Fine Chemical Industry Research Articles

Tendencies of research and development in resources chemicals and materials — Summarization of a Youth's topic forum

The 2022′s Youth Forum on Resources Chemicals and Materials was held on November 12–13, 2022, in Shenyang, Liaoning Province. Panel discussions focus on the cutting-edge researches on “Fine chemicals and advanced alloy materials” and “Utilization of fossil and renewable carbon resources”. This perspective summarizes the major directions of scientific research and technical developments aligned in the discussions. Fine chemical industry tends to pursue green and low-carbon products, intelligent product design, and start manufacturing. In recent years, great efforts have been made for transformation of cellulose into advanced electronic as well as life-service bio-materials and to the high-selectivity extraction of bio-base aromatic chemicals from lignin. Concerning high-end alloy materials, regulating deformation mechanism of crystal to construct bimodal microstructure seems highly prospective in harmonizing precipitate hardening effect and plastic deformation capacity. As we know, utilization of fossil carbon resources constitutes the major anthropogenic carbon emissions, and the related innovations thus should be, for possibly a long period, on increasing energy production efficiency and low-carbon cascaded conversion of fossil fuels, especially of coal.

Efficient synthesis of 5-aryl-5H-pyrido[2′,1′:2,3]imidazo[4,5-b]indoles by double C[sbnd]N coupling reactions using HKUST-1 as recyclable heterogeneous catalyst under air

Fluorescent active small compounds containing 5H-pyrido[2′,1:2,3]imidazo[4,5-b]indole core could be successfully synthesized by double CN coupling reaction from 3-iodo-2-(2-bromophenyl)imidazo[1,2-a]pyridine with different amines in high yields under air atmosphere. HKUST-1 was found to be the most suitable heterogeneous catalyst for this transformation. Interestingly, HKUST-1 catalyst (∼12 mol% Cu loading for each reaction) showed highly active, robust, and recyclable properties with the tolerance of broad substrate scope. Remarkably, the mechanism for the CN coupling reaction undergoing Cu1+/ Cu3+ catalytic cycle was proposed from several observed important evidence. Cu2+ sites in the node of HKUST-1 structure could be reduced to Cu1+ which initiated the formation of radical amine species. This method may give potential applications in the pharmaceutical and fine chemical industries.

Highly Efficient Selective Hydrogenation of Cinnamaldehyde to Cinnamyl Alcohol over CoRe/TiO2 Catalyst.

Allylic alcohols typically produced through selective hydrogenation of α,β-unsaturated aldehydes are important intermediates in fine chemical industry, but it is still a challenge to achieve its high selectivity transformation. Herein, we report a series of TiO2-supported CoRe bimetallic catalysts for the selective hydrogenation of cinnamaldehyde (CAL) to cinnamyl alcohol (COL) using formic acid (FA) as a hydrogen donor. The resultant catalyst with the optimized Co/Re ratio of 1:1 can achieve an exceptional COL selectivity of 89% with a CAL conversion of 99% under mild conditions of 140 °C for 4 h, and the catalyst can be reused four times without loss of activity. Meanwhile, the Co1Re1/TiO2/FA system was efficient for the selective hydrogenation of various α,β-unsaturated aldehydes to the corresponding α,β-unsaturated alcohols. The presence of ReOx on the Co1Re1/TiO2 catalyst surface was advantageous to the adsorption of C=O, and the ultrafine Co nanoparticles provided abundant hydrogenation active sites for the selective hydrogenation. Moreover, FA as a hydrogen donor improved the selectivity to α,β-unsaturated alcohols.

Nanostructured Carbon Nitride for Continuous-Flow Trifluoromethylation of (Hetero)arenes.

Efficient catalytic methods for the trifluoromethylation of (hetero)arenes are of particular importance in organic and pharmaceutical manufacturing. However, many existing protocols rely on toxic reagents and expensive or sterically hindered homogeneous catalysts. One promising alternative to conduct this transformation involves the use of carbon nitride, a non-toxic photocatalyst prepared from inexpensive precursors. Nonetheless, there is still little understanding regarding the interplay between physicochemical features of this photocatalyst and the corresponding effects on the reaction rate. In this work, we elucidate the role of carbon nitride nanostructuring on the catalytic performance, understanding the effect of surface area and band gap tuning via metal insertion. Our findings provide new insights into the structure-function relationships of the catalyst, which we exploit to design a continuous-flow process that maximizes catalyst-light interaction, facilitates catalyst reusability, and enables intensified reaction scale-up. This is particularly significant given that photocatalyzed batch protocols often face challenges during industrial exploitation. Finally, we extrapolate the rapid and simplified continuous-flow method to the synthesis of a variety of functionalized heteroaromatics, which have numerous applications in the pharmaceutical and fine chemical industries.

Single-Atom Catalysts for Hydrogen Activation.

Selective hydrogenation is one of the most important reactions in fine chemical industry, and the activation of H2 is the key step for hydrogenation. Catalysts play a critical role in selective hydrogenation, and some single-atom catalysts (SACs) are highly capable of activating H2 in selective hydrogenation by virtue of the maximized atom utilization and the highly uniform active sites. Therefore, more research efforts are needed for the rational design of SACs with superior H2 -activating capabilities. Herein, the research progress on H2 activation in typical hydrogenation systems (such as alkyne hydrogenation, hydroformylation, hydrodechlorination, hydrodeoxygenation, nitroaromatics hydrogenation, and polycyclic aromatics hydrogenation) is reviewed, the mechanismsof SACs for H2 activation are summarized, and the structural regulation strategiesfor SACs are proposed to promote H2 activation and provide schemes for the design of high-selectivity hydrogenation catalysts from the atomic scale. At the end of this review, an outlook on the opportunities and challenges for SACs to be developed for selective hydrogenation is presented.

Dynamics of the role of LacMeta laccase in the complete degradation and detoxification of malachite green.

Laccases highlight for xenobiotic bioremediation, as well as application in the fine chemical, textile, biofuel and food industries. In a previous work, we described the preliminary characterization of laccase LacMeta, a promising enzyme for the bioremediation of dyes, able to decolorization malachite green (MG), trypan blue, methylene blue. Here we demonstrate that LacMeta is indeed suitable for the complete degradation and detoxification of MG dye, not just for its discoloration, since some works show false positives due to the formation of colorless intermediates such as leucomalachite. The optimal pH and temperature parameters of LacMeta were 5.0 and 50°C, respectively (MG as substrate). LacMeta was tolerant of up to 10 mmol L- 1 EDTA (82%) and up to 5% (V/V) acetone (91%) and methanol (71%), while SDS promoted severe inhibition. For ions, a high tolerance to cobalt, zinc, manganese, and calcium (10 mmol L- 1) was also observed (> 90%). Even under high-salinity conditions (1mol L- 1 NaCl), the residual bleaching activity of the dye remained at 61%. Furthermore, the bleaching product of MG did not inhibit the germination of sorghum and tomato seeds and was inert to the vegetative structures of the germinated seedlings. Additionally, this treatment effectively reduced the cytotoxic effect of the dye on microorganisms (Escherichia coli and Azospirillum brasilense), which can be explained by H-NMR spectral analysis results since LacMeta completely degraded the peak signals corresponding to the aromatic rings in the dye, demonstrating extreme efficiency in the bioremediation of the xenobiotic at high concentrations (50mg L- 1).

Efficient hydrogenation of N-heteroarenes into N-heterocycles over MOF-derived CeO2 supported nickel nanoparticles

The selective hydrogenation of N-heteroarenes into N-heterocycles is a highly important organic transformation in fine chemical industry, as N-heterocycles are moieties in a variety of pharmaceutical and bioactive compounds. Here, we report highly efficient mesoporous CeO2 supported Ni catalysts prepared by the incipient wet impregnation and following high-temperature reduction for the selective hydrogenation of N-heteroarenes. The experiments indicated that the synergistic effect between CeO2 and Ni nanoparticles was responsible to the superior catalytic performance. Various kinds of N-heterocycles were obtained at 120 °C with yields of 86 ∼ >99%, demonstrating the versatility of the developed method. This work is valuable for guiding the design and manipulation of low metal loading, cost-effective and robust hydrogenation catalysts.

Electron-rich platinum single sites anchored on sulfur-doped covalent organic frameworks for boosting anti-Markovnikov hydrosilylation of alkenes

Selective catalytic hydrosilylation of alkenes for the synthesis of organosilicon products is very important in the fine chemical industry. Nevertheless, conventional Pt-based homogeneous catalysts are hindered by their low reaction selectivity, catalyst residues, and Pt leaching. In this study, a series of covalent organic frameworks (COFs)-anchored single-site Pt catalysts for achieving high-performance alkene hydrosilylation were prepared, and comprehensive characterizations confirmed that the actual coordination environment of Pt active sites is NS-Pt-Cl2. The resulting Pt(0.75%)@BTT-BPh-COF catalyst exhibited superior activity for the anti-Markovnikov hydrosilylation of alkenes with an excellent selectivity (>99%) under solvent-free conditions. Experimental and theoretical analysis revealed that the excellent catalytic performance is attributed to the effective charge transfer and strong coordination effect between Pt and S, N-co-doped COFs, which is conducive to the generation of electron-rich and highly active Pt single sites. High catalyst stability was maintained during recycling experiments due to the strong anchoring effect of the COFs support on atomically dispersed Pt single sites as well as the pore confinement effect. This study not only describes the precise design for the state-of-the-art catalysts with accurate active sites but also affords in-depth insights into alkene hydrosilylation.

A Scalable Balz-Schiemann Reaction Protocol in a Continuous Flow Reactor.

The demand for aromatic fluorides is steadily increasing in the pharmaceutical and fine chemical industries. The Balz-Schiemann reaction is a straightforward strategy for preparing aryl fluorides from aryl amines, via the preparation and conversion of diazonium tetrafluoroborate intermediates. However, significant safety risks exist in handling the aryl diazonium salts when scaling up. In order to minimize the hazard, we present a continuous flow protocol that has been successfully performed at a kilogram scale that eliminates the isolation of aryl diazonium salts while facilitating efficient fluorination. The diazotization process was performed at 10 °C with a residence time of 10 min, followed by a fluorination process at 60 °C with a residence time of 5.4 s with about 70% yield. The reaction time has been dramatically reduced by introducing this multi-step continuous flow system.

Photochemical Synthesis of Pyrazolines from Tetrazoles in Flow

AbstractPyrazolines and their pyrazole congeners are important heterocyclic building blocks with numerous applications in the fine chemical industries. However, traditional routes towards these entities are based on multistep syntheses generating substantial amounts of chemical waste. Here we report an alternative approach using UV-light to convert tetrazoles into pyrazolines via a reagent-free photo-click strategy. This route generates nitrile imine dipoles in situ that are trapped with different dipolarophiles rendering a selection of these heterocyclic targets in high chemical yields. A continuous flow method is ultimately realized that generates multigram quantities of product in a safe and readily scalable manner thus demonstrating the value of this photochemical approach for future exploitations in industry.

Direct Conversion of Cellulose into 5-HMF by Transition-Metal Doped Montmorillonite Catalyst in Water

AbstractCatalysts are very important in the use of cellulose, the main component of biomass, as a raw material for the large-scale production of liquid fuels and chemicals. 5-Hydroxymethylfurfural (HMF) is an extremely important intermediate in the fine chemical industry. HMF can be synthesized by acid-catalyzed dehydration of fructose, glucose, cellulose, or sucrose. The conversion of cellulose to HMF is challenging due to its chemical structure. The objective of the present study was to devise a more facile synthesis method using transition metal-doped montmorillonite catalysts (10Cr-Mnt, 10Cu-Mnt, 10Fe-Mnt, and 10Zn-Mnt) by wet impregnation. Samples were characterized by X-ray powder diffraction, specific surface area, and NH3-TPD analyses. The synthesized catalysts were used for the conversion of cellulose to 5-HMF in an aqueous medium. Among the metals studied, Cr showed the greatest catalytic activity. With the use of this catalyst, efficient conversion of cellulose to 5-HMF was achieved, affording a conversion yield of 93.47% and 5-HMF yield of 9.07% within 6 h at 200°C. The study described here could be useful for the efficient conversion of cellulose into 5-HMF, as well as into other biomass-derived chemicals.

Turning thermostability of Aspergillus terreus (R)-selective transaminase At-ATA by synthetic shuffling

As versatile and green biocatalysts for the asymmetric amination of ketones, the insufficient thermostability of transaminases always limits its broad application in the pharmaceutical and fine chemical industries. Here, synthetic shuffling technology was used to enhance stability of (R)-selective transaminase from Aspergillus terreus. The results showed that 30 out of 5000 mutants had improved thermostability by color-based screening method, among which mutants with residual enzyme activity higher than 50% at 45 °C for 10 min were selected for further analysis. Especially, the half-inactivation temperature (T5010), half-life (t1/2), and melting temperature (Tm) of the best mutant M14 (M280C-H210N-M150C-F115L) were 13.7 °C, 165.8 min, and 13.9 °C higher than that of the wild type (WT), respectively. M14 also exhibited a significant biocatalytic efficiency toward acetophenone and 1-acetylnaphthalene, the yield of which were 265.6% and 117.5% higher than WT, respectively. Based on molecular dynamics simulation, improved catalytic efficiency of M14 could be attributed to its increased hydrogen bonds interaction around the mutation sites. Additionally, the introduction of disulfide bond combined with above mutations has a synergistic effect on the improved protein thermostability.

Determination of Particle Size Distributions of Bulk Samples Using Micro-Computed Tomography and Artificial Intelligence.

The knowledge of product particle size distribution (PSD) in crystallization processes is of high interest for the pharmaceutical and fine chemical industries, as well as in research and development. Not only can the efficiency of crystallization/production processes and product quality be increased but also new equipment can be qualitatively characterized. A large variety of analytical methods for PSDs is available, most of which have underlying assumptions and corresponding errors affecting the measurement of the volume of individual particles. In this work we present a method for the determination of particle volumes in a bulk sample via micro-computed tomography and the application of artificial intelligence. The particle size of bulk samples of sucrose were measured with this method and compared to classical indirect measurement methods. Advantages of the workflow are presented.

Improving the Separation Properties of Polybenzimidazole Membranes by Adding Acetonitrile for Organic Solvent Nanofiltration.

In research on membranes, the addition of co-solvents to the polymer dope solution is a common method for tuning the morphology and separation performance. For organic solvent nanofiltration (OSN) applications, we synthesized polybenzimidazole (PBI) membranes with high separation properties and stability by adding acetonitrile (MeCN) to the dope solution, followed by crosslinking with dibromo-p-xylene. Accordingly, changes in the membrane structure and separation properties were investigated when MeCN was added. PBI/MeCN membranes with a dense and thick active layer and narrow finger-like macrovoids exhibited superior rejection properties in the ethanol solution compared with the pristine PBI membrane. After crosslinking, they displayed superior rejection properties (96.56% rejection of 366-g/mol polypropylene glycol). In addition, the membranes demonstrated stable permeances for various organic solvents, including acetone, methanol, ethanol, toluene, and isopropyl alcohol. Furthermore, to evaluate the feasibility of the modified PBI OSN membranes, ecamsule, a chemical product in the fine chemical industry, was recovered. Correspondingly, the efficient recovery of ecamsule from a toluene/methanol solution using the OSN process with PBI/MeCN membranes demonstrated their applicability in many fine chemical industries.

Continuous hydrogenation of nitriles to primary amines with high selectivity in flow

Hydrogenation of nitriles is considered to be an atom-economic route in the pharmaceutical industry to synthesize amines, crucial building blocks in the fine chemical industry. However, high selectivity of primary amines and high efficiency are difficult to achieve in conventional batch reactors due to that severe back mixing and poor mass transfer performance producing a mixture of secondary, tertiary amines and hydrogenolysis byproducts. In this study, a continuous flow system based on a micro-packed bed is developed for the hydrogenation of nitriles to primary amines and the hydrogenation of benzonitrile (BN) is selected as the model reaction. With the optimal reaction conditions, maximal conversion of BN (100%) and selectivity to benzylamine (99.1%) are obtained. The reaction kinetics is also determined after the internal and external diffusion limitations are eliminated. Moreover, the continuous flow system based on the micro-packed bed exhibited remarkable substrate suitability in other nitrile hydrogenation systems.

A COF template-derived mesoporous CeO2-supported Au nanoparticles catalyst for the oxidative esterification of benzaldehydes and benzyl alcohols.

The direct oxidative esterification of benzaldehydes and benzyl alcohols to high value-added aromatic esters under mild and green reaction conditions is significant in the fine chemical industry. The accurate design of catalysts with high catalytic performance is crucial for this process. Herein, 2,4,6-trimethylpyridine, benzoic anhydride, and terephthalaldehyde were used to prepare a covalent organic framework (COF) material, which was then used as a template to construct a mesoporous CeO2-supported Au nanoparticles catalyst. The obtained Au@CeO2 catalyst was thoroughly characterized, and it possessed a mesoporous structure with a high surface area. Meanwhile, the as-prepared Au@CeO2 exhibited excellent catalytic performance in the oxidative esterification of benzaldehydes and benzyl alcohols with methanol, affording the corresponding aromatic esters under mild and green reaction conditions. Furthermore, the Au@CeO2 catalyst could also be recycled. Therefore, this study provides a green and sustainable pathway for the synthesis of high-value-added esters through a direct oxidative esterification strategy.

Selective adsorption of trace morpholine impurities over N-ethyl morpholine by tetralactam solids.

The separation and especially the removal of morpholine (MOR) impurities from N-ethyl morpholine (NEM) is of great significance in the fine chemical industry. Herein, we offer a novel strategy for the selective adsorption of MOR over NEM by tetralactam solids. The adsorbent realized the purification of NEM by adsorbing traces of MOR impurities, such that the purity can be improved from around 98% to over 99.5%. Single crystal structures indicate that N-H⋯O and N-H⋯N hydrogen bonding interactions are essential in the selective separation.

Effects of phosphorus application on carbohydrate metabolism in cottonseed kernel during the key development period provided a new insight for phosphorus management in cotton production

Cottonseed provides abundant and high-quality raw materials for biodiesel, fine chemical, and other industries due to its rich oil, but phosphorus-deficient farmland and finite phosphate resource hinder its production. Cottonseed development is based on its carbohydrate, and exploring the response of cottonseed carbohydrate metabolism to phosphorus could contribute to optimizing phosphorus management in cotton production and continuously obtaining high-quality cottonseed. Here, the experiment on phosphorus rates [0 (phosphorus deficient), 100 (phosphorus critical), and 200 (phosphorus excess) kg P2O5 ha−1] was conducted using Lu 54 (low-phosphorus sensitive) and Yuzaomian 9110 (low-phosphorus tolerant) in a field containing 16.9 mg kg−1 available phosphorus to assess the effects of phosphorus on cottonseed yield, cottonseed total phosphorus, ash, and oil contents, carbohydrate metabolism related carbohydrate contents, and enzymes activities. The results showed that phosphorus application increased cottonseed yield and oil content by 32.4%−54.2% and 14.8%−20.1% on average, respectively, which could be attributed to the improvements in sucrose transport and hydrolysis in cottonseed kernel during 18–26 days post anthesis induced by higher total phosphorus content (17.1%−26.7%). During the key development period of cottonseed kernel, phosphorus application increased sucrose content (13.0%−19.4%) by increasing the expression of sucrose transporter genes, and promoted sucrose hydrolysis by elevating enzymes activities, especially sucrose synthase (11.2%−19.1%) in cottonseed kernel. Consequently, phosphorus application increased hexose levels in cottonseed kernel and thus provided more substrates for its development, which promoted the formation of cottonseed kernel biomass (6.2%−10.6%), cottonseed and oil yields. Additionally, carbohydrate metabolism in Lu 54 was more sensitive to phosphorus than Yuzaomian 9110 during the key development period, resulting in greater increases in cottonseed kernel biomass, cottonseed yield, and oil content for Lu 54. Notably, the increments generated by unit phosphate fertilizer on the above indicators attenuated markedly with phosphorus application. Based on sucrose content, the key substance, the critical phosphorus concentration in the subtending leaf to cotton boll (LPC) needed by the efficient operation of the key carbohydrate metabolic pathway was 0.38% for Lu 54 versus 0.34% for Yuzaomian 9110. This report first unveiled the key carbohydrate metabolic pathway regulated by phosphorus for cottonseed and oil yield formation and its demand for LPC during the key development period, providing a new insight for diagnosing and regulating phosphorus in cotton production.

Homogenous Iron-Catalysed hydrogenation of polar substrates with precise chemoselectivity

Hydrogenation of different types of unsaturated substrates with a single catalyst has always been a challenge for transition-metal-based catalysts. In this paper, an iron tetraphosphine complex shows high catalytic efficiency for selective hydrogenation of aldehydes, conjugated ketones and nitroarenes in the presence of other easily reduced functional groups like ketone, alkenyl, ester and alkynyl groups. The catalytic efficiency, chemoselectivity and robustness of this Fe/P2C‑PPh22NBn2 catalyst found its merit in the preparation of several important drug intermediates. A diamagnetic trans-iron dihydride complex formed under the reaction conditions was supposed to be an on-cycle catalytically active species. We are looking forward to the application of this method in pharmaceutical and fine chemical industries.

A perspective on automated advanced continuous flow manufacturing units for the upgrading of biobased chemicals toward pharmaceuticals.

Biomass is a renewable, almost infinite reservoir of a large diversity of highly functionalized chemicals. The conversion of biomass toward biobased platform molecules through biorefineries generally still lacks economic viability. Profitability could be enhanced through the development of new market opportunities for these biobased platform chemicals. The fine chemical industry, and more specifically the manufacturing of pharmaceuticals is one of the sectors bearing significant potential for these biobased building blocks to rapidly emerge and make a difference. There are, however, still many challenges to be dealt with before this market can thrive. Continuous flow technology and its integration for the upgrading of biobased platform molecules for the manufacturing of pharmaceuticals is foreseen as a game-changer. This perspective reflects on the main challenges relative to chemical, process, regulatory and supply chain-related burdens still to be addressed. The implementation of integrated continuous flow processes and their automation into modular units will help for tackling with these challenges.Graphical abstract