Industrial Synthesis Research Articles

Identification research of chemical process leakage based on deep learning and correlation-distance graph coding

As a leak identification method in chemical processes, deep learning is limited by inadequate sample labels and highly coupled, nonlinear process variables, therefore difficult to model with a high identification accuracy. To address these problems, a fusion correlation-distance graph (CDG) coding aided deep learning method is proposed. First, the mechanism model is built based on dynamic process data with different leakage labels. Then, the weighted degree and spatial distribution of the dynamic dataset are computed through innovatively designed correlation and distance coding, aided by sliding window fusion into a correlation-distance matrix. Finally, the well-trained long short-term memory (LSTM) is constructed to learn the deep features of the leakage process and identify them. The applications in two industrial cases, CO2 capture and ammonia synthesis, show that CDG-LSTM presents state-of-the-art identification performance with R2 scores of 0.994 and 0.986. 6.6% and 18.4% improvement over LSTM. In addition, the proposed method effectively categorizes the unknown leak samples into known labels with nearby locations, providing a valuable reference for operators to determine the unknown leak locations.

Aqueous extract of Sea buckthorn berries: A greener and ecofriendly medium for synthesis of pyrazolopyranopyrimidines

Sustainable development and environmental consciousness have become increasingly important, leading to a revolution of industrial processes and organic synthesis methods. The use of organic solvents and their associated emissions has emerged as a significant environmental issue. Consequently, there is a growing emphasis on finding substitutes for volatile solvents and halogenated organic solvents in various synthetic processes. This study focuses on a greener and more eco-friendly approach to synthesizing pyrazolopyrimidine derivatives using sea buckthorn aqueous extract as a sustainable medium. Sea buckthorn berries, rich in phenolic compounds, fatty acids, and vitamins A, C, E, along with high organic acid content, are conducive to multicomponent reactions. Pyrazolyl derivatives are of particular interest due to their role as essential components in various biologically active compounds. Overall, this methodology offers a green and environmentally sustainable alternative to current protocols, with positive implications for both sustainability and economic factors. Additionally, Sea buckthorn berry extract proves to be a recyclable medium, with minimal decrease in product yields upon recycling.

Identification of hyperthermophilic D-allulose 3-epimerase from Thermotoga sp. and its application as a high-performance biocatalyst for D-allulose synthesis.

D-Allulose 3-epimerase (DAE) is a vital biocatalyst for the industrial synthesis of D-allulose, an ultra-low calorie rare sugar. However, limited thermostability of DAEs hinders their use at high-temperature production. In this research, hyperthermophilic TI-DAE (Tm = 98.4 ± 0.7 ℃) from Thermotoga sp. was identified via in silico screening. A comparative study of the structure and function of site-directed saturation mutagenesis mutants pinpointed the residue I100 as pivotal in maintaining the high-temperature activity and thermostability of TI-DAE. Employing TI-DAE as a biocatalyst, D-allulose was produced from D-fructose with a conversion rate of 32.5%. Moreover, TI-DAE demonstrated excellent catalytic synergy with glucose isomerase CAGI, enabling the one-step conversion of D-glucose to D-allulose with a conversion rate of 21.6%. This study offers a promising resource for the enzyme engineering of DAEs and a high-performance biocatalyst for industrial D-allulose production.

An Old Material for a New World: Prussian Blue and Its Analogues as Catalysts for Modern Needs

Prussian blue analogues (PBAs) have recently emerged as effective materials in different functional applications, ranging from energy storage to electrochemical water splitting, thence to more “traditional” heterogeneous catalysis. Their versatility is due to their open framework, compositional variety, and fast and efficient internal charge exchange, coupled with a self-healing ability that makes them unique. This review paper presents and discusses the findings of the last decade in the field of the catalytic and photocatalytic application of PBAs in water remediation (via the degradation of organic pollutants and heavy metal removal) and the catalytic oxidation of organics and production or organic intermediates for industrial synthesis. Analysis of the catalytic processes is approached from a critical perspective, highlighting both the achievements of the research community and the limits still affecting this field.

Transaminase-catalysis to produce trans-4-substituted cyclohexane-1-amines including a key intermediate towards cariprazine

Cariprazine—the only single antipsychotic drug in the market which can handle all symptoms of bipolar I disorder—involves trans-4-substituted cyclohexane-1-amine as a key structural element. In this work, production of trans-4-substituted cyclohexane-1-amines was investigated applying transaminases either in diastereotope selective amination starting from the corresponding ketone or in diastereomer selective deamination of their diasteromeric mixtures. Transaminases were identified enabling the conversion of the cis-diastereomer of four selected cis/trans-amines with different 4-substituents to the corresponding ketones. In the continuous-flow experiments aiming the cis diastereomer conversion to ketone, highly diastereopure trans-amine could be produced (de > 99%). The yield of pure trans-isomers exceeding their original amount in the starting mixture could be explained by dynamic isomerization through ketone intermediates. The single transaminase-catalyzed process—exploiting the cis-diastereomer selectivity of the deamination and thermodynamic control favoring the trans-amines due to reversibility of the steps—allows enhancement of the productivity of industrial cariprazine synthesis.

PID Control Assessment Using L-Moment Ratio Diagrams

This paper presents an application of L-moments and respective L-moment ratio diagrams (LMRD) to the task of control performance assessment (CPA). An L-moment ratio diagram is a graphical approach to the visualization of statistical properties for a given time series. Moreover, it enables comparing various data, showing their similarities and homogeneity. Simultaneously, CPA aims at measuring the control loop quality, supporting decision-making about their tuning and maintenance. This paper shows that control system quality can be efficiently visualized using LMRDs. The method was analyzed using simulations and further validated at a real chemical engineering industrial ammonia synthesis plant.

Synthesis of zeolite X from fly ash in an impinging stream reactor and its mechanisms

The conventional hydrothermal method with magnetic stirring for the synthesis of zeolite X from fly ash has some problems, such as low micromixing efficiency, low mass transfer rate, and long synthesis time. In this study, impinging stream reactor is used to improve the mass transfer and micromixing and the mechanism how the nucleation and crystallization of zeolite is accelerated is explored. The results show that premixing in the impinging stream reactor can reduce the stirring and aging time from 4 h to 20 min because the hydroxyl free radicals resulting from the cavitation effect can accelerate the crystallization of zeolite. After collision, the viscosity of the system is increased from 0.22 Pa·s to 3 Pa·s, which can increase the residence time of cavitation bubbles in the gel solution and effectively inhibit the aggregation of crystal nuclei. As a result, the crystal nuclei in the system are well dispersed. The impinging stream reactor can also accelerate the mass transfer between liquid and solid phases and improve the micromixing of raw materials, so that the polymerization between Si and Al is increased and the nucleation of zeolite X is accelerated. The degree of order of zeolite X samples obtained by premixing in the impinging stream reactor is much higher than that obtained by magnetic stirring. The relative crystallinity after crystallization for 12 h (100 %) is higher than that obtained by magnetic stirring (94.93 %); and the n(Si/Al) is lower than that obtained by magnetic stirring. It is concluded that premixing in the impinging stream reactor can improve the polymerization of aluminosilicate and accelerate the nucleation and crystallization of zeolite X. Under the same conditions, zeolite X synthesized by premixing in the impinging stream reactor has better CO2 adsorption capacity than those synthesized by magnetic stirring and industrial synthesis.

Recent Advance of Single‐Atom Metal@Support Catalysts and Their Applications in Artificial Electrocatalytic N2 Reduction Reaction

AbstractThe electrochemical nitrogen reduction reaction (ENRR) is the fundamental solution to the high pollution and emissions associated with the industrial synthesis of ammonia (NH3). However, nowadays ENRR still faces some great challenges, such as low NH3 yield rates and low Faradaic efficiency (FE), etc. In this context, single‐atom catalysts (SACs) with high catalytic activity and selectivity have emerged as shining stars in ENRR. Adjusting the support of SAC to leverage strong metal‐support interactions can address the activity limitations of the SAC itself and significantly enhance the activity of ENRR. Therefore, the review covers a range of topics including characterization techniques of single atoms, the mechanism of ENRR, in situ techniques in ENRR, synthesis methods of SACs, design principles of SACs in ENRR, and the application of SACs loaded with different supports in ENRR. Finally, the review offers a prospective outlook on the application of SACs in ENRR.

Characterization and Antimicrobial Properties of Zinc Oxide Nanoflakes Prepared Via Green Chemistry Method Using Corn Silk Extract of Zea Mays

AbstractThe pathogen‐based diseases are prime concern for modern society. Some oxide‐based nanomaterials have been found to show promising antimicrobial activities. However, the industrial synthesis of these oxide materials are harmful to environment. Zinc oxide nano‐flakes were prepared using corn silk (Zea mays) extract. The material was characterized by spectral and microscopic techniques. XRD data shows rutile structure and nano‐crystal size of 36.15 nm. SEM indicates morphology consisting of nano size particles with porous structure. EDX confirms presence of Zn and O. UV‐Vis data shows band gap of 3.62 eV. On excitation, PL exhibits a variety of emission bands in visible spectrum. Dielectric properties suggest the dielectric constant has a well‐dispersed real and imaginary portion. The ZnO NFs were subjected to antimicrobial activities (in dark and under white light) against various strains like E. coli, K. pneumonia and S. aureus. The light induced antibacterial activity is slightly higher as compared to that in dark. Best part of this study is that minimum concentration of ZnO can be used in presence of light thereby reducing the toxicity to the environment due to these metal oxides. Based on the observed results, this material could be used as multi‐dimensional functional material in day‐to‐day life.

Structure–reactivity relationships in the ionic-liquid-catalyzed oxidation of cumene: Cation effects

Cumene oxidation is a key step in the industrial synthesis of phenol via cumyl hydroperoxide (CHP) formation. Ionic liquids (ILs) are attractive as green, metal-free alternatives catalysts for this reaction, but few studies have explored their potential. The study of the relationship between the structure and catalytic performance of ILs is crucial for the development of ionic liquids with excellent performance. In this study, we aimed to establish a theoretical protocol to evaluate the catalytic activity of ILs for cumene oxidation, as well as the structure–activity relationship, using density functional theory calculations. The calculations showed that the catalytic activity of the studied ILs decreased as follows: 1-n-butyl-3-methylimidazolium bromide > 1-butyl-1-methylpyrrolidinium bromide > N-n-butylpyridinium bromide > triethylammonium bromide > 1-n-butyl-2-methylpyrrolinium bromide. Moreover, the polarity, solubility, and maximum electrostatic potential of the ILs were linearly correlated with their catalytic activity. The theoretical predictions were verified by experiment. Additionally, DFT calculation and EPR analysis demonstrated that the catalytic activity of ionic liquids originates from the formation of hydrogen-abstracting radicals. Furthermore, using 1-butyl-1-methylpyrrolidinium bromide as a representative catalyst, we optimized the reaction conditions, a cumene conversion of 24.2 % and a CHP selectivity of > 90 % were obtained. Compared with the aqueous NaOH as a stabilizing agent, the reaction time is reduced by 8 h. This study provides new insights for designing efficient, low-cost, and environmentally friendly catalysts for cumene oxidation.

Simulation approach to study kinetic heterogeneity of gadolinium catalytic system in the 1,4-cis-polyisoprene production

Abstract This article presents a novel simulation approach for solving the inverse problem of kinetic heterogeneity in polymerization processes, specifically focusing on the production of polyisoprene using a gadolinium chloride solvate-based catalytic system. The proposed method is based on the assumption that the distribution of active centers (ACs) can be described by model distributions. By utilizing primary physicochemical data, such as the polymerization rate and molecular weight distribution, the simulation approach automatically identifies the kinetic parameters, determining the Frenkel statistical parameter and solving the problem of kinetic heterogeneity. The experimental results revealed the presence of at least three distinct types of ACs, each contributing different proportions to the polymerization process. The simulation approach offers valuable insights into the complexities of catalytic systems and their role in polymerization, paving the way for optimizing reaction conditions and advancing industrial polymer synthesis processes. This study marks a significant step forward in understanding and controlling polymerization reactions, with potential implications for the development of innovative materials and industrial applications.

Developing the E. coli platform for efficient production of UMP-derived chemicals

5-Methyluridine (5-MU) is a prominent intermediate for industrial synthesis of several antiviral-drugs, however, its availability over the past decades has overwhelmingly relied on chemical and enzymatic strategies. Here, we have realized efficient production of 5-MU in E. coli, for the first time, via a designer artificial pathway consisting of a two-enzyme cascade (UMP 5-methylase and phosphatase). More importantly, we have engineered the E. coli cell factory to boost 5-MU production by systematic evaluation of multiple strategies, and as a proof of concept, we have further developed an antibiotic-free fermentation strategy to realize 5-MU production (10.71 g/L) in E. coli MB229 (a ΔthyA strain). Remarkably, we have also established a versatile and robust platform with exploitation of the engineered E. coli for efficient production of diversified UMP-derived chemicals. This study paves the way for future engineering of E. coli as a synthetic biology platform for acceleratively accessing UMP-derived chemical diversities.

Conditional expression of FumA in Aspergillus niger enhances synthesis of L-malic acid.

Currently, the L-malic acid titer achieved through Aspergillus niger fermentation reaches 201 g/L, meeting industrial demands satisfactorily. However, the co-presence of structurally similar fumaric acid and succinic acid in fermentation products suggests a theoretical potential for further improvement in L-malic acid production. In the tricarboxylic acid cycle, fumarate reductase mediates the conversion of succinic acid to fumaric acid. Subsequently, fumarase catalyzes the conversion of fumaric acid to L-malic acid. Notably, both enzymatic reactions are reversible. Our investigation revealed that A. niger contains only one mitochondria-located fumarase FumA. Employing CRISPR-Cas9 technology, we performed a replacement of the fumA promoter with a doxycycline-induced promoter Tet. Under non-inducing condition, the conditional strain exhibited increased levels of fumaric acid and succinic acid. It strongly suggests that FumA mainly promotes the flow of fumaric acid to L-malic acid. Furthermore, a promoter PmfsA that is exclusively activated in a fermentation medium by calcium carbonate was identified through RNA-sequencing screening. Utilizing PmfsA to regulate fumA expression led to a 9.0% increase in L-malic acid titer, an 8.75% increase in yield (glucose to L-malic acid), and an 8.86% enhancement in productivity. This research serves as a significant step toward expediting the industrialization of L-malic acid synthesis via biological fermentation. Additionally, it offers valuable insights for the biosynthesis of other organic acids.IMPORTANCEThis study focuses on enhancing L-malic acid synthesis by modifying the tricarboxylic acid cycle within the mitochondria of Aspergillus niger. We emphasize the significant role of fumarase in converting fumaric acid into L-malic acid, enhancing our understanding of metabolic pathways in A. niger. The precise regulation of fumA is highlighted as a key factor in enhancing L-malic acid production. Furthermore, this research introduces a stringent conditional promoter (PmfsA), exclusively activated by CaCO3. The utilization of PmfsA for fumA expression resulted in heightened L-malic acid titers. The progress in metabolic engineering and bioprocess optimization holds promise for expediting industrial L-malic acid synthesis via biological fermentation. Moreover, it carries implications for the biosynthesis of various other organic acids.

Catalytic Synthesis of Atropoisomers via Non‐Canonical Friedel‐Crafts Reactions

AbstractThe Friedel‐Crafts reaction stands as a powerful synthetic tool for C−H functionalization of aromatic feedstocks, which is conventionally realized through electrophilic alkylation and acylation. The burgeoning interests in axially chiral compounds across diverse fields have spurred extensive exploration of this classic transformation for catalytic atroposelective synthesis. Consequently, the past decade has witnessed the rapid expansion of various non‐canonical Friedel‐Crafts reactions, including electrophilic arylation, alkenylation, halogenation, sulfenylation, and amination of aryl C−H bonds, thereby delving into new chemical spaces. A range of catalytic atroposelective synthetic methods have been devised for these significant arene C−H functionalization. This review provides a comprehensive overview of the cutting‐edge catalytic synthesis of atropoisomers through non‐canonical Friedel‐Crafts reactions, categorized into three parts based on the type of bond formation on the aromatics: C(sp2)−C(sp3) bond formations, C(sp2)−C(sp2) bond formations and C(sp2)−heteroatom bond formations. The richness of electrophiles and the modulation of atroposelectivity by diverse chiral organocatalysts, particularly chiral Brønsted acids, are elucidated. We anticipate that the repertoire of asymmetric Friedel‐Crafts reaction will continue to flourish and to be demonstrated in not only scientific researches but also industrial organic synthesis.

Fluent Integration of Laboratory Data into Biocatalytic Process Simulation Using EnzymeML, DWSIM, and Ontologies

The importance of biocatalysis for ecologically sustainable syntheses in the chemical industry and for applications in everyday life is increasing. To design efficient applications, it is important to know the related enzyme kinetics; however, the measurement is laborious and error-prone. Flow reactors are suitable for rapid reaction parameter screening; here, a novel workflow is proposed including digital image processing (DIP) for the quantification of product concentrations, and the use of structured data acquisition with EnzymeML spreadsheets combined with ontology-based semantic information, leading to rapid and smooth data integration into a simulation tool for kinetics evaluation. One of the major findings is that a flexibly adaptive ontology is essential for FAIR (findability, accessibility, interoperability, reusability) data handling. Further, Python interfaces enable consistent data transfer.

Improved biocatalytic activity of steapsin lipase in supercritical carbon dioxide medium for the synthesis of benzyl butyrate: A commercially important flavour compound

Enzymatic synthesis of flavours, fragrances and food additives compounds have great demand and market value. Benzyl butyrate is commercially important flavour and food additive compound having global use around 100 metric tons/year and widely used in various industrial sectors. However, industrial synthesis of food additive benzyl butyrate is carried out by conventional chemical process which demands for the green biobased sustainable synthetic process. The present work reports steapsin catalyzed synthesis of benzyl butyrate for the first time in supercritical carbon dioxide (Sc-CO2) reaction medium. All reaction variables are optimized in details to obtain competent conversion of 99% in Sc-CO2 reaction medium. The developed steapsin catalyzed synthesis in Sc-CO2 medium offered almost four-fold higher conversion to benzyl butyrate than organic (conventional) solvent. The steapsin biocatalyst was effectually recycled up to five reaction cycles in Sc-CO2 medium. Moreover, the developed steapsin catalyzed protocol in Sc-CO2 medium was extended to synthesize different TEN industrially significant flavour fragrance compounds that offers 99% conversion and three to five-folds higher conversion than organic (conventional) medium. Thus, the present steapsin catalyzed protocol offered improved synthesis of various commercially significant flavour compounds in Sc-CO2. medium.

Selective Construction of C-S/S-N Bonds from N-Substituted O-Thiocarbamates and Indoles under Transition-Metal-Free Conditions.

A method for the selective construction of S-N/C(sp2)-S bonds using N-substituted O-thiocarbamates and indoles as substrates is reported. This protocol features good atom utilization, mild conditions, short reaction time, and wide substrate scope, which can provide a convenient path for the functionalization of indoles. In addition, the reaction could be scaled up on gram scale, showing potential application value in industry synthesis.

Solvents in the industrial synthesis of naphazoline nitrate: implementation of the principles of "Green chemistry" and analysis

The aim: implementation of the principles of green chemistry by regenerating the synthesis solvent 1,2,4-trichlorobenzene and reusing it during the synthesis of the Naphazoline nitrate substance. Study of the influence of the regenerated solvent on the quality of the final product by controlling analytical quality parameters. Development of a method for the quantitative determination and validation of synthesis solvents in a substance. Materials and methods: samples of the substance were synthesized according to the optimized proprietary technology of Farmak JSC. The obtained batches of fresh and regenerated 1,2,4-trichlorobenzene were analyzed according to the monograph of the European Pharmacopoeia on Naphazoline nitrate 0147. Results: the possibility of using regenerated 1,2,4-trichlorobenzene for the synthesis of the substance Naphazoline nitrate has been proven. It is shown that the regenerated solvent does not have a negative effect on the profile of impurities and the polymorphic form of the substance. Analytical quality parameters met the requirements of the internal specification and the requirements of the European Pharmacopoeia monograph. The developed and validated method of quantitative determination of synthesis solvents makes it possible to determine them at the required level. Conclusions: the introduction of regenerated 1,2,4-trichlorobenzene into the synthesis scheme made it possible to significantly reduce the amount of waste per 1 kg of product, which in turn significantly reduced the negative impact on the environment. Analytical quality parameters for regenerated 1,2,4-trichlorobenzene meet the requirements of the internal specification. Industrial series obtained on the regenerated solvent meet the requirements of the monograph of the European Pharmacopoeia. The polymorphic form of the substance batches manufactured on regenerated 1,2,4-trichlorobenzene corresponds to the polymorphic form of the substance batches manufactured on the fresh solvent. The obtained results on the influence of the regenerated solvent on the profile of impurities in the finished substance show the similarity of the profile of the series manufactured on both solvents. According to the requirements of ICH Q3C Impurities: Guideline for residual solvents, a method for quantitative determination of the residual content of 1,2,4-trichlorobenzene in the final product by gas chromatography was developed and validated. The absence of synthesis solvents at the limit of detection is shown

Investigation on dynamic VOC production from industrial, high solids content emulsion polymerizations

Volatile Organic Compounds (VOC) pose a serious threat to human health and the environment. Unfortunately, many processes from fine chemistry involve VOCs as reagents, solvents, products or by-products. International standards and market requirements keep asking for lower VOC content in commercial goods, with the final aim of VOC-free products. Accomplishing such a task is a challenge because VOCs, due to their high vapour pressure, are hard to remove with traditional industrial methods, such as vacuum stripping or absorption. For this reason, it is important to know and understand how VOCs evolve throughout a chemical reaction. In this field, adhesives, which are usually developed exploiting polymerizations, represent an interesting subject, due to the complexity of their industrial synthesis: VOCs appear as reagents (monomers), conversion enhancers (post-polymerization), and by-products (hydrolysis and small chains). In this work, a study on the evolution and content of VOCs of an industrial recipe involving emulsion polymerizations is carried out. The industrial recipe is characterized by high solids content (about 70% w/w) and is mainly composed of 2-ethylhexyl acrylate (up to 50% w/w), anionic and nonionic surfactants. The evolution of the main VOCs found under different working conditions is discussed. The main VOCs found are acetaldehyde, acetone, t-butanol, vinyl acetate, butanol, methyl-methacrylate, butyl acrylate, 2-ethyl-exyl-alcohol, 2-ethyl-exyl-acetate and 2-ethyl-exyl-acrylate.

Enhancing l-Malic Acid Production in Aspergillus niger via Natural Activation of sthA Gene Expression.

The efficient production of l-malic acid using Aspergillus niger requires overcoming challenges in synthesis efficiency and excessive byproduct buildup. This study addresses these hurdles, improving the activity of NADH-dependent malate dehydrogenase (Mdh) in the early stages of the fermentation process. By employing a constitutive promoter to express the Escherichia coli sthA responsible for the transfer of reducing equivalents between NAD(H) and NADP(H) in A. niger, the l-malic acid production was significantly elevated. However, this resulted in conidiation defects of A. niger, limiting industrial viability. To mitigate this, we discovered and utilized the PmfsA promoter, enabling the specific expression of sthA during the fermentation stage. This conditional expression strain showed similar phenotypes to its parent strain while exhibiting exceptional performance in a 5 L fermenter. Notably, it achieved a 65.5% increase in productivity, reduced fermentation cycle by 1.5 days, and lowered succinic acid by 76.2%. This work marks a promising advancement in industrial l-malic acid synthesis via biological fermentation, showcasing the potential of synthetic biology in A. niger for broader applications.