Nucleophilic Displacement Reactions Research Articles

Nucleophilic Displacement Reactions of Silver-Based Metal-Organic Chalcogenolates.

We report nucleophilic displacement reactions that can increase the dimensionality or coordination number of silver-based metal-organic chalcogenolates (MOChas). MOChas are crystalline ensembles containing one-dimensional (1D) or two-dimensional (2D) inorganic topologies with structures and properties defined by the choice of metal, chalcogen, and ligand. MOChas can be readily prepared from a variety of small-molecule ligands and metals or metal ions. Although MOChas offer ligand diversity, most reported examples use relatively small ligands, typically involving short alkyl chains, aryl rings, or molecular cages. This is because larger, more complex molecules often yield poor product morphologies with indeterminate structures. In this study, we overcame this limitation by employing a ligand exchange strategy whereby a 1D MOCha, silver(I) methyl 2-mercaptobenzoate (2MMB), is used as a silver source for preparing 2D examples. The reaction proceeds generally toward products composed of the stronger nucleophile. We show that the reaction prefers displacing 1D topologies to yield 2D ones and replacing thiolates with selenolates. We performed a study to characterize the mechanism by which organic chalcogenols and dichalcogenides exchange with MOChas. The collected data and product analysis support a proposed mechanism of nucleophilic substitution, explaining how both organic chalcogenols and dichalcogenides can displace ligands in MOChas. This work provides a new synthetic route that will enable the preparation of more elaborate MOChas and heterostructures thereof. This approach enabled the preparation of previously inaccessible oligophenyl MOChas, which were successfully solved via small-molecule serial femtosecond crystallography (smSFX) at the SPring-8 Ångström Compact Free Electron LAser (SACLA) facility.

Chemo- and Regioselective Demethylation of 2-Bromo-α-resorcylic Acid Derivatives Using Alkylthiolate Salts

AbstractWe report here the chemo- and regioselective demethylation of 2-bromo-3,5-dimethoxy-α-resorcylic acid esters by a thiolate nucleophilic displacement reaction. Optimized conditions facilitate yields up to 93% for o-bromo-selective demethylation of diverse ester derivatives of dimethoxy 2-bromo-α-resorcylic acid. Our results highlight a new, efficient, and reliable demethylation reagent, as well as a useful steric bias directing strategy.

Photochemical Wolff Rearrangement Initiated Generation and Subsequent α-Chlorination of C1 Ammonium Enolates.

The enantioselective synthesis of α-chlorinated carboxylic acid esters with er up to 99:1 and yields up to 82% was achieved via a one-pot multistep protocol starting from α-diazoketones. This process proceeds via a photochemical Wolff rearrangement, trapping of the generated ketene with a chiral Lewis base catalyst, subsequent enantioselective α-chlorination, and a final nucleophilic displacement of the bound catalyst. The obtained products were successfully utilized for stereospecific nucleophilic displacement reactions with N- and S-nucleophiles.

Substituted naphthoxy-phthalonitrile derivatives: Synthesis, substituent effects, DFT, TD-DFT Calculations, antimicrobial properties and DNA interaction studies

Herein, substituted-naphthol derivatives 4a–e were synthesized in two steps, namely the Diels Alder cycloaddition and Cu-catalyzed aromatization reactions, respectively. Then, pththalonitrile derivatives 7–12 have been prepared by a nucleophilic displacement reaction of 3-nitrophthalonitrile with the naphthol derivatives 4a-e, 5 and, obtained in excellent yields. Structural characterization of the compounds was identified by different spectroscopic techniques. Antimicrobial properties of the synthesized compounds were determined by the microdilution procedure against Gram-positive, Gram-negative bacteria, and yeast. Furthermore, the DNA interaction of the compounds were determined by gel electrophoresis. One of the most prominent findings is that compounds 9 and 10 have more inhibitory effects on Gram-positive bacteria than Gram-negative bacteria. These compounds especially exhibited the highest antibacterial potency against S. aureus (625 µg/mL) among Gram-positive bacteria. According to the plasmid DNA interaction results, the synthesized compounds caused changes in the structure and mobility of the plasmid DNA. Then, geometry optimizations and frequency calculations were conducted at B3LYP/6–311 G(d,p) level of DFT, and optimized structures were used for further analyses. The NBO results revealed that the π→π * and n→π * interactions were greatly contributed to lowering the stabilization energy of all compounds (7–12). FMO energy analyses showed that compound 9 has the biggest electrodonating power.

Recent Advances in the Synthesis of 5'-deoxynucleoside Phosphonate Analogs.

The present review focuses on the synthesis of cyclic 5'-deoxynucleoside phosphonate analogs. The formation of various phosphonate alkyl moieties is accomplished through (i) Wittig (or HWE) type condensation to the nucleoside aldehyde moiety; (ii) nucleophilic displacement reaction using phosphonate anion or Lewis acid; (iii) Arbuzov reaction; (iv) olefin cross-metathesis between vinyl phosphonates and vinylated nucleosides; and (v) radical reaction and Pd catalyzed alkyne. For the coupling of nucleobases with cyclic moieties, the Mitsunobu reaction and Sonogashira-type cross-coupling are usually applied. For the coupling of furanose moieties with nucleobases, Vorbrüggentype condensation is generally applied. Addition reactions mediated by selenium ions are mainly applied for the coupling of carbocyclic moieties. Their biological activity results have been summarized.

Electrophilic and nucleophilic displacement reactions at the bridgehead borons of tris(pyridyl)borate scorpionate complexes.

Although a wide variety of boron-based "scorpionate" ligands have been implemented, a modular route that offers facile access to different substitution patterns at boron has yet to be developed. Here, we demonstrate new reactivity patterns at the bridgehead positions of a ruthenium tris(pyrid-2-yl)borate complex that allow for facile tuning of steric and electronic properties.

From Stoichiometric Reagents to Catalytic Partners: Selenonium Salts as Alkylating Agents for Nucleophilic Displacement Reactions in Water

AbstractThe ability of chalcogenium salts to transfer an electrophilic moiety to a given nucleophile is well known. However, up to date, these reagents have been used in stoichiometric quantities, producing a substantial amount of waste as byproducts of the reaction. In this report, we disclose further investigation of selenonium salts as S‐adenosyl‐L‐methionine (SAM) surrogates for the alkylation of nucleophiles in aqueous solutions. Most importantly, we were able to convert the stoichiometric process to a catalytic system employing as little as 10 mol % of selenides to accelerate the reaction between benzyl bromide and other alkylating agents with sodium cyanide in water. Probe experiments including 77Se NMR and HRMS of the reaction mixture have unequivocally shown the presence of the selenonium salt in the reaction mixture.magnified image

Oxidation of amines and their derivatives with persulfate without activation: Impact of mineral oxides and stoichiometric efficiency

Persulfate (PS; peroxydisulfate and peroxymonosulfate) activation on aquifer materials via a single-electron chain reaction can generate various reactive oxygen species (ROS) for aqueous contaminant degradation by in situ chemical oxidation (ISCO). However, this process may be altered when amino compounds (AMCs) are present in the groundwater due to their rapid reaction with PS without activation. In this study, we investigate these reaction processes by employing a series of probe AMCs. The nucleophilic displacement and polymerization reactions of AMCs with PS in water are enhanced by deprotonation or electron-donating substitutions on the AMCs, and the obtained rate constants are 2–4 orders of magnitude higher than those of phenolic or nitro compounds. In addition, the presence of mineral oxides changes both the oxidation rates and stoichiometric efficiency (η) of the AMCs because the oxides compete with AMCs to interact with PS in a low-efficiency and heterogeneous manner. Unlike electrophilic pollutants such as nitrobenzene, the higher reactivity of PS with nucleophilic AMCs compared with mineral oxides results in the dominance of heterolytic PS decomposition via two-electron oxidation. On this basis, we can predict the value of η for PS in this complicated heterogeneous system using the property-related parameters (RM) of mineral oxides and Hammett constants (σ+) of AMCs. This study highlights the overestimation of η for AMCs as the specific contaminants in persulfate-based ISCO. Moreover, the coexistence of AMCs as nucleophilic agents contributes to natural oxidant demand, which may impact the remediation of contaminated groundwater and oxidant stoichiometry.

Determination of the Mechanism of Nucleophilic Reaction of Fenitrothion Using Substituted Phenoxide Nucleophiles in Aqueous Media

The mechanism of the nucleophilic displacement reaction at the phosphorus centre of organophosphates was determined. Phenoxide nucleophiles were reacted with fenitrothion (O,O-dimethyl O-(3-methyl-4-nitrophenyl) phosphorothioate) in water at 25oC and pseudo-first order rate constant measurements taken. Second-order rate constant (kNuc) was determined for the different concentrations of nucleophiles while the second-order rate constant (klg) for the investigation of 2,4-dichlorophenoxide ion with and series of aryl phosphorothioate esters was also determined. Linear free energy relationship was further determined using the Brϕnsted-type plot. The plots are linear over a range of pKaNuc of 7.15-11.10 that straddles the pKa of the leaving 3-methyl-4-nitrophenoxide ion (pKa = 7.20) with statistically acceptable linear correlations (R2 = 0.987) and (R2 = 0.980). The linearity in the traditional Brϕnsted-type plots shows the sensitivity of the nucleophilic displacement to the basicity of the nucleophiles and hence is consistent with a single transition-state mechanism whose barrier to decomposition is low hence concerted. Analysis of the values of βNuc, βLg and βeq (0.734) with the effective charge distribution in the transition state shows that it has no positive character. The Leffler index presents bond formation being slightly ahead of bond rupture.

Fast Fluorine-18 labeling and preclinical evaluation of novel Mucin1 and its Folate hybrid peptide conjugate for targeting breast carcinoma

BackgroundThere is a need to develop new and more potent radiofluorinated peptide and their hybrid conjugates for multiple-receptors targeting properties that overexpress on many cancers.MethodsWe have synthesized MUC1-[18F] SFB and MUC1-FA-[18F] SFB hybrid conjugates using a convenient and one-step nucleophilic displacement reaction. In vitro cell binding and in vivo evaluation in animals were performed to determine the potential of these radiolabeled compounds.ResultsRadiochemical yields for MUC1-[18F] SFB and MUC1-FA-[18F] SFB conjugates were greater than 70% in less than 30 min synthesis time. Radiochemical purities were greater than 97% without HPLC purification, which makes these approaches amenable to automation. In vitro studies on MCF7 breast cancer cells showed that the significant amounts of the radiofluorinated conjugates were associated with cell fractions and held good affinity and specificity for MCF7 cells. In vivo characterization in Balb/c mice revealed rapid blood clearance with excretion predominantly by urinary as well as hepatobiliary systems for MUC1-[18F] SFB and MUC1-FA-[18F] SFB, respectively.Biodistribution in SCID mice bearing MCF7 xenografts, demonstrated excellent tumor uptake (12% ID/g) and favorable kinetics for MUC1-FA-[18F] SFB over MUC1-[18F]SFB. The tumor uptake was blocked by the excess co-injection of cold peptides suggesting the receptor-mediated process.ConclusionInitial PET/CT imaging of SCID mice with MCF7 xenografts, confirmed these observations. These results demonstrate that MUC1-FA-[18F] SFB may be a useful PET imaging probe for breast cancer detection and monitoring tumor response to the treatment.

Nucleophilic Displacement Reaction on Tosyl Cellulose by L-Methionine to the Synthesis of Novel Water-Soluble Cellulose Derivative and Its Antibacterial Activity

A novel ampholytic cellulose derivative, cellulose-L-methionine, has been synthesized by means of an esterification reaction of microcrystalline cellulose with tosyl chloride (p-TsCl) in DMAc/LiCl (8%) at 8°C that was followed by nucleophilic displacement (SN) of the tosyl group by the L-methionine amino acid. The resulting structure of cellulose-L-methionine has been characterized by elemental analysis (CHNSO), Fourier-transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H-NMR), and scanning electron microscopy (SEM). The antibacterial activity of the synthesized product was screened against Gram-positive and Gram-negative microbial strains such as Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, by the agar well diffusion method, and compared with commercial antibiotics such as ampicillin and chloramphenicol. It was found that antibacterial experiment revealed excellent antibacterial activity of the cellulose-methionine with respect to a minimal inhibitory concentration (MIC) reference.

Novel peripherally substituted metal-free, zinc (II), and cobalt (II) phthalocyanines with 1,1’-thiobis(2-napthol) and additional tetraphthalonitrile groups: Synthesis, aggregation behavior, electrochemical redox and electrocatalytic oxygen reducing properties

Novel phthalocyanines containing only 1,1′-thiobis(2-napthol) groups or 1,1′-thiobis(2-napthol) and phthalonitrile groups at peripheral positions were prepared by nucleophilic displacement reaction through cyclotetramerization of phthalonitrile derivatives, benzo[b]dinaphtho[1,2-h:2′,1′-e][1,4,7] dioxathionine-5,6-dicarbonitrile and 4,4′-[thiobis(naphthalene-1,2-diyloxy)]diphthalonitrile in penthanol. The aggregation tendencies and electrochemical redox properties of all phthalocyanines were investigated on the basis of central metal, solvent medium and subsituent effects, using UV-Vis spectral and classical electroanalytical techniques. The compounds exhibited metal-and/or phthalocyanine ring-based electron transfer processes which were coupled by distinct spectral changes and thus, net color transformations pointing out the possibility for their usage in electrochromic applications. Furthermore, remarkable enhancement in catalytic activity towards oxygen reduction and high tolerance to methanol during this reaction have been observed when the zinc (II) or 2H center was replaced with cobalt (II).

Elucidation of Selectivity for Silver Ion Based on Metal-Induced H-Type Aggregation of Fluorescent Receptor.

In present work, a new substituted phthalonitrile derivative was prepared by the nucleophilic displacement reaction and then highly soluble zinc phthalocyanine (ZnPc) with four peripheral 1-hydroxyhexan-3-ylthio groups was synthesized by cyclotetramerization and characterized by FTIR, 1H and 13C NMRs spectroscopies, fluorescence and UV-vis measurements. The optical property and quantum yield of ZnPc were elucidated in mixed solvent of ethanol/water with varying compositions. The pH-dependent fluorescence and absorbance spectra of ZnPc in the absence and presence of Ag+ ions were obtained to elucidate the optimum pH value that is convenient for stable complex formation in predetermined mixture. A comparative study for recognition of Ag+ ion has been carried out to evaluate the effect of the solution parameters on selective sensing ability of ZnPc as a fluorescent receptor. Interference effect was investigated by spectrofluorometric titration based on fluorescence quenching of ZnPc upon addition of Ag+ ion in the presence of foreign metal ions. Stepwise complexation/decomplexation cycles with Na2S-titration by fluorescence quenching/enhancement were investigated to establish the reversible response rate and reusability of ZnPc toward Ag+ ions. Graphical Abstract Selective determination of silver ion based on H-type aggregation of zinc phthalocyanine.

Graphene covalently functionalized with 2,6-diaminoanthraquinone (DQ) as a high performance electrode material for supercapacitors

2,6-Diaminoaquinone molecules were covalently modified onto the surface of GO via a nucleophilic displacement reaction between the epoxy groups on the surface of GO and the –NH2 groups of DQ molecules in the presence of ammonia to form a composite material.

Decarboxylative Phosphine Synthesis: Insights into the Catalytic, Autocatalytic, and Inhibitory Roles of Additives and Intermediates

Phosphines are among the most widely used ligands, catalysts, and reagents. Current synthetic approaches to phosphines are dominated by nucleophilic displacement reactions with organometallic reage...

Novel benzimidazole and pyridine-containing poly(ether ether ketone) s with good solubility, thermal properties and fluorescence

3,5-bis(2-benzimidazolyl) pyridine (3,5-BP) is synthesized and a series of benzimidazolyl and pyridyl-containing poly (ether ether ketone) s (mPEEK-BPs) with precise structures and high yield are prepared through a nucleophilic displacement reaction of 3,5-BP, m-dihydroxybenzene and 4,4′-difluorobenzophenone. X-ray diffraction results show that mPEEK-BPs are amorphous. All the synthesized polymers posses high glass transition temperatures (Tg = 211~270 °C) and high thermal stability (Td5% = 506~549 °C in N2, 471~564 °C in air). The polymers have good solubilities in common organic solvents. With the increase of benzimidazole and pyridine units content, the thermal properties and solubility of the as-prepared polymers improved. Additionally, the resulted polymers exhibit excellent fluorescence performance and the fluorescence emission peak appears at 425 nm.

Lignin as a Functional Green Coating on Carbon Fiber Surface to Improve Interfacial Adhesion in Carbon Fiber Reinforced Polymers.

While intensive efforts are made to prepare carbon fiber reinforced plastics from renewable sources, less emphasis is directed towards elaborating green approaches for carbon fiber surface modification to improve the interfacial adhesion in these composites. In this study, we covalently attach lignin, a renewable feedstock, to a graphitic surface for the first time. The covalent bond is established via aromatic anchoring groups with amine functions taking part in a nucleophilic displacement reaction with a tosylated lignin derivative. The successful grafting procedures were confirmed by cyclic voltammetry, X-ray photoelectron spectroscopy, and field emission scanning electron microscopy coupled with energy dispersive X-ray spectroscopy. Both fragmentation and microdroplet tests were conducted to evaluate the interfacial shear strength of lignin coated carbon fiber samples embedded in a green cellulose propionate matrix and in a commercially used epoxy resin. The microdroplet test showed ~27% and ~65% increases in interfacial shear strength for the epoxy and cellulose propionate matrix, respectively. For the epoxy matrix covalent bond, it is expected to form with lignin, while for the cellulosic matrix hydrogen bond formation might take place; furthermore, plastisizing effects are also considered. Our study opens the gates for utilizing lignin coating to improve the shear tolerance of innovative composites.

Photodegradation of Napropamide in Aqueous Methanol under UV Light and Sunlight

Photolysis of napropamide is reported under UV light (λ≥ 290 nm) and sunlight (λ≥ 250 max max nm). The rate of photodegradation of napropamide in aqueous methanol (10 μg mL−1) followed the first-order kinetics under UV (T½=1.09h.) and sunlight (7.72h.). On photolysis in aqueous methanol, it furnished four photoproducts (F1, F2, F3 and F4) of which F1 was a common photolysis product isolated from both sunlight and UV light. Photoproducts F2 and F3 were generated from UV irradiated solution and only F4 from sunlight irradiated solution. The plausible mechanism of photo transformation involved oxidation, dimerization, hydrolysis as well as nucleophilic displacement reactions.

Selective chemosensor phthalocyanines for Pd2+ ions; synthesis, characterization, quantum chemical calculation, photochemical and photophysical properties

In this study, ligand (1) was prepared by a nucleophilic displacement reaction of (4-bromophenyl)methanethiol with 4-nitrophthalonitrile according to literature and its novel type peripheral substituted tetra phthalocyanines [CuPc (2), ZnPc (3) and GaPc (4)] were prepared. The phthalocyanines obtained from compound (1) were characterized by FT-IR, 1H NMR, UV–Vis spectral data, elemental analysis, and MALDI-TOF. The novel phthalocyanines [CuPc (2), ZnPc (3) and GaPc (4)] were highly soluble in common organic solvents such as CHCl3, THF, CH2Cl2, DMSO and DMF. The effect of Pd2+ ions on the fluorescence emission and UV–Vis spectra were performed with addition of increasing amounts of Pd2+ ions. This functional phthalocyanines exhibited H-type aggregation versus Pd2+ ions due to special chemical structures, which can be used as a selective chemosensor for Pd2+ ions. Also, the molecular reactivity of the ligand (1) and related metallo phthalocyanines [CuPc (2), ZnPc (3) and GaPc (4)] were investigated and compared with the analysis of frontier molecular orbitals. In addition, photochemical and photophysical properties of these new phthalocyanines (fluorescence quantum yields, fluorescence behavior, singlet oxygen and photodegradation quantum yields) were studied in DMSO.

Sacrificial Cobalt-Carbon Bond Homolysis in Coenzyme B12 as a Cofactor Conservation Strategy.

A sophisticated intracellular trafficking pathway in humans is used to tailor vitamin B12 into its active cofactor forms, and to deliver it to two known B12-dependent enzymes. Herein, we report an unexpected strategy for cellular retention of B12, an essential and reactive cofactor. If methylmalonyl-CoA mutase is unavailable to accept the coenzyme B12 product of adenosyltransferase, the latter catalyzes homolytic scission of the cobalt-carbon bond in an unconventional reversal of the nucleophilic displacement reaction that was used to make it. The resulting homolysis product binds more tightly to adenosyltransferase than does coenzyme B12, facilitating cofactor retention. We have trapped, and characterized spectroscopically, an intermediate in which the cobalt-carbon bond is weakened prior to being broken. The physiological relevance of this sacrificial catalytic activity for cofactor retention is supported by the significantly lower coenzyme B12 concentration in patients with dysfunctional methylmalonyl-CoA mutase but normal adenosyltransferase activity.