Synthesis Of Fine Chemicals Research Articles

Transforming carbon dioxide and carbon monoxide into value-added products: boracarboxylation and boracarbonylation

This review surveys the current state-of-the-art of catalytic difunctionalization of unsaturated substrates with easily accessible feedstocks CO2/CO and heteroelement boron for the synthesis of fine chemicals and medicinally important molecules.

Sustainable synthesis of fine chemicals using biocatalysis

Sustainable synthesis of fine chemicals using biocatalysis

Green microfluidics in microchemical engineering for carbon neutrality

• Characteristics of green microfluidics and feasibility of applying green microfluidics in microchemical engineering industry for realizing carbon neutrality are elucidated. • Development of green microfluidic systems is interpreted. • Representative low carbon applications of green microfluidics in microchemical engineering are summarized. • Challenges and perspectives for further advancing green microfluidics in microchemical engineering for carbon neutrality are proposed and discussed. The concept of “carbon neutrality” poses a huge challenge for chemical engineering and brings great opportunities for boosting the development of novel technologies to realize carbon offsetting and reduce carbon emissions. Developing high-efficient, low-cost, energy-efficient and eco-friendly microfluidic-based microchemical engineering is of great significance. Such kind of “green microfluidics” can reduce carbon emissions from the source of raw materials and facilitate controllable and intensified microchemical engineering processes, which represents the new power for the transformation and upgrading of chemical engineering industry. Here, a brief review of green microfluidics for achieving carbon neutral microchemical engineering is presented, with specific discussions about the characteristics and feasibility of applying green microfluidics in realizing carbon neutrality. Development of green microfluidic systems are categorized and reviewed, including the construction of microfluidic devices by bio-based substrate materials and by low carbon fabrication methods, and the use of more biocompatible and non-destructive fluidic systems such as aqueous two-phase systems (ATPSs). Moreover, low carbon applications benefit from green microfluidics are summarized, ranging from separation and purification of biomolecules, high-throughput screening of chemicals and drugs, rapid and cost-effective detections, to synthesis of fine chemicals and novel materials. Finally, challenges and perspectives for further advancing green microfluidics in microchemical engineering for carbon neutrality are proposed and discussed.

Ultrafine Ru nanoparticles integrated on ordered mesoporous carbon for solvent-free hydrogenation of nitroarenes.

The hydrogenation of nitroarenes to aromatic amines with H2 under solvent-free conditions in place of organic solvents is a crucial process for the synthesis of fine chemicals. However, the catalysts that have been identified so far are relatively inactive with primary nitroarenes under solvent-free conditions. Herein, ordered mesoporous carbon (OMC)-supported highly dispersed Ru nanoparticles (Ru NPs) were easily prepared by using a coordination-assisted solvent evaporation induced co-assembly method, where 8-hydroxyquinoline exerts a significant influence on the mesostructure ordering and specific surface area of the Ru/OMC composites. The ultrasmall-sized Ru NPs (∼2.0 nm) supported on ordered mesoporous carbon were then applied in the hydrogenation of nitroarenes, exhibiting high activity and selectivity for numerous structurally diverse nitroarenes under solvent-free conditions. Compared with Ru/OMC-imp and Ru/AC-imp, Ru/OMC-800 exhibited a much higher activity and selectivity for hydrogenation of nitroarenes, suggesting its overwhelmingly better performance than OMC or AC supporting noble NPs by simple impregnation method. The strong metal-support interaction is capable of stabilizing the Ru NPs and achieving good recyclability as well as high selectivity.

Continuous stirred tank reactors in fine chemical synthesis for efficient mixing, solids-handling, and rapid scale-up

CSTRs and series: what are the typical applications, strengths and limitations in continuous process chemistry

Base metal iron catalyzed sustainable oxidation of vanillyl alcohol to vanillic acid in deep eutectic solvents and implementation of vanillic acid for fine-chemical synthesis

In the modern era, sustainable development for the production of fine chemicals from abundant biomass by utilizing various chemical transformations has become a strong trend of research in the scientific community.

Iodine‐modified Pt nanoparticles accelerate the hydrogenative ring‐opening of furfurals to linear alcohols

AbstractThe hydrogenative ring‐opening of furfurals (furfural and 5‐methylfurfural) to linear diols (1,4‐pentanediol and 2,5‐hexanediol) is of great significance for bioderived fine chemical synthesis. Unfortunately, the catalytic activity and selectivity are unsatisfactory because of the interference of various side reactions, such as overhydrogenation to tetrahydrofurans. Herein, the preparation of an iodine (I) modified Pt‐based catalyst with abundant Pt‐I pairs is reported for the first time and shows high catalytic efficiency for linear diol synthesis with a yield of 80%–90% via the hydrogenative ring‐opening route, whereas bare Pt counterpart only shows tetrahydrofuran synthesis via the overhydrogenation route. The catalytic reaction mechanism shows the in‐situ hydrogen spillover‐promoted H−‐Pt‐I‐H+ pairs not only supply hydrogenation sites for the C=O hydrogenation step but also provide Brønsted acidic sites for the ring‐opening step. This work presents a feasible and convenient strategy for bifunctional catalysis with powerful linear diol synthesis over iodine‐modified noble metals.

Photosensitized biohybrid for terminal oxygenation of n-alkane to α, ω-dicarboxylic acids

To date, oxyfunctionalization of saturated hydrocarbons in a selective fashion is a prime challenge in industry. Currently, Inorganic-biohybrid catalysts have shown tremendous potential for sustainable conversion of fine chemicals by integrating light harvesting potential of inorganic materials with metabolic activity of microbes. Herein, we have developed a biohybrid system combining a highly efficient light-harvesting inorganic material MoS2-CNT-Eosin-Y and yeast Candida tropicalis (C.tropicalis) for efficient preparation of α, ω- dicarboxylic acid (α, ω-DCA) using saturated n-alkanes. The yeast C.tropicalis harvests photo generated electrons from the illuminated MoS2-CNT-Eosin-Y and uses them for the activation of the P450 catalytic cycle. This process enables the efficient regeneration of nicotinamide cofactors (NADH/NAD+) facilitating production of α, ω-DCA. Under irradiation condition the biohybrid catalyst shows 4.01 times higher dodecanedioic acid production compared to that of native yeast strain. Analysis of NADH/NAD+ ratio and alcohol dehydrogenases (ADH) activity clearly indicates that light illumination on MoS2-CNT-Eosin-Y/C.tropicalis promotes regeneration of cofactor during cellular metabolism of C. tropicalis thereby improving the activity of ADH enzyme resulting higher production of α, ω-DCA. The present work opens up a new avenue for the sustainable synthesis of fine chemicals through tailoring of complex biohybrid pathways.

High Nitrile Yields of Aerobic Ammoxidation of Alcohols Achieved by Generating •O2– and Br• Radicals over Iron-Modified TiO2 Photocatalysts

Catalytic ammoxidation of alcohols into nitriles is an essential reaction in organic synthesis. While highly desirable, conducting the synthesis at room temperature is challenging, using NH3 as the nitrogen source, O2 as the oxidant, and a catalyst without noble metals. Herein, we report robust photocatalysts consisting of Fe(III)-modified titanium dioxide (Fe/TiO2) for ammoxidation reactions at room temperature utilizing oxygen at atmospheric pressure, NH3 as the nitrogen source, and NH4Br as an additive. To the best of our knowledge, this is the first example of catalytic ammoxidation of alcohols over a photocatalyst using such cheap and benign materials. Various (hetero) aromatic nitriles were synthesized at high yields, and aliphatic alcohols could also be transformed into corresponding nitriles at considerable yields. The modification of TiO2 with Fe(III) facilitates the formation of active •O2- radicals and increases the adsorption of NH3 and amino intermediates on the catalyst, accelerating the ammoxidation to yield nitriles. The additive NH4Br impressively improves the catalytic efficiency via the formation of bromine radicals (Br•) from Br-, which works synergistically with •O2- to capture H• from Cα-H, which is present in benzyl alcohol and the intermediate aldimine (RCH═NH), to generate the active carbon-centered radicals. Further, the generation of Br• from the Br- additive consumes the photogenerated holes and OH• radicals to prevent over-oxidation, significantly improving the selectivity toward nitriles. This amalgamation of function and synergy of the Fe(III)-doped TiO2 and NH4Br reveals new opportunities for developing semiconductor-based photocatalytic systems for fine chemical synthesis.

Engineering Single Atom Catalysts for Flow Production: From Catalyst Design to Reactor Understandings

ConspectusIn heterogeneous catalysis, the long-standing challenge is to achieve extremely high activity and chemoselectivity in liquid-phase organic transformations comparable to that of homogeneous or enzymatic processes. Single-atom catalysts (SACs) with atomically precise coordination are developed with the objectives to mimic the homogeneous pathways but face stability issues due to metal leaching or clustering. Additionally, the practical application of SACs in chemical production is hampered by the lack of standard preparation protocols and low conversion using laboratory batch reactors.This Account focuses on our recent studies in both catalyst design and reactor-level engineering for the flow synthesis of fine chemicals via SACs. At the catalyst and reaction level, we will discuss the intrinsic mechanism that controls reactivity and chemoselectivity in the SAC-catalyzed process and highlight examples where SACs outperform other catalytic approaches. Specifically, we reported the SAC-mediated preparation and late-stage functionalization of pharmaceutical drugs, including lonidamine, Tamiflu, cavosonstat, indomethacin, and many others by chemoselective transformations in a sequential or multicomponent manner. The ability of ultrahigh loading SACs in providing a multisite pathway for organic transformations involving two or more reactants is highlighted and contrasted with the single-site pathway in conventional SACs. Molecular-level understanding on the dynamic catalytic cycle obtained using operando X-ray absorption spectroscopies provides guidance for the design of more effective and leach resistant SACs. This also calls for the transformation of laboratory powder-based catalysts into industrially viable monolithic catalysts via formulation to further enhance the leach resistance. At the reactor level, we will highlight the importance of continuous-flow techniques in maximizing productivity and simplifying process transfer from laboratory to commercial production. Particularly, we discuss the use of fuel cell-type flow stacks for quantitative production of fine chemicals, including the synthesis of multifunctional anilines at a 5.8 g h–1 productivity using a Pt SAC module (3.2 mg Pt). Insight into multiscale reactor processes, for instance, the fluid diffusion kinetics, heat transfer, and influence of porosity and the gas–liquid–solid interface are provided by computational fluidic dynamics calculations as well as experimental techniques. In many cases, catalytic processes are more limited by mass diffusion than the intrinsic activity of the catalyst, calling for process optimization and engineering at the reactor level to enhance the productivity. Finally, we also identify technical barriers that need to be overcome in SAC research and offer our perspective on standardized and scalable protocols for mass production, the production cost analysis of typical SACs, high-throughput screening platforms, and novel flow reactor designs involving photochemical and electrochemical reactions for up-scaling chemical production by SACs.

Three-Dimensional Silver-Containing Polyoxotungstate Frameworks for Photocatalytic Aerobic Oxidation of Benzyl Alcohol.

Photocatalytic organic transformation derived by functionalized polyoxometalate (POM)-based metal-organic frameworks provides a feasible route for fine chemical synthesis. Herein, three kinds of photoactive three-dimensional silver-containing polyoxotungstate frameworks are synthesized with the formulas [Ag3L2(OH)][Na(H2O)0.5][PW12O40]·H2O (1), [Ag4L3][SiW12O40] (2), and [Ag(H2O)][Ag4L3][BW12O40]·9H2O (3) (L = 1,4-di(4H-1,2,4-triazol-4-yl)benzene). In compounds 1-3, the cationic Ag-triazole clusters with diverse nuclei serve as nodes to assemble with rigid bridging ligands (L) and polyoxoanions to extend into stable three-dimensional frameworks, in which Keggin-type anions act as guests or pendants. When using them as heterogeneous photocatalysts, compounds 1-3 show high catalytic activity and selectivity for the photocatalytic aerobic oxidation of benzyl alcohol to benzoic acid under 10 W 365 nm light irradiation. Among them, compound 1 exhibits the highest performance with ca. 99% benzyl alcohol conversion and 99% selectivity of benzoic acid in 9 h. Compounds 2 and 3 show ca. 79 and 88% conversions of benzyl alcohol, respectively, which are higher than those of the individual Keggin-type precursors. Moreover, mechanism investigation suggests that the synergistic cooperation occurring between cationic Ag-triazole clusters and Keggin-type polyoxoanions modulates the energy band structures of compounds 1-3, resulting in the efficient separation of photogenerated carriers and accelerating the aerobic oxidation of benzyl alcohol. This work provides some important guidance for the design and development of efficient POM-based photocatalysts for practical organic transformation.

Beyond traditional synthesis of zeolites: The impact of germanosilicate chemistry in the search for new materials

Zeolites are one of the key materials in the chemical industry with their applications ranging from water purification to gas separation or oil refining. In the recent years, the research of zeolites focuses more and more on specialised applications including fine chemical synthesis or separation of small organic compounds, which increase the demand for new types of zeolites with unique structural and chemical properties. Introduction of tailored organic structure-directing agents and especially the introduction of germanium stimulated the discovery of new zeolite frameworks and particularly led to a discovery of numerous new extra-large pore zeolites with attractive properties for selective catalysis. However, the germanosilicate chemistry also opened up an unparalleled opportunity for tailoring even more new zeolites and zeolite-derived materials by controlled post-synthetic transformation of the germanosilicates into layered zeolites or to new zeolite frameworks by solid-, liquid- or vapour-phase transformations such as the Assembly-Disassembly-Organisation-Reassembly process. The following research provided new strategies for preparation of porous materials with characteristics and properties tailored on-demand.

Interfacial engineering of CdS for efficient coupling photoredox

Ternary composites of reduced graphene oxide (GR)-CdS-Pd have been successfully synthesized via solvothermal and photodeposition methods for photocatalytic selective conversion of benzyl alcohol (BA) coupled with hydrogen (H2) production, which exhibit significantly improved photoactivity and selectivity than bare CdS. Mechanistic studies unveil that the cooperative effect of the close interface contact and matched energy level alignment between electrical conducting GR nanosheets (NSs) and CdS nanoparticles (NPs) in GR-CdS-Pd composite not only benefits the separation and transfer of photogenerated carriers but also improves the photocorrosion resistance of CdS. The photodeposited Pd NPs further promote the photogenerated charge separation and accelerate the formation of intermediate products (α-hydroxybenzyl radicals), thereby contributing to enhanced conversion of BA. This work would facilitate the rational design of GR as cocatalyst to construct an efficient and stable CdS-based composite photocatalyst for cooperative coupling of fine chemical synthesis and H2 evolution.

The De Novo Synthesis of 2-Phenylethanol from Glucose by the Synthetic Microbial Consortium Composed of Engineered Escherichia coli and Meyerozyma guilliermondii.

Synthetic microbial consortia show promising applications for fine chemical production, especially with long metabolic pathways. In this study, a synthetic microbial consortium consisting of Escherichia coli YLC20 and Meyerozyma guilliermondii MG57 was successfully constructed, which could achieve efficient de novo 2-phenylethanol (2-PE) production from glucose. A tyrosine-deficient E.coli YLC20 overexpressing genes of aroF and pheA was first constructed, which could accumulate 29.5 g/L of l-phenylalanine (l-Phe) within 96 h from glucose accompanied by the coproduction of acetate and α-ketoglutarate (α-KG). Furthermore, the engineered M.guilliermondii MG57 was constructed through the stepwise metabolic engineering strategy, which could facilitate the 2-PE synthesis from l-Phe. Moreover, the cosubstrate and material intervention strategies were applied to improve the stability of the microbial consortium and 2-PE production. Finally, the synthetic microbial consortium could de novo synthesize 3.77 g/L of 2-PE from 80 g/L of glucose, providing a reference for the de novo synthesis of fine chemicals with long metabolic pathways.

Metal-free radical difunctionalization of ethylene

<h2>Summary</h2> Owing to its simplicity, ethylene, as the most abundant organic feedstock, only finds limited applications in fine chemical synthesis, resulting in molecules of modest complexity. Ethylene difunctionalization allows for the synthesis of much more complex chemicals, but it is rare and almost always relies on transition-metal catalysis. Herein, we report an unprecedented metal-free radical difunctionalization of ethylene through a functional group migration strategy. The use of sulfone-based bifunctional reagents enables straightforward access to a wide range of diheteroarylated compounds under mild conditions in a highly selective manner. The precise modulation of radical polarity and kinetic preference arising from intramolecular functional group migration guarantee the success of the cascade three-bond forming process in a controllable manner.

Integrated nickel/polymer dual catalytic system for visible-light-driven sulfonamidation between aryl halides and aryl sulfonamides

By merging transition metal and heterogeneous photocatalyst, a metal-photoredox system has attracted more attention for cross-coupling of various dual photoredox catalysis. However, there is a grand challenge for the attenuated nucleophilicity of sulfonamides relative to alkyl amines. Herein, an integrated dual catalytic system of porous carbon nitride nanosheet with nitrogen vacancies (N V -P-C 3 N 4 ) as a conjugated polymer semiconductor host in combination with transition-metal nickel (Ni) was constructed by a defect and morphology regulation strategy toward visible-light-driven sulfonamidation between aryl halides and aryl sulfonamides. The excellent nickel/photoredox-catalyzed C–N coupling reaction performance is ascribed to the large specific surface area, abundant active sites, long carrier lifetime, and efficient transfer and separation of photoexcited electrons and holes. This work highlights the opportunity to cooperate with heterogeneous catalysts and active metal sites for challenging cross-coupling reactions. • Dual catalytic system of photoredox and transition metal • Carbon nitride with defect and morphology characteristics • C–N cross-coupling • Heterogeneous catalysts are used for sulfonamidation reactions For the fine chemical and pharmaceutical synthesis communities, it is crucial to determine the formation of anilines through C–N bond transformation approach. Considerable progress has been reported on dual catalytic systems of homogeneous photocatalysts combined with transition metals. However, the progress of heterogeneous catalysts for dual catalysis has not been satisfactory. Carbon nitride (C 3 N 4 ) is a class of metal-free conjugated polymer semiconductor with great potential for photoredox/Ni dual catalytic cross-couplings due to its thermal and chemical stability, facile fabrication, and cheapness. Herein, porous carbon nitride nanosheets with nitrogen vacancies (N V -P-C 3 N 4 ) were fabricated by a defect and morphology regulation strategy for visible-light-driven sulfonamidation between aryl halides and aryl sulfonamides. This work highlights the opportunity to cooperate with heterogeneous catalysts and active metal sites for challenging cross-coupling reactions. An integrated dual catalytic system of N V -P-C 3 N 4 in combination with transition-metal Ni was constructed toward visible-light-driven sulfonamidation between aryl halides and aryl sulfonamides. This work not only realizes the sulfonamidation reaction in a heterogeneous catalytic system for the first time but also demonstrates that defect engineering and morphology strategies are effective for enhancing photoredox dual catalytic performance.

Designing Enzymatic Redox Mediators: Quantifying the Impact of Molecular Structure on Biocatalytic Activity

Enzymatic bioelectrocatalysis involves the application of enzymes to facilitate the conversion of chemical to electrical energy. This approach has been widely applied in the fields of biosensing, biofuel cells, and to a lesser degree the synthesis of fine chemicals. While direct electrochemical communication between the enzymes and electrodes is generally preferable, it is often the case that efficient electron transfer rates can only be achieved when redox mediators are employed to shuttle electrons reversibly from the redox site of the enzyme to the electrode interface. Unfortunately, there still exist many oxidoreductases for which no effective exogenous mediator is known. This may be due to insufficient understanding of the role that molecular structure of the mediator plays in determining its ability to facilitate electron transfer to a given enzyme. Consequently, selection and/or design of novel redox mediators remains a challenge that is often accomplished using a “guess and check” approach to maximize electron transfer rates. Developing a rapid, and convenient method of predicting the role played by other structural and chemical features beyond redox potential of a mediator is an important goal in advancing mediated bioelectrocatalysis. This talk will describe our recent efforts in identifying structure - function relationships of redox mediators that control efficient electron transfer rates. I will highlight results from stopped-flow spectrophotometry experiments which review the nature of electron transfer events between quinone redox couples in altering bioelectrocatalytic activity.

Highly Chemoselective Reduction of Amides to Amines over a Ruthenium‐Molybdenum Bimetallic Catalyst

AbstractThe chemoselective reduction of amides is important in the synthesis of fine chemicals and inter‐mediates. However, the highly stable amide bond due to the orbital overlap between the nitrogen lone pair and the antibonding orbital of the carbonyl group poses a significant limitation in developing suitable heterogeneous catalysts. In this work, we have developed a highly efficient and robust Ru‐(0.2)Mo/TiO2 catalyst for the chemoselective reduction of primary amides. As a consequence, the catalyst afforded 83.1 % conversion with 80 % selectivity of the primary amine after reaction for 12 h for the HDO of cyclohexanecarboxamide at 160 °C. Moreover, the catalyst also presented excellent reusability and substrate diversity. The characterizations of the catalyst revealed that Ru promoted the reduction of Mo6+ to Mo5+ and Mo0, and the resultant low‐coordinated Mo5+ is responsible for the selective activation of the C=O bond of the amide, while RuMo alloy promoted the activation of hydrogen.

Accelerated parametrization of catalyst performance in organic electrosynthesis

The increasing availability of renewable electrical energy from wind and solar power is becoming an enabler for the next phase in the global energy transition, namely the coupling of different energy sectors. Besides electrochemical energy conversion for daily and seasonal energy storage, the synthesis of organic fine chemicals or commodities by direct utilization of electricity has enormous potential to contribute to the reduction of greenhouse gas emissions. Electrical energy has already proven to be a perfect replacement for reducing and oxidizing chemical reagents in various reactions, sometimes even succeeding with superb selectivity or even unique molecular interconnectivity. Non-aqueous electrochemical processes in organic media have received much attention over the last decades as a methodology to achieve high electrode potentials and stability of generated active species, inaccessible in an aqueous medium. Because of the exceptional flexibility of the approach and the many influential parameters, however, the discovery and development of novel electrochemical processes commonly comprise extensive experimentation based on batch cell preparation accompanied by post-mortem analysis. The state-of-the-art approaches are cumbersome and time-consuming and often lack the information depth that could be obtained with direct analysis of intermediates and products. This perspective aims to overview current advances in the development of intensive methods for organic electrosynthetic catalyst search protocols and optimization. Novel high-throughput experimentation strategies for fast probing of large numbers of materials and solution compositions, combined with time-resolved product analysis and automated data analysis as well as artificial intelligence, will in the future accelerate the implementation of renewable energy in chemical industry processes.

The Control of the Coordination Chemistry for the Genesis of Heterogeneous Catalytically Active Sites in Oxidation Reactions**

AbstractThis Review provides a summary of the use and the role of coordination complexes as precursors for the generation of heterogeneous catalysts for oxidation reactions of interest for fine chemical synthesis. Specific attention is paid to the comprehension of phenomena explaining the formation of active sites in heterogeneous catalysts. Different families of coordination precursors are considered. For each example, a brief critical description of the synthesis, characterization, and catalytic performance is reported. Special attention is paid to the chemical environment of the first coordination sphere of the active metal centre. The catalysts obtained by heterogenization, grafting, or anchoring of homogeneous catalysts can therefore exhibit enhanced catalytic performance by merging advantages of both homogeneous and heterogeneous systems. The deposition of coordination complexes over a preformed support is indeed a conceptually versatile strategy to design novel catalysts with tuned and controlled properties.