Local Electrophilicity Indices Research Articles

Valuable insights into the structural, electronic, and aromaticity aspects of azulene and its monophospha-derivatives

Azulene-based conjugated systems have garnered considerable interest owing to their atypical structures. The incorporation of a phosphorous atom into the azulene framework offers an enticing prospect for the creation of unique organophosphorous π-conjugated compounds. No such phosphaazulene skeleton however has been reported to date. Here, density functional theory calculations were employed to examine the physicochemical properties and aromaticity of azulene and its monophospha-derivatives. The electronic, magnetic, and structural properties were taken into consideration. The reactivity of azulene and its monophospha-analogs including 1-phospha (1p), 2-phospha (2p), 4-phospha (3p), 5-phospha (4p), and 6-phosphaazulene (5p), was examined through local electrophilicity and local nucleophilicity indices. The stability and aromaticity of these compounds were determined using DFT calculations with the B3LYP/6–311 + G(d,p) method. The stability of monophosphaazulene derivatives is significantly influenced by the position of the phosphorus atom, as indicated by the energy calculations. The order of stability was found to be 1p > 2p > 5p > 3p > 4p. Aromaticity studies based on HOMA, ΔBl, FLUπ, SA, and NICS indices indicated that the incorporation of a phosphorus atom into the 5-membered ring decreased its aromaticity while simultaneously increasing the aromaticity of the 7-membered ring. However, replacing the carbon atom with phosphorus atom in the 7-membered ring reduced the aromaticity of both rings. Additionally, the ability of π-stacking, as determined by the LOLIPOP criterion, was reduced in the monophosphaazulene derivatives compared to azulene, except for compound 5p. The order of π-stacking ability was 5p > azulene > 2p > 1p > 4p > 3p. Overall, there was a good agreement between the various aromaticity indices, providing consistent results for both rings in azulene and monophosphaazulenes.

New insights into H2 activation by intramolecular frustrated Lewis pairs based on aminoboranes: the local electrophilicity index of boron as a suitable indicator to tune the reversibility of the process.

A large set of intramolecular aminoborane-based FLPs was studied employing density functional theory in the H2 activation process to analyze how the acidity and basicity of boron and nitrogen atoms, respectively, affect the reversibility of the process. Three different linkers were employed, keeping the C-C nature in the connection between both Lewis centers: -CH2-CH2-, -CH[double bond, length as m-dash]CH-, and -C6H4-. The results show that significant differences in the Gibbs free energy of the process are found by considering all the combinations of substituents. Of the 75 systems studied, only 9 showed the ability to carry out the process reversibly (ΔGH2 in the range of -3.5 to 2.0 kcal mol-1), where combinations of alkyl/aryl or aryl/alkyl in boron/nitrogen generate systems capable of reaching reversibility. If the alkyl/alkyl or aryl/aryl combination is employed, highly exergonic (non-reversible H2 activation) and endergonic (unfeasible H2 activation) reactions are found, respectively. No appreciable differences in the linker were found, allowing us to continue the analysis with the most entropically favorable linker, the -C6H4- linker. From this, 25 different FLP systems of type 2-[bis(X)boryl]-(Y)aniline (X: H, CF3, C6F5, PFtB, FMes and Y: H, CH3, t-but, Ph, Mes) can be formed. By analyzing the electronic properties of each system, we have found that the condensed-to-boron electrophilicity index ωB+ is inversely related to the ΔGH2. Interestingly, two relationships were found; the first is for alkyl groups (Y: CH3 and t-but) and the second for aryl groups (Y: H, Ph, and Mes), which is intimately related to the proton affinity of each aniline. In addition, it is quite interesting when the frustration degree, given by B⋯N distance dB-N, is brought together with ωB+, since the quotient has unit energy/length corresponding to unit force; concomitantly, a measure of the FLP strength in H-H bond activation can be defined. With this finding, a rational design of this kind of FLP can be performed by analyzing the acidity of boron through condensed-to-boron electrophilicity and knowing the nature of the substituent of nitrogen according to whether the Y is alkyl or aryl, optimizing the H2 reversible activation in a rational way, which is crucial to improve the catalytic performance.

Photoionization of stable mesoionic compounds

The electronic structures and valence ionizations of three mesoionic compounds: 3-methylsydnone, 3-phenylsydnone and 3-methyl-2-phenyl-1,3,4-thiadiazole-5-thione have been studied using high-level ab initio methods: electron-propagator theory (EPT) and coupled cluster method (IP-EOM-CCSD). We discuss the influence of valence electronic structure on chemical reactivity using global and local electrophilicity indices. We also discuss (non)aromatic character of the studied molecules using information pertaining to photoelectron spectra.

One pot synthesis of novel pregnane-sulphur prodrugs, spectroscopic investigation, conformational analysis, chemical reactivity, Fukui function and their mathematical model

Novel sulphur derivatives have been synthesized for the first time from 16-Dehydropregnenolone acetate (16-DPA) by adopting thia-Michael addition reaction yielding 2-[(3β-acetoxy) pregn–5-ene-20-one −16 –thio] propanoic acid, 2-[(3β-acetoxy) pregn–5-ene-20-one–16–thio] ethanoic acid, 3β-acetoxy 16α-(2-hydroxyethylthio)-pregn-5-ene-20-one and 3β-acetoxy-16β-(2-amino phenylthio)-pregn-5-ene-20-one. All the compounds were characterized with the help of 1H, 13C NMR, FT-IR spectroscopy and mass spectrometry. The molecular geometry and vibrational frequency of these compounds were calculated in ground state by density functional theory (DFT/B3LYP) using 6-31G (d, p) basis set. Conformational analysis of all the compounds was carried out to determine the most stable conformation. The electronic properties such as HOMO-LUMO energy were calculated by using time dependent density functional theory (TD-DFT). The topological parameters-electron density (ρBCP), Laplacian of electron density (∇2ρ(rBCP)), energy parameters-kinetic electron energy density (GBCP), potential electron density (VBCP) and the total electron energy density (HBCP) at the bond critical points (BCP) were analyzed by ‘Atoms in molecules’ AIM theory. Local reactivity descriptors like Fukui functions (fk+, fk−, fk0), local softness (sk+, Sk−, Sk0) and local electrophilicity indices (ωk+, ωk−, ωk0) analysis were performed to find out the reactive sites within the molecules. Molecular electrostatic potential of the synthesized compounds were also determined. Lastly a nonlinear mathematical model has been proposed and analyzed to study the effect of catalysts on these reactions. Local and global stability analysis of the mathematical model along with the persistence of the system was checked using theory of nonlinear ordinary differential equations.

Microwave-assisted synthesis of novel 5-aminouracil-based compound with DFT calculations

In this investigation, microwave assisted synthesis of novel pyrazole ring formation via three reaction steps. In the beginning, nucleophilic acyl substitution reaction of the 5-aminouracil with ethyl cyanoacetate to afford 2-cyano-N-(2,4-dioxo-1,2,3,4-tetrahydropyridine-5-yl)acetamide (3). Knoevenagel Condensation of acetamide 3 with benzaldehyde afforded the corresponding acrylamide derivative 6 under microwave irradiation. Finally, Michael addition reaction of acrylamide with hydrazine hydrate to afford the novel 5-aminouracil-based compound 9. Computational studies for the three reactions have been carried out utilizing DFT/B3LYP/6-31 + G(d) theory level. The regioselectivity elucidated in terms of frontier molecular orbital (FMO), local electrophilicity, global electrophilicity and nucleophilicity indexes. The analysis of FMO showed the selectivity of these reactions was controlled through HOMO–LUMO interaction. Also, the molecular electrostatic potential (ESP) associated the hydrogen bonding interactions between electrophiles and nucleophiles. The IR of the optimized structures were examined by DFT/B3LYP/6 + 31G(d) and compared with experimental FT-IR. Furthermore, comparative study between experimental UV–Vis and calculated utilizing TD-DFT.

Synthesis, Antioxidant Activity and Theoretical Investigation of Isoxazolines Derivatives of Monoterpenoids

The 3+2 cycloaddition reactions are important to generate five-membered heterocyclic compounds as well as altering biological activity effects based on structure. In the study, we synthesized new isoxazoline derivatives of different monoterpenoids and examined the structure analysis using spectroscopical analysis methods, reveal changes in the theoretical analysis related to the biological activity. These new compounds exhibit antioxidant activities; DPPH radical scavenging, ferric reducing, metal chelating activities which are significantly higher than the related commercial monoterpenoids. Theoretical approaches on the compounds containing isoxazole moiety have been performed by the DFT/B3LYP/method, 6-31G(d,p) basis set in the ground state. The global and local chemical reactivity properties of the compounds were investigated by considering the values of electronegativity, global hardness-softness, electronic chemical potential, electrophilicity index and condensed Fukui functions, local softness and local electrophilicity index. Furthermore, total energy, FMOs energy values and the dipole moment (µ), mean polarizability (α), and first order hyperpolarizability (β) values were analysed at the theoretical level to examine the polarizability characteristics of the compounds. The antioxidant activity values of the newly synthesized compounds were compared with a finding of the computational study. The results obtained exhibited good correlation on some parameters.

Unraveling the regioselectivity of odd electron halogen bond formation using electrophilicity index and chemical hardness parameters.

Odd electron halogen bonding of freons with five different free radicals have been investigated using M06-2X/6-311G++(d,p). Conceptual density functional theory parameters such as Fukui functions, electrophilicity index and chemical hardness have been utilised to examine the regioselectivity and strength of free radical induced halogen bonding. The strong electrophilic radical Cl˙ forms three-electron bonds upon interacting with the nucleophilic ring surrounding the sigma hole or fk- regions. This behavior is also observed for moderately electrophilic radicals OH˙ and OCl˙ for complexation with CHFCl2 only. In other complexes, these radicals along with least nucleophilic radicals ˙NO and ˙Ph form one-electron bond with sigma hole or fk+ regions of freons. This regioselectivity of radicals and the interaction energy upon complexation have been explained in terms of local electrophilicity index and chemical hardness. We hope that this finding will shed light on the understanding of non-covalent interactions in terms of conceptual density functional theory for halogen bonding as well as in pnictogen, chalcogen and tetrel bonding systems. This result may find applications in understanding the radical mediated reactions and ozone depletion in the stratosphere.

Electrophilicity Indices for Peroxyl Radicals

In this work, electrophilicity indices are calculated for 50 peroxyl radicals with density-functional theory (B3LYP hybrid functional and the 6-311+G(d,p) basis set). There is a relationship between general and local electrophilicity indices of peroxyl radicals and Taft inductive constants (σ*) of the substituents at the–OO• group.

Prediction of the Regioselectivity of 1,3-Dipolar Cycloaddition Reactions of Nitrile Oxides with 2(5H)-Furanones Using Recent Theoretical Reactivity Indices

The regioselectivity of a series of 16 1,3-dipolar cycloaddition reactions of nitrile oxides with 2(5 H)-furanones has been analysed by means of global and local electrophilic and nucleophilic reactivity indices using density functional theory at the B3LYP level together with the 6-31G(d) basis set. The local electrophilicity and nucleophilicity indices, based on Fukui and Parr functions, have been calculated for the terminal sites, namely the C1 and O3 atoms of the 1,3-dipole and the C4 and C5 atoms of the dipolarophile. These local indices were calculated using both Mulliken and natural charges and spin densities. The results obtained show that the C5 atom of the 2(5 H)-furanones is the most electrophilic site whereas the O3 atom of the nitrile oxides is the most nucleophilic centre. It turns out that the experimental regioselectivity is correctly reproduced, indicating that both Fukui- and Parr-based indices are efficient tools for the prediction of the regiochemistry of the studied reactions and could be used for the prediction of new designed reactions of the same kind.

Electrophilicity and Nucleophilicity of Boryl Radicals.

We carried out a survey of the relative reactivity of a collection of 91 neutral boryl radicals using density functional calculations. Their reactivities were characterized by four indices, i.e., the global electrophilicity, global nucleophilicity, local electrophilicity, and local nucleophilicity. Particularly, the global electrophilicity and nucleophilicity indices span over a moderately wider range than those of carbon radicals, indicating their potentially broader reactivity. Thus, boryl radicals may be utilized in electrophilic radical reactions, while traditionally they are only considered for nucleophilic radical reactions. In contrast, the local electrophilicity and nucleophilicity indices at the boron center show a different reactivity picture than their global counterparts. The inconsistency is rooted in the low and varying spin density on boron (for most radicals, less than 50%) in different boryl radicals, which is a combinative result of radical stabilization via electron delocalization and the low electronegativity of boron (compared to carbon). In short, the boron character in boryl radicals may be weak and their reactivity is not reflected by the local indices based on boron but by the global ones.

Photostability of Coumarin Laser Dyes - a Mechanistic Study Using Global and Local Reactivity Descriptors.

Using density functional theory approach, the trend in photostability of fluorescent coumarin laser dyes were investigated with the help global reactivity descriptors. The effect of different basis sets on global reactivity descriptors i.e. electrophilicity index (ω) is studied. The local reactivity descriptors such as Fukui function, local softness and local electrophilicity index have been used to understand the reactive site in the molecule. Photodegradation mechanism of fluorescent coumarin laser dyes in presence of singlet oxygen is explained using density functional theory.

Regioselectivity of 1,3-dipolar cycloadditions between aryl azides and an electron-deficient alkyne through DFT reactivity descriptors

Conceptual density functional theory, including chemical hardness, electronic chemical potential, global and local electrophilicity index and Fukui functions, is used to predict reactivity and regioselectivity of 1,3-dipolar cycloadditions (13DCs) between five aryl azides (1–5) and an electron-deficient alkyne at the B3LYP/6-31G(d,p) level. Two reaction paths (a) and (b) are considered which result in the corresponding regioisomeric 1,2,3-triazoles P(1-5)a and P(1-5)b, respectively. All the 13DCs proceed via rather asynchronous TSs and the path (b) is clearly more synchronous than the path (a). All the reactions are high exoergic [∆Go = −45.1 to −51.4 kcal/mol for path (a) and −47.7 to −55.9 kcal/mol for path (b)] with the moderate and nearly similar activation barriers (E a = 15.4–16.7 kcal/mol) referring a relatively low regioselectivity. All reactivity descriptors but one clearly suggest that path (a) is somewhat preferred over path (b). FMO interactions occur between HOMO13DP and LUMODPh due to the corresponding lower energy gap. All the reactions considered in this work classified as polar 13DCs with NED character. Our theoretical results are in good agreement with those reported experimentally.

1,3-Dipolar cycloadditions of nonstabilized azomethine ylides to planar chalcones via regio- and stereoselective route: A three-component strategy

ABSTRACTSimple and efficient strategies toward the synthesis of trisubstituted pyrrolizidines and disubstituted oxazolidine systems by 1,3-dipolar cycloaddition reactions using arylaldehydes and α-amino acids have been developed, followed by a one-pot, three-component strategy. Electron-deficient dipolarophiles, chalcones, were reacted with nonstabilized azomethine ylides derived from arylaldehyde and L-proline in dry dimethyl formamide, leading to substituted pyrrolizidines. The route to substituted oxazolidines involved cycloaddition to the C˭O bond of a second molecule of the aldehyde. The structures and stereochemistry of the cycloadducts were established by infrared (IR), NMR spectroscopy, and single-crystal x-ray crystallographic analyses. Condensed Fukui functions and local electrophilicity indices have been computed to characterize the reactive sites and predict the preferred interactions of azomethine ylides to planar chalcones. The softness-matching indices have been evaluated to determine the regioselectivity of the cycloaddition reactions. The theoretical predictions were found to be in complete agreement with the experimental results, implying that the density functional theory (DFT)-based reactivity indices correctly predict the regioselectivities of 1,3-dipolar cycloadditions of azomethine ylides to planar chalcones. The frontier molecular orbital (FMO) energies, electronic chemical potentials, chemical hardness, chemical softness, and global electrophilicity indices of azomethine ylides have been calculated at the DFT/B3LYP/6-31 + G (d, p) level of theory.

State-Dependent Global and Local Electrophilicity of the Aryl Cations

Two alternative approaches—vertical and adiabatic—are used to estimate global and local electrophilicity (ω and ωk+) indexes for a series of aryl cations in both the ground and first excited electronic states using the well-known Parr scheme. The energy parameters used in these methods are obtained by the B3LYP/6-311++G(2d,2p) calculations of the aryl cations and of their oxidized and reduced forms in acetonitrile medium. The ground state ω values are lower than those for the excited state, which is in accord with the maximum hardness principle. Analysis of the ω indexes calculated with more reliable adiabatic approach reveals a dependence of the ground and first excited state ω indexes on the singlet–triplet energy gap of the aryl cations. A plot of the above dependence has a hyperbola-like shape; thus, the maximum (ground state) and minimum (first excited state) ω indexes correspond to the aryl cation, for which the singlet–triplet splitting is close to zero. Moreover, the ωk+ index distribution at the ipso-carbon atoms does not obey the maximum hardness principle, since it depends on spin multiplicity, not on the electronic state spatial type. For many singlet ground state aryl cations, the ωk+ indexes at the ipso-carbon atom are lower when calculated in the excited triplet state; that is due to a strong ω delocalization onto two electrophilic centers. This explains a higher chemoselectivity of the triplet aryl cations in reactions with the π-nucleophiles compared to the corresponding singlet arylium species. Applicability of the adiabatic approach for calculation of the ω and ωk+ indexes is supported by the experimental data on the nucleophile-independent parameter E for the singlet and triplet state of the p-Me2NC6H4+ cation.

1, 3-dipolar cycloaddition of C-phenyl carbamoyl-N-phenyl nitrone with some dialkyl-substituted 2-benzylidenecyclopropane-1,1-dicarboxylates: theoretical analysis of mechanism and regioselectivity

The regiochemistry of 1,3-dipolar cycloaddition reactions of C-phenyl carbamoyl-N-phenyl nitrone with some dialkyl-substituted 2-benzylidenecyclopropane-1,1-dicarboxylates as dipolarophile was investigated using density functional theory-based reactivity indexes and activation energy calculations at B3LYP/6-31G(d) level of theory. Analysis of the geometries and bond orders at the TS structures associated with the different reaction pathways shows that these 1,3-dipolar cycloaddition reactions occur via an asynchronous concerted mechanism. Analysis of the local electrophilicity and nucleophilicity indexes based on Parr functions only for reaction between 1 + 2a and based on Fukui functions only for 1 + 2b gives correct regioselectivity. The theoretical results obtained in the work clearly predict the regiochemistry of the isolated cycloadducts and agree to experimental results.

Reactivity and regioselectivity in the ring opening of 2-substituted non-activated aziridines: A density functional theory based analysis

Non-activated aziridines are the aziridines with an electron-donating group at nitrogen. Conceptual Density Functional Theory (DFT) based descriptors have been used to rationalize the observed activation and regioselectivity in the ring opening of 2-substituted non-activated aziridines via aziridinium intermediate. Reactivity indices such as electrophilicity index (ω), condensed Fukui function for nucleophilic attack (fk+) and local electrophilicity index (ωk+) have adequately and efficiently rationalized the observed activation and regioselectivity.

Prediction of the chemo- and regioselectivity of Diels–Alder reactions of o-benzoquinone derivatives with thiophenes by means of DFT-based reactivity indices

Global and local reactivity indices derived from density functional theory were used to elucidate the regio- and chemoselectivity of Diels–Alder reactions of masked o-benzoquinones with thiophenes acting as dienophiles. The polarity of the studied reactions is evaluated in terms of the difference of electrophilicity powers between the diene and dienophile partners. Preferential cyclisation modes of these cycloadditions are predicted using Domingo's polar model based on the local electrophilicity index, ωk, of the electrophile and the local nucleophilicity index, Nuk, of the nucleophile. The theoretical calculations, carried out at the B3LYP/6-311G(d,p) level of theory, are in good agreement with experimental findings.

Polar Diels-Alder Reactions Developed in a Protic Ionic Liquid: 3-Nitroindole as Dienophile. Theoretical Studies Using DFT Methods

N-Tosyl-3-nitroindole reacts with moderate and strong nucleophilic dienes in a polar Diels-Alder reaction using protic ionic liquid (PIL) [HMIM][BF4] as reaction media. In the cases in which the diene has oxygenated substituents, the PIL favors the aromatization of the formal [4+2] cycloadducts. Although the presence of the PIL in the reactions of Ntosyl- 3-nitroindole as electrophile shows a clear tendency to the aromatization of the [4+2] cycloadducts, we observed that the neoteric solvent did not increase the yields in relation to a molecular solvent. Part of this work is specifically concerned with theoretical studies using DFT reactivity indices. The global and local electrophilicity and nucleophilicity indices were calculated for N-tosyl-3-nitroindole, and the dienes used in this study. For the studied reactions, the regioselectivity involved in the polar Diels-Alder reaction is well predicted. Keywords: Dienophile, Diels-Alder, nitroindole, protic ionic liquid

Understanding the Bond Formation in Hetero-Diels-Alder Reactions. An ELF Analysis of the Reaction of Nitroethylene with Dimethylvinylamine

The bonding evolution in hetero-Diels-Alder (HDA) reactions has been studied by an ELF analysis of the electron reorganization along the HDA reaction between nitroethylene 6 and dimethylvinylamine (DMVA) 9 at the B3LYP/6-31G* level. This cycloaddition takes place along a two-stages one-step mechanism. In the first stage of the reaction, the C1-C6 bond is formed by coupling of two pseudoradical centers positioned at the most electrophilic carbon of nitroethylene 6 and the most nucleophilic center of DMVA 9. In the second stage, the formation of the second O4-C7 bond takes place between a pseudoradical center positioned at the C7 carbon of DMVA and some electron-density provided by the lone pairs of the O4 oxygen. This behavior is in complete agreement with the analyses of the local electrophilicity and nucleophilicity indices, and the spin density of the radical anion of nitroethylene 6 and of the radical cation of DMVA 9. Finally, a relationship between the polar character of the reaction and the regioselectivity is established.

Electronic fluxes during diels‐alder reactions involving 1,2‐benzoquinones: mechanistic insights from the analysis of electron localization function and catastrophe theory

By means of the joint use of electron localization function (ELF) and Thom's catastrophe theory, a theoretical analysis of the energy profile for the hetero-Diels-Alder reaction of 4-methoxy-1,2-benzoquinone 1 and methoxyethylene 2 has been carried out. The 12 different structural stability domains obtained by the bonding evolution theory have been identified as well as the bifurcation catastrophes (fold and cusp) responsible for the changes in the topology of the system. This analysis permits finding a relationship between the ELF topology and the evolution of the bond breaking/forming processes and electron pair rearrangements through the reaction progress in terms of the different ways of pairing up the electrons. The reaction mechanism corresponds to an asynchronous electronic flux; first, the O1-C5 bond is formed by the nucleophilic attack of the C5 carbon of the electron rich ethylene 2 on the most electrophilically activated carbonyl O1 oxygen of 1, and once the σ bond has been completed, the formation process of the second O4C6 bond takes place. In addition, the values of the local electrophilicity and local nucleophilcity indices in the framework of conceptual density functional theory accounts for the asychronicity of the process as well as for the observed regioselectivity.