Revisiting Aromaticity and Chemical Bonding of Fluorinated Benzene Derivatives

The electron delocalization of benzene (C₆H₆) and hexafluorobenzene (C₆F₆) was analyzed in terms of the induced magnetic field, nucleus-independent chemical shift (NICS), and ring current strength (RCS). The computed out-of-plane component of the induced magnetic field at a distance (r) greater than or equal to 1.0 Å above the ring center correlates well (R²>0.99) with the RCS value. According to these criteria, fluorination has two effects on the C₆ skeleton; concomitantly, the resonant effects diminish the π electron delocalization and the inductive effects decrease the charge density at the ring center and therefore reduce the magnitude of the paratropic current generated in this region. The equilibrium between both effects decreases aromaticity in the fluorinated benzene derivatives. These results can be extrapolated to determine the aromaticity of any derivative within the series of fluorinated benzene derivatives (C₆H_(6−n)F_n, where n=1–5).     

Theoretical study of the internal rotational barriers in nitrobenzene, 2‐nitrotoluene, 2‐nitrophenol,and 2‐nitroaniline

The molecular geometries and internal rotational barriers of the nitro group of nitrobenzene (NB), 2‐nitrotoluene (2‐NT), 2‐nitroaniline (2‐NA), and 2‐nitrophenol (2‐NP) were calculated by five different types of density functional theory (DFT) methods with three different levels of basis sets. Analysis of the torsional angles of the nitro, methyl, amino, and hydroxyl groups indicate that NB, 2‐NA, and 2‐NP are planar molecules, but 2‐NT is not a planar molecule. Internal rotational barriers of the nitro group were calculated as V₂ barriers, and the NO₂ torsional potentials for each molecule were given. The values of the V₂ barriers depend on the DFT methods and basis sets. The average values of the V₂ barriers for NB, 2‐NT, 2‐NA, and 2‐NP are 6.47 kcal/mol, 3.00 kcal/mol, 10.20 kcal/mol, and 13.26 kcal/mol, respectively. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 83: 332–337, 2001     

Method and basis set dependence of the NICS indexes of aromaticity for benzene

The role of theory level in prediction of benzene magnetic indexes of aromaticity is analysed and compared with calculated nuclear magnetic shieldings of ³He used as NMR probe. Three closely related nucleus‐independent chemical shift (NICS) based indexes were calculated for benzene at SCF‐HF, MP2, and DFT levels of theory and the impact of basis set on these quantities was studied. The changes of benzene NICS(0), NICS(1), and NICS(1)zz parameters calculated using SCF‐HF, MP2 and several density functionals were within 1 to 3 ppm. Similar deviations between magnetic indexes of aromaticity were observed for values calculated with selected basis sets. Only very small effect of polar solvent on benzene aromaticity was predicted. The ³He nuclear magnetic isotropic shielding (σ) and its zz‐components (σ_zz) of helium atom approaching the centre of benzene ring from above produced similar curves versus benzene‐He distance to NICS parameters calculated for similarly moving Bq ghost atom. We also propose an experimental verification of NICS calculations by designing the ³He NMR measurement for benzene saturated with helium gas or in low temperature matrices.     

Theoretical studies on the structures,properties, and aromaticities of fluorinated arsabenzenes

The electronic structures and properties of the fluorinated arsabenzenes series have been investigated using the basis set 6–311+G(d,p) and hybrid density functional theory. The basic measures of aromatic character derived from molecular orbitals and magnetic criteria (anisotropic susceptibilities and nucleus-independent chemical shifts) are considered. The energy criteria suggest that the F3, F36, H36, and H3 isomers are the most stable isomers in the mono-, di-, tri-, and tetrafluorinated species, respectively. Analysis of χ_aniso and the HOMO-LUMO gaps showed that these were not compatible with NICS data. The NICS values show that aromaticity is greater in the fluorinated derivatives.     

Detection of NO2 by hexa-peri-hexabenzocoronene nanographene: A DFT study

It has been previously indicated that pristine graphene cannot detect NO₂ gas. Nanographene is a segment of graphene whose end atoms are saturated with hydrogen atoms and its properties are different from those of graphene. Herein, we investigated the reactivity, electronic sensitivity, and structural properties of hexa-peri-hexabenzocoronene (HBC) nanographene toward NO₂ gas using density functional theory calculations. It was found that the central and peripheral rings of HBC are aromatic but the middle rings are non-aromatic, following Clar's sextet rule of aromaticity. The NO₂ molecule prefers to be adsorbed on the central ring with a nitro configuration, releasing an energy of about 13.2 kJ/mol. The NO₂ molecule significantly stabilizes the LUMO level of the HBC, thereby reducing the HOMO–LUMO energy gap from 3.60 to 1.35 eV. This indicates that the HBC is converted from a semiconductor to a semimetal. It was shown that the adsorption of NO₂ gas by HBC can produce an electrical signal selectively in the presence of O₂, H₂, N₂, CO₂, and H₂O gases. A short recovery time about 1.9 ns is predicted and the effect of density functional is investigated.     

Impact of Fluoroalkyl Substituents on the Physicochemical Properties of Saturated Heterocyclic Amines

The physicochemical properties (pK_a(H), log P, and aqueous solubility) of fluoroalkyl-substituted heterocyclic amines were profiled to facilitate the amines’ rational application in medicinal chemistry research. The features of fluorine-containing compounds were compared to those of the corresponding parent non-fluorinated heterocycles and the corresponding fluorinated n-alkylamines. Amine basicity was observed to change in a monotonic fashion depending on the fluorination pattern. Although the introduction of fluoroalkyl groups had complex effects on the lipophilicity and aqueous solubility of the compounds, possible contributions of the fluorination pattern, ring size, and conformation of the substituent in the ring were addressed for a series of derivatives. The summarized data provide a useful guideline for the application of fluorinated motifs for fine-tuning a compound's properties related to drug discovery.     

A computational study of tetrafluoro-[2.2]cyclophanes

A computational study of the isomers of tetrafluorinated [2.2]cyclophanes persubstituted in one ring, namely F4-[2.2]paracyclophane (4), F4-anti-[2.2]metacyclophane (5a), F4-syn-[2.2]metacyclophane (5b), and F4-[2.2]metaparacyclophane (6a and 6b), was carried out. The effects of fluorination on the geometries, relative energies, local and global aromaticity, and strain energies of the bridges and rings were investigated. An analysis of the electron density by B3PW91/6-31+G(d,p), B3LYP/6-31+G(d,p), and MP2/6-31+G(d,p) was carried out using the natural bond orbitals (NBO), natural steric analysis (NSA), and atoms in molecules (AIM) methods. The analysis of frontier molecular orbitals (MOs) was also employed. The results indicated that the molecular structure of [2.2]paracyclophane is the most affected by the fluorination. Isodesmic reactions showed that the fluorinated rings are more strained than the nonfluorinated ones. The NICS, HOMA, and PDI criteria evidenced that the fluorination affects the aromaticity of both the fluorinated and the nonfluorinated rings. The NBO and NSA analyses gave an indication that the fluorination increases not only the number of through-space interactions but also their magnitude. The AIM analysis suggested that the through-space interactions are restricted to the F4-[2.2]metacyclophanes. In addition, the atomic properties, computed over the atomic basins, gave evidence that not only the substitution, but also the position of the bridges could affect the atomic charges, the first atomic moments, and the atomic volumes.     

Solvent impact on the planarity and aromaticity of free and monohydrated zinc phthalocyanine: a theoretical study

A theoretical investigation on the planarity of molecular structure of zinc phthalocyanine (ZnPc) and its aromaticity has been performed using B3LYP and M06-2X density functionals combined with selected Pople-type basis sets. The effect of the applied calculation method on the optimized structure of ZnPc and ZnPc???H₂O, both in the gas phase and in the polar solvent, was analyzed. To quantify the aromaticity of the ZnPc and ZnPc???H₂O complexes, both the geometric and magnetic criteria, i.e., Harmonic Oscillator Model of Aromaticity (HOMA) index and the nucleus-independent chemical shift (NICS) values at the centers or 1 Å above the centers of structural subunits, were calculated. The energies of highest energy occupied molecular orbital (HOMO) and lowest energy unoccupied molecular orbital (LUMO) and energy gaps were also estimated. The results show that the free ZnPC molecule is flat in the gas phase and nonplanar in the polar environments (DMSO and water). ZnPC???H₂O is nonpolar in the gas phase and polar solvent which is in agreement with recent X-ray reports. Both HOMA and NICS indexes indicate the presence of highly aromatic macrocycle and benzene rings while these parameters for pyrrolic ring are significantly smaller than in free pyrrole. The presence of polar solvents practically does not change aromaticity of the ring subunits of the studied compounds.     

Chemical bonding and properties in [Ni(N-heterocylic carbene)(NO)(R)] (R = H, Me, HC=CH2, and C≡CH) complexes: Theoretical insights

A series of N-heterocyclic carbene nickel complexes of the type [Ni(N-heterocylic carbene)(NO)(R)] (R = H, Me, HC=CH₂, and C≡CH) are examined to study the influence of a substituent on the molecular structure and bonding of these complexes. Geometrical and AIM analyses of the interaction between Ni and the carbene fragment reveal that for the metal-carbene bond donation is more important than back-donation. The NICS values suggest that aromaticity in the heterocyclic ring is less than in the free heterocycle.     

A Theoretical Study of NBO,NICS, and 14N NQR Parameters of Adenine Tautomers in the Gas Phase via DFT

The natural bond orbital (NBO) analysis, nucleus independent chemical shift (NICS), and ¹⁴N NQR parameters of the most stable tautomers of adenine in the gas phase were predicted using density functional theory method. The NBO analysis revealed that the resonance interaction between lone pair of the nitrogen atom and empty non‐Lewis NBO increases with increasing the p character of the nitrogen lone pair. The present investigation indicated the π clouds in both the considered heterocyclic rings containing six electrons, and these tautomers has the aromatic character. The NICS study utilizing the gauge‐invariant atomic orbital method showed that there are diatropic currents in the heterocyclic rings of the tautomers, so we determined the order of overall aromaticity of these tautomers. The results of NQR parameter calculations showed three parameters are effective on nuclear quadrupole coupling constant; the p character value of lone pair electrons of nitrogens, and the related occupancies and whenever, the lone pair electrons of nitrogens participate in the formation of chemical bond and/or π system of the ring, the q_zz and consequently its χ decreases.     

Three‐dimensional aggregation in 2‐hydroxy‐3‐iodo‐5‐nitrobenzaldehyde involving C—H⋯O,iodo–nitro and aromatic π–π stacking interactions,and isolated dimers in disordered 2,4‐diiodo‐6‐nitroanisole

In 2‐hydroxy‐3‐iodo‐5‐nitro­benz­aldehyde, C₇H₄INO₄, the mol­ecules are linked into sheets by a combination of C—H⋯O hydrogen bonds and two‐centre iodo–nitro interactions, and these sheets are linked by aromatic π–π stacking interactions. Molecules of 2,4‐di­iodo‐6‐nitro­anisole, C₇H₅I₂NO₃, are disordered, with the nitro group and one of the I substituents each occupying common sets of sites with 0.5 occupancy. The mol­ecules are linked into isolated centrosymmetric dimeric units by a single iodo–nitro interaction.     

Probing the aromaticity in 2,3-pyrido-annulated N-heterocyclic carbene and its heavier analogues

The aromaticity in 2,3-pyrido-annulated 1,3,2λ²-diazatetroles C₅H₃N(NR)₂E^II (E^II = C, Si, Ge, Sn, Pb) was studied using a set of experimental and calculated criteria: UV-VIS, Raman, ISE, NICS, GIMIC and EDDB. The data obtained indicate either a slight decrease in aromaticity (NICS, GIMIC, ISE methods) or equal aromaticity (UV-VIS, ISE methods) compared to benzo-annulated analogues C₆H₄(NR)₂E. The π-aromaticity increases down the group from Si to Pb.     

Is nucleus-independent chemical shift scan a reliable aromaticity index for planar and neutral A2B2 clusters?

Nucleus-independent chemical shift (NICS) scan has been employed in order to explain the aromaticity in eleven planar, neutral and tetrameric mixed clusters of trans-A₂B₂ type. The results suggest that for seven A₂B₂ clusters, although very high negative NICS values are obtained while performing the NICS scan, yet the typical minimum is not present in the scanning curve. The NICS scanning procedure thus fails to account for the aromatic behavior in those four-membered A₂B₂ clusters. Amongst them, interestingly it has been observed that for four such clusters the scan shape looks like the mirror image of a typical scan of an antiaromatic system. Based on the NICS scan, at the most, those four clusters can be said to possess nonaromatic behavior. In case of the remaining four clusters, the NICS scan shape passes through a distinct minimum and successfully explains their aromatic behavior. Hence, the overall investigation indicates that NICS scan alone cannot be used as a reliable aromaticity index for planar and neutral A₂B₂ clusters.     

13C, 14N, 15N and 17O NMR spectra of nitropyrroles and nitroimidazoles

Carbon, nitrogen and oxygen NMR spectra of some nitro derivatives of pyrrole and imidazole have been investigated. The ¹³C chemical shifts of para-carbons and the ¹⁷O chemical shifts of the nitro group correlate qualitatively with the electron densities on these carbon and oxygen atoms, which in turn depend upon the degree of conjugation of the nitro groups with the heterocyclic ring. Conjugation of several nitro groups with the benzene ring is in most cases not impaired by mutual interactions and the ¹³C shifts show good additivity. Such additivity is much worse in pyrrole and imidazole derivatives. Taken together with the diamagnetic nature of these deviations from additivity, this leads to a possible conclusion about the less pronounced conjugation of the nitro groups with the heterocyclic ring in heterocyclic dinitro derivatives.     

Crystal and molecular structure of [RuNO(NO2)4OHCuPy n ] heterometallic complexes

Heterometallic complexes [RuNO(NO₂)₄OHCuPy₂(H₂O)] (I) and [RuNO(NO₂)₄OHCuPy₃] (II) are described structurally for the first time. In complex I, the ruthenium anion is coordinated to the copper atom by the bridging OH group and two bridging nitro groups; in complex II, by the bridging OH group and one bridging nitro group. Dimers are formed in the crystal lattice of complex II due to the interaction of the copper atom and the nitro group of the ruthenium anion in trans position to the bridging NO₂ group.     

The Influence of Aromaticity in Gas Chromatography Retention: The Case of Polycyclic Aromatic Sulfur Heterocycles

Aromaticity has been used as a criterion to explain the gas chromatographic (GC) retention of cata-condensed polycyclic aromatic sulfur heterocycles (PASHs) C₁₂H₈S, C₁₆H₁₀S, C₂₀H₁₂S; and peri-condensed PASHs C₁₈H₁₀S, in a GC column with 50% phenyl/50% dimethyl silphenylene polymer. To establish the aromaticity, nucleus-independent chemical shifts at the level of the molecular plane, NICS(0), and at 1 Å above the surface of the molecular plane, NICS(1), have been used. It has been found that the GC retention of cata-condensed PASHs C₁₂H₈S, C₁₆H₁₀S, and C₂₀H₁₂S is satisfactorily defined by the aromaticity of the entire molecule, and the GC retention of peri-condensed PASHs C₁₈H₁₀S is satisfactorily defined by the local aromaticity in the sulfur pentagonal ring. In addition, the positive slope between GC retention and NICS(0) of the entire molecule for cata-condensed PASHs, C₁₂H₈S and C₁₆H₁₀S, and by NICS(1) in the pentagonal ring for peri-condensed PASHs, C₁₈H₁₀S, is explained by the interaction between the electrons of the heterocycle molecule and the positive pole of the silicon atom in the GC column, as suggested with PAHs. In contrast, the negative slope between GC retention and aromaticity for cata-condensed C₂₀H₁₂S is explained by the presence of bay, cove, or fjord regions in the vicinity of the sulfur atom that generates either higher GC retention and lower aromaticity or lower GC retention and higher aromaticity.     

Local aromaticity mapping in the vicinity of planar and nonplanar molecules

We report on nucleus-independent magnetic shielding (NICS) scans over the centers of six- and five-membered rings in selected metal phthalocyanines (MPc) and fullerene C60 for more accurate characterization of local aromaticity in these compounds. Detailed tests were conducted on model aromatic molecules including benzene, pyrrole, indole, isoindole, and carbazole and subsequently applied to H₂Pc, ZnPc, Al(OH)Pc, and CuPc. Similar behavior of three selected magnetic probes, Bq, ³He, and ⁷Li⁺, approaching perpendicularly the ring centers, was observed. For better visualization of shielding zone over the centers of aromatic rings, we introduced a simple mathematical procedure: the first and second derivatives of scan curves with respect to magnetic probe position enabled their additional examination. It allowed an easier localization of curve minimum and discrimination between areas in space varying by the magnetic field magnitude and to illustrate local aromaticity of two different kinds of rings in MPc with better resolution. Our results supported earlier reports on very low aromaticity indexes of pyrrole ring incorporated into MPc and significant aromaticity of the central macrocycle. No direct dependence between harmonic oscillator model of aromaticity and NICS was observed. Instead, a correlation between position of scan curve minimum and its magnitude were observed. In addition, the NICS values and ³He chemical shifts in the middle of neutral C60 and C60⁶⁻ anion agreed well with the reported experimental NMR values for He@C60 and He@C60⁶⁻.     

Influence of peripheral substituents on the stability of sandwich-type complexes of crown ether-containing anthraquinoneimines

Benzo-15-crown-5 ether derivatives of 1-hydroxy-9,10-anthraquinone-9-imine bearing a substituted benzoylamino group, NHCO(p-C₆H₄NO₂) or NHCOC₆F₅, in position 2 were synthesized by a photochemical method. The structure of the fluorine-containing compound was determined by single-crystal X-ray diffraction. Both synthesized dyes, as well as their analogue without substituents on the benzoyl ring, are capable of binding Sr²⁺ and Ba²⁺ to form sandwich-type 2:1 (ligand:metal) complexes. In MeCN, these complexes exhibit higher stability constants (K_2:1) than the corresponding 1:1 complexes (K_1:1). The para-substitution of the benzoyl ring with a nitro group leads to a significant increase in both the K_2:1 constant and the K_2:1/K_1:1 ratio. The fluorination of the benzoyl ring insignificantly affects the stability of sandwich complexes. Density functional theory calculations showed that this is related to steric interactions in the benzoylamino group. The calculated structures of the dyes and their sandwich complexes with Ba²⁺ are consistent with the 2D NOESY data.