Electron-deficient Aromatic Systems Research Articles

Synthesis and Electrophilic Trifluoromethylthiolation Properties of 1-Methyl-4-(trifluoromethylthio)piperazine (MTTP).

A cyclic diamine, 1-methyl-4-(trifluoromethylthio)piperazine (MTTP, 1), prepared by a one-step reaction from commercial materials, is a shelf-stable and powerful electrophilic trifluoromethylthiolating (CF3S) reagent with wide reactivity profile. Activation of 1 with triflic acid (TfOH) yields two reactive species A and B, depending on the molar ratios of TfOH/1. B showed unprecedented high reactivity, making possible the trifluoromethylthiolation of electron-deficient aromatic systems. In addition, B accomplished the trifluoromethylthiolation of active methylene compounds under acidic conditions.

Divergent synthesis of fused Benzo-xanthene and oxazine derivatives via Cu-catalyst

Cu-Cu2O combination showed synergic effects in catalyzing intramolecular Ullmann coupling reaction for halo-Betti bases to afford fused benzo-xanthenes from both electron-rich and electron-deficient aromatic systems in good yield under mild reaction conditions. The sterically hindered halo-Betti bases also provided products in excellent yield. Under optimized condition, a gram scale reaction was also performed to afford the product in excellent yield. However, without ortho-halo substituted Betti-bases failed to afford fused benzo-xanthene derivatives. Exploring the reaction optimization without Cu metal, serendipitously it was produced 1,3-oxazine derivatives in excellent yield via intramolecular cross-dehydrogenative coupling (CDC) reaction. Similarly, electron-rich, electron-deficient and sterically hindered Betti-bases provided the products in good to excellent yield under mild condition.

4-Amino-2-butyl-7-methoxycarbonylthiazolo[4,5-c]quinoline

4-Amino-imidazo-, oxazolo-, and thiazoloquinolines are key structural scaffolds in the design of nucleoside base analogs for use as therapeutic agents. Current strategies for arriving at diverse substitutions at the C6–C9 positions of the thiazolo- and oxazoloquinolines, however, are limited due to difficulties in arriving at the thiazoloquinoline-5N-oxide intermediate using electron deficient aromatic systems. Here, we demonstrate a synthetic route to obtain substituted thiazoloquinolines with electron-withdrawing groups at the C7 position. The target compound, 4-amino-2-butyl-7-methoxycarbonylthiazolo[4,5-c]quinoline, is obtained in eight steps using a 7-bromo surrogate as a precursor to the successful generation of the N-oxide intermediate, and final transformation via Pd-mediated C7-acylation.

Friedel-Crafts Type Methylation with Dimethylhalonium Salts.

The dimethylchloronium salt [Me2Cl][Al(OTeF5)4] is used to methylate electron‐deficient aromatic systems in Friedel–Crafts type reactions as shown by the synthesis of N‐methylated cations, such as [MeNC5F5]+, [MeNC5F4I]+, and [MeN3C3F3]+. To gain a better understanding of such fundamental Friedel–Crafts reactions, the role of the dimethylchloronium cation has been evaluated by quantum‐chemical calculations.

Synthesis of a perylenediimide-fullerene C60 dyad: A simple use of a nitro leaving group for a Suzuki-Miyaura coupling reaction

We describe herein a straightforward synthesis of a fullerene C60 – perylenediimide (C60-PDI) dyad. A simple and original cross-coupling Suzuki-Miyaura reaction was carried out using mononitro-bay substituted PDI as an electron-deficient aromatic system playing the role of electrophilic partner. Optical and electrochemical characterizations of this C60-PDI dyad are also reported.

Solvent Directed Morphogenesis and Electrical Properties of a Peptide-Perylenediimide Conjugate.

Molecular organization of electron-deficient aromatic systems like perylenediimides (PDI) is extremely appealing, as they are potential candidates for organic electronics. The performance of these molecules in such applications primarily depends on the self-organization of the molecules. However, any correlation between the morphology of these self-assembled semiconducting molecules and their electrical performances has not yet been formulated. Herein, for the first time, we have made an effort to find such a correlation by studying the self-assembly, morphology, and their conducting properties for a peptide-PDI conjugate. The PDI conjugate formed fiber-like morphology in relatively nonpolar solvents (THF and CHCl3) while in more polar solvents (HFIP, MeOH, ACN, and acetone), spherical morphology could be found. Interestingly, the self-assembly and the morphologies showed a clear dependence on the solvent polarity. In polar solvents, the conjugate aggregates more efficiently than in the nonpolar solvents, and with decrease in solvent polarity, the dimension of the nanostructures increased. However, in all the tested solvents, irrespective of their polarity, the PDI-peptide conjugate adopts a right-handed helicity. To find a correlation between the morphologies with the conducting property, detailed electrical characterization of these nanostructures was carried out. While no significant change could be observed for the dc conductivities of these nanostructures, the ac conductivities show prominent difference at the low-frequency region. A dispersion of conductivity was observed for the nanospheres due to the polarization effect. A critical correlation between the nanostructures and the activation energy was observed as with decrease in radii of curvature of the aggregates the activation energy increases with an exception in the case of MeOH. The observed results suggest that the long-range transport of charge carriers is less favorable when the aggregates are small and closely packed.

CH‐Directed Anion–π Interactions in the Crystals of Pentafluorobenzyl‐Substituted Ammonium and Pyridinium Salts

Simple pentafluorobenzyl-substituted ammonium and pyridinium salts with different anions can be easily obtained by treatment of the parent amine or pyridine with the respective pentafluorobenzyl halide. Hexafluorophosphate is introduced as the anion by salt metathesis. In the case of the ammonium salt 4, water co-crystallisation seems to suppress effective anion-pi interactions of bromide with the electron-deficient aromatic system, whereas with salts 5 and 6 such interactions are observed despite the presence of water. However, due to asymmetric hydrogen-bonding interactions with ammonium side chains, the anion of 5 is located close to the rim of the pentafluorophenyl group (eta(1) interaction). In 6 the CH-anion hydrogen bonding is more symmetric and fixes the anion on top of the ring (eta(6)). A similar structure-controlling effect is observed in case of the 1,4-diazabicyclo[2.2.2]octane derivatives 7. Here the position of the anion (Cl, Br, I) is shifted according to the length of the weak CH-halide interaction. The hexafluorophosphate 7 d reveals that this "non-coordinating" anion can be located on top of an aromatic pi system. In the methyl-substituted pyridinium salts 9 and 10 different locations of the bromide anions with respect to the pi system are observed. This is due to different conformations of the mono- versus disubstituted pyridine, which leads to different directions of the weak, but structurally important, H(Me)-Br bonds.

Synthesis of Divinylsulfides

Arylacetylenes react with sodium sulfide in the presence of water to yield divinylsulfides. The reaction proceeds in good to excellent yield for both electron-neutral and electron-deficient aromatic systems; for electron-rich aryls, longer reaction times are necessary. The sulfides represent useful substrates for further transformations, for example, oxidation to the corresponding divinylsulfoxides and divinylsulfones. Three selected divinylsulfide derivatives were oxidized selectively to the corresponding sulfoxides or sulfones.

Molecular Complexes of Simple Anions with Electron‐Deficient Arenes: Spectroscopic Evidence for Two Types of Structural Motifs for Anion–Arene Interactions

Anion-pi interactions between a pi-acidic aromatic system and an anion are gaining increasing recognition in chemistry and biology. Herein, the binding features of an electron-deficient aromatic system (1,3,5-trinitrobenzene (TNB)) and selected anions (OH-, Br-, and I-) are examined in the gas phase by using the combined information derived from collision-induced dissociation experiments at variable energy, infrared multiple-photon dissociation spectroscopy, and quantum chemical calculations. We provide spectroscopic evidence for two different structural motifs of anion-arene complexes depending on the nature of the anion. The TNB-OR- complexes (R=H, or alkyl groups which were studied earlier) adopt an anionic sigma-complex structure whereby RO- attacks the aromatic ring with covalent bond formation, and develops a tetrahedral ring carbon bound to H and OR. The halide complexes rather conform to a structure in which the TNB moiety is hardly altered, and the halogen is placed on an unsubstituted carbon atom over the periphery of the ring at a C-X distance that is appreciably longer than a typical covalent bond length. The ensuing structural motif, previously characterized in the solid state and named weak sigma interaction, is now confirmed by an IR spectroscopic assay in the gas phase, in which the sampled species are unperturbed by crystal packing or solvation effects.

Anion-π interactions

This tutorial review provides an overview of the theoretical and experimental investigations that resulted in the recognition of anion-pi interactions, i.e., non-covalent forces between electron deficient aromatic systems and anions. Several pioneering theoretical studies revealed that these interactions are energetically favorable (approximately 20-50 kJ mol(-1)). Anion-pi interactions are gaining significant recognition, and their pivotal role in many key chemical and biological processes is being increasingly appreciated. The design of highly selective anion receptors and channels represent important advances in this nascent field of supramolecular chemistry.

Solution and Solid-State Structure of 2- and 4-Bis(trimethylsilyl)methylpyridinium Cations

N-Methylation of the 2- and 4-bis(trimethylsilyl)methyl pyridines 7 and 9 gives the ions 5 and 6 and results in a significant decrease in the 13CH−29SiMe3 coupling constant, consistent with increased C−Si−π hyperconjugation between the trimethylsilyl substituents and the electron-deficient aromatic system of the pyridinium cations. The rotation barrier about the Cipso−CH bond, which was measured for both 5 and 7 using variable-temperature 13C NMR and calculated at the B3LYP/6-311G** level, reveals that steric effects make a larger contribution than hyperconjugative effects to this barrier. The crystal structure of the protonated salt 11 shows that the conformation of the CH(SiMe3)2 substituent is similar to that predicted by calculations and allows for both C−SiMe3 bonds to interact with the aromatic π-system.

ChemInform Abstract: Selective Anion Binding and Solid‐State Host—Guest Chemistry of an Extended Cavity Calix[6]pyrrole.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Quantum Chemical Analysis ofpara-Substitution Effects on the Electronic Structure of Phenylnitrenium Ions in the Gas Phase and Aqueous Solution

Ab initio calculations for para-substituted phenylnitrenium ions predict larger singlet−triplet splittings, shorter singlet C−N+ bond lengths, and higher singlet aromatic ring stretching frequencies for substituents with greater electron-donating character. Trends in these properties correlate linearly with para-substituent constants σR+, indicating that phenylnitrenium ions closely resemble other electron-deficient aromatic systems where resonance interactions with substituents are dominant. Sensitivity to substitution is large as judged by the slope of the correlating line for aqueous singlet−triplet splittings, ρ = 6.4. For 13 of 15 substituted cases, aqueous solvation preferentially stabilizes the singlet state by 0.9 to 4.4 kcal/mol; for the p-CO2H and p-CF3 cases, the triplet state is better solvated by less than 1 kcal/mol.

Modulation of Flavin Recognition and Redox Properties through Donor Atom−π Interactions

Computational and experimental model studies establish the importance of donor atom−π bonding on the recognition and function of flavins. This noncovalent interaction arises from electrostatic attraction between electron-rich (donor) atoms and electron-deficient aromatic systems. The electrostatic origin of this bonding was verified through comparison of binding of model receptors to flavin in both oxidized (Flox) and radical anion (Flrad-) forms: Interaction was strongest with the electron-poor Flox and was greatly attenuated with the comparatively electron-rich Flrad-. Other factors determining the magnitudes of these donor−π interaction are the size and polarizability of the donor atom.

The donor atom-? interaction of sulfur with flavin. A density functional investigation

Thiols and sulfides interact strongly with electron-deficient aromatic systems such as flavins. Using density functional methodology, we have shown that this interaction is electrostatic in nature, with very little polarization of the sulfur electron cloud. © 1998 John Wiley & Sons, Inc. Heteroatom Chem 9: 605–606, 1998

On the relevance of face-to-edge π-π interactions to chiral recognition

Several chiral selectors have been developed in our laboratory on the premise that a cleft having an electron-deficient aromatic system as a “wall” and an electron-rich aromatic system as a “floor” would be conducive to chiral recognition. As a test of this hypothesis, six racemates, 5a-c and 6a-c, each containing electron-deficient and electron-rich aromatic systems, were prepared and studied chromatographically on a chiral stationary phase derived from the N,N-diallyl amide of naproxen. The endo stereoisomers, 5a-c, contain the aforementioned clefts whereas the exo stereoisomers, 6a-c, do not. The enantiomers of the former show much larger separation factors than do the enantiomers of the latter, supportive of the importance of the preorganized cleft. For comparative purposes, chromatographic data are provided for the enatiomers of both the selector used in the commercially available CSP 1 and its trans isomer.