Electron-deficient Aromatic Rings Research Articles

A [3+3] Aldol-SNAr-Dehydration Approach to 2-Naphthol and 7-Hydroxyquinoline Derivatives.

A one-pot [3+3] aldol-SNAr-dehydration annulation sequence was utilized to fuse hindered phenols onto aromatic substrates. The transformation joins doubly activated 1,3-disubstituted acetone derivatives (dinucleophiles) with C5-activated 2-fluorobenzaldehyde SNAr acceptors (dielectrophiles) in the presence of K2CO3 in DMF at 65-70 °C to form polysubstituted 2-naphthols and 7-hydroxyquinolines. The reaction is regioselective in adding the most stable anionic center to the aldehyde followed by SNAr closure of the less stabilized anion to the electron-deficient aromatic ring. Twenty-seven examples are reported, and a probable mechanism is presented. In two cases where SNAr activation on the acceptor ring was lower (a C5 trifluoromethyl group on the aromatic ring or a 2-fluoropyridine), diethyl 1,3-acetonedicarboxylate initiated an interesting Grob-type fragmentation to give cinnamate esters as the products.

Inner and Interfacial Environmental Nanoarchitectonics of Supramolecular Assemblies Formed by Amphiphiles: from Emergence to Application.

The inner and interfacial environments of self-assemblies provide fascinating nano-space for selective and efficient chemical reactions and processes. In biological systems, various chemical reactions, molecular recognition, and transport occur precisely and selectively by virtue of effective molecular interactions on biological membranes and proteins. Considering these advantages and the concept of nanoarchitectonics, we demonstrated that the photochromism of a lophine dimer was accelerated by using confined nano-spaces formed by surfactant micelles. The photoresponsive micelles were used for the rapid controlled release of a model drug upon ultraviolet light irradiation. Furthermore, selective ion recognition inside the self-assembled molecular films at the interfaces was investigated. The anion-π interaction between the anion and an electron-deficient aromatic ring was evaluated on a solid substrate modified with a naphthalenediimide (NDI) analog. Force curve measurements afforded a quantitative analysis of anion-π interactions on the NDI film. The strength of anion-π interactions is regulated by the electric fields on the electrode. An optical probe was developed to visualize the distribution of Cs ions in the soil, plant bodies, and aqueous media using an optode system. Advances in the development of molecular functional systems are expected based not only on molecular structures but also on the spaces and environments produced by them.

Hydrogenation of benzoic acid derivatives over Pt/TiO2 under mild conditions

Hydrogenation of benzoic acid (BA) to cyclohexanecarboxylic acid (CCA) has important industrial and academic significance, however, the electron deficient aromatic ring and catalyst poisoning by carboxyl groups make BA hydrogenation a challenging transformation. Herein, we report that Pt/TiO2 is very effective for BA hydrogenation with, to our knowledge, a record TOF of 4490 h−1 at 80 °C and 50 bar H2, one order higher than previously reported results. Pt/TiO2 catalysts with electron-deficient and electron-enriched Pt sites are obtained by modifying the electron transfer direction between Pt and TiO2. Electron-deficient Pt sites interact with BA more strongly than electron-rich Pt sites, helping the dissociated H of the carboxyl group to participate in BA hydrogenation, thus enhancing its activity. The wide substrate scope, including bi- and tri-benzoic acids, further demonstrates the high efficiency of Pt/TiO2 for hydrogenation of BA derivatives.

Naphthalenothiophene imide-based polymer exhibiting over 17% efficiency

Summary Developing novel electron-deficient monomers is crucially important for the future development of non-fullerene organic solar cells. Here, we report a new electron-deficient monomer naphthalenothiophene imide (NTI) and NTI-based copolymers PNTB and PNTB-2T. The strong electron-withdrawing ability of NTI could effectively lower the HOMO level of the polymer that facilitates the tuning of the polymer’s physical properties while simultaneously maintaining the low-lying HOMO value. Polymer chains modification by introducing extra thiophenes results in the closed π−π stacking and ordered polymer chain packing of PNTB-2T and is proven to be an effective strategy to increase the device performance. Thus, solar cell devices for PNTB-2T:Y6 exhibit an efficiency of 16.72%, which is further enhanced to 17.35% by the third component PC71BM, whereas that for PNTB:Y6 is only 3.81%. Importantly, PNTB-2T-based devices exhibit excellent batch-to-batch reproducibility. These features make this family of polymer donors very promising and the design strategies will enlighten future development of high-performance polymer donors for organic solar cells (OSC).

Super-strong interactions between multivalent anions and graphene* *Project supported by the National Natural Science Foundation of China for Outstanding Young Scholars (Grant No. 11722548), the China Postdoctoral Science Foundation (Grant No. 2019M651462), the National Natural Science Foundation of China (Grant No. U1932123), the Innovative Research Team of High-Level Local Universities in Shanghai, the Open Project of State Key Laboratory of

Based on the density functional theory (DFT) calculations, we showed that the interactions between different valence anions (, , ) and graphene significantly increased as the valence of anion increased from negative monovalence to negative trivalence. The adsorption energy of on the electron-rich graphene flake (C84H24) is −8.3 kcal/mol. The adsorption energy of on the electron-rich graphene flake (C84H24) is –48.0 kcal/mol, which is about six times that of adsorption on electron-rich graphene flake (C84H24) and is even much larger than that of adsorption on electron-deficient aromatic ring C6F6 (–28.4 kcal/mol). The adsorption energy of on the electron-rich graphene flake (C84H24) is –159.2 kcal/mol, which is about 20 times that of adsorption on the graphene flake (C84H24). The super-strong adsorption energy is mainly attributed to the orbital interactions between multivalent anions and graphene. This work provides new insights for understanding the interaction between multivalent anions and π–electron-rich carbon-based nanomaterials and is helpful for the design of graphene-based DNA biosensor.

How Do Aromatic Nitro Compounds React with Nucleophiles? Theoretical Description Using Aromaticity, Nucleophilicity and Electrophilicity Indices.

In this study, we present a complete description of the addition of a model nucleophile to the nitroaromatic ring in positions occupied either by hydrogen (the first step of the SNAr-H reaction) or a leaving group (SNAr-X reaction) using theoretical parameters including aromaticity (HOMA), electrophilicity and nucleophilicity indices. It was shown both experimentally and by our calculations, including kinetic isotope effect modeling, that the addition of a nucleophile to the electron-deficient aromatic ring is the rate limiting step of both SNAr-X and SNAr-H reactions when the fast transformation of σH-adduct into the products is possible due to the specific reaction conditions, so this is the most important step of the entire reaction. The results described in this paper are helpful for better understanding of the subtle factors controlling the reaction direction and rate.

On the sulfonation of fluorinated aromatic polymers: Synthesis, characterization and effect of fluorinated side groups on sulfonation degree

Series of partially sulfonated poly(F-STs-co-ST) copolymers and poly(TFMST-ter-ST-ter-FMST) terpolymer have been successfully synthesized via post-sulfonation method using acetyl sulfate as a sulfonating agent. The identical and mild sulfonation conditions with a controlled sulfonation degree (SD) in the range of 18–27 mol%, were designed for comprehensive evaluation of the effect of fluorine content on the efficiency of the electrophilic -SO3H substitution. The SD values of the sulfonated FAPs were determined using elemental analysis (EA). The identical, effective and versatile isolation method for all sulfonated polymers, regardless the amphiphilic dual nature of the resulting polymers (hydrophobic fluorine-containing, and also hydrophilic sulfonated unit) and also the presence of different fluorinated methyl moieties (-CH2F, -CF2H and -CF3) in polymeric chain, was developed. The resulting novel sulfonated FAPs were characterized by NMR and FTIR spectroscopies that evidenced a satisfactory incorporation of -SO3H functions into aromatic rings of polymer chain. Studies clearly revealed that the electron-deficient aromatic rings of F-ST units did not undergo sulfonation in comparison with electron-rich aromatic rings of ST units. The FTIR and 1H NMR analysis showed that the sulfonation occurred only in aromatic rings of the ST units and -SO3H functions were introduced at the para position. Moreover, with an increase of the fluorine content in polymer structure, a decrease in the resulting SD values was noticed. The presence of fluorine reduced the electron density directly in fluorinated aromatic units (F-STs), and surprisingly gently affected neighboring ST units. The thermal properties of the resulting copolymers were investigated by differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). The observed higher Tgs values of sulfonated polymers than those of unsubstituted counterparts indicated that the increase in the structural rigidity of the resulting materials as a function of the increase of the amount of sulfonic groups. Finally, the XPS analysis proved that under these conditions undesired sulfone crosslinking did not occur.

Crystal Engineering for Intramolecular π–π Stacking: Effect of Sequential Substitution of F on Molecular Geometry in Conformationally Flexible Sulfonamides

A small library of ten sulfonamide derivatives comprising two aromatic rings was synthesized to investigate the effect of chronological positioning of the F-atom on the intramolecular π-stacking assembly. The sequential positioning of F-atoms was carried out on one of the aromatic rings that is linked to the sulfonamide moiety directly while the other aromatic ring (phenyl or pyridine) is linked by an ethyl spacer with the sulfonamide moiety. The ethyl spacer is provided to achieve the required flexibility so that both aromatic rings can bend to acquire syn conformation facilitated π-stacking between electron-deficient and electron-rich aromatic rings. The idea was to study the interplay between hydrogen bonding and π-stacking synthons in the conformationally flexible sulfonamide derivatives. The solid-state conformation of all the derivatives was investigated using the single-crystal X-ray diffraction technique. Crystal structure analysis revealed that the syn conformation was achieved only in trifluoro and pentafluoro sulfonamide derivatives with benzene substitution while in all other derivatives the molecules take either midway or anti conformations. None of the sulfonamide molecules with a pyridine moiety showed syn conformation. It could be because of the involvement of the pyridine N-atom in the hydrogen bonding dimeric synthon. The molecular conformation study in solution state using 2D NOESY and HOESY NMR experiments also substantiated syn conformation in a pentafluoro sulfonamide molecule with benzene substitution. The conformational analysis carried out employing density functional theory (DFT) calculations confirmed higher stability for the syn conformation over midway and anti orientations.

Unravelling nucleophilic aromatic substitution pathways with bimetallic nucleophiles.

The reaction of a metal complex containing a polar Fe-Mg bond with 2-(pentafluorophenyl)pyridine leads to selective C-F bond activation. A stepwise SNAr mechanism involving attack of the bimetallic nucleophile on the electron-deficient aromatic ring has been identified by DFT calculations. Despite the long and rich history of metal anions in organic synthesis, this is the first time the SNAr mechanism has been elucidated in detail for metal-based nucleophiles.

Intramolecular Nitro-Aromatic Interactions Within a Molecular Torsion Balance: A Quantitative Assessment

Interactions between a nitro group and an aromatic ring have been identified as an important aspect within the solid-state structures of many energetic materials. We investigated nitro-aromatic interactions within a molecular “torsion balance”, both in solid-state as well as in solution. Our balance features a Troger’s base and a nitroalkene functionality substituted at 1 and 8 positions of a naphthalene ring. Because of restricted rotation around a biaryl axis, the balance can adapt two principal atropisomeric conformations: folded and unfolded. Intramolecular nitro-aromatic interactions are feasible only in the folded state. A torsion balance containing a highly electron deficient aromatic ring crystallized in the folded state leading to the formation of a short (<3.4 A) intramolecular NO···aromatic contact. On the other hand, with an electron rich aromatic, the balance crystallized in the unfolded conformation in which the nitro group avoids the aromatic surface. In solution, the strength of the intera...

α-Chlorobenzylation of Nitroarenes via Vicarious Nucleophilic Substitution with Benzylidene Dichloride: Umpolung of the Friedel-Crafts Reaction.

Readily available α,α-dichlorotoluenes enter a vicarious nucleophilic substitution (VNS) reaction with electron-deficient arenes to give α-chlorobenzylated nitrobenzenes, as well as six- and five-membered heterocycles. Oxidation of the initially formed α-chlorobenzylic carbanions instead of protonation results in formation of diaryl ketones, providing a means for overall nucleophilic C-H benzoylation of electron-deficient aromatic rings. Alternatively, benzoylated nitroarenes can be obtained via the reaction of isolated α-chlorodiarylmethanes with sodium azide.

Nucleophilic Aromatic Substitution—Addition and Identification of an Amine

The addition of a nucleophilic functional group to an electron-deficient aromatic ring is a versatile reaction in the modern organic chemistry arsenal. The proper positioning of a leaving group on this ring effectively allows for a substitution reaction to occur. A 3 h laboratory experiment is described in which students utilize a common electrophilic aromatic ring and affect a substitution with an unknown amine, the identity of which is later characterized by the melting point and 1H NMR spectrum of the product.

Intramolecular Cycloaddition of Azomethine Ylides Activated by Aromatic Rings: Scope and Limitations

Simple aromatic substituents in the substrate molecule, including pyrimidine, pyridine, and benzene rings, directly facilitated the intramolecular cycloaddition of azomethine ylide to alkene. All of these aromatic substituents aided the formation of azomethine ylides, which then underwent highly diastereospecific sequential cycloaddition. It was shown that both the presence of an electron-deficient aromatic ring and a substituent at ortho position of the aromatic ring relative to the aminomethyl group enhanced the reactivity of azomethine ylides towards cycloaddition.

Identification and SAR Evaluation of Hemozoin-Inhibiting Benzamides Active against Plasmodium falciparum.

Quinoline antimalarials target hemozoin formation causing a cytotoxic accumulation of ferriprotoporphyrin IX (Fe(III)PPIX). Well-developed SAR models exist for β-hematin inhibition, parasite activity, and cellular mechanisms for this compound class, but no comparably detailed investigations exist for other hemozoin inhibiting chemotypes. Here, benzamide analogues based on previous HTS hits have been purchased or synthesized. Only derivatives containing an electron deficient aromatic ring and capable of adopting flat conformations, optimal for π-π interactions with Fe(III)PPIX, inhibited β-hematin formation. The two most potent analogues showed nanomolar parasite activity, with little CQ cross-resistance, low cytotoxicity, and high in vitro microsomal stability. Selected analogues inhibited hemozoin formation in Plasmodium falciparum causing high levels of free heme. In contrast to quinolines, introduction of amine side chains did not lead to benzamide accumulation in the parasite. These data reveal complex relationships between heme binding, free heme levels, cellular accumulation, and in vitro activity of potential novel antimalarials.

Additive Mediated Syn-Anti Conformational Tuning at Nucleation to Capture Elusive Polymorphs: Remarkable Role of Extended π-Stacking Interactions in Driving the Self-Assembly

Understanding the process of prenucleation clustering at supersaturating stage is of significant importance to envisage the polymorphism in crystalline materials. Preferential formation of a thermodynamically stable crystal form suggests energetically favored patterns of interactions which control molecular aggregation during nucleation. Introduction of additives during crystallization is sometimes used as a suitable strategy to obtain metastable polymorphs in cases where it is not easy to capture the same by conventional crystallization methods. Comparative analysis of energy relationships and intermolecular interactions between thermodynamically stable and metastable crystal forms provides valuable clues about the nature of growth synthons at prenucleation clustering and preferential crystallization of the thermodynamic form. Conformationally flexible sulfonamide/sulfoester derivatives constituting electron rich and electron-deficient aromatic rings were synthesized to study the interplay between π-stac...

Mechanistic Insights into the Mode of Action of Bifunctional Pyrrolidine-Squaramide-Derived Organocatalysts.

The catalytic modes of action of three squaramide-derived bifunctional organocatalysts have been investigated using DFT methods. The [5+2] cycloaddition between oxidopyrylium ylides and enals was used as the model reaction. Two primary modes were possible for the different catalysts studied. The preference for one mode over the other was due to the possibility of additional favorable π-π interactions between the hydrogen-bond activated pyrylium ylide and an electron-deficient aromatic ring bonded to the squaramide NH group. The model can be extended to other reactions catalyzed by the same catalysts, such as formal [2+2] cycloadditions between nitroalkenes and α,β-unsaturated aldehydes. The computational results were in excellent concurrence with the available experimental reports on the observed total enantioselectivity and differences in diastereoselectivity depending on the substrate and the reaction.

9-Anthracenecarboxamide fluorescent probes for selective discrimination of picric acid from mono- and di-nitrophenols in ethanol

A new class of ‘switch off’ anthracenecarboxamide-based sensing probes (1–3) for the detection of picric acid (PA) was designed and synthesized. Probe 1 exhibited the highest sensitivity and selectivity toward PA, enabling complete fluorescence quenching and exhibiting a high association constant (4.14×105M−1) with a 1:1 stoichiometric ratio of 1 to PA in EtOH. Probe 1 was able to detect PA through multiple synergic interactions such as hydrogen bonding, π–π interactions between the electron-rich aromatic rings of anthracene and the electron-deficient aromatic ring of PA that resulted in a favorable fluorescence resonance energy transfer from the latter to the former. The ability of probe 1 to sense PA was investigated by UV–visible, fluorescence, and 1H NMR spectroscopies, as well as DFT calculations.

Atmospheric pressure variability over Western North America and the North Pacific reconstructed using tree-ring records

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.

Carbon-Dot-Sensitized, Nitrogen-Doped TiO2 in Mesoporous Silica for Water Decontamination through Nonhydrophobic Enrichment-Degradation Mode.

Mesoporous silica synthesized from the cocondensation of tetraethoxysilane and silylated carbon dots containing an amide group has been adopted as the carrier for the in situ growth of TiO2 through an impregnation-hydrothermal crystallization process. Benefitting from initial complexation between the titania precursor and carbon dot, highly dispersed anatase TiO2 nanoparticles can be formed inside the mesoporous channel. The hybrid material possesses an ordered hexagonal mesostructure with p6mm symmetry, a high specific surface area (446.27 m(2) g(-1) ), large pore volume (0.57 cm(3) g(-1) ), uniform pore size (5.11 nm), and a wide absorption band between λ=300 and 550 nm. TiO2 nanocrystals are anchored to the carbon dot through TiON and TiOC bonds, as revealed by X-ray photoelectron spectroscopy. Moreover, the nitrogen doping of TiO2 is also verified by the formation of the TiN bond. This composite shows excellent adsorption capabilities for 2,4-dichlorophenol and acid orange 7, with an electron-deficient aromatic ring, through electron donor-acceptor interactions between the carbon dot and organic compounds instead of the hydrophobic effect, as analyzed by the contact angle analysis. The composite can be photocatalytically recycled through visible-light irradiation after adsorption. The narrowed band gap, as a result of nitrogen doping, and the photosensitization effect of carbon dots are revealed to be coresponsible for the visible-light activity of TiO2 . The adsorption capacity does not suffer any clear losses after being recycled three times.

ChemInform Abstract: 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.