Reaction Of Reagents Research Articles

Biasing Divergent Polycyclic Aromatic Hydrocarbon Oxidation Pathway by Solvent-Free Mechanochemistry.

Precise control in reaction selectivity is the goal in modern organic synthesis, and it has been widely studied throughout the synthetic community. In comparison, control of divergent reactivity of a given reagent under different reaction conditions is relatively less explored aspect of chemical selectivity. We herein report an unusual reaction between polycyclic aromatic hydrocarbons and periodic acid H5IO6 (1), where the product outcome is dictated by the choice of reaction conditions. That is, reactions under solution-based condition give preferentially C-H iodination products, while reactions under solvent-free mechanochemical condition provide C-H oxidation quinone products. Control experiments further indicated that the iodination product is not a reaction intermediate toward the oxidation product and vice versa. Mechanistic studies unveiled an in situ crystalline-to-crystalline phase change in 2 during ball-milling treatment, where we assigned it as a polymeric hydrogen-bond network of 1. We believe that this polymeric crystalline phase shields the more embedded electrophilic I═O group of 1 from C-H iodination and bias a divergent C-H oxidation pathway (with I═O) in the solid state. Collectively, this work demonstrates that mechanochemistry can be employed to completely switch a reaction pathway and unmask hidden reactivity of chemical reagents.

On matching and mismatching in protein chemistry

Post-translational protein editing methods that rely upon precise chemical alteration of sequence and hence function are of increasing utility. Whilst the role of proteins as chiral environments is functionally ubiquitous in their interaction with substrates or ligands, the influence of stereochemical ‘matching/mismatching’ effects upon the reactivity of chemical reagents designed for such editing is essentially unexplored. The reagent dibromohexanediamide (DBHDA) is a useful reagent for the chemical transformation of cysteine to dehydroalanine (Dha) in proteins and peptides. Differences in reactivities of the stereoisomers of DBHDA, if any, in different protein substrates are unknown. Here, we report synthetic access to these isomers and reveal apparent stereochemically ‘matched vs mismatched’ differences in reactivity, that, in principle, in the future might be exploited to expand the methods available for residue- and site-selective editing.

Transition‐Metal‐Catalyzed Direct Substitution of Alcohols in Aqueous Media

AbstractThe direct use of alcohols as the much greener and more sustainable alkylated reagents in substitution reactions is one of the emerging areas in green chemisty. However, owing to the poor leaving character of OH group, the direct substitution of alcohols is not an easy thing. Transition metal (TM) catalysis such as Pd‐catalyzed allylic/benzyl substitution and Ir‐catalyzed borrowing hydrogen provides efficient protocols for the direct substitution of alcohols, however, an organic solvent and servely anhydrous conditions are generally required. In recent decade, TM‐catalyzed direct substitution of alcohols in aqueous media was developed as a much greener alternative. In this review, the recent develpoments of this area are summarized. The activation mechanism of alcohols in aqueous reactions are emphatically discussed.

Peptide‐Hypervalent Iodine Reagent Chimeras: Enabling Peptide Functionalization and Macrocyclization**

AbstractHerein, we report a novel strategy for the modification of peptides based on the introduction of highly reactive hypervalent iodine reagents—ethynylbenziodoxolones (EBXs)—onto peptides. These peptide‐EBXs can be readily accessed, by both solution‐ and solid‐phase peptide synthesis (SPPS). They can be used to couple the peptide to other peptides or a protein through reaction with Cys, leading to thioalkynes in organic solvents and hypervalent iodine adducts in water buffer. Furthermore, a photocatalytic decarboxylative coupling to the C‐terminus of peptides was developed using an organic dye and was also successful in an intramolecular fashion, leading to macrocyclic peptides with unprecedented crosslinking. A rigid linear aryl alkyne linker was essential to achieve high affinity for Keap1 at the Nrf2 binding site with potential protein‐protein interaction inhibition.

Peptide-Hypervalent Iodine Reagent Chimeras: Enabling Peptide Functionalization and Macrocyclization.

Herein, we report a novel strategy for the modification of peptides based on the introduction of highly reactive hypervalent iodine reagents-ethynylbenziodoxolones (EBXs)-onto peptides. These peptide-EBXs can be readily accessed, by both solution- and solid-phase peptide synthesis (SPPS). They can be used to couple the peptide to other peptides or a protein through reaction with Cys, leading to thioalkynes in organic solvents and hypervalent iodine adducts in water buffer. Furthermore, a photocatalytic decarboxylative coupling to the C-terminus of peptides was developed using an organic dye and was also successful in an intramolecular fashion, leading to macrocyclic peptides with unprecedented crosslinking. A rigid linear aryl alkyne linker was essential to achieve high affinity for Keap1 at the Nrf2 binding site with potential protein-protein interaction inhibition.

Insights into the borohydride reduction of dialdehyde cellulose: the dilemma of competing reduction and β-elimination reactions

Borohydride reduction of dialdehyde cellulose (DAC) is a promising strategy to generate dialcohol cellulose as bio-based alternative to petroleum-based materials. However, the degradation of the polymer backbone according to β-elimination mechanisms limits the practical applications of the reaction. Therefore, we aimed at optimizing the process to suppress degradation reactions by varying reaction time, pH, and reagent stoichiometry. The degree of oxidation (DO) of the DAC intermediates significantly impacts the yields and molecular weights of the isolated dialcohol celluloses, with a “leveling-off” effect at higher DO values. Increasing the amount of sodium borohydride can minimize—but not entirely prevent—chain scissions. Lowering the pH value during reduction slows down the degradation but results in incomplete conversion of the aldehyde functionalities. Our study provides valuable insights into the consequences of side reactions during borohydride reduction of DAC as well as into chemistry and analysis of the dialdehyde cellulose/dialcohol cellulose system.Graphical abstractAbout a dilemma in cellulose chemistry: Dialcohol cellulose derived by periodate oxidation and subsequent borohydride reduction of cellulose has received increasing attention in the development of sustainable thermoplastic materials. The present study highlights the challenge of suppressing β-elimination and favoring the reduction pathway to optimize reaction conditions and minimize chain degradation.

Diethylenetriamine and serine as synergists used in FA/OII based alkaline solution to realize enhanced cleaning efficiency of the organic corrosion inhibitor

In industrial chemical mechanical polishing (CMP), 5-methyl benzotriazole (MBTA) as a substitute organic inhibitor of benzotriazole has shown great effect in low usage compared to other benzo derivatives. However, it also brings considerable challenges to subsequent post-CMP cleaning due to its hydrophobic property. In this work, diethylenetriamine (DETA) and serine were used as synergists in FA/OII-based alkaline solutions to achieve enhanced removal of MBTA. Contact angle and electrochemical tests proved the weak cleaning performance of FA/OII was generally improved after adding DETA or serine. Especially, 400 ppm serine displayed its superiority with the lowest contact angle and the highest corrosion current density of 24.2° and 1.023 μA/cm2. Then, static observation and X-ray photoelectron spectra analysis confirmed they could break Cu(I)-MBTA and form precipitates like DETA/serine-MBTA. Copper loss after cleaning was also measured by an atomic force microscope and the corresponding surface morphology still needed to be improved by adding proper surfactants. Finally, with the assistance of density functional theory calculation and molecular dynamic simulation, the active sites and reactivity of both reagents were concluded by comparing their intrinsic properties and interaction configurations. Serine turned out to work better than DETA with a lower interaction energy of − 724.83 Kcal/mol.

Preparation and Reactivity Study of a Versatile Trifluoromethylthiolating Agent: S-Trifluoromethyl Trifluoromethanesulfonothioate (TTST).

A novel, air and thermally stable, yet highly reactive trifluoromethylthiolating reagent, CF3SO2SCF3 (1), was prepared easily in one step from commercially inexpensive CF3SO2Na and Tf2O. 1 is a highly versatile and atom-efficient reagent that can generate one equivalent of CF3S+, two equivalents of CF3S-, or a combination of CF3S./CF3. species. Many high-yielding CF3S reactions of C, O, S, and N-nucleophiles were achieved, including the simple-step preparations of many reported CF3S reagents. 1 delivered a hitherto hard-to-synthesize ArSOCF3 that was followed by a novel CF3SII-rearrangement. Through Cu or TDAE/Ph3P combinations, 1 generated two equivalents of CF3S anion species, and the photo-catalyzed reactions of alkenes with 1 provided CF3/CF3S-containing products in high atom-efficiency.

Preparation and Reactivity Study of a Versatile Trifluoromethylthiolating Agent: S‐Trifluoromethyl Trifluoromethanesulfonothioate (TTST)

AbstractA novel, air and thermally stable, yet highly reactive trifluoromethylthiolating reagent, CF3SO2SCF3 (1), was prepared easily in one step from commercially inexpensive CF3SO2Na and Tf2O. 1 is a highly versatile and atom‐efficient reagent that can generate one equivalent of CF3S+, two equivalents of CF3S−, or a combination of CF3S⋅/CF3⋅ species. Many high‐yielding CF3S reactions of C, O, S, and N‐nucleophiles were achieved, including the simple‐step preparations of many reported CF3S reagents. 1 delivered a hitherto hard‐to‐synthesize ArOSCF3 that was followed by a novel CF3SII‐rearrangement. Through Cu or TDAE/Ph3P combinations, 1 generated two equivalents of CF3S anion species, and the photo‐catalyzed reactions of alkenes with 1 provided CF3/CF3S‐containing products in high atom‐efficiency.

Experimental hazardous risk investigation of energetic styphnic acid analytical reagent in calorimetric analysis

Analytical reagents identify and manage metal pollution, a major environmental issue. Regrettably, these compounds' safety concerns, especially when heated, have been neglected. This research examines the thermal hazard of the extremely reactive analytical reagent styphnic acid. Differential scanning calorimetry, thermogravimetric analysis, and accelerating rate calorimetry examined styphnic acid's thermodynamics. Thermogravimetric analysis showed weight loss reactions starting at 127 °C and peaking at 208 °C. Differential scanning calorimetry showed an endothermic peak at 176 °C. The accelerating rate calorimetry test showed that styphnic acid self-accelerates at 237 °C after 196.5 °C. Kissinger, Ozawa-Flynn-Wall, and Kissinger-Akahira-Sunose thermokinetic models calculated apparent activation energy from 131.677 to 155.718 kJ/mol. A nonlinear regression analysis showed that styphnic acid undergoes a two-step autocatalytic reaction during heat degradation. Thermal safety was assessed by measuring time to conversion limit, maximum rate, total energy release, self-accelerating decomposition temperature, and adiabatic temperature rise. Styphnic acid is less stable at higher temperatures and its thermal hazards depend on heating rate. The computed SADT was 109.04 °C, with alarm and control temperatures of 104.04 and 99.04 °C, respectively. The risk matrix analysis based on Tad and TMRad suggests reducing thermal instability. This study on styphnic acid's thermal risks and safe storage and transit during analytical applications is beneficial.

Rediscovering Cyanogen Gas for Organic Synthesis: Formation of 2-Cyanothiazole Derivatives.

The expeditious synthesis of an API building block, 2-cyanothiazole, from cyanogen gas and a readily available dithiane is reported. A previously undisclosed partially saturated intermediate is formed, which can be further functionalized and isolated by the acylation of the hydroxy group. Dehydration using trimethylsilyl chloride furnished 2-cyanothiazole, which could be further converted to the corresponding amidine. The sequence provided a 55% yield over 4 steps. We envision that this work will spark further interest in cyanogen gas as a reactive and cost-effective synthetic reagent.

W-Phos Ligand Enables Copper-Catalyzed Enantioselective Alkylation of N-Sulfonyl Ketimines with Grignard Reagents

Catalytic asymmetric addition of reactive Grignard reagents to ketimines poses a considerable challenge. Herein, a PNP-type W-Phos ligand developed recently by our group showed a unique effect toward this end, paving the way to a Cu(I)-catalyzed asymmetric alkylation reaction of N-sulfonyl ketimines, delivering optically active α-tertiary amines in high enantioselectivities. This catalytic protocol shows an unprecedented substrate scope with more than 80 examples, not only compatible with benzo five- and six-membered cyclic N-sulfonyl ketimines but also suitable for geometrically unstable (E or Z) acyclic N-sulfonyl ketimines. The application potential of the protocol is featured by the extensive presence of α-tertiary amines in natural products and pharmaceutical compounds and also demonstrated by downstream transformations with maintenance of the enantioselectivity.

Preparation of Supertough Polylactide/Polybutylene Succinate/Epoxidized Soybean Oil Bio-Blends by Chain Extension

Poly(lactic acid) (PLA) was toughened using ductile biodegradable poly(butylene succinate) (PBS) and biobased epoxidized soybean oil (ESO). A reactive reagent (Joncryl ADR 4370 S) was introduced for preparing reactive compatibilized bio-blends by melt-processing in situ. The compatibility, rheology, crystallization, mechanical properties, and microstructures of the PLA, PBS, and ESO bio-blends were measured using theoretical compatibility predication, Fourier transform infrared (FTIR) spectroscopy, dynamic mechanical analysis (DMA), dynamic rheological analysis, wide-angle X-ray diffraction (WAXD), mechanical tests, field-emission scanning electron microscopy (FESEM), and optical stereomicroscopy (OM). The introduction of 4370 S induced “graft copolymerization in situ” among PLA, PBS, and ESO and considerably improved the bio-blend compatibility. The PBS and PLA crystal structures were not altered, while the PBS crystallinity reduced in the bio-blends because of chain extensions among the components. The refined PBS particles and evenly distributed ESO drops in the PLA matrix were ascribed to enhanced adhesion and improved compatibility due to the “formation of graft copolymers in situ”. Owing to the combination of ESO and 4370 S, the supertough PLA and PBS bio-blends exhibited a tensile strain at break and notched impact strength above 300% and 30 kJ/m2, respectively.

An integrated digital polymerase chain reaction chip for multiplexed meat adulteration detection.

Meat adulteration detection is a common concern of consumers. Here, we proposed a multiplex digital polymerase chain reaction method and a low-cost device for meat adulteration detection. Using a polydimethylsiloxane microfluidic device, polymerase chain reaction reagents could be pump-free loaded into microchambers (40×40 chambers) automatically. Due to the independence of multiplex fluorescence channels, deoxyribonucleic acid templates extracted from different animal species could be distinguished by one test. In this paper, we designed primers and probes for four types of meat (beef, chicken, pork, and duck) and labeled each of the four fluorescent markers (hexachlorocyclohexane [HEX], 6-carboxyfluorescein [FAM], X-rhodamine [ROX], and cyanine dyes 5 [CY5]) on the probes. Specific detection and mixed detection experiments were performed on four types of meat, realizing a limit of detection of 3 copies/µL. A mixture of four different species can be detected by four independent fluorescence channels. The quantitative capability of this method is found to meet the requirements of meat adulteration detections. This method has great potential for point-of-care testing together with portable microscopy equipment.

Programmable Low-Pressure Chromatographic Sub-90 s Assay of Parabens in Cosmetics with Post-Column Chemiluminescence Detection

This work describes a new programmable low-pressure chromatography method with post-column chemiluminescence (CL) detection for the rapid and cost-effective determination of four parabens in cosmetic products. Elution of the target analytes was achieved using a programmable mobile phase prepared by implementing a linear solvent gradient protocol based on appropriate flow rate modulation of 2 MilliGAT pumps. A 5 mm monolithic C18 column was used to separate the parabens. Post-column reaction of the eluted parabens with an acidic Ce(IV)-rhodamine 6G (Rho 6G) medium was carried out by introducing a flow stream of the reactants into the column eluate. The light generated from the CL reaction was detected with a flow-through CL detector fabricated in-house. The whole sequence of operations (including sample injection, generation of the mobile phase, addition of the post-column reaction reagents and signal acquisition) was under full computer control. Various operational parameters (the mobile phase composition and gradient conditions, the CL reagents’ concentrations and flow rates and the length of the reaction coil) were studied. The method was validated and applied to the analysis of various cosmetic products. The proposed approach allows sub-90 s separation of the four parabens and their determination with a limit of quantification of 0.2 μg L−1 with a sample throughput of 24 samples h−1. In addition, the method is economical, makes use of low-cost low-pressure components, is fully automated and produces a low amount of waste.

Synthesis of an "all-in-one" nanotherapeutic platform for triple-amplification chemodynamic therapy of osteosarcoma

High recurrence rates after surgery and unacceptable side effects of chemotherapy and radiotherapy are challenges in the treatment of osteosarcoma (OS). Therefore, the development of nanoplatforms with combined tumor inhibition efficiency and fewer side effects is a promising strategy for the treatment of OS. In this paper, a biocompatible therapeutic nanoplatform (Fe-Zr@PDA@GOx) was constructed with a simple and efficient strategy for the treatment of OS. First, as an excellent Fenton reaction reagent, iron ions in the nanoplatform can generate highly toxic hydroxyl radicals (•OH) with hydrogen peroxide (H2O2) in the tumor microenvironment and induce tumor cell death. Then, the modification of polydopamine endows the nanoplatform with photothermal responsiveness, with a photothermal conversion efficiency of 28.0%. Importantly, the conversed heat by polydopamine both promotes the release of glucose oxidase (GOx) and increases the rate of the Fenton reaction. Furthermore, GOx-mediated starvation treatment (SDT) can also provide suitable reaction conditions and sufficient H2O2 to realize the amplification of chemodynamic therapy (CDT). Finally, the doping of Zr ions can interact with Fe to form dual active centers in the Fenton reaction and further accelerate the generation of •OH. Both in vitro and in vivo experiments reveal the synergistic photothermal/CDT/SDT anti-tumor effect. Therefore, this work provides an effective strategy for the treatment of OS.

TELLURO-INDUCED CYCLISATION 2-(BUT-2-ENYLTHIO)QUINOLINECARBALDEHYDE AND QUINOLINE-4-ONE

Aryltellurium trichlorides have proven themselves as good cyclizing reagents in electrophilic intramolecular cyclization reactions, mainly of propenyl derivatives of heterocycles. On the other hand, information on the use of butenyl derivatives in reactions with p-alkoxyphenyltellurtrichlorides is limited. In this work, the regioselectivity of the process of electrophilic intramolecular cyclization of but-2-enyl thioethers of quinoline-3carbaldehyde and quinazolin-4-one with p-methoxyphenyltellurium trichloride was investigated.
 It was established that, as a result of the tellurium-induced cyclization with p-methoxyphenyltellurium trichloride of but-2-enyl thioethers of quinoline and quinazoline, angular tricyclic chlorides – 2-(dichloro(4-methoxyphenyl)-tellanyl)-1-methyl-5-formyl-2,3- dihydro-1H-[1,3]thiazino[3,2-a]quinolin-11-ium and 2-(dichloro(4-methoxyphenyl)-tellanyl)-1-methyl-6-oxo-5-phenyl-2, 3,5,6-tetrahydro-1H-[1,3]thiazino[3,2-a]quinazolin-11-ium, respectively, with an annealed six-membered ring in the form of complexes with p-methoxyphenyltellurium trichloride. Optimal conditions for the electrophilic intramolecular cyclization reaction were selected.
 Keywords: electrophilic heterocyclization; p-methoxyphenyltellurium trichloride; organotellurium compounds; chloride 2-(dichloro(4-methoxyphenyl)-tellanyl)-1-methyl-5-formyl-2,3-dihydro-1H-[1,3]thiazino[3,2 -a]quinolin-11-ium, chloride 2-(dichloro(4-methoxyphenyl)-tellanyl)-1-methyl-6-oxo-5-phenyl-2,3,5,6-tetrahydro-1H-[1,3]thiazino[3,2-a]quinazolin-11-ium

Degradation of Azo Dye by Ultrasound in Rotating Flow Field

Azo dyes such as Congo red can easily cause cancer when they come into contact or are absorbed by the human body, so it is urgent to find a fast and simple method for degrading Congo red. In order to better achieve this research goal, an ultrasonic method was used to degrade Congo red solution in a rotating flow field. The concentration of hydroxyl radical in the solution was significantly increased under the action of ultrasonic cavitation, chemical action of zero valent iron, and mechanochemistry. Under the strong oxidation of hydroxyl radical and the reduction of nano zero valent iron peeled off in the reaction process, the reaction speed is significantly accelerated and should promote the reaction. The effect of increasing stirring and adding iron powder particles on ultrasonic cavitation was studied by numerical simulation, and the yield of hydroxyl radical in the system was measured by fluorescence analysis. The experimental results show that, first, the rotating field formed by mixing increases the uniformity of ultrasonic sound field distribution and the amplitude of sound pressure, and it improves the cavitation intensity. In the effective dispersion area, the strong ultrasonic wave can form a temporary high-energy microenvironment in the suspension through cavitation, generate high strength shockwaves and micro jets, and thus significantly deagglomerate the iron powder aggregates. The addition of iron powder particles then provides a complementary Fenton reagent for the degradation reaction. The concentration of hydroxyl radicals in the solution was significantly increased by the synergy of the two actions. The degradation rate of Congo red reached more than 99% after 30 min of reaction.

Tropylium Ion, an Intriguing Moiety in Organic Chemistry.

The tropylium ion is a non-benzenoid aromatic species that works as a catalyst. This chemical entity brings about a large number of organic transformations, such as hydroboration reactions, ring contraction, the trapping of enolates, oxidative functionalization, metathesis, insertion, acetalization, and trans-acetalization reactions. The tropylium ion also functions as a coupling reagent in synthetic reactions. This cation's versatility can be seen in its role in the synthesis of macrocyclic compounds and cage structures. Bearing a charge, the tropylium ion is more prone to nucleophilic/electrophilic reactions than neutral benzenoid equivalents. This ability enables it to assist in a variety of chemical reactions. The primary purpose of using tropylium ions in organic reactions is to replace transition metals in catalysis chemistry. It outperforms transition-metal catalysts in terms of its yield, moderate conditions, non-toxic byproducts, functional group tolerance, selectivity, and ease of handling. Furthermore, the tropylium ion is simple to synthesize in the laboratory. The current review incorporates the literature reported from 1950 to 2021; however, the last two decades have witnessed a phenomenal upsurge in the utilization of the tropylium ion in the facilitation of organic conversions. The importance of the tropylium ion as an environmentally safe catalyst in synthesis and a comprehensive summary of some important reactions catalyzed via tropylium cations are described.

Synthesis of Aminoalkyl Sclareolide Derivatives and Antifungal Activity Studies.

Sclareolide was developed as an efficient C-nucleophilic reagent for an asymmetric Mannich addition reaction with a series of N-tert-butylsulfinyl aldimines. The Mannich reaction was carried out under mild conditions, affording the corresponding aminoalkyl sclareolide derivatives with up to 98% yield and 98:2:0:0 diastereoselectivity. Furthermore, the reaction could be performed on a gram scale without any reduction in yield and diastereoselectivity. Additionally, deprotection of the obtained Mannich addition products to give the target sclareolide derivatives bearing a free N-H group was demonstrated. In addition, target compounds 4-6 were subjected to an antifungal assay in vitro, which showed considerable antifungal activity against forest pathogenic fungi.