Six-membered Aromatic Rings Research Articles

Advancements in Pyrazine Derivatives as Anticancer Agents: A Comprehensive Review (2010-2024).

Cancer, an intricate and formidable disease, continues to challenge Medical Science with its diverse manifestations and relentless progression. In the pursuit of novel therapeutic strategies, organic heterocyclic compounds have emerged as promising candidates due to their versatile chemical structures and intricate interactions with biological systems. Among these, pyrazine derivatives are characterized by a six-membered aromatic ring containing four carbon and two nitrogen atoms situated in a 1,4-orientation. These compounds garnered significant attention for their potential as anticancer agents. This comprehensive review provides a detailed analysis of the advancements made during this timeframe, encompassing the chemical diversity of pyrazine derivatives, their mechanisms of action at the cellular level, and structure-activity relationships, spanning the years 2010 to 2024. By examining their therapeutic potential, challenges, and future prospects, this review offers valuable insights into the evolving landscape of pyrazine derivatives as potent tools in the fight against cancer.

Metal-Free Reversible Double Cyclization of Cyanuric Diazide to an Asymmetric Bitetrazolate via Cleavage of the Six-Membered Aromatic Ring.

Crystallization of the reaction mixture of 2-amino-4,6-diazido-1,3,5-triazine and excess tert-butylamine results in the isolation of tert-butylammonium N,N-[1'H-(1,5'-bitetrazol)-5-yl]cyanamidate, suggesting a complex decyclization/cyclization rearrangement involving breakage of the six-membered aromatic ring and the formation of two new five-membered azole rings mediated by deprotonation of the precursor by the amine. The addition of tert-butylamine to 2-amino-4,6-diazido-1,3,5-triazine gives spectroscopic indication of thermodynamically unfavorable reactivity in low-dielectric solvents, and high-level quantum chemical computations also suggest its formation to be unfavorable. A computed interconversion pathway describes the likely reaction mechanism and supports the general thermodynamic unfavorability of the reaction and the requirement for a high-dielectric environment to template formation of the ionic product and its trapping by crystallization.

Recent advances in the biological activity of quinazoline

The aim of this review is to produce an outline of numerous pharmacologic activities of quinazoline moiety. Quinazoline has become a famous topic up of two fused six-membered simple aromatic rings, a benzene ring and a pyrimidine ring because of its manifold uses. various quinazoline derivatives have been found to gives a broad spectrum of biological activities, which stimulated the research activity in this field. Quinazolines and its derivatives represent one in all the foremost active categories of compounds, that possess wide selection of biological activities like anti-bacterial, analgesic, anti-microbial, anti-inflammatory drug, anticancer, and anti-hypertensive, antifungal, anti-HIV, inhibitor, analgesic, medicament, antiprotozoal, antitumor, anti-tubercular activities. This review is an effort to magnify the immense potentiality of this ring system. This study may accelerate the designing process to come up with a lot of range of therapeutically viable clinical candidates.

2 approaches to new pyridines

Pyridines, molecules consisting of one nitrogen and five carbons in a six-membered aromatic ring, are an important chemical stepping stone for a variety of drugs, agricultural products, and materials. These molecules are hard to modify, however, particularly at the meta position—or two spots over from the N—in the ring. This forces chemists to use high heat, strong acids, or metal catalysts to coerce pyridines to react. Now, two groups of scientists have developed different techniques to take pyridines apart and put them back together with new functionality at the meta position without using harsh reaction conditions. Both are mild, one-pot methods that may offer an easier way to create important commercial compounds and materials. In the two approaches, the overall simplified reaction looks the same: start with a pyridine compound and end with a meta-substituted pyridine (shown). Chemists have a notoriously hard time adding functional groups to pyridines because the

The LAM of the Rings: Large Amplitude Motions in Aromatic Molecules Studied by Microwave Spectroscopy.

Large amplitude motions (LAMs) form a fundamental phenomenon that demands the development of specific theoretical and Hamiltonian models. In recent years, along with the strong progress in instrumental techniques on high-resolution microwave spectroscopy and computational capacity in quantum chemistry, studies on LAMs have become very diverse. Larger and more complex molecular systems have been taken under investigation, ranging from series of heteroaromatic molecules from five- and six-membered rings to polycyclic-aromatic-hydrocarbon derivatives. Such systems are ideally suited to create families of molecules in which the positions and the number of LAMs can be varied, while the heteroatoms often provide a sufficient dipole moment to the systems to warrant the observation of their rotational spectra. This review will summarize three types of LAMs: internal rotation, inversion tunneling, and ring puckering, which are frequently observed in aromatic five-membered rings such as furan, thiophene, pyrrole, thiazole, and oxazole derivatives, in aromatic six-membered rings such as benzene, pyridine, and pyrimidine derivatives, and larger combined rings such as naphthalene, indole, and indan derivatives. For each molecular class, we will present the representatives and summarize the recent insights on the molecular structure and internal dynamics and how they help to advance the field of quantum mechanics.

Construction and Functionalization of Highly Strained N -Doped Zigzag Hydrocarbon Belts

Construction and Functionalization of Highly Strained <i>N</i> -Doped Zigzag Hydrocarbon Belts

Total Synthesis of Gukulenin B via Sequential Tropolone Functionalizations.

The synthesis of functionalized aromatic compounds is a central theme of research for modern organic chemistry. Despite the increasing finesse in the functionalization of five- and six-membered aromatic rings, their seven-membered-ring sibling, tropolone (2-hydroxy-2,4,6-cycloheptatrien-1-one), remains a challenging target for synthetic derivatization. This challenge primarily emanates from the unique structural and chemical properties of tropolonoid compounds, which often lead to unexpected and undesired reaction outcomes under conditions developed for the functionalizations of other aromatic moieties. Herein, we describe the total synthesis of one of the most complex natural tropolonoids, gukulenin B. Our synthetic route features a series of site-selective aromatic C-H bond functionalizations and C-C bond formations, whose reaction conditions are judiciously tuned to allow uncompromised performance on the tropolone nucleus. The flexibility and modularity of our synthesis are expected to facilitate further synthetic and biological studies of the gukulenin family of cytotoxins. In addition, the methods and tactics developed herein for the functionalization of the tropolone moiety could inspire and enable chemists of multiple disciplines to take advantage of this privileged yet underexplored structural motif.

Solid-State Pathway Control via Reaction-Directing Heteroatoms: Ordered Pyridazine Nanothreads through Selective Cycloaddition.

Nanothreads are one-dimensional nanomaterials composed of a primarily sp3 hydrocarbon backbone, typically formed through the compression of small molecules to high pressures. Although nanothreads have been synthesized from a range of precursors, controlling reaction pathways to produce atomically precise materials remains a difficult challenge. Here, we show how heteroatoms within precursors can serve as "thread-directing" groups by selecting for specific cycloaddition reaction pathways. By using a less-reactive diazine group within a six-membered aromatic ring, we successfully predict and synthesize the first carbon nanothread material derived from pyridazine (1,2-diazine, C4H4N2). Compared with previous nanothreads, the synthesized polypyridazine, shows a predominantly uniform chemical structure with exceptional long-range order, allowing for structural characterization using vibrational spectroscopy and X-ray diffraction. The results demonstrate how thread-directing groups can be used for reaction pathway control and the formation of chemically precise nanothreads with a high degree of structural order.

Surface-Induced Keto-Enol Tautomerization of DNA Base Molecules and Consequent [4 + 2]-like Cycloaddition on Si(111)7×7.

Adsorption and film growth of deoxyribonucleic acid (DNA) base molecules (cytosine, guanine, thymine, and adenine) on Si(111)7×7 have been studied by combining X-ray photoelectron spectroscopy (XPS) with ab initio calculations based on the density functional theory (DFT). Multiple tautomeric forms and keto-enol tautomerization are revealed by the O 1s, N 1s, and C 1s XPS spectra of the O-containing DNA bases: cytosine, guanine, and thymine. While the carbonyl group-containing keto tautomer is more stable in a thick film and in powder, the hydroxyl group-containing enol tautomer is found at the interface. The keto-enol tautomerization, as induced by the reactive Si(111)7×7 surface, leads to the formation of a conjugated aromatic six-membered ring with a delocalized π electron system and to the consequent [4 + 2]-like cycloaddition between the enol tautomer and the 7×7 surface. The DFT calculation suggests that the enol tautomer exhibits a kinetic advantage over the keto one for the [4 + 2]-like cycloaddition. Among the several plausible pathways for the cycloaddition provided by the enol tautomer, the experimentally determined one involves a ring N and ring C atom (a polar pair), rather than two ring C atoms (a nonpolar pair), to better match the polar Si adatom-restatom pair of the 7×7 surface. Furthermore, the reacted ring C atom does not have any attached terminal functional group (e.g., -NH2 and -OH). Further deposition leads to continuous film growth in the keto tautomeric form for cytosine and guanine. For the only O-free DNA base molecule, adenine, dative bonding N → Si, rather than the [4 + 2]-like cycloaddition, is observed on the 7×7 surface. Of the four DNA base molecules, adenine is also the only one with its aromaticity maintained when adsorbed on the Si(111)7×7 surface. A reactive surface like the 7×7 surface could therefore provide a new control to trigger tautomerization that is often associated with genetic mutation.

Transition-metal-mediated reduction and reversible double-cyclization of cyanuric triazide to an asymmetric bitetrazolate involving cleavage of the six-membered aromatic ring.

Cyanuric triazide reacts with several transition metal precursors, extruding one equivalent of N2 and reducing the putative diazidotriazeneylnitrene species by two electrons, which rearranges to N-(1′H-[1,5′-bitetrazol]-5-yl)methanediiminate (biTzI2−) dianionic ligand, which ligates the metal and dimerizes, and is isolated from pyridine as [M(biTzI)]2Py6 (M = Mn, Fe, Zn, Cu, Ni). Reagent scope, product analysis, and quantum chemical calculations were combined to elucidate the mechanism of formation as a two-electron reduction preceding ligand rearrangement.

Chemoselective C−C σ‐Bond Activation of the Most Stable Ring in Biphenylene**

The chemoselective cleavage of a six-membered aromatic ring in biphenylene is reported using an aluminum(I) complex. This type of selectivity is unprecedented. In every example of transition metal mediated C-C σ-bond activation reported to date, the reaction occurs at the central four-membered ring of biphenylene. Insight into the origin of chemoselectivity was obtained through a detailed mechanistic analysis (isolation of an intermediate, DFT studies, activation strain analysis). In conclusion, the divergent reactivity can be attributed to differences in both the symmetry and radial extension of the frontier molecular orbitals of the aluminum(I) fragment compared to that of common transition metal fragments.

Ionic liquid-modified graphene oxide sponge for hexavalent chromium removal from water

Chromium pollution in groundwater is a major cause of concern due to significant health risks of hexavalent chromium (Cr(VI)) ions. Graphene oxide (GO) covalently modified with 1-aminopropyl-3-methylimidazolium bromide (mimNH2) and freeze-dried to give 1-aminopropyl-3-methylimidazolium bromide functionalized graphene oxide sponge (mimGO sponge). mimGO sponge effectively adsorbed hexavalent chromium (Cr(VI), toxic) by electrostatic interactions and reduced Cr(VI) to trivalent chromium (Cr(III), less toxic) by an indirect mechanism with the contribution of delocalized π-electrons on the six-membered aromatic ring of mimGO sponge. The change in contact time, adsorbent loading, initial Cr(VI) solution concentration, and different types of adsorbents were investigated. The experimental data were fitted to the pseudo-second order kinetic model, which showed hydro-chromate adsorption on mimGO sponge was surface adsorption with chemical interaction. The adsorption process was well-defined by the Langmuir isotherm model, and equilibrium adsorption capacity was 208.3 mg/g at 23 ℃ in an acidic environment. The electrostatic interaction between the chromate ions and mimGO sponge also caused a reduction of Cr(VI) to less benign Cr(III) on the adsorbent surface. Thus, mimGO sponge has a green adsorbent that showed the potential for Cr(VI) removal from water.

A Review on Modern Synthetic Route for the Construction of 1, 3-Diazanaphthalene Moiety

Quinazoline is an organic heterocyclic molecule in which two six-membered aromatic rings are fused. Two nitrogen atoms are present in the quinazoline molecule at 1 and 3 positions that is why it is also known as 1,3-diazanaphthalene. The presence of these two nitrogen atoms in 1,3-diazanaphthalene increases the usefulness of this molecule in the field of pharmaceutical sciences. Many reactions have been reported to prepare 1,3- diazanaphthalene by aminobenzonitrile, o-aminobenzohydrazide, aminobenzamide, aminoacetophenone, and aminobenzoketone under different solvent conditions, but condensation of anthranilic acid with an aromatic aldehyde is the most common method. Later, metal-free and solvent-free conditions dominated over the old methods. This review describes the synthesis of 1,3-diazanaphthalene under different metal catalysts, reagents, solvent- free conditions and under microwave radiation through nucleophilic substitution reaction, condensation, and aromatization. In biological sciences, 1,3-diazanaphthalene derivatives have got an important place due to their ability to bind to different target sites and subsequent discovery of many drug structures.

Collision-induced luminescence spectra of pyridine bombarded by 1000 eV He+ cations

Here we show collision-induced luminescence spectra measured for collisions of the He+ cations with the aromatic six-membered ring of the pyridine molecule (C5H5N). Distinct emission bands due to the CH(A2Δ → X2Πr; B2Σ+ → X2Πr; C2Σ+ → X2Πr), CN(B2Σ+ → X2Σ+), C2(d3Πg → a3Πu), and NH(A3Π → X3Σ−) transitions, as well as atomic H, He, and C lines have been observed. Apart from the He atoms, all the emitters arise from the fragmentation of the pyridine ring. The identification of the helium lines indicates a single electron transfer reaction from the pyridine molecule to the He+ cations. The products’ intensities relative to the Hβ intensity have also been obtained and compared with the intensity ratios determined for He+ + furan collisions.

Predicting the photoresponse of soot nuclei: Spectroscopic characteristics of aromatic aggregates containing five-membered rings

Establishing the mechanism for soot nucleation will require in situ experimental characterization of the identity and intermolecular interactions of the initial precursors, and electronic spectroscopy methods have the potential to do both. However, the optical response of polycyclic aromatic hydrocarbon (PAH) dimers and complexes differs significantly from that of the constituent monomers, and studies of soot precursor complexes have largely been limited to PAHs containing only six-membered aromatic rings. Hydrocarbons containing unsaturated five-membered rings are also present in high concentration in flames, and the photoresponse of complexes containing five-membered rings has not yet been examined. In this work, we elucidate the spectroscopic properties of small hydrocarbon complexes containing cyclopentadienyl groups or cyclopenta-fused groups, calculating ground- and excited-state binding energies, optimal excited-state geometries, repulsion energies, and fluorescence emission wavelengths. We show that excited-state distortion of cyclopentadienyl groups allows strong binding and low-energy fluorescence emission compared to similar-sized PAHs, and that a cyclopenta-fused group dramatically lowers the absorption and emission energies for acenaphthylene, dominating excited-state noncovalent interactions—findings that could shed light on the complex electronic properties of flames.

Stitching up the Belt[n]arenes

A synthetic strategy reported recently in the Journal of the American Chemical Society by Wang and coworkers, who used laser irradiation in the final key step of the synthesis, has led to the formation of highly strained belt[8]arene derivatives. This breakthrough could open doors to more controlled and precise syntheses of zigzag carbon nanotubes.

Theoretical study on carbonaceous materials as high efficient carriers for crizotinib drug in liquid water by density functional theory approach

In order to get a precise insight into the nature of the intermolecular interaction of crizotinib drug with carbon nanomaterials, i.e., fullerene C70 and graphene nanosheet as high efficient carriers, the density functional theory calculations are applied on the binding strength, the molecular structures, electronic properties, and charge transfer in the water phase. Based on the calculated adsorption energy values, the physical nature for the interaction of the adsorbed drug with carbon nanostructures is approved. The obtained results suggest that crizotinib drug exhibits the strongest affinity for the adsorption on graphene nanosheet in comparison to fullerene C70. By considering the optimized geometries of the considered complexes, the π–π stacking interactions between π orbitals of the carbon nanostructures and the six-membered aromatic ring of the adsorbed molecule are observed. As a result of the physisorption process, no structural or electronic change of the adsorbed drug is found. Analysis of the energetic parameter of atoms-in-molecule method suggests medium strength intermolecular interaction of crizotinib drug with carbon nanostructures with partially covalent nature. The interactions of crizotinib drug and carbon nanostructures on the basis of two reactivity descriptors such as the overall stabilization energy and the fractional number of electrons transferred have been explained. The theoretical results show that the interaction of graphene nanosheet with crizotinib agent is more favorable than fullerene C70. The analysis of the natural bond orbital shows the capability of the carbon nanostructures to accept precisely the electron from crizotinib drug molecule during the adsorption process.

Influence of Solvent in Crystal Engineering: A Significant Change to the Order-Disorder Transition in Ferrocene.

We present the structure of a novel solvate adduct formed by dissolving ferrocene, FeCp2, in hexafluorobenzene, C6F6. This adduct demonstrates the remarkably strong interactions between the five-membered aromatic rings of FeCp2 and the six-membered aromatic ring of C6F6. These molecular interactions are sufficiently strong and anisotropic to change the temperature of the order-disorder transition of the ferrocene molecule from below ca. 164 K to RT. No solvate adduct could be formed between benzene and FeCp2. These observations will be of particular relevance to the crystal engineering community, whose goal is the design of solids with bespoke properties.

Toward tailoring of robust organobases based on extended π-systems: A density functional theory study of the carbonyl basicity

The gas phase proton affinity (PA) and basicity (GB) of a series of extended π-systems, possessing carbonyl as the most basic sites, were calculated using the DFT-B3LYP theoretical method. The backbone of the polycyclic π-electron networks contains either pyrone, pyrolidine or thiopyrane substructures, which can be in α or λ isomer forms. The PAs of designed molecules were reported in the range of 868–1089 kJ mol−1, indicating that some of the molecules have the basicity higher than 1,8-bis(dimethylamino) naphthalene. Such high basicity is a consequence of stabilization in protonated forms, due to the formation of the six-membered aromatic rings upon protonation which stabilize the positive charge. The aromaticity indices of the rings before and after protonation were calculated. The results show that aromaticity indices in the protonated form of the designed molecules is significantly higher than the neutral one.

Benzo[c][1,2,5]selenadiazole organoselenium derivatives: Synthesis, X-ray, DFT, Fukui analysis and electrochemical behavior

Organo-selenium compounds are of a broad spectrum of potential technical applications. To date, many efforts have been devoted to develop their chemistry. In this context, two benzo[c][1,2,5]selenadiazole compounds have been synthesized and characterized by 1H NMR, 13C NMR, 19F NMR, MS and UV–Vis spectroscopic techniques. Both structures were confirmed using single-crystal X-ray diffraction analysis. Each compound crystallizes in monoclinic systems, space group P21/c forming dimeric units due to the intermolecular Se⋯N interactions. The dimmers are further linked by weak π···π stacking interactions between 1,2,5-selenadiazole and the six-membered aromatic rings. The electrochemical behavior of the compounds has been investigated by cyclic voltammetry. Additionally, the structural geometrical parameters, vibrational, electronic transition, Fukui analysis and redox properties of the molecules have been rationalized by DFT and TD-DFT methods using B3LYP level of theory in conjunction with 6-311G(d,p) basis set implemented in Gaussian 09 program. As a result, an excellent correlation between the electronic transitions and the electrochemical behavior was found.