Mild Reagent Research Articles

Synthesis of 6-(Fluoromethyl)-19-norcholest-5(10)-en-3-ol, a Fluorinated Analogue of NP-59, using the Mild Fluorinating Reagent, TBAF(Pinacol)2

For 45 years, efforts to prepare a fluorinated analogue of the scintiscanning/SPECT agent 6-(iodomethyl)-19-norcholest-5(10)-en-3-ol (NP-59) for development of a PET imaging agent have failed due to undesired elimination reactions and unexpected rearrangements observed­ while utilizing a wide variety of fluorinating conditions (e.g., cesium­ fluoride, silver fluoride, (2-chloro-1,1,2-trifluoroethyl)diethylamine (FAR), diethylaminosulfur trifluoride (DAST), and hexa­fluoro­propene diethylamine FPA). Herein, we report the full synthesis of NP-59, followed by the four-step synthesis of 6-(fluoromethyl)-19-norcholest-5(10)-en-3-ol (FNP-59) using a recently developed mild fluorinating reagent, less prone to producing elimination reactions in the preparation of primary fluorides, TBAF(pinacol)2, with an overall yield of 16% (four steps). Also included is an evaluation of the TBAF(pinacol)2 reagent on eight test substrates to investigate its scope.

Selective Protection of Secondary Alcohols by Using Formic Acid as a Mild and Efficient Deprotection Reagent for Primary tert-Butyldimethylsilyl Ethers

A mild, efficient, and environmentally friendly method for the selective protection of secondary hydroxyl groups is described. The method involves the protection of both primary and secondary hydroxyl groups as tert-butyldimethylsilyl (TBDMS) ethers and selective deprotection of the primary TBDMS group with formic acid in acetonitrile/water. The rates of desilylation of primary and secondary TBDMS ethers by different concentrations of formic acid are determined. Formic acid of 5–20% concentration is found to selectively deprotect primary TBDMS ethers while keeping more than 95% of their secondary counterparts intact.

Introducing Oxo-Phenylacetyl (OPAc) as a Protecting Group for Carbohydrates.

A series of oxo-phenylacetyl (OPAc)-protected saccharides, with divergent base sensitivity profiles against benzoyl (Bz) and acetyl (Ac) were synthesized, and KHSO5/AcCl in methanol was identified as an easy, mild, selective, and efficient deprotecting reagent for their removal in the perspective of carbohydrate synthesis. Timely monitoring of AcCl reagent was supportive in both sequential and simultaneous deprotecting of OPAc, Bz, and Ac. The salient feature of our method is the orthogonal stability against different groups, its ease to generate different valuable acceptors using designed monosaccharides, and use of OPAc as a glycosyl donar.

Clean Preparation of Quinolin-2-yl Substituted Ureas in Water

An environmentally-friendly method for the clean preparation of various quinolin-2-yl substituted ureas in water under mild and toxic reagent-, base-, and organic solvent-free conditions was established. In the large-scale synthesis, the products could be rapidly collected via simple filtration and washing with ethanol. The usage of readily available raw materials, 100% atom economy, high yield, and excellent regioselectivity enhanced the practicability of this protocol.

One-step rapid synthesis of fluorescent silicon nanodots for a hydrogen peroxide-related sensitive and versatile assay based on the inner filter effect.

In this work, a kind of environment-friendly and water-dispersible silicon nanodot (SiND) was rapidly synthesized by using the mild reagents (3-aminopropyl)triethoxysilane (APTES) and glucose. It was found that the fluorescence of the as-prepared SiNDs can be quenched obviously by permanganate due to the inner filter effect. Inspired by this finding, a novel fluorescent sensor for sensitive detection of hydrogen peroxide (H2O2) was developed through the oxidation-reduction reaction between permanganate and H2O2. The detection limit of H2O2 is down to 2.8 nM. Since H2O2 is an important molecule and involved in various studies, this sensor could be applied in various H2O2-related biological analyses. As a proof-of-application demonstration, a sensitive biosensor for glucose detection was constructed through the catalytic oxidation of glucose to generate H2O2. The as-constructed sensor showed good linear response to glucose over the range from 0.16 to 16 μM with a detection limit of 0.11 μM. Moreover, the biosensor can be readily extended to other sensors for different targets, which indicates the broad applications of the proposed sensing strategy in biomedical analysis.

SuFEx-based strategies for the preparation of functional particles and cation exchange resins

A predictable and reproducible number of sulfuric acid sites have been achieved for cation exchange resins by employing a mild SuFEx-based reagent system to effect the hydrolysis of fluorosulfonated polymer beads. The resultant poly(hydrogen sulfate) beads effectively demonstrate their utility as cation exchange resins in ion-capture experiments. Furthermore, their polyfluorosulfonated precursors have also proven to be suitable substrates for traditional SuFEx-type click reactions in both small molecule and protein immobilization applications.

Silica-supported ceric ammonium nitrate (CAN): a simple, mild and solid-supported reagent for quickest oxidative aromatization of Hantzsch 1,4-dihydropyridines

An efficient and environmentally benign methodology for the oxidative aromatization of 1,4-dihydropyridines to their corresponding pyridine derivatives is developed. The oxidative aromatization of 1,4-dihydropyridines was explored using silica-supported ceric ammonium nitrate as catalyst in CH3CN with or without sonication at room temperature. This supported catalyst acts as a more efficient oxidising reagent and offers several advantages over other reported reagents in terms of reaction time and yields. The supported reagent is found to be more efficient and selective when compared with its unsupported form. The Belousov–Zhabotinskii reaction was not observed in present reaction. The dealkylation observed in case of 4-n-alkyl/n-alkenyl with other oxidising agents is also not observed in the present case.

A Class of N–O-Type Oxidants To Access High-Valent Palladium Species

This article presents a new class of mild reagents that is capable of oxidizing palladacycle(II) complexes to high-valent palladium species, promoting the formation of C–N bonds in stoichiometric a...

N-Acyl-5,5-dimethylhydantoin, a New Mild Acyl-Transfer Reagent in Pd Catalysis: Highly Efficient Synthesis of Functionalized Ketones

The palladium-catalyzed Suzuki–Miyaura cross-coupling of N-acyl-5,5-dimethylhydantoins with arylboronic acids has been developed via selective amides C–N bond cleavage. The new reagent is commercially available and air-/moisture-stable, and it offers a variety of ketones in good yields through Suzuki coupling under mild conditions (up to 95%).

A new strategy to efficiently cleave and form C-H bonds using proton-coupled electron transfer.

Oxidative activation and reductive formation of C-H bonds are crucial in many chemical, industrial, and biological processes. Reported here is a new strategy for these transformations, using a form of proton-coupled electron transfer (PCET): intermolecular electron transfer coupled to intramolecular proton transfer with an appropriately placed cofactor. In a fluorenyl-benzoate, the positioned carboxylate facilitates rapid cleavage of a benzylic C-H bond upon reaction with even weak 1e- oxidants, for example, decamethylferrocenium. Mechanistic studies establish that the proton and electron transfer to disparate sites in a single concerted kinetic step, via multi-site concerted proton-electron transfer. This work represents a new elementary reaction step available to C-H bonds. This strategy is extended to reductive formation of C-H bonds in two systems. Molecular design considerations and possible utility in synthetic and enzymatic systems are discussed.

O-Xylylene Bis(Triethyl Ammonium Tribromide) as a Mild and Recyclable Reagent for Rapid and Regioselective Bromination of Anilines and Phenols

o-Xylylene Bis(Triethyl Ammonium Tribromide) as a Mild and Recyclable Reagent for Rapid and Regioselective Bromination of Anilines and Phenols

Reduction Rate of 1-Phenyl Phospholane 1-Oxide Enhanced by Silanol Byproducts: Comprehensive DFT Study and Kinetic Modeling Linked to Reagent Design.

Important stoichiometric transformations like Wittig and Appel reactions have been implemented in a catalytic fashion in the past decade. The phosphine oxide generated in situ can be reintroduced as phosphine into the catalytic cycle using mild and selective silane reagents (redox-driven catalysis). While the field of experimental investigation has been fully expanding in the past decade, theoretical studies are still sparse. In this present work, density functional theory (DFT) has been used to characterize the free energy surfaces of the reduction of 1-phenyl phospholane 1-oxide with four different silanes. Found stationary points have been studied in-depth to highlight mechanistic peculiarities, like the effect of substituents at the silicon center and the parallel and competitive reactivity between the precursor silanes and their semioxidized byproducts. Calculated thermodynamic parameters in combination with "real" values for concentrations have been used in the formulation of rate equations for simple bimolecular and monomolecular steps of the mechanism. The deterministic integration concentrations versus time of such rate equations led to a realistic description of the systems under study and paved the way to strategic and rational design of new silanes with increased reactivity.

Synthesis of 5,6-dehydrokawain and some fluorinated analogues

ABSTRACTAn efficient methodology for the synthesis of 6-styrenylpyrone in a four-step sequence is reported. The reactions were performed under catalyst-free conditions with mild and affordable reagents to produce 5,6-dehydrokawain and fluorinated derivatives in good to excellent overall yields (72–86%) on a multigram scale. Two novel difluorinated derivatives are reported here for the first time.

Theoretical investigation of the superoxide anion free radical elimination by quercetin–metal complexes

The elimination of superoxide anion free radical O 2 ·− by the complexes of quercetin and physiological metal ions has been investigated theoretically. It turns out that Ca(II) and Zn(II) quercetin complexes are mild and efficient reagent on O 2 ·− fixing, and Fe(II) and Ni(II) quercetin complexes are excellent reagent on O 2 ·− elimination, and Cu(II) and Co(II) quercetin complexes are mainly no effect on O 2 ·− , which is consistent with some experiments, and Cu(I) and Co(I) complexes are active on O 2 ·− elimination on some sites of –OH. Some metal ion complexes herein only have one active center on metal ion itself, and none of their OH sites is active on O 2 ·− fixing such as Cr(III) and Fe(III) and Mn(II). The possible transition states of the interaction between quercetin molecule and O 2 ·− on different OH sites also have been investigated. We get the similar transition states for different OH sites, the activation energy is heavily high from reactants to transition states, and the transition states are near to the final products, which indicates that though the quercetin molecule can eliminate O 2 ·− , metal ions quercetin complexes are quite good at it, and some complexes can eliminate more than one O 2 ·− at the same time, which may be the potential effective medicines for O 2 ·− elimination to protect β cells from O 2 ·− attacking and helpful for diabetics and other relative diseases.

Fatty acid methyl ester production via ferric sulfate catalyzed interesterification

While biodiesel production is on the rise, so too is the production of the low-value product, glycerol. Interesterification is an alternative reaction that produces fatty acid methyl esters (FAME) and avoids the production of glycerol. In this work, ferric sulfate is used as a potential heterogeneous catalyst for interesterification of model triglyceride, triolein, using methyl acetate. Reaction conditions were optimized by varying reaction temperature, methyl acetate to oil mole ratio (MAOMR), catalyst loading, as well as FAME as co-solvents. Additionally, this work also evaluated the effect of typical triglyceride feedstock contaminants, water and free fatty acids (FFA). The optimal reaction conditions were found to be 120 °C, 20:1 MAOMR and a mass loading of 7.5% ferric sulfate with yields up to 83%. The addition of FAME and water in the system is shown to have potential benefits on reaction rate and yield while FFA addition had mildly negative impacts on initial reaction rate. The results in this work show relatively high yields at mild temperatures and reagents loadings and could be a promising means of alternative FAME production.

Determination and geochemical implication of multiple series of long-chain oxygen-bearing compounds trapped in kerogen in the Lucaogou Formation, Santanghu Basin, NW China

Studies of occluded oxygen-bearing compounds inside kerogen are scarce, although such studies are important in understanding early-stage transformation of organic matter. A relatively low-maturity kerogen from the late Permian mudstone of the Lucaogou Formation of the Santanghu Basin, northwestern China, was successively extracted with n-hexane, acetone and dichloromethane to release the adsorbed components, and the extracted kerogen was treated with a mild oxidation reagent H2O2 to release the occluded components. Gas chromatography–mass spectrometry analysis of the adsorbed and occluded components revealed a suite of oxygen-bearing compounds, including n-alkan-2-ones, n-aldehydes and fatty acid methyl esters. The n-alkan-2-ones were mainly detected in the adsorbed fraction and n-aldehydes in the occluded component. Comparison of the long-chain oxygen-bearing compound distributions and their individual stable carbon isotope characteristics both suggest that the oxygen-bearing compounds released by H2O2 treatment were occluded in the kerogen. The shorter-chain (C15 to C19) occluded n-aldehydes reflected similar isotopic distribution trends to the adsorbed n-alkan-2-ones, and the δ13C values of the mid-length (C21 to C25) occluded n-aldehydes were much closer to the adsorbed n-alkanes. Bacterially mediated methylation and decarbonylation of the n-aldehydes during kerogen formation may be important source(s) of n-alkan-2-ones and n-alkanes, respectively. The mid-chain ketones mainly originated from hydrothermal alteration of n-alkanes after kerogen formation. Uplift of the Lucaogou Formation in the Yuejingou section allowed surface-enhanced aerobic reactions.

Diastereoselective conjugate addition/cyclization/bromination: Access to four stereocenters in a single step

A stereoselective tandem conjugate addition reaction with a chiral amine-derived nucleophile is reported in which the enolate intermediate is quenched with 1,2-dibromotetrachloroethane as a mild brominating reagent. X-ray analysis of a subsequent derivative was used to prove the configuration at each of the four newly formed stereocenters. The resulting α-bromoester underwent selective transesterification catalyzed by mild base to allow selective manipulation of the two ester groups of the product.

Palladium-Catalyzed Reductive Coupling Reaction of Terminal Alkynes with Aryl Iodides Utilizing Hafnocene Difluoride as a Hafnium Hydride Precursor Leading to trans-Alkenes.

Herein, we describe a reductive cross-coupling of alkynes and aryl iodides by using a novel catalytic system composed of a catalytic amount of palladium dichloride and a promoter precursor, hafnocene difluoride (Cp2 HfF2 , Cp=cyclopentadienyl anion), in the presence of a mild reducing reagent, a hydrosilane, leading to a one-pot preparation of trans-alkenes. In this process, a series of coupling reactions efficiently proceeds through the following three steps: (i) an initial formation of hafnocene hydride from hafnocene difluoride and the hydrosilane, (ii) a subsequent hydrohafnation toward alkynes, and (iii) a final transmetalation of the alkenyl hafnium species to a palladium complex. This reductive coupling could be chemoselectively applied to the preparation of trans-alkenes with various functional groups, such as an alkyl group, a halogen, an ester, a nitro group, a heterocycle, a boronic ester, and an internal alkyne.

Ultrasonically assisted extraction of calcium and ash from char

This study characterized and removed calcium and ash content from char to improve the chemical quality of char as reductant for titanium smelting application. Calcium in char can be classified in two parts: mineral matter and cationic metals associated with organic matrix. Virgin and chemically treated char was characterized by using ISO 1171, wet chemistry methods, ISO 19579, XRF, and B.E.T. methods. In this present work, demineralization of char with mild chemical leachants such as acetic acid, citric acid, gluconic acid and Ethylene Diamine Tetra Acetic acid with three different ultrasonic power input (150 W, 270 W and 300 W) and semi-dual frequency of 40 kHz tank was investigated. Actual power dissipated into the system was calculated from the calorimetric measurement. An optimum set of process parameters are identified and validated. The ultrasound technology was compared with soaking technology to determine the efficiency of ultrasound system for the removal of calcium. The removal of calcium was exponentially higher with ultrasonic treatment than without it. Results revealed that mild chemical reagents do not harm the carbon content of char. It is evident from the results that amongst the leachants used; acetic and citric acid has caused significant removal of mineral phases.

Dibromomalononitrile-potassium bromide complex as a mild bromination and oxidation reagent for the synthesis of mono-, di- and trimethoxyphenyl bromopyridines

The synthesis of mono-, di- and trimethoxyphenyl bromopyridines using the dibromomalononitrile-potassium bromide complex as a mild bromination and oxidation reagent is described.