Synthesis Of Fine Chemicals Research Articles

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

This 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.

Direct activation of PMS by highly dispersed amorphous CoOx clusters in anatase TiO2 nanosheets for efficient oxidation of biomass-derived alcohols

Developing a green and cost-effective catalytic system for the selective oxidation of biomass-derived alcohols is vital for the sustainable synthesis of fine chemicals. Herein, highly dispersed subnanometric amorphous CoOx clusters in anatase TiO2 nanosheets (Co-TiO2) fabricated by green solvent CO2-assisted approach could directly activate peroxymonosulfate (PMS) for the highly selective oxidation of various biomass-derived alcohols. Advanced characterizations (e.g., EXAFS, EPR, AC HAADF-STEM) reveal that a strong interaction of CoOx clusters and the anatase TiO2 support exist in Co-TiO2 and Co atom in Co-TiO2 is mainly consisted of Co2+ and Co3+. The Co-TiO2 catalyst offers superior catalytic performance in the conversion of six types of alcohols (e.g., benzyl alcohol (BAL), 5-hydroxymethylfurfural (HMF)) with high selectivity to produce corresponding aldehydes. Highly dispersed CoOx clusters and the interaction between CoOx clusters and TiO2 support contribute to the superior performance. Mechanism studies show that SO4•− radicals play the dominant role in the selective oxidation of model reactant BAL and 1O2 participates in the non-radical pathway. DFT calculations are well matched with experiment and decipher that the strong interaction between CoOx clusters and TiO2 support promotes the formation of SO4•– and SO5•–.

Tailoring Lignin-Based Spherical Particles as a Support for Lipase Immobilization

Lignin-based spherical particles have recently gained popularity due to their characteristic and the usage of biopolymeric material. In this study, lignin-based spherical particles were prepared using choline chloride at different pH values, ranging from 2 to 10. Their dispersive, microstructural, and physicochemical properties were studied by a variety of techniques, including scanning electron microscopy, Fourier transform infrared spectroscopy, and zeta potential analysis. The best results were obtained for the particles prepared at pH 5 and 7, which had a spherical shape without a tendency to form aggregates and agglomerates. The lignin-based spherical particles were used for the immobilization of lipase, a model enzyme capable of catalyzing a wide range of transformations. It was shown that the highest relative activity of immobilized lipase was obtained after 24 h of immobilization at 30 °C and pH 7, using 100 mg of the support. Moreover, the immobilized lipase exhibited enhanced stability under harsh process conditions, and demonstrated high reusability, up to 87% after 10 cycles, depending on the support used. In the future, the described approach to enzyme immobilization based on lignin spheres may play a significant role in the catalytic synthesis of organic and fine chemicals, with high utility value.

Synthesis of 2-Alkylaryl and Furanyl Acetates by Palladium Catalysed Carbonylation of Alcohols

The one-pot alkoxycarbonylation of halo-free alkylaryl and furanyl alcohols represents a sustainable alternative for the synthesis of alkylaryl and furanyl acetates. In this paper, the reaction between benzyl alcohol, chosen as a model substrate, CH3OH and CO was tested in the presence of a homogeneous palladium catalyst, an activator (isopropenyl acetate (IPAc) or dimethyl carbonate (DMC)) and a base (Cs2CO3). The influence of various reaction parameters such as the CO pressure, ligand and palladium precursor employed, mmol% catalyst load, temperature and time were investigated. The results demonstrate that decreasing the CO pressure from 50 bar to 5 bar at 130 °C for 18 h increases yields in benzyl acetate from 36% to over 98%. Further experiments were performed in the presence of piperonyl and furfuryl alcohol, interesting substrates employed for the synthesis of various fine chemicals. Moreover, furfuryl alcohol is a lignocellulosic-derived building block employed for the synthesis of functionalized furans such as 2-alkylfurfuryl acetates. Both the alcohols were successfully transformed in the corresponding acetate (yields above 96%) in rather mild reaction conditions (5–0.01 mol% catalyst, 5–2 bar CO pressure, 130 °C, 4–18h), demonstrating that the alkoxycarbonylation of alcohols represents a promising sustainable alternative to more impactful industrial practices adopted to date for the synthesis of alkylaryl and furfuryl acetates.

Development of Carbon Dioxide Incorporation Reactions for Fine Chemicals Synthesis

Development of Carbon Dioxide Incorporation Reactions for Fine Chemicals Synthesis

Ordered silica matrices supported ionic liquids as highly efficient catalysts for fine chemical synthesis

Ordered silica matrices supported ionic liquids as highly efficient catalysts for fine chemical synthesis

Oxidation of Organic Compounds Using Water as the Oxidant with H2 Liberation Catalyzed by Molecular Metal Complexes.

ConspectusOxidation reactions of organic compounds play a central role in both industrial chemical and material synthesis as well as in fine chemical and pharmaceutical synthesis. While traditional laboratory-scale oxidative syntheses have relied on the use of strong oxidizers, modern large-scale oxidation processes preferentially utilize air or pure O2 as an oxidant, with other oxidants such as hydrogen peroxide, nitric acid, and aqueous chlorine solution also being used in some processes. The use of molecular oxygen or air as an oxidant has been very attractive in recent decades because of the abundance of air and the lack of wasteful byproduct generation. Nevertheless, the use of high-pressure air or, in particular, pure oxygen can lead to serious safety concerns with improper handling and also necessitates the use of sophisticated high-pressure reactors for the processes.Several research groups, including ours, have investigated in recent times the possibility of carrying out catalytic oxidation reactions using water as the formal oxidant, with no added conventional oxidants. Along with the abundant availability of water, these processes also generate dihydrogen gas as the reaction coproduct, which is a highly valuable fuel. Several well-defined molecular metal complexes have been reported in recent years to catalyze these unusual oxidative reactions with water. A ruthenium bipyridine-based PNN pincer complex was reported by us to catalyze the oxidation of primary alcohols to carboxylate salts with alkaline water along with H2 liberation, followed by reports by other groups using other complexes as catalysts. At the same time, ruthenium-, iridium-, and rhodium-based complexes have been reported to catalyze aldehyde oxidation to carboxylic acids using water. Our group has combined the catalytic aqueous alcohol and aldehyde oxidation activity of a ruthenium complex to achieve the oxidation of biomass-derived renewable aldehydes such as furfural and 5-hydroxymethylfurfural (HMF) to furoic acid and furandicarboxylic acid (FDCA), respectively, using alkaline water as the oxidant, liberating H2. Ruthenium complexes with an acridine-based PNP ligand have also been employed by our group for the catalytic oxidation of amines to the corresponding lactams, or to carboxylic acids via a deaminative route, using water. Similarly, we also reported molecular complexes for the catalytic Markovnikov oxidation of alkenes to ketones using water, similar to Wacker-type oxidation, which, however, does not require any terminal oxidant and produces H2 as the coproduct. At the same time, the oxidation of enol ethers to the corresponding esters with water has also been reported. This account will highlight these recent advances where water was used as an oxidant to carry out selective oxidation reactions of organic compounds, catalyzed by well-defined molecular complexes, with H2 liberation. The oxidation of alcohols, aldehydes, amines, alkenes, and enol ethers will be discussed to provide an outlook toward other functional groups’ oxidation. We hope that this will aid researchers in devising other oxidative dehydrogenative catalytic systems using water, complementing traditional oxidative processes involving strong oxidants and molecular oxygen.

Sustainable Synthesis of Aryl and Heteroaryl Aldehydes

AbstractAromatic aldehydes are important intermediates for the synthesis of valuable fine and specialty chemicals and many procedures for their preparation have been developed but, nowadays, most of these synthetic methods require large amounts of reagents and multiple steps, with production of wastes. In this paper, we focused on the synthesis of some (hetero)aromatic aldehydes, used either as industrial flavor/fragrances of commercial interest, such as Heliotropine®, or as key intermediates for the preparation of some APIs and of other fragrances such as Lioral® and Helional®, by reductive carbonylation of halo derivative precursors. In order to carry out an easier and more applicable process, hydrogen donors, instead of gaseous flammable and explosive hydrogen, and recyclable phosphine free low metal content catalysts, were employed.

Mechanochemical Synthesis of Fluorinated Imines.

A number of imines, including 12 new compounds, previously not reported in the literature, derived from variously fluorinated benzaldehydes and different anilines or chiral benzylamines were synthesized by a solvent-free mechanochemical method, which was based on the manual grinding of equimolar amounts of the substrates at the room temperature. In a very short reaction time of only 15 min, the method produced the expected products with good-to-excellent yields. The yields were comparable or significantly higher than those reported in the literature for the imines synthesized by other methods. Importantly, the conditions used for the reactions with aniline derivatives also resulted in the high yields of imines obtained from chiral benzylamines, and can be extended to the synthesis with other similar amines. Structures of all imines were confirmed by NMR spectroscopy: 1H, 13C and 19F. For four compounds, X-ray structures were also obtained. The synthetic approach presented in this paper contributes to the prevention of environmental pollution and can be easily extended for larger-scale syntheses. The mechanochemical solvent-free method provides a convenient strategy particularly useful for the preparation of fluorinated imines being versatile intermediates or starting material in the synthesis of drugs and other fine chemicals.

NHC-Ni(II)-catalyzed cyclopropene-isocyanide [5 + 1] benzannulation

Isocyanides are common compounds in fine and bulk chemical syntheses. However, the direct addition of isocyanide to simple unactivated cyclopropene via transition metal catalysis is challenging. Most of the current approaches focus on 1,1-insertion of isocyanide to M-R or nucleophilc insertion. That is often complicated by the competitive homo-oligomerization reactivity occurring at room temperature, such as isocyanide 1,1-insertion by Ni(II). Here we show a (N-heterocyclic carbene)Ni(II) catalyst that enables cyclopropene-isocyanide [5 + 1] benzannulation. As shown in the broad substrate scope and a [trans-(N-heterocyclic carbene)Ni(isocyanide)Br2] crystal structure, the desired cross-reactivity is cooperatively controlled by the high reactivity of the cyclopropene, the sterically bulky N-heterocyclic carbene, and the strong coordination ability of the isocyanide. This direct addition strategy offers aromatic amine derivatives and complements the Dötz benzannulation and Semmelhack/Wulff 1,4-hydroquinone synthesis. Several sterically bulky, fused, and multi-substituted anilines and unsymmetric functionalized spiro-ring structures are prepared from those easily accessible starting materials expediently.

Facile synthesis of Ni/Fe3O4 derived from layered double hydroxides with high performance in the selective hydrogenation of benzaldehyde and furfural

Efficient upgrading of biomass-derived platform chemicals plays a crucial role in the sustainable synthesis of fine chemicals. Herein, the noble-metal free and robust Ni/Fe3O4 catalysts originated from NiFe-layered double hydroxides (LDHs) was efficient for the selective upgrading of benzaldehyde (BzH) and furfural (Fur), accordingly, the highest yield of fine chemical benzyl alcohol (99.0%, BAL) and biofuel 2-methylfuran (78.4%, 2-MF) were obtained under mild conditions over the Ni/Fe ratio of 1, respectively. These performance is far superior to most of preciously reported candidates and their counterpartners. Systematic characterizations further revealed that Ni2+/Fe3+ ratio was closely related to the dispersion and the surface acidity of catalysts, which played crucial roles in achieving excellent catalytic performance. Besides, the solvent effect, reaction parameters and reusability of catalysts in the hydrogenation process of benzaldehyde were then studied as example. Finally, the reaction pathways of benzaldehyde and furfural hydrogenation were rationally proposed. This work provides a promising way to upgrade biomass-derived chemicals.

A Reliable and Precise Protocol for Urea Quantification in Photo/Electrocatalysis.

To comply with the trend toward green and sustainable development of the fine chemical industry, multitudinous promising technologies (e.g., photocatalysis and electrocatalysis) are beginning to dabble in the green synthesis of fine chemicals, particularly urea synthesis. Whilst numerous advances are made in mechanistic understanding, the low yield reported so far also imposes more stringent requirements on the reliability and anti-interference of the detection method. Herein, the applicability of frequently used methods for urea quantification is methodically compared. In terms of the experimental results, a precise and methodical protocol for urea quantification or evaluation in photo/electrocatalysis is explored and established, with emphasis on screening quantitative methods under specific conditions and indispensable isotopic tracing experiments. The budding urea photo/electrosynthesis urgently demands a rigorous protocol, including the rapid isotopic identification and evaluation criteria, capable of promoting healthy development in the future.

Characterization of four diol dehydrogenases for enantioselective synthesis of chiral vicinal diols

Enantiopure vicinal diols are important building blocks used in the synthesis of fine chemicals and pharmaceutical compounds. Diol dehydrogenase (DDH) mediated stereoselective oxidation of racemic vicinal is an efficient way to prepare enantiopure vicinal diols. In this study, four new bacterial DDHs (AnDDH from Anoxybacillus sp. P3H1B, HcDDH from Hazenella coriacea, GzDDH from Geobacillus zalihae and LwDDH from Leptotrichia wadei ) were mined from the GenBank database and expressed in E. coli T7. The four DDHs were purified and biochemically characterized for oxidation activity toward ( R )-1-phenyl-1,2-ethanediol, with the optimal reaction condition of pH9.0 (AnDDH), 10.0 (HcDDH) and 11.0 (GzDDH and LwDDH) and the temperatures at 40 °C (AnDDH), 50 °C (HcDDH) and 60 °C (GzDDH and LwDDH), respectively. The four enzymes were stable at the pH from 7.0 to 9.0 and below 40 °C. Kinetic parameters of four DDHs showed that the HcDDH from Hazenella coriacea had high activity toward a broad range of vicinal diols. A series of racemic vicinal diols were successfully resolved by recombinant E. coli (HcDDH-NOX) resting cells co-expression of an NADH oxidase (NOX), affording ( S )-diols and (1 S , 2 S )- trans -diols in ≥99% ee. The synthetic potential of HcDDH was proved by E. coli (HcDDH-NOX) via kinetic resolution of racemic trans -1,2-indandiol on a 100 ml scale reaction, ( S , S )- trans -1,2-indandiol was prepared in 46.7% yield and >99% ee. In addition, asymmetric reduction of four α-hydroxy ketones (10–300 mmol·L −1 ) by E. coli (HcDDH-GDH) resting cells resulted in >99% ee and 69–98% yields of ( R )-vicinal diols. The current research expands the toolbox of DDHs to synthesize chiral vicinal diols and demonstrated that the mined HcDDH is a potential enzyme in the synthesis of a broad range of chiral vicinal diols.

An Efficient Bifunctional Ionic Liquid [BIL] as Solvent and Catalyst System for O-Alkylation of Phenols Under Solvent-Free Conditions: An Environmental Benign Approach

Background: Bifunctional ionic liquid [BIL] was found to be a highly effective catalyst for ether synthesis without any inorganic base or solvent. Using this protocol, different aryl substitutions were reacted with different phenols in good to excellent yields. The BIL is reusable without any loss in catalytic activity for nine consecutive cycles. The Williamson reaction is a convenient renovation in fine chemical synthesis since the ethers are important in both bulk and fine industrial chemicals preparation and academic applications. Method: The mixture of the phenol (1mmol), alcohol (1.2 mmol), and BIL ionic liquid (0.3 mol%) was added to a round-bottomed flask (100 mL) with continuous stirring for 1 hour. Objective: The aim of this study is to highlight the use of BIL to synthesize mixed ethers using substituted phenols and to study the reusability in the next cycle. Results: The products obtained were phenol and substituted phenols containing withdrawing substituents in respectable yields. However, the reactions involving substituted phenols containing electron-donating groups often afford the corresponding products in low yields. Conclusion: BIL is found to be an effective catalyst in the etherification of various unsymmetrical ethers under mild conditions. Bifunctional ionic liquid as a solvent and catalyst will show real rewards by providing a ‘green’ method with the safer procedure, less reaction time periods, mild conditions, easy separation, and ionic liquid recycle.

Synthesis of odorants in flow and their applications in perfumery.

Continuous flow technology is a key technology for sustainable manufacturing with numerous applications for the synthesis of fine chemicals. In recent years, the preparation of odorants utilizing the advantages of flow reactors received growing attention. In this review, we give an overview of selected methods for the synthesis of odorants in flow, including heterogeneously catalyzed reactions, gas reactions, and photochemical C–H functionalization processes. After a brief introduction on types of odorants, the presented odorant syntheses are ordered according to the main odor families “fruity”, “green”, “marine”, “floral”, “spicy”, “woody”, “ambery”, and “musky” and their use and importance for perfumery is briefly discussed.

Diverse Applications of Biomass-Derived 5-Hydroxymethylfurfural and Derivatives as Renewable Starting Materials.

This Review summarizes recent efforts to capitalize on 5-hydroxymethylfurfural (HMF) and related furans as emerging building blocks for the synthesis of fine chemicals and materials, with a focus on advanced applications within medicinal and polymer chemistry, as well as nanomaterials. As with all chemical industries, these fields have historically relied heavily on petroleum-derived starting materials, an unsustainable and polluting feedstock. Encouragingly, the emergent chemical versatility of biomass-derived furans has been shown to facilitate derivatization towards valuable targets. Continued work on the synthetic manipulation of HMF, and related derivatives, for access to a wide range of target compounds and materials is crucial for further development. Increasingly, biomass-derived furans are being utilized for a wide range of chemical applications, the continuation of which is paramount to accelerate the paradigm shift towards a sustainable chemical industry.

Crystal Structure of an Intramolecular Mesaconyl-Coenzyme A Transferase From the 3-Hydroxypropionic Acid Cycle of Roseiflexus castenholzii.

Coenzyme A (CoA) transferases catalyze reversible transfer of CoA groups from CoA-thioesters to free acids, playing important roles in the metabolism of carboxylic acids in all organisms. An intramolecular CoA transferase, Mesaconyl-CoA C1-C4 CoA transferase (MCT) was identified in the autotrophic CO2 fixation pathway, 3-hydroxypropionic acid cycle of filamentous anoxygenic phototrophs (FAPs). Different from the well-known CoA transferases that catalyze CoA transfer between two distinct substrates, MCT specifically catalyzes the reversible transformation of mesaconyl-C1-CoA to mesaconyl-C4-CoA, a key reaction intermediate for carbon fixation. However, the molecular mechanism of MCT in employing one substrate is enigmatic. Here we determined the crystal structure of MCT from a chlorosome-less FAP Roseiflexus castenholzii at 2.5 Å resolution, and characterized the catalytic mechanisms through structural analyses and molecular dynamic simulations. The structure of R. castenholzii MCT consists of a Rossmann fold larger domain and a small domain that are connected by two linkers. Two MCT subunits are cross interlocked at the linker regions to form a functional dimer in solution, in which the substrate binding pockets are located at the interface of the Rossmann fold larger domain from one subunit and the small domain from the other subunit. In the simulated binding structures, both the substrate mesaconyl-C1-CoA and product mesaconyl-C4-CoA form extensive electrostatic and hydrogen bonding interactions with MCT. But some differences exist in the binding mode of these two CoA analogs, Arg314’ from the second subunit of the dimer presenting dramatic conformational changes in binding with mesaconyl-C4-CoA. Together with Arg47 and one water molecule, a strictly conserved residue Asp165 are essential for catalyzing the reversible intramolecular CoA transfer reaction, through the electrostatic and hydrogen bonding interactions with the mesaconic tail of both the substrate and product. This study revealed a previously unrecognized mechanism for the uncommon intramolecular CoA transfer reaction, which will not only broaden the knowledge on the catalytic mechanisms of CoA transferases, but also contribute to enzyme engineering or biosynthetic applications of the 3-HP cycle for synthesis of fine chemicals and important metabolites.

Catalytically active atomically thin cuprate with periodic Cu single sites.

Rational design and synthesis of catalytically active two-dimensional (2D) materials with an abundance of atomically precise active sites in their basal planes remains a great challenge. Here, we report a ligand exchange strategy to exfoliate bulk [Cu4(OH)6][O3S(CH2)4SO3] cuprate crystals into atomically thin 2D cuprate layers ([Cu2(OH)3]+). The basal plane of 2D cuprate layers contains periodic arrays of accessible unsaturated Cu(II) single sites (2D-CuSSs), which are found to promote efficient oxidative Chan-Lam coupling. Our mechanistic studies reveal that the reactions proceed via coordinatively unsaturated CuO4(II) single sites with the formation of Cu(I) species in the rate-limiting step, as corroborated by both operando experimental and theoretical studies. The robust stability of 2D-CuSSs in both batch and continuous flow reactions, coupled with their recyclability and good performance in complex molecule derivatization, render 2D-CuSSs attractive catalyst candidates for broad utility in fine chemical synthesis.

Accelerating the Photocatalytic Atom Transfer Radical Addition Reaction Induced by Bi2O3 with Amines: Experiment and Computation

AbstractMetal oxide semiconductors are widely used in photocatalysis for the sustainable synthesis of fine chemicals and fuels. However, the mechanisms and the actual catalytically active species involved in these photocatalytic processes are not yet fully understood. Herein, we reveal that the addition of certain amines can effectively accelerate the photocatalytic atom transfer radical addition (ATRA) reaction by stabilizing a soluble Bi‐species formed through a reaction between Bi2O3 and diethyl bromomalonate using either N, N‐dimethylformamide (DMF) or dimethyl sulfoxide (DMSO) as a solvent. Moreover, thermodynamic calculations revealed that N, N, N’, N’‐tetramethylethylenediamine (TMEDA), and DMF yield the most stable complexes [(κ2‐TMEDA)2BiBr3], ultimately accelerating the formation of the targeted ATRA product.

A Light(er) Approach for the Selective Hydrogenation of 5-Hydroxymethylfurfural to 2,5-Bis(hydroxymethyl)furan without External H2.

The selective conversion of 5-hydroxymethyfurfural (HMF), a biomass-derived platform molecule, to value added chemicals can ease the burden on petroleum-based fine chemical synthesis. The active contribution of renewable energy sources along with low cost, environmental friendliness, and a simple reaction system must be adopted for better sustainability. In this context, photocatalytic selective hydrogenation of HMF to 2,5-bis(hydroxymethyl)furan (BHMF) was achieved over P25 titania nanoparticles without chemical squander. Simultaneously the photo-oxidation of p-methoxybenzyl alcohol (MeOBA) to p-methoxybenzaldehyde (MeOBaL), similar to biomass-derived vanillin, was carried out, abolishing the need of additional redox reagents. This system put forward the competent employment of photogenerated excitons for the valorization of lignocellulosic biomass to fine chemicals, which is an urgent requirement for sustainable chemical synthesis.