Addition-elimination Reaction Research Articles

Fast Production of Covalent Organic Frameworks for Covalent Enzyme Immobilization with Boosted Enzymatic Catalysis by Solar-Driven Photothermal Effect.

Developing new enzyme-immobilization systems to stabilize their dynamic structures and meanwhile enhance their catalytic activity is of great significance but very challenging. Herein, we design and fabricate a class of robust mesoporous covalent organic frameworks (COFs) via Michael addition-elimination reaction. It is found that highly crystalline COFs can be produced in 10 min, which is attributed to the promoting effect of the intramolecular hydrogen bond activation. The COFs rich in hydroxyl groups can be facilely post-modified by epibromohydrin to covalently immobilize enzymes with both high loading and activity. Furthermore, we create a solar-driven photothermal-promoted strategy by introducing photoactive azo groups to COF carriers, which can boost the enzyme catalytic performance (lipase) with much higher conversion of various racemic substrates and chiral resolution upon solar light irradiation. The heterogeneous biocatalysts also demonstrate exceptional reusability and stability. This work provides a green and energy-efficient approach to facilitate the scale application of enzyme-immobilized biocatalysts.

Michael addition-elimination reaction derived covalent organic polyrotaxane xerogels for ultra-high-efficiency capture of iodine pollutants

Herein, covalent organic polyrotaxane xerogels (COPRs), were developed as comprehensive and recyclable “three birds with one stone” platform effectively handling organic/radioactive iodine pollutants challenges. COPRs were synthesized rapidly from β-ketoenamine and aromatic amines β-cyclodextrin (β-CD) inclusion via Michael addition-elimination reaction in water at room temperature and pressure, avoiding the usage of any organic solvents. The formation of β-CD inclusion significantly increases the solubility and reactivity of monomers in water. The threading of β-CD endows multiple absorption sites within the porous skeleton, improving its iodine capture capacity. The integration of β-CD ring throughout the carbon skeleton not only provides a green and ultra-low-cost approach for preparing COPRs with brand-new structure, but also offers direct and effective methods realizing the carbon neutrality from the source of production. This work could be used as a general method for the specifically modifying COPs, providing opportunities to meet the growing needs of society.

Oxidation of butane-2,3-dione at high pressure: Implications for ketene chemistry

Ketene (CH2CO) mechanism is a building block for developing combustion kinetic models of practical fuels. To revisit the combustion chemistry related to ketene, oxidation experiments of butane-2,3‑dione (diacetyl, CH3COCOCH3), considered as an effective precursor of CH2CO, are conducted in a jet-stirred reactor (JSR) at 10 bar and temperatures ranging from 650 to 1160 K. Identification and quantification of intermediates are achieved by Fourier transform infrared spectrometry, gas chromatography, and mass spectrometry. A kinetic model of diacetyl is constructed based on recent theoretical and modeling studies on diacetyl and ketene, which has been validated against the present data and experimental data of diacetyl and CH2CO in literature. Generally, the present model can adequately predict most of them, and better predict the methyl-related intermediates under wide pyrolysis and combustion conditions than previous models. Based on modeling analyses, the unimolecular decomposition reaction of diacetyl is the dominant reaction pathway for fuel consumption under different equivalence ratio conditions, especially at high temperatures. Under lean conditions, both the H-atom abstraction reactions by methyl (i.e. CH3COCOCH3 + CH3 = CH4 + CH2CO + CH3CO, R3) and by OH (i.e. CH3COCOCH3 + OH = H2O + CH2CO + CH3CO, R5) are important for diacetyl consumption, while under rich conditions R5 becomes negligible. As the most important intermediates in diacetyl oxidation, the main consumption pathways of CH2CO and CH3 are dependent on the equivalence ratio conditions. Under lean conditions, CH2CO mainly reacts with OH to produce CH2OH and CO (i.e. CH2CO + OH = CH2OH + CO, R10), while methyl reacts with HO2 to produce CH3O and OH (i.e. CH3 + HO2 = CH3O + OH, R20). In contrast, under rich conditions, the addition-elimination reaction between CH2CO and H becomes competitive with R10, while the CH3 self-combination producing C2H6 plays a more important role than the CH3 oxidation pathway R20. Sensitivity analysis of CH2CO shows that not only the reactions of CH2CO, but also those of CH3 are sensitive to CH2CO formation. This is because CH3 related reactions influence the distribution of radical pool, which determines the oxidation reactivity of the reaction system.

A Regioselective Domino Benzannulation Route to Indeno[1,2-a]fluorene-7,12-diones

AbstractA base-promoted domino benzannulation reaction of 2,3-dibromoindenone with acyclic 1,3-dicarbonyls resulted in an efficient synthetic protocol for a series of novel polycyclic indeno[1,2-a]fluorenes. The reaction proceeds via the two sequential addition-elimination reactions of nucleophilic species generated from the 1,3-dicarbonyls under basic conditions, serendipitously leading to the benzannulation with two molecules of 2,3-dibromoindenone. The second addition-elimination occurs on the initially formed adduct of 1,3-dicarbonyl with 2,3-dibromoindenone, setting the stage for further intramolecular cyclization and aromatization. Interestingly, unsymmetrical 1,3-dicarbonyls furnished a single regioisomer. The origin of the regioselectivity and plausible mechanism is discussed.

Aging mechanisms and kinetics of bis(2,2 dinitropropyl) formal facilitated by transition state bifurcation and HONO catalysis

Serving as energetic plasticizer, revealing the aging mechanisms and kinetics of bis(2,2-dinitropropyl) formal is helpful to remove the safety hazards. Here, based on the DFT barrier of methylene-H abstraction by nitro group (HONO elimination) and the continuous reaction model, an experimentally comparable half-life of BDNPF is reported by transition state theory simulation. Rather than the HONO elimination-addition reactions, HONO bimolecular decompositions are preferred, where the energetically preferred pathway involves formation of N2O3, and generation of N2O4 and HNO catalyzed by HONO. Interestingly, newly reported transition state bifurcations lower the barriers and accelerate HONO decomposition, which also leads to the rate constant of generating HNO consistent with experiments. Moreover, HNO undertakes hydrogen transferred bimolecular pathway and HONO-catalyzed pathway to decompose into N2O and H2O. This work clarifies the degradation pathways and species, and is helpful to the deep understanding of the aging procedures of energetic materials.

Asymmetric Construction of Ethenyl-Substituted Acyclic Quaternary Stereocenters at the α-Position of Carbonyl Surrogates via Stereoselective Sulfonylvinylation-Reductive Desulfonylation.

N-Sulfinyl metalloenamines, derived from geometry-defined β,β-disubstituted enesulfinamides, undergo conjugate addition-elimination reaction with β-tosyl nitroolefin to afford α-sulfonylvinylated ketimines with high stereocontrol. Further desulfonylation using sodium naphthalenide gives carbonyl surrogates bearing a less-accessible acyclic quaternary α-stereocenters substituted with an ethenyl group and two sterically and electronically similar groups (e.g., methyl and ethyl). Synthetic application of the described protocol was demonstrated by enantioselective synthesis of (S)-bakuchiol.

Simulation-Guided Conformational Space Exploration to Assess Reactive Conformations of a Ribozyme.

Self-splicing ribozymes are small ribonucleic acid (RNA) enzymes that catalyze their own cleavage through a transphosphoesterification reaction. While this process is involved in some specific steps of viral RNA replication and splicing, it is also of importance in the context of the (putative) first autocatalytic RNA-based systems that could have preceded the emergence of modern life. The uncatalyzed phosphoester bond formation is thermodynamically very unfavorable, and many experimental studies have focused on understanding the molecular features of catalysis in these ribozymes. However, chemical reaction paths are short-lived and not easily characterized by experimental approaches, so molecular simulation approaches appear as an ideal tool to unveil the molecular details of the reaction. Here, we focus on the model hairpin ribozyme. We show that identifying a relevant initial conformation for reactivity studies, which is frequently overlooked in mixed quantum-classical studies that predominantly concentrate on the chemical reaction itself, can be highly challenging. These challenges stem from limitations in both available experimental structures (which are chemically altered to prevent self-cleavage) and the accuracy of force fields, together with the necessity for comprehensive sampling. We show that molecular dynamics simulations, combined with extensive conformational phase space exploration with Hamiltonian replica-exchange simulations, enable us to characterize the relevant conformational basins of the minimal hairpin ribozyme in the ligated state prior to self-cleavage. We find that what is usually considered a canonical reactive conformation with active site geometries and hydrogen-bond patterns that are optimal for the addition-elimination reaction with general acid/general base catalysis is metastable and only marginally populated. The thermodynamically stable conformation appears to be consistent with the expectations of a mechanism that does not require the direct participation of ribozyme residues in the reaction. While these observations may suffer from forcefield inaccuracies, all investigated forcefields lead to the same conclusions upon proper sampling, contrasting with previous investigations on shorter timescales suggesting that at least one reparametrization of the Amber99 forcefield allowed to stabilize aligned active site conformations. Our study demonstrates that identifying the most pertinent reactant state conformation holds equal importance alongside the accurate determination of the thermodynamics and kinetics of the chemical steps of the reaction.

An efficient EPR spin-labeling method enables insights into conformational changes in DNA

Electron paramagnetic resonance (EPR) is a powerful tool for elucidating both static and dynamic conformational alterations in macromolecules. However, to effectively utilize EPR for such investigations, the presence of paramagnetic centers, known as spin labels, is required. The process of spin labeling, particularly for nucleotides, typically demands intricate organic synthesis techniques. In this study, we introduce a unique addition-elimination reaction method with a simple spin-labeling process, facilitating the monitoring of structural changes within nucleotide sequences. Our investigation focuses on three distinct labeling positions with a DNA sequence, allowing the measurement of distance between two spin labels. The experimental mean distances obtained agreed with the calculated distances, underscoring the efficacy of this straightforward spin-labeling approach in studying complex biological processes such as transcription mechanism using EPR measurements.

Design of degradable hybrid dual-crosslinked polymer for high-efficiency profile control in high temperature reservoirs

Profile control and water plugging are key technologies to enhance oil and gas recovery. Traditional plugging materials, due to short gelation time, low mechanical strength, and difficulty in balancing plugging and protection, thus limiting application in high temperature reservoirs. Herein, a degradable hybrid dual-crosslinked polymer was prepared by employing a copolymerization - dual-grafting and physical adsorption design strategy. The dual-crosslinked process and reaction mechanism were analyzed using infrared spectroscopy and differential scanning calorimetry. The mechanical properties, water dilution resistance, aging stability and degradability of the dual cross-linked composite were also investigated. The solvation forces enable silica particles to exhibit excellent suspension stability in a PEG solvent. The temperature ranges from normal atmospheric temperature (20 °C) to reservoir temperature (140 °C), with the apparent viscosity falling within the range of 10–1200 mPa·s, meeting the requirements for mixing and injection. The combination of free radical copolymerization and click reaction is utilized to control the gelation time (2–10 h) in high temperature environment (140 °C), which is favorable for regulating the action position of the plugging agent in the reservoir. The cured material exhibits excellent mechanical strength owing to the presence of dual-crosslinking and inorganic hybridization, with a compressive strength of 0.221 MPa and a peak strain of 55.3 %. Furthermore, this composite material undergoes hydrolysis through an addition-elimination reaction, transitioning from a solid to a liquid state within 24 h, thereby aiding in the restoration of productivity in the temporarily shielded target layer. Compared to traditional materials, this dual-crosslinked composite system have the advantages of controllable gelation time, high mechanical strength, aging resistance, and degradability, making it suitable for profile control in high temperature reservoirs (140 ℃, 21.81×104 mg/L).

Visible-Light Induced Radical Addition-Elimination Reaction for Constructing Allylic Sulfones from Sulfonyl Chlorides and Allyl Bromides.

Allyl sulfones are commonly present in bioactive compounds and organic building blocks. This work introduces a photocatalytic radical addition-elimination reaction involving readily accessible sulfonyl chlorides and allyl bromides. It delivers structurally diverse allylic sulfones in moderate to excellent yields, showcasing a high tolerance to functional groups. Notably, this method operates under mild reaction conditions without the need for oxidants, stoichiometric reducing metals, or additives.

Covalent organic polymers based on special dithioureas for efficient removal of Hg2+ from aqueous solutions

The damage caused by mercury ions (Hg2+) to human beings motivates the development of highly efficient technologies for the removal of Hg2+ from water. Here, based on the coordination theory between functional groups and Hg2+, two covalent organic polymers (COPs) materials were successfully prepared by a more environmentally friendly Michael addition elimination reaction, and the thiourea structure, which has a particularly strong affinity for Hg2+, was successfully introduced into the material framework. The introduction of the special dithiourea structure created a rich environment of S and N atoms within the COPs structure, which exhibited high adsorption performance for Hg2+. Adsorption experiments showed that the dithiourea-functionalized COPs exhibited high adsorption capacities for Hg2+, with the maximum adsorption capacities of 840.9 and 880 mg g−1 for the two materials, respectively. The adsorption performance remained relatively good after four adsorption-desorption cycles, and the adsorption selectivity for Hg2+ was intense. Mechanistic studies by X-ray photoelectron spectroscopy and density flooding theory calculations suggest that it is the S atoms within the structure that chelate with the Hg2+ and contribute to the adsorption capacity of the Hg2+. Therefore, this study provides a new strategy for the development of COP adsorbents for efficient removal of Hg2+ in aqueous solutions during remediation activities.

2,3-Dichloronaphthoquinone derivatives: Synthesis, antimicrobial activity, molecular modelling and ADMET studies

In the present study, an intermediate namely 2-(3-bromopropylamino)-3-chloronaphthalene-1,4-dione was initially synthesized via the nucleophilic addition–elimination reaction between 2,3-dichloro-1,4-naphthoquinone and 3-bromo-1-aminopropane. Then a coupling reaction between the intermediate and piperazine derivatives yielded a number of 1,4-naphthoquinone derivatives. Spectroscopic analysis successfully characterized the products that were obtained in good yields. In vitro antibacterial properties of the compounds were examined against different bacterial strains. In vitro antibacterial properties of the compounds were examined against the bacterial strains S. Aureus, E. Faecalis, E. Coli and P. Aeruginosa. While compound 9 was found to be effective against all bacterial strains used, compound 12 was active against three strains and compounds 10 and 11 were effective against the two. None of the compounds are effective against C. albicans strain. In silico molecular docking studies revealed that all compounds had docking scores comparable to the antibacterial drugs ciprofloxacin and gentamicin and might be considered as DNA gyrase B inhibitors. Molecular dynamics simulations were also conducted for a better understanding of the stability and the selected docked complexes. Additionally, the drug similarity of the synthesized compounds and ADMET characteristics were examined in conjunction with the antibiotic ciprofloxacin, and drug potentials were then evaluated. Compatible predictions were found with the drug similarity and ADMET parameters.

Construction of Diverse Pyrrolidine-Based Skeletons through the Ag-Catalyzed Stereoselective Addition-Elimination Reaction of Azomethine Ylides with Nitroallyl Acetates.

Because scaffold diversity has a pronounced impact on biological screening, the efficient and expedient construction of skeletally diverse compound collections is a fundamental demand in drug discovery. In this regard, we report here an asymmetric tandem conjugate addition-elimination reaction of pyrroline esters with nitroallyl acetates and its application to the construction of various types of fused or spirocyclic pyrrolidines. A AgOAc/(R,Sp)-ThioClickFerrophos (TCF) catalyst efficiently promotes the addition-elimination reaction, setting vicinal chiral stereocenters featuring a tetrasubstituted carbon with excellent enantio- and diastereoselectivity while leaving the versatile nitroolefin moiety. The broad substrate scope of this reaction and the transformability of the resulting nitroolefin, imine, and ester moieties allow for the construction of diverse pyrrolidine-based fused or spiro bicyclic skeletons in optically active forms by various intramolecular cyclization processes.

Adventures in CH-Arylation Chemistry

AbstractThe present article provides a personalized account on CH-arylation reactions employed for the synthesis of heterocycles. The presence of a nitro group allowed for direct and regioselective CH-arylations of pyrazoles, imidazoles, indoles and a variety of purine analogues. Direct CH-arylations without the presence of an activating nitro-group were employed for inter- and intramolecular reactions of purine derivatives, which allowed for the synthesis of a great variety of polycyclic systems. Domino C–N coupling / hydroamination / CH-activation reactions of diarylacetylenes with anilines allowed for the synthesis of polycondensated N-heterocycles. Products include indolo- and azaindolo[1,2-f]phenanthridines, quinolino[3′,4′:4,5]pyrrolo[1,2-f]phenanthridines, pyrimido[5′,4′:4,5]pyrrolo[1,2-f]phenanthridines, and benzothieno[2′,3′:4,5]pyrrolo[1,2-f]phenanthridines. The reaction of N-heterocycles, such as indoles, with 1,1-difluoroalkenes resulted in a twofold addition-elimination reaction to give 1,1-diaminoalkenes, which were transformed by CH-arylation into various polycondensated heterocycles, such as indoloisoquinolines, thienoindolizines, oxepines and helicenes. Pyridofluoranthenes, diindenopyrene and azadiindenopyrenes were prepared by a combination of Pd-catalyzed cross-coupling reactions with acid-mediated cycloisomerizations and Pd-catalyzed intramolecular CH-arylations. Bis(carbazoles), benzodithiazoles, benzodithiophenes and 2,5-diarylpyrroles were prepared by inter- and intramolecular CH-arylation reactions.

Base catalyzed one-pot thia-Michael addition-oxidation reaction of hetero-aromatic thiols to 2-aryl-3-nitro-2H-chromenes and their antibacterial evaluation

A thia-Michael addition reaction was developed for the synthesis of heteroaromatic thiol-based 2H-chromenes and the antibacterial activity was studied against two pathogenic bacterial strains, E. coli, and S. aureus.

Resolving discrepancies between theory and experiment for the NCN + H reaction

Flame modeling studies have highlighted the role of branching in the kinetics for the prompt NO switch reaction, NCN + H. In this reaction, there is strong competition between the CH + N2 (R1) and HCN + N (R2) product channels. Increased branching towards reaction R2 promotes the subsequent formation of Fenimore or Prompt NO. Recent direct shock tube studies on this complex reaction conclude that branching to reaction R2 is much more favorable than the predicted branching from theoretical studies. The experimentally predicted prompt NO switch temperature (TS), i.e., the temperature at which k2/(k1+k2) = 0.5, is at 1670 K, in contrast to theory that predicts Ts > 3200 K. The present theory/modeling work was initiated to highlight potential causes for this significant discrepancy between experiment and theory. Our analysis of the simulations reported in the experimental studies indicate that including a fall-off representation for C2H5 radical dissociation (with C2H5 produced from C2H5I dissociation and acting as an H-atom source) has a noticeable influence on the simulations for NCN decay and HCN formation in the shock tube studies. With the inclusion of a theory-based pressure fall-off representation for C2H5 dissociation, we show that this radical persists for much longer timescales even at the high-temperatures in the shock tube studies. This persistence then facilitates the rapid conversion of reactive H-atoms to CH3 radicals at the shock tube conditions via the H + C2H5 → CH3 + CH3 reaction. An updated theoretical analysis for this classic addition-elimination reaction is also provided in this work. The rapid formation of CH3 radicals necessitates the inclusion of additional reactions to adequately simulate the NCN and HCN data. Our simulations conclude that, with the inclusion of these additional reactions, the NCN and HCN profiles can be reasonably well simulated by the most recent theoretical predictions.

Design, Synthesis, Crystal Structure, Biological Activity and Molecular Modeling of Novel Schiff Bases Derived from Chalcones and 5-Hydrazino-1,3-Dimethyl-4-Nitropyrazole as Anticancer Agents

The synthesis of novel 5-(2-((1(E/Z),2E)-1,3-disubstitutedallylidene)hydrazinyl)-1,3-dimethyl-4-nitro-1H-pyrazole (4a–k) was attempted via reaction involves a nucleophilic attack which takes place at the carbonyl group of the α,β-unsaturated carbonyls. The transformation proceeds via an effective addition-elimination reaction in the presence of catalytic amount of concentrated H2SO4. The cytotoxicity of synthesized compounds was evaluated against two tumor cell lines, MCF-7 and MDA-MB-231, via MTT assay. The compounds 4a–d showed better toxicity than tamoxifen on MCF-7 cells, ranging from 26.28 to 12.96 µM with 4b having the lowest IC50 among the compounds tested. On the other hand, the compounds have moderate toxicity on MDA-MB-231 with 4c showing the lowest IC50. The docking study suggests that these Schiff bases chalcone scaffolds might facilitate the further development of investigated compounds as anticancer agents.

Addition-elimination reactions of 2,2-disubstituted malononitriles and α-aryl nitriles. Subsequent transformations.

Addition-elimination reactions of 2,2-disubstituted malononitriles and α-aryl nitriles. Subsequent transformations.

Density functional theory investigation of mechanisms of degradation reactions of sulfonated PEEK membranes with OH radicals in fuel cells: addition–elimination reactions and acid catalyzed water elimination

Sulfonated polyether (ether) ketone or sulfonated PEEK (sPEEK) membranes are one possible candidate for proton-transfer membranes in hydrogen fuel cells. Reaction with hydroxy radicals is expected to be a significant source of degradation of these membranes during fuel cell operation. In this work, the reactivity of the sPEEK polymer molecule with OH radicals is studied by M062X hybrid density functional calculations of the energetics of several reaction paths in a water environment as modeled by polarized continuum model calculations. Reactants, products, encounter minima and transition states are optimized for a reaction pathway in which OH addition is followed by acid-catalyzed water elimination which cationizes the polymer, degradation is expected to follow this reaction as the unstable cation then undergoes bond-breaking or other reactions. Two pathways for this acid-catalyzed cationization, one in which a water molecule plays the role of an additional co-catalyst, are reported. Further calculations explore reaction pathways in which addition of OH to the polymer is followed by bond breaking reactions which would break the polymer chain or the bond between the polymer and sulfonyl groups. Examination of the free energy barriers to all these reactions, relative to reactants, suggests that these direct bond-breaking reactions may compete somewhat with acid-catalyzed water elimination following OH addition.

Ultrasound-Assisted Efficient Synthesis of Azomethine Derivatives of 1-Phenylimidazo[1,5-a]Pyridine

In the present research work, ultrasound-assisted synthesis of a series of novel azomethine derivatives of 1-phenylimidazo[1,5-a]pyridine has been achieved. The synthetic route involves the conversion of ethyl-1-phenylimidazo-[1,5-a]pyridine-3-carboxylate to 1-phenylimidazo[1,5-a]pyridine-3-carbohydrazide followed by nucleophilic addition-elimination reaction with diverse aromatic aldehydes. The developed clean and simple protocol offers a set of advantages such as mild reaction conditions, environment friendliness, and high atom economy apart from excellent yields (70–92%). All compounds were found to be stable in atmospheric conditions for a long period of time and were soluble in polar solvents.