Methodology In Organic Synthesis Research Articles

INCLUSION OF AZULENE STRUCTURAL UNITS IN THE BASIS OF CONJUGATED POLYMERS: IMPROVEMENT OF PROTON SENSITIVITY AND FLUORESCENCE

The growing interest in aromatic polymer compounds with an extended π-electron coupling system is explained by their importance as functional materials for organic optoelectronics. At present, much attention is paid to arylated, as well as substituted by electron acceptor and/or electron donor groups, aromatic and heteroaromatic compounds. One of the advantages of such conjugated aromatic systems is that they can fine-tune the electronic structure of materials in order to optimize their performance and morphology. In this regard, the structural isomer of naphthalene - azulene is of considerable interest. The nonalternant aromatic hydrocarbon azulene has unique electronic and spectral properties, including a polarized structure with a dipole moment of the order of 1,08 D and abnormal Anti-Kasha fluorescence S2→S0. The article discusses the synthesis of two fluorene-azulene π-conjugated copolymers using the modern methodology of organic synthesis as the Suzuki − Miyaura -cross−coupling reaction. It was shown that the interaction of 1,3-dibromazulene, as well as 2,7-Bis(3-bromoazulen-1-yl)-9,9-dioctyl-fluorene with 2,2'-(9,9-dioctyl-9H-fluorene-2,7-diyl)bis(1,3,2-dioxaborinane) under Suzuki − Miyaura cross-coupling conditions, azulene conjugate copolymers were synthesized: poly[2,7-(9,9-dioctylfluorenyl)-alt-(1ꞌ,3ꞌ - azulenyl)] and poly[1,3-bis(9ꞌ,9ꞌ-dioctylfluoren-2ꞌ-yl)azulenyl]-alt-[1ꞌꞌ,3ꞌꞌ - azulenyl]. It is revealed that neutral solutions of the obtained copolymers are nonfluorescent, but they become luminescent upon addition of trifluoroacetic acid. The «launching» of fluorescence occurs as a result of the formation of a 6 π-electron azulenyl cation, which rearranges the general electronic character of polymers, in particular, HOMO-LUMO levels and band gap. The obtained results demonstrate that the introduction of azulene units into a conjugated polymer framework has great potential for application as new protic functional materials.

Marine-derived magnetic nanocatalyst in sustainable ultrasound-assisted synthesis of 2,3-diphenyl-2,3-Dihydroquinazolin-4(1H)-One derivatives

This research presents a sustainable approach to fabricate iron oxide nanoparticles by employing phytochemicals derived from marine grass extract as both reducing and stabilizing agents. Formation of magnetic nanoparticles (MNPs) initially confirmed by ultraviolet–visible spectroscopy (UV–vis) showing absorption peak at 370 nm. X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques unveiled magnetic iron oxide NPs with a rod shape, an average size of 21 nm, and an inverse spinel crystal structure. The participation of organic compounds in the production and stabilization of MNPs was evidenced through Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). A vibrating sample magnetometer (VSM) demonstrated the magnetic properties of iron oxide NPs showing a saturation magnetization value of 21.46 emu/g. The catalytic efficiency of these marine-assisted MNPs was evaluated in a one-pot three-component reaction involving isatoic anhydride, aromatic aldehydes, and amines under ultrasonic conditions. Under optimal conditions, a low dose of 1.5 mg of biobased magnetite nanoparticles yielded dihydroquinazolin-4(1H)-One products with up to 95 % efficiency in a brief duration of 15 min at an ultrasonic power intensity of 130 W. Different directing groups were investigated, and control experiments were carried out to enhance the understanding of the reaction mechanism. The obtained results highlight the synergistic effect of marine grass-mediated magnetic nanocatalysts combined with ultrasonic-assisted synthesis in developing sustainable green methodologies in organic synthesis.

Cobalt Nanoparticles Catalyzed N-Heterocycles Synthesis via Acceptorless Dehydrogenative Coupling.

The acceptorless dehydrogenation reaction is a sustainable and atom-economical methodology in organic synthesis, resulting in the byproducts of only hydrogen or water. Herein, a robust Co-Si/CN catalyst (derived from ZIF@SiO2 composite) has been synthesized through a one-step assembly process via pyrolysis and etching. This catalyst has been employed for the acceptorless dehydrogenative coupling of 2-aminoalcohols with secondary alcohols, enabling efficient conversion of various substrates into desired quinoline or pyridine derivatives with a yield of up to 94 %.

Structural Reassignment of Covalent Organic Framework-Supported Palladium Species: Heterogenized Palladacycles as Efficient Catalysts for Sustainable C-H Activation.

Recent decades have witnessed remarkable progress in ligand-promoted C-H activation with palladium catalysts. While a number of transformations have been achieved with a fairly broad substrate scope, the general requirements for high palladium loadings and enormous challenges in catalyst recycling severely limit the practical applications of C-H activation methodologies in organic synthesis. Herein, we incorporate N,C-ligand-chelated palladacycles into rigid, porous, and crystalline covalent organic frameworks for the C-H arylation of indole and pyrrole derivatives. These heterogeneous palladium catalysts exhibit superior stability and recyclability compared to their homogeneous counterparts. We not only produce several highly reactive palladacycles embedded on new framework supports to facilitate C-H activation/C-C bond-forming reactions but also reassign heterogenized palladium species on frameworks containing a benzaldehyde-derived imine moiety as imine-based palladacycles via comprehensive characterization. Our findings provide guidance for the rational design of framework-supported metallacycles in the development of heterogeneous transition-metal catalysis.

Pot-Economical Approaches to the Synthesis and Functionalization of Phthalocyanines for Clean Energy Production

The last decades have witnessed a growing interest in reducing the ecological and economic impact of chemical processes, with an important focus on the development of more environmentally friendly procedures and methodologies in organic synthesis. Given the extreme versatility and technological importance of phthalocyanines for a variety of applications, of which clean energy production is among the most relevant, the design and study of alternative and less-impacting synthetic approaches to the conventional ones have gained importance in the last years. Their synthesis in solution frequently requires reaction media such as high boiling point alcohols (pentanol, hexanol), dimethylaminoethanol, chlorobenzene, quinoline, and α-chloronaphthalene, most of which are toxic and non-environmentally friendly. Some green synthetic approaches based on solvothermal methods [1,2], mechanochemistry [3], or alternative sources of energy such as microwaves [4-6] and ultraviolet radiation [7], have been developed in order to minimize if not overcome this issue and provide less-impacting experimental conditions for their production. A less studied but very promising approach concerns the development of pot-economical processes, in which two or more reactions take place in the same reaction vessel. The advantage of this approach is twofold: on the one hand it significantly reduces the amount of chemicals required to synthesize and purify a target product, on the other it minimizes the total time required to obtain it. Clearly, the process must be carefully designed in order to avoid yield decreases due to side reactions.In this contribution, the rational design of symmetrical and unsymmetrical substituted phthalocyanines by means of pot-economical approaches in solution will be shown and discussed, along with an estimation of the environmental and economic impact with respect to the related conventional procedures. Examples will be shown both of derivatization of already formed macrocycles, following a “late-stage functionalization” approach [8], and of derivatization of phthalonitriles followed by in-situ metal-templated cyclotetramerization. Furthermore, their optical and electrochemical characterization will be shown, discussed and compared with each other by relating the obtained data to their different chemical structures. Finally, examples of their implementation in the field of organic optoelectronics, with a focus on perovskite solar cells, will be presented. D. Li et al CrystEngComm 2018, 20, 2749–2758.D. Li, et al RSC Adv. 2021, 11, 31226–31234.D. Langerreiter et al Angew. Chem. Int. Ed. 2022, 61, e202209033.A. Shaabani et al Dyes Pigm. 2007, 74, 279–282.D. Villemin et al Molecules 2001, 6, 831–844.A.C.S. Gonzalez et al. J. Porphyr. Phthalocyanines 2020, 24, 947–958.Y. Saito et al Chem-NanoMat 2015, 1, 92–95.G. Zanotti et al ChemPlusChem 2020, 85, 1–12

Light-responsive Polymers: Developments in Drug Delivery Systems

Abstract: Photoresponsive polymers have emerged as innovative tools in the domain of drug delivery, presenting advanced solutions for controlled and targeted release of therapeutic agents. This review explores recent advances in the design and application of photoresponsive polymers, focusing on their pivotal role in light-triggered drug delivery systems. It also encompasses organic synthesis methodologies, key advancements in polymer design, and the integration of photoresponsive elements into drug carriers. Moreover, this review also focuses on the applications, challenges, and future prospects, providing a comprehensive overview of the evolving landscape of light-responsive drug delivery technologies. The information about the synthesis presented herein aims to contribute to the understanding and advancement of this dynamic field, offering insights for researchers and practitioners engaged in the development of next-generation drug delivery systems.

Synthesis of New Isoxazolidine Derivatives Utilizing the Functionality of N-Carbonylpyrazol-Linked Isoxazolidines.

Using Ni(II) as the catalyst, electron-deficient 3,5-dimethylacryloylpyrazole olefin was reacted with C,N-diarylnitrones alone for 10 min to prepare novel five-member heterocyclic products, 4-3,5-dimethylacryloylpyrazole isoxazolidines with 100% regioselectivity and up to 99% yield. And then, taking these cycloadducts as substrates, six kinds of derivatization reactions, like ring-opening, nucleophilic substitution, addition-elimination and reduction, were studied. Experimental results showed that all kinds of transformations could obtain the target products at a high conversion rate under mild conditions, a finding which provided the basic methods for organic synthesis methodology research based on an isoxazolidine skeleton.

Tungsten Oxide Dispersed on Silica as Robust and Readily Available Oxo/Imido Heterometathesis Catalyst.

Continuing our investigation of catalytic oxo/imido heterometathesis as novel water-free method for C=N bond construction, we report here the application of classical transition metal oxides dispersed on silica (MOx/SiO2, M=V, Mo, W) as cheap, robust and readily available alternative to the catalysts prepared via Surface Organometallic Chemistry (SOMC). The oxide materials demonstrated activity in heterometathetical imidation of ketones, WO3/SiO2 being the most efficient. We also describe a new well-defined supported W imido complex (≡SiO)W(=NMes)2(Me2Pyr) (Mes=2,4,6-Me3C6H2, Me2Pyr=2,5-dimethylpyrrolyl) and characterize it with SOMC protocols, which allowed us to identify the position of W on the oxo/imido heterometathesis activity scale (Mo<W<Ta) and showed that W in fact provides an optimal balance between activity and stability. Noteworthy, the performance of WO3/SiO2 was only slightly inferior to that of the SOMC analog enabling the efficient synthesis of a broad range of ketimines hardly accessible by classical methods, in most cases W being a competitive and robust alternative to the most active albeit highly sensitive Ti imido systems. Combined with the availability of the catalyst, this facilitates a more widespread application of heterometathesis methodology in organic synthesis including potential larger scale applications.

Synthesis and Biological Evaluation of Novel Amino and Amido Substituted Pentacyclic Benzimidazole Derivatives as Antiproliferative Agents.

Newly designed pentacyclic benzimidazole derivatives featuring amino or amido side chains were synthesized to assess their in vitro antiproliferative activity. Additionally, we investigated their direct interaction with nucleic acids, aiming to uncover potential mechanisms of biological action. These compounds were prepared using conventional organic synthesis methodologies alongside photochemical and microwave-assisted reactions. Upon synthesis, the newly derived compounds underwent in vitro testing for their antiproliferative effects on various human cancer cell lines. Notably, derivatives 6 and 9 exhibited significant antiproliferative activity within the submicromolar concentration range. The biological activity was strongly influenced by the N atom's position on the quinoline moiety and the position and nature of the side chain on the pentacyclic skeleton. Findings from fluorescence, circular dichroism spectroscopy, and thermal melting assays pointed toward a mixed binding mode-comprising intercalation and the binding of aggregated compounds along the polynucleotide backbone-of these pentacyclic benzimidazoles with DNA and RNA.

Recent Strategies in the Nucleophilic Dearomatization of Pyridines, Quinolines, and Isoquinolines.

Dearomatization reactions have become fundamental chemical transformations in organic synthesis since they allow for the generation of three-dimensional complexity from two-dimensional precursors, bridging arene feedstocks with alicyclic structures. When those processes are applied to pyridines, quinolines, and isoquinolines, partially or fully saturated nitrogen heterocycles are formed, which are among the most significant structural components of pharmaceuticals and natural products. The inherent challenge of those transformations lies in the low reactivity of heteroaromatic substrates, which makes the dearomatization process thermodynamically unfavorable. Usually, connecting the dearomatization event to the irreversible formation of a strong C-C, C-H, or C-heteroatom bond compensates the energy required to disrupt the aromaticity. This aromaticity breakup normally results in a 1,2- or 1,4-functionalization of the heterocycle. Moreover, the combination of these dearomatization processes with subsequent transformations in tandem or stepwise protocols allows for multiple heterocycle functionalizations, giving access to complex molecular skeletons. The aim of this review, which covers the period from 2016 to 2022, is to update the state of the art of nucleophilic dearomatizations of pyridines, quinolines, and isoquinolines, showing the extraordinary ability of the dearomative methodology in organic synthesis and indicating their limitations and future trends.

Front Cover Picture: Harnessing the Power of the De Mayo Reaction: Unveiling a Photochemical and Photocatalytic Masked [2+2] Methodology for Organic Synthesis (Adv. Synth. Catal. 2/2024)

Front Cover Picture: Harnessing the Power of the De Mayo Reaction: Unveiling a Photochemical and Photocatalytic Masked [2+2] Methodology for Organic Synthesis (Adv. Synth. Catal. 2/2024)

Progress of Polycyclic Boron-Doped Molecular Carbons

Molecular carbons, namely molecular cutout of carbon materials, are of importance for understanding accurate structures of carbon allotropes and developing functional π-electron materials. Doping the boron atoms into π-conjugated skeletons of molecular carbons enables the construction of boron-doped molecular carbons (BMCs), further leading to new chemistry and attractive material systems, which are distinct from carbon-based and other heteroatom-doped molecular carbons. Herein, the bottom-up organic synthesis methodologies have been employed to synthesize BMCs that feature the boron atoms at the edge or in the center of π-skeletons. They have not only amazing topological structures and good stability but also intriguing photophysical and electronic properties. Moreover, they have sufficient Lewis acidity and can coordinate with Lewis bases to form Lewis acid–base complexes, which exhibit stimuli-responsive functions. Notably, some of these BMCs can be utilized in the fields of organic reactions, optical and electronic devices, as well as supramolecular chemistry and photothermal materials. In this short review, we aim to highlight the design and synthetic strategies of polycyclic BMCs, and their unique physical properties and practical applications.

Streamlining the synthesis of amides using Nickel-based nanocatalysts

The synthesis of amides is a key technology for the preparation of fine and bulk chemicals in industry, as well as the manufacture of a plethora of daily life products. Furthermore, it constitutes a central bond-forming methodology for organic synthesis and provides the basis for the preparation of numerous biomolecules. Here, we present a robust methodology for amide synthesis compared to traditional amidation reactions: the reductive amidation of esters with nitro compounds under additives-free conditions. In the presence of a specific heterogeneous nickel-based catalyst a wide range of amides bearing different functional groups can be selectively prepared in a more step-economy way compared to previous syntheses. The potential value of this protocol is highlighted by the synthesis of drugs, as well as late-stage modifications of bioactive compounds. Based on control experiments, material characterizations, and DFT computations, we suggest metallic nickel and low-valent Ti-species to be crucial factors that makes this direct amide synthesis possible.

Harnessing the Power of the De Mayo Reaction: Unveiling a Photochemical and Photocatalytic Masked [2+2] Methodology for Organic Synthesis

AbstractIn 1962, Paul J. de Mayo initially described the photochemical reaction involving 1,3‐diketones and double bonds, resulting in the formation of 1,5‐diketones. Since then, this reaction has been extensively utilized for the synthesis of a wide range of fascinating natural products. Over time, this synthetic methodology has been applied to various carbonyl systems, including locked enol‐tautomers of diketones, β‐keto esters, and β‐enaminones. Additionally, it has found application in other unsaturated systems such as allenes and alkynes. In this review article, we provide a comprehensive overview of the classical de Mayo reaction, highlighting its scope and potential. Furthermore, we focus on recent advances achieved through photocatalytic conditions. Special emphasis is placed on the regioselectivity of the process and the underlying reaction mechanism, particularly within the context of photocatalysis.

Halide‐Triel Bonds between R3SiX (X=F, Cl and Br) and TrY3 (Tr=Al, B and Ga)

AbstractHalide‐triel bonds between halosilane donors and alane/borane/gallane acceptors are investigated considering 24 model complexes using quantum chemical calculations. Nature and strength of Si−X….Tr interactions (X=F, Cl, Br and Tr=Al, B, Ga) binding these complexes has been studied using Electrostatic Potential (ESP), Quantum Theory of Atoms in Molecules (QTAIM), Natural Bond Orbital (NBO), and Energy Decomposition Analysis (EDA) techniques. Basis Set Superposition Error (BSSE) corrected binding energy of the complexes ranges from −3.19 to −29.40 kcal mol−1. QTAIM parameters Laplacian and the total electron density at the Bond Critical Points (BCPs) indicate that the halide‐triel bonds studied here are largely electrostatic in nature (closed‐shell interactions); this has also been revealed through ESP analysis and EDA scheme. In addition, role of charge transfer in these halide‐triel bonds has also been established through NBO analysis. Two charge transfer orbital interactions are responsible for the primary interaction Si−X….Tr: and σ(Si−X) . EDA analysis identifies electrostatic term as the biggest contributor towards the binding of the complexes followed by the polarisation and dispersion terms in most of the complexes. Results of this study have relevance in the Si−F bond activation methodology in organic synthesis.

Retrosynthesis

The American chemist Elias James Corey was awarded the 1990 Nobel Prize in chemistry for developing the theoryand methodology of organic synthesis. He called his method “retrosynthetic analysis,” a technique for simplifying thesynthesis of large complex molecules. He worked out and described in detail a new and fruitful systematic approach tosynthetic chemistry. He has synthesized over 100 substances, including ginkgolide B (a compound extracted from theginkgo tree and used experimentally to treat asthma) and prostaglandins (hormone-like compounds used to induce laborand treat infertility). Corey—Nobel Prize for Retrosynthetic Analysis

Transition-Metal-Free Approach to Acridone Derivatives by TBHP-Promoted Oxidative Annulation of Isatins with Arynes

A tert-butyl hydroperoxide-promoted oxidative annulation reaction of isatins with 2-(trimethylsilyl)aryl triflates for the convenient synthesis of acridone derivatives has been established. Mechanistic investigation suggested that the reaction may proceed via consecutive Baeyer-Villiger-type rearrangement followed by an intermolecular cyclization. This synthetic approach offers several advantages, including broad substrate scope, good functional group tolerance, and simplicity of operation. Additionally, successful late-stage modification of the obtained compounds was achieved, expanding the application potential of this methodology in organic synthesis.

One pot synthesis of some novel indole derivatives and their antimicrobial activity

&lt;p&gt;In this study, we describe the creation of a straightforward and incredibly effective protocol for the synthesis of new 3-Substituted indole derivatives. This multicomponent reaction involved indole, acetylacetone and active aldehyde derivatives in the presence of ethanol as solvent followed by acetonitrile as a base. We go through current developments in organic synthesis methodology for multicomponent reactions that produce substituted indole derivatives with a more environmentally friendly base catalytic condition, as well as the applications that go along with them. FT-IR, 1H-NMR and MS are used to characterise the synthesized compound of indole derivatives. Antibacterial activity of synthesized compounds has also been done. &lt;/p&gt;

Silver-Catalyzed 1,3-Aza-Benzyl Migration of Allyl Alcohol.

Carbon migration of alkenyl alcohols has been recognized as an increasingly viable methodology in organic synthesis. Herein, we disclose a silver-catalyzed 1,3-aza-benzyl migration of allyl alcohols by utilizing chelation-assisted selective cleavage of an unstrained C(sp3)-C(sp3) bond. This approach provides an available, efficient, high atom-economic, and environmentally benign procedure, leading to alkylation products with broad substrate scopes and excellent yields. The migration proceeds via a one-pot, two-step process involving a free-state alkyl metal species.

Palladium-Catalyzed Cascade Cyclization/Alkylation of Oxime Ethers: Assembly of 4-Alkylisoxazoles by "Chain-Walking" Strategy.

A reliable and efficient palladium-catalyzed cascade cyclization/alkylation of oxime ethers with unactivated alkenes is described, affording a whole variety of structurally diverse isoxazole derivatives in moderate to good yields with excellent functional group compatibility. Ionic liquid [Aeim]Br not only acts as an environmentally friendly solvent but also acts as an accelerating agent to provide excess bromine source to eliminate bromomethane from oxime ethers. More importantly, the use of "chain-walking" strategy provides a novel methodology in organic synthesis to rapid generation of molecular complexity from readily available starting materials.