Presence Of Nucleophiles Research Articles

Intramolecular Electrostatic Interactions Regulate Reactivity of Zwitterionic Functionalities in Amphiphilic Assemblies

AbstractThe consequences of intramolecular ionic interactions in determining the reactivity of functional groups are of interest because they provide insights into how nature deploys seemingly reactive functionalities to be rather ubiquitous. Of specific interest are the quaternary ammonium ions in lipids. In this work, we investigate the effect of intramolecular electrostatic interactions in zwitterionic functionalities by judiciously incorporating them as leaving groups at the α‐position of α,β‐unsaturated ester‐based lipid head groups. We find that electrostatic stabilization indeed plays a critical role in both the reaction kinetics with nucleophiles and the thermodynamics of lipid formation. We further leverage these findings to fabricate both triggerable assembly and disassembly of liposomal supramolecular assemblies in the presence of nucleophiles.

Intramolecular Electrostatic Interactions Regulate Reactivity of Zwitterionic Functionalities in Amphiphilic Assemblies.

The consequences of intramolecular ionic interactions in determining the reactivity of functional groups are of interest because they provide insights into how nature deploys seemingly reactive functionalities to be rather ubiquitous. Of specific interest are the quaternary ammonium ions in lipids. In this work, we investigate the effect of intramolecular electrostatic interactions in zwitterionic functionalities by judiciously incorporating them as leaving groups at the α-position of α,β-unsaturated ester-based lipid head groups. We find that electrostatic stabilization indeed plays a critical role in both the reaction kinetics with nucleophiles and the thermodynamics of lipid formation. We further leverage these findings to fabricate both triggerable assembly and disassembly of liposomal supramolecular assemblies in the presence of nucleophiles.

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles.

In this work, we report an efficient approach to 2-oxoazetidine-3-carboxylic acid derivatives based on a thermally promoted Wolff rearrangement of diazotetramic acids in the presence of nucleophiles. The method allows easy variation of the substituent in the exocyclic acyl group by introducing different N-, O-, and S-nucleophilic reagents into the reaction. The reaction of chiral diazotetramic acids leads exclusively to trans-diastereomeric β-lactams. The use of variously substituted diazotetramic acids, including spirocyclic derivatives, as well as a wide range of nucleophiles provides access to a structural diversity of medically relevant 2-oxoazetidine-3-carboxylic acid amides and esters.

Nucleophiles promotes the decomposition of electrophilic functional groups of tetracycline in ZVI/H2O2 system: Efficiency and mechanism

When zero-valent iron (ZVI) is prepared and applied under neutral conditions, it is easy to form oxides or hydroxides on its surface, which hinders the electron release of ZVI. To this end, a nucleophile was introduced into the ZVI system to inhibit the precipitation of iron ions, improve the conductivity of the solution, and promote the removal efficiency of electrophilic functional groups in organic compounds. In this study, the addition of nucleophiles such as ethylenediamine, methylamine and dimethylamine to the ZVI/H2O2 system resulted in an enhanced removal efficiency of tetracycline (TC) under neutral condition, while electrophiles such as EDTA-2Na and oxalic acid dihydrate impeded the removal of TC. Experimental results demonstrated that the presence of nucleophiles could effectively promote the release of iron ions and increase the proportion of ferrous in both aqueous solution and solid surface of ZVI. Experimental and theoretical calculation results revealed that the electrophilic functional group was eliminated in the TC molecule, and the toxicity of the treated solution was reduced significantly. Overall, this work provides a selection of the conditions and pollutants applicable to ZVI under neutral pH conditions.

Divergent and Nucleophile-Assisted Rearrangement in the Construction of Pyrrolo[2,1-b][3]benzazepine and Pyrido[2,1-a]isoquinoline Scaffolds.

Under microwave (MW) irradiation at 150 °C in toluene and in the presence of nucleophiles (DMAP, triphenylphosphine and tetrahydrothiophene) 1-substituted 1-ethynyl-2-vinyldi- and tetrahydroisoquinolines undergo [3,3]-sigmatropic rearrangement providing pyrrolo[2,1-b][3]benzazepines in good yields. The replacement of toluene with acetonitrile directs the rearrangement towards the formation of 7,11b-dihydro-6H-pyrido[2,1-a]isoquinolines.

Transannular Selenocyclofunctionalization of 1,5-cyclooctadiene: The Antioxidant Properties of 9-selenabicyclo[3.3.1]nonane Derivatives and the Discovery of Increasing Both GPx and GR Activities

Oxidative stress is the cause of various pathologies and disorders of cellular functions. Substances that reduce the pathological effect of oxidative stress on homeostasis include organoselenium compounds of natural and synthetic origin. Depending on the structure, organoselenium compounds can exhibit different biological activities, for example, reducing oxidative stress, participating in the regulation of signaling systems, influencing the synthesis of cytokines, etc. This makes them promising products for the development of new means of metabolic correction and drugs with enzyme-like activity. This study is aimed at developing an effective method for the synthesis of functional organoselenium compounds and studying their antioxidant effect in vivo under stress conditions. A one-pot catalyst-free method of transannular addition-functionalization of cis,cis-1,5-cyclooctadiene with selenium dihalides in the presence of nucleophiles was developed. For the first time, the antioxidant activity of functionalized 9-selenabicyclo[3.3.1]nonanes was studied in vivo. Quantitative characteristics of the effect on the level of lipid peroxidation and the activity of glutathione peroxidase and glutathione reductase under stress conditions were obtained. The effect of substituents in the selenium-containing scaffold on the biological activity of the compounds was studied. The water-soluble 9-selenabicyclo[3.3.1]nonane derivatives, containing hydroxyl and 2-hydroxyethoxy groups, which increased the activity of both glutathione peroxidase and glutathione reductase, were discovered.

One-Pot Synthesis of Strain-Release Reagents from Methyl Sulfones.

Sulfone-substituted bicyclo[1.1.0]butanes and housanes have found widespread application in organic synthesis due to their bench stability and high reactivity in strain-releasing processes in the presence of nucleophiles or radical species. Despite their increasing utility, their preparation typically requires multiple steps in low overall yield. In this work, we report an expedient and general one-pot procedure for the synthesis of 1-sulfonylbicyclo[1.1.0]butanes from readily available methyl sulfones and inexpensive epichlorohydrin via the dialkylmagnesium-mediated formation of 3-sulfonylcyclobutanol intermediates. Furthermore, the process was extended to the formation of 1-sulfonylbicyclo[2.1.0]pentane (housane) analogues when 4-chloro-1,2-epoxybutane was used as the electrophile instead of epichlorohydrin. Both procedures could be applied on a gram scale with similar efficiency and are shown to be fully stereospecific in the case of housanes when an enantiopure epoxide was employed, leading to a streamlined access to highly valuable optically active strain-release reagents.

27 Years of Catalytic Carbonylative Coupling Reactions in Hungary (1994-2021).

Palladium-catalyzed carbonylation reactions, in the presence of nucleophiles, serve as very potent tools for the conversion of aryl and alkenyl halides or halide equivalents to carboxylic acid derivatives or to other carbonyl compounds. There are a vast number of applications for the synthesis of simple building blocks as well as for the functionalization of biologically important skeletons. This review covers the history of carbonylative coupling reactions in Hungary between the years 1994 and 2021.

Quest for Zinc Methoxyisoporphyrin Molecules: Experimental and Theoretical Studies

AbstractThis study describes the synthesis, characterization and theoretical studies of two new zinc isoporphyrin compounds, [5‐(methoxy)‐5,10,15,20‐tetrakis(4‐hydroxy)‐5,15H‐porphinato]zinc(II) 1 b, and [5‐(methoxy)‐5,10,15,20‐tetrakis(4‐methyl)‐5,15H‐porphinato]zinc(II) 2 b. Meso‐tetra(4‐hydroxyphenyl)zinc porphyrin, [ZnT(4‐OH)PP], 1 a and, meso‐tetra(4‐methylphenyl)zinc porphyrin, [ZnT(4‐CH3)PP] 2 a were used as a parent porphyrins to synthesize the respective isoporphyrin complexes in the presence of ceric ammonium nitrate (CAN) in methanol medium. The synthesized isoporphyrin compounds are characterized using all standard spectroscopic techniques like UV‐Visible, IR, 1HNMR, and ESI‐Mass spectrometric method. Theoretical calculations at the DFT level was performed to understand the properties and reactivity of the isoporphyrins. To get some insight into the mechanism of isoporphyrin formation via zinc porphyrin dication, the geometry of zinc porphyrin dication [ZnT(4‐OH)PP]++ was optimized and the distribution of Mulliken charge in the dication ring was calculated. The higher positive charge at the meso C‐atoms of the zinc porphyrin dication with respect to other ring carbon atoms supports the proposed nucleophilic attack at the meso carbon of the dication. The DFT calculations studied here is suitable to understand the mechanism of formation of isoporphyrins in the presence of nucleophiles, unique electronic spectra, and redox properties of isoporphyrins.

TCT-mediated click chemistry for the synthesis of nitrogen-containing functionalities: conversion of carboxylic acids to carbamides, carbamates, carbamothioates, amides and amines.

Here, we report a s-trichlorotriazine (TCT, also known as cyanuric chloride) mediated one-pot general method for the conversion of carboxylic acids into ubiquitous functionalities such as carbamides, carbamates, carbamothioates, amides, and amines. The TCT-mediated activation of acids followed by azidation and heating led to the isocyanate formation via Curtius rearrangement which involves click chemistry in the presence of nucleophiles and provided the coupled product. The TCT was employed at ≤40 mol% with respect to the starting materials; however, its bulk availability and low cost provide a unique opportunity towards its applicability in the synthesis of functional molecules. The optimized conditions have also been successfully demonstrated for gram scale synthesis and late-stage functionalization of natural products and drugs such as podophyllotoxin, eugenol, diosgenin, geraniol and fluvoxamine.

Anodic Substitution Reaction of Cyclic Carbamates in Stable Nanoemulsion Solution Using a Flow Microreactor

Carbocations are important reactive intermediates in organic synthesis. Although a variety of reactions involving carbocations have been developed so far, nucleophilic reactions between chemically and electrochemically generated carbocations and nucleophiles have been widely utilized in organic synthesis1. Since carbocations are usually unstable intermediates, the oxidative generation of carbocations often has to be conducted in the presence of nucleophiles so that the nucleophile can trap the carbocation immediately as it is generated. However, the oxidation potentials of the nucleophiles are usually lower than those of the corresponding organic substrates, and therefore the presence of nucleophiles would prevent oxidation of organic substrates. In this regard, introduction of an electro-auxiliary into substrates2and the “cation pool” method3have been developed, but thesenecessarily include multi-step reactions.In order to overcome this problem, we developed a novel electrolytic system for anodic substitution reactions using acoustic emulsification in our previous work4. In this system, the substrate is predominantly oxidized to give corresponding carbocation intermediate because the acoustically emulsified nucleophile phase which is insoluble in an electrolytic medium is electro-inactive.In this work, we have tried to improve further the current efficiency of this reaction system by using a flow microreactor which offers advantages such as large specific interfacial area and precise control of reaction time. Moreover, the emulsion electrolytic solution was prepared by sequential ultrasonic irradiations in order to stabilize the emulsion droplets before the electrolysis in a flow microreactor5.We chose an anodic substitution reaction of N-(methoxycarbonyl) pyrrolidine (oxidation potential E ox = 1.91 V vs. Ag/AgCl) as a substrate with allyltrimethylsilane (oxidation potential E ox = 1.75 V vs. Ag/AgCl) as a nucleophile for the model reaction (Scheme). We prepared a stable two-phase emulsified solution composed of ionic liquid [EMIM] [BF4] phase containing the substrate and nucleophile phase by sequential ultrasonication with 1.6 MHz treatment after 20 kHz ultrasonication. This solution was introduced into an electrolytic flow microreactor using a syringe pump, and then galvanostatically electrolyzed (Figure).Especially in this work, we have investigated the effect of four parameters (nucleophile amount, electrode distance, flow rate and current density) on the current efficiency of desired product and determined the best electrolysis condition in a flow microreactor. As a result, it was confirmed that the current efficiency (38％) was much higher compared with that obtained by the use of a batch type reactor (13%).References1) Moeller, K. D. Tetrahedron, 2000,56, 9527.2) Yoshida, J.; Sugawara, M. et. al. J. Org. Chem. 1998, 63, 5950.3) Yoshida, J.; Suga, S. et. al. J. Am. Chem. Soc. 1999, 121, 9546.4) Asami, R.; Fuchigami, T.; Atobe, M. Chem. Commun. 2008, 244.5) Nakabayashi, K.; Atobe, M. et. al. Chem. Commun. 2011. 47. 5765 Figure 1

Photolysis of Trenbolone Acetate Metabolites in the Presence of Nucleophiles: Evidence for Metastable Photoaddition Products and Reversible Associations with Dissolved Organic Matter.

Photolysis of trenbolone acetate (TBA) metabolites in the presence of various nitrogen-, sulfur-, or oxygen-containing nucleophiles (e.g., azide, ammonia, or thiosulfate, respectively) results in rapid (half-lives ∼20-60 min), photochemically induced nucleophile incorporation across the parent steroid's trienone moiety. The formation of such nucleophile adducts limits formation of photohydrates, suggesting competition between the nucleophile and water for photochemical addition into the activated steroid structure. Analogous to previously reported photohydration outcomes, LC/MS analyses suggest that such photonucleophilic addition reactions are reversible, with more rapid elimination rates than thermal dehydration of photohydrates, and regenerate parent steroid structures. Beyond photonucleophilic addition pathways, we also found that hydroxylamine and presumed nucleophilic moieties in model dissolved organic matter (DOM; Fluka humic acid) can react via thermal substitution with TBA metabolite photohydrates, although this reaction with model DOM was only observed for photohydrates of trendione. Most nucleophile addition products [i.e., formed via (photo)reaction with thiosulfate, hydroxylamine, and ammonia] are notably more polar relative to the parent metabolite and photohydration products. Thus, if present, both nucleophilic adducts and bound residues in organic matter will facilitate transport and help mask detection of TBA metabolites in surface waters and treatment systems.

Nucleophilic substitution reaction mechanisms: An atomic-molecular perspective on chemical speciation and transport properties in silicate melts

There has been no systematic attempt to determine if nucleophilic substitution (SN) reactions proceed in silicate melts, even though they commonly occur in gaseous and liquid phases containing C, Si, P, and Ge centered tetrahedra. The oversight is here rectified by providing such an analysis. Conditions required for nucleophilic substitution reactions to occur are: (1) the presence of nucleophiles (Lewis bases) which in silicate melts are bridging oxygen (BO), non-bridging oxygen (NBO−) and free oxygen (O2−); (2) the presence of tetrahedra (Q species) with strongly electrophilic centers (i.e., Si atoms); (3) the presence of Si transition species containing pentahedrally coordinated Si (i.e., VSi species); (4) rapid reaction rates among tetrahedral species. All conditions are met for silicate melts. For example, the strong nucleophile, NBO− exists at high temperatures in binary alkali and alkaline earths silicate melts due primarily to thermal agitation whereby some Si-NBO-M bonds are ruptured to produce the nucleophilic Si-NBO− moiety. This nucleophile attacks the Si center of an adjacent tetrahedron to form a SiO bond thereby producing a VSi transition species. The transition species decomposes by rupture of another SiO bond located on the polar opposite side of the transition species. Three types of SN reaction are recognized and all involve VSi transition species. They are NBO-BO exchange reactions (e.g., Q3 + Q4 → Q4 + Q3), disproportionation reactions (e.g., 2Q3 → Q4 + Q2) and polymerization reactions (e.g., Q3 → Q4 + 1/2O2−). H2O and OH− are also nucleophiles and their reaction with Q species proceeds via SN reaction mechanisms, and may cause depolymerization of melts. Hydrogen bonding of H2O to BO and NBO may also occur, as in ice and water, thereby enhancing H2O solubilities in melts. These latter reactions should neither depolymerize melts nor affect NBO/T values.The diffusivity of Si and O in melts, anionic conductivity and chemical speciation (e.g. Q species abundances) proceed via one or other SN reaction, with the transition species assuming a critical role in diffusivity, conductivity and viscosity. The SN reaction mechanism, coupled with transition state theory, provides explanations for: (1) the formation of pentahedrally coordinated Si (VSi) and its apparent restriction to highly siliceous glasses; (2) the remarkably similar diffusivities of Si and O in silicate melts; (3) the ‘jump distance’ (α) of the Eyring equation, which by the SN mechanism is ~3.5 Å (i.e., diameter of the VSi transition species); (4) the minimum number of monomeric units (i.e., Q species) involved in the ‘cooperative region’ of the Adam-Gibbs equation; and (5) the quantitative distribution of Q species in Na silicate glasses up to ~50 mol% Na2O.

Asymmetric Borylative Coupling of Vinylazaarenes and Ketones Catalyzed by a Copper(I) Complex

Azaarenes are attractive structural units widely found in chiral pharmaceuticals, agrochemicals, and biologically active natural products. An ongoing strategy has been the construction of new chira...

Heterogeneous photocatalysis of azides: extending nitrene photochemistry to longer wavelengths.

The photodecomposition of azides to generate nitrenes usually requires wavelengths in the <300 nm region. In this study, we show that this reaction can be readily performed in the UVA region (368 nm) when catalyzed by Pd-decorated TiO2. In aqueous medium the reaction leads to amines, with water acting as the H source; however, in non-protic and non-nucleophilic media, such as acetonitrile, nitrenes recombine to yield azo compounds, while azirine-mediated trapping occurs in the presence of nucleophiles. The heterogeneous process facilitates catalyst separation while showing great chemoselectivity and high yields.

Isocyanurate transformation induced healing of isocyanurate–oxazolidone polymers

ABSTRACTIsocyanurate–oxazolidone (ISOX) polymers have been reported as a novel, intrinsically self‐healable thermoset, and their healing mechanism under the effect of nucleophiles, such as tertiary amines and pyridines during polymerization, is thoroughly investigated in this study. This work provides evidence that the healing behavior of the polymers results part from the transformation of isocyanurate to oxazolidone on the fracture surfaces of the ISOX polymers at elevated temperatures. The isocyanurate transformation is characterized by chemical composition of the ISOX polymers before and after a predetermined healing procedure, through a combination characterization of Fourier transform infrared spectroscopy and carbon nuclear magnetic resonance spectroscopy. From the chemical composition of the ISOX polymers, an increased oxazolidone fraction is observed after the healing event, which verifies the hypothesized healing mechanism. By correlating the change in oxazolidone fraction in the polymers during the healing event, with the corresponding healing performance of the polymers, healing efficiencies of the polymers are shown to be inversely proportional to the ratio of oxazolidone to isocyanurate in the polymers. The transformation to oxazolidone is also shown to be dependent on two variables, nucleophilicity of the polymerization catalyst and duration of the postcure. The isocyanate and epoxide polymerization mechanism in the presence of nucleophiles is also investigated to explain the effect of the catalyst nucleophilicity on the chemical composition as well as the healing performance of the ISOX polymers. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48698.

Electrodeposition from Tannic acid-polyamine blends at pH = 5.0 is due to aggregate deposition and oxidation

Polyphenols like tannic acid, and others, adsorb spontaneously to the surface of a vast repertoire of materials to coat them with a conformal and functional thin film. Since polyphenols can be oxidized, their deposition can also be controlled at the surface of conductive materials. Since the oxidized form of polyphenols contains reactive quinone groups it could be of interest to electropolymerize them in the presence of nucleophiles, like polyamines to obtain composite coatings with properties different from those displayed by a coating obtained from the polyphenol alone. However in conditions where polyamines are reactive and unprotonated, polyphenols undergo spontaneous, non controlled oxidation. In this article, the electropolymerization of tannic acid (TA) by means of cyclic voltammetry is performed at pH = 5.0. The obtained TA based coatings are compared to those obtained from blends with poly(allylamine hydrochloride) (PAH) as a primary polyamine and with poly(diallyldimethyl ammonium chloride) (PDADMAC) containing quaternary ammonium groups. In these conditions, the polyamines form complexes with TA. It will be shown by means of electrochemical impedance spectroscopy, that the higher the PAH concentration in the blend, the higher is the pseudocapacitance of the film. This finding is explained by the incorporation of positively charged PAH or PDADMAC into the film during the oxidation of TA and by the increase in film roughness/porosity in the presence of the polycation.

Synthesis of Sugar-Based Enones and Their Transformation into 3,5-Disubstituted Furans and 2-Acyl-Substituted 1,2,3-Trideoxy Sugars in the Presence of Lewis Acids.

Pd-catalyzed carbonylative cross-coupling reactions of 2-iodoglycals have been developed for the synthesis of sugar-based arylones and ynones using formic acid as the carbonyl source. Whereas acetyl-protected arylones lead to the formation of highly substituted furan derivatives in the presence of Lewis acid, benzyl-protected arylones furnished the 3-deoxy sugar derivative. In the presence of nucleophiles, an attack took place on the C-1 or C-3 carbon regio- and stereoselectively depending on the nature of the nucleophiles.

Influence of position of methoxy groups in Zn-methoxyphenylporphyrins

The crystal structure of the compound, Zn(II) 5,10,15,20-tetrakis(meta-methoxyphenyl)porphyrin chloroform trisolvate, $$[\hbox {ZnT}(m\hbox {-OCH}_{3})\hbox {PP}]{\cdot } 3\hbox {CHCl}_{3}$$ 1 reveals that it forms a weak one-dimensional chain structure through interaction between Zn of porphyrin and the oxygen atom of the methoxy group of a neighbouring porphyrin. The zinc–oxygen interaction observed in compound 1 is compared with Zn(II) 5,10,15,20-tetrakis(para-methoxyphenyl)porphyrin $$[\hbox {ZnT}(p\hbox {-OCH}_{3})\hbox {PP}]$$ 2 and Zn(II) 5,10,15,20-tetrakis(3,4,5-tri-methoxyphenyl)porphyrin $$[\hbox {ZnT}(3,4,5\hbox {-triOCH}_{3})\hbox {PP}]$$ 3 to understand the preferred methoxy-position of interaction. The strength of the non-covalent zinc–oxygen (methoxy group of a neighboring porphyrin) interaction in compound 1 is in between that of similar interactions observed in compounds 2 and 3. The Mulliken charge analysis using theoretical calculation at the DFT level shows that the meta-methoxy oxygen has a higher probability of binding to the metal than the para-methoxy oxygen. In the presence of nucleophiles, the formation of one-dimensional chain structure stops due to the binding of the nucleophiles to the metal zinc. The photoluminescence and differential scanning calorimetric studies were also performed for compound 1. SYNOPSIS A zinc porphyrin $$[\hbox {ZnT}(m\hbox {-OCH}_{3})\hbox {PP}]{\cdot } 3\hbox {CHCl}_{3}$$ 1 has been synthesized and structurally characterized using single crystal X-ray diffraction and other spectroscopic methods. The crystal structure of 1 shows a weak interaction between Zn of porphyrin and the oxygen atom of the methoxy group of a neighbouring porphyrin. The Zn-oxygen interaction observed in compound 1 is compared with Zn-oxygen interaction present in other methoxy-substituted porphyrins $$[\hbox {ZnT}(p\hbox {-OCH}_{3})\hbox {PP}]$$ 2 and [ZnT(3,4, 5- $$\hbox {triOCH}_{3})\hbox {PP}$$ ] 3.

Novel Antihypertensive Prodrug from Grape Seed Proanthocyanidin Extract via Acid-Mediated Depolymerization in the Presence of Captopril: Synthesis, Process Optimization, and Metabolism in Rats.

Grape seed extract contains a high content of proanthocyanidins that can be depolymerized into C-4-substituted (epi)catechin derivatives in the presence of nucleophiles. However, the biological and medicinal values of depolymerization products have been rarely investigated. Recently, we developed a novel depolymerization product (-)-epicatechin-4β- S-captopril methyl ester (ECC) derived from the reaction of grape seed proanthocyanidin extract with captopril in the presence of acidified methanol. A central composite design was employed to select the most appropriate depolymerization temperature and time to obtain the target product ECC with a high yield. A total of 16 metabolites of ECC in rat urine, feces, and plasma were identified using liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The in vivo results suggested that ECC could release captopril methyl ester and epicatechin, followed by the generation of further metabolites captopril and epicatechin sulfate conjugates. Therefore, ECC may be used as a potential prodrug with synergistic or additive hypotensive effects.