Classical Reaction Research Articles

Piecewise second kind Chebyshev functions for a class of piecewise fractional nonlinear reaction–diffusion equations with variable coefficients

In this paper, a new type of piecewise fractional derivative (PFD) is introduced. The ordinary and distributed-order fractional derivatives in the Caputo sense are used to define this type of PFD. A new version of nonlinear reaction–diffusion equations with variable coefficients is defined using this type of PFD. The orthonormal piecewise second kind Chebyshev functions (CFs), as a new family of basic functions, are generated. An explicit formula is extracted for PFD of these piecewise functions. A hybrid method based on the orthonormal piecewise second kind CFs and orthonormal second kind Chebyshev polynomials is proposed to solve the aforementioned problem. The established approach transforms solving the expressed problem into solving an algebraic system of equations. To illustrate the accuracy of the developed method, some numerical examples are considered.

Synthesis and Antitumour Activity of Hybrid Compounds Based on 4-Aminophenylarsonic Acid and Spatially Hindered Phenols.

One of the main modern approaches to the creation of effective drugs is the design of new biologically active substances containing two or more pharmacophore groups in their structure. In recent years, there have been many publications on the synthesis and study of biological activity, including antitumour activity, of new organo-arsenic compounds. It is known that spatially hindered phenols can also have antitumor activity, so the synthesis and study of hybrid compounds based on organo-arsenic compounds and spatially hindered phenols is a relevant area of research. In this work, the modification of 4-aminophenylarsonic acid with 3,5-di-tert-butyl-4-hydroxybenzylacetate was carried out. In contrast to a similar transformation of 2-aminophenylarsonic acid, in this case it was possible to obtain both mono- and di-benzyl derivatives of the acid. Using the Zandmeyer method, the oxime isatin containing an arsonic acid fragment in the fifth position of the heterocycle was synthesised. Azo derivatives containing fragments of para-aminophenylarsonic acid and sterically hindered phenols were obtained. 4-((3,5-Di-tert-butyl-2-hydroxyphenyl)diazenyl)phenylarsonic acid was isolated in pure form. At the same time, it was found that the reaction of the diazonium azo salt of 4-aminophenylarsonic acid with 2-hydroxymethyl-4-tert-butylphenol proceeds in two directions. In addition to the classical diazotisation reaction at the 6-position of 2-hydroxymethyl-4-tert-butylphenol, a diazotisation accompanied by a dehydroxymethylation process occurs. The obtained compounds showed cytotoxic activity against human tumor cell lines M-HeLa (cervical epithelioid carcinoma) and HuTu 80 (duodenal adenocarcinoma cells). The most promising is the sodium salt of 4-((3,5-di-tert-butyl-2-hydroxyphenyl)diazenyl)phenylarsonic acid, which is superior to Tamoxifen and 5-fluorouracil in terms of selectivity index towards M-HeLa and HuTu 80 cells.

Construction of Spiro Systems from Tetrathiafulvalene Derivatives by a Pinacol‐like Rearrangement

An efficient and generalized pinacol‐like rearrangement of tetrathiafulvalene (TTF) derivatives has been achieved using 2, 2, 6, 6‐tetramethylpiperidine oxide (TEMPO) as a key reagent, in place of a traditional metal catalyst. Examination of numerous TTF derivatives demonstrates the reaction's exceptional tolerance to a variety of substituents, achieving an overall yield of up to 97%. The optimization of reaction conditions and evaluation of reaction applicability were achieved by varying factors such as the redox potential (E11/2) of the substrate molecule, substituent type, substituent position, number of substituents, and structural symmetry. Additionally, the reaction mechanism was explored using isotopic labeling, real‐time monitoring UV‐Vis absorption spectroscopy, and X‐ray diffraction (XRD) analysis. Specifically, TTF is oxidized to TTF+• by p‐toluenesulfonic acid (TsOH·H2O). TTF+• subsequently reacts with TEMPO and H2O to form a pinacol‐like intermediate, which undergoes a rearrangement to release a 2, 2, 6, 6‐tetramethylpiperidin‐1‐ol (TEMPOH) molecule, forming the rearranged product as a hydrogenated cation, this intermediate undergoes deprotonation, leading to the formation of the final spiro product. This investigation led to the identification of a class of reactions for the efficient conversion of TTF derivatives into their spiro products via pinacol‐like rearrangement reaction.

Comparison of MIB‐1‐Specific Membrane Staining in Hyalinising Trabecular Tumor Using Mainstream Automated Immunohistochemical Staining Platforms

ABSTRACTBackgroundMIB‐1, a monoclonal antibody against Ki‐67, exhibits specific membrane staining in the immunohistochemistry of hyalinising trabecular tumor (HTT). This specific staining pattern is crucial in diagnosing HTT. Although manual immunohistochemical staining remains the established method for MIB‐1 staining, this process is complicated, inconsistent, and prone to false negatives.MethodsThis study aimed to explore whether the classical reaction pattern can be replicated by utilizing the current mainstream automated immunohistochemical staining platforms. Furthermore, we examined the effect of different conditions on staining efficiency and their value in clinical diagnosis assistance.ResultsSpecimens obtained from eight and six cases of HTT and non‐HTT, respectively, from a single center were stained using the manual staining method and the Dako Autostainer Link 48 (AS48), Dako Omnis, Ventana BenchMark ULTRA, and Leica BOND‐III automated immunohistochemical staining platforms. The Autostainer Link 48 was found to be the most stable staining platform, while the BenchMark ULTRA with primary antibody incubation at room temperature (RT) and the Omnis platform with antigen retrieval at pH 9.0 were able to reproduce membrane‐positive staining for MIB‐1 in the HTT specimens.ConclusionsOur results offer crucial reference value for clinical diagnostic assistance.

Gold-Catalyzed Cope Rearrangements

Over decades, Cope rearrangements have attracted significant research interest in the field of synthetic organic chemistry relying on their ability to undergo stereoselective structural reorganization. Despite substantial progress, the development of this field remained confined to the use of parent 1,5-hexadienes. Against the backdrop of classical Cope reaction, we reported the utilization of unconventional 1,6-heptadienes to develop the arylative Cope rearrangement by harnessing the interplay between the π-activation and cross-coupling reactivity mode of gold complexes. Several mechanistic investigations such as 31P NMR study, HRMS analysis, cross-over experiment, control experiments were performed to support the proposed cyclization-induced [3,3]-rearrangement mechanism in arylative Cope reaction.

Stepwise or Concerted Mechanisms? Rethinking of the Classical Carbocation Rearrangement Reaction

Stepwise or Concerted Mechanisms? Rethinking of the Classical Carbocation Rearrangement Reaction

Hydroxyl Radical Mediated Heterogeneous Photocatalytic Baeyer‐Villiger Oxidation over Covalent Triazine/Heptazine‐Based Frameworks

The Baeyer‐Villiger oxidation of ketones to the corresponding lactones/esters is a classic and essential reaction in the chemical industry. However, this oxidation process has not yet been achieved in ambient conditions with the aid of oxygen and heterogeneous photocatalysts. In this study, we developed an organic photocatalytic system using covalent triazine/heptazine‐based frameworks (CTF‐TB/CHF‐TB) to enable the B‐V oxidation reaction under mild conditions through a cascade reaction pathway. Experimental data and theoretical calculations showed that heptazine/triazine units can "chelate” and decompose the in situ generated H2O2 into hydroxyl radicals (•OH). Compared to conventional methods that primarily involve metal‐activated benzaldehyde at elevated temperatures (e.g., 60 oC), the •OH generated in our study can readily cleave the C‐H bond of benzaldehyde, forming an active intermediate that drives subsequent sequential processes: O2→H2O2→•OH→Ph‐CO•→Ph‐COOO•. By employing this photocatalytic process, a yield of 91% and a selectivity of over 99 % were obtained in the oxidation of cyclohexanone to caprolactone at room temperature. This performance is comparable to the state‐of‐the‐art catalysts, and our CHF‐TB catalyst demonstrates impressive reusability, maintaining a high yield after 5 consecutive runs. This work presents a straightforward approach for C‐H cleavage by organocatalysts to produce ε‐caprolactone in a mild manner by Baeyer‐Villiger oxidation.

Reducing Stoichiometric Excess of Base to Catalytic Amount: Revisiting Staudinger Reaction for -lactam Synthesis

Background: -lactams have been primarily utilized as a leading class of effective antibiotics. They have been found to show activity against various diseases, prompting the scientific community to prioritise innovative protocols for their synthesis. The general and well-known synthetic strategy involves the classical Staudinger reaction exhibiting [2+2] cycloaddition reaction. However, the protocol utilizes stoichiometric excess of base for efficient product formation. Objective: A smarter and more acceptable approach for the synthesis of -lactams would be to reduce the excess base to a catalytic amount, furnishing a catalytic version of the Staudinger reaction. The modified version can eliminate the hazards arising out of excess use of the base, ultimately promoting the environmentally benign approach. Methods: With this hypothesis, a base-catalyzed approach in dimethyl formamide (DMF) towards the synthesis of -lactam via Staudinger reaction has been endorsed under moderate reaction conditions. Results: The scope of the substrates was explored with both electron-withdrawing and electronreleasing substitutions in the formation of -lactam. The reduction of the base amount from stoichiometric to catalytic amount was justified by the involvement of DMF in generating the basic condition for the reaction. Conclusion: It was hypothesized that the decomposition of DMF under the base-catalysed reaction condition can generate dimethylamine, which produces the required basic environment. conclusion: A base-catalysed approach in dimethyl formamide (DMF) towards the synthesis of β-lactam via Staudinger reaction has been endorsed under moderate reaction conditions. The substrates scope was explored with both electron withdrawing and electron releasing substitutions in the formation of β-lactam. The reduction of base amount from stoichiometric to catalytic was justified by the involvement of DMF in generating the basic condition for the reaction. It was hypothesized that the decomposition of DMF under the base catalysed reaction condition can generate dimethylamine which produces the required basic environment.

Hydroxyl Radical Mediated Heterogeneous Photocatalytic Baeyer-Villiger Oxidation over Covalent Triazine/Heptazine-Based Frameworks.

The Baeyer-Villiger oxidation of ketones to the corresponding lactones/esters is a classic and essential reaction in the chemical industry. However, this oxidation process has not yet been achieved in ambient conditions with the aid of oxygen and heterogeneous photocatalysts. In this study, we developed an organic photocatalytic system using covalent triazine/heptazine-based frameworks (CTF-TB/CHF-TB) to enable the B-V oxidation reaction under mild conditions through a cascade reaction pathway. Experimental data and theoretical calculations showed that heptazine/triazine units can "chelate" and decompose the in situ generated H2O2 into hydroxyl radicals (•OH). Compared to conventional methods that primarily involve metal-activated benzaldehyde at elevated temperatures (e.g., 60 oC), the •OH generated in our study can readily cleave the C-H bond of benzaldehyde, forming an active intermediate that drives subsequent sequential processes: O2→H2O2→•OH→Ph-CO•→Ph-COOO•. By employing this photocatalytic process, a yield of 91% and a selectivity of over 99 % were obtained in the oxidation of cyclohexanone to caprolactone at room temperature. This performance is comparable to the state-of-the-art catalysts, and our CHF-TB catalyst demonstrates impressive reusability, maintaining a high yield after 5 consecutive runs. This work presents a straightforward approach for C-H cleavage by organocatalysts to produce ε-caprolactone in a mild manner by Baeyer-Villiger oxidation.

Navigating Ball Mill Specifications for Theory-to-Practice Reproducibility in Mechanochemistry.

The rising prospects of mechanochemically assisted syntheses hold promise for both academia and industry, yet they face challenges in understanding and, therefore, anticipating respective reaction kinetics. Particularly, dependencies based on variations in milling equipment remain little understood and globally overlooked. This study aims to address this issue by identifying critical parameters through kinematic models, facilitating the reproducibility of mechanochemical reactions across the most prominent mills in laboratory settings, namely planetary and mixer mills. Through a series of selected experiments replicating major classes of organic, organometallic, transition metal-catalyzed, and inorganic reactions from literature, we rationalize the independence of kinematic parameters on reaction kinetics when the accumulated energy criterion is met. As a step forward and to facilitate the practicability of our findings, we provide a freely accessible online tool[†] that allows the calculation of respective energy parameters for different planetary and mixer mills. Our work advances the current understanding of mechanochemistry and lays the foundation for future rational exploration in this rapidly evolving field.

Navigating Ball Mill Specifications for Theory‐to‐Practice Reproducibility in Mechanochemistry

AbstractThe rising prospects of mechanochemically assisted syntheses hold promise for both academia and industry, yet they face challenges in understanding and, therefore, anticipating respective reaction kinetics. Particularly, dependencies based on variations in milling equipment remain little understood and globally overlooked. This study aims to address this issue by identifying critical parameters through kinematic models, facilitating the reproducibility of mechanochemical reactions across the most prominent mills in laboratory settings, namely planetary and mixer mills. Through a series of selected experiments replicating major classes of organic, organometallic, transition metal‐catalyzed, and inorganic reactions from literature, we rationalize the independence of kinematic parameters on reaction kinetics when the accumulated energy criterion is met. As a step forward and to facilitate the practicability of our findings, we provide a freely accessible online tool[†] that allows the calculation of respective energy parameters for different planetary and mixer mills. Our work advances the current understanding of mechanochemistry and lays the foundation for future rational exploration in this rapidly evolving field.

Umpolung Approach to Aldol Products via Isoxazoline N-Oxides as Intermediates.

A two-step umpolung approach to the diastereoselective synthesis of aldols was developed, in which a conjugated nitroalkene is used as the synthetic equivalent of the enolonium cation, while a sulfur ylide acts as the equivalent of the α-carbinol anion. The resulting isoxazoline N-oxides undergo catalytic reductive cleavage to aldols under mild conditions at room temperature and under 1 atm hydrogen pressure. The efficiency of the method was demonstrated by the synthesis of a series of polysubstituted β-hydroxyketones that are difficult to synthesize using the classical aldol reaction. The developed approach allows for the regiodivergent assembly of aldols by selecting a nitroalkene isomer with the appropriate position of the C,C double bond.

Illuminating tandem reactions characterized by temporal separation of catalytic activities via DFT calculations: A case study of Ni-catalyzed alkyne semi-hydrogenation

The concept of “temporal separation of catalytic activities” outlines a scenario where multiple transformations within a catalytic tandem reaction proceed sequentially over time without mutual interference. After presenting several examples of such reactions, we specifically focus on an example of the Ni-catalyzed alkyne semi-hydrogenation as a significant case study. By performing density functional theory (DFT) calculations, we illuminate the unique dynamic character of the reaction that the intermediate remains dormant until the reactant exhausted. The insights gained from the present calculations have led us to propose a comprehensive energy landscape model for the catalytic tandem reactions with temporal separation of catalytic activities, which offers a logical explanation for the temporal dormancy of the intermediate. This class of reactions is expected to be highly valuable as it presents the opportunity to fine-tune individual reaction steps, thereby introducing fresh concepts for precise control of reactions in one-pot chemistry.

Green Diesel Production Through Deoxygenation Reaction with Natural Zeolite-supported Nickel and Copper Catalyst

The depletion of fossil fuels and their environmental impact necessitate sustainable alternatives. Green diesel, a biofuel with a chemical structure similar to conventional diesel, has gained traction as a viable alternative. This study explores the development of a cost-effective catalyst for green diesel production using deoxygenation. Deoxygenation refers to a broad class of chemical reactions where oxygen atoms are stripped from a molecule. This research employed abundant Indonesian natural zeolite (NZ) as a catalyst support, impregnated with non-noble metals, nickel (Ni), and copper (Cu). The investigation revealed that the NiCu/NZ catalyst achieved the highest oleic acid conversion (90.40%) and green diesel yield. The product distribution, ranging from C15 to C18 hydrocarbons, reflects the moderate acidity of the catalyst, promoting diverse cracking patterns compared to highly acidic catalysts. Additionally, the high specific surface area of NZ facilitates the conversion and good product distribution. Furthermore, the optimization process demonstrated that increasing hydrogen pressure during deoxygenation enhances both conversion rate and green diesel production.

Radical Polarity.

The polarity of a radical intermediate profoundly impacts its reactivity and selectivity. To quantify this influence and predict its effects, the electrophilicity/nucleophilicity of >500 radicals has been calculated. This database of open-shell species entails frequently encountered synthetic intermediates, including radicals centered at sp3, sp2, and sp hybridized carbon atoms or various heteroatoms (O, N, S, P, B, Si, X). Importantly, these computationally determined polarities have been experimentally validated for electronically diverse sets of >50 C-centered radicals, as well as N- and O- centered radicals. High correlations are measured between calculated polarity and quantified reactivity, as well as within parallel sets of competition experiments (across different radical types and reaction classes). These multipronged analyses show a strong relationship between the computed electrophilicity, ω, of a radical and its relative reactivity (krel vs Δω slopes up to 40; showing mere Δω of 0.1 eV affords up to 4-fold rate enhancement). We expect this experimentally validated database will enable reactivity and selectivity prediction (by harnessing polarity-matched rate enhancement) and assist with troubleshooting in synthetic reaction development.

Programmable Chemical Reactions Enable Ultrastrong Soft Pneumatic Actuation.

Soft pneumatic actuation is widely used in wearable devices, soft robots, artificial muscles, and surgery machines. However, generating high-pressure gases in a soft, controllable, and portable way remains a substantial challenge. Here, a class of programmable chemical reactions that can be used to controllably generate gases with a maximum pressure output of nearly 6MPa is reported. It is proposed to realize the programmability of the chemical reaction process using thermoelectric material with programmable electric current and employing preprogrammed reversible chemical reactants. The programmable chemical reactions as soft pneumatic actuation can be operated independently as miniature gas sources (∼20-100g) or combined with arbitrary physical structures to make self-contained machines, capable of generating unprecedented pressures of nearly 6MPa or forces of about 18kN in a controllable, portable, and silent manner. Striking demonstrations of breaking a brick, a marble, and concrete blocks, raising a sightseeing car, and successful applications in artificial muscles and soft assistive wearables illustrate tremendous application prospects of soft pneumatic actuation via programmable chemical reactions. The study establishes a new paradigm toward ultrastrong soft pneumatic actuation.

Enhancing selectivity through forced dynamic operation with intraparticle diffusion limitations: Ethane oxidative dehydrogenation

During steady state operation (SSO) of industrial fixed-bed reactors diffusion limitations are often present. Well-known impacts include the reduced rate of a positive order reaction and reduced selectivity of the desired intermediate product in a sequential reaction system. This work presents an approach for circumventing diffusion limitations through forced dynamic operation (FDO) of metal oxide catalyzed partial oxidation reactions. Through coupled experiments and modeling, we examine the use of FDO to mitigate selectivity losses of the intermediate product in a parallel-consecutive reaction. With the oxidative dehydrogenation (ODH) of ethane (C2H6) to ethylene (C2H4) over an Al2O3 supported VOx catalyst as the model reaction system, FDO is shown to mitigate undesired C2H4 overoxidation to COx that predominates in steady state diffusion-limited pellets, resulting in C2H4 selectivities that are 15 % (absolute) higher compared to SSO in 2.6 mm catalyst pellets. A kinetic model reveals that FDO beneficially alters the distribution of chemisorbed (O*) and lattice (OL) oxygen, which respectively primarily participate in reactions consuming C2H4 and C2H6. FDO is shown to lead to less detrimental impact of diffusion on the ethylene selectivity and yield compared to SSO. During FDO, generated C2H4 reacts with unselective O*, leaving behind selective OL. The reduced bulk phase O2 in the reductive half cycle leads to accumulation of OL, suppressing C2H4 overoxidation. This effect is amplified via C2H4 trapping in the catalyst pellet. Thus, larger catalyst pellets exhibit selectivities that more rapidly increase with reduction time, inducing higher FDO cycle averages compared to SSO. The findings raise the prospect of applying FDO through feed switching or chemical looping as a way to increase intermediate yield in the class of partial oxidation reactions.

Asymmetric autocatalytic reactions and their stationary distribution

We consider a general class of autocatalytic reactions, which has been shown to display stochastic switching behaviour (discreteness-induced transitions (DITs)) in some parameter regimes. This behaviour was shown to occur either when the overall species count is low or when the rate of inflow and outflow of species is relatively much smaller than the rate of autocatalytic reactions. The long-term behaviour of this class was analysed in Bibbona et al. (Bibbona et al. 2020 J. R. Soc. Interface 17 , 20200243 (doi:10.1098/rsif.2020.0243)) with an analytic formula for the stationary distribution in the symmetric case. We focus on the case of asymmetric autocatalytic reactions and provide a formula for an approximate stationary distribution of the model. We show this distribution has different properties corresponding to the distinct behaviour of the process in the three parameter regimes; in the DIT regime, the formula provides the fraction of time spent at each of the stable points.

Amide synthesis from DDQ-mediated electrochemical Beckmann rearrangement

Beckmann rearrangement, a classical reaction of introducing nitrogen to carbon skeleton compounds for amide synthesis, is widely used in academia and industry. Herein, an electrochemical Beckmann rearrangement is reported, utilizing 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a mediator to prevent the over-electro-oxidation of products, which could afford amide in excellent yield.

Serendipity as a Driving Force in the Synthesis of Isatins Substituted with Electron-Donating Groups

AbstractAn efficient synthetic procedure for the synthesis of isatins was found after careful analysis of the serendipitous results of the unexpected products obtained by aromatic nucleophilic substitution when it was attempted to introduce 6-fluoroisatins to the classic Pfitzinger reaction. Attentive analysis of these results led to elaborating a methodology for synthesizing electron-enriched isatins, including those with hydroxy-, alkoxy-, alkylthio-, and dialkylamino-substituted aromatic rings. Limitations of the method were established. The reaction conditions were optimized according to the understanding of water’s role. Finally, the classic Pfitzinger reaction procedure was modified to yield the expected 2-substituted 7-fluoroquinoline-4-carboxylic acids.