Manufacture Of Fine Chemicals Research Articles

Roles of the N-terminal motif in improving the activity and soluble expression of phenylalanine ammonia lyases in Escherichia coli

Phenylalanine ammonia-lyase (PAL) has various applications in fine chemical manufacturing and the pharmaceutical industry. In particular, PAL derived from Anabaena variabilis (AvPAL) is used as a therapeutic agent to the treat phenylketonuria in clinical settings. In this study, we aligned the amino acid sequences of AvPAL and PAL derived from Nostoc punctiforme (NpPAL) to obtain several mutants with enhanced activity, expression yield, and thermal stability via amino acid substitution and saturation mutagenesis at the N-terminal position. Enzyme kinetic experiments revealed that the kcat values of NpPAL-N2K, NpPAL-I3T, and NpPAL-T4L mutants were increased to 3.2-, 2.8-, and 3.3-fold that of the wild-type, respectively. Saturation mutagenesis of the fourth amino acid in AvPAL revealed that the kcat values of AvPAL-L4N, AvPAL-L4P, AvPAL-L4Q and AvPAL-L4S increased to 4.0-, 3.7-, 3.6-, and 3.2-fold, respectively. Additionally, the soluble protein yield of AvPAL-L4K increased to approximately 14 mg/L, which is approximately 3.5-fold that of AvPAL. Molecular dynamics studies further revealed that maintaining the attacking state of the reaction and N-terminal structure increased the rate of catalytic reaction and improved the solubility of proteins. These findings provide new insights for the rational design of PAL in the future.

Selective electrooxidation of 5-hydroxymethylfurfural at low working potentials promoted by 3D hierarchical Cu(OH)2@Ni3Co1-layered double hydroxide architecture with oxygen vacancies.

Selective electrooxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) is of great significance in the manufacture of fine chemicals, liquid fuels, pharmaceuticals, plastics, etc., but still suffers from the high potential input, resulting in high electricity consumption. Developing active, low-cost and stable electrocatalysts is crucial for this electrochemical reaction at low working potentials. Herein, a three-dimensional (3D) hierarchical Cu(OH)2@Ni3Co1-layered double hydroxide architecture with abundant oxygen vacancies (Vo) was synthesized by facile electrodeposition of Ni3Co1-LDH nanosheets on copper foam (CF) supported-Cu(OH)2 nanorods (CF/Cu(OH)2@Ni3Co1-LDH) for the selective electrooxidation of HMF to FDCA. The 3D hierarchical architecture of the Cu(OH)2 nanorod core loaded with Ni3Co1-LDH nanosheet shell facilitates the rapid transfer of charges and exposes more active sites. The synergistic effect of the core-shell nanoarray structure, atomic level dispersion of Ni and Co on LDH laminates, and rich Vo gives 98.12% conversion of HMF, 98.64% yield and 91.71% selectivity for FDCA at a low working potential of 1.0 V vs. RHE. In addition, CF/Cu(OH)2@Ni3Co1-LDH exhibits superior stability by maintaining 93.26% conversion of HMF, 93.65% yield and 91.57% selectivity of FDCA after eight successive cycles, showing the immense potential of utilizing electrochemical conversion for biomass.

Direct Synthesis of N-formamides by Integrating Reductive Amination of Ketones and Aldehydes with CO2 Fixation in a Metal-Organic Framework.

Formamides are important feedstocks for the manufacture of many fine chemicals. State-of-the-art synthesis of formamides relies on the use of an excess amount of reagents, giving copious waste and thus poor atom-economy. Here, we report the first example of direct synthesis of N-formamides by coupling two challenging reactions, namely reductive amination of carbonyl compounds, particularly biomass-derived aldehydes and ketones, and fixation of CO2 in the presence of H2 over a metal-organic framework supported ruthenium catalyst, Ru/MFM-300(Cr). Highly selective production of N-formamides has been observed for a wide range of carbonyl compounds. Synchrotron X-ray powder diffraction reveals the presence of strong host-guest binding interactions via hydrogen bonding and parallel-displaced π⋅⋅⋅π interactions between the catalyst and adsorbed substrates facilitating the activation of substrates and promoting selectivity to formamides. The use of multifunctional porous catalysts to integrate CO2 utilisation in the synthesis of formamide products will have a significant impact in the sustainable synthesis of feedstock chemicals.

Geminal-atom catalysis for cross-coupling.

Single-atom catalysts (SACs) have well-defined active sites, making them of potential interest for organic synthesis1-4. However, the architecture of these mononuclear metal species stabilized on solid supports may not be optimal for catalysing complex molecular transformations owing to restricted spatial environment and electronic quantum states5,6. Here we report a class of heterogeneous geminal-atom catalysts (GACs), which pair single-atom sites in specific coordination and spatial proximity. Regularly separated nitrogen anchoring groups with delocalized π-bonding nature in a polymeric carbon nitride (PCN) host7 permit the coordination of Cu geminal sites with a ground-state separation of about 4 Å at high metal density8. The adaptable coordination of individual Cu sites in GACs enables a cooperative bridge-coupling pathway through dynamic Cu-Cu bonding for diverse C-X (X = C, N, O, S) cross-couplings with a low activation barrier. In situ characterization and quantum-theoretical studies show that such a dynamic process for cross-coupling is triggered by the adsorption of two different reactants at geminal metal sites, rendering homo-coupling unfeasible. These intrinsic advantages of GACs enable the assembly of heterocycles with several coordination sites, sterically congested scaffolds and pharmaceuticals with highly specific and stable activity. Scale-up experiments and translation to continuous flow suggest broad applicability for the manufacturing of fine chemicals.

Facile synthesis of hierarchical NaX zeolite from natural kaolinite for efficient Knoevenagel condensation

Zeolite catalysts have found extensive applications in the synthesis of various fine chemicals. However, the micropores of zeolites impose diffusion limitations on bulky molecules, greatly reducing the catalytic efficiency. Herein, we explore an economic and environmentally friendly method for synthesizing hierarchical NaX zeolite that exhibits improved catalytic performance in the Knoevenagel condensation reaction for producing the useful fine chemical 2-cyano-3-phenylacrylate. The synthesis was achieved via a low-temperature activation of kaolinite and subsequent in-situ transformation strategy without any template or seed. Systematic characterizations reveal that the synthesized NaX zeolite has both inter-crystalline and intra-crystalline mesopores, smaller crystal size, and larger external specific surface area compared to commercial NaX zeolite. Detailed mechanism investigations show that the inter-crystalline mesopores are generated by stacking smaller crystals formed from in-situ crystallization of the depolymerized kaolinite, and the intra-crystalline mesopores are inherited from the pores in the depolymerized kaolinite. This synthesis strategy provides an energy-saving and effective way to construct hierarchical zeolites, which may gain wide applications in fine chemical manufacturing.

Robotic Modules for the Programmable Chemputation of Molecules and Materials.

Before leveraging big data methods like machine learning and artificial intelligence (AI) in chemistry, there is an imperative need for an affordable, universal digitization standard. This mirrors the foundational requisites of the digital revolution, which demanded standard architectures with precise specifications. Recently, we have developed automated platforms tailored for chemical AI-driven exploration, including the synthesis of molecules, materials, nanomaterials, and formulations. Our focus has been on designing and constructing affordable standard hardware and software modules that serve as a blueprint for chemistry digitization across varied fields. Our platforms can be categorized into four types based on their applications: (i) discovery systems for the exploration of chemical space and novel reactivity, (ii) systems for the synthesis and manufacture of fine chemicals, (iii) platforms for formulation discovery and exploration, and (iv) systems for materials discovery and synthesis. We also highlight the convergent evolution of these platforms through shared hardware, firmware, and software alongside the creation of a unique programming language for chemical and material systems. This programming approach is essential for reliable synthesis, designing experiments, discovery, optimization, and establishing new collaboration standards. Furthermore, it is crucial for verifying literature findings, enhancing experimental outcome reliability, and fostering collaboration and sharing of unsuccessful experiments across different research labs.

C-S cleavage of dibenzothiophenes with or without steric hindrance by the interface between PtSx and ZnO

Desulfurization plays a critical role in refining crude oil to produce fuel and the manufacture of fine chemicals. However, its low efficiency becomes a great challenge for the present desulfurization if only the C-S cleavage is considered a promising approach to reducing hydrogen consumption under atmospheric pressure. Accordingly, we investigate the critical factors necessary to achieve high C-S cleavage of dibenzothiophenes under mild conditions of 0.1 MPa and H2/oil = 100. The mechanism of reactive adsorption desulfurization of dibenzothiophenes with or without steric hindrance at atmospheric pressure on Pt/ZnO is proposed by studying the adsorption model of active metal sites, the Pt efficiency in C-S cleavage influenced by the steric hindrance and the structural evolution of Pt active centers in the presence of sulfur adsorption/deposition. Based on both experimental and DFT results, we report C-S cleavage of dibenzothiophenes with (TOF = 15 h−1) or without steric hindrance (TOF = 128 h−1) that can be highly efficiently fractured (99.9%) by the interface between PtSx and ZnO. This work has great practical significance for developing atmospheric industrial adsorbents for ultra-deep reactive adsorption desulfurization.

Inhibiting COx formation on WOx-loaded Au/TiO2 photocatalyst for selective oxidation of p-xylene to p-methyl benzaldehyde

Photocatalytic selective oxidation of p-xylene with O2 offers a mild pathway to synthesize p-methyl benzaldehyde (p-MBA), which is one of the primary precursors in the manufacture of fine chemicals. Here, we report that Au/WOx/TiO2 photocatalyst selectively catalyzes the oxidation of p-xylene to p-MBA with 88.6% selectivity at 1.0% conversion, the formation of COx is suppressed to 0.8%. Kinetic experiments indicate that p-methylbenzyl alcohol and p-MBA are initial products. p-Methylbenzyl alcohol is further oxidized to form p-MBA, p-methylbenzyl acid and COx; p-MBA is further oxidized to p-methylbenzyl acid and COx. On TiO2 surface, p-methylbenzyl alcohol is more prone to directly combust to COx by O2–. Loading of WOx can weaken the adsorption ability of p-methylbenzyl alcohol on the catalyst surface to avoid the combustion. Meanwhile, WOx and Au can facilitate the separation of photo-generated carriers to attain high activity and suppress the O2– formation to obtain high selectivity.

Photo‐Mediated Reduction of Carbon Dioxide to Formic and Other Carboxylic Acids by Ni‐Catalysis with Chelating Ligand

In this minireview, photo-mediated reductions of CO2 to formic and other carboxylic acids by Ni-chelate catalysts were discussed with mechanistic details. Formic and other carboxylic acid products are formed exclusively over CO by insertion of CO2 in Ni−H/Ni−C bonds in these Ni-catalysed light-mediated CO2 reductions. Role of chelating ligands in modulating the catalytic efficiency and product selectivity of such catalysis has also been encompassed in the minireview.

Renewable Electricity Enables Green Routes to Fine Chemicals and Pharmaceuticals.

Syntheses of chemicals using renewable electricity and when generating high atom economies are considered green and sustainable processes. In the present state of affairs, electrochemical manufacturing of fine chemicals and pharmaceuticals is not as common place as it could be and therefore, merits more attention. There is also a need to turn attention toward the electrochemical synthesis of valuable chemicals from recyclable greenhouse gases that can accelerate the process of circular economy. CO2 emissions are the major contributor to human-induced global warming. CO2 conversion into chemicals is a valuable application of its utilisation and will contribute to circular economy while maintaining environmental sustainability. Herein, we present an overview of electro-carboxylation, including mechanistic aspects, which forms carboxylic acids using molecular carbon dioxide. We also discuss atom economies of electrochemical fluorination, methoxylation and amide formation reactions.

Improved accessibility of Na-LTA zeolite catalytic sites for the Knoevenagel condensation reaction

The use of zeolites in basic catalysis is limited when large molecules are involved, such as in the manufacture of fine chemicals, due to difficulty in accessing the micropores of the catalyst. A solution to this problem is to synthesize zeolites containing mesopores that improve the accessibility of the active sites. This work investigates the synthesis of zeolites 4A according to a bottom-up method employing the organosilane surfactant [3-(trimethoxysilyl) propyl] octadecyldimethylammonium chloride (TPOAC), at different concentrations in the synthesis mixture (TPOAC/Al2O3 = 0–0.09), to produce mesopores. The zeolites were evaluated in the Knoevenagel condensation reaction, which is strongly influenced by the accessibility of the catalytic sites, due to the large sizes of the molecules involved. Zeolites 4A with mesopores, showing higher external surface areas, were formed in the presence of TPOAC at the different concentrations tested. Higher conversions were achieved using the zeolites with mesopores, compared to conventional zeolite 4A, due to improved access of the reactant molecules to the catalytic sites. In addition, the reaction catalyzed by the zeolite with mesopores had lower activation energy, compared to use of the conventional zeolite 4A.

Sustainability case studies on the use of continuous manufacturing in pharmaceutical production

Continuous processing is now commonly used in the manufacturing of fine chemicals including agrochemicals and pharmaceuticals. Datasets are now available, including some on environmental sustainability aspects, that enable more direct comparison between related batch and flow processes. This article examines six continuous processes where an environmental sustainability concept or metric (e.g. process mass intensity) can be compared to that from a closely-related batch process in order to assess the impact that continuous manufacturing has on that theme. Some current case studies where additional Green Chemistry concepts are exemplified are shared along with how continuous processing impacts the manufacture. We illustrate situations where continuous processing can reasonably be expected to show sustainability advantages over batch, as well as a scenario where increased solvent usage in flow mode worsened the environmental profile. While we believe that continuous processing can provide sustainability benefits, there are cases where its application can have a negative effect on environmental metrics. Our hope is to provide impartial guidance for development and manufacturing scientists so they may best utilize continuous technologies in an environmentally responsible way.

Semi-Hydrogenation of Alkynes by a Tandem Photoredox System Free of Noble Metal

The selective hydrogenation reactions play a key role in industrial manufacture of fine chemicals, which mainly rely on noble metal catalysts. Herein, a noble-metal-free hybrid photosystem is estab...

Green Oxidation of Amines by a Novel Cold-Adapted Monoamine Oxidase MAO P3 from Psychrophilic Fungi Pseudogymnoascus sp. P3

The use of monoamine oxidases (MAOs) in amine oxidation is a great example of how biocatalysis can be applied in the agricultural or pharmaceutical industry and manufacturing of fine chemicals to make a shift from traditional chemical synthesis towards more sustainable green chemistry. This article reports the screening of fourteen Antarctic fungi strains for MAO activity and the discovery of a novel psychrozyme MAOP3 isolated from the Pseudogymnoascus sp. P3. The activity of the native enzyme was 1350 ± 10.5 U/L towards a primary (n-butylamine) amine, and 1470 ± 10.6 U/L towards a secondary (6,6-dimethyl-3-azabicyclohexane) amine. MAO P3 has the potential for applications in biotransformations due to its wide substrate specificity (aliphatic and cyclic amines, pyrrolidine derivatives). The psychrozyme operates at an optimal temperature of 30 °C, retains 75% of activity at 20 °C, and is rather thermolabile, which is beneficial for a reduction in the overall costs of a bioprocess and offers a convenient way of heat inactivation. The reported biocatalyst is the first psychrophilic MAO; its unique biochemical properties, substrate specificity, and effectiveness predispose MAO P3 for use in environmentally friendly, low-emission biotransformations.

Mesoporous tin phosphate as an effective catalyst for fast cyclodehydration of bio-based citral into p-cymene

Effective synthesis of aromatic compounds from renewable biomass is highly important yet challenging. p-Cymene is an attractive aromatic compound with various promising applications in the manufacture of fine chemicals. In this study, a novel and effective catalytic system based on mesoporous tin phosphate (M-SnPO) with Lewis-Brønsted dual acidity was developed for the fast synthesis of p-cymene from the cyclodehydration of bio-based citral. Up to 78.5% yield of p-cymene was achieved from the cyclodehydration of citral at 180 °C within only 0.5 h, superior to the results reported for benchmark homogeneous acid catalysts. Characterization of as-prepared M-SnPO catalyst via various techniques indicates that the synergic effect of Lewis and Brønsted acidic sites, large pore-sized structure, and high surface area are responsible for its remarkable catalytic performance. In addition, the effectiveness of the M-SnPO catalyst could be almost sustained over multiple cycles without significant loss. The work herein is the first example of developing a Lewis-Brønsted dual acidic heterogeneous catalyst for the fast synthesis of p-cymene from the cyclodehydration of citral.

Chitosan derived N-doped carbon nanotubes for selective hydrogenation of nitroarenes to anilines

Selective hydrogenation of nitroarene to aniline is a key reaction for the manufacture of fine chemicals, pharmaceuticals, and dyes. In this study, N-doped carbon nanotubes (NCNTs) are prepared by the pyrolysis of chitosan-CNTs composite. The outside diameter of CNTs, concentration of chitosan, pyrolysis temperature and heating rate are tuned to improve the catalytic performance. The catalyst of CS/CNTs-800 doped with 0.33% pyrrolic N and 0.30% graphitic N exhibits good activity and high selectivity for the hydrogenation of nitroarenes. The kinetics data reveal that the hydrogenation reaction is zero-order for 4-nitrophenol and first-order dependence to H2 pressure, and H2 dissociation on the active sites is the rate-determining step. On CS/CNTs-800, the nitro groups of 12 different substrates can be selectively reduced with the protection of the other reducible groups. Nonpolar H radicals are found to be formed on CS/CNTs-800 for efficient hydrogenation. In addition, the catalyst showed good stability.

Solar Photooxygenations for the Manufacturing of Fine Chemicals-Technologies and Applications.

Photooxygenation reactions involving singlet oxygen (1O2) are utilized industrially as a mild and sustainable access to oxygenated products. Due to the usage of organic dyes as photosensitizers, these transformations can be successfully conducted using natural sunlight. Modern solar chemical reactors enable outdoor operations on the demonstration (multigram) to technical (multikilogram) scales and have subsequently been employed for the manufacturing of fine chemicals such as fragrances or biologically active compounds. This review will highlight examples of solar photooxygenations for the manufacturing of industrially relevant target compounds and will discuss current challenges and opportunities of this sustainable methodology.

Corymbia citriodora: A Valuable Resource from Australian Flora for the Production of Fragrances, Repellents, and Bioactive Compounds

AbstractAs global chemical manufacturing has historically relied on inexpensive feedstocks from the petrochemical industry, the identification of new naturally derived feedstocks represents an important and sustainable alternative. This review introduces Corymbia citriodora (Hook.) K.D.Hill & L.A.S.Johnson as an attractive renewable resource of natural compounds for organic chemical transformations. Although native to Australia, this plant species is now grown and harvested worldwide. The chemical composition of citriodora oils varies with location, harvesting season and age of leaves. Beyond their historic uses as fragrances or repellents, the more abundant terpenes found in citriodora oils such as citronellal, citronellol, and isopulegol have notable roles in the manufacture of fine chemicals. This review highlights several industrial processes intimately related to the citriodora terpenes, some advances in fragrances and repellents, as well as the use of these terpenes in the most recently reported synthesis of bioactive compounds. Where relevant, processes highlighting the adoption of green chemistry principles are presented and briefly discussed.

Regulating Electronic Status of Platinum Nanoparticles by Metal–Organic Frameworks for Selective Catalysis

Selective hydrogenation of alkynes to alkenes remains challenging in the field of catalysis due to the ease of over-hydrogenated of alkynes to alkanes. Favorably, the incorporation of metal nanopar...

Single-layer BSA-NH<sub>2</sub>/PNIPAAm membrane with modulated lipase biocatalytic reaction

Biocatalysis, utilizing enzymes or live microbial cultures to catalyze or speed up specific or cascade reactions, has broad applications in the manufacturing of fine chemicals, pharmaceuticals, and agrochemical intermediates. However, how to effectively adjust the biocatalytic process and the dose of enzymes during the reaction becomes one intriguing issue to be addressed. Smart porous membranes are desirable candidates for regulating substance permeability, which provides the possibility to adjust the biocatalysis. Herein, inspired by the temperature-sensitive stomatal size of plant leaves, we prepare a free-standing single-layer membrane through the self-assembly at oil-water interface, which is composed of thermosensitive amphiphilic protein-polymer conjugates, i.e., BSA-NH2/PNIPAAm (poly(N-isopropylacrylamide)). The membrane thickness is only about 4 nm, with a wide range of molecular cut-offs by tuning the molecular weight of PNIPAAm. Moreover, by virtue of the property of PNIPAAm, the pore size of the membrane could be tunable by changing temperature, through which the catalytic reaction of triglyceride by lipase was successfully controlled. Taken together, this work not only provides a simple method for preparing single-layer protein hybrid membranes, but also offers great potential applications in the controlled biocatalysis, smart gating systems and molecular separation.