Sequential Addition Reactions Research Articles

Intracluster reaction dynamics of NO+(H2O)n.

Nitric oxide (NO) and NO-water clusters play crucial roles in the D-region of the atmosphere because it is postulated that NO+ reacts with H2O to produce nitrous acid (HONO) and H3O+. HONO is the major precursor of the hydroxyl radicals leading to the formation of secondary pollutants. The sources of atmospheric HONO, however, are not fully understood. Previously, the sequential H2O addition reaction, H2O + NO+(H2O)n, and the bi-molecular collision reaction, NO+ + (H2O)n, have been investigated by both experiments and theoretical calculations to determine the formation mechanism of HONO. However, the photo-reactions from NO(H2O)n neutral clusters were not considered for the formation mechanism of HONO. In this study, the intra-cluster reactions of NO+(H2O)n clusters, following ionization of the parent neutral cluster of NO(H2O)n, were investigated using the direct abinitio molecular dynamics method. When n = 4, [NO+(H2O)4]ver [vertical ionization state of NO(H2O)n] yielded HONO and hydrated H3O+ after the intra-cluster reaction, and the reaction time was calculated to be 150fs. The reaction is expressed as [NO+(H2O)n]ver → HONO + H3O+(H2O)n-2 (reactive) (n > 3). Larger clusters of [NO+(H2O)n]ver (n = 5-8) also yield HONO. In contrast, in smaller clusters (n = 1-3), only solvent re-orientation around NO+ occurred after the ionization: [NO+(H2O)n]ver → NO+(H2O)n (solvent re-orientation) (n = 1-3). The hydration energy of H3O+, which depends on the cluster size (n), plays an important role in promoting the formation of HONO. The reaction mechanism is discussed based on theoretical results.

Synthesis of Polycyclic Chromeno[4,3,2‐ij]Isoquinoline‐3‐Carbonitriles in the Presence of Ammonium acetate as a Dual Rule Reagent‐Catalyst

AbstractIn this paper, a two‐step process is described for the chemoselective synthesis of highly fluorescent polycyclic chromeno[4,3,2‐ij]isoquinoline‐3‐carbonitriles using a sequential nucleophilic addition reaction involving 4‐chloro‐3‐vinyl coumarins, α,α‐dicyanoolefins and ammonium acetate as a source of nitrogen. In this process, it is believed that ammonium acetate is converted into ammonia and acetic acid during the reaction. Ammonia is the source of nitrogen, and the acid produced can catalyze the progress of the reaction. Single‐crystal X‐ray analysis was performed to confirm the structure of one of the typical products. In addition, the photophysical characteristics of the product 3 a were investigated through absorption and emission spectroscopy. This analysis reveals that the new heterocyclic system has impressive fluorescence characteristics. Several advantages of the presented synthetic strategy can be found in its simplicity, readily available starting materials, high‐efficiency products, highly chemoselective route, metal‐free catalyst, and ability to purify products by washing them with EtOH (96 %), a technique called GAP (Group‐Assisted‐Purification) chemistry.

One-Pot Three-Component Reaction for the Synthesis of 3,4-Dihydroquinazolines and Quinazolin-4(3H)-ones.

A highly efficient and straightforward one-pot synthesis of diversely substituted 3,4-dihydroquinazolines and quinazolin-4(3H)-ones has been achieved through a domino three-component assembly reaction of arenediazonium salts, nitriles, and bifunctional aniline derivatives. This new protocol involves three C-N bond formations through the initial formation of N-arylnitrilium intermediates from arenediazonium salts and nitriles, followed by the sequential nucleophilic addition and cyclization reactions with bifunctional anilines, leading to such N-heterocyclic compounds of biological and pharmacological importance. This method offers a simple, expedient, and robust approach with the use of amenable and easily accessible reactants/reagents under metal-free mild conditions, good functional group tolerance, and high efficiency. The synthetic applications were also demonstrated by derivatization of the products obtained from these processes and syntheses of a diverse range of valuable polycyclic N-heterocycles.

Synthesis of Alkyl Thiochromano[2,3-c]pyrrole-9-carboxylate Derivatives Utilizing Benzo[b]thiofuran-2,3-dione, Maleimides, and Alkyl Alcohol/Water Mixtures

AbstractA set of thiochromano[2,3-c]pyrrolidine-1,3-diones, incorporating α-hydroxy esters and their acids at the C-9 position, was prepared via direct interaction involving benzo[b]thiofuran-2,3-diones, maleimides, and alkyl alcohols in water at 90 °C. Structures of the new products were deduced from HRMS and NMR spectral data and confirmed by single-crystal X-ray crystallography. An insight into a proposed pathway involving a sequential Michael conjugate addition (initiated by the sulfur atom) and an aldol-type reaction is presented.

Revealing the low to moderate temperature oxidation kinetics of 1,2,4-trimethylbenzene sensitized by dimethyl ether

Low to moderate temperature oxidation has been a vital topic in the combustion chemistry due to its critical role in controlling the combustion characteristics such as autoignition and pollutant emissions. Low temperature oxidation kinetics of alkanes and oxygenated biofuels have been widely explored, while that of branched aromatics is poorly understood. This work aims to investigate the low to moderate temperature oxidation kinetics of 1,2,4-trimethylbenzene (TMB, C9H12), which is a multi-branched alkylbenzene with weak low temperature oxidation reactivity. To enhance the low temperature oxidation reactivity of TMB, dimethyl ether (DME) was added to efficiently provide chain initiators. The oxidation experiment of TMB/DME mixture was performed with an atmospheric jet stirred reactor coupled with synchrotron vacuum ultraviolet radiation photoionization mass spectrometry. The negative temperature coefficient (NTC) behavior, as well as featured aromatic intermediates, especially phenyl hydroperoxides and unexpected highly oxygenated molecules (HOMs), were observed in the experiment. The detection of these fingerprint aromatic intermediates provide crucial evidence for revealing the low to moderate oxidation kinetics of TMB. In addition, a kinetic model was developed to provide in-depth kinetic analysis. The results demonstrate that the active chain initiators produced from DME oxidation trigger the low temperature chain-branching reactions of TMB. The chain recycling process is further sustained due to the regeneration of active intermediates such as phenyl hydroperoxides and •OH radicals. Aromatic intermediates with chemical compositions of C9H12Ox and C9H10Ox were measured and identified to be key indicators for the low temperature chemistry of TMB. In particular, the aromatic HOMs (C9H12O6 and C9H10O5) are fingerprint intermediates produced from the third O2 addition and subsequent reactions of TMB. Besides, the sensitivity analysis indicates that the interaction kinetics between TMB and DME by sharing the highly sensitive reactions of hydroperoxides and •OH radicals. The present work extends the conceptual reaction schemes proposed in alkanes towards branched aromatics, especially sequential O2 addition reactions that contributing to the formation of phenyl hydroperoxides and HOMs.

Design and Synthesis of Co-initiators via Base-Catalysed Sequential Conjugate Addition: Application in Photoinduced Radical Polymerisation Reaction.

Applications of photochemistry are becoming very popular in modern-day life due to its operational simplicity, environmentally friendly and economically sustainable nature in comparison to thermochemistry. In particular photoinduced radical polymerisation (PRP) reactions are finding more biological applications and especially in the areas of dental restoration processes, tissue engineering and artificial bone generation. A type-II photoinitiator and co-initiator-promoted PRP turned out to be a cost-effective protocol, and herein we report the design and synthesis of a new efficient co-initiator for a PRP reaction via a barrierless sequential conjugate addition reaction. Experimental mechanistic observations have been further complemented by computational data. Time for newly synthesised 1,2-benzenedithiol (DTH) based co-initiator promoted polymerisation of urethane dimethacrylate (UDMA, 70 %) and triethylene glycol dimethacrylate (TEGDMA, 30 %) in presence of 450 nm LED (15 W) under the aerobic conditions is 38 seconds. Polymeric material has high glass transition temperature, improved mechanical strength (860 BHN) and longer in-depth polymerisation (3 cm).

Green Synthesis of Five-Membered Hetarene N-Oxides: A Designed Approach to the Synthesis of Substituted Chromeno[3,4-c]pyrrole-2-oxides

AbstractAn efficient and chemoselective synthesis of biologically valuable chromeno[3,4-c]pyrrole 2-oxides containing one chiral stereocenter is described. In this method, by using a sequential nucleophilic addition reaction involving coumarins (α,β-unsaturated coumarins or 3-acetylcoumarins), activated acetylenic compounds, triphenylphosphine as a catalyst, and hydroxylammonium chloride (HAC) as an NO source, substituted chromeno[3,4-c]pyrrole 2-oxides were prepared with excellent efficiency. Readily available starting materials, absence of a metal catalyst, green and mild conditions, chemoselectivity, easy purification (the products can be purified by simple filtration and washing with EtOH), and synthetically useful yields are some highlighted advantages of this unprecedented transformation.

Branched hydrophobic tails in lipid nanoparticles enhance mRNA delivery for cancer immunotherapy

Efficient and safe delivery of vulnerable mRNA is a long-standing challenge for the broad application of the emerging mRNA-based therapeutics. Herein, a combinatorial library containing 119 novel lipids was constructed via sequential aza-Michael addition reactions of arylates and varying amines to tackle the ongoing challenge in mRNA delivery. Through in vitro screening of the lipid library on IGROV 1 cells, we identified several synthetic lipids with superior mRNA delivery efficacy. The delivery capability of these lipids was verified by the potent expression of luciferase in BALB/c mice upon intravenous administration of luciferase-encoding mRNA lipid nanoparticles (LNPs). Further investigations on the structure-activity relationship revealed that lipids with branched hydrophobic tails were better at delivering mRNA than those containing linear tails at the similar total number of carbons. In comparison to linear tails, the branched tails endowed LNPs with less inner hydrophobicity, fewer surface charges, and proper stability, which benefits the cellular uptake of LNPs and the intracellular trafficking of mRNA, thus improves the delivery efficacy of mRNA. The therapeutical potential of the lead LNPs was evaluated by delivering ovalbumin (OVA)-encoding mRNA to mice bearing B16-OVA melanoma tumors. The results demonstrated that the administration of OVA mRNA LNPs significantly activated CD8+ T cells in tumor microenvironment and substantially prohibited the growth of the aggressive B16-OVA tumors. The robust antitumor efficacy highlights the great potential of these LNPs in cancer immunotherapy.

PhIO‐Mediated Cascade Reactions of Activated Acetylamides and Cyclic Amidines: Access to Polysubstituted Imidazolidin‐2‐ones

AbstractA facile and efficient synthesis of polysubstituted imidazolidin‐2‐ones has been developed via an oxidative cyclization reaction of activated acetyl amides and cyclic amidines mediated by iodosobenzene (PhIO). A mechanism is proposed for this transformation, which involves sequential intermolecular addition, Hofmann‐type rearrangement and intramolecular cyclization reactions. The novel protocol features readily available starting materials, mild reaction conditions, simple execution, metal‐free oxidative cyclization, and one‐pot procedure.

Digitizing protocols into single reactors for the one-pot synthesis of nanomaterials

Digitizing protocols into single reactors for the one-pot synthesis of nanomaterials

Ortho-Lithiation driven one-pot synthesis of quinazolines via [2 + 2 + 2] cascade annulation of halofluorobenzenes with nitriles.

A one-pot synthesis of 2,4-disubstituted quinazoline derivatives from halofluorobenzenes with nitriles was reported, via sequential nucleophilic addition and SNAr reaction. The advantages of the present approach are transition metal free, easy to operate, and all the starting materials are commercially available.

Synthesis and anti-inflammatory activity of paeonol derivatives with etherized aryl urea by regulating TLR4/MyD88 signaling pathway in RAW264.7 cell

Thirty-three novel paeonol etherized aryl urea derivatives (PEUs) were synthesized via a bromination-Williamson Ether Synthesis-deprotection-nucleophilic addition reaction sequence. The structures of PEUs were characterized by LC-MS, HRMS, 1H NMR and 13C NMR spectra. The levels of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages were initially employed to evaluate the anti-inflammatory effects of all compounds. Remarkably, b16 exhibited a good anti-inflammatory activity at 2.5 μm which is the same as the potency of paeonol at 20 μm. The results of mechanism research displayed that the anti-inflammatory effect of b16 was ascribed to the inhibition of the TLR4/MyD88 signaling pathway and inflammatory factors. Additionally, b16 distinctly reduced the generation of free radicals in macrophages and strikingly increased the mitochondrial membrane potential. According to the structure-activity relationships (SAR) of PEUs, the incorporation of halogens on the benzene ring and the hydrogen of phenol hydroxyl substituted by aryl urea, were beneficial to enhance the anti-inflammatory activities. Molecular docking results illustrated that the binding ability of b16 to TLR4 was stronger than that of paeonol. In summary, the novel aryl urea-derivied paeonol b16 could be a new promising candidate for the treatment of inflammation-related diseases.

Synthesis of N-Heterocyclic Carbenes and Their Complexes by Chloronium Ion Abstraction from 2-Chloroazolium Salts Using Electron-Rich Phosphines.

N‐Heterocyclic carbenes (NHCs) are commonly prepared by deprotonation of azolium salts using strong anionic bases. This reaction is often unselective, yielding alkali metal NHC complexes or dimerized NHCs. Alternatively, free NHCs are obtained by the dechlorination of 2‐chloroazolium salts using electron‐rich phosphines. PPh3, PCy3, and PtBu3 are unsuitable for Cl+ abstraction, while the sterically encumbered tris(1,3‐tert‐butylimidazolidin‐2‐ylidenamino)phosphine 1 selectively removes Cl+ from 2‐chloroazolium salts. Since bulky 1 does not bind to metal complexes, it was used for the preparation of NHC complexes via in situ Cl+ abstraction from 2‐chloroazolium salts. The dechlorination was employed for the site‐selective monometallation with IrI, IrIII, RhI, RhIII, and RuII of a bis‐NHC precursor composed of a 2‐chlorobenzimidazolium and a 2‐chlorobenzimidazole group, followed by the preparation of the heterobimetallic IrIII/PdII complex [18](BF4)2 by a dechlorination/oxidative addition reaction sequence.

Density functional theory (DFT) investigation of the oxidative degradation of NaAsO2 via hydroxyl radical

Arsenic is an environmentally ubiquitous health hazard due to its toxicity combined with its natural abundance and heavy industrial applications. Due to its role in cardiovascular disease, neurotoxicity, and various cancers, it is important to understand environmental fate of arsenic-containing compounds to take steps towards remediation. Sodium arsenite (NaAsO2) is one such compound that has been used worldwide as an herbicide, rodenticide, and insecticide. It is also toxic by ingestion, inhalation, and skin absorption. In aqueous environments, arsenite (As(III))-containing compounds can be oxidized to the less-toxic arsenate (As(V)) form. We have investigated the oxidation of sodium arsenite in water solution at the density functional theory level using the Minnesota 06 hybrid (M06-2X) functional and Pople basis sets (6-31G(d,p) and 6-311G(d,p)) with polarizable continuum model (PCM) solvation approach. Our computational results indicate that the oxidation mechanism of NaAsO2 by hydroxyl radical proceeds via sequential addition reactions where sodium arsenite (III) converts to sodium arsenate (V) via an arsenic (IV) intermediate.

One-Pot Synthesis of Melt-Processable Supramolecular Soft Actuators.

The application of reprocessable and reprogrammable soft actuators is limited by the synthetic strategies, 3D‐shaping capabilities, and small deformations. In this work, melt‐processable supramolecular soft actuators based on segmented copolymers containing thiourethane and liquid crystal segments have been prepared via sequential thiol addition reactions in a one‐pot approach using commercially available building blocks. The actuators demonstrated immediate, reversible response and weightlifting capabilities with large deformations up to 32 %. Through exploiting the supramolecular cross‐links, the material could be recycled and reprogrammed into 3D actuators and welded into an actuator assembly with different deformation modes. Our work offers a one‐pot synthesis and straightforward melt‐processable approach to prepare supramolecular soft actuators with large deformations that can be reprocessed and reprogrammed into arbitrary 3D shapes.

One‐Pot Synthesis of Melt‐Processable Supramolecular Soft Actuators

AbstractThe application of reprocessable and reprogrammable soft actuators is limited by the synthetic strategies, 3D‐shaping capabilities, and small deformations. In this work, melt‐processable supramolecular soft actuators based on segmented copolymers containing thiourethane and liquid crystal segments have been prepared via sequential thiol addition reactions in a one‐pot approach using commercially available building blocks. The actuators demonstrated immediate, reversible response and weightlifting capabilities with large deformations up to 32 %. Through exploiting the supramolecular cross‐links, the material could be recycled and reprogrammed into 3D actuators and welded into an actuator assembly with different deformation modes. Our work offers a one‐pot synthesis and straightforward melt‐processable approach to prepare supramolecular soft actuators with large deformations that can be reprocessed and reprogrammed into arbitrary 3D shapes.

Experimental and kinetic modeling study of α-methyl-naphthalene pyrolysis: Part II. PAH formation

α-Methyl-naphthalene plays an important role as a functional material in petrochemical industries and as a precursor of soot particles. The formation chemistry of polycyclic aromatic hydrocarbons (PAHs) from α-methyl-naphthalene, therefore, warrants detailed investigations. In this work, we studied PAH formation from its pyrolysis using experiments and kinetic models. Flow reactor pyrolytic experiments at low and atmospheric pressures (30 and 760 Torr) were performed using synchrotron vacuum ultraviolet photoionization molecular beam mass spectrometry (SVUV-PI-MBMS). A kinetic model was then developed to predict PAH formation from α-methyl-naphthalene. According to the kinetic analysis of the proposed model, naphth-1-yl-methyl, benzo-fulvenallene, and benzo-fulvenallenyl are three critical intermediates in the formation of large PAHs. Other than the traditional H-abstraction acetylene-/vinylacetylene-addition mechanisms, three prototypical PAH formation pathways are identified in α-methyl-naphthalene pyrolysis: 1) addition and cyclization reactions of naphth-1-yl-methyl and naphth-1-yl radicals; 2) recombination of resonance stabilized radicals (indenyl, benzo-fulvenallenyl, phenalenyl, etc.) and the subsequent ring expansion reactions; 3) sequential propargyl addition reactions.

Synthesis of dibenzocyclohepta[1,2-a]naphthalene derivatives from phenylacetaldehyde and alkynyl benzyl alcohols via sequential electrophilic addition and double Friedel-Crafts reactions.

A simple methodology has been developed for the synthesis of substituted 9H-dibenzo[3,4:6,7]-cyclohepta[1,2-a]naphthalenes from phenylacetaldehydes and ortho-alkynyl benzyl alcohols in the presence of a Lewis acid in moderate to good yields within a short reaction time. Interestingly, the reaction proceeds through a highly regioselective electrophilic addition followed by double Friedel-Crafts reaction to form uncommon dibenzo-fused seven-membered carbocycles.

Extreme Low-Temperature Combustion Chemistry: Ozone-Initiated Oxidation of Methyl Hexanoate.

The accelerating chemical effect of ozone addition on the oxidation chemistry of methyl hexanoate [CH3(CH2)4C(═O)OCH3] was investigated over a temperature range from 460 to 940 K. Using an externally heated jet-stirred reactor at p = 700 Torr (residence time τ = 1.3 s, stoichiometry φ = 0.5, 80% argon dilution), we explored the relevant chemical pathways by employing molecular-beam mass spectrometry with electron and single-photon ionization to trace the temperature dependencies of key intermediates, including many hydroperoxides. In the absence of ozone, reactivity is observed in the so-called low-temperature chemistry (LTC) regime between 550 and 700 K, which is governed by hydroperoxides formed from sequential O2 addition and isomerization reactions. At temperatures above 700 K, we observed the negative temperature coefficient (NTC) regime, in which the reactivity decreases with increasing temperatures, until near 800 K, where the reactivity increases again. Upon addition of ozone (1000 ppm), the overall reactivity of the system is dramatically changed due to the time scale of ozone decomposition in comparison to fuel oxidation time scales of the mixtures at different temperatures. While the LTC regime seems to be only slightly affected by the addition of ozone with respect to the identity and quantity of the observed intermediates, we observed an increased reactivity in the intermediate NTC temperature range. Furthermore, we observed experimental evidence for an additional oxidation regime in the range near 500 K, herein referred to as the extreme low-temperature chemistry (ELTC) regime. Experimental evidence and theoretical rate constant calculations indicate that this ELTC regime is likely to be initiated by H abstraction from methyl hexanoate via O atoms, which originate from thermal O3 decomposition. The theoretical calculations show that the rate constants for methyl ester initiation via abstraction by O atoms increase dramatically with the size of the methyl ester, suggesting that ELTC is likely not important for the smaller methyl esters. Experimental evidence is provided indicating that, similar to the LTC regime, the chemistry in the ELTC regime is dominated by hydroperoxide chemistry. However, mass spectra recorded at various reactor temperatures and at different photon energies provide experimental evidence of some differences in chemical species between the ELTC and the LTC temperature ranges.

The kinetic mechanism of acetylene hydrogenation to prepare ethane over FexOy clusters: A DFT study

The acetylene hydrogenation reaction over FeO, Fe2O3 and Fe3O4 clusters are theoretically investigated, via C2H2 adsorption, approach of molecular H2 to cluster, H2 dissociation on FeO bond, and the sequential addition reaction of H atom. Over FeO cluster, the extremely high barrier for the addition reaction of H atom adsorbed on O atom (of cluster) predicts the impossible acetylene hydrogenation. Over Fe2O3 cluster, the overall barriers for H2 dissociation, addition reaction of two hydrogen atom are respectively 26.6, 32 and 31.8 kcal·mol−1 during the acetylene hydrogenation to form ethylene and 26.5, 35.5 and 9.1 kcal·mol−1 for its further hydrogenation to produce ethane. During the further hydrogenation pathway, the migration of semi-hydrogenated product C2H3 requires extra energy of 30.7 kcal mol−1. These barriers are lower than those of the pathways over Fe3O4 cluster. Hence, among three FexOy clusters, hydrogenation of acetylene to produce ethane on Fe2O3 cluster is kinetically most favorable.