Electron-deficient Aromatic Rings Research Articles

Friedel-Crafts Coupling of Electron-Deficient Benzoylacetones Tuned by Remote Electronic Effects.

Acid-catalyzed electrophilic aromatic substitution for C-C bond formation, commonly referred to as the Friedel-Crafts reaction in recognition of its discoverers, has been one of the most useful reactions in organic chemistry for over a century. However, the Friedel-Crafts reaction cannot occur on a benzene ring having a strongly electron withdrawing group, such as an acyl group, which deactivates the aromatic ring toward electrophilic substitutions and remains a major challenge. Herein, the synthesis of naphthoquinones and 1,3-indandiones, bearing two acyl groups at positions ortho to each other on a benzene ring, are demonstrated by means of copper-catalyzed intramolecular aerobic oxidative acylation of benzoylacetone derivative precursors. This unusual Friedel-Crafts reaction reveals a new activation mode for the in situ polarity reverse of an electron-deficient aromatic ring to a reactive, electron-rich ring tuned by remote electronic effects.

Rapid synthesis and antimicrobial activity of novel 4-oxazolidinone heterocycles.

The synoxazolidinone family of marine natural products bear an unusual 4-oxazolidinone heterocyclic core and promising antimicrobial activity against several strains of pathogenic bacteria. As part of our research program directed at the synthesis and chemical biology of this family of natural products we have developed a one-step method for the generation of variously substituted 4-oxazolidinone scaffolds from readily available materials. These studies revealed the importance of an electron deficient aromatic ring for antimicrobial activity and serve as the basis for future SAR studies around the 4-oxazolidinone core.

Reconciling experiment and theory in the use of aryl-extended calix[4]pyrrole receptors for the experimental quantification of chloride-π interactions in solution.

In this manuscript we consider from a theoretical point of view the recently reported experimental quantification of anion–π interactions (the attractive force between electron deficient aromatic rings and anions) in solution using aryl extended calix[4]pyrrole receptors as model systems. Experimentally, two series of calix[4]pyrrole receptors functionalized, respectively, with two and four aryl rings at the meso positions, were used to assess the strength of chloride–π interactions in acetonitrile solution. As a result of these studies the contribution of each individual chloride–π interaction was quantified to be very small (<1 kcal/mol). This result is in contrast with the values derived from most theoretical calculations. Herein we report a theoretical study using high-level density functional theory (DFT) calculations that provides a plausible explanation for the observed disagreement between theory and experiment. The study reveals the existence of molecular interactions between solvent molecules and the aromatic walls of the receptors that strongly modulate the chloride–π interaction. In addition, the obtained theoretical results also suggest that the chloride-calix[4]pyrrole complex used as reference to dissect experimentally the contribution of the chloride–π interactions to the total binding energy for both the two and four-wall aryl-extended calix[4]pyrrole model systems is probably not ideal.

Phosphine-Catalyzed Aza-MBH Reactions of Vinylpyridines: Efficient and Rapid Access to 2,3,5-Triarylsubstituted 3-Pyrrolines.

Vinylpyridines have been developed in aza-Morita-Baylis-Hillman (MBH) reaction to construct triarylsubstituted 3-pyrrolines. The first electron-deficient aromatic ring is marked as an activating mode for the vinyl group in the MBH reaction. This method provides efficient and rapid access to a range of triarylpyrrolines in good yields and at an excellent level of diastereoselectivity. Moreover, the synthetic potential of this protocol is further enhanced by the straightforward synthesis of unsymmetrical tri- and polyarylsubstituted pyrroles.

The effects of σ(C-Se)-π hyperconjugation in 1-methoxy- and 1-nitro-4-[(phenylselanyl)methyl]benzene.

The structures of 1-methoxy-4-[(phenylselanyl)methyl]benzene, C14H14OSe, (1), and 1-nitro-4-[(phenylselanyl)methyl]benzene, C13H11NO2Se, (2), were determined at 130 K. The two structures, which differ in that (1) contains an electron-rich aromatic ring and (2) contains an electron-deficient aromatic ring, both adopt conformations which allow for σ(C-Se)-π hyperconjugation. However, although there are significant differences in the (77)Se chemical shifts for these two compounds, they do not display significantly different H2C-Se or H2C-C(ar) bond lengths, suggesting that the effects of σ(C-Se)-π hyperconjugation in (1) and (2) are not strong enough to be manifested in measurable differences in the structural parameters.

Functionalized thienoacridines: synthesis, optoelectronic, and structural properties

The preparation and characterization of hexylated, brominated, and 5-hexyl-2-thienyl-substituted tetrathienoacridine (TTAc) is described. Comparative electrochemical, optical, computational, and solid-state studies with their thienoanthracene (TTAn) analogs demonstrate that replacement of CH with nitrogen leads to an overall lowering of the frontier molecular energy levels and decrease in the HOMO–LUMO energy gap. While the brominated TTAc and TTAn derivatives are isostructural, as indicated by X-ray diffraction studies, the lower sublimation temperature and thermochromic behaviour exhibited by bromo-TTAc is attributed to an additional dipole−dipole interaction resulting from the dipole moment afforded by carbon/nitrogen substitution in the core aromatic ring. This work represents a fundamental study of heteroatom substitution in 2-D conjugated small molecules and investigates how inclusion of an electron deficient aromatic ring into the molecular framework (i.e., acridine versus anthracene) can influence the physical properties.

Electronically tunable anion-π interactions in pyrylium complexes: experimental and theoretical studies.

Noncovalent interactions of anions with electron-deficient aromatic rings that have been studied so far involve non-heteroaromatic or nitrogen-based heteroaromatic systems. Here we report the first case of an organic oxygenated aromatic system, in particular the tri-aryl-pyrylium tetrafluoroborate system, for which noncovalent anion-π interactions of the pyrylium cation with the tetrafluoroborate anion have been experimentally detected and demonstrated by means of (19)F NMR spectroscopy in solution. A series of pyrylium tetrafluoroborate salts were synthesized in the presence of BF3·Et2O, by direct reaction of 4-substituted benzaldehydes with 4-substituted acetophenones or via the previously obtained chalcone of the less reactive ketone. Correlations of (19)F NMR chemical shifts of tetrafluoroborate anion for most of the synthesized tri-arylpyrylium tetrafluoroborate complexes with both the pyrylium cation molecular weight and the standard substituent Hammett constants, demonstrate anion-π(+) interaction to act between the polyatomic anion BF4(-) and the pyrylium aromatic system. DFT calculations reveal that an additional (C-H)(+)-anion hydrogen bond involving the H(5) of pyrylium ring exists for these fluorescent dyes that show a tunable cup-to-cap shape cavity. The strong fluorescence emission observed for some representative pyrylium tetrafluoroborates described herein, makes them a promising class of tunable emission wavelength dyes for laser technology applications.

Multifunctional white-light-emitting metal-organic gels with a sensing ability of nitrobenzene.

In this study, three novel luminescent nanofibrous metal-organic gels (MOGs) have been synthesized by the reaction of 1,3,5-tris(3-pyridylmethoxyl)benzene (L) with chloride salts of Cd(II), Hg(II), and Cu(II). The metal-ligand coordination, intermolecular π-π stacking and several other weak interactions found to play an important role in the formation of nanofibrous materials. The gel materials are characterized by rheology, diffuse reflectance spectra and various microscopic techniques such as TEM, FESEM, and AFM. The gels MOG-1 and MOG-2 were found to exhibit significant white photoluminescence, whereas the MOG-3 exhbits green emission upon excitation at 325 nm. Furthermore, the MOG-1 has shown its application as a chemosensor for the remarkable detection of nitroaromatics such as nitrobenzene (NB), 2,4-dinitrophenol (DNP). The significant quenching response for NB and DNP is attributed to the strong charge-transfer interactions between the electron-deficient aromatic ring of NB and the electron rich aromatic group of L in MOG-1. The crystal structure of Cd(II) complex of L reveals the formation one-dimensional network which contains strong π-π interactions within and between the networks and these strong π-π interactions generate the free charge carrier in all these nanofibrous gels.

Design and Syntheses of Anti-Tuberculosis Agents Inspired by BTZ043 Using a Scaffold Simplification Strategy.

Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (Mtb), is a global public health concern because of the emergence of various resistant strains. Benzothiazin-4-ones (BTZs), represented by BTZ043, are a promising new class of agents for the treatment of tuberculosis and have been shown to kill Mtb in vitro, ex vivo, and in mouse models of TB. Herein we report the design and syntheses of nitroaromatic sulfonamide, reverse-amide, and ester classes of anti-TB agents using a scaffold simplification strategy based on BTZ043. The presented work explores the effect of functional groups such as sulfonamides, reverse-amides, and esters that are attached to the nitroaromatic rings on their anti-TB activity. The in vitro activity of the compounds evaluated against the H37Rv strain of Mtb show that nitroaromatic sulfonamides and nitrobenzoic acid esters with two nitro substituents were most active and highlights the importance of the electronic character (electron deficient aromatic ring) of the nitroaromatic ring as a central theme in these types of nitroaromatic anti-TB agents.

Electrochemiluminescence Detection of TNT by Resonance Energy Transfer through the Formation of a TNT-Amine Complex

2,4,6-Trinitrotoluene (TNT) is a widely used nitroaromatic explosive with significant detrimental effects on the environment and human health. Its detection is of great importance. In this study, both electrochemiluminescence (ECL)-based detection of TNT through the formation of a TNT-amine complex and the detection of TNT through electrochemiluminescence resonance energy transfer (ECRET) are developed for the first time. 3-Aminopropyltriethoxysilane (APTES)-modified [Ru(phen)3](2+) (phen=1,10-phenanthroline)-doped silica nanoparticles (RuSiNPs) with uniform sizes of (73±3) nm were synthesized. TNT can interact with APTES-modified RuSiNPs through charge transfer from electron-rich amines in the RuSiNPs to the electron-deficient aromatic ring of TNT to form a red TNT-amine complex. The absorption spectrum of this complex overlaps with the ECL spectrum of the APTES-modified RuSiNPs/triethylamine system. As a result, ECL signals of the APTES-modified RuSiNPs/triethylamine system are turned off in the presence of TNT owing to resonance energy transfer from electrochemically excited RuSiNPs to the TNT-amine complex. This ECRET method has been successfully applied for the sensitive determination of TNT with a linear range from 1×10(-9) to 1×10(-6) M with a fast response time within 1 min. The limit of detection is 0.3 nM. The method exhibits good selectivity towards 2,4-dinitrotoluene, p-nitrotoluene, nitrobenzene, phenol, p-quinone, 8-hydroxyquinoline, p-phenylenediamine, K3[Fe(CN)6], Fe(3+), NO3(-), NO2(-), Cr(3+), Fe(2+), Pb(2+), SO3(2-), formaldehyde, oxalate, proline, and glycine.

Cyanide–Arene Meisenheimer Complex Generated in Electrospray Ionization Mass Spectrometry Using Acetonitrile as a Solvent

The C - C bond formation activated under negative electrospray ionization of an acetonitrile solution of 1,3,5-trinitrobenzene is reported. The solvent function is to provide a source of cyanide ion, a highly problematic reagent, which is found to attack the electron-deficient aromatic ring to form a covalently bound anionic complex (Meisenheimer complex). The structure of the complex is elucidated by means of collision induced dissociation mass spectrometry and IR multiple photon dissociation spectroscopy in the 'fingerprint' region.

Strong lone pair⋯π interactions between amine and tri-s-triazine derivatives: A theoretical investigation

For a better understanding of the interesting lone pair⋯π (lp⋯π) interaction, MP2 and CCSD(T) calculations have been carried out to investigate the nitrogen lp⋯π interactions between amine and tri-s-triazine derivatives. New strong attractive lp⋯π interactions are observed when the lone pairs of NH3 and NMe3 point toward the large π system, tri-s-triazine ring. At the CCSD(T)/6-311++G(d,p)//MP2/6-311G(d,p) level, the BSSE corrected interaction energy of the C6N7H3⋯NH3 complex is −6.3kcalmol−1,which is larger than those of the most previously reported lp⋯π systems. The substitution effects on interaction energy of the present studied systems were studied to probe how to manipulate lp⋯π interaction and obtain stronger one. The results indicate that the very strong lp⋯π interaction can form between electron-rich amines and electron-deficient large aromatic ring. But the lp⋯π interactions between the electron-deficient amine such as NF3 and aromatic ring are very weak. The C6N7F3⋯NMe3 complex has interaction energy of −9.8kcalmol−1. This interaction is much stronger than previously reported lp⋯π bindings. The AIM analysis of the nine studied complexes shows that their molecular graphs are obvious different from previously reported benzene⋯amine complexes and X–H/π systems, which may result from the tri-s-triazine ring’s characteristic.

Ion-π interactions in ligand design for anions and main group cations.

Interactions between ions and aromatic rings are now a mainstay in the field of supramolecular chemistry. The prototypical cation-π interaction, first characterized in the gas phase, is now well-known as an important contributor to protein structure and enzyme function and as a noncovalent force found in many synthetic systems. The complementary "anion-π interaction"-defined as an electrostatic attraction between an anion positioned over the centroid of an aromatic ring-has recently emerged as another reversible ion-π interaction in supramolecular systems. This type of interaction could offer new selectivity in binding poorly basic, strongly solvated anions and may also affect structure, biological function, and anion transport. This Account describes our group's efforts in ion-π interactions in two areas. We first describe a series of self-assembled Group 15 (pnictogen)-thiolate complexes, all featuring prominent cation-π interactions between the trivalent pnictogen and an aromatic ring of the ligand. This structural feature appears to stabilize a variety of self-assembled dinuclear macrocycles, dinuclear M2L3 cryptand-analogues, and a tetranuclear As4L2 metallocyclophane. These complexes are all remarkably robust and feature intramolecular cation-π interactions, which suggest that these interactions could be an important feature in ligand design for the Group 15 elements. We also highlight our efforts to characterize the interaction between anions and electron-deficient aromatic rings in solution. Complementary crystallographic and computational studies suggest that off-center weak-σ interactions play the dominant role in stabilizing the anion-arene adducts unless an acidic CH bond is present to participate in favorable CH···anion hydrogen bonds. In solution the weak-σ complexes show downfield shifts of the proton resonances in their NMR spectra. With more polarizable anions such as bromide and iodide, we also observe anion binding by UV/vis spectroscopy. Initial solution studies suggest these reversible interactions are weak in organic solvents, but the Hofmeister bias in anion binding could be mitigated, if not reversed, in the halides using these anion-π type interactions.

Sensing behavior of silica-coated Au nanoparticles towards nitrobenzene

In the present work, we report silica-stabilized gold nanoparticles (SiO2/Au NPs) as a wide-range sensitive sensing material towards nitrobenzene (NB). Surface hydroxyl groups of silica selectively form Meisenheimer complex with electron-deficient aromatic ring of NB and facilitate its immobilization and subsequent catalytic reduction by Au cores. Silica-coated Au NPs were synthesized and characterized for their chemical, morphological, structural, and optical properties. SiO2/Au NPs-modified electrodes were characterized with impedometric and cyclic voltammetric electrochemical techniques. SiO2/Au NPs are found to have a higher optical detection window of range, 0.1 M to 1 μM and a lower electrochemical detection window of range, 10−4 to 2.5 × 10−2 mM with a detection limit of 12.3 ppb. A significant enhancement in cathodic peak current, C1, and sensitivity (102 μA/mM) was observed with modified electrode relative to bare and silica-modified electrodes. The IP was found to be linearly co-related to NB concentration (R2 = 0.985). The interference of cationic and anionic species on sensor sensitivity was also studied. Selectivity in the present sensing system may be further improved by modifying silica with specific functional moieties.

Synthesis and Structure of Oxacalix[2]arene[2]triazines of an Expanded π-Electron-Deficient Cavity and Their Interactions with Anions

Novel macrocyclic anion receptors based on the principle of anion-π interactions were reported. By means of both post-macrocyclization modification protocol and the stepwise fragment coupling approach, functionalized oxacalix[2]arene[2]triazines bearing two other electron-deficient (hetero)aromatic rings on the lower rim were efficiently synthesized. The resulting oxacalix[2]arene[2]triazine macrocyclesadopt 1,3-alternate conformation, yielding therefore an expanded electron-deficient cavity or space consisting of two triazine rings and two appending aromatic rings. Spectroscopic titration study showed the selective interaction of the pentafluorophenyl-substituted oxacalix[2]arene[2]triazine with azide and fluoride in solution with the binding constants (K(1:1)) ranging from 1.33 × 10(3) to 3.52 × 10(3) M(-1).

Fluorescent organic–inorganic hybrid polyphosphazene microspheres for the trace detection of nitroaromatic explosives

Highly cross-linked, intrinsically fluorescent organic–inorganic hybrid polymer microspheres bearing primary amine groups on the surface have been successfully prepared through a one-pot polycondensation of hexachlorocyclotriphosphazene with benzidine. Just by the single-step introduction of plentiful π-conjugated benzidine units in the structure, the resulting microspheres easily obtain both the luminescence and abundant active amino groups, with no need for more modification. Thus further using the microspheres as fluorescence-based nitroaromatic sensor, 2,4,6-trinitrotoluene, 2,4-dinitrotoluene, and picric acid can be effectively and sensitively detected. Because the nitroaromatic analytes can be effectively enriched on the surface of the microspheres by the charge-transfer complexing interaction between electron-deficient aromatic rings and electron-rich amino groups, which facilitates the electron transfer and energy transfer from microspheres to nitroaromatics, and finally leads to a significant and sensitive fluorescence quenching response. Moreover, the microspheres also exhibit remarkable thermal stability, photobleaching stability, and solvent resistance and dispersion ability in various solvents including both aqueous and organic media, owing to the highly cross-linked and organic–inorganic hybrid structure.

Amino functionalized mesoporous silica microspheres with perpendicularly aligned mesopore channels for electrochemical detection of trace 2,4,6-trinitrotoluene

Core–shell structured mesoporous silica microspheres with a SiO 2 particles core and an ordered perpendicularly aligned mesoporous silica shell to the surface have been prepared. The perpendicular orientation mesoporous silica microspheres (SiO 2@mSiO 2) then were functionalized with 3-aminopropyltriethoxysilane (APTS) to graft amino functional groups (SiO 2@mSiO 2@NH 2). The SiO 2@mSiO 2@NH 2 was used to modify glassy carbon electrodes (GCE) as sensing material. Square-wave voltammetry was used to detect the reduction peak of 2,4,6-trinitrotoluene (TNT) in a three-electrode system. The results demonstrate that the SiO 2@mSiO 2@NH 2/GCE can greatly improve the response to TNT due to the large active surface area and high preconcentration efficiency via specific interaction between electron-rich amino groups and electron-deficient aromatic rings. The first reduction peak current of TNT at the SiO 2@mSiO 2@NH 2/GCE is ca. 4.6 times larger than that at the un-functionalized SiO 2@mSiO 2/GCE. A limit of determination of 0.5 nM and a sensitivity of 0.011 μA nM −1 was obtained. Excellent wide linear range (2.0–50.0 nM) and good repeatability (relative standard deviation of 2.4%) were obtained for TNT. Moreover, the SiO 2@mSiO 2@NH 2/GCE shows a higher electrochemical response to TNT than to 1,3,5-trinitrobenzene (TNB) and 2,4-dinitrotoluene (DNT), and the first reduction peak current of TNT at the SiO 2@mSiO 2@NH 2/GCE is 2.9 and 4.8 times larger than that of DNT and TNB, respectively, which shows the as-prepared SiO 2@mSiO 2@NH 2/GCE has a much higher sensitivity to TNT than other kinds of nitroaromatics.

Anion–π Interactions in Salts with Polyhalide Anions: Trapping of I42−

The directionality of interaction of electron-deficient π systems with spherical anions (e.g,. halides) can be controlled by secondary effects like NH or CH hydrogen bonding. In this study a series of pentafluorophenyl-substituted salts with polyhalide anions is investigated. The compounds are obtained by aerobic oxidation of the corresponding halide upon crystallization. Solid-state structures reveal that in bromide 2, directing NH-anion interactions position the bromide ion in an η(1)-type fashion over but not in the center of the aromatic ring. The same directing forces are effective in corresponding tribromide salt 3. In the crystal, the bromide ion is paneled by four electron-deficient aromatic ring systems. In addition, compounds 4 and 6, which have triiodide and the rare tetraiodide dianion as anions, are described. Computational studies reveal that the latter is highly unstable. In the present case it is stabilized by the crystal lattice, for example, by interaction with electron-deficient π systems.

Inverted Opal Fluorescent Film Chemosensor for the Detection of Explosive Nitroaromatic Vapors through Fluorescence Resonance Energy Transfer

This paper reports an inverted opal fluorescence chemosensor for the ultrasensitive detection of explosive nitroaromatic vapors through resonance-energy-transfer-amplified fluorescence quenching. The inverted opal silica film with amino ligands was first fabricated by the acid-base interaction between 3-aminopropyltriethoxysilane and surface sulfonic groups on polystyrene microsphere templates. The fluorescent dye was then chemically anchored onto the interconnected porous surface to form a hybrid monolayer of amino ligands and dye molecules. The amino ligands can efficiently capture vapor molecules of nitroaromatics such as 2,4,6-trinitrotoluene (TNT) through the charge-transfer complexing interaction between electron-rich amino ligands and electron-deficient aromatic rings. Meanwhile, the resultant TNT-amine complexes can strongly suppress the fluorescence emission of the chosen dye by the fluorescent resonance energy transfer (FRET) from the dye donor to the irradiative TNT-amino acceptor through intermolecular polar-polar resonance at spatial proximity. The quenching response of the highly ordered porous films with TNT is greatly amplified by at least 10-fold that of the amorphous silica films, due to the interconnected porous structure and large surface-to-volume ratio. The inverted opal film with a stable fluorescence brightness and strong analyte affinity has lead to an ultrasensitive detection of several ppb of TNT vapor in air.

Copolypeptide-doped polyaniline nanofibers for electrochemical detection of ultratrace trinitrotoluene

This paper demonstrates a new electrochemical method for the detection of ultratrace amount of 2,4,6-trinitrotoluene (TNT) with synthetic copolypeptide-doped polyaniline nanofibers. The copolypeptide, comprising of glutamic acid (Glu) and lysine (Lys) units, is in situ doped into polyaniline through the protonation of the imine nitrogen atoms of polyaniline by the free carboxylic groups of Glu segments, resulting in the formation of polyaniline nanofibers of emeraldine salt. The free amino groups of Lys segments at the surface of nanofibers provide the receptor sites of TNT through the formation of charge–transfer complex between the electron-rich amino groups and the electron-deficient aromatic rings. Adsorptive stripping voltammetry results demonstrate that the poly(Glu-Lys)-doped nanofibers confined onto glassy carbon electrodes exhibit a remarkable enriching effect and thus sensitive electrochemical response to TNT with a linear dynamic range of 0.5–10 μM and a detection limit down to 100 nM. Moreover, other kinds of nitro compounds show different redox behaviors from TNT at the doped nanofibers, and thus do not interfere with the electrochemical detection of TNT. This study essentially offers a new and simple method for electrochemical detection of ultratrace TNT.