Search Results (130)

Flavone–thiazole–aryl hybrid molecules based on 6-aminoflavone and 5-arylidene-4-aminothiazol-2(5H)-ones were synthesized and subjected to physicochemical and biological studies. Microwave-assisted synthesis was performed in two steps. First, an aminolysis reaction of isorhodanine with 6-aminoflavone was carried out to achieve the corresponding hybrid flavone-thiazole 3, which was later subjected to a Knoevenagel condensation with selected aromatic aldehydes, yielding 5-arylidene derivatives 5a–5i. The resulting hybrids were purified and characterized by UV–Vis, NMR, and HR-MS (ESI). In the UV–Vis spectra of all compounds, two characteristic bands were noted. The UV–Vis spectra in DMF of the studied flavone–thiazole–aryl hybrids consist of two major bands with maxima appearing at 280–288 nm, corresponding to band II and 383–399 nm, corresponding to band I, which clearly distinguish them from the large group of modified flavonoids. Among the compounds tested on human bladder cancer 5637 cells, (5Z)-5-[(4-hydroxyphenyl)methylene]-4-[(4-oxo-2-phenyl-chromen-6-yl)amino]thiazol-2-one (5b) exhibited interesting micromolar activity (IC₅₀ 2.37 µM). In addition, four of the tested compounds (3, 5f, 5d, and 5b) presented noteworthy antiplasmodial activity against P. falciparum in the low micromolar range (IC₅₀ 1.90–4.90 µM). The obtained group of flavone–thiazole–aryl hybrid molecules constitutes valuable starting points for further structural optimisation, which could usher in future novel active pharmaceutical ingredients and pave the way for novel therapeutic strategies. Full article

Spirocyclic compounds are experiencing a research surge due to their unique 3D structure, offering enhanced pharmacological, industrial, and material applications. They are increasingly used in medicinal chemistry to improve drug-like properties, such as solubility and target binding, and are also being utilized for advanced material applications, including electronics and photonics. In this communication, 3-(4-hydroxyphenyl)-1′,3′,6-trimethyl-2′H,3H,4H-spiro[furo[3,2-c]pyran-2,5′-pyrimidine]-2′,4,4′,6′(1′H,3′H)-tetraone was prepared via a two-stage transformation including a tandem Knoevenagel–Michael reaction and NBS-induced cyclization. At the first stage, a previously unknown ionic scaffold, morpholin-4-ium 5-((4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)(4-hydroxyphenyl)methyl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate was also isolated. Structures of the newly synthesized compounds were established by ¹H and ¹³C NMR, IR spectroscopy, high-resolution mass spectrometry, and elemental analysis. Full article

The development of sustainable catalysts is the main objective in green chemistry approaches. In this study, a catalytically active polymer based on a tertiary amine was synthesized, functionalized with a photo-crosslinker, and structured into nanofibers via electrospinning technique with polycaprolactone (PCL) as a stabilizing additive. Subsequent photo-crosslinking yielded hierarchically porous polymers with high swelling properties and increased surface areas, thereby improving the accessibility of the immobilized catalytically active sites. The nanofiber mats were incorporated into a microfluidic reactor (MFR) setup and utilized as heterogeneous catalysts for the Knoevenagel reaction of malononitrile with different aldehydes. It was observed that the system demonstrated a substantial improvement in NMR yields (40–60%) and turnover frequencies (50–80 h⁻¹) in comparison to catalytical systems that had been previously published. Reusability studies showed reproducibility of NMR yields over up to three cycles. The obtained results demonstrate the potential of electrospun, photo-crosslinked nanofibers as efficient heterogeneous catalysts in microfluidic synthesis, thus contributing to more sustainable production of valuable malononitrile derivatives. Full article

The present study focuses on the kinetics of the Knoevenagel condensation reaction between 7-methoxy-1-tetralone (1) and glyoxylic acid (2), catalyzed by potassium tert-butoxide in tert-butanol as a solvent, using a batch-type system under nitrogen atmosphere. The objective of this study was to synthesize the product (E)-2-(7-methoxy-1-oxo-3,4-dihydronaphthalen-2(1H)-ylidene) acetic acid (3). The reaction was conducted under controlled temperature conditions (65 °C, 75 °C and 85 °C), considering five specified time intervals to monitor its progress by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC). The kinetic data obtained was analyzed through three different mathematical methods: integral, differential, and nonlinear regression method, in order to determine the most suitable kinetic model. Applying the power law, the findings indicated that the pseudo-second order model, which was estimated via nonlinear regression, showed the best fit with the experimental data, characterized by minimal discrepancy between the calculated and observed values. The kinetic constants (k) obtained at temperatures of 65 °C, 75 °C and 85 °C were 0.89, 1.77 and 3.42 mL mmol⁻¹ min⁻¹, respectively. The pre-exponential factor (A) was calculated to be 2.194 × 10¹⁰ mL mmol⁻¹ min⁻¹, and the activation energy (Ea) was determined to be 67.22 kJ mol⁻¹. The product yield at these temperatures was 17.01%, 81.40% and 72.59%, respectively. The final product was characterized by GC-MS, FTIR, and UV-Vis. In conclusion, the kinetic study of the reaction was able to determine the optimal Knoevenagel condensation reaction conditions between (3) and (2) catalyzed by potassium tert-butoxide, and to facilitate understanding of the mechanism involved. Full article

In this work we report the stereoselective synthesis of 2H-flavenes via an Aminocatalytic privileged Diversity-Oriented Synthesis (ApDOS) strategy. An oxa-Michael cyclization between salicylaldehydes and an iminium intermediate from cinnamaldehyde and the Hayashi–Jørgensen catalyst produced flavenes at up to 81% yield and 90% ee under optimal conditions (PhCOOH, toluene, 40 °C, 18 h). In general, the reaction proceeds with good yields. Further, reactions with a stabilized carbanion produced Knoevenagel-type adducts, explained by electronic delocalization, HSAB considerations, and kinetic/thermodynamic factors. The resulting polycyclic products show potential as dienophiles in Diels–Alder reactions, offering a valuable framework for future bioactive compound development. Full article

This work reports progress in the semi-synthetic modification of cassane-type diterpenes isolated from Coulteria platyloba, a plant of ethnopharmacological relevance. The approach involves a sequence of transformations, including oxidative aromatization, ring opening, and Knoevenagel condensation, to generate key intermediates for further diversification. Preliminary studies demonstrated the feasibility of organocatalytic reactions under trienamine activation, including a successful Diels–Alder cycloaddition. The initial steps were achieved with good yields and high purity, underscoring the potential of this strategy to access novel molecular scaffolds through efficient and sustainable methods aligned with the principles of Diversity-Oriented Synthesis (DOS). Full article

It is known that thioamides containing hydrogen atoms in the α-position of the thiocarbamoyl group exhibit a CH-acidic character. The purpose of the work: synthesis of new nicotinamide derivatives based on monothiomalondianilide and investigation of their properties. According to the known method, we synthesized the initial monothiomalondianilide starting from phenyl isothiocyanate and acetylacetone. The reaction of monothiomalondianilide with arylidenemalonitriles, available by the Knoevenagel reaction, or with aromatic aldehydes and malonitrile in the presence of a base leads to the formation of cyclic Michael adducts—nicotinamide derivatives. New compounds have been studied spectrally (FTIR, NMR ¹H, ¹³C). Full article

Dicyanovinyl (DCV) oligothiophenes are interesting materials due to their unique optical and electronic properties. They are relatively easy to prepare using Knoevenagel condensation reactions from the corresponding aldehydes. Understanding their optical and electrochemical characteristics is important for both building structure/property relationships and for optimizing their performance in various applications. We report on the electrochemical and photophysical properties of three oligothiophenes end-capped with dicyanovinyl -CH=C(CN)₂ or DCV groups. The compounds included in this study are DCV-T-DCV (1), DCV-2T-DCV (2), and DCV-3T-DCV (3), where T represents one thiophene unit. Introduction of the DCV groups into oligothiophenes results in unique evolution of their electrochemical and optical behavior. First, new reversible two-electron reduction processes in the series DCV-nT-DCV start to appear with a gradual increase in the reduction potential with an increasing number of thiophene units. This was consistent with the electronic spectroscopic results. These results demonstrate that the DCV groups can be used in molecular design and fine-tuning of the optical and redox properties of oligothiophene and presumably this strategy can be extended to other conjugated organic molecules. We also report on the photophysical and vibrational spectroscopic properties of these compounds. The C=C stretching bands in Raman and IR spectra reveal more quinoidal nature in shorter molecules and more dominant benzoidal character in longer molecules. The DCV-induced modulation of electrochemical, optical, and vibrational properties highlights their potential in diverse optoelectronic applications. Full article

Using an environmentally friendly approach, we successfully synthesized an asymmetric monomethine cyanine dye, 7-chloro-1-ethyl-4-((3-ethylbenzo[d]thiazol-2(3H)-ylidene)methyl) quinolin-1-ium iodide, named CHLoris (CHL), via a modified Knoevenagel-type condensation. The reaction was carried out mechanochemically in an ethanol–water medium using 1-ethyl-2-methylbenzothiazolium iodide and 4,7-dichloro-1-ethylquinolin-1-ium iodide in the presence of sodium carbonate as a base and catalytic amounts of Hünig’s base. The UV/VIS absorption spectra of CHL in both the buffer solution and ethanol revealed the formation of aggregates in aqueous media. Density Functional Theory (DFT) and Time-Dependent DFT (TDDFT) calculations were employed to support the experimental findings further and provide insights into the self-association behavior of CHL in an aqueous solution. The photophysical properties of the dye were examined in the presence of DNA and RNA, and its performance was compared to that of the commercial dye Thiazole Orange (TO) under identical conditions. The results show that CHL is more sensitive towards RNA. Full article

This study introduces an efficient and sustainable catalytic system utilizing cobalt ferrite nanoparticles (CoFe₂O₄-NPs) for the synthesis of valuable 6-amino-2-oxo-4-phenyl (or 4-chlorophenyl)-1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives. Recognizing the limitations of traditional methods for the Biginelli reaction, we thoroughly characterized CoFe₂O₄-NPs, alongside individual iron oxide nanoparticles (Fe₂O₃-NPs) and cobalt oxide nanoparticles (CoO-NPs), using FTIR, XRD, TEM, SEM, XPS, TGA, and BET analysis. These characterizations revealed the unique structural, morphological, and physicochemical properties of CoFe₂O₄-NPs, including an optimized porous structure and significant bimetallic synergy between Fe and Co ions. Catalytic studies demonstrated that CoFe₂O₄-NPs significantly outperformed individual Fe₂O₃-NPs and CoO-NPs under mild conditions. While the latter only catalyzed the Knoevenagel condensation, CoFe₂O₄-NPs uniquely facilitated the complete Biginelli reaction. This superior performance is attributed to the synergistic electronic environment within CoFe₂O₄-NPs, which enhances reactant activation, intermediate stabilization, and proton transfer during the multi-step reaction. This work highlights the potential of CoFe₂O₄-NPs as highly efficient and selective nanocatalysts for synthesizing biologically relevant 1,2,3,4-tetrahydropyrimidines, offering a greener synthetic route in organic chemistry. Full article

A new π-conjugated acceptor–donor–acceptor small molecule, designed for applications in organic solar cells, containing a terthiophene core and indandione- and benzonitrile-based electron-withdrawing units, was synthesized via a multi-step process involving Suzuki–Miyaura cross-coupling and Knoevenagel condensation reactions. The structure was confirmed by NMR spectroscopy, HRMS, and its optoelectronic properties were evaluated by UV–vis spectroscopy and cyclic voltammetry. Full article

In this study, novel fluorescent 5-aryl-2-styryl-3H-indole derivatives were efficiently synthesized from 4-bromophenylhydrazine hydrochloride using the microwave-accelerated one-pot technique, which includes Fischer synthesis, Suzuki cross-coupling, and Knoevenagel condensation. The structural assignments of the synthesized compounds were based on ¹H, ¹³C, ¹⁵N, and ¹⁹F NMR; IR spectroscopy; and HRMS spectral data. The optical properties of the newly obtained styryl-indole dyes were studied using UV-vis and fluorescence spectroscopy, which clearly demonstrated that the derivatives substituted with electron-donating or -withdrawing groups exhibited varying emission shifts and quantum yields ranging from negligible to high. Full article

In the present work, we report the synthesis and characterization of 2-(4-(diphenylamino)benzylidene) malononitrile (DPAM) via a piperidine-catalyzed Knoevenagel condensation reaction. Two distinct crystal forms (A-1 and A-2) of this product were obtained by controlling the crystallization conditions, exhibiting orthorhombic and monoclinic crystal systems, respectively. Single-crystal X-ray diffraction revealed that both forms exhibited highly twisted benzene rings, which suppressed exciplex or excimer formation, enhancing luminescence. Crystal A-1, with a higher density, showed stronger hydrogen bonding and more rigid molecular packing, while A-2, with a lower density, exhibited weaker π–π interactions. Both crystals demonstrated high thermal stability. Notably, the A-2 crystal displayed a mechanochromic behavior: grinding or applying pressure induced a structural transformation into A-1, accompanied by a fluorescence shift from red to yellow. This transformation was attributed to increased steric hindrance and changes in molecular packing. This study highlights the relationship between crystal structure and optoelectronic properties, offering insights into the design of organic crystalline materials for applications in pressure sensing, anti-counterfeiting, and information encryption. Full article

The use of organo-catalysis in continuous-flow reactor systems is gaining attention in medicinal chemistry due to its cost-effectiveness and reduced chemical waste. In this study, bioactive curcumin (CUM) derivatives were synthesized in a continuously operated microfluidic reactor (MFR), using piperidine-based polymeric networks as catalysts. Piperidine methacrylate and piperidine acrylate were synthesized and subsequently copolymerized with complementary monomers (MMA or DMAA) and crosslinkers (EGDMA or MBAM) via photopolymerization, yielding different polymeric networks. Initially, batch reactions were optimized for the organo-catalytic Knoevenagel condensation between CUM and 4-nitrobenzaldehyde, under various conditions, in the presence of polymer networks. Conversion was assessed using offline ¹H NMR spectroscopy, revealing an increase in conversion with enhanced swelling properties of the polymer networks, which facilitated greater accessibility of catalytic sites. In continuous-flow MFR experiments, optimized polymer gel dots exhibited superior catalytic performance, achieving a conversion of up to 72%, compared to other compositions. This improvement was attributed to the enhanced swelling in the reaction mixture (DMSO/methanol, 7:3 v/v) at 40 °C over 72 h. Furthermore, the MFR system enabled the efficient synthesis of a series of CUM derivatives, demonstrating significantly higher conversion rates than traditional batch reactions. Notably, while batch reactions required 90% catalyst loading in the gel, the MFR system achieved a comparable or superior performance with only 50% catalyst, resulting in a higher turnover number. These findings underscore the advantages of continuous-flow organo-catalysis in enhancing catalytic efficiency and sustainability in organic synthesis. Full article