Cascade Process Research Articles

Reaction of acetylenic carbanions with C=N bond: dynamics of development, synthetic divergence, environmental safety

This review highlights dynamics of development and synthetic application of the recently discovered reaction of acetylenic carbanions, generated in superbase media, with C=N bond of different classes of substrates. A fundamental feature of this reaction is its synthetic divergence, i.e. its ability to proceed in various directions that manifests in novel transformations to selectively deliver (depending on structure of the acetylenes and substrates with C=N bond) structurally different synthetically important products. The review also discusses cascade processes, in which the key intermediates containing the C=N bond add acetylenes thereby participating in the self-organization of diverse and potentially useful compounds. The competitive advantage of the reaction and its daughter branches is environmental safety (neutrality), based on the fundamental chemical nature of these reactions as addition processes that occur without the release of by-products.<br> The bibliography includes 133 references.

L‐Cysteine‐Catalysed Hydration of Activated Alkynes

Hydration reactions consist of the introduction of a molecule of water into a chemical compound and are particularly useful to transform alkynes into carbonyls, which are strategic intermediates in the synthesis of a plethora of compounds. Herein we demonstrate that L‐cysteine can catalyse the hydration of activated alkynes in a very effective and fully regioselective manner to access important building blocks in synthetic chemistry such as β‐ketosulfones, amides and esters, in aqueous media. The mild reaction conditions facilitated the integration with enzyme catalysis to access chiral β‐hydroxy sulfones from the corresponding alkynes in a one‐pot cascade process in good yields and excellent enantiomeric ratios. These findings pave the way towards establishing a general method for metal‐free, cost‐effective, and more sustainable alkyne hydration processes.

Potassium tert-Butoxide Promoted α-Keto Ester Synthesis through C(O)–N Bond Cleavage of Isatins

AbstractWe present a novel and cost-effective method for synthesizing biologically important α-keto esters in a single-step reaction. This approach involves a sequential cascade process within a single reaction vessel facilitated by t-BuOK, which promoted the cleavage of the sp2 C(O)–N bond of an isatin and the formation of a new N–C(sp2)(O) bond with benzoyl chloride. To the best of our knowledge, this is the first instance of the construction of an α-keto ester scaffold adjacent to an amide group through a one-pot process. In comparison to existing methods, our protocol offers several advantages: readily available starting materials, mild reaction conditions, a concise synthetic pathway, high sustainability, and excellent tolerance towards various functional groups. Given these strengths, we anticipate widespread use of this method in the synthesis of related α-keto ester scaffolds.

L-Cysteine-Catalysed Hydration of Activated Alkynes.

Hydration reactions consist of the introduction of a molecule of water into a chemical compound and are particularly useful to transform alkynes into carbonyls, which are strategic intermediates in the synthesis of a plethora of compounds. Herein we demonstrate that L-cysteine can catalyse the hydration of activated alkynes in a very effective and fully regioselective manner to access important building blocks in synthetic chemistry such as β-ketosulfones, amides and esters, in aqueous media. The mild reaction conditions facilitated the integration with enzyme catalysis to access chiral β-hydroxy sulfones from the corresponding alkynes in a one-pot cascade process in good yields and excellent enantiomeric ratios. These findings pave the way towards establishing a general method for metal-free, cost-effective, and more sustainable alkyne hydration processes.

In-situ observation of irradiation-induced amorphization on fluorapatites doped with REEs (REE = La, Nd, Sm, Tb, Er, and Lu) of various ionic radii

The immobilization of nuclear waste containing various actinides requires the actinide host phases to maintain long-term stability under alpha decay damage. In this study, the irradiation resistance to amorphization of fluorapatite compounds with the formula of Ca9REE(PO4)5(SiO4)F2 (REE: rare earth element, REE = La, Nd, Sm, Tb, Er, and Lu) were investigated, where REEs3+ with decreased ionic radii were used to simulate actinides in immobilization wastes. In-situ 800 keV Kr2+ irradiation was performed with varying temperatures. The critical amorphization temperature, Tc, for these apatites were found to be 513.8, 503.7, 494.1, 493.7, 483.1 and 460.9 K, respectively. Tc shows a distinct decreasing trend with the decrease of ionic radii of doped REEs3+, indicating enhanced irradiation resistance. The selected REEs exhibited increasing electronegativity, which correlated with an increase in bonding ionic properties. This trend is unfavourable for the formation of a covalent network, thereby enhancing irradiation resistance. Besides, the decreased ionic radii of doped REEs3+ enhanced the migration and diffusion rates of smaller REE3+ after the collision cascade process. Additionally, the dopant REEs3+ showed a significant preference for CaⅡ sites. This preference decreased as the ionic radius of doped REE3+ and reduced the average ionic radius of CaⅠ sites. Consequently, the one-dimensional channel in apatite became larger, facilitating the rearrangement of F− ion. This study investigated the irradiation-induced amorphization of REE-silicon doped fluorapatites and the results highlighted the importance of composition of immobilization materials on irradiation performance.

Continuous flow synthesis of the antiviral drug tecovirimat and related sp3-rich scaffolds.

Herein we report a 2-step continuous flow synthesis of the antiviral drug tecovirimat, which is used for the treatment of monkeypox and smallpox. This work exploits a high-temperature pericyclic cascade process between cycloheptatriene and maleic anhydride generating a key sp3-rich scaffold, which affords the desired API after further condensation with an acyl hydrazide. Additional investigations of the key intermediate in reactions with different hydrazines revealed the accessibility of different heterocyclic chemotypes, depending on the substitution pattern of the hydrazine used. Ultimately, the streamlined and scalable access to these sp3-rich scaffolds enables improved access to tecovirimat and structurally related entities with high drug-like character.

Memory effects in a sequence of measurements of noncommuting observables

We use continuous, stochastic quantum trajectories within a framework of quantum state diffusion (QSD) to describe alternating measurements of two noncommuting observables. Projective measurement of an observable completely destroys memory of the outcome of a previous measurement of the conjugate observable. In contrast, measurement under QSD is not projective and it is possible to vary the rate at which information about previous measurement outcomes is lost by changing the strength of measurement. We apply our methods to a spin 1/2 system and a spin 1 system undergoing alternating measurements of the Sz and Sx spin observables. Performing strong Sz measurements and weak Sx measurements on the spin 1 system, we demonstrate return to the same eigenstate of Sz to a degree beyond that expected from projective measurements and the Born rule. Such a memory effect appears to be greater for return to the ±1 eigenstates than the 0 eigenstate. Furthermore, the spin 1 system follows a measurement cascade process where an initial superposition of the three eigenstates of the observable evolves into a superposition of just two, before finally collapsing into a single eigenstate, giving rise to a distinctive pattern of evolution of the spin components. Published by the American Physical Society 2024

Dynamic Asymmetric Diamination of Allylic Alcohols through Borrowing Hydrogen Catalysis: Diastereo-Divergent Synthesis of Tetrahydrobenzodiazepines.

We present herein a catalytic enantioconvergent diamination of racemic allylic alcohols with the construction of two C-N bonds and 1,3-nonadjacent stereocenters. This iridium/chiral phosphoric acid cooperative catalytic system operates through an atom-economical borrowing hydrogen amination/aza-Michael cascade, and converts readily available phenylenediamines and racemic allylic alcohols to 1,5-tetrahydrobenzodiazepines in high enantioselectivity. An intriguing solvent-dependent switch of diastereoselectivity was also observed. Mechanistic studies suggested a dynamic kinetic resolution process involving racemization through a reversible Michael addition, making the last step of asymmetric imine reduction the enantiodetermining step of this cascade process.

A soft processing technology for the extraction of cellulose from plant residues and agri-food wastes

In this study, cellulose was extracted from giant cane (GC), Posidonia oceanica seagrass (PO), coffee silverskin (CS), and brewer's spent grain (BSG) as alternatives to conventional sources of cellulose. The extraction protocol involved three steps: i) hemicellulose and lignin removal through alkaline hydrolysis in a 5% (w/v) NaOH solution (solid-to-liquid ratio = 1:100 g/mL, T = 25 °C, t = 2 h, ω = 300 rpm), ii) removal of organic compounds and ashes through a 95% (v/v) ethanol solution (solid-to-liquid ratio = 1:25 g/mL, T = 25 °C, t = 0.5 h, ω = 500 rpm), and iii) double bleaching in a 1% (w/v) acidic (pH = 4) NaClO2 solution (solid-to-liquid ratio = 1:50 g/mL, T = 90 °C, t = 1.5 h, ω = 500 rpm). Yield, purity, crystallinity degree, and morphology of cellulose extracted through a soft-chemical cascade process were assessed by gravimetric, infrared (FT-IR), nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM) analyses. Averaged cellulose extraction yields of 36.4, 38.6, 23.1, and 22.2% for GC, PO, CS, and BSG were obtained, respectively. All cellulose samples had high purity, though lower than the ultra-pure bacterial cellulose, which was due to the slight contamination from unremoved hemicellulose and lignin residues. Cellulose samples exhibited similar chemical features and the typical fibril-like morphology of microcrystalline cellulose (6–13 μm in width). The versatility of the proposed extraction procedure supports the sustainable conversion of low-cost organic biomasses to valuable products with manifold industrial applications (e.g., food packaging).

Exploring Marine-Based Food Production: The Challenges for a Sustainable and Fast Biotechnology-Based Development

Marine-derived nutrients and bioactive compounds may offer a myriad of biological benefits, such as anticancer and anti-inflammatory properties, and technological potential, enhancing food quality as additives. Their role in the sustainable development of food technology is fundamental, especially in advancing the knowledge of functional foods and related technologies. Algae are considered one of the major sources of marine-derived ingredients and the subject of several recent studies. Despite their potential, the translation of marine ingredients’ potential into a marine-based competitiveness of the food industry faces hurdles in the extraction process and operational systems scale-up that the industry needs to tackle. The complexity of marine matrices with diverse compounds and solubilities adds complexity to extraction processes and may lead to low yields or bioactivity loss. Contaminants, like heavy metals and pesticide residues in marine organisms, require rigorous purification processes for product safety. The use of biorefinery systems in marine-based ingredients’ production, particularly cascade processes, offers zero-waste solutions, contributing to the blue economy and aligning with UN sustainability goals. Sustainability assessment tools are critical for evaluating marine-based food production’s environmental, social, and economic impacts. A continued exploration and collaboration are essential for the future, fostering innovation and sustainability to create a resilient, equitable, and eco-friendly food system.

Machine-learning classification with additivity and diverse multifractal pathways in multiplicativity

Evidence of multifractal structures has spread to a wider set of physiological time series supporting the intricate interplay of biological and psychological functioning. These dynamics manifest as random multiplicative cascades, embodying nonlinear relationships characterized by recurring division, branching, and aggregation processes implicating noise across successive generations. This investigation focuses on how well the diversity of multifractal properties can be specific to the type of cascade relationship between generation (i.e., multiplicative, additive, or a mixture) as well as to the type of noise (i.e., including additive white Gaussian noise, fractional Gaussian noise, and various amalgamations) among 15 distinct types of binomial cascade processes. Cross-correlation analysis of multifractal spectral features confirms that these features capture nuanced aspects of cascading processes with minimal redundancy. Principal component analysis using 13 distinct multifractal spectral features shows that different cascade processes can manifest multifractal evidence of nonlinearity for distinct reasons. This transparency of multifractal spectral features to underlying cascade dynamics becomes less amenable to machine-learning strategies. Fully connected neural networks struggled to classify the 15 distinct types of cascade processes based on the respective multifractal spectral features (45.5% accuracy) yet demonstrated improved accuracy when addressing single categories of cross-generation relationships, that is, additive (91.6%), multiplicative (75.4%), or additomultiplicative (70.6%). While traditional principal component analysis reveals distinct loadings attributed to individual noise processes, multiplicative relationships between generations effectively make the constituent noise processes less discernible to neural networks. Neural networks may lack sufficient hierarchical depth required to effectively distinguish among nonadditive cascading processes, recommending either elaborating multifractal geometry or using alternate architectures for machine-learning classification of cascades with multiplicative relationships. Published by the American Physical Society 2024

γ-CF3-Allenamides versus 3-CF3-Cyclopentenylamines: Substituent-Controlled Divergent Reaction of β-CF3-1,3-Enynamides with β-Dicarbonyl Compounds.

A distinctive N-substituent-controlled regioselective 1,4-hydrocarbonation or 1,4-hydrocarbonation/5-endo-trig cyclization cascade reaction of β-CF3-1,3-enynamides with β-dicarbonyl compounds in the presence of a simple base is reported. β-CF3-1,3-enynamides having a Ts group N-substituent produce γ-CF3-allenamides via a 1,4-hydrocarbonation process, whereas β-CF3-1,3-enynamides bearing a Ms group N-substituent lead to 3-CF3-cyclopentenylamines through a 1,4-hydrocarbonation/5-endo-trig cyclization cascade process.

Criticality and universality in neuronal cultures during "up" and "down" states.

The brain can be seen as a self-organized dynamical system that optimizes information processing and storage capabilities. This is supported by studies across scales, from small neuronal assemblies to the whole brain, where neuronal activity exhibits features typically associated with phase transitions in statistical physics. Such a critical state is characterized by the emergence of scale-free statistics as captured, for example, by the sizes and durations of activity avalanches corresponding to a cascading process of information flow. Another phenomenon observed during sleep, under anesthesia, and in in vitro cultures, is that cortical and hippocampal neuronal networks alternate between "up" and "down" states characterized by very distinct firing rates. Previous theoretical work has been able to relate these two concepts and proposed that only up states are critical whereas down states are subcritical, also indicating that the brain spontaneously transitions between the two. Using high-speed high-resolution calcium imaging recordings of neuronal cultures, we test this hypothesis here by analyzing the neuronal avalanche statistics in populations of thousands of neurons during "up" and "down" states separately. We find that both "up" and "down" states can exhibit scale-free behavior when taking into account their intrinsic time scales. In particular, the statistical signature of "down" states is indistinguishable from those observed previously in cultures without "up" states. We show that such behavior can not be explained by network models of non-conservative leaky integrate-and-fire neurons with short-term synaptic depression, even when realistic noise levels, spatial network embeddings, and heterogeneous populations are taken into account, which instead exhibits behavior consistent with previous theoretical models. Similar differences were also observed when taking into consideration finite-size scaling effects, suggesting that the intrinsic dynamics and self-organization mechanisms of these cultures might be more complex than previously thought. In particular, our findings point to the existence of different mechanisms of neuronal communication, with different time scales, acting during either high-activity or low-activity states, potentially requiring different plasticity mechanisms.

Thermo-enviro-economic analyses of a landfill biogas-fed polygeneration process combined with a liquefied natural gas cold energy utilization unit

Landfill biogas offers a promising opportunity to supply society’s energy requirements, following the waste-to-energy approach, which issuitable for sustainable production. However, structural modification for its utilization is the main gap, requiring additional research efforts. Considering this issue, the current study aims to design an eco-friendly polygeneration method for landfill biogas utilization for a cutting-edge heat recovery system that integrates a cold energy recovery and utilization unit for liquefied natural gas. The liquefied natural gas recovery section, the organic Rankine cycle with a zeotropic mixture, and the Kalina cycle are all started using the flue gas from the combustion of biogas in a cascade process. In addition, the waste heat of the Kalina cycle is recovered by a single-effect desalination cycle and liquefied natural gas recovery section. Also, a water electrolysis process is integrated into the whole system. As a result, the products include hydrogen, electricity, natural gas, hot and cold water, and freshwater. The Aspen HYSYS software is utilized to design the system and investigate its thermodynamic, environmental, and economic aspects. The results demonstrate an energy efficiency of 57.54 % and an exergy efficiency of 18.78 %. Also, the carbon dioxide footprint associated with the system equals 0.34 kg/kWh, and the specific cost of products is 73.96 $/GJ. An optimal exergy efficiency of 25.8 % and a specific cost of products of 69.7 $/GJ are obtained by means of an intelligent optimization approach that ultimately makes use of non-dominated sorting genetic algorithm-II and artificial neural networks.

Mapping of Some Further Alkylation-Initiated Pathways to Polyheterocyclic Compounds from Indigo and Indirubin.

The reaction of indigo with two equivalents of the electrophile ethyl bromoacetate with caesium carbonate as a base result in the formation of structurally complex polyheterocyclics, including a fused spiroimidazole and a spiro[1,3]oxazino derivative, together with a biindigoid-type derivative, through a convenient one-pot reaction. Further assessment of the reaction using five equivalents of the electrophile gave rise to other molecules incorporating the 2-(7,13,14-trioxo-6,7,13,14-tetrahydropyrazino[1,2-a:4,3-a']diindol-6-yl) scaffold. The reaction of ethyl bromoacetate with the less reactive indirubin resulted in the synthesis of three derivatives of a new class of polyheterocyclic system via a cascade process, although yields were low. These compounds were derived from the parent indolo[1,2-b]pyrrolo[4,3,2-de]isoquinoline skeleton. Despite the modest yields of the reactions, they represent quick cascade routes to a variety of heterocycles from cheap starting materials, with these structures otherwise being difficult to synthesise in a traditional stepwise manner. These outcomes also contribute significantly to the detailed understanding of the indigo/indirubin cascade reaction pathways initiated by base-catalysed N-alkylation.

Spatial segregation of catalytic sites within Pd doped H-ZSM-5 for fatty acid hydrodeoxygenation to alkanes

Spatial control over features within multifunctional catalysts can unlock efficient one-pot cascade reactions, which are themselves a pathway to aviation biofuels via hydrodeoxygenation. A synthesis strategy that encompasses spatial orthogonality, i.e., one in which different catalytic species are deposited exclusively within discrete locations of a support architecture, is one solution that permits control over potential interactions between different sites and the cascade process. Here, we report a Pd doped hierarchical zeolite, in which Pd nanoparticles are selectively deposited within the mesopores, while acidity is retained solely within the micropores of ZSM-5. This spatial segregation facilitates hydrodeoxygenation while suppressing undesirable decarboxylation and decarbonation, yielding significant enhancements in activity (30.6 vs 3.6 moldodecane molPd−1 h−1) and selectivity (C12:C11 5.2 vs 1.9) relative to a conventionally prepared counterpart (via wet impregnation). Herein, multifunctional material design can realise efficient fatty acid hydrodeoxygenation, thus advancing the field and inspiring future developments in rationalised catalyst design.

Cascade processes of induced and triggered earthquakes-Case study in the Weiyuan shale gas development area in Sichuan Basin, China

Identifying accurate seismogenic faults is critical for studying the mechanisms of induced earthquakes. On February 24th and 25th, 2019, three moderate earthquakes with magnitudes of MS 4.7, MS 4.3, and MS 4.9 occurred successively in the shale gas development area of Weiyuan, China. We utilized high-resolution three-dimensional (3D) seismic data to identify two pre-existing faults (F1 and F2) that were responsible for the three moderate earthquakes. InSAR data were used to validate the rationality of the two seismogenic faults. Furthermore, we analyzed the impact of fluid diffusion on fault F1 near the fracturing well and calculated the Coulomb failure stress (CFS) generated on fault F2 by the MS 4.7 and MS 4.3 earthquakes to analyze the interactions between these events. The results indicated that fluid diffusion caused by hydrofracturing induced the MS 4.3 and MS 4.7 earthquakes on F1. The static Coulomb stress changes from these two earthquakes subsequently triggered the larger MS 4.9 earthquake on F2. This study provides a case of a cascading process in which induced earthquake events triggered a more distant and higher-magnitude earthquake. This triggering scenario reminds us that earthquake-to-earthquake interactions may be more hazardous than a “typical” inducing mechanism and challenges current risk management practices.

Remote C─H Bond Activation via Enantioselective Carbopalladation and 1,4-Pd Migration Cascade Process.

Carbopalladation-initiated cascade reaction involving 1,4-Pd migration is a straightforward and powerful approach to activate remote C─H bond, forging versatile fused polycyclic compounds containing fluorene fragment which are highly valuable synthetic targets. However, its asymmetric variants pose considerable challenges and have not been explored. Here the first asymmetric palladium-catalyzed tandem carbopalladation is reported, 1,4-Pd migration reaction of ortho-iodophenol-derived allyl ether under mild conditions, allowing the transformation of a wide range of substrates in good to excellent enantioselectivities, and providing a facile and straight forward access to tetracyclic dihydroindeno[1,2,3-de]chromene bearing a chiral fluorene skeleton. A good functional group tolerance, high stereoselectivity, as well as the good chiroptical properties (high fluorescence quantum yields, circular dichroism) of the products make this approach highly attractive. Moreover, density functional theory (DFT) calculations indicate that the protonation of five-membered palladacycle intermediate is more favorable rather than its direct reductive elimination process.

Efficient treatment of polyacrylamide wastewater by cascade heterogeneous Fenton and magnetic flocculation process

A large quantity of polyacrylamide containing wastewater is generated during polymer flooding every year and it poses great threats to the environment. As highly efficient technology for polyacrylamide wastewater treatment with potential for engineering application is rare, magnetic flocculation represents a promising alternative. It usually takes minutes for complete sedimentation to occur. However, we found in experiments that viscosity reduction in advance was essential to improve the performance of magnetic flocculation. So, a cascade of heterogeneous Fenton and magnetic flocculation process was proposed. Effect of Fe3O4 dosage, flocculants type and dosage, flocculation pH, stirring conditions and flocculation methods on the removal efficiency of PAM was investigated. The cascade process turned out to be one of the most efficient technologies and achieved 92% PAM removal rate in the shortest time (45 min) for 500 mg/L of PAM when Fe3O4 dosage was 1.5 g/L, AlCl3 dosage was 100 mg/L and flocculation pH was 8.0 under optimized stirring conditions. Nano-Fe3O4 exhibited good stability after at least 3 successive runs. The water quality of polymer flooding wastewater from Nanyang Oilfield reached the required standards for reinjection after treatment by the cascade process. The study provides a new and highly efficient technology for PAM wastewater treatment with promising potential for engineering application.

Yb(OTf)<sub>3</sub>‐Catalyzed C=C Bond Cleavage‐Reassembly Enabling Bicyclization: Regioselective Synthesis of Heteroarylated Pentacyclic Indoles

A Yb(OTf)<sub>3</sub>‐catalyzed [2 + 2] cycloaddition /retro‐electrocyclization (CA‐RE)/ bicyclization of 1‐(2‐aminoarylaklynyl)‐naphthalen‐2‐ols and 3‐ylideneoxindoles is reported, enabling a direct C=C bond cleavage‐reassembly process to regioselectively synthesize a variety of quinoline‐tethered benzo[5,6]chromeno[2,3‐b]indoles in 31‐84% yields. Exchanging the amino group for the hydroxyl group in the arylalkynyl unit of the naphthalen‐2‐ol substrate resulted in chromenyl chromeno[2,3‐b]indoles via a similar cascade process.