Utilizing MEDT analysis of [3 + 2] cycloaddition reaction: x-ray crystallography of spirooxindole linked with thiophene/furan heterocycles and triazole framework.

Hybridization of spirooxindole with different pharmacophores such as triazole and heterocycle such as thiophene and furan moiety was achieved by the [3 + 2] cycloaddition (32CA) reaction approach. Structural investigations of the compounds 4a and 4b were performed using X-ray single crystal structure determinations and Hirshfeld analysis. Both compounds crystallized in monoclinic crystal system.

Novel spirooxindole-triazole derivatives: unveiling [3+2] cycloaddition reactivity through molecular electron density theory and investigating their potential cytotoxicity against HepG2 and MDA-MB-231 cell lines.

A novel analogue of hybrid spirooxindoles was synthesized employing a systematic multistep synthetic approach. The synthetic protocol was designed to obtain a series of spirooxindole derivatives incorporating triazolyl--triazine framework via [3 + 2] cycloaddition (32CA) reaction of azomethine ylide ( with the corresponding chalcones . Unexpectedly, the reaction underwent an alternate route, leading to the cleavage of the s-triazine moiety and yielding a series of spirooxindole derivatives incorporating a triazole motif.

A molecular electron density theory study of the bimolecular nucleophilic substitution reactions on monosubstituted methyl compounds.

The nucleophilic substitution reactions involving methyl monosubstituted compounds have been studied within the Molecular Electron Density Theory (MEDT) at the B97X-D/6-311+G(d,p) computational level in DMSO. This study aims to characterize the electronic nature of the transition state structures (TSs) involved in the so-called S2 and Si reactions. Both electron localization function and atom-in-molecules topological analyses indicate that the TSs involved in these nucleophilic substitutions can be described as a central methyl CH carbocation, which is strongly stabilized by the presence of two neighbouring nucleophilic species through electron density transfer.

Understanding the Electronic Effects of Lewis Acid Catalysts in Accelerating Polar Diels-Alder Reactions.

The electronic effects of Lewis acid (LA) catalysts in reducing the activation energies of polar Diels-Alder (P-DA) reactions have been studied within Molecular Electron Density Theory. To this end, a quantum topological energy partitioning scheme, namely, the Relative Interacting Atomic Energy (RIAE) analysis, is applied to the transition state structures (TSs) and the ground state of the reagents of two different LA-catalyzed P-DA reactions. Analyses of the ξ total energies of the two interacting frameworks (X) show that the electronic energy stabilization of the electrophilic frameworks, resulting from the global electron density transfer (GEDT), is the cause of an effective decrease of the activation energies.

MEDT analysis of mechanism and selectivities in non-catalyzed and lewis acid-catalyzed diels-alder reactions between R-carvone and isoprene.

Within the context of Molecular Electronic Density Theory (MEDT), this study investigates the Diels-Alder reaction among isoprene (2) and R-carvone (1R) applying DFT simulations, with and without Lewis acid (LA) catalysis. The results show that carvone (1R) acts as an electrophile and isoprene (2) as a nucleophile in a polar process. LA catalysis increases the electrophilicity of carvone, thereby improving the reactivity and selectivity of the reaction by reducing the activation Gibbs free energy.

Spin-Polarized Conceptual Density Functional Theory from the Convex Hull.

We present a new, nonarbitrary, internally consistent, and unambiguous framework for spin-polarized conceptual density-functional theory (SP-DFT). We explicitly characterize the convex hull of energy, as a function of the number of electrons and their spin, as the only accessible ground states in spin-polarized density functional theory. Then, we construct continuous linear and quadratic models for the energy.

Revealing the Critical Role of Global Electron Density Transfer in the Reaction Rate of Polar Organic Reactions within Molecular Electron Density Theory.

The critical role of global electron density transfer (GEDT) in increasing the reaction rate of polar organic reactions has been studied within the framework of Molecular Electron Density Theory (MEDT). To this end, the series of the polar Diels-Alder (P-DA) reactions of cyclopentadiene with cyanoethylene derivatives, for which experimental kinetic data are available, have been chosen. A complete linear correlation between the computed activation Gibbs free energies and the GEDT taking place at the polar transition state structures (TSs) is found; the higher the GEDT at the TS, the lower the activation Gibbs free energy.

Synthesis and Characterization of New Spirooxindoles Including Triazole and Benzimidazole Pharmacophores via [3+2] Cycloaddition Reaction: An MEDT Study of the Mechanism and Selectivity.

A new series of spirooxindoles based on benzimidazole, triazole, and isatin moieties were synthesized via a [3+2] cycloaddition reaction protocol in one step. The single X-ray crystal structure of the intermediate triazole-benzimidazole was solved. The new chemical structures of these spirooxindole molecules have been achieved for the first time.

A Molecular Electron Density Theory Study of the Domino Reaction of -Phenyl Iminoboranes with Benzaldehyde Yielding Fused Bicyclic Compounds.

The reaction of -phenyl iminoborane with benzaldehyde yielding a fused aromatic compound, recently reported by Liu et al., has been studied within the Molecular Electron Density Theory (MEDT). Formation of the fused aromatic compound is a domino process that comprises three consecutive reactions: (i) formation of a weak molecular complex between the reagents; (ii) an intramolecular electrophilic attack of the activated carbonyl carbon of benzaldehyde on the position of the -phenyl substituent of iminoborane; and (iii) a formal 1,3-hydrogen shift yielding the final fused aromatic compound.

A combined BET and IQA-REG study of the activation energy of non-polar zw-type [3+2] cycloaddition reactions.

A combined Bonding Evolution Theory (BET) and Interacting Quantum Atoms-Relative Energy Gradient (IQA-REG) study is carried out on a non-polar zw-type [3+2] cycloaddition (32CA) reaction. BET is the joint use of Catastrophe Theory and the topology of the Electron Localization Function (ELF) to characterise molecular mechanisms, while IQA is a quantum topological energy partitioning method and REG is a method to compute chemical insight at atomistic level, usually in connection with energy. This 32CA reaction involves the simplest nitrone with ethylene and has been studied here at B3LYP/6-311G(d,p) level within the context of Molecular Electron Density Theory (MEDT), which is based on the idea that changes in electron density, and not molecular orbital interactions, are responsible for chemical reactivity.

Unveiling the high reactivity of experimental pseudodiradical azomethine ylides within molecular electron density theory.

The [3+2] cycloaddition (32CA) reactions of -methyl azomethine ylide (AY) with styrene, benzaldehyde and methyl 2-formyl-benzoate (MFB) were studied within molecular electron density theory (MEDT), at the ωB97X-D/6-311G(d) computational level, in order to characterize the reactivity of an experimental pseudodiradical TAC for the first time. ELF topological analysis indicates that AY presents a pseudodiradical structure. Analysis of CDFT reactivity indices allows classifying AY as a supernucleophile; while styrene is classified as a moderate electrophile, benzaldehyde and MFB are classified as strong electrophiles.

A Molecular Electron Density Theory Study of the [3+2] Cycloaddition Reaction of an Azomethine Ylide with an Electrophilic Ethylene Linked to Triazole and Ferrocene Units.

The [3+2] cycloaddition (32CA) reaction of an azomethine ylide (AY) with an electrophilic ethylene linked to triazole and ferrocene units has been studied within the Molecular Electron Density Theory (MEDT) at the B97X-D/6-311G(d,p) level. The topology of the electron localization function (ELF) of this AY allows classifying it as a species characterized by the presence of two monosynaptic basins, integrating a total of 0.76 e, at the C1 carbon.

Unveiling the non-polar [3+2] cycloaddition reactions of cyclic nitrones with strained alkylidene cyclopropanes within a molecular electron density theory study.

The role of cyclopropane substitution on the ethylene in [3+2] cycloaddition (32CA) reactions of cyclic nitrones has been studied within Molecular Electron Density Theory (MEDT) at the B97X-D/6-311G(d,p) computational level. Electron Localization Function (ELF) analysis of the ethylenes shows that the presence the cyclopropane only slightly increases the electron density in the C-C bonding region. Analysis of the Conceptual DFT reactivity indices indicates that the presence of the cyclopropane does not produce any remarkable change in the reactivity of these strained ethylenes.

Understanding the different reactivity of ()- and ()-β-nitrostyrenes in [3+2] cycloaddition reactions. An MEDT study.

The experimental reactivity of isomeric ()- and ()-β-nitrostyrenes participating in [3+2] cycloaddition (32CA) reactions has been analysed on the basis of molecular electron density theory (MEDT) at the HF/6-311G(d,p), B3LYP/6-311G(d,p) and B97X-D/6-311G(d,p) computational levels. It was found that the polar 32CA reactions with 5,5-dimethylpyrroline--oxide proceed a one-step mechanism, characterised by the attack of the nucleophilic oxygen centre of the nitrone on the electrophilically activated β-position of these nitrostyrenes. This behaviour is completely understood by means of the analysis of the conceptual DFT reactivity indices.

A Comprehensive Experimental and Theoretical Study on the [{(η-CH)Zr[P(µ-PNEt)P(NEt)P]}]O Crystalline System.

The structure of tetraphosphetane zirconium complex CHNOPZr was determined by single crystal X-ray diffraction analysis. The crystal belongs to the monoclinic system, space group P21/c, with a = 19.6452(14), b = 17.

The Participation of 3,3,3-Trichloro-1-nitroprop-1-ene in the [3 + 2] Cycloaddition Reaction with Selected Nitrile -Oxides in the Light of the Experimental and MEDT Quantum Chemical Study.

The regioselective [3 + 2] cycloaddition (32CA) reactions of a series of aryl-substituted nitrile -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.

The catalytic effects of a thiazolium salt in the oxa-Diels-Alder reaction between benzaldehyde and Danishefsky's diene: a molecular electron density theory study.

The oxa-Diels-Alder (ODA) reaction of benzaldehyde with Danishefsky's diene in the presence of a [thiazolium][Cl] salt, as a model of an ionic liquid, has been studied within Molecular Electron Density Theory (MEDT) at the M06-2X/6-311G(d,p) computational level. The formation of two hydrogen bonds (HBs) between the thiazolium cation and the carbonyl oxygen of benzaldehyde modifies neither the electrophilic character of benzaldehyde nor its electronic structure substantially but accelerates the reaction considerably. This ODA reaction presents an activation energy of 4.

Understanding the Participation of Fluorinated Azomethine Ylides in Carbenoid-Type [3 + 2] Cycloaddition Reactions with Ynal Systems: A Molecular Electron Density Theory Study.

The carbenoid-type () 32CA reaction of 1,1-difluoroated azomethine ylide (DFAY) with phenylpropynal has been studied using the molecular electron density theory (MEDT). Electron localization function (ELF) characterizes DFAY as a carbenoid species participating in 32CA reactions. The supernucleophilic character of DFAY and the strong electrophilic character of the ynal cause this polar 32CA reaction to have an unappreciable barrier; the reaction, which is highly exothermic, presents total chemo- and regioselectivity.

Unveiling the Ionic Diels-Alder Reactions within the Molecular Electron Density Theory.

The ionic Diels-Alder (I-DA) reactions of a series of six iminium cations with cyclopentadiene have been studied within the Molecular Electron Density Theory (MEDT). The superelectrophilic character of iminium cations, ω > 8.20 eV, accounts for the high reactivity of these species participating in I-DA reactions.

Divulging the various chemical reactivity of trifluoromethyl-4-vinyl-benzene as well as methyl-4-vinyl-benzene in [3+2] cycloaddition reactions.

In the present paper, an investigation about the [3 + 2]cycloaddition (32 C A) reactions of benzonitrile oxide with 1-trifluoromethyl-4-vinyl-benzene, and with 1-methyl-4-vinyl-benzene, using the Molecular Electron Density Theory (MEDT) through DFT/B3LYP/6-311++G (d,p), is performed. A deep mechanistic study beside an accurate electronic description of different stationary points along the IRC paths of the two 32 C A reactions have performed by examining the two competitive regioisomericortho/metareaction pathways, and providing the mechanism associated with them. The presence of the CF group reduces the activation energy, which makes it possible to increase the experimental yield of the reaction in good agreement with the experimental results.

Unveiling the Lewis Acid Catalyzed Diels-Alder Reactions Through the Molecular Electron Density Theory.

The effects of metal-based Lewis acid (LA) catalysts on the reaction rate and regioselectivity in polar Diels-Alder (P-DA) reactions has been analyzed within the molecular electron density theory (MEDT). A clear linear correlation between the reduction of the activation energies and the increase of the polar character of the reactions measured by analysis of the global electron density transfer at the corresponding transition state structures (TS) is found, a behavior easily predictable by analysis of the electrophilicity ω and nucleophilicity indices of the reagents. The presence of a strong electron-releasing group in the diene changes the mechanism of these P-DA reactions from a to a two-step one via formation of a zwitterionic intermediate.

A molecular electron density theory study of the participation of tetrazines in aza-Diels-Alder reactions.

The reactions of eight tetrazines of increased electrophilic character with nucleophilic tetramethyl ethylene (TME) and with electrophilic tetracyanoethylene (TCE) have been studied using Molecular Electron Density Theory. These reactions are domino processes comprising an aza-Diels-Alder (ADA) reaction followed by an extrusion of molecular nitrogen, yielding a dihydropyridazine. Analysis of the conceptual DFT (CDFT) indices showed an increase of the electrophilicity and a decrease of the nucleophilicity of tetrazines with an increase of the electron-withdrawing character of the substituent.

Unveiling the Different Chemical Reactivity of Diphenyl Nitrilimine and Phenyl Nitrile Oxide in [3+2] Cycloaddition Reactions with (R)-Carvone through the Molecular Electron Density Theory.

The [3+2] cycloaddition (32CA) reactions of diphenyl nitrilimine and phenyl nitrile oxide with (R)-carvone have been studied within the Molecular Electron Density Theory (MEDT). Electron localisation function (ELF) analysis of these three-atom-components (TACs) permits its characterisation as carbenoid and zwitterionic TACs, thus having a different reactivity. The analysis of the conceptual Density Functional Theory ( DFT) indices accounts for the very low polar character of these 32CA reactions, while analysis of the DFT energies accounts for the opposite chemoselectivity experimentally observed.

A molecular electron density theory study of the enhanced reactivity of aza aromatic compounds participating in Diels-Alder reactions.

The enhanced reactivity of a series of four aza aromatic compounds (AACs) participating in the Diels-Alder (DA) reactions with ethylene has been studied using Molecular Electron Density Theory (MEDT). The analysis of the electronic structure of these AACs allows establishing that the substitution of the C-H unity by the isoelectronic N: unity linearly decreases the ring electron density (RED) of these compounds and concomitantly decreases their aromatic character and increases their electrophilic character. These behaviours not only decrease drastically the activation energies of these DA reactions, but also increase the reaction energies when they are compared with the very unfavourable DA reaction between benzene and ethylene.