Traditional Synthetic Methods Research Articles

Lactonization of Diols Over Highly Efficient Metal-Based Catalysts.

Lactones has gained increasing attention in recent years due to wide application in polymer and pharmaceutical industries. Traditional synthetic methods of lactones often involve harsh operating temperature, use of strong alkalis and toxic oxidants. Therefore, lactonization of diols under milder conditions have been viewed as the most promising route for future commercialization. A variety of metal catalysts (Ru, Pt, Ir, Au, Fe, Cu, Co, and Zn) have been developed for highly efficient oxidant-, acceptor-, base- and additive-free lactonization processes. However, only a few initial attempts have been reported with no further details on catalytic mechanism being disclosed in literature. There demands a systematic study of the mechanistic details and the structure-function relationship to guide the catalyst design. In this work, we critically reviewed and discussed the structure-function relationship, the catalytic reaction mechanism, the catalyst stability, as well as the effect of oxidant and solvent for lactonization of diols. This work may provide additional insights for the development of other oxygen-containing functional molecules for material science and technologies.

Dialkylation of CF2 unit enabled by cobalt electron-shuttle catalysis

The incorporation of difluoromethylene (CF2) group into chemical molecules often imparts desirable properties such as lipophilicity, binding affinity, and thermal stability. Consequently, the increasing demand for gem-difluoroalkylated compounds in drug discovery and materials science has continued to drive the development of practical methods for their synthesis. However, traditional synthetic methods such as deoxofluorination often confront challenges including complicated substrate synthesis sequences and poor functional group compatibility. In this context, we herein report a metal electron-shuttle catalyzed, modular synthetic methodology for difluoroalkylated compounds by assembling two C(sp3) fragments across CF2 unit in a single step. The approach harnesses a difluoromethylene synthon as a biradical linchpin, achieving the construction of two C(sp3)-CF2 bonds through radical addition to two different π-unsaturated molecules. This catalytic protocol is compatible with broad range of coupling partners including diverse olefins, iminiums, and hydrazones, supporting endeavors in the efficient construction of C(sp3)-rich difluoroalkylated molecules.

Synthesis of Sulfilimines via Visible-Light-Mediated Triplet Energy Transfer to Sulfonyl Azides.

Sulfilimines and their derivatives have garnered considerable interest in both synthetic and medicinal chemistry. Photochemical nitrene transfer to sulfides is known as a conventional synthetic approach to sulfilimines. However, the existing methods have a limited substrate scope stemming from the incompatibility of singlet nitrene intermediates with nucleophilic functional groups. Herein, we report the synthesis of N-sulfonyl sulfilimines via visible-light-mediated energy transfer to sulfonyl azides, uncovering the previously overlooked reactivity of triplet nitrenes with sulfides. This reaction features broad functional group tolerance, water compatibility, and amenability to the late-stage functionalization of drugs. Thus, this work represents an important example of energy transfer chemistry that overcomes challenges in traditional synthetic methods.

A comparative study of in vivo toxicity in zebrafish embryos synthesized CuO nanoparticles characterized from Salacia reticulata.

The Salacia reticulata, a medicinal woody climbing shrub, was utilized for our study, the green synthesis of CuO nanoparticles, which were analyzed through SEM, EDX, FTIR, XRD, and UV‒Vis spectroscopy. This study assessed the toxicity to zebrafish embryos and explored the antibacterial, cytotoxic, antidiabetic, and anti-inflammatory properties of the synthesized nanoparticles. In results, the UV absorption of the CuO NPs showed that the intensity of nanoparticle green colloidal suspension changed from blue to green, which also confirmed that the spectrum of the green CuO NPs changed from colorless to black. in FT-IR and XRD spectral analysis to identify functional groups and determine the particle size of CuO NPs prepared by green and chemical methods. Its showed that CuO NPs (green) had a size of approximately 42.2nm, while CuO NPs (chemical) had a size of approximately 84nm. The morphology of these NPs was analyzed using SEM-EDX. Compared with their chemically prepared counterparts, the green-synthesized CuO nanoparticles demonstrated superior dispersion. Additionally, both green and chemical CuO nanoparticles at a concentration of 200 µL/mL caused developmental anomalies and increased mortality in zebrafish embryos and larvae. The green and chemical CuO NPs inhibited α-glucosidase enzyme activity at concentrations between 10 and 50 µL/mL, with IC50 values of 22 µL/mL and 26 µL/mL, respectively. The extract exhibited anti-inflammatory activity, with IC50 values of 274 and 109 µL/mL. The authors concluded that this green nanoparticle method has potential as a more eco-friendly and cost-effective alternative to traditional synthetic methods. NPs are widely used in human contact fields (medicine and agriculture), hence synthesis methods that do not involve toxic substances are becoming increasingly important.

Microwave Assisted Fast Synthesis of a Donor‐Acceptor COF Towards Photooxidative Amidation Catalysis

AbstractThe synthesis of covalent organic frameworks (COFs) at bulk scale require robust, straightforward, and cost‐effective techniques. However, the traditional solvothermal synthetic methods of COFs suffer low scalability as well as requirement of sensitive reaction environment and multiday reaction time (2–10 days) which greatly restricts their practical application. Here, we report microwave assisted rapid and optimized synthesis of a donor‐acceptor (D−A) based highly crystalline COF, TzPm‐COF in second (10 sec) to minute (10 min) time scale. With increasing the reaction time from seconds to minutes crystallinity, porosity and morphological changes are observed for TzPm‐COF. Owing to visible range light absorption, suitable band alignment, and low exciton binding energy (Eb=64.6 meV), TzPm‐COF can efficaciously produce superoxide radical anion (O2.−) after activating molecular oxygen (O2) which eventually drives aerobic photooxidative amidation reaction with high recyclability. This photocatalytic approach works well with a variety of substituted aromatic aldehydes having electron‐withdrawing or donating groups and cyclic, acyclic, primary or secondary amines with moderate to high yield. Furthermore, catalytic mechanism was established by monitoring the real‐time reaction progress through in situ diffuse reflectance infrared Fourier transform spectroscopic (DRIFTS) study.

Microwave Assisted Fast Synthesis of a Donor-Acceptor COF Towards Photooxidative Amidation Catalysis.

The synthesis of covalent organic frameworks (COFs) at bulk scale require robust, straightforward, and cost-effective techniques. However, the traditional solvothermal synthetic methods of COFs suffer low scalability as well as requirement of sensitive reaction environment and multiday reaction time (2-10 days) which greatly restricts their practical application. Here, we report microwave assisted rapid and optimized synthesis of a donor-acceptor (D-A) based highly crystalline COF, TzPm-COF in second (10 sec) to minute (10 min) time scale. With increasing the reaction time from seconds to minutes crystallinity, porosity and morphological changes are observed for TzPm-COF. Owing to visible range light absorption, suitable band alignment, and low exciton binding energy (Eb=64.6 meV), TzPm-COF can efficaciously produce superoxide radical anion (O2⋅-) after activating molecular oxygen (O2) which eventually drives aerobic photooxidative amidation reaction with high recyclability. This photocatalytic approach works well with a variety of substituted aromatic aldehydes having electron-withdrawing or donating groups and cyclic, acyclic, primary or secondary amines with moderate to high yield. Furthermore, catalytic mechanism was established by monitoring the real-time reaction progress through in situ diffuse reflectance infrared Fourier transform spectroscopic (DRIFTS) study.

Construct Phenylethanoid Glycosides Harnessing Biosynthetic Networks, Protein Engineering and One‐Pot Multienzyme Cascades

AbstractPhenylethanoid glycosides (PhGs) exhibit a multitude of structural variations linked to diverse pharmacological activities. Assembling various PhGs via multienzyme cascades represents a concise strategy over traditional synthetic methods. However, the challenge lies in identifying a comprehensive set of catalytic enzymes. This study explores biosynthetic PhG reconstruction from natural precursors, aiming to replicate and amplify their structural diversity. We discovered 12 catalytic enzymes, including four novel 6′‐OH glycosyltransferases and three new polyphenol oxidases, revealing the intricate network in PhG biosynthesis. Subsequently, the crystal structure of CmGT3 (2.62 Å) was obtained, guiding the identification of conserved residue 144# as a critical determinant for sugar donor specificity. Engineering this residue in PhG glycosyltransferases (FsGT61, CmGT3, and FsGT6) altered their sugar donor recognition. Finally, a one‐pot multienzyme cascade was established, where the combined action of glycosyltransferases and acyltransferases boosted conversion rates by up to 12.6‐fold. This cascade facilitated the reconstruction of 26 PhGs with conversion rates ranging from 5–100 %, and 20 additional PhGs detectable by mass spectrometry. PhGs with extra glycosyl and hydroxyl modules demonstrated notable liver cell protection. This work not only provides catalytic tools for PhG biosynthesis, but also serves as a proof‐of‐concept for cell‐free enzymatic construction of diverse natural products.

Construct Phenylethanoid Glycosides Harnessing Biosynthetic Networks, Protein Engineering and One-Pot Multienzyme Cascades.

Phenylethanoid glycosides (PhGs) exhibit a multitude of structural variations linked to diverse pharmacological activities. Assembling various PhGs via multienzyme cascades represents a concise strategy over traditional synthetic methods. However, the challenge lies in identifying a comprehensive set of catalytic enzymes. This study explores biosynthetic PhG reconstruction from natural precursors, aiming to replicate and amplify their structural diversity. We discovered 12 catalytic enzymes, including four novel 6'-OH glycosyltransferases and three new polyphenol oxidases, revealing the intricate network in PhG biosynthesis. Subsequently, the crystal structure of CmGT3 (2.62 Å) was obtained, guiding the identification of conserved residue 144# as a critical determinant for sugar donor specificity. Engineering this residue in PhG glycosyltransferases (FsGT61, CmGT3, and FsGT6) altered their sugar donor recognition. Finally, a one-pot multienzyme cascade was established, where the combined action of glycosyltransferases and acyltransferases boosted conversion rates by up to 12.6-fold. This cascade facilitated the reconstruction of 26 PhGs with conversion rates ranging from 5-100 %, and 20 additional PhGs detectable by mass spectrometry. PhGs with extra glycosyl and hydroxyl modules demonstrated notable liver cell protection. This work not only provides catalytic tools for PhG biosynthesis, but also serves as a proof-of-concept for cell-free enzymatic construction of diverse natural products.

Narrowing the photoluminescence bandwidth of InP‐based colloidal quantum dots through photon‐triggered isolation

AbstractThe optimization of photoluminescence (PL) spectral bandwidths in InP‐based colloidal quantum dots (QDs) faces limitations with traditional synthetic methods. This study introduces a novel approach utilizing light‐induced thiolate ligand detachment to selectively precipitate QDs within an ensemble, triggered by photons whose energy matches the red tail of the band‐edge absorption peak. We demonstrate that incorporating benzoquinone as an electron acceptor under inert conditions crucially enhances the efficiency of photoexcited hole‐induced ligand detachment. Through careful optimization of laser exposure conditions, we successfully narrowed the PL bandwidth of InP/ZnSe/ZnS QDs from 39 to 35 nm. Our findings offer significant insights into the development of high‐performance QD‐based displays, promising advancements in color purity.

Rb‐Promoted Au/CeO2 Nanocatalyst for Remarkably‐Enhanced Aniline Conversion to Azoxybenzene with Ultrahigh Selectivity

Aromatic azo compounds have proven to be a relevant class of building blocks in chemical synthesis. However, uncontrollable selectivity towards azo compounds and low reactant conversion in traditional synthetic methods seriously impede their applications. Herein, Rb‐doped Au/CeO2 nanocatalyst (Rb‐Au/CeO2) was prepared and utilized as a highly efficient supported metal catalyst for the selective oxidation of anilines to azocompounds using hydrogen peroxide as an oxidant, which reached ultrahigh selectivity (92%) towards azoxybenzene and complete aniline conversion (100%). The addition of Rb+ accelerates the electron transformation of Au to produce Au+, which is ready for catalysis. This research presents a promising Rb‐doped strategy for achieving complete aniline conversion and high selectivity towards azoxybenzene, opening up new possibilities for the application of aromatic azo compounds in chemical synthesis.

Fabricating a Structured Single‐Atom Catalyst via High‐Resolution Photopolymerization 3D Printing

AbstractThis study introduces a novel solution to the design of structured catalysts, integrating single‐piece 3D printing with single‐atom catalysis. Structured catalysts are widely employed in industrial processes, as they provide optimal mass and heat transfer, leading to a more efficient use of catalytic materials. They are conventionally prepared using ceramic or metallic bodies, which are then washcoated and impregnated with catalytically active layers. However, this approach may lead to adhesion issues of the latter. By employing photopolymerization printing, a stable and active single‐atom catalyst is directly shaped into a stand‐alone, single‐piece structured material. The battery of characterization methods employed in the present study confirms the uniform distribution of catalytically active species and the structural integrity of the material. Computational fluid dynamics simulations are applied to demonstrate enhanced momentum transfer and light distribution within the structured body. The materials are finally evaluated in the continuous‐flow photocatalytic oxidation of benzyl alcohol to benzaldehyde, a relevant reaction to prepare biomass‐derived building blocks. The innovative approach reported herein to manufacture a structured single‐atom catalyst circumvents the complexities of traditional synthetic methods, offering scalability and efficiency improvements, and highlights the transformative role of 3D printing in catalysis engineering to revolutionize catalysts’ design.

Enhancing Energy Storage Capacity of 3D Carbon Electrodes Using Soft Landing of Molecular Redox Mediators.

The incorporation of redox-active species into the electric double layer is a powerful strategy for enhancing the energy density of supercapacitors. Polyoxometalates (POM) are a class of stable, redox-active species with multielectron activity, which is often used to tailor the properties of electrochemical interfaces. Traditional synthetic methods often result in interfaces containing a mixture of POM anions, unreactive counter ions, and neutral species. This leads to degradation in electrochemical performance due to aggregation and increased interfacial resistance. Another significant challenge is achieving the uniform and stable anchoring of POM anions on substrates to ensure the long-term stability of the electrochemical interface. These challenges are addressed by developing a mass spectrometry-based subambient deposition strategy for the selective deposition of POM anions onto engineered 3D porous carbon electrodes. Furthermore, positively charged functional groups are introducedon the electrode surface for efficient trapping of POM anions. This approach enables the deposition of purified POM anions uniformly through the pores of the 3D porous carbon electrode, resulting in unprecedented increase in the energy storage capacity of the electrodes. The study highlights the critical role of well-defined electrochemical interfaces in energy storage applications and offers a powerful method to achieve this through selective ion deposition.

Regiodivergent Radical Termination for Intermolecular Biocatalytic C-C Bond Formation.

Radical hydrofunctionalizations of electronically unbiased dienes are challenging to render regioselective, because the products are nearly identical in energy. Here, we report two engineered FMN-dependent "ene"-reductases (EREDs) that catalyze regiodivergent hydroalkylations of cyclic and linear dienes. While previous studies focused exclusively on the stereoselectivity of alkene hydroalkylation, this work highlights that EREDs can control the regioselectivity of hydrogen atom transfer, providing a method for selectively preparing constitutional isomers that would be challenging to prepare using traditional synthetic methods. Engineering the ERED from Gluconabacter sp. (GluER) furnished a variant that favors the γ,δ-unsaturated ketone, while an engineered variant from a commercial ERED panel favors the δ,ε-unsaturated ketone. The effect of beneficial mutations has been investigated using substrate docking studies and the mechanism probed by isotope labeling experiments. A variety of α-bromo ketones can be coupled with cyclic and linear dienes. These interesting building blocks can also be further modified to generate difficult-to-access heterocyclic compounds.

Towards Industrially Important Applications of Enhanced Organic Reactions by Microfluidic Systems.

This review presents a comprehensive evaluation for the manufacture of organic molecules via efficient microfluidic synthesis. Microfluidic systems provide considerably higher control over the growth, nucleation, and reaction conditions compared with traditional large-scale synthetic methods. Microfluidic synthesis has become a crucial technique for the quick, affordable, and efficient manufacture of organic and organometallic compounds with complicated characteristics and functions. Therefore, a unique, straightforward flow synthetic methodology can be developed to conduct organic syntheses and improve their efficiency.

Molybdenum trioxide as a newer diversified economic catalyst for the transformation of nitroarenes to arylamine and 5-substituted-1H-tetrazole.

The present work has developed a straightforward, gentle, and effective approach for synthesizing arylamines and 5-substituted-1H-tetrazole derivatives, and among the two tested catalysts, molybdenum trioxide (MoO3) proved to be highly effective. The selective hydrogenation of nitroarenes to arylamines presents a significant challenge due to the complex reaction mechanism and the competitive hydrogenation of other reducible functional groups. It facilitated the transfer hydrogenation of nitrobenzene using hydrazine hydrate-produced amino compounds and enabled the [3 + 2] cycloaddition of sodium azide with aromatic nitriles to yield 5-substituted-1H-tetrazoles. The structure of compound 5-(4-bromophenyl)-1H-tetrazole (5k) was verified through single-crystal X-ray analysis, and the calculation of Green Chemistry Metrics showed the optimal range. Notably, the MoO3 catalyst can be reutilized for up to seven cycles with minimal loss of effectiveness. These attributes make molybdenum trioxide particularly attractive for industrial applications. This methodology offers several advantages over traditional synthetic methods.

Evaluation of Endoplasmic Reticulum Targeting Isoquinol‐Based BODIPY Dyes and Their Properties as Molecular Rotors

AbstractA series of six new isoquinol‐based BODIPY dyes have been synthesized by a two‐step method. Unlike traditional synthetic methods, synthesis did not require the use of oxidizing agents or solvent. Spectroscopic, electrochemical and DFT calculations indicate that the properties associated with the six dyes are very similar with little influence of the meso‐substituents. Viscosity studies identified three of the new dyes having properties of molecular rotors for applications in the detection of changes in cellular viscosity. Incubation of the dyes with the HEK cell line show no toxicity up to 10 μM over a 72 h. period. The dyes show the ability to localize within the endoplasmic reticulum (ER) of cells. With two of the dyes showing favorable comparisons to commercially available ER dyes.

On‐Surface Synthesis and Real‐Space Visualization of Aromatic P3N3

AbstractOn‐surface synthesis is at the verge of emerging as the method of choice for the generation and visualization of unstable or unconventional molecules, which could not be obtained via traditional synthetic methods. A case in point is the on‐surface synthesis of the structurally elusive cyclotriphosphazene (P3N3), an inorganic aromatic analogue of benzene. Here, we report the preparation of this fleetingly existing species on Cu(111) and Au(111) surfaces at 5.2 K through molecular manipulation with unprecedented precision, i.e., voltage pulse‐induced sextuple dechlorination of an ultra‐small (about 6 Å) hexachlorophosphazene P3N3Cl6 precursor by the tip of a scanning probe microscope. Real‐space atomic‐level imaging of cyclotriphosphazene reveals its planar D3h‐symmetric ring structure. Furthermore, this demasking strategy has been expanded to generate cyclotriphosphazene from a hexaazide precursor P3N21 via a different stimulation method (photolysis) for complementary measurements by matrix isolation infrared and ultraviolet spectroscopy.

On-Surface Synthesis and Real-Space Visualization of Aromatic P3N3.

On-surface synthesis is at the verge of emerging as the method of choice for the generation and visualization of unstable or unconventional molecules, which could not be obtained via traditional synthetic methods. A case in point is the on-surface synthesis of the structurally elusive cyclotriphosphazene (P3N3), an inorganic aromatic analogue of benzene. Here, we report the preparation of this fleetingly existing species on Cu(111) and Au(111) surfaces at 5.2 K through molecu-lar manipulation with unprecedented precision, i.e., voltage pulse-induced sextuple dechlorina-tion of an ultra-small (about 6 Å) hexachlorophosphazene P3N3Cl6molecule by the tip of a scan-ning probe microscope. Real-space atomic-level imaging of cyclotriphosphazene reveals its planarD3h-symmetric ring structure. Furthermore, this demasking strategy has been expanded to generate cyclotriphosphazene from a hexaazide precursor P3N21via a different stimulation method (photolysis) for complementary measurements baby matrix isolation infrared and ultraviolet spectroscopy.

Room-Temperature, Multigram-Scale Synthesis and Conversion Mechanism of Highly Luminescent Lead Sulfide Quantum Dots.

PbS quantum dots (QDs) are attractive near-infrared (NIR) materials, but traditional synthetic methods require inert atmosphere and/or high temperature. Herein we develop a facile, room-temperature synthetic route for in situ halide passivated PbS QDs through controllable reactions between lead halide, N,N'-diphenyl thiourea, and oleyamine (OLA) in toluene. Contrast experiments and theoretical calculations reveal that the OLA plays a bifunctional role as a mild base to initiate the formation of PbS monomers and as a dynamic ligand to control the crystallization of PbS QDs and further ligand exchange. The oleic acid-capped PbS QDs exhibit high photoluminescence quantum yields up to 45%. The scaled-up synthesis on multigram scales shows great batch-to-batch consistency. We further demonstrate high-power NIR light-emitting diodes using the PbS QDs as color converters, delivering NIR optical power of 9.2 mW at 160 mA. This work provides a simple and versatile synthetic route for high-quality PbS QDs and boosts the applications of NIR materials.

Terrace-Like 2D Hierarchically Porous Iron/Cobalt Metal-Organic Framework: Ambient Fast Synthesis and Efficient Oxygen Evolution Reaction Application.

It is urgent to design a low-cost electrocatalyst with high activity to enhance the efficiency of oxygen evolution reaction (OER), which is limited by the slow four-electron transfer kinetics process. Nevertheless, traditional synthetic methods, including calcination and solvothermal, of the electrocatalysts are high-cost, low-yield, and energy-hogging, which limits their industrial application. Herein, an ambient fast synthetic method is developed to prepare terrace-like Fe/Co bimetal-organic framework (TFC-MOF) electrocatalyst materials in gram scale in 1h. The method in this paper is designable based on coordination chemistry. Fe and Co ions can coordinate with the carboxyl groups on benzene-1,3,5-tricarboxylic acid (H3 BTC) to form a 2D-MOF structure. Structural characterizations, including SEM, TEM, and XRD are conducted to verify that the TFC-MOF is a terrace-like layered structure with uniform-sized mesoporous, which reduces the adsorption steric hindrance and facilitates the mass and electron transfer efficiency of OER. The TFC-MOF shows low overpotential, 255mV at a current density of 10mAcm-2 , and a low Tafel slope of 49.9mVdec-1 , in an alkaline solution. This work provides a planar coordination strategy to synthesize 2D-MOF OER electrocatalyst on a large scale with low cost and low energy consumption, which will promote its practical OER applications.