Imidazolium ionic liquids (IMILs) with a piperidine moiety appended via variable length methylene spacers (with n = 1–4) were studied computationally to assess their potential to act as internal base for N-heterocyclic carbene (NHC) generation. Proton transfer energies computed by B3LYP/6-311+G(2d,p) were least endothermic for the basic-IL with n = 3, whose optimized structure showed the shortest C₂-H----N(piperidine) distance. Inclusion of counter anion (Cl or NTf₂) caused dramatic conformational changes to enable close contact between the acidic C₂-H and the anions. To examine the prospect for internal C₂-H----N coordination, multinuclear NMR data (¹H, ¹⁵N, and ¹³C) were computed by gauge independent atomic orbitals–density functional theory (GIAO-DFT) in the gas phase and in several solvents by the PCM method for comparison with the experimental NMR data for the basic ILs (with n = 2–4) synthesized in the laboratory. These studies indicate that interactions with solvent and counter ion are dominant forces that could disrupt internal C₂-H----N coordination/proton transfer, making carbene generation from these basic-ILs unlikely without an added external base. Therefore, the piperidine-appended IMILs appear suitable for application as dual solvent/base in organic/organometallic transformations that require the use of mild base, without the necessity to alkylate at C-2 to prevent N-heterocyclic carbene formation. Copyright © 2016 John Wiley & Sons, Ltd.

The reagent 4-(pentafluorosulfanyl)benzenediazonium tetrafluoroborate (1) was synthesized and isolated as a stable salt for the first time; its application in a wide assortment of transformations was subsequently investigated. A series of novel SF₅-bearing alkenes, alkynes, and biaryl derivatives were synthesized by employing Heck–Matsuda, Sonogashira, and Suzuki coupling protocols. Dediazoniation with TMSX (X = Hal; N₃; and CN) and NH₄SCN in [BMIM][BF₄] as solvent furnished the corresponding p-SF₅–C₆H₄X derivatives. The azide derivative p-SF₅–C₆H₄N₃ entered into click chemistry with phenylacetylenes to furnish the corresponding triazoles. The 4,4′-bis(pentafluorosulfanyl)biphenyl was synthesized by homo-coupling using Pd(OAc)₂. The corresponding azo compounds were obtained through azo-coupling with reactive aromatic nucleophiles (1,3-dimethoxybenzene, 1,3,5-trimethoxybenzene, 1,2,4-trimethoxybenzene, aniline and phenol). Fluorodediazoniation in [BMIM][PF₆] and [BMIM][BF₄] selectively furnished the fluoro derivative p-SF₅–C₆H₄F. Dediazoniation in [BMIM][NTf₂] gave p-SF₅–C₆H₄OS(O)(CF₃)=NSO₂CF₃ as the major and p-SF₅–C₆H₄-NTf₂ as the minor products. Homolytic dediazoniation in MeCN/NaI gave the unsymmetrical biaryls p-SF₅–C₆H₄-Ar (ArH = mesitylene and p-xylene) along with p-SF₅–C₆H₄I. Analysis of the dediazoniation product mixtures indicated that dediazoniation of p-SF₅–C₆H₄N₂⁺ BF₄^– in low nucleophilicity, highly ionizing, solvents (TfOH, TFE, HFIP, TFAH) is mainly heterolytic, while in MeOH it is mainly homolytic. The isodesmic reaction p-SF₅–C₆H₄⁺ + R-C₆H₅  SF₅–C₆H₅ + p-R-C₆H₄⁺ (with R = NO₂, CF₃, H) was gauged by DFT at various levels and by PCM.

Propargylic cations, generated by the ionization of propargyl alcohols with catalytic amounts of Bi(OTf)₃, react with aryl-substituted allenes to generate incipient allylic cations that are quenched in the presence of TMSCl to form a number of sterically crowded chloro-enynes as a mixture of Z and E isomers with a strong preference for the Z alkenes. Several other metallic triflates, M(OTf)₃ (M = Sc, Yb, La), as well as bismuth nitrate Bi(NO₃)₃·5H₂O also promote this reaction with similar conversions and stereoselectivity. Although trapping with TMSBr and TMSI gave intractable mixtures, trapping with TMSN₃ in a couple of cases led to the isolation of the corresponding isomeric azido-enynes, albeit in lower isolated yields and lower stereoselectivity. Competitive formation of the Meyer–Schuster rearrangement products was also observed. Sterically crowded chloro-allenes did not form adducts with propargyl alcohols, instead they underwent a skeletal rearrangement under the influence of Bi(OTf)₃ to form 2-chloro-butadienes. The results of DFT calculations indicated that the relative anti/syn energies of the propargyl cation and the energy difference between the Z/E isomeric products are too small to explain the stereochemical preference observed for the enynes. A study of the transition state in the crucial C–C bond-forming step by DFT indicated that rotation of the benzylic portion away from the propargyl cation may be a key factor in favoring the anti isomer of the allylic cation.

A computational density functional theory study on the structural and electronic properties of several polycyclic aromatic hydrocarbon (PAH) ortho-quinones was performed and the possible mechanism of DNA-adduct formation was analyzed to evaluate its thermodynamic viability. Molecular docking techniques were applied to examine the noncovalent interactions developed when a model PAH ortho-quinone intercalates between the DNA double helix. Quantum-chemical ONIOM (our Own N-layer Integrated molecular Orbital molecular Mechanics) calculations within the structure of a DNA fragment were carried out to evaluate the significant steps of noncovalent complex and covalent adduct formation. The solvent effect was also considered by employing a continuum solvation model. The present calculations suggest that initial noncovalent interactions of the PAH o-quinone within the DNA double helix could determine the feasibility of benzo[a]pyrene-7,8-dione-DNA covalent adduct formation, and that dispersion-corrected functionals are more suitable for locating the noncovalent complex. Copyright © 2012 John Wiley & Sons, Ltd.

A series of 5-substituted 1H-tetrazoles were synthesized through [3+2] cycloaddition reactions between nitriles RCN and NaN₃ in the presence of Cu–Zn alloy nanopowder as catalyst. The 1,5-dibutyl, 1-butyl-5-hexyl, 2,5-dibutyl, and 2-butyl-5-hexyl derivatives were then used as building blocks to synthesize several novel tetrazolium ionic liquids (ILs) with EtSO₄^–, OTf^–, and NTf₂^– counterions. Whereas alkylation of the 2,5-dialkyltetrazoles selectively gave the N-4 alkylated onium salts, with the 1,5-dialkyl derivatives approximately 1:1 mixtures of two tetrazolium salts were formed by alkylation at N-3 and N-4. The triflate and ethyl sulfate salts are room-temperature ILs that are hydrophilic, whereas the NTf₂ salts are low-melting ILs and are hydrophobic. The resulting tetrazolium-based ionic liquids were studied by various multinuclear and 2D NMR techniques including natural abundance ¹⁵N and ¹H/¹⁵N correlations.

¹⁵N and ¹³C NMR chemical shifts were computed by GIAO-DFT and GIAO-MP2 for a series of p-substituted benzenediazonium mono- and dications in order to probe the electronic effects of the substituents on the diazonium moiety. Optimized geometries and N/N vibrational frequencies werealso considered for comparison. The GIAO-DFT derived¹⁵N chemical shifts correlate more closely with the experimental values as compared to GIAO-MP2. Energyminimizations at the B3LYP/6-311+G(2d,p), M062X-6-311+G(2d,p), MP2/6-311+G(2d,p), G2(MP2), and CBS-Q levels were carried out. Relative dication stability order HCO⁺ > HOMe⁺ > HN(Me)₂⁺ > HOH⁺ > HCN⁺ > HNO₂⁺ was derived from isodesmic proton transfer reactions. The N_β-protonated dications were less stable than the corresponding p-R⁺ dications. Among the regioisomeric N_β-protonated dications (with R = –F, –Cl, and –CN), those with the R group in the para position were preferred. For the regioisomeric, ring-protonated benzenium-diazonium dications, the meta-protonated dications were more favored (by DFT and MP2). Influence of the counterion and solvent on the computed ¹⁵N NMR chemical shifts in PhN₂⁺ X^– were also assessed.

1-Aryl/alkyl-1H-1,2,3,4-tetrazoles can conveniently be synthesized in one-pot reactions from the corresponding amines by reaction with TMSN₃ and CH(OEt)₃ using the readily available, recyclable, Brønsted acidic ionic liquids [EtNH₃][NO₃] IL-1 and [PMIM(SO₃ H)][OTf] IL-2 under mild conditions in high yields. Based on comparative reactions, whereas both ILs are excellent promoters, reactions are completed with shorter reaction times and in higher yields with IL-2. Among 24 examples provided, identical products were obtained via the two ILs, except in the case of 2-aminobenzoic acid where tetrazole was formed with IL-2 and 2-ethylquinazolin-4(3H)-one was formed with IL-1. By leaving out TMS-N₃ from the reaction, the in-situ formed CH(OEt)₂⁺ and EtC(OEt)₂⁺ (via their corresponding orthoesters) react under sonication with o-phenylenediamine bearing various substituents, o-aminothiophenol and o-aminophenol to form a wide array of benzazoles (benzimidazole, benzothiazole and benzoxazole) and quinazolin-4(3H)-one in high yields (18 examples). The two ILs reacted differently in reaction with 2-aminobenzamide, whereas quinazolin-4(3H)one was formed with IL-2/CH(OEt)₃, the “unexpected” N-ethylquinazolin-4(3H)one was isolated with IL-1/CH(OEt)₃. The latter was also formed from 2-aminobenzoic acid in IL-1/CH(OEt)₃. Mechanistic implications are addressed. The reported protocols enable rapid assembly of a host of heterocyclic systems in high yields with the added advantage of recycling and re-use of the ILs.

A density functional theory (DFT) study aimed at understanding structure–reactivity relationships in the oxidized metabolites of cyclopenta-fused polycyclic aromatic hydrocarbons (CP-PAHs) is reported. Epoxidation at various positions was examined in order to identify the most stable epoxide in each class of CP-PAHs. Relative energies of the carbocations resulting from O-protonation and epoxide ring opening were analyzed and compared, taking into account the available biological activity data on these compounds. Geometrical, electronic, and conformational issues were considered. Charge delocalization modes in the resulting carbocations were deduced via the natural population analysis (NPA)-derived changes in charges. Computational results pointed to the importance of the unsaturated cyclopenta ring on the reactivity of these compounds. The reported bioactivity of this highly mutagenic/carcinogenic family of PAHs was observed to parallel their relative carbocation stabilities. A different behavior was observed in crowded non-planar structures possessing a distorted aromatic system. A covalent adduct formed between a CP-PAH epoxide and a purine base was computed inside a DNA fragment employing the ONIOM method. Copyright © 2010 John Wiley & Sons, Ltd.

Mono- and diprotonation of the tri-, tetra-, and pentabridged cyclophanes [3₃](1,3,5)cyclophane (4), [3₄](1,2,3,5)cyclophane (5), and [3₅](1,2,3,4,5)cyclophane (6) were realized, and NMR spectroscopic studies of the resulting carbocations are reported. Unlike [2.2]paracyclophane and its fluorinated analogs that are protonated at a position ipso to the ethano-bridge, the monocations derived from 4, 5, and 6 are protonated at the unsubstituted ring positions. Protonation regioselectivity in the dications is pseudo-meta for 4 and 5 at unsubstituted ring positions, but for more-crowded 6 the second protonation occurs at a position that is ipso to the trimethylene bridge. Transannular π–π interactions in the monocations are manifested in the observed proton deshielding in the unprotonated π-deck. DFT and GIAO-DFT were employed to study the mono- and dications for comparison with the solution studies in superacids. GIAO-derived ΔNICS(1)_zz data for the [3_n]cyclophane monocations imply decreased aromaticity in the cofacial unprotonated arene, consistent with transannular donor–acceptor interactions.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)