Aromatic Ring Research Articles

Emerging Aspects of Triazole in Organic Synthesis: Exploring its Potential as a Gelator.

Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) - commonly known as the "click reaction" - serves as the most effective and highly reliable tool for facile construction of simple to complex designs at the molecular level. It relates to the formation of carbon heteroatomic systems by joining or clicking small molecular pieces together with the help of various organic reactions such as cycloaddition, conjugate addition, ring-opening, etc. Such dynamic strategy results in the generation of triazole and its derivatives from azides and alkynes with three nitrogen atoms in the five-membered aromatic azole ring that often forms gel-assembled structures having gelating properties. These scaffolds have led to prominent applications in designing advanced soft materials, 3D printing, ion sensing, drug delivery, photonics, separation, and purification. In this review, we mainly emphasize the different mechanistic aspects of triazole formation, which includes the synthesis of sugar-based and non-sugar-based triazoles, and their gel applications reported in the literature for the past ten years, as well as the upcoming scope in different branches of applied sciences.

Environmental risk mitigation of lambda-cyhalothrin using tryptophan-modified magnetic nanoparticles: A sustainable emergency response strategy

Lambda-cyhalothrin, a synthetic pyrethroid pesticide extensively used in agriculture, poses significant environmental challenges due to its extensive and long-term application. To remediate pollution caused by such organic contaminants, our study introduces a rapid and convenient one-pot synthesis method for creating amino acid-modified magnetic nano-adsorbents (AA-MNPs). Research found that after modification with tryptophan (Trp), the adsorption effectiveness of MNPs on Lambda-cyhalothrin significantly increases. This modification enhances the carbon content of the magnetic nanoparticles, while minimally affecting the magnetic saturation of the MNPs. Trp-MNP exhibited an approximate particle size of 450 nm and a specific surface area of 52.36 m2/g. The isotherm and kinetic experiments were well-fitted to the Liu isotherm model and the pseudo-second-order model, respectively. Thermodynamic assessments suggested that the adsorption process is spontaneous and exothermic. Results indicated that the maximum adsorption capacity 144.34 mg g−1 for Trp-MNPs at 298 K, outperforming adsorbents reported in the literature. The half-adsorption time was reduced to 8 min at 298 K with an initial concentration of 60 mg/L. This enhancement was likely influenced by the aromatic ring modification and hydrophobicity of Trp-MNPs. The study explored potential removal mechanisms from a tri-phase perspective, investigating the interactions between the adsorbent, adsorbate, and solvent.

Exploring Quinoxalinone Derivatives as Promising Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors for Cancer Therapy

E GFR plays an extensive role in the signaling pathway such as proliferation, migration, invasion. However, the malfunctioning of the epidermal growth factor receptor (EGFR) is a crucial factor in cancer progression. The search for new kinase inhibitors is necessary due to the evolving nature of diseases and the emergence of resistant strains, prompting the need for novel compounds that can effectively target and inhibit specific kinases for therapeutic purposes. This study explores quinoxalinone derivatives, comprised of benzene and pyrazine aromatic rings, as novel potential EGFR kinase inhibitors for cancer therapy, fulfilling an essential need in targeted cancer treatments. We utilized molecular docking to examine 46 synthesized quinoxalinone derivatives for their interaction with the tyrosine kinase domain of EGFR. Fifteen compounds exhibited strong binding affinities. Notably, LS3c, MN333, and MN343 displayed significant inhibitory effects on A431 cells with half-maximum inhibitory concentration (IC50) values comparable to gefitinib, erlotinib, and afatinib in enzymatic kinase assays. Subsequent experiments revealed that LS3c and MN343 effectively inhibit EGFR-expressing cell lines with low hepatotoxicity. MN343, the most potent compound, was selected for molecular dynamic simulation to understand its interaction with the tyrosine kinase of EGFR. To investigate the interaction between MN343 and EGFR’s tyrosine kinase, MM-PBSA analysis identified key residues (L694, V702, L768, M769, and L820) crucial for interaction, highlighting the potential of MN343 as a clinical EGFR tyrosine kinase inhibitor. The need for discovering new kinase inhibitors arises from the dynamic nature of diseases and the appearance of resistant strains, emphasizing the requirement for innovative compounds capable of targeting and inhibiting specific kinases effectively for therapeutic applications.

Biogenic synthesis of CoO and ZnO nanoparticles using rosemary extract: Synergistic antimicrobial activity and insights from DFT simulations

Plant extracts with stabilizing and emulsifying qualities are commonly used in nanotechnology for the eco-friendly production of metallic nanoparticles. The study focused on synthesizing CoO and ZnO nanoparticles by the use of rosemary leaf extract. Quantum chemical calculations were performed using the DFT method to determine the active sites of the main chemical compounds in rosemary extract that catalyze the bi-reduction of Co+2 and Zn+2, resulting in the eco-friendly production of CoO and ZnO nanoparticles. Rosemary leaf extracts include a significant quantity of hydroxyl groups (–OH), oxygen atoms as heteroatoms, and many aromatic rings. The enhanced amount of π-electrons, resulting from aromatic rings and electron-releasing groups connected to these rings, facilitates the simultaneous reduction of Co and Zn metals. This happens because the π-electrons are more likely to interact with the vacant d-orbitals of Co and Zn. Antibacterial activity tests show that CoO and ZnO nanoparticles manufactured using green methods are effective against both gram-negative and gram-positive bacteria, as well as the fungal isolate C. albicans with superior activity of CoO nanoparticles. The MIC assay results show that the synthesized nanoparticles are more effective against gram-negative E. coli bacteria than gram-positive S. aureus bacteria and C. albicans. CoO nanoparticles showed about 1.5x - 3x fold more antibacterial activity compared to ZnO nanoparticles. The results emphasize the possibility of using green synthesis of nanoparticles as an environmentally benign and cost-efficient technique for mass manufacturing, showing potential applications in the fields of medicine and industry.

Plasma Engineering toward Improving the Microwave-Absorbing/Shielding Feature of a Biomass-Derived Material.

During the past decade, ever-increasing electromagnetic pollution has excited a global concern. A sustainable resource, facile experimental scenario, fascinating reflection loss (RL), and broad efficient bandwidth are the substantial factors that intrigue researchers. This research led to the achievement of a brilliant microwave-absorbing material by treating pampas as biomass. The carbon-based microfibers attained by biowaste were treated by plasma under diverse environments to amplify their microwave-absorbing features. Moreover, a pyrolysis scenario was performed to compare the results. The reductive processes were performed by H2 plasma and carbonization. However, the CO2 plasma was performed to regulate the heteroatoms and defects. Interestingly, polystyrene (PS) was applied as a microwave-absorbing matrix. The aromatic rings existing in the absorbing medium establish electrostatic interactions, elevating interfacial polarization, and physical characteristics of PS augment the practical applications of the final product. The manipulated biomasses were characterized by Raman, X-ray diffraction, energy-dispersive spectroscopy, field emission scanning electron microscopy, and diffuse reflection spectroscopy analyses. Eventually, the microwave-absorbing features were estimated by a vector network analyzer. The plasma-treated pampas under H2/Ar blended with PS gained a maximum RL of -90.65 dB at 8.79 GHz and an efficient bandwidth (RL ≤ -10 dB) of 4.24 GHz with a thickness of 3.20 mm; meanwhile, plasma treatment under CO2 led to a maximum RL of 97.99 dB at 14.92 GHz and an efficient bandwidth of 7.74 GHz with a 2.05 mm thickness. Particularly, the biomass plasmolyzed under Ar covered the entire X and Ku bands with a thickness of 2.10 mm. Notably, total shielding efficiencies of the treated bioinspired materials were up to ≈99%, desirable for practical applications.

Nanoarchitectonics of an acetogenin-enriched nanosystem mediated by an aqueous extract of Annona cherimola Mill with anti-inflammatory and proapoptotic activity against HepG2 cell line

For the first time, this study shows the nanoarchitectonic process to obtain an acetogenin-enriched nanosystem (AuNPs-Ac) using an aqueous extract from Annona cherimola Mill (ACM) composed of gold nanoparticles embedded in an organic matrix that acts as stabilizing agent and presents anti-inflammatory activity and cytotoxical effect against HepG2 cell line, promoting apoptosis. The synthesis of AuNPs-Ac was confirmed by x-ray diffraction analysis, showing metallic gold as the only phase, and the scanning transmission microscope showed an organic cap covering the AuNPs-Ac. Fourier-transformed infrared suggests that the organic cap comprises a combination of different annonaceous acetogenins, alkaloids, and phenols by the presence of bands corresponding to aromatic rings and hydroxyl groups. High-Performance Liquid Chromatography has demonstrated the presence of annonacin, a potent acetogenin, in the extract of ACM. An in vitro anti-inflammatory activity of the extract of ACM and the AuNPs-Ac was performed using the albumin denaturation method, showing a nonlinear response, which is better than sodium diclofenac salt in a wide range of concentrations that goes from 200 to 400 μg ml−1 with both samples. The viability assay was studied using trypan blue, treating IMR90 and HepG2 at different concentrations of AuNPs-Ac. The results defined a median lethal dose of 800 μg ml−1 against HepG2 through apoptosis according to the ratio of caspase-cleaved 9/alpha-tubulin evaluated. It was also demonstrated that the nanosystem presents a higher cytotoxic effect on the HepG2 cell line than in IMR90, suggesting a targeted mechanism. In addition, the nanosystem performs better than using only the extract of ACM in the anti-inflammatory or antiproliferative test, attributed to their higher surface area.

Ultra‐Small Au Nanoclusters with Tailored Photoluminescence Properties using Modified Thiol Ligands: A Computational and Experimental Demonstration

AbstractAu nanoclusters with tailored photoluminescence can be obtained through controlled nanoparticle ligand interface chemistry. The present work reports molecular gold nanoclusters with tuneable photoluminescence emission from 600 to 700 nm using N,N′,N″‐trialkyl (11‐mercaptoundecyl)ammonium chloride ligands as capping‐agents. The tunability within red spectral region is regulated through specific interface chemistry between gold nanoclusters of molecular range and functional groups of the quaternary ammonium head over N,N′,N″‐trialkyl(11‐mercaptoundecyl)ammonium chloride. Combined understanding obtained from the spectroscopy, microscopy, and density functional theory studies demonstrate that the functional group specific electronic interactions at the interfaces steer the emission characteristics of “molecular” Au nanoparticles. The study clearly identifies that bulkier functional groups, i.e., triethyl, tripropyl, tributyl, and dimethyl benzene over N+ (of thiol ligand) through their steric effects minimize the particle size giving rise to tunable photoluminescence emission in red spectral region. However, the red shift seen in the emission Au nanoclusters with N‐(11‐mercaptoundecyl)‐N,N′‐dimethylbenzenammonium chloride ligand in contradiction to particle size effect is computationally proved to be due to the delocalization of electron density from benzene aromatic ring to N+ of ammonium head leading to a reduction in the HOMO‐LUMO energy gap.

Radiolytic degradation of 4-hydroxybenzoate in aerated and deoxygenated aqueous solutions

ABSTRACT The radiolytic degradation of 4-hydroxybenzoate (4-HBA–) in aerated, oxygen-free and N2O-saturated aqueous solutions at concentrations of 0.10 and 0.25 mmol/dm3 were gamma irradiated at different doses in a source of Co-60. The results show that ·OH adds predominantly to the third position of the aromatic ring, and elimination of the acid group leads to the degradation of 4-HBA–. With an N2O-saturated 0.10 mmol/dm3 4-HBA– solution, total degradation occurred at 1.6 kGy, and with a 0.25 mmol/dm3 solution, total degradation occurred at 3.5 kGy. In the aerated and oxygen-free 0.25 mmol/dm3 4-HBA– solutions, the behavior was similar, degradation occurring at a dose of 13.1 kGy. At the concentration of 0.10 mmol/dm3, total degradation occurred at 7.0 kGy, with small amounts of radiolytic products and byproducts. We propose a mechanism for the degradation of 4-HBA– caused by water radicals produced in the three environments, leading to formation of the identified stable products. Oxidation was followed by chemical oxygen demand (COD), which decreased as the 4-HBA− concentration increased. The kinetics showed a pseudo-first-order behavior. The rate constant of degradation was similar for the solutions with and without oxygen.

A Fluorescent Furan-based Probe with Protected Functional Groups for Highly Selective and Non-Toxic Imaging of HT-29 Cancer Cells and 4T1 Tumors.

Most of the previously reported fluorescent organic probes for tumor imaging have significant limitations including chemical toxicity, low Stokes shift value, and the inability for selective accumulations in tumors. To overcome these challenges, we synthesized two fluorescent probes with protected polar functional groups to enhance the non-toxicity nature and increase the selectivity toward tumors. In addition, the structural rigidity of the fluorescent probes was increased by embedding aromatic rings in the probe structure. This issue enables us to obtain ultrabright cell images due to enhanced fluorescence quantum yield (ФFL) values. After spectral characterizations, the applicability of two furan-based and imidazole-based fluorescent probes (abbreviated as DCPEF and DBPPI, respectively) was investigated for in vitro and in vivo imaging of cancer cells. The MTT cytotoxicity assay showed that probe DCPEF has minimal effects against HT-29 (cancer) and Vero (normal) cells. The probe DCPEF produced ultrabright fluorescence images from HT-29 cells. In addition, in vivo imaging of cancer cells showed that probe DCPEF selectively accumulates in the 4T1 tumor in mice. The chemical stability and high degree of selectivity for tumor cells make DCPEF an appropriate candidate to be used as a standard probe for cancer cell imaging.

Pd‐Pt Bimetallic Catalysts for Enhanced Low‐Temperature Hydrodeoxygenation of Vanillin

AbstractTo make pyrolytic bio‐oil useful as a transportation fuel, the oxygen content must be reduced, and this can be carried out by using catalytic hydrodeoxygenation (HDO) reaction. The greatest challenge is associated with the removal of strongly bound oxygenated groups without saturating the aromatic ring while preserving the number of carbons. However, the development of a stable catalyst that can selectively remove such oxygenated groups with low hydrogen consumption is still challenging. In this context, a systematic study on HDO of vanillin on bimetallic Pd−Pt catalysts was carried out. It aims to study the effect of bimetallic synergy in terms of activity and selectivity to creosol. Metallic nanoparticles of Pd and Pt were synthesized by sol immobilization technique and deposited on TiO2. The conversion of vanillin was correlated to the Pd−Pt atomic ratio, while the production of the creosol was correlated to the Pd(0)/(Pd+Pt) ratio at the surface. Full conversion of vanillin was obtained at low reaction temperature (20 °C) achieving nearly 100 % selectivity to creosol. These results represent a step forward in advancing the development of more efficient and sustainable processes for bio‐oil upgrading.

Visible-Light-Promoted [4π + 2σ] Annulation of Dienes and Alkylamines via Dual Inert C(sp3)-H Bond Activation.

Herein, visible-light-promoted [4π + 2σ] annulation of dienes and alkylamines was achieved via dual C(sp3)-H bond functionalization of alkylamines. The elusive enamine precursors are generated under mild conditions by photoredox catalysis, efficiently annulated by the diene, and simultaneously functionalized with two aliphatic C(sp3)-H bonds, resulting in the productive synthesis of new aromatic rings. The aromatic ring construction provides direct access to 2-hydroxybenzophenone derivatives in high yields (up to 90%). This [4π + 2σ] annulation reaction demonstrates mild reaction conditions, high reaction efficiency, and broad functional group tolerance, and this synthetic protocol has been made available for the late-stage transformation of natural products and commercial drugs.

The synthesis, structure, and catalytic properties of Cl‐substituted tridentate ONO Schiff base molybdenum(VI) complexes: Expeditious synthesis of 1,8‐dioxo‐octahydro‐xanthene derivatives

A family of molybdenum complexes with a general formula of [MoO2L]2 have been synthesized and fully characterized, where L is a tridentate ONO Schiff base ligand featuring a Cl substituent in different positions on the aromatic ring of salicylidene‐2‐aminophenolato backbone. The solvent molecule stabilized the monomeric structure of [MoO2LD] (D = DMF or DMSO) allowing single‐crystal X‐ray diffraction of the three new complexes. The dimeric complexes are utilized to catalyze the reaction of aldehydes/ketones with dimedone, leading to 1,8‐dioxo‐octahydro‐xanthene derivatives in N,N‐dimethylformamide. We found that their catalytic activity is enhanced by the electron‐withdrawing group of the Cl substituent on the ONO ligand. In addition, the position of the Cl substituent can also positively influence the catalysis performance: (ortho (L1) > para (L3) > meta (L2) ≈ meta (L4)). The high efficiency of the catalysts promises high yields and selectivity with a low catalyst loading and allows a wide substrate scope of aldehydes/ketones for the reaction. In addition, the method employs recrystallization for purifying products and can be easily scaled up to gram levels, indicating a strong potential for industrial utilization.

CASE-DFT Structure Elucidation of Proton-Deficient Chlorodepsidones from the Indonesian Lichen Teloschistes flavicans and Structure Revision of Flavicansone.

Biodiscovery efforts in Indonesia have aimed to explore the understudied chemical diversity of its rich lichen flora, seeking to find new products endowed with significant biological properties. The chemical screening of a Teloschistes flavicans extract led to selection of this species for further investigation. LC/MS and 1H NMR-based dereplication pinpointed six chlorodepsidones from the thallus of a sample of this lichen. This led to the streamlined isolation and the subsequent structure elucidation of the three new compounds norflavicansone 1, flavicansone 2, and isocaloploicin 3, along with the known chlorodepsidones 4-6, stictic acid 7, aurantiamide acetate 8, and parietin 9. The challenging structure elucidation of these proton-deficient metabolites benefited from a state-of-the-art workflow involving a synergistic combination of Computer-Assisted Structure Elucidation (CASE) and Density Functional Theory (DFT) calculations of the top-ranked candidates. This investigation also led to the revision of flavicansone's structure, previously described from this species. The three new molecules that are being reported here are remarkable in that they represent hybrid depsidones in which one of the aromatic rings is derived from orsellinic acid and the other is derived from β-orcinol, a rare structural feature for lichen depsidones.

Theoretical screening of N-[5'-methyl-3'-isoxasolyl]-N-[(E)-1-(-2-thiophene)] methylidene]amine and its isoxazole based derivatives as donor materials for bulk heterojunction organic solar cells: DFT and TD-DFT investigation.

In the present work, the influence of aromatic ring substitution on a series of small-donor organic molecules (A, B, C, D, and E) with isoxazole cores was investigated for photovoltaic applications in organic solar cells. Frontier molecular orbital analysis, chemical reactivity descriptors, dipole moment, and population analysis showed that all the organic materials have intramolecular charge transfer abilities capable of donating electrons to the acceptor material (PCBM). The required photovoltaic parameters such as Voc, FF, Jsc, LHE, and other associated optoelectronic parameters are reported. The results demonstrate that aromatic ring substitution influences charge transfer and power conversion efficiencies of solar cells. That is, an increase in the aromatic character of a material increases its charge transfer, and as a result, its photovoltaic properties are increased. Additionally, all the investigated derivatives are good charge transporters with suitable electron reorganization energies, which are beneficial for minimizing energy loss. Hence, these organic derivatives with isoxazole backbones are promising materials and may provide fresh insights into the design of new materials for organic solar cell applications. All calculations were performed using DFT and the ORCA 4.1.0 program package as the main tool for geometry optimization and frequency calculations. The Avogadro 1.2.1 visualization tool was used to prepare all input files executed by ORCA 4.1.0. The BP86, B3LYP, and wB97M series of functionals coupled with the def2/TZVP basis set were employed for geometry optimization. All energy-related calculations were carried out using the M06-2x functional. Multiwfn version 3.7 was used for aromaticity and population analysis. Excited state and UV-visible spectra were simulated using the TD-DFT method at the CAM-B3LYP-D3, wB97X-D3, and PBE0-D3 coupled with the ma-def2-TZVP basis set. Moreover, solvent effects were incorporated using the SMD scheme as incorporated in the ORCA software. Lastly, the RIJCOSX approximations were used to speed up calculations while maintaining accuracy.

Can Aromaticity be Evaluated Using Atomic Partitions based on the Hilbert-space?

Aromaticity is a fundamental concept in chemistry that explains the stability and reactivity of many compounds by identifying atoms within a molecule that form an aromatic ring. Reliable aromaticity indices focus on electron delocalization and depend on atomic partitions, which give rise to the concept of an atom-in-the-molecule(AIM). Real-space atomic partitions present two important drawbacks: a high computational cost and numerical errors, limiting aromaticity measures to medium-sized molecules with rings up to 12 atoms. This restriction hinders the study of large conjugated systems like porphyrins and nanorings. On the other hand, traditional Hilbert-space schemes are free of the latter limitations but can be unreliable for the large basis sets required in modern computational chemistry. This paper explores AIMs based on three robust Hilbert-space partitions --meta-Löwdin, Natural Atomic Orbitals (NAO), and Intrinsic Atomic Orbitals (IAO)--which combine the advantages of real-space partitions without their disadvantages. These partitions can effectively replace real-space AIMs for evaluating the aromatic character. For the first time, we report multicenter index (MCI) and \iring values for large rings and introduce ESIpy, an open-source Python code for aromaticity analysis in large conjugated rings.

Modular Synthesis of Conjugated Aromatic Boronate Esters by Radical Xanthate Addition

AbstractConjugated aromatic boronate esters serve as crucial intermediates in the synthesis of pharmaceuticals and polymer materials. Traditional methods for their synthesis typically involve organoboration of aromatic ring compounds, where pre-constructions of aromatic rings are required. Here, we present a general strategy for the synthesis of diverse conjugated aromatic boronate esters based on the radical addition of xanthates. Through this method, we synthesized various boronate ester xanthates that could be utilized as a platform to furnish conjugated aromatic building blocks, including thiophenes, pyrroles, tetralones, naphthols, and naphthylamines. This cost-effective strategy holds promise as a viable method for the industrial-scale production of (hetero)aromatic boronate esters.

Boosting potassium and sodium-ion storage performance by in-situ self-assembly of a Co-based π-d conjugated coordination polymer on graphene nanosheets

To obtain anode materials with good electrochemical performances in both potassium ion batteries (PIBs) and sodium-ion batteries (SIBs), a Co-based π-d conjugated coordination polymer (Co-HHTP) is in-situ assembled on graphene (G) nanosheets using a facile one-step solvothermal method. The resulting Co-HHTP/G composite shows improved electrochemical performances over pure Co-HHTP. After 300 cycles of using as an anode of PIBs/SIBs for the first time, the reversible specific capacity of the Co-HHTP/G composite is found to be 381/277 mAh g−1 at 100 mA g−1. After undergoing 500 cycles at 1000 mA g−1, the material's reversible specific capacities remain at 234/164 mAh g−1 for PIBs/SIBs. The improved performances of the Co-HHTP/G composite electrode are due to the incorporation of graphene. This incorporation not only reduces structural stacking and promotes active site utilization, but also increases electrical conductivity and structural stability. According to the ex-situ X-ray photoelectron spectrometer (XPS) spectra, the Co-HHTP/G's energy storage mechanism throughout the process of potassisation/depotassisation is found to be linked to the aromatic rings presented in the organic ligands.

Facile fabrication of magnetite nanoparticles with new hydrophobic amides and their application in oil spill remediation.

In this study, inexpensive magnetite nanoparticles (Fe3O4) were prepared and applied to oil spill remediation. To do so, two novel hydrophobic amides, HADN and HATN, were prepared and applied to Fe3O4 surface modification, producing HAN-Fe3O4 and HAT-Fe3O4, respectively. The efficiency of HAN-Fe3O4 and HAT-Fe3O4 for oil spill remediation (EOSR) was investigated using different HAN-Fe3O4 and HAT-Fe3O4 weights and at various contact times. The data indicated that the EOSR increased with increased HAN-Fe3O4 and HAT-Fe3O4 weights, as their EOSR reached 100% and 89%, respectively, using 100 mg. The results also revealed that the optimum time for HAN-Fe3O4 and HAT-Fe3O4 (50 mg) to achieve the highest EOSR is 8 min, as their EOSR reached 98% and 84%, respectively, at this time. In addition, HAN-Fe3O4 exhibited higher EOSR than HAT-Fe3O4, which could be linked to the presence of an aromatic ring in HADN that is used for surface modification of Fe3O4, making them more compatible with crude oil components.

Site‐Selective Radical Aromatic C−H Functionalization of Alloxazine and Flavin through Ground‐State Single Electron Transfer

AbstractFlavins and their alloxazine isomers are key chemical scaffolds for bioinspired electron transfer strategies. Their properties can be fine‐tuned by functional groups, which must be introduced at an early stage of the synthesis as their aromatic ring is inert towards post‐functionalization. We show that the introduction of a remote metal‐binding redox site on alloxazine and flavin activates their aromatic ring towards direct C−H functionalization. Mechanistic studies are consistent with a synthetic sequence involving ground‐state single electron transfer (SET) with an electrophilic source followed by radical‐radical coupling. This unprecedented reactivity opens new opportunities in molecular editing of flavins by direct aromatic post‐functionalization and the utility of the method is demonstrated with the site‐selective C6 functionalization of alloxazine and flavin with a CF3 group, Br or Cl, that can be further elaborated into OH and aryl for chemical diversification.

Ultrasound-Assisted, BF3·OEt2-Promoted, Multicomponent Synthesis of Chromene-Based Podophyllotoxin Analogues

AbstractA novel method was developed to synthesise chromene-lactone analogues of podophyllotoxin using an ultrasound-assisted multicomponent reaction (MCR). The MCR involved tetronic acid, phenols, and aromatic aldehydes and was promoted by BF3·OEt2, resulting in the production of ten derivatives with different substituents on the aromatic rings in yields ranging from 32% to 93%. These compounds are of interest due to their reported activity against tumour cells. Their ease of synthesis through the MCR may allow for more in-depth studies on anticancer activity, as well as investigations of other biological targets. The synthesised derivatives contain important pharmacophoric groups for potential applications in medicinal chemistry.