Excellent Yields Research Articles

Flexible green synthesis of 2-benzyl-3‑hydroxy-1H-pyrazolo([1,2-b]phthalazine and [1,2-a]pyridazine)‑dione derivatives using CuI@KSF nanocatalyst under solvent-free conditions

In the frame of research that examines the use of task CuI@KSF nanoparticles as an efficient catalyst, new 1H-pyrazolo[1,2-b]phthalazine-5,10‑dione (HPPhD) and 1H-pyrazolo[1,2-a]pyridazine-5,8‑dione (HPPyD) derivatives were prepared. Using the four-multicomponent condensation reaction (4MCRs) of phthalic anhydride, hydrazine monohydrate, aromatic aldehydes, and ethyl 3-oxo-3-phenylpropanoate under solvent free conditions at 80 °C. This method has several advantages, including, operational, simplicity, mild conditions, and maximum product yield. To monitor the progress of the reactions, new organic salty catalysts were used. New catalysts are cheap, benign, recyclable, and environmentally friendly. In addition, they are easy to prepare and use. They also showed good catalytic activity, which in conclusion led to the synthesis of new phthalazine derivatives with good to excellent yields. The new catalysts were characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), thermal gravimetric analysis (TGA), and scanning electron microscopy (SEM). To check the possible effect of these compounds in anticancer therapy, two types of proteins were selected and examined through docking calculations. In the case of 1DHT as an oxidoreductase enzyme compound 7e with the score of amount -8.99 represent the highest tendency toward interaction with the desired enzyme, while in the case of 6LQA by the dominance hydrophobic character, compound 7c seems likely to be more efficient.

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides.

An eco-friendly selective hydrolysis of chain α-oxo ketene N,S-acetals in water for the switchable synthesis of β-keto thioesters and β-keto amides is reported. In refluxing water, the hydrolysis reactions of α-oxo ketene N,S-acetals in the presence of 1.0 equiv of dodecylbenzenesulfonic acid effectively afforded β-keto thioesters in excellent yield, while β-keto amides were successfully obtained in excellent yield when the hydrolysis reactions were carried out in the presence of 3.0 equiv of NaOH. The green approach to β-keto thioesters and β-keto amides avoids the use of harmful organic solvents, thiols and thiolacetates as well as amines, which could result in serious environmental and safety issues.

Modular Synthesis of Azines Bearing a Guanidine Core from N-Heterocyclic Carbene (NHC)-Derived Selenoureas and Diazo Reagents.

N-Heterocyclic carbene (NHC)-derived selenoureas comprise a fundamentally important class of NHC derivatives, with key applications in coordination chemistry and the determination of NHC electronic properties. Considering the broad reactivity of chalcogen-containing compounds, it is surprising to note that the use of NHC-derived selenoureas as organic synthons remains essentially unexplored. The present contribution introduces a novel, straightforward transformation leading to azines bearing a guanidine moiety, through the reaction of a wide range of NHC-derived selenoureas with commercially available diazo compounds, in the presence of triphenylphosphine. This transformation offers a new approach to such products, having biological, materials chemistry, and organic synthesis applications. The guanidine-bearing azines are obtained in excellent yields, with all manipulations taking place in air. A reaction mechanism is proposed, based on both experimental mechanistic findings and density functional theory (DFT) calculations. A one-pot, multicomponent transesterification reaction between selenoureas, α-diazoesters, alcohols, and triphenylphosphine was also developed, providing highly functionalized azines.

Harnessing Solar Power for Oxidation of Organic Compounds by Re(I)Dipyrrinato Complexes.

Metal dipyrrinato complexes of 4d and 5d metals have distinctive features such as high absorption coefficients in the visible section and room temperature phosphorescence in the red region. This work demonstrates the light-assisted oxidation of organic compounds employing rhenium(I)dipyrrinato complexes as catalysts. The heavy atom effect in rhenium(I)dipyrrinato complexes leads to the formation of long-lived triplet excited states, and these complexes can generate singlet oxygen in excellent yields (up to 84 %). A method was developed for photocatalytic aerobic oxidation of sulfides and amines using only 0.05 mol % and 0.025 mol % of the rhenium(I)dipyrrinato complexes, respectively. The method is efficient, and within 2 h, a variety of substrates were oxidized to produce sulfoxides and imines in high yields (up to 97 %). Rhenium(I)dipyrrinato complexes work very well both in visible light and sunlight, making them promising candidates for photocatalytic applications.

Ru(II)-Catalyzed Decarboxylative (4 + 2)-Annulation of Benzoic Acids and Benzamides with Propargyl Cyclic Carbonates.

Propargyl cyclic carbonates have emerged as versatile precursors in synthetic chemistry. However, their reactivity has so far been limited to transition metal-catalyzed substitution and cyclization reactions. Herein, we illustrate the successful employment of propargyl cyclic carbonates as coupling partners in Ru(II)-catalyzed C-H annulation of benzoic acids and benzamides. This approach allowed us to access a broad range of biologically relevant isocoumarin and isoquinolinone derivatives in good to excellent yields, utilizing bench-stable and easily accessible precursors. Preliminary mechanistic studies indicated that the C-H metalation step is both reversible and rate-determining in the reaction pathway. Furthermore, the utility of the developed methodology has been illustrated by scale-up and postfunctionalization experiments.

Pyridine-Catalyzed Chemoselective Four-Component Cascade Reaction of Aromatic Aldehydes, Malononitrile/Cyanoacetates, MBH Carbonates, and Alcohols.

An efficient pyridine-catalyzed chemoselective four-component cascade reaction of aromatic aldehydes, malononitrile/cyanoacetates, Morita-Baylis-Hillman (MBH) carbonates, and alcohols has been established. This one-pot reaction progressed in an unusual reaction with solvent participation via a Knoevenagel condensation/oxa-Michael addition/SN2' substitution sequence. This method allowed for facile access to an array of functionalized chain alkylbenzenes and dihydroquinolinones bearing one all-carbon quaternary center in moderate to excellent yields. It is worth noting that the configuration of the all-carbon quaternary center could be modulated by changing only the electron-withdrawing groups via a tandem reduction/cyclization reaction.

Selectfluor-triggered C–H halogenations of enaminones with copper(I) halide (CuX) for the synthesis of 3-halochromones

Abstract A practical and efficient synthetic route to construct a variety of 3-halochromones has been realized using Selectfluor reagent as a fluorine source, or Selectfluor-copper(I) halide combination as halogen source under mild conditions. This reaction proceeds via a sequence of electrophilic cation addition, and cyclization leading to a broad range of 3-halochromones in good to excellent yields in a short period of time. Additionally, the utilization of commercially available and cost-effective Selectfluor and copper(I) halide renders this system highly practical.

Efficient cyanosilylation of carbonyls using a well-defined dimeric sodium complex

We present the synthesis and structural characterization of a novel dimeric sodium complex with the chemical composition [{Ph2Si(H)PhN}Na(THF)2]2 (Na-1) supported by N,1,1-triphenylsilanamine fragment. The single-crystal X-ray diffraction analysis of complex Na-1 in the solid state reveals the coordination of sodium ion with N and O atoms of the triphenylsilanamine unit, forming a four-membered ring. The sodium complex also demonstrates excellent activity as a pre-catalyst towards the cyanosilylation of a wide array of ketones with trimethylsilyl cyanide (TMSCN) to afford trimethylsilyloxypropanenitriles in excellent yield (up to 99 %) in a shorter time under mild and solvent-free reaction conditions and exhibits a greater tolerance to a variety of ketones bearing electron-withdrawing and electron-donating functional groups. The plausible mechanism of cyanosilylation of ketones catalyzed by the complex Na-1 is also proposed.

Cool white light emitting Dy3+ activated KNaCa2(PO4)2 phosphor for outdoor lighting and optical thermometric applications

Dy3+ incorporated KNaCa2(PO4)2 phosphor (KNCP) with doping concentrations ranging from 0.005 to 0.7 mol were synthesised via high-temperature solid state reaction route. The morphological characteristics were examined using FESEM images and found agglomerated structure in micrometers with an average particle size of 4.037 µm. Photoluminescence emission spectra under 350 nm excitation reveal nearly equal intense blue and yellow emission bands owing to 4F9/2→6H15/2 and 4F9/2→6H13/2 Dy3+ transitions, respectively. The concentration-dependent emission properties were examined and the optimum concentration was found to be 0.03 mol. The synthesized phosphor exhibits a quantum yield of 69.06 % at the optimal Dy³⁺ doping concentration. The time-correlated emission characteristics were analysed from the TRES plot. Furthermore, the emission bands at 479 nm (4F9/2→6H15/2) and 572 nm (4F9/2→6H13/2) under 350 nm excitation follow bi-exponential decay having an average lifetime in the range of 0.90–0.37 ms. The prepared phosphors exhibit an intense cool white light regardless of doping concentration and delay time. Optical thermometric properties of KNCP Dy phosphor were investigated by fluorescence intensity ratio (FIR) technique and exhibit relative thermal sensitivity of 2.57 and 0.7 %K−1 in the temperature range of 90 −230 K and 250–500 K respectively. The excellent quantum yield, sub-millisecond lifetime, cool colour temperature, and higher temperature sensitivities make them ideal for outdoor lighting and optical thermometric applications.

Photoredox-catalyzed self-dimerization and cross-addition as well as Zn(OTf)2-mediated nucleophile coupling: A novel route to structurally diverse 2,2-disubstituted indolin-3-ones

An efficient protocol for the synthesis of 2,2-disubstituted indolin-3-ones from both 2-aryl and 2-alkyl indoles via photoredox-catalyzed self-dimerization and cross-addition as well as Zn(OTf)2-mediated nucleophile coupling is described. The photoredox reactions feature low catalyst loading, mild reaction conditions, and broad functional group tolerance, generating indolin-3-ones in moderate to excellent yields. The Zn(OTf)2-mediated transformation using indolin-3-one dimer as a newly active species provides a much gentle way to access structurally diverse indolin-3-ones.

One-pot Synthesis of Bicarbazole-substituted Triary-methanols based on α-Keto Acids

In this work, carbazoles, one of the most important types of nitrogenous compounds, were used as substrates to synthesize bicarbazolyl-substituted triaryl-methanols in moderate to excellent yields (up to 95%). This simple and efficient strategy can regioselectively form a sp3 quaternary carbon with two large sterically hindered carbazole rings, one benzene ring and an active hydroxyl group in a one-pot reaction. These obtained triarylmethane products are all new products, and have the high potential as building blocks for medicinal chemistry or material science.

Photo-catalyzed dearomative coupling of benzylmalonates and alkynes with CO2 leading to spiro-1,4-cyclohexadiene carboxylic acids

A dearomative coupling reaction of benzylmalonates and alkynes with CO2via visible-light catalysis is developed, leading to a series of spiro-1,4-cyclohexadiene carboxylic acids. This three-component transformation achieves sequential dearomatization, alkenylation, and carboxylation of non-activated bezene ring, building spiro architecture and installing two functional groups in one reaction step. The strategy has the advantages of mild conditions, broad substrate scope, low loading of photocatalyst, redox neutral, excellent yield and high selectivity. Gram-scale reaction and product derivatizations indicate promising application prospects. Mechanistic studies reveal that the reaction might proceed through tandem radical addition, dearomatization and nucleophilic addition.

An efficient, catalyst-free synthesis of novel indenoquinoxaline fused hydrazinylthiazoles and their antimicrobial evaluation with molecular docking study

An efficient catalyst-free synthesis of Indenoquinoxaline fused hydrazinyl thiazoles through a one-pot reaction of 11-H-indeno[1,2-b]quinoxalin-11-ones, substituted phenacyl bromide and thiosemicarbazide at room temperature in ethanol is disclosed for the first time. All indenoquinoxaline fused hydrazinyl thiazoles were obtained in excellent yields within a shorter reaction time. The structure of synthesized indenoquinoxaline fused hydrazinyl thiazoles are supported by FT-IR, 1H NMR spectroscopy, and mass analysis. The synthesized indenoquinoxaline fused hydrazinyl thiazoles were screened for antimicrobial activity against the Gram-positive S. aureus and Gram-negative P. aeruginosa and further supported by molecular docking study, which will provide new ideas to design novel inhibitors.

Automated Synthesis of [11C]PiB via [11CH3OTf]-as Methylating Agent for PET Imaging of β-Amyloid.

Efficient synthesis of precursor from commercially available starting materials and automated radiosynthesis of [11C]PiB using commercially available dedicated [11C]- Chemistry module from the synthesized precursor. [11C]PiB is a promising radiotracer for PET imaging of β-Amyloid, advancing Alzheimer's disease research. The availability of precursors and protocols for efficient radiolabelling foster the applications of any radiotracer. Efficient synthesis of PiB precursor was performed using anisidine and 4-nitrobenzoyl chloride as starting materials in 5 steps, having addition, substitutions, and cyclization chemical methodologies. This precursor was used for fully automated radiosynthesis of [11C]PiB in a commercially available synthesizer, MPS-100 (SHI, Japan). The synthesized [11C]PiB was purified via solid-phase methodology, and its quality control was performed by the quality and safety criteria required for clinical use. The synthesis of desired precursors and standard authentic compounds started with commercially available materials with 70-80% yields. The standard analytical methods were characterized all synthesized compounds. The fully automated [11C]-chemistry synthesizer (MPS-100) used for radiosynthesis of [11C]PiB with [11C]CH3OTf acts as a methylating agent. For radiolabelling, varied amounts of precursor and time of reaction were explored. The resulting crude product underwent purification through solid-phase cartridges. The synthesized radiotracer was analyzed using analytical tools such as radio TLC, HPLC, pH endo-toxicity, and half-life. The precursor for radiosynthesis of [11C]PiB was achieved in excellent yield using simple and feasible chemistry. A protocol for radiolabelling of precursor to synthesized [11C]PiB was developed using an automated synthesizer. The crude radiotracer was purified by solid-phase cartridge, with a decay-corrected radiochemical yield of 40±5% and radiochemical purity of more than 97% in approx 20 minutes (EOB). The specific activity was calculated and found in a 110-121 mCi/μmol range. A reliable methodology was developed for preparing precursor followed by fully automated radiolabeling using [11C]MeOTf as a methylating agent to synthesize [11C]PiB. The final HPLC-free purification yielded more than 97% radiochemical purity tracer within one radionuclide half-life. The method was reproducible and efficient for any clinical center.

Eco-friendly Synthesis of Indole Conjugated Chromeno[d]Pyrimidines as Anti-cancer Agents and their Molecular Modelling Studies

Introduction: Many medicinally active new chemical entities depend on indole conjugated chromeno[d]pyrimidine derivatives as a building block. The synthesis of 4-(1H-indol-3-yl)-3,4- dihydro-1H-chromeno[4,3-d]pyrimidine-2,5-dione 4 were achieved in the current study by treating 4- hydroxy-2H-chromen-2-one 1, indole aldehydes 2, and urea/thiourea 3 in the presence of L-proline. Methods: By adopting the above protocol, we were able to synthesize eight compounds, i.e. 4-(1Hindol- 3-yl)-3,4-dihydro-1H-chromeno[4,3-d]pyrimidine-2,5-diones (4a-4h), in the presence of Lproline as a catalyst in ethanol as solvent for 2-3 hours at 70-75°C with decent yields of 80-85%, and their structures were ascertained by various spectral techniques. They were further screened for their potentiality to inhibit cancer growth in HepG2 and MDA-MD-231 cells. Results: The scope of the synthesis of biological relevant Indole conjugated Chromeno[ d]Pyrimidines by three-component reaction (MCRs) process was investigated. The most optimised conditions obtained were 0.3 eq of L-proline for 2 hours at 70-75°C which gave the best yield (85%). The few advantages of this newly developed method are excellent yields, no metal catalyst, less toxic solvents, simple workup no chromatographic column purifications. On further screening for their anticancer activities, out of all, the compound 4b displayed noteworthy cytotoxicity with IC50 values of 8.1 and 9.2 μM against HepG2 and MDA-MD-231, respectively. Additionally, in silico studies also supported that compound 4b had favourable binding energy (-7.8 kcal/mol) when compared to the co-crystal ligand (LS5) in inhibiting the human cyclin-dependent kinase 2 (CDK2) protein. Conclusion: In conclusion, we have developed a simple, convenient, and efficient method for the synthesis of structurally diverse indole conjugated chromeno[d]pyrimidine analogues in the presence of L-proline as catalyst in ethanol as solvent with good yields. Further, the in vitro cytotoxic studies against HepG2 and MDA-MD-231 cells demonstrated that the synthesized compounds had good to reasonable activity, except for compound 4d.

Glucose-Water Synergy: An Organocatalytic System Driven synthesis of Benzimidazolo[2,3-b]quinazolinone and Benzothiazolo[2,3-b]quinazolinone Derivatives

Introduction: A simple and efficient one-pot synthesis of quinazolinone derivatives has been developed via a multicomponent reaction (MCR) involving the condensation of dimedone, benzaldehyde, and 2-aminobenzimidazole/2-aminobenzothiazole. Method: In this work, glucose water is used as a green, reusable, environmentally benign organocatalytic solvent system to synthesize desired products. Result: The main benefits of this one-pot method include its excellent yields, less time, cost-effectiveness, atom economy, environment benign, and easy workup. Conclusion: In conclusion, we successfully developed a green protocol for the environmentally benign synthesis of benzimidazo/benzothiazolo quinazolinones using glucose water as an organocatalytic medium.

Catalytic Performance of Chiral Tetraaza-Bridged Calix[4]arene[2]triazine Derivatives for Enantioselective Michael Reactions.

Novel chiral tetraaza-bridged calix[4]arene[2]triazine-based organocatalysts were synthesized and used for catalytic asymmetric Michael reaction of acetylacetone to various aromatic nitrostyrenes. Chiral subunits (R)- and (S)-1,2,3,4-tetrahydro-1-naphthylamine were attached to the tetraaza-bridged calix[4]arene[2]triazine platform in both enantiomeric forms. The R configuration of the major enantiomer of the Michael product was obtained when 3a was used as catalyst, and the S configuration was obtained when 3b was used as catalyst. This indicated that the configuration of the Michael product was controlled by the chiral calixarene moiety. The Michael adducts were obtained in excellent yields (91%) and enantioselectivities (98%).

Pyridine-2-olato bridged dirhodium(III) acyl organometallics: Synthesis, spectroscopic, structural and theoretical studies

The heterogeneous phase reaction of [Rh(MeLsb)(PPh3)2Cl2] (1) with the sodium salt of three different pyridine-2-olato ligands [Na(R‒Opy), R = H, Me, NO2] in dichloromethane–acetone–water medium afforded the complexes of type [Rh(Lal)(PPh3)(R-Opy)]2 (2(R)) in excellent yield. These are the first examples of dirhodium(III) acyl complexes with the bridging pyridine-2-olato ligand. The penta coordinated dirhodium(III) acyl complexes are formed by the cleavage of the RhCl and RhPPh3 bonds of the precursor complex 1. The two R-Opy ligands bridge the two rhodium centers through their OOpy donor centers. The conversion of 1→2(R) is attended with the concomitant hydrolysis of the aldiminium function in 1. The spectral (UV–vis, IR, NMR) data of the complexes are reported. The identity of 2(Me) has been established by single crystal X–ray structure determination which revealed distorted trigonal bipyramidal RhCNO2P coordination sphere. The Rh, C, N and Ophenolato atoms define the equatorial plane whereas Rh, OOpy and P atoms define the axial plane. The electronic structures and absorption spectra of the complexes are also scrutinized by the density functional theory (DFT) and time–dependent DFT calculations.

New cyano-acrylamide derivatives incorporating the thiophene moiety: Synthesis, anti-cancer, gene expression, DNA fragmentation, DNA damage, and in silico studies

New cyano-acrylamide derivatives bearing the thiophene structure were prepared and rigorously characterized. Thus, the reaction of diethyl 5-(2-cyanoacetamido)-3-methylthiophene-2,4-dicarboxylate with aldehydes in the presence of piperidine afforded the title compounds in very good to excellent yields (range 81-96%, mean 91%). All the newly synthesized compounds were evaluated as anti-cancer agents against five human cancer cell lines namely, MCF7 (human Caucasian breast adenocarcinoma), PC3 (human prostate cancer cell line), HepG2 (Human hepatocellular carcinoma), PACA2 (epithelial cell line derived from tumor tissue of pancreas), and BJ1 (normal skin fibroblast). While most of the compounds showed good activity against MCF-7, they showed limited activity against PC3, HepG2, and PACA2. Compound 9 showed potent anti-cancer activity against the PACA2 cell line with IC50 131.18 µM compared with the reference drug (doxorubicin, IC50 52.06 µM), while compound 10 exhibited potent anti-cancer activity against HePG2 cell lines with IC50 24.51 µM compared to the positive control (doxorubicin, IC50 39.73 µM). The gene expression, DNA fragmentation, and DNA damage of the most promising compounds were discussed. Additionally, compounds 9 and 10 showed favorable binding energies and strong interactions with CDK2, EGFR, ERα, VEGFFR, and Topoisomerase II receptors in the molecular docking simulation. These results suggest that these compounds have the potential to be effective candidates for anti-cancer therapy. Additionally, the in-silico ADMET profiles indicated that these compounds adhere to the Lipinski rules, indicating favorable physicochemical properties. These findings further support their potential for continued drug development efforts.

Strengthening and deformation mechanisms of laser additively manufactured Ni2CoCrNb0.2V0.2 medium-entropy alloy: Cryogenic to elevated temperatures

To develop a medium-entropy alloy (MEA) with a high yield strength at temperatures ranging from cryogenic (-196 ℃) to elevated (800 ℃) temperatures, a strategy for strengthening nanoparticle precipitation while reducing the MEA stacking fault energy (SFE) is proposed. A novel Ni2CoCrNb0.2V0.2 MEA suitable for additive manufacturing (AM) was designed according to the first-principles calculations and the calculation of phase diagrams (CALPHAD) technique. Bulk MEA samples were printed using laser-directed energy deposition (LDED) with a vibration field. First-principles calculations indicated that V addition could reduce the SFE and stabilize the γ′′ strengthening phase. The aged MEA had excellent yield strengths of ∼1398 MPa and ∼751 MPa at −196 ℃ and 650 ℃, respectively. The specific strength of the MEA reached 94.16 MPa g−1 cm−3 at 650 ℃. The deformational mechanism transforms from stacking fault (SF), deformation twin (DT), and Lomer–Cottrell (L-C) lock synergy to slip-dominated plasticity when the tensile temperature increases from −196 ℃ to 800 ℃. This research provides new theoretical guidance for developing AM-ed MEAs with an ultrastrong combination of strength and ductility for extreme temperatures applications.