Electrophilic Addition Research Articles

Ferrate(VI) assists in reducing cytotoxicity and genotoxicity to mammalian cells and organic bromine formation in ozonated wastewater

Ozonation of wastewater containing bromide (Br−) forms highly toxic organic bromine. The effectiveness of ozonation in mitigating wastewater toxicity is minimal. Simultaneous application of ozone (O3) (5 mg/L) and ferrate(VI) (Fe(VI)) (10 mg-Fe/L) reduced cytotoxicity and genotoxicity towards mammalian cells by 39.8% and 71.1% (pH 7.0), respectively, when the wastewater has low levels of Br−. This enhanced reduction in toxicity can be attributed to increased production of reactive iron species Fe(IV)/Fe(V) and reactive oxygen species (•OH) that possess higher oxidizing ability. When wastewater contains 2 mg/L Br−, ozonation increased cytotoxicity and genotoxicity by 168%-180% and 150%-155%, respectively, primarily due to the formation of organic bromine. However, O3/Fe(VI) significantly (p < 0.05) suppressed both total organic bromine (TOBr), BrO3−, as well as their associated toxicity. Electron donating capacity (EDC) measurement and precursor inference using Orbitrap ultra-high resolution mass spectrometry found that Fe(IV)/Fe(V) and •OH enhanced EDC removal from precursors present in wastewater, inhibiting electrophilic substitution and electrophilic addition reactions that lead to organic bromine formation. Additionally, HOBr quenched by self-decomposition-produced H2O2 from Fe(VI) also inhibits TOBr formation along with its associated toxicity. The adsorption of Fe(III) flocs resulting from Fe(VI) decomposition contributes only minimally to reducing toxicity. Compared to ozonation alone, integration of Fe(VI) with O3 offers improved safety for treating wastewater with varying concentrations of Br−.

Tf2O/2-Chloropyridine-Triggered Synthesis of Benzo[b]thiophene 1,1-Dioxides from Sulfonium α-Acyl Sulfonylmethylides.

Triflic anhydride and 2-chloropyridine-comediated tandem activation, intramolecular aromatic electrophilic addition, and 1,2-sulfonyl shift via spirocyclic intermediates of sulfonium α-acyl sulfonylmethylides realize the efficient synthesis of 2-alkyl/arylthiobenzo[b]thiophene 1,1-dioxides. The deactivated sulfonyl group determines the site-selectivity of the electrophilic addition via the ipso-attack, while the following S-migration controls the regioselectivity. Some of 2-methylthiobenzo[b]thiophene 1,1-dioxides show fluorescence properties in the solid state and in their solutions.

Quantum chemical explanation and APT atomic charge index of substituent orienting effect proposed by DFT calculation and MO Theory

AbstractIn organic chemistry textbooks, the electron resonance states are used to explain the orienting effect of benzene substituent. However, these resonance states do not exist in the C6H5‐S + E+ electrophilic addition, so the resonance state discussions actually are meaningless. The density functional theory (DFT) calculation shows that the C6H5‐S + E+ addition follows the transition state theory and needs to overcome a barrier. Benzene molecule C6H6 has two degenerate highest occupied molecular orbitals (HOMOs), but after becoming substituted benzenes, the two HOMOs split to HOMO and HOMO‐1 with different orbital energies and electron distributions. It makes the addition barrier on two or three benzene ring carbons is low, and the addition rate is fast, but the barrier of other carbons is high, and the rate is slow. Therefore, substituent splits the two degenerate HOMOs of benzene molecule, which is the origin of substituent orienting effect. For the substituted benzenes with halogen group ‐X and electron‐releasing group, their HOMO images alone can determine that the two types of substituents are the ortho‐ and para‐orienting groups, but for the substituted benzenes with electron‐withdrawing group, their HOMO alone cannot determine whether the substituent is a meta‐orienting group. The study found that atomic polar tensor (APT) charges are a good judgment index of substituent orienting effect because based on its physic‐chemical model, the charges represent the number of active electrons on the benzene ring carbons. The DFT calculation gives the APT charges of 19 mono‐substituted and 12 di‐substituted benzenes and some aromatic molecules. The APT charges can all correctly determine their orienting effects, showing that APT atomic charge from quantum theoretical calculation is a good substituent orienting index.

Total Synthesis of the Racemate of Laurolitsine

The total synthesis of laurolitsine was achieved for the first time. This reaction was accomplished in 14 steps with a 2.3% yield (this was calculated using 3-hydroxy-4-methoxybenzaldehyde as the starting material) starting from two simple materials, 3-hydroxy-4-methoxybenzaldehyde and 2-(3-hydroxy-4-methoxyphenyl)acetic acid, and the longest linear sequence consisted of 11 steps. The key steps included an electrophilic addition reaction in which a nitro group was reduced to an amino group using lithium tetrahydroaluminum and a Pd-catalyzed direct biaryl coupling reaction. In this paper, many of the experimental steps were optimized, and an innovative postprocessing method in which 2-(3-(benzyloxy)-4-methoxyphenyl)ethanamine is salted with oxalic acid was proposed.

Ca(II)-Catalyzed Cascade Reaction of Tryptamines with Propargylic Alcohols: Temperature-Driven Ring Opening and Closing via the Allene Migration Pathway for the Synthesis of Pyrrolo[1,2-a]indoles.

A temperature-dependent cascade of reactions between tryptamines and propargylic alcohols was developed to achieve selective formation of pyrroloindoline and pyrrolo[1,2-a]indole heterocycles by Ca(II) catalysis. The cascade consists of electrophilic addition of allene at the C3 carbon of indole followed by intramolecular cyclization at 60 °C to yield pyrroloindolines. Furthermore, simultaneous 1,2-allene migration and pyrrolidine ring opening were followed by intramolecular cyclization via C-N bond formation at reflux temperature to obtain pyrrolo[1,2-a]indole scaffolds. A wide range of substrates, a clean reaction profile, scalability, and good to excellent yields are the advantages of this protocol.

Exploring Electrophilic Hydrophosphination via Metal Phosphenium Intermediates.

Two Mo(0) phosphenium complexes containing ancillary secondary phosphine ligands have been investigated with respect to their ability to participate in electrophilic addition at unsaturated substrates and subsequent P-H hydride transfer to "quench" the resulting carbocations. These studies provide stoichiometric "proof of concept" for a proposed new metal-catalyzed electrophilic hydrophosphination mechanism. The more strongly Lewis acidic phosphenium complex, [Mo(CO)4(PR2H)(PR2)]+ (R=Ph, Tolp), cleanly hydrophosphinates 1,1-diphenylethylene, benzophenone, and ethylene, while other substrates react rapidly to give products resulting from competing electrophilic processes. A less Lewis acidic complex, [Mo(CO)3(PR2H)2(PR2)]+, generally reacts more slowly but participates in clean hydrophosphination of a wider range of unsaturated substrates, including styrene, indene, 1-hexene, and cyclohexanone, in addition to 1,1-diphenylethylene, benzophenone, and ethylene. Mechanistic studies are described, including stoichiometric control reactions and computational and kinetic analyses, which probe whether the observed P-H addition actually does occur by the proposed electrophilic mechanism, and whether hydridic P-H transfer in this system is intra- or intermolecular. Preliminary reactivity studies indicate challenges that must be addressed to exploit these promising results in catalysis.

Unraveling the atmospheric oxidation mechanism and kinetics of naphthalene: Insights from theoretical exploration

Naphthalene, the most abundant polycyclic aromatic hydrocarbon in the atmosphere, significantly influences OH consumption and secondary organic aerosol (SOA) formation. Naphthoquinone (NQ) is a significant contributor to ring-retaining SOA from naphthalene degradation, impacting the redox properties and toxicity of ambient particles. However, inconsistencies persist regarding concentrations of its isomers, 1,2-NQ and 1,4-NQ. In present work, our theoretical investigation into naphthalene's reaction with OH and subsequent oxygenation unveils their role in SOA formation. The reaction kinetics of initial OH and subsequent O2 oxidation was extensively studied using high-level quantum chemical methods (DLPNO-CCSD(T)/aug-ccpVQZ//M052x-D3/6–311++G(d,p)) combined with RRKM/master equation simulations. The reactions mainly proceed through electrophilic addition and abstraction from the aromatic ring. The total rate coefficient of naphthalene + OH at 300 K and 1 atm from our calculation (7.2 × 10−12 cm3 molecule−1 s−1) agrees well with previous measurements (∼1 × 10−11 cm3 molecule−1 s−1). The computed branching ratios facilitate accurate product yield determination. The largest yield of 1-hydroxynaphthalen-1-yl radical (add1) producing the major precursor of RO2 is computed to be 93.8 % in the ambient environment. Our calculated total rate coefficient (5.2 × 10−16 cm3 molecule−1 s−1) for add1 + O2 closely matches that of limited experimental data (8.0 × 10−16 cm3 molecule−1 s−1). Peroxy radicals (RO2) generated from add1 + O2 include 4-cis/trans-(1-hydroxynaphthalen-1-yl)-peroxy radical (add1-4OOadd-cis/trans, 66.0 %/17.5 %), 2-cis/trans-(1-hydroxynaphthalen-1-yl)-peroxy radical (add1-2OOadd-cis/trans, 10.3 %/6.3 %). Regarding the debated predominance of 1,4-NQ (corresponding to the parent RO2, i.e., add1-4OOadd-cis/trans) and 1,2-NQ (corresponding to the parent RO2, i.e., add1-2OOadd-cis/trans) in the atmosphere, our findings substantiate the dominance of 1,4-NQ. This study also indicates potential weakening of 1,4-NQ's dominance due to competition from decomposition reactions of add1-4OOadd-cis/trans and add1-2OOadd-cis/trans. Precise reaction kinetics data are essential for characterizing SOA transformation derived from naphthalene and assessing their climatic impacts within modeling frameworks.

Synthesis of Selenocyanated Indoles via PhICl2‐Induced Electrophilic Intramolecular Cyclization of 2‐Alkynylanilines or 2‐Alkenylanilines

AbstractThe 3‐selenocyanato‐substituted indoles were readily synthesized via (dichloroiodo)benzene (PhICl2)‐induced reaction of 2‐alkynylanilines or 2‐alkenylanilines with KSeCN in MeCN under metal‐free conditions. The reaction sequence was postulated to encompass the formation of a reactive selenocyanogen chloride species, generated in situ from the reaction of PhICl2 and KseCN, followed by electrophilic addition and intramolecular cyclization steps.

Dithiophosphoric Acids for Polymer Functionalization.

Dithiophosphoric acids (DTPAs) are an intriguing class of compounds that are sourced from elemental sulfur and white phosphorus and are prepared from the reaction of phosphorus pentasulfide with alcohols. The electrophilic addition of DTPAs to alkenes and unsaturated olefinic substrates is a known reaction, but has not been applied to polymer synthesis and polymer functionalization. We report on the synthesis and application of DTPAs for the functionalization of challenging poly-enes, namely polyisoprene (PI) and polynorbornene (pNB) prepared by ring-opening metathesis polymerization (ROMP). The high heteroatom content within DTPA moieties impart intriguing bulk properties to poly-ene materials after direct electrophilic addition reactions to the polymer backbone introducing DTPAs as side chain groups. The resulting materials possess both enhanced optical and flame retardant properties vs the poly-ene starting materials. Finally, we demonstrate the ability to prepare crosslinked polydiene films with di-functional DTPAs, where the crosslinking density and thermomechanical properties can be directly tuned by DTPA feed ratios.

Dithiophosphoric Acids for Polymer Functionalization

AbstractDithiophosphoric acids (DTPAs) are an intriguing class of compounds that are sourced from elemental sulfur and white phosphorus and are prepared from the reaction of phosphorus pentasulfide with alcohols. The electrophilic addition of DTPAs to alkenes and unsaturated olefinic substrates is a known reaction, but has not been applied to polymer synthesis and polymer functionalization. We report on the synthesis and application of DTPAs for the functionalization of challenging poly‐enes, namely polyisoprene (PI) and polynorbornene (pNB) prepared by ring‐opening metathesis polymerization (ROMP). The high heteroatom content within DTPA moieties impart intriguing bulk properties to poly‐ene materials after direct electrophilic addition reactions to the polymer backbone introducing DTPAs as side chain groups. The resulting materials possess both enhanced optical and flame retardant properties vs the poly‐ene starting materials. Finally, we demonstrate the ability to prepare crosslinked polydiene films with di‐functional DTPAs, where the crosslinking density and thermomechanical properties can be directly tuned by DTPA feed ratios.

Stereospecific Indium(III)‐Catalysed Tandem Cycloisomerization of Functionalized 1,6‐enynes: Scope and Mechanistic Insights

AbstractTandem cycloisomerization reactions of functionalized 1,6‐enynes under indium(III) catalysis are described. This atom‐economic transformation proceeds smoothly with 5‐exo‐dig regioselectivity using commercial In(III) halides and 1,6‐enynes furnished with alcohol, carboxylic acid or amine functional groups to give bicyclic structures in good yields and diastereoselectivities. The reaction with enynals involves a three–step mechanism to give an oxatricycle and a conjugated 1,3‐diene. In the absence of the internal nucleophile the enyne cycloisomerization evolves through a skeletal rearrangement or a cyclopropanation reaction after the regioselective 5‐exo‐dig cyclization. The 1,6‐enyne cycloisomerization is stereospecific and the stereoselectivity appears to be independent of the internal nucleophile. Experimental data support a common reaction mechanism involving an initial alkyne electrophilic π‐coordination of In(III) followed by Markovnikov electrophilic alkene addition and ring‐closure by nucleophilic attack. DFT studies hold up a stepwise mechanism involving the formation of a chiral non‐classical carbocation intermediate that determines the diastereoselectivity of this tandem cycloisomerization reaction.

Indium(III)‐Catalyzed Three Component Reaction of N‐Bromosuccinimide, Alkenes and N‐Tosylhydrazones

AbstractA three‐component reaction involving alkenes, N‐sulfonylhydrazones, and N‐bromosuccinimide (NBS) is described that uses Indium(III) triflate for the synthesis of bromoethyl sulfonyl hydrazones. Using N‐tosylhydrazones as a nitrogen source and NBS as a bromine source, this intermolecular aminobromination of alkenes is carried out under air in mild conditions. A mechanism of electrophilic addition is proposed based on the GC‐MS analytical result.

A sensitive coumarin fluorescence sensor designed for isoprene detection and imaging research in plants

The release of isoprene by plants is considered to be an adaptation to the environment. Herein, a highly selective coumarin fluorescent probe (DMIC) was designed for detecting isoprene. When isoprene came into contact with the maleimide of DMIC, an electrophilic addition process took place. The powerful push-pull effect of DMIC was disrupted. Simultaneously, intramolecular charge transfer was initiated. This enabled DMIC to achieve rapid detection of isoprene within 5 min. Furthermore, excellent linearity was observed in the concentration range of 1–560 ppm (R2 = 0.996). A limit of detection is 1.6 ppm. DMIC was applied to in vitro studies of plant release of liberated isoprene. By monitoring the release of isoprene from different tree species throughout the day, the dynamics of isoprene release from plants throughout the day have been successfully revealed. In addition, the release of isoprene varied considerably among different tree species. In particular, the biocompatibility of DMIC allowed for the in vivo detection of isoprene using fluorescence imaging. The results successfully revealed the dynamics of isoprene release in plants under stress. The amount of isoprene that a plant produced increased with the severity of the stress it experienced. This suggested that the level of isoprene content in plants could be used as a preliminary indicator of the physiological health status of plants. This research demonstrates great potential for clarifying signal transduction in biological systems. It provided ideas for further understanding the biology of isoprene.

Experimental and computational studies on the palladium-catalyzed intramolecular dearomatization, electrophilic addition, intermolecular coupling sequence

An unprecedented Pd-catalyzed highly stereoselective synthetic strategy for the construction of a broad spectrum polycyclic fused indoline skeletons employing N-halobenzoyl o-haloanilines and N-(prop-2-yn-1-yl)anilines as has been described.

Theoretical investigation of the OH-initiated atmospheric degradation mechanism of CX2CHX (X = H, F, Cl) by advanced quantum chemical and transition state theory methods.

Halogenated olefins are anthropogenic compounds with many industrial applications but at the same time raising many environmental and health concerns. Gas-phase electrophilic addition of the OH radical to the olefinic CC bond represents the primary sink for these chemicals in the atmosphere, with the degree and type of halogenation playing a significant role in their overall reactivity. In this work, we present a theoretical investigation of the reaction mechanisms and kinetics for the reactions between the OH radical and CH2CH2 (ethylene, ETH), CF2CHF (trifluoroethylene, TFE) and CCl2CHCl (trichloroethylene, TCE), simulated by state-of-the-art protocols and methods, with the aim of providing a detailed interpretation of the available experimental results, as well as new data of relevance to tropospheric chemistry. Specifically, potential energy surfaces (PESs) are obtained using the jun-Cheap (jChS) composite scheme, whereas temperature and pressure dependent rate coefficients and product distributions in the 100-600 K temperature range are calculated within the Rice-Ramsperger-Kassel-Marcus/master equation (RRKM/ME) framework. The rates for barrierless channels are obtained from variable reaction coordinate-variational transition state theory (VRC-VTST) combined with the two transition state model. While the reactions with ETH and TFE proceed mainly via the formation of addition adducts at P = 1 atm and T = 298 K, the dominant channel for TCE is the Cl-elimination reaction. Global rate constants for the two halogenated olefins, TFE and TCE, are found to be pressure-independent, contrary to the case of ETH. The computed rate constants, as well as their temperature and pressure dependence, are in remarkable agreement with the available experimental data, and they are used to derive atmospheric lifetimes (τ) for both TFE and TCE as a function of altitude (h) in the atmosphere, by taking into account variations in the rate coefficients (k (T, P)) and [OH] concentration.

Diastereoselective cyclopropanation of α,β-unsaturated carbonyl compounds with vinyl sulfoxonium ylides.

Herein, we report a three-component stereoselective cyclopropanation of vinyl sulfoxonium ylides with indane 1,3-dione and aldehydes under mild reaction conditions. In contrast to previous reports, the present work shows that electrophilic addition selectively takes place at the α-position of the vinyl sulfoxonium ylide. The interesting feature of this approach is that the multicomponent reaction selectively proceeds because of the difference in nucleophilic reactivity of vinyl sulfoxonium ylides and indane 1,3-dione with electrophilic partners, such as aldehydes and in situ generated arylidenes. Additionally, density functional theory (DFT) studies were conducted to investigate the difference in the reactivity of these reactants, as well as to unveil the mechanism of this three-component reaction. Furthermore, non-covalent interactions of selectivity-determining transition states explain the origin of the diastereoselectivity of cyclopropanation.

Cross-linked amidoxime porous resin for selective gallium separation in Bayer solutions: Reaction mechanism and kinetic study

The commercial resin suffers from slow diffusion rates and long mass transfer times, limiting its practical application in gallium extraction in Bayer solution. A novel amidoxime grafted polyacrylonitrile-styrene–divinylbenzene (A-PSD) resin was prepared by suspension acrylonitrile-styrene–divinylbenzene resins and subsequent electrophilic addition of hydroxylamine hydrochloride with amidoxime. Adsorption sites and mechanism study proved that the Ga3+ reacted with the amidoxime groups (CNOH) on the A-PSD resins. The A-PSD resins for Ga3+ adsorption followed the Langmuir model and exhibited excellent adsorption performance in Bayer solution with a Ga3+ capacity of 14.67 mg/g at 25 °C. The kinetic adsorption experiment showed that the adsorption process was controlled by chemical reaction and followed the pseudo-second-order kinetic model. The penetration curves of the column experiments indicate the possibility of industrial application of A-PSD resins, which may lay the groundwork for a new alternative to Ga3+ adsorption resins.

Chlorination of UV Filters with Antioxidant Shield in Swimming Pool Waters - Products Identification and Toxicity Assessment.

This work summarizes our research on synthesis, characterization and toxicity of selected UV-A filters and their antioxidant shield in commercial formulation - resveratrol. Benzophenone type of UV filters react under disinfection conditions with chlorine and form different mono- and dichlorinated products, while dibenzoylmethane derivatives, such as avobenzone, react with chlorine and form two main bridge chlorinated products followed by numerous chlorinated species at the advanced stages of the process. Resveratrol showed three main susceptible centers to chlorination, starting from the electrophilic addition to the double bond and continuing with the chlorination of the phenolic moieties. Several experiments conducted under different disinfection conditions (pool/sea water, addition of salts, irradiation) showed basically similar chlorination patters with some variations in terms of product formation. The results of toxicity assessment using different test organisms (Vibrio fischeri, microalgae, daphnids) have shown different sensitivity of testing organisms to the parent UV filters in comparison with chlorinated products as well as different toxicity for specific UV filter in comparison to the others. As the closing loop of all experiments in the laboratory, an up-scaling to the real human skin is presented.

Cocamidopropyl betaine - a potential source of nitrogen-containing disinfection by-products in pool water.

Water treatment for most public pools involves disinfection with active chlorine leading to the formation of disinfection by-products (DBPs). Among them, nitrogen-containing compounds (N-DBPs) having increased toxicity and adverse effects on human health are of the greatest concern. Being the major component of various body washers for swimmers, cocamidopropyl betaine (CAPB) represents a potential and still underestimated anthropogenic precursor of N-DBPs in pool water. The purpose of this study was to investigate CAPB transformation pathways and mechanisms under the aqueous chlorination conditions. High-performance liquid and two-dimensional gas chromatography hyphenated with high-resolution mass spectrometry were used for the search and tentative identification of the primary and final CAPB transformation products. A wide range of DBPs containing up to five chlorine atoms including these in combination with hydroxyl and additional carbonyl groups has been revealed in model chlorination experiments for the first time. The proposed mechanism of their formation involves nucleophilic substitution of the secondary amide hydrogen atom at the first stage with subsequent free radical and electrophilic addition reactions resulting in non-selective introduction of halogen atoms and hydroxyl groups in the alkyl chain. The deep transformation products include short-chain chlorinated hydrocarbons and their oxidation products as well as dimethylcarbamoyl chloride possessing high toxicity and carcinogenic properties. Targeted analysis of real swimming pool water samples confirmed the results of model experiments enabling semi-quantitative determination of CAPB (0.8µg L-1) and 18 primary DBPs, including 10 chlorine-containing compounds with the total concentration of 0.1µg L-1. Among them, monochloro (50%) and hydroxydichloro (25%) derivatives predominate. The toxicity and health of the main DBPs has been estimated using QSAR/QSTR approach. Thus, the possibility of formation of new classes of potentially toxic chlorine-containing DBPs associated with the widespread use of detergents and cosmetics was shown.

Unusual Single Electron Transfer Reactions between Alkenes and Iodine Electrophiles†

Comprehensive SummaryThe electrophilic addition to an alkene with an electrophile has been widely studied and applied in organic synthesis. The organic chemistry textbook describes the classical reaction between an alkene and an iodine electrophile (such as elemental iodine and N‐iodosuccinimide (NIS)) as a typical ionic reaction, in which an iodonium ion is formed and then attacked by a nucleophile. However, in this article, we report a new and unusual reaction mode between an alkene and NIS; that is, a single electron transfer (SET) process occurs between these two reactants by forming an electron‐donor acceptor complex. Not only does this unusual single electron transfer reaction between an alkene and NIS add fundamentally important knowledge to organic chemistry, it also provides a valuable synthetic method as the new SET reaction mode with opposite regioselectivity as compared with the traditional ionic mode.