Organic Reactions Research Articles

From agricultural waste to value: Integrated chemo and biocatalytic biorefinery processes to produce 2-furoic acid

The integration of biocatalysis in biorefineries can lead to synergies for raw material valorization. Enzymes must perform efficient and selective reactions when using crude effluents (to avoid costly downstream units). Herein, this is showcased with the synthesis of 2-furoic acid, starting from rice husk (agricultural waste), via a sequential organic-acid catalyzed pretreatment – to afford xylose and cellulose and lignin –, followed by the microwave-assisted acidic xylose dehydration to furfural, in situ extraction in ethyl acetate, and the final biocatalytic selective oxidation of furfural to 2-furoic acid (2-FA). To validate the concept, a xylose-rich hydrolysate (∼ 15 g xylose L−1) obtained from rice husk (RH) was used, achieving a furfural yield of 70 % in a biphasic system (water – ethyl acetate). The obtained furfural extracted in the ethyl acetate was subsequently oxidized to 2-furoic acid via an organic peroxide reaction mediated by Candida antarctica lipase B (CALB), with an overall yield of 90 %, and, with a yield of 41.72 % based on the initial xylose in biomass. Notably, 20 mg/mL CALB could tolerate up to 400 mM of furfural under optimum conditions of 40 °C, 48 h. The recyclability of the biocatalyst was investigated, enabling an efficient reuse of four consecutive cycles.

200 Years of The Haloform Reaction: Methods and Applications.

Discovered in 1822, the haloform reaction is one of the oldest synthetic organic reactions. The haloform reaction enables the synthesis of carboxylic acids, esters or amides from methyl ketones. The reaction proceeds via exhaustive a-halogenation and then substitution by a nucleophile to liberate a haloform. The methyl group therefore behaves as a masked leaving group. The reaction methodology has undergone several important developments in the last 200 years, transitioning from a diagnostic test of methyl ketones to a synthetically useful tool for accessing complex esters and amides. The success of the general approach has been exhibited through the use of the reaction in the synthesis of many different complex molecules in fields ranging from natural product synthesis, pharmaceuticals, agrochemicals, fragrants and flavouring. The reaction has not been extensively reviewed since 1934. Therefore, herein we provide details of the history and mechanism of the haloform reaction, as well as an overview of the developments in the methodology and a survey of examples, particularly in natural product synthesis, in which the haloform reaction has been used.

SYNTHESIS AND APPLICATION OF PHOSPHINITE LIGAND-CONTAINING RUTHENIUM CATALYSTS IN TRANSFER HYDROGENATION

Transfer hydrogenation (TH) is a highly significant reaction in organic chemistry, especially in the synthesis of pharmaceuticals, agrochemicals, and fine chemicals. This method involves the transfer of hydrogen from a donor molecule to an unsaturated substrate, offering a safer and more convenient alternative to direct hydrogenation, which typically requires high-pressure hydrogen gas. TH stands out for its ability to selectively reduce multiple functional groups under milder conditions, thereby reducing the risk of overreduction or damage to sensitive functional groups. This technique is particularly valuable in asymmetric synthesis (AS), where chiral catalysts enable the production of enantiomerically pure compounds, crucial for drug development.Ruthenium complexes are particularly noteworthy for their effectiveness in asymmetric TH. Their stability and adaptability to different reaction environments make them ideal for both laboratory-scale and industrial applications. Phosphinite ligands (P(OR)R'2) are used in synthesis of complexes to improve their properties. These ligands are known for their ability to finely tune the electronic and steric properties of metal centers. The electron-donating nature of the phosphorus atom, combined with the variability in the R and R' groups, allows for significant customization of the catalyst's properties.The purpose of the work is to review up-to-date discoveries in the field of TH.The integration of phosphinite ligands into ruthenium catalysts marks a significant advancement in the field of TH. These catalysts exhibit enhanced efficiency, selectivity, and stability, proving crucial in AS. The study's exploration of various hydrogen sources, bases, and mechanisms has provided deeper insight into the process of TH.

Fibrous catalyst based on atomic Pd and N-doped holey graphene functionalized cotton fiber for continuous-flow reaction

Continuous-flow catalysis bridges the gap between bench-scale laboratories and production-scale factories and thus should be a green and promising technology for the manufacture of value-added chemicals. Here, we present the construction of a continuous-flow catalytic system by integrating a tubular reactor with novel catalytic fibers, which are comprised of single-atomic Pd (Pd1) and nitrogen-doped holey graphene (NHG) functionalized cotton fibers (CFs). Due to the loosely packed structure, highly exposed dual-active sites (i.e., single-atomic PdN4 sites and activated C sites in the NHG carbocatalyst) of the CF@(Pd1/NHG) catalytic fibers, the corresponding flowing system exhibites remarkably high catalytic performance (activity and durability) and processing rate in organic reactions, including oxidative hydroxylation of phenylboronic acid and reduction of nitroarenes. Typically, the processing rate of the catalytic system toward 4-nitrophenol (a representative nitroarene) reduction can reach up to 2.46 × 10−3 mmol·mg−1·min−1, significantly higher than that of those packing catalysts reported in recent years.

Recent Advances in On-Line Mass Spectrometry Toolbox for Mechanistic Studies of Organic Electrochemical Reactions.

Electrochemical reactions are very complex and involve a variety of physicochemical processes. Accurate and systematic monitoring of intermediate process changes during the reaction is essential for understanding the mechanism of electrochemical reactions and is the basis for rational design of new electrochemical reactions. On-line electrochemical analysis based on mass spectrometry (MS) has become an important tool for studying electrochemical reactions. This technique is based on different ionization and sampling means and realizes on-line analysis of electrochemical reactions by establishing electrochemistry-MS (EC-MS) coupling devices. In particular, it provides key evidence for elucidating the reaction mechanism by capturing and identifying the reactive reaction intermediates. This review will categorize various EC-MS devices and the organic electrochemical reaction systems they study, highlighting the latest research progress in recent years. It will also analyze the properties of various devices and look forward to the future development of EC-MS.

Sodium thiosulfate modified graphitic carbon nitride for enhancing the photocatalytic production of aldehydes

The oxidation of alcohols to aldehydes is one of the most relevant reactions in organic chemistry. The currently implemented methods based on expensive noble metallic catalysts, toxic solvents, and high temperature and pressure conditions have released the seek for softer and cheaper alternatives such as photocatalysis. In this sense, graphitic carbon nitride has been modified with sodium thiosulfate as a source of S and Na+ incorporation in the structure, aimed at enhancing the photocatalytic performance on the oxidation of alcohols to aldehydes, i.e. cinnamaldehyde, benzaldehyde, and vanillin in aqueous solution. Three g-C3N4 samples synthesized from different precursors, i.e. melamine, thiourea, and urea, were treated with sodium thiosulfate. Urea led to the g-C3N4 with the highest mesoporosity (surface area, 69 m2 g−1) and photocatalytic activity. The modification with 5 % (wt.) of Na2S2O3 enhanced the pseudo-first order rate constant of cinnamyl alcohol oxidation from 0.265 h−1 (bare sample) to 0.792 h−1 (Na2S2O3-modified). The characterization of the material suggests a better charge separation of the photogenerated charges after S and Na+ incorporation in the structure, minimizing the recombination rate of photogenerated charges. The optimum photocatalyst, tested in aqueous solution, was most selective in the production of benzaldehyde (selectivity, >100 %) > cinnamaldehyde (>23 %) > vanillin (∼5 %). The selectivity was considerably boosted under acetonitrile as the solvent medium, raising in the case of cinnamaldehyde the 23 % recorded in water to 51 % in pure acetonitrile. The degradation mechanism suggests a strong influence of the photogenerated holes and the superoxide radical, the latter being more selective in the oxidation of the alcohol.

Recent Routes in Synthesis and Biological Activity of Pyrimido[4,5-b] Quinoline Derivatives: A Review (Part II)

The synthesis of organic molecules has been a tremendous and rapid advance in the recent decade to obtain high biological and pharmacological activities. In this review, the organic synthesis of pyrimido[4,5-b]quinoline derivatives is considered an alternative method to traditional procedures for treating many diseases that affect humans. Also, by transferring electrons, stereoselective syntheses occur via organic reactions in various unnatural and natural conditions at room temperature and normal pressure. We found that the structure of pyrimido[4,5-b]quinoline derivatives was formed by substrates, bases, electrophiles, and low-level and highly stable reagents that can be broadly applied to synthesize more heterocycles. These reagents include: 2- nitrobenzaldehyde; 3-(benzyloxy)-4-methoxy-2-nitrobenzaldehyde; 4,5-dimethoxy-2- nitrobenzaldehyde; 2-aminobenzaldehyde; 2-aminoquinoline-3-carboxamide; 2-chloroquinoline3-carbaldehyde; 2-bromobenzaldehyde; 2-chloroquinoline-3-carbonitrile; 2-chloroquinoline-3- carboxylic acid; aniline; phenyl-methanamine; amino-quinoline-3-carboxylic acid /aminoquinoline-carbonitrile; amino-6,7-dimethoxy-quinoline-3-carbonitrile; amino-oxolo [4,5- g]quinolin-carboxamide; 3-(aminomethyl) quinolin-2-amine; 4-aminobenzo[d][1,3] dioxole-5- carbaldehyde; thiourea; ethyl 3-oxo-butanoate; 2-cyano-acetamide; 2-(bis (methylthio) methylene) malononitrile; ethyl 3,3-diamino-2-cyanoacrylate; naphthalene-1,4-dione; and N-carbamoyl-2- cyanoacetamide derivatives. The prepared pyrimido[4,5-b]quinoline derivatives were described through means of the following chemical reactivity: alkylation, bromination, chlorination, cyclocondensation, cyclization, acylation, oxidation-reduction, dehydration, addition reaction and Vilsmeier-Haack reaction (Vilsmeier reagent).

Generation and Application of Sulfur Ylides in Light‐Mediated Transformations

Sulfur ylides are essential reagents in various organic reactions like epoxidation and cyclopropanation. While traditionally employed in ionic chemistry, recent advancements in visible‐light‐driven photocatalysis reveal their potential as sources of radicals or free carbenes. The photochemical or photocatalytic generation of reactive intermediates using sulfur ylides expands the utility of these reagents in modern organic synthesis, offering sustainable solutions to emerging challenges. Despite early demonstrations in the 1960s, the past years have witnessed a surge in photochemical methods utilizing sulfur ylides as precursors. The use of redox‐active photocatalysts has facilitated numerous radical reactions. This review consolidates key findings in sulfur ylide chemistry, particularly focusing on photo‐mediated reactions, to stimulate further research interest in this dynamic field.

How does using an AR learning environment affect student learning of a radical substitution mechanism?

Abstract As the use of augmented reality (AR) in educational settings grows, it becomes increasingly important to understand how to use AR in classrooms. Here, we present an AR learning environment that we designed for teaching an organic chemistry reaction mechanism in high school chemistry classes. This new environment was tested in six tenth-grade chemistry classes (upper secondary) taught by five different teachers in three different schools over the course of five months and evaluated for effectiveness. Students completed knowledge tests before and after they used the AR learning environment to test their learning gain, and surveys to measure their acceptance of the technology, the cognitive load they experienced, and their attitude toward the use of AR to learn the mechanism for radical substitution. Analysis shows that the knowledge posttest scores were significantly higher than the pretest scores (p < 0.001), with a large effect size (r = 0.8). Student responses showed acceptance of the technology, experience of low extraneous cognitive load, and a positive attitude toward the use of AR to learn this reaction mechanism. These findings indicate that this AR learning environment can be used to teach the mechanism of radical substitution to tenth-grade students in introductory high school chemistry courses.

Synthetic Approaches, Properties, and Applications of Acylals in Preparative and Medicinal Chemistry.

Diesters of geminal diols (R-CH(O-CO-R')2, RR'C(OCOR″)2, etc. with R = H, aryl or alkyl) are termed acylals according to IUPAC recommendations (Rule P-65.6.3.6 Acylals) if the acids involved are carboxylic acids. Similar condensation products can be obtained from various other acidic structures as well, but these related "non-classical acylals", as one might call them, differ in various aspects from classical acylals and will not be discussed in this article. Carboxylic acid diesters of geminal diols play a prominent role in organic chemistry, not only in their application as protective groups for aldehydes and ketones but also as precursors in the total synthesis of natural compounds and in a variety of organic reactions. What is more, acylals are useful as a key structural motif in clinically validated prodrug approaches. In this review, we summarise the syntheses and chemical properties of such classical acylals and show what potentially under-explored possibilities exist in the field of drug design, especially prodrugs, and classify this functional group in medicinal chemistry.

Reactivity Inside Molecular Flasks: Acceleration Modes and Types of Selectivity Obtainable.

There is increasing interest in the discovery and application of molecular flasks - supramolecular host structures capable of catalyzing organic reactions. Reminiscent of enzymes due to possessing a host cavity akin to an active site, molecular flasks can exhibit complex catalytic mechanisms and in many cases provide selectivity not achievable in bulk solvent. In this Review, we aim to organize the increasingly diverse examples through a two-part structure. In part one, we provide an overview of the different acceleration modes that operate within molecular flasks, while in part two we showcase, through selected examples, the different types of selectivity that are obtainable through the use of molecular flasks. Particular attention is given to examples that are relevant to current challenges in synthetic organic chemistry. We believe that this structure makes the field more approachable and thus will stimulate the development of novel applications of molecular flasks.

Advancing Heterogeneous Organic Synthesis With Coordination Chemistry-Empowered Single-Atom Catalysts.

For traditional metal complexes, intricate chemistry is required to acquire appropriate ligands for controlling the electron and steric hindrance of metal active centers. Comparatively, the preparation of single-atom catalysts is much easier with more straightforward and effective accesses for the arrangement and control of metal active centers. The presence of coordination atoms or neighboring functional atoms on the supports' surface ensures the stability of metal single-atoms and their interactions with individual metal atoms substantially regulate the performance of metal active centers. Therefore, the collaborative interaction between metal and the surrounding coordination environment enhances the initiation of reaction substrates and the formation and transformation of crucial intermediate compounds, which imparts single-atom catalysts with significant catalytic efficacy, rendering them a valuable framework for investigating the correlation between structure and activity, as well as the reaction mechanism of catalysts in organic reactions. Herein, comprehensive overviews of the coordination interaction for both homogeneous metal complexes and single-atom catalysts in organic reactions are provided. Additionally, reflective conjectures about the advancement of single-atom catalysts in organic synthesis are also proposed to present as a reference for later development.

Comparison of the Effects of Stirring and Standing on Chemical Reactions

AbstractFor hundreds of years, it seems that people have needed stirring to conduct chemical experiments. This operation can be seen everywhere in chemical, pharmaceutical, and materials laboratories and factories. People generally believe that stirring helps with processes such as material dispersion, dissolution, and collision, thereby enabling more-efficient reactions. However, why do chemical reactions that occur in Nature not require stirring? What are the facts? For this purpose, we investigated a total of 329 organic chemical reactions in eight categories and 25 types, including 26 chemical reactions magnified to gram or even kilogram levels. Under the same conditions of temperature, humidity, pressure, and reaction time, we compared the reaction yields under stirring and standing conditions. More than 600 results showed that stirring or not stirring had almost no effect on the efficiency of chemical reactions in solution. If most chemists performing reactions turned off the agitator, it would not be difficult to imagine how much electricity could be saved!

Modulating Silver Performance in Electrocatalytic Oxidation of HCHO via SMSI between Ag-Co3O4 Interfaces.

The replacement of oxygen evolution reactions with organic molecule oxidation reactions to enable energy-efficient hydrogen production has been a subject of interest. However, further reducing reaction energy consumption and releasing hydrogen from organic molecules continue to pose significant challenges. Herein, a strategy is proposed to produce hydrogen and formic acid from formaldehyde using Ag/Co3O4 interface catalysts at the anode. The key to improving the performance of Ag-based catalysts for formaldehyde oxidation lies in the strong SMSI achieved through the well-designed "spontaneous redox reaction" between Ag and Co3O4 precursors. Nano-sized Ag particles are uniformly dispersed on Co3O4 nanosheets, and electron-deficient Agδ+ are formed by the SMSI between Ag and Co3O4. Ag/Co3O4 demonstrates exceptional formaldehyde oxidation activity at low potentials of 0.32V versus RHE and 0.65V versus RHE, achieving current densities of 10 and 100mA cm-2, respectively. The electrolyzer "Ag/Co3O4||20% Pt/C" achieves over 195% hydrogen efficiency and over 98% formic acid selectivity, maintaining stable operation for 60 hours. This work not only presents a novel approach to precisely modulate Ag particle size and interface electronic structure via SMSI, but also provides a promising approach to efficient and energy-saving hydrogen production and the transformation of harmful formaldehyde.

Solar Light-Induced Synthesis of Biologically Active Compounds

Over the past few years, photocatalytic methods have shown great promise as low-cost, environmentally friendly, and sustainable technologies. During the development of photochemistry, a variety of sources of light were used, including sunlight, compact fluorescent lamps, lasers, and even light-emitting diodes. As a part of preparing diverse organic compounds, the photochemical approach was used, for instance, to form rings, arylated compounds, cycloaddition, functionalized compounds, dehalogenated compounds, oxidized compounds, reduced compounds, isomers, and sensitized compounds. Solar energy is a renewable resource that can be harvested from the sun and this light energy can be changed into chemical energy with the help of photocatalysts. During this green approach, electron-hole pairs are generated in photocatalysts in order to begin reactions by using solar light. It has been highlighted in this article that there have been impressive developments in the use of light, mainly the solar light, to promote important organic reactions, which would otherwise be unattainable under thermal conditions.

CO2/N2 Triggered Aqueous Recyclable Surfactants for Biphasic Catalytic Reactions in the Pickering Emulsions.

The utilization of Pickering emulsions in interfacial catalysis offers a promising environmental platform for biphasic reactions. However, complicated surface coating or chemical grafting methods are always required to prepare the surface-active catalysts for the Pickering emulsions, since most of them are commercially unavailable. Here, we report CO2-switchable Pickering emulsions for biphasic reactions, in which Pd@Al2O3 nanoparticles are in situ modified by a CO2/N2 responsive surfactant. Compared with the chemical grafted methods, the in situ formed Pickering interfacial catalysts avoid complex chemical modification. Furthermore, efficient demulsification and separation of the oil phase and the products without surfactant contaminations can be achieved by CO2 trigger. The Pickering interfacial catalysis system can also be reformed after the aqueous phase containing the catalyst nanoparticles, and the surfactant is recycled and reused. The strategy is universal for nitrobenzene reductions and alcohol oxidations, providing a convenient and green method for the preparation of Pickering catalysts with commercially available nanoparticles, efficient emulsion separation, and recovery of the catalyst nanoparticles and emulsifiers in various two-phase organic reactions.

Oxadiazolines as Photoreleasable Labels for Drug Target Identification.

Photoaffinity labeling is a widely used technique for studying ligand-protein and protein-protein interactions. Traditional photoaffinity labels utilize nonspecific C-H bond insertion reactions mediated by a highly reactive intermediate. Despite being the most widely used photoaffinity labels, diazirines exhibit limited compatibility with downstream organic reactions and suffer from storage stability concerns. This study introduces oxadiazolines as innovative and complementary photoactivatable labels for addition to the toolbox and demonstrates their application in vitro and through in cellulo labeling experiments. Oxadiazolines can be easily synthesized from ketone moieties and cleaved with 302-330 nm light to cleanly liberate a diazo reactive moiety that can covalently modify nucleophilic amino acid residues. Notably, oxadiazolines are compatible with various organic reaction conditions and functional groups, allowing for the exploration of a large chemical space. Several known inhibitors featuring the oxadiazoline functionality were prepared without affecting their binding affinity. Furthermore, we confirmed the ability of oxadiazolines to form covalent bonds with proteins upon UV-irradiation, both in vitro and in cellulo, yielding comparable results to those of the matched diazirine compounds.

Exploring Sulphonated Calix[n]arenes as Catalysts in Organic Reactions

Catalysis plays a crucial role in modern chemistry, with macrocyclic compounds like calixarenes serving as key players in organic transformations through supramolecular chemistry. These macrocycles, synthesized from phenol and formaldehyde condensation, exhibit a variety of conformations, such as cone and partial‐cone, due to their flexible structures. Their effectiveness as catalysts arises from their lipophilic cavities and the ease of functionalization on both the upper and lower rims. Water‐soluble calixarenes, in particular, have gained attention for their ability to interact with hydrophobic cavities, facilitating molecular recognition in aqueous environments. A landmark achievement in this field was Shinkai's synthesis of water‐soluble calix[4]arene in 1984, which involved sulphonation using tert‐butyl groups, resulting in compounds known for their low toxicity and encapsulation capabilities. This review provides a comprehensive overview of the advancements in sulphonated calixarenes as catalysts, emphasizing their diverse applications and potential for future development. Key catalytic reactions and their substrate scopes are discussed, along with future perspectives on how these compounds can further revolutionize catalytic processes.

N-Alkylation of Dopamine and Its Impact on Surface Coating Properties.

Surface coating with dopamine (DA) has received significant attention over the past decade due to its compatibility with other surface coating techniques and versatility, making it applicable to solid surfaces regardless of substrate and shape. Much effort has been made to elucidate the origin of its surface coating capability, and as a result, many important factors affecting the coating properties have been determined. For example, it has been reported that the length of the carbon chain between catechol and amino groups, the attachment of specific functional groups to the catechol ring and amino group, and the replacement of the amino group with another functional group can affect the surface coating properties of DA. Despite these various attempts, there are still many factors that remain unknown. In this study, we investigate the effect of N-alkylation on DA coating. N-Ethyl-DA, N-propyl-DA, and N-isopropyl-DA are newly synthesized through simple organic reactions, and the coating efficiency of DA derivatives is compared with nucleophilicity and steric bulkiness. As a result, the coating efficiency of N-ethyl-DA and N-propyl-DA is lower than for pristine DA and N-methyl-DA, but it is possible to coat solid surfaces with alkyl-functionalized DA. In contrast, the coating with sterically bulky N-isopropyl-DA is almost unsuccessful.

Cobalt-Catalyzed Asymmetric Hydrogenation of Ketones Enabled by the Synergism of an N-H Functionality and a Redox-Active Ligand.

The transition metal-catalyzed asymmetric hydrogenation (AH) of ketones to produce enantioenriched alcohols is an important reaction in organic chemistry with applications in the pharmaceutical and agrochemical fields. Using earth-abundant, biorelevant cobalt as the central metal in the catalyst has a high potential to improve sustainability and achieve hydrogenation reactions that are scalable. However, due to the high d-electron count, designing cobalt catalysts that exhibit turnover numbers (TONs, ≥1000) and enantioselectivities (≥90%) sufficient for synthetic utility and practical scalability (≥1 kg scale) remains a challenge. In this work, an efficient catalyst design strategy utilizing an amino(imino)diphosphine Co(II) bromide precatalyst is presented to achieve this goal. The quantitative production of a wide range of secondary chiral alcohols with TONs of up to 150,000 and an enantiomeric excess (e.e.) of up to 99% at a scale of up to 1.35 kg was achieved, indicating that the proposed cobalt catalyst is highly promising for AH and scale-up reactions. A mechanistic study revealed that the synergism of an N-H functionality and a redox-active ligand endows the cobalt catalyst with a high productivity and excellent enantioselectivity.