Reactivity of Electrophilic Diazoalkanes in [3+2] Cycloaddition Reactions within Molecular Electron Density Theory

2020 ◽  
Author(s):  
Luis R. Domingo ◽  
Mar Ríos-Gutiérrez ◽  
Nivedita Acharjee
Keyword(s):  
Electron Density ◽  
Complete Agreement ◽  
Slowing Down ◽  
Molecular Electron ◽  
One Step ◽  
Molecular Electron Density Theory ◽  
Electrophilic Character ◽  
Step Mechanism ◽  
Computational Level ◽  
Density Transfer

The [3+2] cycloaddition (32CA) reactions of strongly nucleophilic norbornadiene (NBD) with simplest diazoalkane (DAA) and three DAAs of increased electrophilicity have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. These pmr-type 32CA reactions follow an asynchronous one-step mechanism with activation enthalpies ranging from 17.7 to 27.9 kcal·mol-1 in acetonitrile. The high exergonic character of these reactions makes them irreversible. The presence of electron-withdrawing (EW) substituents in the DAA increases the activation enthalpies, in complete agreement with the experimental slowing-down of the reactions, but contrary to the Conceptual DFT prediction. Despite the nucleophilic and electrophilic character of the reagents, the global electron density transfer at the TSs indicates rather non-polar 32CA reactions. The present MEDT study allows establishing that the depopulation of the NNC core in this series of DAAs with the increase of the EW character of the substituents present at the carbon center is responsible for the experimentally found deceleration.

scholarly journals Understanding the domino reaction between 1-diazopropan-2-one and 1,1-dinitroethylene. A molecular electron density theory study of the [3 + 2] cycloaddition reactions of diazoalkanes with electron-deficient ethylenes

RSC Advances ◽  
2017 ◽  
Vol 7 (25) ◽  
pp. 15586-15595 ◽  
Author(s):  
Luis R. Domingo ◽  
Mar Ríos-Gutiérrez ◽  
Saeedreza Emamian
Keyword(s):  
Electron Density ◽  
Domino Reaction ◽  
Cycloaddition Reactions ◽  
Molecular Electron ◽  
Molecular Electron Density Theory

The domino reaction between 1-diazopropan-2-one and 1,1-dinitroethylene yielding a pyrazole and a gem-dinitrocyclopropane has been studied using molecular electron density theory.

scholarly journals Understanding the Reactivity of Trimethylsilyldiazoalkanes Participating in [3+2] Cycloaddition Reactions towards Diethylfumarate with a Molecular Electron Density Theory Perspective

Organics ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 3-18
Author(s):  
Luis R. Domingo ◽  
Nivedita Acharjee ◽  
Haydar A. Mohammad-Salim
Keyword(s):  
Electron Density ◽  
Energy Cost ◽  
Trimethylsilyl Group ◽  
Gibbs Energies ◽  
Molecular Electron ◽  
One Step ◽  
Molecular Electron Density Theory ◽  
Non Covalent Interactions ◽  
Covalent Interactions ◽  
Step Mechanism

A Molecular Electron Density Theory (MEDT) study is presented here for [3+2] cycloaddition (32CA) reactions of three trimethylsilyldiazoalkanes with diethyl fumarate. The presence of silicon bonded to the carbon of these silyldiazoalkanes changes its structure and reactivity from a pseudomonoradical to that of a zwitterionic one. A one-step mechanism is predicted for these polar zw-type 32CA reactions with activation enthalpies in CCl4 between 8.0 and 19.7 kcal·mol−1 at the MPWB1K (PCM)/6-311G(d,p) level of theory. The negative reaction Gibbs energies between −3.1 and −13.2 kcal·mole−1 in CCl4 suggests exergonic character, making the reactions irreversible. Analysis of the sequential changes in the bonding pattern along the reaction paths characterizes these zw-type 32CA reactions. The increase in nucleophilic character of the trimethylsilyldiazoalkanes makes these 32CA reactions more polar. Consequently, the activation enthalpies are decreased and the TSs require less energy cost. Non-covalent interactions at the TSs account for the stereoselectivity found in these 32CA reactions involving the bulky trimethylsilyl group.

scholarly journals Understanding the Origin of the Regioselectivity in Non-Polar [3+2] Cycloaddition Reactions through the Molecular Electron Density Theory

Organics ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 19-35
Author(s):  
Luis R. Domingo ◽  
Mar Ríos Gutiérrez ◽  
Jorge Castellanos Soriano
Keyword(s):  
Electron Density ◽  
Energy Demand ◽  
Lower Energy ◽  
Bond Formation ◽  
Single Bond ◽  
Energy Profiles ◽  
Molecular Electron ◽  
Molecular Electron Density Theory ◽  
Single Bonds ◽  
Bonding Electron

The regioselectivity in non-polar [3+2] cycloaddition (32CA) reactions has been studied within the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311G(d,p) level. To this end, the 32CA reactions of nine simplest three-atom-components (TACs) with 2-methylpropene were selected. The electronic structure of the reagents has been characterized through the Electron Localisation Function (ELF) and the Conceptual DFT. The energy profiles of the two regioisomeric reaction paths and ELF topology of the transition state structures are studied to understand the origin of the regioselectivity in these 32CA reactions. This MEDT study permits to conclude that the least electronegative X1 end atom of these TACs controls the asynchronicity in the C−X (X=C, N, O) single bond formation, and consequently, the regioselectivity. This behaviour is a consequence of the fact that the creation of the non-bonding electron density required for the formation of the new single bonds has a lower energy demand at the least electronegative X1 atom than at the Z3 one.

scholarly journals A molecular electron density theory study of the mechanism, chemo- and stereoselectivity of the epoxidation reaction of R-carvone with peracetic acid

RSC Advances ◽  
2019 ◽  
Vol 9 (49) ◽  
pp. 28500-28509 ◽  
Author(s):  
Abdellah Zeroual ◽  
Mar Ríos-Gutiérrez ◽  
Ouafa Amiri ◽  
Mohammed El Idrissi ◽  
Luis R. Domingo
Keyword(s):  
Electron Density ◽  
Peracetic Acid ◽  
Epoxidation Reaction ◽  
Molecular Electron ◽  
Molecular Electron Density Theory ◽  
Computational Level

The epoxidation reaction of R-carvone 8 with peracetic acid 9 has been studied within the molecular electron density theory at the B3LYP/6-311(d,p) computational level.

scholarly journals Mpro-SARS-CoV-2 Inhibitors and Various Chemical Reactivity of 1-Bromo- and 1-Chloro-4-vinylbenzene in [3 + 2] Cycloaddition Reactions

Organics ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 1-16
Author(s):  
Mohammed El Idrissi ◽  
Mohamed El Ghozlani ◽  
Asli Eşme ◽  
Mar Ríos-Gutiérrez ◽  
Anas Ouled Aitouna ◽  
...  
Keyword(s):  
Electron Density ◽  
Chemical Reactivity ◽  
Cycloaddition Reactions ◽  
Two Stage ◽  
Docking Analysis ◽  
Molecular Electron ◽  
One Step ◽  
Molecular Electron Density Theory ◽  
Step Mechanism ◽  
Computational Level

The regioselectvity and the mechanism of the (32CA) cycloadditions reactions of 1-bromo-4-vinylbenzene 1 and 1-chloro-4-vinylbenzene 2 with benzonitrile oxide 3 were investigated under the molecular electron density theory (MEDT) at the B3LYP/6-311++G(d,p) computational level. Evaluation of the ELF reveals that these zwitterionic type (zw-type) 32CA reactions take place in a two-stage one-step mechanism. This MEDT study shows that the meta isoxazolines are kinetically and thermodynamically favored over the ortho ones, these 32CA reactions being completely regioselective, in agreement with experimental outcomes. In addition, the efficiency of isoxazolines against SARS-CoV-2 have been also investigated. According to the docking analysis, the present study concludes that 5-(p-bromophenyl)-3-phenyl-2-isoxazoline (B-m) shows better interactions for the inhibition of SARS-CoV-2 in comparison to chloroquine.

scholarly journals The Participation of 3,3,3-Trichloro-1-Nitroprop-1-Ene in the [3 + 2] Cycloaddition Reaction with Selected Nitrile N-oxides in the Light of the Experimental and MEDT Quantum Chemical Study

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6774
Author(s):  
Karolina Zawadzińska ◽  
Mar Ríos-Gutiérrez ◽  
Karolina Kula ◽  
Przemysław Woliński ◽  
Barbara Mirosław ◽  
...  
Keyword(s):  
Electron Density ◽  
Quantum Chemical Study ◽  
Cycloaddition Reaction ◽  
Chemical Study ◽  
Free Energies ◽  
Molecular Electron ◽  
One Step ◽  
Molecular Electron Density Theory ◽  
Favorable Reaction ◽  
Type 3

The regioselective zw-type [3 + 2] cycloaddition (32CA) reactions of a series of aryl-substituted nitrile N-oxides (NOs) with trichloronitropropene (TNP) have been both experimentally and theoretically studied within the Molecular Electron Density Theory (MEDT). Zwitterionic NOs behave as moderate nucleophiles while TNP acts as a very strong electrophile in these polar 32CA reactions of forward electron density flux, which present moderate activation Gibbs free energies of 22.8–25.6 kcal·mol−1 and an exergonic character of 28.4 kcal·mol−1 that makes them irreversible and kinetically controlled. The most favorable reaction is that involving the most nucleophilic MeO-substituted NO. Despite Parr functions correctly predicting the experimental regioselectivity with the most favorable O-CCCl3 interaction, these reactions follow a two-stage one-step mechanism in which formation of the O-C(CCl3) bond takes place once the C-C(NO2) bond is already formed. The present MEDT concludes that the reactivity differences in the series of NOs come from their different nucleophilic activation and polar character of the reactions, rather than any mechanistic feature.

scholarly journals Understanding the Reactivity of C-Cyclopropyl-N-Methylnitrone Participating in [3+2] Cycloaddition Reactions Towards Styrene with a Molecular Electron Density Theory Perspective

2021 ◽  
Vol 65 (1) ◽  
Author(s):  
Haydar A. Mohammad-Salim
Keyword(s):  
Electron Density ◽  
Density Functional ◽  
Transition States ◽  
Free Energies ◽  
Conceptual Density Functional Theory ◽  
Covalent Bonds ◽  
Functional Theory ◽  
Molecular Electron ◽  
One Step ◽  
Molecular Electron Density Theory

Abstract. The [3+2] cycloaddition (32CA) reactions of C-cyclopropyl-N-methylnitrone 1 with styrene 2 have been studied within molecular electron density theory (MEDT) at the B3LYP/6-311++G(d,p) level of theory. These zwitterionic type 32CA reactions occur through a one-step mechanism. The 32CA reactions undergo four stereo- and regioisomeric reaction paths to form four different products, 3, 4, 5 and 6.  Analysis of the conceptual density functional theory (CDFT) indices predict the global electronic flux from the strong nucleophilic nitrone 1 to the styrene 2. These 32CA reactions are endergonic with reactions Gibbs free energies between 2.83 and 7.39 kcal.mol-1 in the gas phase. The 32CA reaction leading to the formation of cycloadduct 3 presents the lowest activation enthalpy than the other paths due to a slightly increase in polar character evident from the global electron density transfer (GEDT) at the transition states and along the reaction path. The bonding evolution theory (BET) study suggests that these 32CA reactions occur through the coupling of pseudoradical centers and the formation of new C-C and C-O covalent bonds has not been started in the transition states.   Resumen.

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