Nucleophilic Addition Research Articles

4-Этоксиметилен-2-фенил-5(4Н)-оксазолон в реакциях с различными гетероциклическими аминами

The analysis of the literature data has showed that there is no information on the behavior in 5(4H)-oxazolones with amines under the conditions of a sealed vessel reactor, which makes it possible to obtain heterocyclic systems with different amines. We have developed and presented an easy, fast, reliable and innovative method for the preparation of a new series of compounds with synthetic and biological potential, based on the interaction of 4-ethoxymethylene-2-phenyl-5(4H)-oxazolone and heterocyclic amines with different ring sizes and sets heteroatoms using a sealed vessel reactor. Based on the results obtained, it has been found that the transformation proceeds by the mechanism of nucleophilic addition of Michael. The scheme of the conducted interaction has been discussed. Initially, the amino group of the amine used is attacked at the exocyclic C=C bond of the initial substrate, ethoxymethylenexazolone, proceeding with the elimination of a well-leaving ethoxy group in the form of an ethanol molecule, which leads to the final 4-hetarylaminomethylidene derivatives of oxazol-5(4H)-one. In the course of the work, it has been found that the use of a sealed vessel reactor makes it possible to reduce the time of transformations, to achieve an increase in selectivity and yields of target products compared to the usual type of activation of the reaction mixture, such as boiling in ethanol. It has been shown that not only the type of activation, but also the nature of the solvent used affects the rate of the reaction. It has been found that under these conditions the transfor mation proceeds with the preservation of the oxazol-5(4Н)-one ring. Control over the course of reactions, determination of individuality and identification of the obtained compounds have been carried out by TLC, elemental analysis, IR-, NMR spectroscopy.

A NIR‐II Fluorescent Probe for Hydrogen Sulfide Detection Based on Blocking Intramolecular Charge Transfer

AbstractA NIR‐II fluorescent probe (Et‐1080) for H2S detection was fabricated based on the intramolecular charge transfer blocking mechanism. The enhanced electron density of the indole donor further drove the Et‐1080′s absorption and emission to the NIR‐II region with a high molar absorption coefficient and acceptable fluorescence quantum yield. The C=N double bond of electron‐deficient indole can react with H2S rapidly via a nucleophilic addition mechanism, resulting in the destruction of conjugated structure and fluorescence quenching of the Et‐1080 molecule. The probe showed high selectivity and sensitivity to H2S, which could realize the rapid detection of H2S in NIR‐II band and showed great potential in the further disease diagnosis associated with H2S.

An Efficient One-Step Reaction for the Preparation of Advanced Fused Bistetrazole-Based Primary Explosives.

The first example of [5,6,5]-tricyclic bistetrazole-fused energetic materials has been obtained through a one-step reaction from commercial and inexpensive 4,6-dichloro-5-nitropyrimidine. This one-step reaction including nucleophilic substitution, nucleophilic addition, cyclization, and electron transfer is rarely reported, and the reaction mechanism and scope is well investigated. Among target compounds, organic salts exhibit higher detonation velocities (D: 8898-9077 m s-1) and lower sensitivities (IS: 16-20 J) than traditional high energy explosive RDX (D = 8795 m s-1; IS = 7.5 J). In addition, the potassium salt of 5-azido-10-nitro-bis(tetrazolo)[1,5-c:5',1'-f]pyrimidin (DTAT-K) possesses excellent priming ability, comparable to traditional primary explosive Pb(N3)2, and ultralow minimum primary charge (MPC = 10 mg), which is the lowest MPC among the reported potassium-based primary explosives. The simple synthesis route, free of heavy metal and expensive raw materials, makes it promising to quickly realize this material in large-scale industrial production as a green primary explosive. This work accelerates the upgrade of green primary explosives and enriches future prospects for the design of energetic materials.

Support Vector Machine-Based Global Classification Model of the Toxicity of Organic Compounds to Vibrio fischeri.

Vibrio fischeri is widely used as the model species in toxicity and risk assessment. For the first time, a global classification model was proposed in this paper for a two-class problem (Class - 1 with log1/IBC50 ≤ 4.2 and Class + 1 with log1/IBC50 > 4.2, the unit of IBC50: mol/L) by utilizing a large data set of 601 toxicity log1/IBC50 of organic compounds to Vibrio fischeri. Dragon software was used to calculate 4885 molecular descriptors for each compound. Stepwise multiple linear regression (MLR) analysis was used to select the descriptor subset for the models. The ten molecular descriptors used in the classification model reflect the structural information on the Michael-type addition of nucleophiles, molecular branching, molecular size, polarizability, hydrophobic, and so on. Furthermore, these descriptors were interpreted from the point of view of toxicity mechanisms. The optimal support vector machine (SVM) model (C = 253.8 and γ = 0.009) was obtained with the genetic algorithm. The SVM classification model produced a prediction accuracy of 89.1% for the training set (451 log1/IBC50), of 80.0% for the test set (150 log1/IBC50), and of 86.9% for the total data set (601 log1/IBC50), which are higher than that (80.5%, 76%, and 79.4%, respectively) from the binary logistic regression (BLR) model. The global SVM classification model is successful, although it deals with a large data set in relation to the toxicity of organics to Vibrio fischeri.

Highly effective fractionation chemistry to overcome the recalcitrance of softwood lignocellulose

The efficient fractionation and thus production of individual biomass components are pivotal processes in the biorefinery concept. However, the recalcitrant nature of lignocellulose biomass, especially in the case of softwood, is one of the main obstacles to the wider application of biomass-based chemicals and materials. In this study, the use of aqueous acidic systems in the presence of thiourea was studied for the fractionation of softwood in mild conditions. Despite relatively low temperature (100 °C) and treatment times (30–90 min), notable high lignin removal efficiency (approximately 90 %) was obtained. Chemical characterization and the isolation of minor fraction of cationic, water-soluble lignin indicated that the fractionation proceed via nucleophilic addition of thiourea to lignin, resulting in dissolution of lignin in acidic water in relatively mild conditions. Besides high fractionation efficiency, both fiber and lignin fractions were obtained with bright color, significantly elevating their usability in material applications.

Advancements in the Preparation of 4H‐Chromenes: An Overview

AbstractFunctionalized 4H‐chromenes represent one class of the most important structural scaffolds in both synthetic and medicinal chemistry. They often appear in an arrange of biological natural products, pharmaceutical agents and drug candidates. The significance has stimulated the development of efficient methodologies for the synthesis of such compounds. In this review, a comprehensive discussion on different synthetic approaches to 4H‐chromenes has been presented with an emphasis on reaction features and mechanisms. Three main categories are outlined: 1) nucleophilic addition to 2H‐chromene derivatives, 2) 4H‐chromene ring formation involved cycloaddition or cyclization reactions, and 3) miscellaneous reactions.magnified image

Divergent Asymmetric Total Synthesis of (-)-Voacafricines A and B.

A divergent asymmetric total synthesis of voacafricines A and B, hexacyclic monoterpene indole alkaloids, has been accomplished featuring the following key steps: a) a catalyst-controlled asymmetric Pictet-Spengler reaction of 6-methoxytryptamine with a chiral α-ketoester affording a 1,1-disubstituted tetrahydro-β-carboline in excellent yield and diastereoselectivity; b) oxidative cleavage of a 3,5-disubstituted cyclopentene furnishing a dialdehyde intermediate, which was effectively differentiated through spontaneous cyclization with the neighboring hydroxy and secondary amine functions; c) intramolecular nucleophilic addition of a tertiary amino nitrogen atom to the in situ generated oxonium species generating stereoselectively an unprecedented 8-alkyl octahydro-2H-5,8-methanofuro[2,3-b]azepin-8-ium motif bearing five contiguous stereocenters. The synthesis confirmed the absolute configuration of these two natural products.

Divergent Asymmetric Total Synthesis of (−)‐Voacafricines A and B

AbstractA divergent asymmetric total synthesis of voacafricines A and B, hexacyclic monoterpene indole alkaloids, has been accomplished featuring the following key steps: a) a catalyst‐controlled asymmetric Pictet–Spengler reaction of 6‐methoxytryptamine with a chiral α‐ketoester affording a 1,1‐disubstituted tetrahydro‐β‐carboline in excellent yield and diastereoselectivity; b) oxidative cleavage of a 3,5‐disubstituted cyclopentene furnishing a dialdehyde intermediate, which was effectively differentiated through spontaneous cyclization with the neighboring hydroxy and secondary amine functions; c) intramolecular nucleophilic addition of a tertiary amino nitrogen atom to the in situ generated oxonium species generating stereoselectively an unprecedented 8‐alkyl octahydro‐2H‐5,8‐methanofuro[2,3‐b]azepin‐8‐ium motif bearing five contiguous stereocenters. The synthesis confirmed the absolute configuration of these two natural products.

Design and synthesis of a multifunctional rhodamine-based chemosensor for simultaneous detection of Cu2+, Zn2+ and endogenous histidine (His) and its application in living HeLa cells and zebrafishes

In organisms, the over ingesting of Cu2+ and Zn2+ will result in the poisoning of living cells, which severely damages the human body. Meanwhile, endogenous Histidine (His) can cause metabolic disorders like Histidinemia (His). Therefore, it is a pressing matter to design an effective method that accurately detects the amount of Cu2+, Zn2+, and His. In our study, through the nucleophilic addition and substitution reactions synthesis methods, a novel multifunctional probe, Rhodamine derivatives with vinyl functional groups at the end (RHDA) was designed and synthesized. The probe RHDA can recognize Cu2+ and Zn2+ separately, and the experiment further substantiates that the RHDA probe can demonstrate various turn-on colorimetric and fluorescent signals, i.e., selectively detecting Cu2+ in DMSO/H2O solution (v/v=4/6) with the “naked-eye” show evident and significant color change from colorless to pink and Zn2+ with strong green fluorescence in DMF/H2O (v/v=1/1). Under optimal conditions, they could be identified under the low detection limit of 0.10 μmol·L−1 and 16.0 nmol·L−1 for Cu2+ and Zn2+, respectively. Furthermore, Histidine (His) was recognized by the formed RHDA-Zn2+ with a fluorescence “turn-off” range of 0.03–10.0 μM and a detection limit of 230.0 nmol L−1. This article performed an extensive study of the sensing mechanisms of RHDA toward two metal ions and the ensemble RHDA-Zn2+ toward His. The practical application experiments in DMF/H2O (v/v=1/1) further established that the chemosensor RHDA exhibits good cell permeability and could be employed to monitor free Zn2+. Finally, the complex RHDA-Zn2+ could be applied to assay His in the living HeLa cells and zebrafishes, respectively.

A smart polymer electrolyte coordinates the trade-off between thermal safety and energy density of lithium batteries

In this article, we develop a smart polymer electrolyte through in-situ radical random polymerization of the cyclic carbonate urethane methacrylate monomer and the 2-isocyanatoethyl methacrylate monomer, which coordinates the trade-off between thermal safety and energy density of lithium batteries. It is demonstrated that the as-developed polymer electrolyte can incur the battery thermal shutdown before reaching the thermal runaway temperature. This originates from the highly crosslinking network caused by the nucleophilic addition of carbamate to isocyanate in the polymer matrix under the elevated temperature exceeding 170 °C. Besides, superior cycle performance of 4.5 V-class LiNi0.6Co0.2Mn0.2O2/Li batteries can be achieved, with a capacity retention of 80% after 200 cycles at 0.5 C and 30 °C, owing to enhanced interface compatibility of this polymer electrolyte. Noting that this polymer electrolyte possesses a superior water-scavenging ability, which helps improve the moisture resistance and battery cycle performance. Impressively, this polymer electrolyte can achieve improved energy density and superior safety characteristic of lithium batteries under high cut-off voltage.

Convenient synthesis of N-sulfonyl α-hydroxyamides via DMSO oxidation of N-alk-1-ynylsulfonamides

ABSTRACT N-Arenesulfonyl α-hydroxyamides are conveniently synthesized from N-arylethynylsulfonamides (ynamides) via oxidation with dimethyl sulfoxide (DMSO) in the presence of equivalent of trifluoromethanesulfonic acid (TfOH) followed by treatment with water. In this reaction, ynamides are activated by protonation with TfOH and then undergo double DMSO nucleophilic addition and subsequent hydrolysis. Investigations on the substrate scope indicate N-arenesulfonyl and arylethynyl substituted ynamides proceed the oxidation well. Compared to the previous methods, the current method realizes the direct conversion from N-arylethynylsulfonamides to N-arenesulfonyl α-hydroxyamides with mild DMSO as a nucleophilic oxidant in the presence of strong acid trifluoromethanesulfonic acid.

Ni-Mg/Al Mixed Oxides Prepared from Layered Double Hydroxides as Catalysts for the Conversion of Furfural to Tetrahydrofurfuryl Alcohol

Ni-Mg/Al mixed oxide catalysts (Ni2Al, Ni2Mg1Al, and Ni1Mg1Al) obtained from layered double hydroxides (LDHs) were tested on the one-pot production of tetrahydrofurfuryl alcohol (TFA) from furfural (FF). Upon calcination at 400 °C and reduction at 500 °C, the LDHs gave catalysts containing small nickel crystallites (<4 nm) dispersed on mixtures of metal oxides and spinel structures. Complete conversion of FF (>99.5%) was achieved on all the catalysts after 4 h at 190 °C and 5.0 MPa of H2 using 5 wt.% FF in ethanol and a furfural-to-catalyst mass ratio of 7.44 g/g. TFA evolved from the sequential hydrogenation of FF to furfuryl alcohol (FA) to TFA. Competing reaction routes involved decarbonylation of FF to furan (FUR) followed by hydrogenation to tetrahydrofuran (THF) or hydrogenolysis to n-butane (BU) and the hydrogenation of the carbonyl group in FF to form 2-methyl furan (mFUR) and its hydrogenation to 2-methyltetrahydrofuran (mTHF). A third competing route consisted of the nucleophilic addition of FF with ethanol and with FA to form acetals (such as 2-(diethoxymethyl)furan, FDA), which were later converted to difurfuryl ether (DFE) and tetrahydrofurfuryl ethyl ether (TFEE) as final products. Hydrogen pressure favored the production of TFA and diminished the formation of acetals, while temperature reduced the capacity of the catalyst to hydrogenate the furan ring, thus reducing TFA and increasing FA and FUR. An 80% yield to TFA was achieved with the Ni2Mg1Al catalysts after 6 h at 190 °C and 50 bar H2, but a variety of coproducts were present at low concentration. Testing of the catalysts in gas-phase hydrogenation conditions at atmospheric pressure revealed a poorer performance, with FA as the main product.

A general highly efficient synthesis of biocompatible rhodamine dyes and probes for live-cell multicolor nanoscopy

The development of live-cell fluorescence nanoscopy is powered by the availability of suitable fluorescent probes. Rhodamines are among the best fluorophores for labeling intracellular structures. Isomeric tuning is a powerful method for optimizing the biocompatibility of rhodamine-containing probes without affecting their spectral properties. An efficient synthesis pathway for 4-carboxyrhodamines is still lacking. We present a facile protecting-group-free 4-carboxyrhodamines’ synthesis based on the nucleophilic addition of lithium dicarboxybenzenide to the corresponding xanthone. This approach drastically reduces the number of synthesis steps, expands the achievable structural diversity, increases overall yields and permits gram-scale synthesis of the dyes. We synthesize a wide range of symmetrical and unsymmetrical 4-carboxyrhodamines covering the whole visible spectrum and target them to multiple structures in living cells – microtubules, DNA, actin, mitochondria, lysosomes, Halo-tagged and SNAP-tagged proteins. The enhanced permeability fluorescent probes operate at submicromolar concentrations, allowing high-contrast STED and confocal microscopy of living cells and tissues.

Iodine-Catalyzed Annulation Reaction of Ortho-Formylarylketones with Indoles: A General Strategy for the Synthesis of Indolylbenzo[b]carbazoles

The iodine-catalyzed cascade reaction of ortho-formylarylketones with indoles for the synthesis of indolylbenzo[b]carbazoles is reported. The reaction is initiated in the presence of iodine by two successive nucleophilic additions of indoles with an aldehyde group of ortho-formylarylketones, and the ketone does not undergo a nucleophilic addition and only involves in the Friedel-Crafts-type cyclization. A variety of substrates are tested, and the efficiency of this reaction is demonstrated with gram-scale reactions.

Asymmetric Synthesis of Chiral Sulfimides through the O-Alkylation of Enantioenriched Sulfinamides and Addition of Carbon Nucleophiles.

Chiral sulfimides, the aza-analogues of sulfoxides, are valuable compounds in organic synthesis and medicinal chemistry. Herein, we report an efficient method for preparing chiral sulfimides from easily available enantioenriched sulfinamides. The key step of this method is a stereospecific oxygen-selective alkylation of enantioenriched sulfinamides, which is accomplished by using isopropyl iodide, K2 CO3 , and DMPU. The resulting chiral sulfinimidate esters are transformed to chiral sulfimides by the nucleophilic addition of the Grignard reagents under simple conditions. This transformation enables access to the enantioenriched diaryl or dialkyl sulfimides bearing two similar carbon substituents, which are difficult to synthesize by previous methods.

Asymmetric Synthesis of Chiral Sulfimides through the O‐Alkylation of Enantioenriched Sulfinamides and Addition of Carbon Nucleophiles

AbstractChiral sulfimides, the aza‐analogues of sulfoxides, are valuable compounds in organic synthesis and medicinal chemistry. Herein, we report an efficient method for preparing chiral sulfimides from easily available enantioenriched sulfinamides. The key step of this method is a stereospecific oxygen‐selective alkylation of enantioenriched sulfinamides, which is accomplished by using isopropyl iodide, K2CO3, and DMPU. The resulting chiral sulfinimidate esters are transformed to chiral sulfimides by the nucleophilic addition of the Grignard reagents under simple conditions. This transformation enables access to the enantioenriched diaryl or dialkyl sulfimides bearing two similar carbon substituents, which are difficult to synthesize by previous methods.

Serendipitous discovery of Pd-catalyzed intramolecular cyclization of ortho-bromo(hetero)aryl-substituted (hetero)aryl-1,2-diketones: Applications in the synthesis of carba- and heterocyclic benzoin derivatives

Carbaand heterocyclic benzoin derivatives were prepared by Sonogashira coupling of alkynes with 1,2-dihaloalkenes and subsequent oxidation of the alkyne to a 1,2-diketone. The Pd-catalyzed reaction of the product with (2-bromophenyl)boronic acid in the presence of phenylacetylene resulted in formation of cyclic benzoin derivatives by Suzuki-Miyaura reaction and subsequent Pd catalyzed nucleophilic addition to the carbonyl group. Hitherto unprecedented 5-hydroxy-5-phenylbenzo[b]naphtho[1,2-d]thiophene-6(5H)-ones and their regioisomers were prepared from 2,3-dibromobenzothiophene. Phenanthrene benzoin derivatives were prepared from 2-bromo-1-iodobenzene.

Amide N-C Bond Activation: A Graphical Overview of Acyl and Decarbonylative Coupling.

This Graphical Review provides an overview of amide bond activation achieved by selective oxidative addition of the N-C(O) acyl bond to transition metals and nucleophilic acyl addition, resulting in acyl and decarbonylative coupling together with key mechanistic details pertaining to amide bond distortion underlying this reactivity manifold.

Acetylene-driven multi-molecular assemblies of high complexity: imidazo[1,2-a]pyridines and 5-chloro-N-[2-(imidazo[1,2-a]pyridin-6-yl)vinyl]pyridin-2-amine

Acetylene reacts with 2-aminopyridines in the superbase system KOBut/DMSO (the initial acetylene pressure ∼8 atm, 80 °C, 5 min) to give 2,3-dimethylimidazo[1,2-α]-pyridines in up to 60% yields. In the case of 2-amino-5-chloropyridine, along with ‘normal’ product, (Z)-5-chloro- N-[2-(2,3-dimethylimidazo[1,2-α]pyridin-6-yl)vinyl]pyridin-2-amine is formed in 40% yield. These multi-molecular assemblies involve parallel nucleophilic addition of N-centered anions to the triple bond and ethynylation of the forming C=N bond.

Bio-hyperbranched polyesters synthesized from citric acid and bio-polyols and applications on wood adhesives

Biomass-based adhesives have attracted extensive research interest in recent years as an effective alternative to formaldehyde-based adhesives which are non-renewable and harmful to human health. In this paper, citric acid-based hyperbranched polyester (HBPCA) resins were synthesized by green and simple strategy using natural citric acid (CA) and succinic anhydride (SA) as raw materials. Hyperbranched polyol (HBP) was prepared by nucleophilic addition reaction of SA with diethanolamine and later condensed with CA to produce HBPCA resins. The chemical structure of HBPCA resins was characterized using Fourier transform infrared spectroscopy (FTIR), 13C nuclear magnetic resonance (13C NMR), X-ray photoelectron spectroscopy (XPS), liquid chromatography−mass spectrometry (LC-MS), and gel permeation chromatography (GPC). The introduction of HBP enabled the resins to form a hyperbranched network cross-linked structure, which increased the cross-link density and thus prevented the intrusion of moisture. The results showed that HBPCA resin plywood has excellent adhesive strength and water resistance. The shear strength was 1.49 MPa and 1.47 MPa after immersion in hot water at 63 °C and boiling water at 93 °C for 3 h. The green and simple synthesis of HBPCA resins and their excellent properties provide a novel strategy for preparing biomass-based adhesives.