Organic Reactions Research Articles

Highly modular PDMS microwave-microfluidic chip reactor for MAOS applications

This work demonstrates the potential of microwave-microfluidics for rapid organic synthesis, incorporating modular flow cells with low-power, variable-MW frequency heating.

Phenyliodine bis(trifluoroacetate) as a sustainable reagent: exploring its significance in organic synthesis.

Iodine-containing molecules, especially hypervalent iodine compounds, have gained significant attention in organic synthesis. They are valuable and sustainable reagents, leading to a remarkable surge in their use for chemical transformations. One such hypervalent iodine compound, phenyliodine bis(trifluoroacetate)/bis(trifluoroacetoxy)iodobenzene, commonly referred to as PIFA, has emerged as a prominent candidate due to its attributes of facile manipulation, moderate reactivity, low toxicity, and ready availability. PIFA presents an auspicious prospect as a substitute for costly organometallic catalysts and environmentally hazardous oxidants containing heavy metals. PIFA exhibits remarkable catalytic activity, facilitating an array of consequential organic reactions, including sulfenylation, alkylarylation, oxidative coupling, cascade reactions, amination, amidation, ring-rearrangement, carboxylation, and numerous others. Over the past decade, the application of PIFA in synthetic chemistry has witnessed substantial growth, necessitating an updated exploration of this field. In this discourse, we present a concise overview of PIFA's applications as a 'green' reagent in the domain of synthetic organic chemistry. A primary objective of this article is to bring to the forefront the scientific community's awareness of the merits associated with adopting PIFA as an environmentally conscientious alternative to heavy metals.

Chemically engineered exogenous organic reactions in living cells for in situ fluorescence imaging and biomedical applications.

The unique microenvironment within living cells, characterized by high glutathione levels, reactive oxygen species concentrations, and active enzymes, facilitates the execution of chemical reactions. Recent advances in organic chemistry and chemical biology have leveraged living cells as reactors for chemical synthesis. This review summarizes recent reports on key intracellular in situ synthesis processes, including the synthesis of near-infrared fluorescent dyes, intracellular oxidative cross-linking, bioorthogonal reactions, and intracellular polymerization reactions. These methods have been applied to fluorescence imaging, tumor treatment, and the enhancement of biological functions. Finally, we discuss the challenges and opportunities in the field of in situ intracellular synthesis. We aim to guide the design of chemical molecules for in situ synthesis, improving the efficiency and control of artificial reactions in living cells, and ultimately achieving cell factory-like exogenous biological synthesis, biological function enhancement, and biomedical applications.

A guide to troubleshooting metal sacrificial anodes for organic electrosynthesis.

The development of reductive electrosynthetic reactions is often enabled by the oxidation of a sacrificial metal anode, which charge-balances the reductive reaction of interest occurring at the cathode. The metal oxidation is frequently assumed to be straightforward and innocent relative to the chemistry of interest, but several processes can interfere with ideal sacrificial anode behavior, thereby limiting the success of reductive electrosynthetic reactions. These issues are compounded by a lack of reported observations and characterization of the anodes themselves, even when a failure at the anode is observed. Here, we weave lessons from electrochemistry, interfacial characterization, and organic synthesis to share strategies for overcoming issues related to sacrificial anodes in electrosynthesis. We highlight common but underexplored challenges with sacrificial anodes that cause reactions to fail, including detrimental side reactions between the anode or its cations and the components of the organic reaction, passivation of the anode surface by an insulating native surface film, accumulation of insulating byproducts at the anode surface during the reaction, and competitive reduction of sacrificial metal cations at the cathode. For each case, we propose experiments to diagnose and characterize the anode and explore troubleshooting strategies to overcome the challenge. We conclude by highlighting open questions in the field of sacrificial-anode-driven electrosynthesis and by indicating alternatives to traditional sacrificial anodes that could streamline reaction optimization.

Analysis of organic chemistry students’ developing reasoning elicited by a scaffolded case comparison activity

Recent efforts in organic chemistry education research focus on investigating activities and strategies designed to elicit students’ mechanistic reasoning. This study investigates how a scaffolded case comparison activity implemented in an introductory organic chemistry course elicits and supports students’ mechanistic reasoning in an authentic classroom setting. The activity included an adaptation of a previously reported reasoning scaffold to support small-group student discussions comparing organic reactions. We analyzed students’ written responses to the in-class activity using Hammer's resources framework and Toulmin's argumentation model, interwoven to create an anti-deficit approach to exploring students’ developing reasoning. The analysis of students’ written artifacts sought to identify ways in which a scaffolded case comparison implemented in a collaborative class setting may support students’ engagement in complex reasoning and argumentation development. We found that the in-class activity elicited students’ writing about various aspects of mechanistic reasoning, including identifying explicit and implicit properties, dynamic reasoning, and multivariate reasoning. These findings indicate that the activity can engage students in complex mechanistic reasoning aspects in the classroom setting. Furthermore, this study extends the literature by detailing the nuances of students’ developing causal reasoning with energetic and electrostatic accounts as shown in their writing. The results highlight students’ emerging causal reasoning with varying levels of complexity and conceptual integration. This study provides direct implications for instructors seeking to implement similar classroom activities. The findings indicate directions for future research on the development of instructional activities and tools that further support students’ developing causal reasoning, such as adapting existing scaffolding structures to support argumentation development and the integration of challenging concepts such as energetics.

Titanium in photocatalytic organic transformations: current applications and future developments.

Titanium, as an important transition metal, has garnered extensive attention in both industry and academia due to its excellent mechanical properties, corrosion resistance, and unique reactivity in organic synthesis. In the field of organic photocatalysis, titanium-based compounds such as titanium dioxide (TiO2), titanocenes (Cp2TiCl2, CpTiCl3), titanium tetrachloride (TiCl4), tetrakis(isopropoxy)titanium (Ti(OiPr)4), and chiral titanium complexes have demonstrated distinct reactivity and selectivity. This review focuses on the roles of these titanium compounds in photocatalytic organic reactions, and highlights the reaction pathways such as photo-induced single-electron transfer (SET) and ligand-to-metal charge transfer (LMCT). By systematically surveying the latest advancements in titanium-involved organic photocatalysis, this review aims to provide references for further research and technological innovation within this fast-developing field.

Cu(ii)-catalyzed aerobic oxidative coupling of furans with indoles enables expeditious synthesis of indolyl-furans with blue fluorescence.

With the purpose of incorporating sustainability in chemical processes, there has been a renewed focus on utilizing earth-abundant metal catalysts to expand the repertoire of organic reactions and processes. In this work, we have explored the atom-economic oxidative coupling between two important electron-rich heterocycles - indoles and furans - using commonly available, inexpensive metal catalyst CuCl2·2H2O (<0.25$ per g) to develop an expeditious synthesis of indolyl-furans. Moreover, the reaction proceeded well in the presence of the so-called 'ultimate oxidant' - air, without the need for any external ligand or additive. The reaction was found to be scalable and to work even under partially aqueous conditions. This makes the methodology highly economical, practical, operationally simple and sustainable. In addition, the methodology provides direct access to novel indole-furan-thiophene (IFT)-based electron-rich π-conjugated systems, which show green-yellow fluorescence with large Stokes shift and high quantum yields. Mechanistic investigations reveal that the reaction proceeds through chemoselective oxidation of indole by the metal catalyst followed by the nucleophilic attack by furan.

Eco-Friendly Methods of Silica Extraction from Pyrophyllite Rocks Using Sol-Gel versus Alkali Fusion Method

Silica is the most abundant compound on the Earth’s surface. The content of silica can be found in agricultural waste ash and mineral rocks. Extracting silica from natural sources is advantageous due to its economic feasibility and easily obtained. Silica has a wide range of applications, such as in fertilizers, adsorbents, organic reaction catalysis, biofuels/alternative energy production, and as an antimicrobial agent. One type of rock that contains the highest amount of silica is Pyrophyllite. Recent research trends have focused on various methods and sources for silica extraction, yet extracting silica from mineral rocks presents its own challenges. Pyrophyllite rock contains a high amount of silica, but its extraction is quite difficult due to the presence of crystalline silicate mineral phases. This study aims to compare the silica extraction process on Pyrophyllite rocks from Malang using the sol-gel method versus the alkali fusion method.

A comparative study of two aldehyde dehydrogenases from Sphingobium sp.: the substrate spectrum and catalytic mechanism.

Biocatalytic oxidation is one of the most important and indispensable organic reactions for the development of green and sustainable biomanufacturing processes. NAD(P)+-dependent aldehyde dehydrogenase (ALDH) catalyzes the oxidation of aldehydes to carboxylic acids. Here, two ALDHs, SpALDH1 and SpALDH2, were identified from Sphingobium sp. SYK-6. They belong to different ALDH families and share only 32.30% amino acid identity. Interestingly, SpALDH1 and SpALDH2 exhibit significantly different enzymatic properties and substrate profiles. SpALDH2 has better thermostability than SpALDH1. SpALDH1 is a metalloenzyme and is activated by potassium ions, while SpALDH2 is not metallic-dependent. Compared with SpALDH1, SpALDH2 has a relatively broad substrate spectrum toward aromatic aldehydes. Based on homology modeling and molecular docking analysis, mechanisms underlying the substrate specificity of ALDHs were elucidated. For both ALDHs, hydrophobicity of substrate binding pockets is important for the catalytic properties, especially substrate specificity. Notably, optimization of the flexible loop 444-457 reforms a hydrogen bond between pyridine substrates and SpALDH1, contributing to the high catalytic activity. Finally, a coupling reaction catalyzed by ALDHs and NOX was constructed for efficient production of aromatic carboxylic acids.

Bis-ferrocenyl-hydrazide metal complexes: studying electronic functional groups as newly potent homogeneous photocatalysts for C(sp3)–H and C(sp2)–H bond oxidation utilizing visible light condition

A crucial challenge in using organo-metal complexes for photocatalytic organic reactions is the need to develop applications of homogeneous photocatalysts that can effectively function under visible light conditions.

Specialising and analysing instruction-tuned and byte-level language models for organic reaction prediction

We evaluate FlanT5 and ByT5 across tokenisation, pretraining, finetuning and inference and benchmark their impact on organic reaction prediction tasks.

Multi-walled carbon nanotubes as lipase carriers for organic synthesis: Current trends and recent update

Lipase-catalyzed organic reactions have been widely practiced in the past three decades. Especially interesting are insoluble/immobilized forms due to providing a possibility of facile use and recyclability, thus reducing process costs, and making the procedure more environmentally friendly. Carbon-based supports have been extensively exploited for this purpose, because of neutral and biodegradable nature and thermal and chemical stability. Their high specific surface area, characteristic surface morphology and lower mass transfer resistances play a vital role in the performance of the attached enzyme. This review paper presents an overview of the main aspects of lipase immobilized on multi-walled carbon nanotubes (MWCNTs). Moreover, different immobilization strategies to achieve a biocatalyst with improved performances are discussed. Furthermore, as lipases are considered to have high commercial worth for synthesis of valuable organic molecules, the second part of the paper is dedicated to the overview of the most important industrial sectors in which these nanobiocatalysts have been used. In specific, applications in biodiesel production, flavour ester synthesis and racemization are summarize

A bioinspired bifunctional catalyst: an amphiphilic organometallic catalyst for ring-closing metathesis forming liquid droplets in aqueous media.

Inspired by phase-separated biopolymers with enzymatic activity, we developed an amphiphilic catalyst consisting of alternating hydrophilic oligo(ethylene glycol) and hydrophobic aromatic units bearing a Hoveyda-Grubbs catalyst center (MAHGII). MAHGII served as both a droplet-forming scaffold and a catalyst for ring-closing metathesis reactions, providing a new biomimetic system that promotes organic reactions in an aqueous environment.

Reactivity in Friedel-Crafts aromatic benzylation: the role of the electrophilic reactant.

Density functional theory is employed in understanding the reactivity in the TiCl4 catalyzed Friedel-Crafts benzylation of benzene with substituted benzyl chlorides in nitromethane solvent. A series of ten substituted (in the aromatic ring) benzyl chlorides are characterized by theoretical reactivity indices. The theoretical parameters are juxtaposed to experimental relative rates of benzylation. It is established that the carbon-chlorine ionic bond dissociation energy and the Hirshfeld charge at the chlorine atom for the benzyl chlorides reactants - describe quite satisfactorily the reactivity trends. These results provide further insights into the factors governing reactivity in EAS reactions, which so far have been mostly focused on rate variations induced by changes in the structure of the aromatic substrate. The EAS benzylation investigated is quite unusual since, in contrast to most EAS reactions, the latest experimental kinetic results suggest that the aromatic substrate does not participate in the kinetic equation of the process. To shed more light on this unexpected result, we also conducted a theoretical study on the mechanistic pathway by applying M06-2X density functional computations combined with several basis sets: 6-311+G(d,p), 6-311+G(2df,2p), and def2-TZVPP. Because of the well-known difficulties in evaluating realistic free energy barriers for organic reactions, we tested two solvent models in determining the barrier for the TiCl4-catalyzed Friedel-Crafts benzylation of benzene by benzyl chloride. Since all methods employed did not provide satisfactory results for the free energy barriers, we used a combination of theoretically estimated enthalpy barriers and the available (from kinetic experiments) entropy contribution. This approach enabled us to verify that indeed the rate of this EAS reaction does not depend on the nature of the aromatic substrate. The computations revealed the structure and relative energies of the critical structures along the mechanistic pathway. Four intermediates were established along the reaction route.

Exploring borderline SN1-SN2 mechanisms: the role of explicit solvation protocols in the DFT investigation of isopropyl chloride.

Nucleophilic substitution at saturated carbon is a crucial class of organic reactions, playing a pivotal role in various chemical transformations that yield valuable compounds for society. Despite the well-established SN1 and SN2 mechanisms, secondary substrates, particularly in solvolysis reactions, often exhibit a borderline pathway. A molecular-level understanding of these processes is fundamental for developing more efficient chemical transformations. Typically, quantum-chemical simulations of the solvent medium combine explicit and implicit solvation methods. The configuration of explicit molecules can be defined through top-down approaches, such as Monte Carlo (MC) calculations for generating initial configurations, and bottom-up methods that involve user-dependent protocols to add solvent molecules around the substrate. Herein, we investigated the borderline mechanism of the hydrolysis of a secondary substrate, isopropyl chloride (iPrCl), at DFT-M06-2X/aug-cc-pVDZ level, employing explicit and explicit + implicit protocols. Top-down and bottom-up approaches were employed to generate substrate-solvent complexes of varying number (n = 1, 3, 5, 7, 9, and 12) and configurations of H2O molecules. Our findings consistently reveal that regardless of the solvation approach, the hydrolysis of iPrCl follows a loose-SN2-like mechanism with nucleophilic solvent assistance. Increasing the water cluster around the substrate in most cases led to reaction barriers of ΔH‡ ≈ 21 kcal mol-1, with nine water molecules from MC configurations sufficient to describe the reaction. The More O'Ferrall-Jencks plot demonstrates an SN1-like character for all transition state structures, showing a clear merged profile. The fragmentation activation strain analyses indicate that energy barriers are predominantly controlled by solvent-substrate interactions, supported by the leaving group stabilization assessed through CHELPG atomic charges.

The catalytic performance of (ZrO)n (n = 1-4, 12) clusters for Suzuki-Miyaura cross-coupling: a DFT study.

Superatoms are special clusters with similar physicochemical properties to individual atoms in the periodic table, which open up new avenues for exploring inexpensive catalysts. Given that the ZrO superatom possesses the same number of valence electrons as a Pd atom, the mechanisms of the Suzuki-Miyaura reaction catalyzed by (ZrO)n (n = 1-4) clusters have been investigated and compared with the corresponding Pdn (n = 1-4) species to explore superatom-based catalysts for the formation of C-C bonds via a density functional theory (DFT) study. It was interesting to find that the catalytic activities of (ZrO)n (n = 1-4) towards the Suzuki-Miyaura reaction gradually improved as the cluster size increased. Therefore, to obtain more efficient catalysts, the catalytic activity of a well-designed (ZrO)12 nanocage towards this cross-coupling reaction has been further evaluated. Gratifyingly, this nanocage shows excellent catalytic performance for the considered coupling reaction, which is even comparable to that of the commonly used Pd catalyst and outperforms the corresponding Pd12 cluster. We hope this study can not only provide valuable guidance for the development of noble metal-like catalysts for C-C bond formation, but also expand the application of superatoms in the catalysis of organic reactions.

Single-layer 2D supramolecular-organic-framework-supported polyoxometalates: efficient selective oxidation of toluene in seawater under sunlight

Performing organic reactions in water, in particular in seawater under sunlight, is a desirable objective in chemistry because both are the most abundant and cheapest resources on earth. Herein, we...

Recent advances in the transformation reactions of the Betti base derivatives.

Betti bases are the products resulting from the one-pot multicomponent reaction involving 1-naphthol/2-naphthol, aliphatic/aromatic aldehydes, and secondary amines. This chemical process is commonly referred to as the Betti reaction. The significance of Betti bases in medicinal chemistry has grown substantially due to their diverse array of pharmacological applications. Furthermore, their synthetic utility is considerable, given their use as catalysts and ligands in asymmetric synthesis. Moreover, Mannich products, incorporating diverse functional groups such as -OH and -NH, find application in a range of organic reactions. This utilization enables the synthesis of novel C-C bond linkages and diverse heterocycles, including biologically active naphthoxazines, which hold biological applications such as antibacterial, antifungal and anticancer. The focus of this review article is on the application of aminonaphthol derivatives in transformation reactions and the synthesis of organic compounds, with particular emphasis on heterocycles.

Organofunctionalized borotungstate polyoxometalates as tunable photocatalysts for oxidative dimerization of amines.

Organofunctionalized borotungstate Keggin polyoxometalates, ( n Bu4N)3H[HBW11O39(P(O)Ph)2] (PBW11), ( n Bu4N)3H[HBW11O39(As(O)Ph)2] (AsBW11), and ( n Bu4N)4[HBW11O39(PhSiOSiPh)] (SiBW11), were synthesized and structurally characterized. Cyclic voltammetry showed that the electronic properties of the clusters are dependent on the nature of the appended main group atoms (P, As, or Si). The first reduction potentials were found to shift positively with respect to that of the unmodified parent species ( n Bu4N)5[BW12O40], with PBW11 showing the largest shift at +100 mV. All clusters were evaluated as photocatalysts for the oxidative dimerization of amines where the organophosphonate hybrid PBW11 was found to be the most active. This study demonstrates how organofunctionalization of polyoxometalates may be used to tune and improve their performance as photocatalysts for organic reactions.

Synthesis of a Series of 4H-Pyran Derivatives with Multicomponent Reaction in DBSA/H2O Microemulsion System

A series of 4H-pyran derivatives were synthesized through a three-component condensation reaction in a pot using aromatic aldehyde, cyclohexanedione, and malononitrile in the dodecyl benzenesulfonic acid/H2O microemulsion system. This protocol is attractive because dodecyl benzenesulfonic acid microemulsion is superior for organic reaction due to its dual catalysis. On the one hand, dodecyl benzenesulfonic acid acts as a Brønsted acid to catalyze the reaction; on the other hand, it can form a microemulsion as surfactant to enlarge the boundary area and entrap water produced during esterification reaction. In addition, the reaction process is simple, with high liaison formation efficiency, good yields, and environmentally harmless reaction conditions. The dodecyl benzenesulfonic acid/H2O microemulsion system was equally effective when used in consecutive reactions.