Chemistry and Materials Science

Abstract: The title compound 3-(diphenylamino)-4-ethoxycyclobut-3-ene-1,2-dione (6), was prepared by reaction of diphenylamine (2) with diethyl squarate (DES; 5) as part of our ongoing studies on monosquarate-amides. Following purification and recrystallisation, the product was isolated as a green crystalline solid. Its structure was established by spectroscopic methods including: FTIR, ¹H NMR, ¹³C NMR and HRMS and was unambiguously confirmed by single crystal X-ray diffraction. This work provides access to a previously unreported diphenylamino substituted squaric acid derivative.

Abstract: Chirality has emerged as a critical determinant in the design, efficacy, and environmental behavior of modern insecticides. While a significant proportion of agrochemicals are inherently chiral, most are still commercialized as racemic mixtures, despite well-documented differences in biological activity, toxicity, and degradation pathways between enantiomers. In this review, we provide a comprehensive and critical analysis of advances in the stereoselective synthesis and resolution of chiral insecticides, with particular emphasis on neonicotinoids, pyrethroids, and oxadiazines, including indoxacarb. A systematic survey of the literature (1985–2025), including peer-reviewed articles and patents, reveals that multiple strategies have been developed to access enantiomerically enriched compounds, including asymmetric organocatalysis, transition-metal catalysis, chiral-pool approaches, biocatalytic transformations, and chromatographic resolution techniques. Among these, recent developments in photoredox catalysis, recyclable metal complexes, and enzyme-mediated processes have significantly improved enantioselectivity and scalability, bridging the gap between academic methodologies and industrial applications. Despite these advances, challenges remain in achieving cost-effective, sustainable, and universally applicable asymmetric processes. Importantly, the relationship between stereochemistry and biological performance underscores the need for integrating synthetic chemistry with toxicological and environmental studies. Future directions point toward the incorporation of green chemistry principles, continuous-flow processes, and computational tools, including machine learning and molecular modeling, to accelerate the rational design of enantiopure agrochemicals. This review highlights both the progress achieved and the critical gaps that must be addressed to realize the potential of stereoselective insecticide development fully.

Abstract:

Fluoroalkyl-substituted organoboron compounds are valuable building blocks for organic synthesis and for the development of functional molecules in medicinal chemistry, agrochemicals, and materials science. Building on our previous work on difluoromethyl-substituted borates, we report the synthesis and structural characterization of trifluoromethylated borates, 4,4,5,5-tetramethyl-2-aryl-2-(trifluoromethyl)-1,3,2-dioxaborolan-2-uide salts ([pinB(Aryl)CF₃]^–). Treatment of pinB–Aryl boronates (pinB = 4,4,5,5-tetramethyl-1,3,2-dioxaborolane) with trimethyl(trifluoromethyl)silane (Ruppert–Prakash reagent) in the presence of potassium tert-butoxide and 18-crown-6 (18-cr-6) afforded the corresponding trifluoromethylated borates as isolable crystalline compounds. Compared with the related difluoromethylated borates, the CF₃ substituent increases the tendency of [pinB(Aryl)CF₃]^– to exhibit hygroscopic behavior, as supported by a hydrated crystal structure and the formation of a hygroscopic product. The isolable trifluoromethylborates can serve as reservoirs of electrophilic trifluoromethyl radicals upon oxidation.

Abstract: The formation of side products is often unavoidable in organic synthesis; however, analyzing these secondary species provides practical insights into reaction pathways, mechanisms, and competing processes. This understanding is essential for optimizing reaction conditions, increasing product yields, and improving overall safety and efficiency. Additionally, side products can sometimes reveal unexpected molecular structures with valuable properties. In this study, we present the characterization of a compound that formed as a side product in a modified Pictet-Spengler reaction. The molecular structure of 2,2′-(methylenebis(3,4-dimethoxy-6,1-phenylene))diacetic acid was elucidated using a combination of NMR, FTIR, UV–Vis, and HRMS spectroscopic techniques.

Abstract: The synthesis of hydroxamic acids from sterically hindered substrates, such as abietane-type resin acids, remains a significant challenge due to the extreme congestion of the tricyclic skeleton. This study reports an efficient one-pot protocol for the direct conversion of abietic and dehydroabietic acids into their corresponding hydroxamic derivatives, achieving 65% and 74% isolated yields, respectively. Systematic screening of activating agents identified diethyl chlorophosphate (DCP) as the superior reagent for the hydroxy-amidation. A critical finding of this work is that the optimization of the isolation process specifically minimizing the water amount during aqueous work-up was essential to recover these polar products and prevent significant yield loss. The reaction proceeds through diethyl phosphate mixed anhydride intermediate, which was successfully isolated, providing direct experimental evidence of the activation pathway. The reaction mechanism was further elucidated using density functional theory (DFT) calculations at the M062X/6-31G** level, identifying a concerted transition state for the simultaneous addition of hydroxylamine and expulsion of the phosphate group. Furthermore, the study rationalizes the observed chemoselectivity: although the ester is the more stable thermodynamic product, the formation of the N-hydroxy amide is kinetically favored through a substantially lower activation barrier. This combined experimental and theoretical approach establishes a robust and scalable methodology for the functionaliza-tion of abundant similar natural terpenoids.

Abstract: Herein, we investigated the binding properties of four natural compounds extracted from Mediterranean plants—distachyasin, CxB, CxC, and magnoflorine—toward the G-quadruplex (GQ) formed by the KRAS22-RT sequence, a modified KRAS-derived oligonucleotide commonly used as a model of the KRAS oncogene, which adopts a single, well-defined parallel intramolecular GQ structure. Circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopies revealed that distachyasin, CxC, and mag-noflorine induced only a slight stabilization of the GQ. In contrast, CxB significantly increased the GQ melting temperature, indicating a markedly stronger stabilizing effect. Notably, the reduced stabilizing effect of its diastereomer CxC highlights how the spatial arrangement of substituents around the core structure can strongly influence the binding properties of ligands towards GQs. Finally, the compounds were evaluated in three breast cancer cell lines and showed antiproliferative effects, particularly in the drug-resistant model.

Abstract: This study focuses on the investigation of the influence of chitosan (CS) and the nature of the support on performance of the hybrid catalysts (Pd-CS/support) in low-temperature hydrogenation of allyl alcohol (2-propen-1-ol). CS-containing palladium catalysts were prepared via sequential deposition of the polysaccharide and palladium onto metal oxide supports (commercial MgO, SiO₂, TiO₂ and synthesized alumina). The synthesized CS-modified palladium catalysts were compared with their polymer-free counterparts. The successful formation of catalysts was confirmed using TGA, XPS, HAADF-STEM, and viscosimetric analysis. The results of low-temperature hydrogenation of 2-propen-1-ol indicate that catalytic activity and selectivity are influenced by both the support nature and chitosan modification. Overall, the introduction of chitosan had a positive effect on both the structural (Pd nanoparticle dispersion and convergence of the electronic properties of the catalysts) and catalytic (activity and selectivity) properties. The obtained results may contribute to controlling reaction pathways in the desired direction in the selective valorization of platform molecules.

Abstract: We report the synthesis and single-crystal X ray structures of three novel (Z)-5 arylidene-3-phenylrhodanine derivatives, differing in the substituents on the ben-zylidene fragment (two methoxy groups (compound I), a dioxine ring (compound II), or a dioxole ring (compound III)). Despite the overall similarity of the molecules, their su-pramolecular architectures were found out to be strikingly different. In both compounds I and II, short S···S chalcogen bonds together with forced C–H···O hydrogen bonds generate dimeric motifs, whereas III lacks S···S interactions and instead features an n→π* contact from the rhodanine carbonyl oxygen to the benzodioxole ring, as well as C-H···S bifurcate hydrogen bond. The results of intermolecular interactions in those structures are checked via Hirshfield surface analysis. The fine modulation of the arylidene substituent can switch the primary intermolecular synthon from chalcogen bonding to n→π* interactions, offering new possibilities for crystal engineering of rhodanine-based materials.

Abstract: Following a description of the woad plant and its distribution in the world, the locations in Europe where commercial woad growing took place during the middle ages until the end of the nineteenth century are described. The four unique steps which were used to convert the leaf of the plant into a dye bath for textile dyeing with indigo are described. The 21st century revival of interest in the process is summarised.

Abstract: Herein, starting from (R)-(+)-α-methylbenzylamine, we report an efficient synthesis and full characterization of a new (R)-3-(1-hydroxyethylidene)-1-(1-phenylethyl)piperidine-2,4-dione, a new tetramic acid analogue. The key steps involved a non-classical Corey-Chaykovsky intramolecular cy-clization reaction to access the corresponding zwitterion, followed by a sequential desul-furization/reduction and condensation procedure. The key intermediate was obtained in 5 steps, and the desired product 7 with an overall 58% yield.

Abstract: Benzofuran and indole are structurally similar compounds, but they show different reactivity patterns. Benzofuran can undergo electrophilic substitution at either the  or  position depending on the electrophile, whereas indole reacts preferentially at the  position. Density functional theory (DFT) calculations of the Wheland intermediates in the Vilsmeier-Haack formylation and nitration reactions are consistent with the experimental results for formylation, but cannot explain the regioselectivity observed in the nitration of of benzofuran. A frontier orbital approach successfully explains the regiochemistry of Vilsmeier-Haack reaction: electron density favors substitution at the  position in benzofuran and at the  position in indole. In contrast, nitration at the  position in both benzofuran and indole can be explained by assuming charge control as the dominant factor governing the reaction.

Abstract: 4-Dimethylamino-2’-hydroxy chalcone (DHC) 1 is an important natural compound that is nearly non-fluorescent in solution but highly fluorescent in its crystalline state. At room temperature, the weak fluorescence from DHC solution is exclusively from its keto tautomer, without notable contribution from its enol tautomer. By using low temperature fluorescence, the study found that the enol emission could be detected upon cooling with liquid N₂ in a protic solvent (e.g. EtOH). This led to observation of the fluorescence vibronic structure of enol tautomer, in addition to its enol emission λ_em ≈ 473 nm that is well separated from its keto tautomer emission (λ_em ≈ 600 nm). By freezing DHC in a solvent matrix, the study revealed the fluorescent characteristics of a single molecule in a rigid environment. Further comparison of DHC in a solvent matrix and crystalline state disclosed that the emission of crystalline DHC was primarily from the keto tautomer, along with some minor contribution from the enol tautomer, despite the tight packing environment in the crystalline state.

Abstract: Syzygium polyanthum (Indonesian bay leaf) is widely consumed as a culinary spice and is traditionally used for health related purposes, yet chemical standardization of region specific materials remains limited, particularly for nonpolar fractions that contain volatile and semivolatile constituents. This study aimed to generate a baseline chemical fingerprint of the n hexane fraction of S. polyanthum leaves collected in Paniki Bawah, Mapanget District, Manado, Indonesia. Dried leaf powder was macerated with 96% ethanol for six days with daily solvent renewal, the filtrate was concentrated under reduced pressure, redissolved in warm distilled water, and fractionated by liquid liquid partitioning to obtain the n hexane fraction. The fraction was analyzed by GC MS, and peak identities were assigned by spectral library matching. Twenty constituents were tentatively identified, dominated by fatty acids and fatty acid methyl esters, with additional aliphatic ketones and terpene related compounds. Major annotations included decanoic acid, dodecanoic acid, tetradecanoic acid, 2 undecanone, 2 tridecanone, nerolidol, and 6,10,14 trimethyl 2 pentadecanone. The clustering of multiple library hits at identical retention times suggests potential coelution; therefore, the reported profile is best interpreted as a qualitative screening fingerprint rather than definitive quantification. Overall, these findings provide a region specific reference for future marker selection, batch to batch comparison, and integration with targeted bioactivity assays to support quality control development for S. polyanthum based products.

Abstract: The compound Z-6-heneicosen-11-one, a possible pheromone component of the hickory tussock moth, Lophocampa caryae, and a known pheromone component of the Douglas fir tussock moth, Orgyia pseudotsugata, was synthesized by a new four step procedure with a 39% overall yield and a six-step procedure incorporating a protecting group with a 28% overall yield. This new synthesis is comparable to other similar syntheses for this molecule in the literature.

Abstract: LiAlH₄ reduction of tert-butyl (S)-butyl(1-((2-cycloheptylethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (1) gave imidazolidine 2, while treatment with LDA furnished the β-elimination product, cinnamamide 3. Both products were fully characterized. Reductive cyclization of N-alkylated-N-Boc-protected amino acid amides with LiAlH₄ may be a viable synthetic method for trisubstituted chiral imidazolidines.

Abstract: N-Alkyl urazoles are important heterocyclic compounds that serve as important precursors to potent N-alkyl 1,2,4-triazoline-3,5-dione electrophiles. Traditional methods for urazole synthesis have relied upon the use of toxic isocyanates. We have modified and optimized an overlooked and poorly-described literature method for the synthesis of urazoles that now avoids the use of isocyanates, limits the use of solvents, and provides urazoles without the need for purification steps. A variety of urazoles are afforded in good to high yields.

Abstract:

This study reports the convenient synthesis of a new series of sustainable heterocyclic compounds called 3-N-Substituted 5-aryl(hetaryl)-thieno[2,3-d]pyrimidin-4(3H)-ones, encompassing two biologically important pharmacophores namely thiophen and pyrimidine. A stepwise synthesis of 5-aryl(hetaryl)thieno[2,3-d]pyrimidine-4(3H)-ones with variable substituents at the N 3 position was proposed, which involves the synthesis of aromatic and heteroaromatic substituted 2-aminothiophenes, their condensation with N,N′-dimethylformamide dimethylacetal. Obtained 2-dimethylaminomethyleneamino-thiophenes condense with primary amines. This sequence of reactions leads to the production of new polyheteroconjugated systems with advantages like simple work up, easy separation of the products and chromatography-free purification. Structural elucidation was done by spectroscopic method and elemental analysis and have confirmed their molecular structure. The synthesized compounds were tested on their antibacteriial activity against Gram positive and Gram negative bacteria. Compound 6k showed notable antibacterial activity compared to the standard drug (Gentamicin) against S. aureus bacteria. Compounds 6e and 6k were evaluated for their antimicrobial potential via molecular docking against S. aureus Aminoglycoside Phosphotransferase and P. aeruginosa TrmD. Compound 6k exhibited superior binding affinity and an enhanced pharmacokinetic profile, positioning it as a promising lead for further optimization and development as an antimicrobial agent. However, as this study represents an initial screening, further in silico investigations are required for predicting antibacterial activity of target derivatives with calculated substituents. Overall, this work highlights the efficiency of a convenient approach for synthesizing 3-N-Substituted 5-aryl(hetaryl)-thieno[2,3-d]pyrimidin-4(3H)-ones and underscores their potential as promising scaffolds for the development of potent antibacterial agents.

Abstract:

Aiming at p53-reactivating compounds, a convergent scheme for the preparation of conjugates with the dispiro-indolinone-pyrrolidine-thioimidazolone and glutarimide moieties connected via a triazole-containing linker were proposed. Target conjugates were synthesized by azide-alkyne cycloaddition reactions between propargylthio-substituted dispiro-indolinone-pyrrolidine-imidazolones and an azido-glutarimide derivative. The starting compounds were available isothiocyanates, glycine, substituted benzaldehydes, chloroacetamide, and ethyl acrylate. The key azide-alkyne cycloaddition step was carried out using TBTA as a catalyst, achieving >70% product yields. The resulting bifunctional compounds contained a fragment of dispiroindolinone (p53-MDM2 interaction inhibitor) and glutarimide, an ubiquitin ligase ligand. The dispiroindolinone-glutarimide conjugate with 5-bromoisatine and 4-bromophenyl moieties showed a potential for p53 re-activation as determined by preferential cytotoxicity against HCT116 colon carcinoma cells (wild type53) compared to the isogenic HCT116p53^-/- subline.

Abstract: Over the last 20 years Deep-Eutectic-Solvents (DES) have been making a significant impact in the field of chemistry, with applications in nanotechnology, biomass transformation, electrochemistry pharmaceuticals and a host of other applications that includes catalysis. Considering the importance of chiral organocatalysis for the selective synthesis of drugs, pharmaceuticals and fragrances etc. DESs were quickly harnessed as the media for carrying out organocatalytic transformations. In this review, we discuss some of the most important examples from the literature that have made an impact in the field over the last 5 years. A more recent development has been the incorporation of DESs in structured and self-organized gel-like assemblies that are known as EutectoGels. These soft structures offer a more defined and compact environment that can influence stereoselectivity by pre-organizing the reactants in three-dimensional space, and potential control the types of transition states that can be formed.

Abstract: cycloaddition of isatin ketonitrone 1,3-dipoles, generated from the condensation of various substituted isatins and arylhydroxylamines, with coumarins. The pentacyclic products bearing four consecutive stereocenters, including two quaternary carbon stereocenters fused in one ring structure, were smoothly acquired in moderate to high yields (22-98%) with high regio- (α and exo type) and diastereoselectivities (>20:1 dr). The synthesized compounds (>45 examples) were well characterized through different spectroscopic techniques, such as single crystal XRD, FTIR, NMR, and mass spectral analysis.