Reaction Of Reagents Research Articles

Heterofunctional β-diketones incorporating ester linkages: Mesomorphism and solvatochromic effect

In this work a series of mesogens derived from 4-(4-octyloxybenzoyloxy)benzoic acid were synthesized and characterized. They acted as the main reagents in the Claisen condensation reaction to obtain a heterofunctional β-diketone containing both mesogenic long alkyloxybenzoic fragment and carbazole derivatives as chromophore unit in its structure. The results of the study of phase behavior showed that the synthesized elongated derivatives, including 4-(4-octyloxybenzoyloxy)benzoic acid as a key precursor for further modification, exhibit an enantiotropic mesomorphism, SmA and nematic mesophases, whereas the target β-diketone shows SmA mesophase only upon cooling from the isotropic melt. In addition, β-diketone demonstrates bright emission in the solvents of different polarity and in the solid state. The fluorescence quantum yield reaches values from 14 to 64 % depending on the nature of the solvent.

Nickel‐Catalyzed Difluoroalkylation of β,γ‐Unsaturated α‐Amino Nitrile Derived Lithium Reagents

Organolithium reagents, known for their low cost, ready availability, and high reactivity, allow fast cross‐coupling under ambient conditions. However, their direct cross‐coupling with fluoroalkyl electrophiles remains a formidable challenge due to the easy formation of thermo‐unstable fluoroalkyl lithium species during the reaction, which are prone to decomposition via rapid α/β‐fluoride elimination. Here, we exploit heteroatom‐stabilized allylic anions to harness the exceptional reactivity of organolithium reagents, enabling the compatibility of difluoroalkyl halides and facilitating versatile and precise fluorine functionality introduction under mild conditions. In this process, a nickel‐catalyzed difluoroalkylation of β,γ‐unsaturated α‐amino nitrile derived lithium reagents (N‐stabilized allyl lithium reagents) with various difluoroalkyl bromides has been developed, opening a new avenue to access fluorinated compounds through catalytic cross‐coupling of organolithium reagents with fluoroalkyl electrophiles. This approach allows for the efficient and precise construction of secondary C(sp3)‐CF2R bonds, previously challenging in transition‐metal‐catalyzed fluoroalkylation reactions due to β‐hydride elimination. The rapid fluorine‐editing of drugs demonstrates the synthetic versatility and utility of this protocol, showing the perspective in modern drug discovery.

Nickel-Catalyzed Difluoroalkylation of β,γ-Unsaturated α-Amino Nitrile Derived Lithium Reagents.

Organolithium reagents, known for their low cost, ready availability, and high reactivity, allow fast cross-coupling under ambient conditions. However, their direct cross-coupling with fluoroalkyl electrophiles remains a formidable challenge due to the easy formation of thermo-unstable fluoroalkyl lithium species during the reaction, which are prone to decomposition via rapid α/β-fluoride elimination. Here, we exploit heteroatom-stabilized allylic anions to harness the exceptional reactivity of organolithium reagents, enabling the compatibility of difluoroalkyl halides and facilitating versatile and precise fluorine functionality introduction under mild conditions. In this process, a nickel-catalyzed difluoroalkylation of β,γ-unsaturated α-amino nitrile derived lithium reagents (N-stabilized allyl lithium reagents) with various difluoroalkyl bromides has been developed, opening a new avenue to access fluorinated compounds through catalytic cross-coupling of organolithium reagents with fluoroalkyl electrophiles. This approach allows for the efficient and precise construction of secondary C(sp3)-CF2R bonds, previously challenging in transition-metal-catalyzed fluoroalkylation reactions due to β-hydride elimination. The rapid fluorine-editing of drugs demonstrates the synthetic versatility and utility of this protocol, showing the perspective in modern drug discovery.

Homologation of Carboxylic Acids Using a Radical-Polar Conjunctive Reagent.

Homologations of organic molecules that add a carbon atom to the substrate are useful in drug discovery to access compounds with improved properties that otherwise present a synthetic challenge. Carboxylic acids are present in many bioactive molecules and are widely available building blocks for chemical synthesis, yet their direct homologation is unknown. This valuable transformation currently necessitates implementation of multistep processes that require the use of carboxylic acid derivatives rather than the native substrates, and commonly involves highly reactive and toxic reagents. Herein, we report the first one-step homologation directly from native carboxylic acids using a novel, bench-stable (1-phosphoryl)vinyl sulfonate reagent under mild conditions. This strategy was applied to a wide range of aliphatic carboxylic acid building blocks and biologically relevant complex molecules to access an array of ester, amide, and carboxylic acid homologues in a single step. The (1-phosphoryl)vinyl sulfonate reagent participates in complementary homologation protocols featuring either radical-chain transfer or organic photoredox catalysis and introduces a new synthon, the distonic acylium radical, for molecular diversification. We anticipate this strategy, which addresses a long-standing challenge in organic synthesis, will expedite drug discovery by enabling the rapid synthesis of diversified homologues.

Mechanistic Exploration of N-Heterocyclic Carbene Boranes as the Hydrogen Atom Transfer Reagent in Selective Hydrodefluorination Reactions

Mechanistic Exploration of <i>N</i>-Heterocyclic Carbene Boranes as the Hydrogen Atom Transfer Reagent in Selective Hydrodefluorination Reactions

Comparison of Different Organometallics Towards Electrophilic Aromatic 211At-Astatinations of Highly Reactive Tetrazines.

Organometallics can be used as precursors for electrophilic 211At-statinations. In this report, we compared the potential of aryl trimethylsilanes, -germanes, or -stannanes to be used as precursors to 211At-label highly reactive tetrazines. Tetrazines can be used for pretargeted radioligand therapies or be applied as synthons to radiolabel rapidly and orthogonally a broad set of precursors such as peptides, mAbs or nanomedicines. All precursors could successfully be synthesized and radiolabeled. The reactivity of organogermanium reagents ranged between those of respective organotin and organosilicon precursors. Moreover, organogermanium reagents proved promising for accessing more complex and polar tetrazine scaffolds. In contrast to organotin derivatives, the use of protecting groups could be avoided for organogermanium and -silicon precursors. The developed 211At-labeled tetrazines could be labeled in radiochemical conversions of 60-90%. Organogermanium and -silicon precursors were clearly advantaged as additional deprotection steps could avoided. Reported labeling procedures allow astatinations of highly reactive tetrazines to be used for pretargeted approaches or to applied as highly reactive synthons to label the next-generation of 211At-labeled radiopharmaceuticals.

Development of paper-based microfluidic analytical device (μPAD) for the determination of paracetamol in water samples: Optimization using response surface methodology (RSM)

Detecting and quantifying pharmaceutical compounds in various environmental matrices is complex and challenging. This difficulty stems from the trace levels at which these compounds are found and the lack of analytical methods that are rapid, cost-effective, and portable. To address these challenges, this study aimed to develop microfluidic paper-based analytical devices (μ-PADs) using beeswax screen printing for fabrication. Key parameters, including reaction time, concentration, reagent volume, and channel length, were optimized using response surface methodology. Under optimal conditions of 5 ppm sample concentration, 10 μL reagent volume, 10 min reaction time, and 2 cm channel length, the analytical performance of the μPAD was evaluated and compared with the standard UV–Vis spectrophotometry method. The microfluidic analytical device demonstrated detection limits at 0.03 μg/ml, compared to 0.01 μg/ml for the UV–Vis spectrophotometer. Although the sensitivity of µ-PADs in this study (0.03 μg/ml) is lower than that of UV–Vis (0.01 μg/ml), it represents an improvement over the previous µ-PAD report (1 μg/ml) on the same analytes. Both methods exhibited commendable precision, with a relative standard deviation below 2%. Additionally, recovery rates were acceptable and comparable, ranging from 86.8 to 99.6% for µ-PADs and 96.5–99% for UV–Vis. The analytical performance evaluation suggests that µPADs provide excellent sensitivity, precision, and accuracy for trace-level paracetamol analysis. A paired t-test further confirmed no statistically significant difference between the two methods, underscoring the promising potential of µ-PADs for trace-level paracetamol quantification in water samples without conventional analytical instruments.

Epidemiology of Acute Infectious Diarrhea-Associated Viruses in Children in Hangzhou, China, 2023

Abstract Objective To investigate the epidemiological characteristics of children infected with diarrheal virus in Hangzhou, China, 2023. Methods From January 2023 to December 2023, 20,939 stool samples from children with acute infectious diarrhea were collected for the detection of rotavirus A and human adenovirus (HAdV), using latex agglutination detection kits; 7,584 stool samples were collected for the detection of norovirus, using real-time polymerase chain reaction reagent. Results A total of 639 (3.0%, 639/20,939) tested positive for rotavirus A, and 1,201 (5.7%, 1,201/20,939) positive samples were detected by colloidal gold method. The positive rates of norovirus were 42.2% (3,203/7,585). Among all age groups, the rotavirus A positive detection rate was the highest in participants aged 3 to 6 years (6.46%, 260/4,024). The monthly distribution of patients with rotavirus A showed that the number of cases was the lowest in October (0.45%, 8/1,779) and reached the peak in April (7.97%, 144/1,806). The highest and lowest positive rates among all age groups for HAdV were found in children aged 3 to 6 years(8.27%, 333/4,024) and in those aged 0 to 6 months (2.21%, 60/2,717). The monthly positivity rates of HAdV spanning from January to November 2023 were 1.38, 1.44, 2.34, 3.65, 6.64, 7.71, 7.54, 7.13, 6.82, 4.15, and 6.50%, and reached the peak in December (8.17%). For norovirus, children aged 1 to 3 years had the highest positive detection rate (57.95%, 1,349/2,328), while infants aged 0 to 6 months had the lowest positive detection rate (19.60%, 205/1,046). The results show that January had the lowest number of cases (14.63%, 6/41), while September had the highest (50.51%, 545/1,079). Conclusion The detection rate of rotavirus A and HAdV was highest among participants aged 3 to 6 years, whereas the detection rate of norovirus was highest among those aged 1 to 3 years. The monthly distribution peaks for the three enteric viruses varied significantly.

Generation and Application of Sulfur Ylides in Light‐Mediated Transformations

AbstractSulfur ylides are essential reagents in various organic reactions like epoxidation and cyclopropanation. While traditionally employed in ionic chemistry, recent advancements in visible‐light‐driven photocatalysis reveal their potential as sources of radicals or free carbenes. The photochemical or photocatalytic generation of reactive intermediates using sulfur ylides expands the utility of these reagents in modern organic synthesis, offering sustainable solutions to emerging challenges. Despite early demonstrations in the 1960s, the past years have witnessed a surge in photochemical methods utilizing sulfur ylides as precursors. The use of redox‐active photocatalysts has facilitated numerous radical reactions. This review consolidates key findings in sulfur ylide chemistry, particularly focusing on photo‐mediated reactions, to stimulate further research interest in this dynamic field.

N-Chlorosuccinimide: A Versatile Reagent in Organic Synthesis

N-Chlorosuccinimide (NCS) is a five-membered N-containing heterocyclic molecule. This is a versatile reagent and is successfully employed for different types of reactions. Initially, this was employed for chlorination only but soon became an excellent reagent for many reactions, including halocyclizations, functional group transformations, formation of carbon-carbon bonds, etc. This review article covers representative applications of NCS for aliphatic and aromatic chlorination, chlorination of atoms other than carbon, oxidation, and other reactions.

Aminosulfonylation of Rhodium Carbene via Ylide Formation and 1,4-Sulfonyl Rearrangement.

We report here the use of pyridin-2-yl benzenesulfonates as sulfonylation reagents in a difunctionalization reaction based on oxy-pyridinium ylide chemistry, providing an effective protocol for the installation of both a sulfonyl group and a pyridone moiety into one molecule. Density functional theory (DFT) calculations disclose that the reaction process might proceed through sequential metal-bound ylide formation, keto-enol tautomerism, and the migratory rearrangement of the sulfonyl group.

Formate Salt as a Bifunctional Reagent for Hydroxylation and Carbonylation Reactions Under Photochemically Driven Nickel Catalysis.

In this study, we disclose for the first time that formate salt can be used as a bifunctional reagent for the synthesis of phenol derivatives and as a CO source for carbonylative cross-coupling processes using the COware gas reactor under activation free conditions. Key to this success is the in-situ synthesis of aryl formate via an unprecedented nickel/organophotocatalyst system under blue LED irradiation. This developed system demonstrated high applicability to various aryl iodide substrates for synthesizing phenol derivatives. Moreover, the generated CO could be utilized in a range of carbonylative C-heteroatom and C-C processes. Notably, commercially available H13COONa salt can serve as a bifunctional reagent for both synthesizing phenols and generating 13CO.

Synthesis, Structures, and Reactivity of Organostannanides and Organogermanides of Copper(I).

Organogermane and organostannane compounds are valuable reagents in cross coupling reactions, and copper(I) germanide and stannanide complexes can provide convenient access to these compounds. This review presents the chemistry of copper(I) germanide and stannanide complexes, with a particular focus on systems at the frontier of organic and inorganic chemistry where structural characterisation of coordination complexes facilitates rationalisation of organic mechanisms. These species show both similarities to, and significant divergences from their lighter silanide congeners. For example, they are all viable sources of the relevant organotetranide anion, but in the cases of both germanium and tin, the tetranides can be accessed via direct deprotonation of the corresponding tetranes, a reaction unknown for silicon. Further divergences between copper(I) germanides and stannanides are highlighted; whilst both can be used in productive organic transformations to access organotetranes, catalytic reactions are only reported for germanium. The rather striking ability of triphenylstannanides to acts as sources of the phenyl anion are discussed; the mechanism of this reaction is still subject to discussion, but its absence in the chemistry of germanium and silicon is now well-rationalised. We conclude this review by considering potential research directions in the synthesis and exploitation of copper(I) germanides and stannanides.

Synthesis and Characterization of Extremely Bulky Aminopyridinate Ligands and a Series of Their Groups 1 and 2 Metal Complexes

High-yielding synthetic routes to five new extremely bulky aminopyridine pro-ligands were developed, viz. (C5H3N-6-Ar1)N(H)Ar2-2; Ar1 = Trip, Ar2 = TCHP (HAmPy1), Ar* (HAmPy2) or Ar† (HAmPy3); Ar1 = TCHP, Ar2 = Ar* (HAmPy4) or Ar† (HAmPy5) (Trip = 2,4,6-triisopropylphenyl, TCHP = 2,4,6-tricyclohexylphenyl, Ar* = C6H2(CHPh2)2Me-2,6,4, Ar† = C6H2(CHPh2)2Pri-2,6,4. Four of these were deprotonated with LiBun in diethyl ether to give lithium aminopyridinate complexes which were dimeric for the least bulky ligand, [{Li(AmPy1)}2] or monomeric for the bulkier aminopyridinates, i.e., in [Li(AmPy2−4)(OEt2)]. One aminopyridine was deprotonated with MeMgI to give monomeric [Mg(AmPy3)I(OEt2)2]. When treated with sodium or potassium mirrors or 5% w/w Na/NaCl, over-reduction occurred, leading to the alkali metal aminopyridinates, [M(AmPy3)(η6-toluene)] (M = Na or K) or [{Na(AmPy3)}∞]. An attempted reduction of [Mg(AmPy3)I(OEt2)2] with a dimagnesium(I) compound led only to partial loss of diethyl ether and the formation of [(AmPy3)Mg(μ-I)2Mg(AmPy3)(OEt2)]. All prepared complexes have potential as ligand transfer reagents in salt metathesis reactions with metal halide complexes.

Recent Progress in the Photocatalytic Synthesis of α‐Tertiary Primary Amines

Abstractα‐Tertiary primary amines (α‐TPAs) bearing a fully substituted carbon center adjacent to the N‐unsubstituted amino group (−NH2) exhibit unique biochemical and physicochemical activities. While due to the sterically congested structure and strong nucleophilic and alkaline natures of these primary amine compounds, their facile synthesis remains an inherent challenge. Traditional methods commonly rely on tedious N‐protection/deprotection operations and highly reactive organometallic reagents, thus leading to poor atom and step‐economy and limited functional group compatibility. Modern photoredox catalysis offers a robust tool to prepare such structurally unique and synthetically valuable amine architectures via a radical pathway under extremely mild conditions. In this review, the recent progress in photocatalytic synthesis of α‐TPAs is systematically reviewed, and the reaction scope, limitations, and mechanisms for the reactions are discussed.

Antifouling slippery liquid infused porous surface for surfactant-free PCR on digital microfluidics platform

Digital microfluidics technology has immense potential for multiplexing biological processes, reducing reagents, and minimizing process time. However, biofouling of surfaces causes cross-contamination, slow droplet movement, and prolonged experiment time, hindering its full potential. Traditionally surfactants are used to combat this issue but can interfere with biological reactions leading to low efficiency. An alternative is the use of slippery liquid-infused porous surfaces (SLIPS), which do not interfere with the reactions and offer a solution to the biofouling problem. In this study, we compare Teflon surfaces with SLIPS to address the challenge of biofouling in Digital MicroFluidic (DMF) devices. More specifically, we demonstrate that SLIPS in an Electrowetting-on-Dielectric (EWOD)-based DMF device not only prevents biofouling but also enhances PCR efficiency, reducing reaction times and reagent consumption. These advancements eliminate the need for surfactants, which can interfere with biological reactions, thereby ensuring higher fidelity in PCR amplification. Our findings reveal that SLIPS facilitate faster droplet movement and maintain reaction integrity, showcasing their potential for high-throughput biological assays.

Organoboron catalysis for direct amide/peptide bond formation.

Amides and peptides are ubiquitous functional groups found in several natural and artificial materials, and they are essential for the advancement of life and material sciences. In particular, their relevance in clinical medicine and drug discovery has increased in recent years. Dehydrative condensation of readily available carboxylic acids with amines is the most "direct" method for amide synthesis; however, this methodology generally requires a stoichiometric amount of condensation agent (coupling reagent). Catalytic direct dehydrative amidation has become an "ideal" methodology for synthesizing amides from the perspective of green chemistry, with water as the only byproduct in principle, high atom efficiency, environmentally friendly, energy saving, and safety. Conversely, organoboron compounds, such as boronic acids, which are widely used in various industries as coupling reagents for Suzuki-Miyaura cross-coupling reactions or pharmaceutical structures, are environmentally friendly molecules that have low toxicity and are easy to handle. Based on the chemical properties of organoboron compounds, they have potential Lewis acidity and the ability to form reversible covalent bonds with dehydration, making them attractive as catalysts. This review explores studies on the development of direct dehydrative amide/peptide bond formation reactions from carboxylic acids using organoboron catalysis, classifying them based on chemical bonding and catalysis over approximately 25 years, from the early developmental days to 2023.

Benzoyl cyanide, a general radical acylating reagent for photoredox-catalyzed benzylic site-selective acylation reactions

Benzoyl cyanide, a general radical acylating reagent for photoredox-catalyzed benzylic site-selective acylation reactions

Late-Stage Halogenation of Complex Substrates with Readily Available Halogenating Reagents.

ConspectusLate-stage halogenation, targeting specific positions in complex substrates, has gained significant attention due to its potential for diversifying and functionalizing complex molecules such as natural products and pharmaceutical intermediates. Utilizing readily available halogenating reagents, such as hydrogen halides (HX), N-halosuccinimides (NXS), and dichloroethane (DCE) reagents for late-stage halogenation shows great promise for expanding the toolbox of synthetic chemists. However, the reactivity of haleniums (X+, X = Cl, Br, I) can be significantly hindered by the presence of various functional groups such as hydroxyl, amine, amide, or carboxylic acid groups. The developed methods of late-stage halogenation often rely on specialized activating reagents and conditions. Recently, our group (among others) has put great efforts into addressing these challenges and unlocking the potential of these readily available HX, NXS, and DCE reagents in complex molecule halogenation. Developing new methodologies, catalyst systems, and reaction conditions further enhanced their utility, enabling the efficient and selective halogenation of intricate substrates.With the long-term goal of achieving selective halogenation of complex molecules, we summarize herein three complementary research topics in our group: (1) Efficient oxidative halogenations: Taking inspiration from naturally occurring enzyme-catalyzed oxidative halogenation reactions, we focused on developing cost-effective oxidative halogenation reactions. We found the combination of dimethyl sulfoxide (DMSO) and HX (X = Cl, Br, I) efficient for the oxidative halogenation of aromatic compounds and alkenes. Additionally, we developed electrochemical oxidative halogenation using DCE as a practical chlorinating reagent for chlorination of (hetero)arenes. (2) Halenium reagent activation: Direct electrophilic halogenation using halenium reagents is a reliable method for obtaining organohalides. However, compared to highly reactive reagents, the common and readily available NXS and dihalodimethylhydantoin (DXDMH) demonstrate relatively lower reactivity. Therefore, we focused on developing oxygen-centered Lewis base catalysts such as DMSO, 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) and nitromethane to activate NXS or DXDMH, enabling selective halogenation of bioactive substrates. (3) Halogenation of inert substrates: Some substrates, such as electron-poor arenes and pyridines, are inert toward electrophilic functionalization reactions. We devised several strategies to enhance the reactivity of these molecules. These strategies, characterized by mild reaction conditions, the ready availability and stability of catalysts and reagents, and excellent tolerance for various functional groups, have emerged as versatile protocols for the late-stage aromatic halogenation of drugs, natural products, and peptides. By harnessing the versatility and selectivity of these catalysts and methodologies, synthetic chemists can unlock new possibilities in the synthesis of halogenated compounds, paving the way for the development of novel functional materials and biologically active molecules.

Phosphonium SF5 - Salts Derived from Sulfur Hexafluoride as Deoxyfluorination Reagents.

Sulfur based deoxyfluorination reagents are usually derived from the corrosive gas SF4. Herein, we report the synthesis and properties of an easily accessible phosphonium salt [(tmg)3PF]+SF5 - (1) which was obtained from the reaction of sulfur hexafluoride (SF6) with tris(tetramethylguanidinyl)phosphine. The performance of this crystalline SF5 - salt as a reagent in deoxyfluorination reactions was investigated together with a second SF5 - salt [(R1)3PF]+SF5 - (2) containing bulky substituents (R1=1,3-di-tert-butylimidazolidin-2-ylidenamino). Both reagents proved to be effective for the deoxyfluorination of various functional groups including alcohols, anhydrides, and amides.