Understanding the molecular mechanism of the [3 + 2] cycloaddition reaction of benzonitrile oxide toward electron‐rich N‐vinylpyrrole: a DFT study

The [3 + 2] cycloaddition (32CA) reaction of benzonitrile oxide, BNO 2 , with an electron‐rich N‐vinylpyrrole derivative, NVP 3a , in the presence of dichloromethane, has been theoretically studied using density functional theory (DFT) methods at the B3LYP/6‐31G(d) level. This 32CA reaction presents a relatively high activation Gibbs free energy as a result of the low polar character of this zwitterionic‐type (zw‐type) reaction. Analyses of the calculated relative Gibbs free energies and transition state geometries indicate that the studied 32CA reaction, in excellent agreement with experimental outcomes, takes place in a complete regioselective manner as a consequence of the steric repulsions that appear at the most unfavorable transition state. An electron localization function (ELF) topological analysis of the bonding changes along this 32CA reaction supports a non‐concerted two‐stage one‐step molecular mechanism in which the formation of the O3‐ C5 single bond takes place at the end of the reaction after the complete formation of the C1‐C4 one. Copyright © 2016 John Wiley & Sons, Ltd.     

A DFT‐based exploration augmented by X‐ray and NMR of the stereoselectivity in the 1,3‐dipolar cycloaddition of 1‐pyrroline‐1‐oxide to methyl cinnamate and benzylidene acetophenone

A B3LYP/6–31G* study was carried out for the reactions of 1‐pyrroline‐1‐oxide (N1) with methyl cinnamate (E1) and benzylidene acetophenone (E2) for getting a quantitative rationalization of the experimental findings. The product ratios were determined by NMR studies of the crude reaction mixtures. The conformation and stereochemistry of the isolated cycloadducts were finally confirmed by 2D NMR and X‐ray diffraction. The endo/exo‐selectivities were predicted through the computation of activation parameters on the basis of assumed concerted mechanism. The regioselectivity and reactivity were amply predicted by local and global electrophilicity indices and were found to be in good agreement with the experimental findings which were supportive of polar character and of the direction of charge transfer (CT) accompanying the cycloaddition. It was found that the cycloaddition involving methyl cinnamate was endo‐selective, while that with benzylidene acetophenone produced the exo‐isomer as the major adduct. Copyright © 2010 John Wiley & Sons, Ltd.     

Mechanism and regioselectivity of the 1,3‐dipolar cycloaddition of thiocarbonyl S‐imide with cyclopent‐3‐ene‐1,2‐dione and methoxyethene: a density functional theory approach

A theoretical study on the regioselectivity of 1,3‐dipolar cycloaddition reaction between an uncommon dipole (thiocarbonyl S‐imide) with cyclopent‐3‐ene‐1,2‐dione (DPh1) and methoxyethene (DPh2) has been carried out by means of several theoretical approaches, namely, activation energy, Houk's rule based on the frontier molecular orbital theory and density functional theory (DFT) reactivity indices. The calculations were performed at the DFT‐B3LYP/6‐31G(d) level of theory using GAUSSIAN 09. The present analysis shows that the 1,3‐dipolar cycloaddition of thiocarbonyl S‐imide with DPh1 and DPh2 has normal‐electron demand and inverse‐electron demand character, respectively. Moreover, the results obtained from energetic point view are in agreement with electronic approaches, and the Houk's rule is capable to predict true regioselectivity. Copyright © 2012 John Wiley & Sons, Ltd.     

A theoretical study of the mechanisms for 1,3‐dipolar cycloadditions of diphenyldiazomethane to C60 and C70

The 1,3‐dipolar cycloaddition (1,3‐DPCA) reaction plays a crucial role during the functionalization of fullerenes, which have broad applications in the materials and pharmaceutical fields. In concert with previous experiments, we theoretically investigated the mechanisms of 1,3‐DPCA of diphenyldiazomethane (DDMf) to two fullerenes (C₆₀ and C₇₀) using the M06‐2X density functional method under vacuum and in solvents. To understand the influence of the dipolarophile on these reactions, the 1,3‐DPCA of DDMf to three common acceptors, specifically tetracyanoethylene (TCNE), 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ), and chloranil (CA), was also studied at the same computational level. The substituent effects on the five reactions were investigated by modeling 1,3‐DPCA reactions with 12 different substituted DDMf (DDMs) with five dipolarophiles, totaling 60 reactions. Including the five unsubstituted DDMf reactions, 65 1,3‐DPCA reactions were studied. The stereoselectivity, relative reactivity, solvent effects, and distortion/interaction energy model were carefully considered and analyzed based on their corresponding electronic structures, electrostatic potential surfaces, interaction models, solvent models, and thermodynamic data. An intermediate was identified for each of the 65 reactions. A possible biradical pathway for the reactions between DDMf and the two fullerenes was also investigated. The calculated results corroborate and enrich the experimental observations. The conclusion and detailed discussion are generally important for understanding the 1,3‐DPCA reactions to fullerenes. Copyright © 2014 John Wiley & Sons, Ltd.     

Experimental and theoretical push‐pull Chemo‐ and regioselectivity in 1,3‐Dipolar cycloaddition reactions: the case of benzotriazepin‐5‐one with mesitylnitrile oxide

A novel heterocyclic compound 3‐mesityl‐5‐methyl‐4,5,11,11a‐tetrahydro‐6H‐[1,2,4]oxadiazolo [5,4‐b][1,3,4]benzotriazépin‐6‐one 4 has been synthesised by a 1,3 dipolar cycloaddition (13DC) reaction of 1,3,4‐benzotriazepin‐5‐one 1 with mesitylnitrile oxide 3 . The reaction, beside its synthetic interest, has shown to be completely chemo‐ and regioselective. The structure of the compound was determined by X‐ray crystallography and analysed by spectral methods (NMR and mass spectrometry). The molecular mechanism for the reaction has been studied using quantum mechanical calculations at the B3LYP/6‐31G* theory level. Two mechanisms are possible for the formation of the cycloadduct 4 . The first one involves a 13DC reaction between 1 , as dipolarophile and 3 , as dipole. Analysis of the results indicates that it takes place along asynchronous concerted bond‐formation process with a very low polar character. The regioselectivity obtained from the calculations are in complete agreement with the unique formation of the cycloadduct 4 . The second mechanism is initiated by the nucleophilic attack of the N3 nitrogen of the tautomer form of 2 , to the C5 carbon of the nitrile oxide 3 to yield an amidoxime. However, the large energy involved in this addition prevents this mechanism. The large energy difference between the tautomers 1 and 2 , makes that only the C?N site of benzotriazepin‐5‐one 1 could act as a dipolarophile site. This fact makes the 13DC reaction to be chemoselective. The analysis of global electrophilicity of the reagents allows explaining the low polar character of these 13DC reactions. Copyright © 2007 John Wiley & Sons, Ltd.     

Steric effect in alkylation reactions by N‐alkyl‐N‐nitrosoureas: a kinetic approach

The alkylation reactions of 4‐(p‐nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to DNA bases, by five N‐alkyl‐N‐nitrosoureas (methyl‐, ethyl‐, propyl‐, butyl‐, and allylnitrosourea) were investigated in 7:3 (v/v) water/dioxane medium in the 5.0–6.5 pH range. Decomposition of alkylnitrosoureas (ANU) gives rise to alkyldiazonium ions that yield NBP‐R adducts directly or through carbocations in certain instances. The NBP alkylation rate constants by these species were determined. The following sequence of alkylating potential was found: methyl‐ > ethyl‐ > allyl‐ > propyl‐ > butyl group. Application of Ingold–Taft correlation analysis to the kinetic results revealed that the NBP alkylation reactions occur mainly through steric control. The values of the molar absorption coefficients of the NBP‐R adducts also reveal the determinant influence of a steric effect in the formation of alkylation adducts. The kinetic results are consistent with the biological activity of ANU. Copyright © 2008 John Wiley & Sons, Ltd.     

Cycloaddition of CS2 to N‐benzylaziridine to synthesize N‐benzylthiazolidine‐2‐thione: a novel reaction route proposed by DFT Study

N‐Benzylthiazolidine‐2‐thione is the key intermediate for the synthesis of pharmaceutically important compounds. A novel route for the synthesis of N‐benzylthiazolidine‐2‐thione through cycloaddition of CS₂ with N‐benzylaziridine in the presence of 1,3‐di‐tert‐butylimidazolium‐2‐dithocarboxylate ( catalyst I ) has been proposed by reliable computations performed within the formalism of density functional theory. The mechanism of the proposed reaction is similar to the cycloaddition of tertiary aziridines and carbon dioxide using a recyclable catalyst that is reported to provide access to 3‐substituted 2‐oxazolidones with excellent yield. Because the rate determining step needs to surmount a high energy barrier, the reaction route has been deciphered in high boiling solvent (1, 2‐ethanediol). The highlight of the mechanistic route detailed here is that the proposed pathway is a cyclic process that is exothermic in nature with the regeneration of the catalyst and involves simple reagents. Copyright © 2016 John Wiley & Sons, Ltd.     

Mechanism of magnesium carbenoid 1,3‐C–H insertion: a DFT study

The 1,3‐C–H insertion of magnesium carbenoid and related species was investigated via density functional theory (DFT) calculations. The 1,3‐C–H insertion occurred according to an S_N2‐like mechanism wherein the nucleophilic C–H bond attacked the electrophilic carbenoid carbon atom. The activation energies for the 1,3‐C–H insertion of (1‐chloropropyl)magnesium chloride, (1‐methoxypropyl)magnesium chloride, and [1‐(methylthio)propyl]magnesium chloride were 20.0, 33.8, and 47.1 kcal/mol, respectively. Copyright © 2015 John Wiley & Sons, Ltd.     

DFT study of the 1,3‐dipolar cycloaddition of azomethine ylides with maleimide,maleic anhydride,methylacrylate and some simple substituted alkenes

DFT calculations involving the B3LYP functional and 6‐31G(d) basis set have been performed to rationalize the reactivity, regioselectivity, enantioselectivity and diasteriofacial selectivity in the context of 1,3‐dipolar cycloaddition (13DC) reactions of a few acyclic and two cyclic azomethine ylides (AY) leading to enantiomeric/ diasteriomeric excess of the products. In particular, N‐substituted and C‐substituted AYs have been considered for reactions with the substituted ethylenes, maleimide, maleic anhydride and methyl acrylate. From an analysis of the results of calculation for the selected reactions, the regio‐ and exo/endo‐stereoselectivity have been explained. Reactions were followed through transition state (TS) structure optimization, calculation of IRC and activation energies. A rationalization of the trends in regioselectivity and enantioselectivity was attempted with the help of HOMO–LUMO energies, electrophilicity differences (Δω) and an analysis of Pauling's bond order (PBO) in the TS. Copyright © 2009 John Wiley & Sons, Ltd.     

Computational study on intramolecular electron transfer in 1,3‐dintrobenzene radical anion

1,3‐Dinitrobenzene radical anion (DNB^?), which is a typical mixed valence compound, undergoes intramolecular electron transfer (ET) in solution. It is reported that the ET rates exceed 10¹⁰ s^?1 in polar aprotic solvent such as acetonitrile. Formulation based on a simple one‐dimensional model cannot quantitatively account for the observed ET rates, and further study has been desired for better understanding of the solvent effects on the ET. In the present study, molecular dynamics simulations were performed for DNB^? in the vacuum and in acetonitrile solution. In the vacuum, ET was induced by the antisymmetric C–N stretching mode on a timescale of ~100 fs, and the charge transferring between the nitro groups was much less than unity. For the acetonitrile solution, short‐timescale and long‐timescale simulations were performed using a droplet model of solvated DNB^? at 298 K. Although the mean C–N distance in the charged nitro group was longer than that in the vacuum, no ET took place in the short (~150 fs) simulations. The solvent coordinate, which was defined as the difference in the solute–solvent interaction energy between the reactant and the product, significantly fluctuated even in short‐time simulations. The reorganization energies in acetonitrile were evaluated on the basis of molecular orbital (MO) calculations, and the ratio of the inner sphere and outer sphere parts, λ_i/λ_o, was estimated to be ~0.6. The results suggest that the intramolecular mode and fast solvent mode may play an important role in the present ET reaction. Copyright © 2014 John Wiley & Sons, Ltd.     

Thermal reaction of electron deficient 4‐oxo‐4H‐pyrazole 1,2‐dioxide with cycloheptatriene: the first examples of the formation of an endo‐[4π + 6π]‐cycloadduct and an intramolecular 1,3‐dipolar reaction leading to a heterocage

The reaction of 3,5‐bis(methoxycarbonyl)‐4‐oxo‐4H‐pyrazole 1,2‐dioxide (1a) with 1,3,5‐cycloheptatriene (2b) gave a mixture of the novel endo‐[4 + 6]‐cycloadduct (4ab), anti‐exo‐[4 + 2]‐cycloadduct (5ab), and the heterocage (6ab) derived from the intramolecular 1,3‐dipolar cycloaddition reaction of the syn‐endo‐[4 + 2]‐cycloadduct. Analogous endo‐[4 + 6] selectivity in 1,3‐dipolar cycloadditions has not been reported previously. The X‐ray analysis indicates that 6ab has a very long N_sp3–N_sp3 bond distance of 1.617(4) Å. The cycloaddition behaviour is discussed on the basis of transition‐state structures optimized at the B3LYP/6‐31G(d) level of theory, from which predictions of the peri‐, regio‐, and stereoselectivities agreed well with the experimental results. Copyright © 2012 John Wiley & Sons, Ltd.     

Pressure effects on structural,electronic, absorption,and thermodynamic properties of crystalline 2,4,6‐triamino‐3,5‐dinitropyridine‐1‐oxide: A DFT study

Density functional theory calculations have been performed to study the structural, electronic, absorption, and thermodynamic properties of crystalline 2,4,6‐triamino‐3,5‐dinitropyridine‐1‐oxide (TANPyo) in the pressure range of 0–50 GPa. The variation trends of the lattice constants, bond lengths, bond angles, intramolecular H‐bonds, and dihedral angles under compression show that there are two structural transformations at 17 and 38 GPa, respectively. The remarkable changes in the bond lengths indicate that there are two possible initiation decomposition mechanisms of TANPyo under compression. As the pressure increases, the intramolecular H‐bond strengthens. The obvious changes of the dihedral angles show that the planar structure of the TANPyo molecule is damaged under compression. Its absorption spectra show that as the pressure increases, the absorption coefficient of the N–H stretching decreases, while that of the O–H stretching increases. TANPyo has relatively high optical activity at high pressure. An analysis of thermodynamic properties indicates that both two structural transformations are endothermic and not spontaneous at room temperature. Copyright © 2013 John Wiley & Sons, Ltd.     

An experimental and theoretical study on the preparation of 4,4′‐methylene‐bis(N,N‐dimethylaniline) in ionic liquid

The reaction of N,N‐dimethylaniline with tetrachloromethane in ionic liquid was found to give 4,4′‐methylene‐bis (N,N‐dimethylaniline) in considerable yield. The ionic liquid was prepared from N,N‐dimethylaniline which is also the one of raw materials for the preparation of 4,4′‐methylene‐bis (N,N‐dimethylaniline), and acts as both solvent and catalyst in the reaction. Mild reaction conditions, enhanced rates, improved yields, and reagents' reactivity which is different from that in conventional organic solvents are the remarkable features observed in ionic liquids. In addition, the results of calculations are in good accordance with the experimental outcomes. Copyright © 2016 John Wiley & Sons, Ltd.     

DFT study of graphene oxide reduction by a dopamine species

Recently a large interest has arisen for using less active reducers of graphene oxide, GO, that are friendly with the environment. In the present work, a DFT theoretical study on the reduction process of GO model surfaces is performed taking into account zwitterionic dopamine, ZDA, as reducing agent. Several periodic models representing epoxy and hydroxyl patches on GO basal plane are proposed. As the number of oxide groups in a patch of epoxies or hydroxyls on the surface of graphene increases from 1 to 5, these systems become more stable. Whereas the adsorption of ZDA on patches of GO with 5 epoxy groups is non-dissociative, that of ZDA on patches of GO with 5 hydroxyl groups is fundamentally dissociative, reducing the surface of graphene oxide. The H₂O molecule produced in the GO reduction becomes trapped to ZDA through a hydrogen bond. The ZDA binding to GO was analysed by considering electrostatic effects and attractive non-covalent contributions due to vdW interactions.     

Combined 1H NMR and DFT study of the solvent effects on the iron pentacarbonyl‐catalyzed photo‐assisted isomerization of allyl alcohol

The relative rates of iron pentacarbonyl‐catalyzed photo‐induced isomerization of allyl alcohol to propanal in various solvents have been measured using ¹H NMR spectroscopy. The reactions were run in linear and cyclic alkanes, alcohols, and amines in order to investigate solvent effects on the isomerization mechanism upon ultraviolet irradiation. The isomerization was efficient in nonane, hexane, cyclohexane, and benzene. The isomerization was very slow or completely suppressed in ethanol, propanol, isopropanol, triethylamine, and pyridine. Density functional theory calculations predicted thermodynamically favorable (ΔG^o < 0) formation of Fe(CO)₄–solvent compounds in the suppressing alcohol/amine solvents and unfavorable (ΔG^o > 0) formation in the hydrocarbon solvents. The strong solvent ligation likely prevents formation of Fe(CO)₃●(η²‐alkene) necessary for isomerization. Copyright © 2013 John Wiley & Sons, Ltd.     

Density functional theory study and vibrational analysis of FT‐IR and FT‐Raman spectra of N‐hydroxyphthalimide

The Fourier transform infrared (FT‐IR) spectrum of N‐hydroxyphthalimide has been recorded in the range of 4000–400 cm⁻¹, and the Fourier transform Raman (FT‐Raman) spectrum of N‐hydroxyphthalimide has been recorded in the range of 4000–50 cm⁻¹. With the hope of providing more and effective information on the fundamental vibrations, the Density Functional Theory (DFT)‐Becke3‐Lee‐Yang‐Parr (B3LYP) level with 6‐31G* basis set has been employed in quantum chemical analysis, and normal coordinate analysis has been performed on N‐hydroxyphthalimide by assuming C_s symmetry. The computational wavenumbers are in good agreement with the observed results. The theoretical spectra obtained along with intensity data agree well with the observed spectra. Copyright © 2009 John Wiley & Sons, Ltd.     

Excited‐state hydrogen bond strengthening of coumarin 153 in ethanol solvent: a TDDFT study

So far, coumarin dyes have been extensively studied with various means to understand their photophysical behaviors and photochemical properties. Here, our performing time‐dependent density functional theory calculation is aimed at exploring the excited‐state hydrogen bonding dynamics of coumarin 153 (C153) in protic ethanol (EtOH) solvent. The calculated results suggest that the excited‐state hydrogen bond C?O?H?O between C?O group and O?H group in the C153‐EtOH complex is strengthened, and the S₀ → S₁ transition of the complex corresponds to the highest occupied molecular orbital (HOMO) hopping to the lowest unoccupied molecular orbital (LUMO). The excited‐state hydrogen bond strengthening has been further confirmed by its larger binding energy in the S₁ state than in the S₀ state. In addition, because of the formation of the hydrogen bond C?O?H?O, a red shift of about 7 nm occurs in the electronic spectra of the C153‐EtOH complex, which is in good accordance with the experiment result. Copyright © 2016 John Wiley & Sons, Ltd.     

Palladium‐catalyzed cyclization of 2‐alkynyl‐N‐ethanoyl anilines to indoles: synthesis,structural, spectroscopic,and mechanistic study

This study reports a facial regio‐selective synthesis of 2‐alkyl‐N‐ethanoyl indoles from substituted‐N‐ethanoyl anilines employing palladium (II) chloride, which acts as a cyclization catalyst. The mechanistic trait of palladium‐based cyclization is also explored by employing density functional theory. In a two‐step mechanism, the palladium, which attaches to the ethylene carbons, promotes the proton transfer and cyclization. The gas‐phase barrier height of the first transition state is 37 kcal/mol, indicating the rate‐determining step of this reaction. Incorporating acetonitrile through the solvation model on density solvation model reduces the barrier height to 31 kcal/mol. In the presence of solvent, the electron‐releasing (–CH₃) group has a greater influence on the reduction of the barrier height compared with the electron‐withdrawing group (–Cl). These results further confirm that solvent plays an important role on palladium‐catalyzed proton transfer and cyclization. For unveiling structural, spectroscopic, and photophysical properties, experimental and computational studies are also performed. Thermodynamic analysis discloses that these reactions are exothermic. The highest occupied molecular orbital?lowest unoccupied molecular orbital gap (4.9–5.0 eV) confirms that these compounds are more chemically reactive than indole. The calculated UV–Vis spectra by time‐dependent density functional theory exhibit strong peaks at 290, 246, and 232 nm, in good agreement with the experimental results. Moreover, experimental and computed ¹H and ¹³C NMR chemical shifts of the indole derivatives are well correlated. Copyright © 2015 John Wiley & Sons, Ltd.     

Solvatochromism of 2‐(N,N‐dimethylamino)‐7‐nitrofluorene and the natural dye β‐carotene: application for the determination of solvent dipolarity and polarizability

The effects of solvents on chemical phenomena (rate and equilibrium constants, spectroscopic transitions, etc.) are conveniently described by solvation free‐energy relationships that take into account solvent acidity, basicity and dipolarity/polarizability. The latter can be separated into its components by manipulating the UV–vis spectra of two solvatochromic probes, 2‐(N,N‐dimethylamino)‐7‐nitrofluorene (DMANF) and a di‐(tert‐butyl)‐tetramethyl docosanonaen probe (ttbP9) whose synthesis is laborious and expensive. Recently, we have shown that the natural dye β‐carotene can be conveniently employed instead of ttbP9 for the determination of solvent polarizability (SP) of 76 molecular solvents and four ionic liquids. In the present work, we report the polarizabilities of further 24 solvents. Based on the solvatochromism of β‐carotene and DMANF, we have calculated solvent dipolarity (SD) for 103 protic and aprotic molecular solvents, and ionic liquids. The dependence of SD and SP on the number of carbon atoms in the acyl‐ or alkyl group of several homologous series (alcohols; 2‐alkoxyethanols; carboxylic acid‐ anhydrides, and esters, ionic liquids) is calculated and briefly discussed. Copyright © 2013 John Wiley & Sons, Ltd.     

A DFT study of the mechanism and selectivities of the [3 + 2] cycloaddition reaction between 3‐(benzylideneamino)oxindole and trans‐β‐nitrostyrene

The mechanism and regioselectivities and stereoselectivities of the [3 + 2] cycloaddition (32CA) reaction of 3‐(benzylideneamino) oxindole (AY) and trans‐β‐nitrostyrene have been studied using both B3LYP and ωB97XD density functional theory methods together with the standard 6‐31G(d) basis set. Four reactive pathways associated with the ortho and meta regioselective channels and endo and exo stereoselective approaches modes have been explored and characterized. While the B3LYP functional fails to predict the experimental regioselectivity, the ωB97XD one succeeds to predict the experimentally observed meta regioselectivity favoring the formation of meta/endo cycloadduct as the major isomer. Inclusion of solvent effects increases the regioselectivity and decreases the experimentally observed stereoselectivity. Analysis of the density functional theory global reactivity indices and the Parr functions of the reagents in its ground state allows explaining the reactivity and the meta regioselectivity of this zwitterionic‐type 32CA reaction, which account for the high polar character of this reaction. Non‐covalent interaction analysis of the most favorable meta/endo transition state structure reveals that the formation of a hydrogen‐bond between 1 nitro oxygen and the AY N–H hydrogen is responsible for the selectivity experimentally found in this polar zwitterionic‐type 32CA reaction.