Action Of Nucleophiles Research Articles

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles.

Pyrrolo[2,1-b][1,3]benzothiazoles are an important class of fused sulfur and nitrogen-containing heterocycles intensively studied in medicinal chemistry and pharmacology. In the present paper, a new synthetic approach to pyrrolobenzothiazoles is developed based on 1,4-thiazine ring contraction in 3-aroylpyrrolo[2,1-c][1,4]benzothiazine-1,2,4-triones under the action of nucleophiles. The proposed approach works well with alkanols, benzylamine, and arylamines. The scope and limitations of the developed approach are studied. The synthesized pyrrolobenzothiazole derivatives represent an interest to pharmaceutics, since their close analogs show CENP-E inhibitory activity, interesting for the targeted cancer therapy development.

Uncovering the Synchronous Role of Bis‐borane with Nucleophilic Solvent as Frustrated Lewis Pair in Metal‐Free Catalytic Dehydrogenation of Ammonia‐borane**

AbstractMetal free catalysis has emerged as a viable alternative for transition metal based catalysts for enabling different chemical processes, particularly for de/hydrogenation reactions. Herein, employing theoretical studies we reveal the unexpected Frustrated Lewis Pair like reactivity of a boron based catalyst, 9,10‐dichlorodiboraanthracene and the ethereal solvent to enable dehydrogenation of ammonia‐borane (NH3BH3, AB) under moderate conditions. The mechanistic channels thus uncovered reveal that the boron catalyst abstracts a hydride from NH3BH3 followed by crucial stabilization of the NH3BH2+ moiety by the nucleophilic action of the solvent. H2 is released by the combination of hydride and proton from the borohydride moiety and the solvated NH3BH2+ respectively. Catalysis becomes unfeasible if the Lewis base‐like action of the ethereal solvent is not taken into consideration. Thus, it is suggested that the clandestine partnership of the Lewis Acid, Boron catalyst and the Lewis Base, ethereal solvent, i. e. FLP like action enables dehydrogenation of NH3BH3 in the instant case.

Advancing the boundaries of the covalent functionalization of graphene oxide

The synthesis of a derivatized graphene oxide with a particularly high degree of functionalization is achieved through a facile wet‑chemistry procedure. Graphene oxide is a highly reactive graphene derivative, especially with nucleophiles or dipolarophiles. However the reductive action of nucleophiles, as well as of other reactants or solvents usually prevails over functionalization. Therefore, the reactions of graphene oxide lead almost exclusively into reduced graphene derivatives with low functionalization degree. Here we report that tuning the reaction conditions during functionalization can alter the competition outcome of the two simultaneous reactions in a 1,3 dipolar cycloaddition on graphene oxide. Under these conditions, the cycloaddition pathway was dramatically favoured against the unspecific reduction/oxygen elimination side reactions, affording a selectively and densely functionalized graphene oxide. This property can be exploited for enhancing the interactions with target molecules (very effective immobilization of pharmaceutic compounds, as demonstrated here), as well as in other applications such as in preparing catalysts with high content of active sites by coordinating metal nanoparticles or atoms.

Iodine-induced stepwise reactivity of coordinated white phosphorus: A mechanistic overview

The main role of the Ruthenium metal in the stepwise demolition of the P4 ligand upon the reaction with I2 is to enhance the basicity of the phosphorus atoms. The first step of reaction goes through the η2 coordination of the P4 moiety. The bounded phosphorus atoms are able to interact with the di-iodine molecule allowing the formation of tri-iodide anions. The latter, once released, may exert their nucleophilic action toward the transient unsaturated coordinated phosphorus centre. Such a vacancy is partially fulfilled by the metal through the formation of a partial Ru=P double bond. A detailed analysis of the evolution of the electronic structure at the various intermediates allows to discriminate in between the possible different initial adducts and to predict the most stable product. In contrast with the unassisted reaction, no concerted mechanism has been pointed out but the process evolves through a stepwise cleavage of the three PP bonds involving the coordinated phosphorus up to the final PI3 ligand formation and a cyclo-P3I3 moiety.

Nucleophilic C—H functionalization of arenes: a contribution to green chemistry

The review is focused on premises, features and scope of the reactions leading to the direct functionalization of the C—H bond in arenes by the action of nucleophiles. Practical importance and a contribution of synthetic approaches with minimal steps, the so called PASE- (pot-, atom-, and step-economic) processes, to green chemistry are also discussed.

Base Catalysis by Mono- and Polyoxometalates

In sharp contrast with acid-, photo-, and oxidation-catalysis by polyoxometalates, base catalysis by polyoxometalates has scarcely been investigated. The use of polyoxometalates as base catalysts have very recently received much attention and has been extensively investigated. Numerous mono- and polyoxometalate base catalyst systems effective for the chemical fixation of CO2, cyanosilylation of carbonyl compounds, and C–C bond forming reactions have been developed. Mono- and polyoxometalate base catalysts are classified into four main groups with respect to their structures: (a) monomeric metalates; (b) isopolyoxometalates; (c) heteropolyoxometalates; and (d) transition-metal-substituted polyoxometalates. This review article focuses on the relationship among the molecular structures, the basic properties, and the unique base catalysis of polyoxometalates on the basis of groups (a)–(d). In addition, reaction mechanisms including the specific activation of substrates and/or reagents such as the abstraction of protons, nucleophilic action toward substrates, and bifunctional action in combination with metal catalysts are comprehensively summarized.

Oxime-mediated in vitro reactivation kinetic analysis of organophosphates-inhibited human and electric eel acetylcholinesterase

Organophosphate (OP)-based pesticides and nerve agents are highly toxic compounds which interrupt the catalytic mechanism of acetylcholinesterase (AChE) by phosphorylating the hydroxyl moiety of serine residue. The inhibited enzyme can be reactivated by the nucleophilic action of oxime reactivators. To analyze the effect of different AChE sources on reactivation efficacy of reactivators, several in vivo studies have carried out using variety of AChE sources like pig, rat and monkey. Investigations on species differences provide a better insight for the development of new reactivators. Hence, present study was mainly targeted on comparative analysis of the reactivation of electric eel and human AChE inhibited by different OP. A series of butene-linked bis-pyridinium mono oximes which vary in functional groups present at the second pyridinium ring have been examined against sarin, VX, tabun and ethyl-paraoxon-poisoned AChE. In case of tabun-inhibited AChEs, tested oximes were better than reference oximes. For VX-poisoned human AChE, reactivator K251 (kr2;1.51 mM − 1 min − 1) showed good reactivation efficacy with standard oximes. Studies stipulated that butene-linked oximes consisting of different functional moieties are good reactivators and found to have better efficacy to reactivate nerve agent-inhibited human AChE in comparison to eel AChE.

Organophosphorous Poisoning: Treatment and Analytical Methodologies Applied in Evaluation of Reactivation and Inhibition of Acetylcholinesterase

Organophosphorus derivatives inhibit the enzyme acetylcholinesterase promoting cholinergic hyperstimulation, irreversible damage and death. These compounds are used by civil and military organizations as pesticides or chemical weapons, respectively, and are responsible for over three million annual cases of poisoning, as well as more than 250,000 deaths per year from intentional self-poisoning, accounting 30% of suicides in the world. The organophosphorus sarin, soman, tabun and VX are been employed as weapons of war by different terrorist groups. Oxime derivatives (pralidoxime and obidoxima) have been used as antidote in detoxification step, but the results are still not satisfactory, because these drugs have low penetration into blood-brain barrier and an inefficient nucleophilic action against organophosphorus. Thus, different analytical methods can be used to monitor the efficiency of drugs with property to reactivate or inhibit the acetylcholinesterase enzyme. This paper provides an overview of the derivatives of oximes currently used as potential reactivators and inhibitors, as well as of the main methodologies used in monitoring or reactivation or inhibition of acetylcholinesterase. DOI: 10.5935/1984-6835.20160056

Anionic chromogenic chemosensors highly selective for cyanide based on the interaction of phenyl boronic acid and solvatochromic dyes

Solutions of two solvatochromic dyes, Reichardt's pyridinium N-phenolate betaine (1) and Brooker's merocyanine (2), are colored in acetonitrile but become colorless when phenyl boronic acid (PBA) is added due to the formation of covalently linked dye-PBA species. Of the various anions added, only F− and CN− caused the reappearance of the original color related to the free dye in solution. These anions act as nucleophiles in acetonitrile and displace the dye leaving group. On the addition of very small amounts of water the system becomes highly selective toward CN− because of the ability of water to strongly solvate F−, inhibiting its nucleophilic action, while CN− is sufficiently naked to react with dye-PBA species. The titrations of the dye-PBA complexes with CN− revealed that the shape of the curves is dependent on the experimental conditions. With the use of large amounts of PBA, the dye, after being displaced, interacts with the free PBA forming hydrogen-bonded complexes, which are disrupted with the addition of an excess of the anion. This was not observed in aqueous acetonitrile since water can form hydrogen bonds with the boronic acid and with the dye, preventing the formation of dye-PBA hydrogen-bonded complexes.

Synthesis of functionalized tetrahydro-1,3-diazepin-2-ones and 1-carbamoyl-1H-pyrroles viaring expansion and ring expansion/ring contraction of tetrahydropyrimidines

A general approach to 6-phenylthio-substituted 2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones based on the ring expansion reaction of 1,2,3,4-tetrahydropyrimidin-2-ones under the action of nucleophiles has been developed. The first step of the synthesis was preparation of N-[(2-benzoyloxy-1-tosyl)ethyl]urea by three-component condensation of 2-benzoyloxyethanal, urea and p-toluenesulfinic acid. Nucleophilic substitution of the tosyl group in the obtained sulfone with sodium enolates of α-phenylthioketones followed by cyclization-dehydration, and debenzoylation gave 4-hydroxymethyl-5-phenylthio-1,2,3,4-tetrahydropyrimidin-2-ones which were transformed into the 4-mesyloxymethyl-derivatives. Treatment of the latter with nucleophilic reagents, such as NaCN, sodium diethyl malonate, PhSNa, MeONa, NaBH(4), sodium succinimide, or potassium phthalimide, afforded the target multi-functionalized diazepinones. The obtained 6-phenylthio-diazepinones and their 6-tosyl-substituted analogues were converted into 3-substituted 1-carbamoyl-1H-pyrroles under acidic conditions as a result of ring contraction. Effective one-pot synthesis of the latter from 4-mesyloxymethyl-pyrimidines was realized using a ring expansion/ring contraction sequence.

ChemInform Abstract: Activated Carbonyl Species for the Preparation of ortho-Acylarylsydnones.

ortho-Acylarylsydnones can be prepared in moderate to good yield by the action of nucleophiles upon suitable activated carbonyl species.

Nitropyrazoles 15. Synthesis and some transformations of 1-(2,4-dinitrophenyl)-4-methyl-3,5-dinitropyrazole

The method for preparation of 1-(2,4-dinitrophenyl)-4-methyl-3,5-dinitropyrazole has been developed. Due to the larger CH-acidity of 4-Me-group compared to 1,4-dimethyl-3,5-dinitropyrazole, 1-(2,4-dinitrophenyl)-4-methyl-3,5-dinitropyrazole is capable of reacting with substituted benzaldehydes to afford 4-[(E)-2-arylvinyl]-1-(2,4-dinitrophenyl)-3,5-dinitropyrazoles. Under the action of nucleophiles, dinitrophenyl group is detached from the former compounds leading to previously unknown N-unsubstituted 4-[(E)-2-arylvinyl]-3,5-dinitropyrazoles.

Chemical protection fabrics via surface oximation of electrospun polyacrylonitrile fiber mats

Polyacrylonitrile (PAN) submicron fiber mats were modified to become reactive components of self-detoxifying chemical protection fabrics. Oximation of the mats with excess hydroxylamine resulted in functionalization of the fibers to form polyacrylamidoxime (PAAO). The fiber morphology remains intact after oximation, with fiber diameters ranging from 250 to 500 nm. Nucleophilic amidoxime groups enable the fiber mats to react with organophosphate pesticides or chemical warfare agents (CWA), as demonstrated using diisopropyl fluorophosphate (DFP) as a CWA simulant. The DFP decomposition kinetics were investigated using 31P MAS NMR, which afforded measurement of the observed pseudo-first order reaction rate constant, kobs. The values of kobs with PAAO-functionalized fibers exceed those of the parent PAN fibers by as much as 80-fold at a water content of 130% by weight. The observed reaction rates depend on the amount of the reactive fiber mats, yielding an apparent second-order rate constant, k2 = 1.0 × 10−6 s−1mg−1. The hydrolytic degradation of DFP occurs only in the presence of free water, which serves as a medium to promote the nucleophilic action of the amidoxime groups in the fibers by facilitating proton transfer and stabilizing the transition state.

Formation of 4‐Arylpyridines from Pyridinium Salts under the Action of Methylammonium Sulfite.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Decyclization of 5‐Aryl‐4‐methyl‐2,3‐dihydrofuran‐2,3‐diones by the Action of Nucleophiles.

Ring cleavage in 4-methyl-5-phenyl-2,3-dihydrofuran-2,3-dione by the action of methanol and in 5-aryl-4-methyl-2,3-dihydrofuran-2,3-diones by the action of aniline and N-methylaniline results in formation of, respectively, methyl 3-methyl-4-phenyl-2,4-dioxobutanoate and 4-aryl-3-methyl-2,4-dioxobutananilides. The reaction mechanism was studied by 1H NMR spectroscopy.

Thermal Decomposition of Specifically Phosphorylated d-Glucoses and Their Role in the Control of the Maillard Reaction

One of the main shortcomings of the information available on the Maillard reaction is the lack of knowledge to control the different pathways, especially when it is desired to direct the reaction away from the formation of carcinogenic and other toxic substances to more aroma and color generation. The use of specifically phosphorylated sugars may impart some elements of control over the aroma profile generated by the Maillard reaction. Thermal decomposition of 1- and 6-phosphorylated glucoses was studied in the presence and absence of ammonia and selected amino acids through pyrolysis/gas chromatography/mass spectrometry using nonpolar PLOT and medium polar DB-1 columns. The analysis of the data has indicated that glucose-1-phosphate relative to glucose undergoes more extensive phosphate-catalyzed ring opening followed by formation of sugar-derived reactive intermediates as was indicated by a 9-fold increase in the amount of trimethylpyrazine and a 5-fold increase in the amount of 2,3-dimethylpyrazine, when pyrolyzed in the presence of glycine. In addition, glucose-1-phosphate alone generated a 6-fold excess of acetol as compared to glucose. On the other hand, glucose-6-phosphate enhanced retro-aldol reactions initiated from a C-6 hydroxyl group and increased the subsequent formation of furfural and 4-cyclopentene-1,3-dione. Furthermore, it also stabilized 1- and 3-deoxyglucosone intermediates and enhanced the formation of six carbon atom-containing Maillard products derived directly from them through elimination reactions such as 1,6-dimethyl-2,4-dihydroxy-3-(2H)-furanone (acetylformoin), 2-acetylpyrrole, 5-methylfurfural, 5-hydroxymethylfurfural, and 4-hydroxy-2,5-dimethyl-3-(2H)-furanone (Furaneol), due to the enhanced leaving group ability of the phosphate moiety at the C-6 carbon. However, Maillard products generated through the nucleophilic action of the C-6 hydroxyl group such as 2-acetylfuran and 2,3-dihydro-3,5-dihydroxy-4H-pyran-4-one were retarded, due to the blocked nucleophilic atom at C-6.

Formation of 4-arylpyridines from pyridinium salts under the action of methylammonium sulfite

Reactions of pyridinium salts or nonquaternized pyridine with 4-methylpyridinium salts in the presence of methylammonium sulfite in aqueous methylamine afford 4-phenylpyridine in 29—57% yields. The probable mechanism of ring transformation in simplest pyridine derivatives under the action of nucleophiles is discussed.

Decyclization of 5-Aryl-4-methyl-2,3-dihydrofuran-2,3-diones by the Action of Nucleophiles

Ring cleavage in 4-methyl-5-phenyl-2,3-dihydrofuran-2,3-dione by the action of methanol and in 5-aryl-4-methyl-2,3-dihydrofuran-2,3-diones by the action of aniline and N-methylaniline results in formation of, respectively, methyl 3-methyl-4-phenyl-2,4-dioxobutanoate and 4-aryl-3-methyl-2,4-dioxobutananilides. The reaction mechanism was studied by 1H NMR spectroscopy.

Synthesis of 4,6-dinitro-3-R-benzo[d]isoxazoles and their transformations under the action of nucleophiles

A new procedure was developed for the preparation of 4,6-dinitro-3-R-benzo[d]isoxazoles (R are derivatives of the aldehyde group) based on 2,4,6-trinitrophenylacetaldehyde. The resulting compounds are characterized by the regiospecific substitution of the nitro group at position 4 under the action of anionic nucleophiles RS–, RO–, F–, or N3 –, which allowed the development of a new method for the preparation of previously unknown 4-Nu-6-nitro-3-R-benzo[d]isoxazoles (Nu is the residue of a nucleophile). At the same time, oxidative nucleophilic substitution under the action of anions of some β-dicarbonyl compounds leads to the replacement of the hydrogen atom at position 7 with the corresponding C-nucleophiles.

Activated carbonyl species for the preparation ofortho-acylarylsydnones

ortho-Acylarylsydnones can be prepared in moderate to good yield by the action of nucleophiles upon suitable activated carbonyl species.