Letters in Organic Chemistry - Volume 22, Issue 2, 2025

Michael addition reaction is widely accepted as the most important reaction for making carbon-carbon bonds in the synthesis of organic compounds. In this reaction, an enone is attacked by a nucleophile in a conjugated manner across a carbon-carbon double bond. The present work reported the Michael reaction of indole with α,β-unsaturated ketones via alkylation to yield 3-(3-oxoalkyl) indole or β-indolyl ketones. Naturally available orange juice has been demonstrated to be an efficient green catalyst for the Michael addition reaction of indoles with various cyclic and acyclic unsaturated ketones. The products were characterised by ¹H NMR spectroscopy and compared with literature. This one-step, simple process has afforded the 3-indolyl carbonyl compounds in short reaction times and excellent yields at room temperature. The present method developed an inexpensive synthetic process to prepare substituted indoles in a simple and eco-friendly way.

Piperazines, a class of heterocyclic compounds, have garnered significant attention in the field of organic synthesis due to their diverse pharmacological activities and widespread applications in medicinal chemistry. This review provides a comprehensive overview of the recent advancements in the synthesis of piperazines, highlighting innovative methodologies, novel reagents, and green synthesis approaches adopted by researchers. The synthesis of piperazines has witnessed remarkable progress, with a focus on developing efficient and sustainable synthetic routes. Various strategies, such as transition-metal-catalyzed reactions, microwave-assisted synthesis, photo-redox reactions, and bio-inspired methods, have emerged as powerful tools for constructing piperazine scaffolds. The review also encompasses discussions on the stereochemistry and regioselectivity issues associated with piperazine synthesis, shedding light on the intricacies of achieving specific substitution patterns. The impact of newly synthesized piperazines in drug discovery and development is also explored, emphasizing the therapeutic potential of these compounds in various disease areas. In conclusion, this review provides a comprehensive and up-to-date account of the recent advancements in piperazine synthesis, offering insights into the current state of the field and guiding future research directions. The integration of innovative methodologies and the exploration of sustainable practices underscore the ongoing efforts to streamline the synthesis of piperazines, contributing to the expansion of their applications in medicinal chemistry and related disciplines.

Nanocatalysis is the newest invention in the area of synthetic chemistry that has changed the process of chemical transformation. The nanocatalysts have various benefits as compared to traditional catalysts, such as simple and economical methods of synthesis, high surface-to-volume ratio, large number of active sites, excellent selectivity, increased stability, rapid recovery, and recyclability. In recent years, nanomaterials have been extensively employed in the production of heterocyclic moieties. This study intends to emphasize the function of distinct nanocatalysts in the synthesis of various nitrogen-containing heterocyclic compounds. An update on the catalytic efficiency of different nanocatalysts, such as magnetic nanocatalysts, nanomixed metal oxides, core-shell nanocatalysts, nano-supported catalysts, and graphene-based nanocatalysts for the production of heterocycles has been provided in this article.

In the six-membered heterocyclic compound piperazine, two nitrogen atoms are positioned within the ring at 1 and 4 positions. Numerous studies have shown that piperazine has the potential to be a useful pharmacophore in many harmful pharmacological conditions such as microbiocidal, anti-inflammatory, anticancer, antioxidant, etc. In this present review, we highlighted the synthetic protocols for piperazine and its analogs, as well as the synthetic protocol for piperazine via rearrangement reaction, which have been adopted in recent years. The study also involved a listing of several patents (granted), which comprised important work on piperazine and its derivatives. Among all the methods, the most commonly adopted synthetic methods included the synthesis of piperazine analogs by diza-cope, hydrolytic, mumm, multi-component, ugi-smiles, [2+3]-stevens, aza-Wittig, Curtius, Schmidt rearrangement reactions, etc. These synthetic protocols have also been compared based on different reaction conditions, feasibility, and economy to help the researchers in designing their work.

Oxadiazole is an organic compound featuring a heterocyclic ring housing carbon, oxygen, and nitrogen atoms. Due to their heightened stability in biological environments, oxadiazole rings exhibit significant biological activities, effectively addressing health challenges like infectious diseases and chronic conditions in medicinal chemistry. The main objective of this review is to discuss various synthetic approaches related to oxadiazole and its derivatives, along with their biological activities. The diverse reactivity positions oxadiazole as a valuable building block in organic synthesis, with derivatives exhibiting promising pharmacological activities. It involves a systematic literature review, critical analysis, and synthesis of existing research. This review comprises the ever-expanding chemical knowledge but also holds significant implications for drug development. The various synthetic approaches, such as Suzuki-Miyaura, Stille coupling [3+2] cycloaddition reaction, and many more methods used for the synthesis of oxadiazole through different schemes, have been discussed thoroughly. This review also concisely associated the pharmacological activities of new oxadiazole and its derivatives, such as prenoxdiazine, dapagliflozin, nesapidil, pleconaril, and so on. This review highlights the importance of continued research into the structure-activity relationships of oxadiazole derivatives, paving the way for developing novel and more potent therapeutic agents.

This research work has explored the application of a magnetic catalyst composed of core shell nanoparticles [Fe3O4@SiO2@CS@EDTA/Co(II)], known as NCM@EDTA/Co(II), in the conversion of various alcohols containing electron-donating or electron-withdrawing groups into their respective secondary or primary amine derivatives. The investigation has focused on optimizing reaction conditions by considering factors, such as the inclusion of a base, duration of reaction time, reaction temperature, catalyst quantity, and choice of transition metal, in order to determine the optimal parameters. The most favorable outcomes have been achieved by using 0.2 mmol of catalyst per 1 mmol of substrate under reflux conditions for a duration ranging from 3 to 24 hours. The reaction has demonstrated high efficiency, with the catalyst's easy separation via an external magnetic field, stability, and recyclability, highlighting its potential applications in chemistry and industrial environments.

In the present investigation, we report the multistep synthesis of pyranoquinolinyl acrylic acid (PQAA)/furoquinolinyl acrylic acid (FQAA) diastereomers via perkin condensation and reduction, followed by one-pot inverse electron demand Diels-Alder reaction among 2,3 dihydropyran, amine, and aromatic aldehyde mediated by indium (III) triflate in 1-butyl-3-methylimidazolium tetrafluoroborate (In(OTf)3/ [bmim]BF4) at 25.0-27.0°C. The pyranoquinolinyl acrylic acid/furoquinolinyl acrylic acid diastereomers were evaluated for their in vitro antibacterial activity. Molecular docking studies were carried out employing iGEMDOCK software to evaluate the mode of binding between UDP-N-acetylenolpyruvoyl glucosamine reductase and PQAA adducts. All the pyranoquinolinyl/furoquinolinyl/tetrahydro-cyclopentaquinolinyl acrylic acid (PQAA/FQAA/CPQAA) diastereomers were thoroughly characterized by NMR, FT-IR, mass spectral, and CHN analysis.