Organic Chemistry Research Research Articles

Recent Advances on the Construction of Functionalized Indolizine and Imidazo[1,2-a]pyridine Derivatives.

Indolizines and imidazo[1,2-a]pyridines are commonly found in natural products, synthetic drugs, and bioactive molecules. These two types of derivatives possess good antibacterial, antiparasitic, anticancer activities, and so on. The functionalization of indolizines and imidazo[1,2-a]pyridines has always been a hot topic in organic chemistry research and has made significant progress. In recent years, our group has been dedicated to developing diverse synthetic methods for the preparation of such important compounds. 1) We have developed diverse C-H functionalization reactions for efficient modification of the parent indolizines and imidazo[1,2-a]pyridines. 2) A variety of cycloaddition reactions were established for the construction of indolizine and imidazo[1,2-a]pyridine derivatives from simple raw materials. 3) We have developed intriguing deconstruction-functionalization reactions of indolizines, enabling the reorganization of heterocyclic frameworks. This paper outlines our group's latest advancements in constructing structurally diverse indolizine and imidazo[1,2-a]pyridine derivatives. We hope that this work will offer valuable insights and inspiration for the ongoing research in the field of N-heterocyclic compounds.

Recent Advances in the Multicomponent Synthesis of Heterocycles using Thiosemicarbazide

AbstractThis review provides an overview of the recent advances in the synthesis of diverse heterocyclic compounds using thiosemicarbazide as a key building block via multicomponent reactions. Thiosemicarbazide is a versatile reagent that has gained significant attention in organic synthesis due to its ability to participate in diverse multicomponent reactions for the efficient and sustainable construction and assembly of novel bioactive molecules and pharmaceuticals. This review discusses the potential applications and future directions in this rapidly evolving area of research. It provides valuable insights into the innovative approaches for the synthesis of heterocycles using thiosemicarbazide, showcasing its significance in modern organic chemistry research. In summary, this review provides an overview of the current state of the art, highlighting the use of thiosemicarbazide in the synthesis of novel heterocyclic compounds reported between 2015 and early 2024.

Application of 2-Azabicyclo[2.2.1]Hept-5-En-3-One (Vince Lactam) in Synthetic Organic and Medicinal Chemistry.

2-Azabicyclo[2.2.1]hept-5-en-3-one (Vince lactam) is known to be a valuable building block in synthetic organic chemistry and drug research. It is an important precursor to access of some blockbuster antiviral drugs such as Carbovir or Abacavir as well as other carbocyclic neuraminidase inhibitors as antiviral agents. The ring C=C bond of the Vince lactam allows versatile chemical manipulations to create not only functionalized γ-lactams, but also γ-amino acid derivatives with a cyclopentane framework. The aim of the current account is to summarize the chemistry of Vince lactam, its synthetic utility and application in organic and medicinal chemistry over the last decade.

Pt/CB-Catalyzed Chemoselective Hydrogenation Using In Situ-Generated Hydrogen by Microwave-Mediated Dehydrogenation of Methylcyclohexane under Continuous-Flow Conditions

Hydrogen gas (H2) has attracted attention as a next-generation clean energy source. Its efficient and safe preparation and utilization are crucial in both the industry and organic chemistry research. In this study, a Pt/CB (platinum on carbon bead)-catalyzed MW-mediated continuous-flow hydrogenation reaction was developed using methylcyclohexane (MCH) as the reducing agent (hydrogen carrier). Alkynes, alkenes, nitro groups, benzyl esters, and aromatic chlorides were chemoselectively hydrogenated using Pt/CB under MW-assisted continuous-flow conditions. This methodology represents a safe and energy-efficient hydrogenation process, as it eliminates the need for an external hydrogen gas supply or heating jackets as a heating medium. The further application of MW-mediated continuous-flow hydrogenation reactions is a viable option for the efficient generation and utilization of sustainable energy.

A Decennial Update on the Applications of Trifluroacetic Acid

Abstract: Since its discovery at the beginning of the 20th century, trifluoroacetic acid, commonly known as TFA, has seen extensive application in organic synthesis both as a solvent and as a catalyst/ reagent. TFA can be used to facilitate a wide variety of chemical transformations, including rearrangements, functional group deprotections, condensations, hydroarylations and trifluoroalkylations, among others. The decennial mini-review examines key TFA synthetic applications from the middle of 2013 to the present, providing the organic chemistry research community with an opportunity to delve deeply into the numerous and varied applications of this strong acid, water-miscible, and low boiling point reagent.

Transition‐Metal Free Arylation of Therapeutically Important Heterocycles

AbstractThe transition‐metal‐free synthesis of organic compounds especially heterocycles is in resonance with one of the twelve principles proposed by Prof. Paul Anastas in his renowned work towards the sustainable development of green chemistry. Traditional‐metal‐catalyzed reactions often involve expensive or toxic metal catalysts, and there is a growing interest in developing more sustainable and environmentally friendly methods. The arylation of heterocycles is an important area of research in organic chemistry, particularly in the synthesis of biologically active compounds and pharmaceuticals. Arylation of heterocycles at different positions enhances the potency and stability of biologically and pharmaceutically important scaffolds. In this review, an overview of the synthetic protocols developed for the arylation of a variety of heterocyclic compounds including, pyrroles, pyridines, thiophene, indole, oxindoles, purines, xanthene, etc. has been described.

Quinoline based viologen as a multifunctional organic material – From crystal structures to photophysical and electrochemical properties, and application in DNA sensing and bioimaging

Developing new multifunctional organic materials is one of the current themes of research in organic materials chemistry. The class of N,N'-dialkylated bis-pyridinium compounds, namely, the viologens have been proven to offer such multifunctional materials. Herein, syntheses and crystal structure elucidation of trans-1,2-bis(4-quinolinyl)ethylene (BQE) and analogous N,N-dimethylated trans-1,2-bis(4′-quinolinium)ethylene (M2BQE) are discussed with their multifaceted materials properties. Two different crystal structures with significantly different molecular structures, namely, BQE and BQE⋅2H2O were obtained by tuning the solvent of crystallization. M2BQE showed a bathochromic shift both in its absorption by ∼ 3300 cm−1 and in emission by ∼2900 cm−1 in compared to BQE, which is the effect of quaternization. Large Stokes shifts were observed for both the BQE (∼8500 cm−1) and M2BQE (∼8050 cm−1). Both compounds showed two-step reduction events in cyclic voltammetry, of which the first steps were reversible. The pH dependent absorption and emission properties of BQE have been explored which revealed the stronger effect by methylation than protonation. M2BQE exhibited selective binding to ct-DNA, as confirmed by selective quenching of emission intensity, over AMP and ATP. Furthermore, both the BQE and M2BQE displayed very intriguing features in bioimaging by intracellular co-localization in HeLa cells. While BQE is predominantly localizes in lysosomes over mitochondria, M2BQE dication, on the other hand, explicitly localizes in mitochondria.

Computational Mapping of Indian Organic Chemistry Research: An Analysis with Data Mining Tools

Computational Mapping of Indian Organic Chemistry Research: An Analysis with Data Mining Tools

Applications of Transition Metal-Catalyzed ortho-Fluorine-Directed C-H Functionalization of (Poly)fluoroarenes in Organic Synthesis.

The synthesis of organic compounds efficiently via fewer steps but in higher yields is desirable as this reduces energy and reagent use, waste production, and thus environmental impact as well as cost. The reactivity of C-H bonds ortho to fluorine substituents in (poly)fluoroarenes with metal centers is enhanced relative to meta and para positions. Thus, direct C-H functionalization of (poly)fluoroarenes without prefunctionalization is becoming a significant area of research in organic chemistry. Novel and selective methodologies to functionalize (poly)fluorinated arenes by taking advantage of the reactivity of C-H bonds ortho to C-F bonds are continuously being developed. This review summarizes the reasons for the enhanced reactivity and the consequent developments in the synthesis of valuable (poly)fluoroarene-containing organic compounds.

Making it organic: the Garg Lab’s approach to excellence in research while teaching the next generation of chemists

Making it organic: the Garg Lab’s approach to excellence in research while teaching the next generation of chemists The Garg Lab, nestled within UCLA’s Chemistry and Biochemistry department, is a pioneering force in organic chemistry research. Under the guidance of Professor Neil Garg, the Lab has achieved breakthroughs in synthetic methodologies, notably contributing to the total synthesis of complex molecules like lissodendoric acid and (-)N-Methylwelwitindolinone C isonitrile. This accomplishment showcases the Lab’s commitment to advancing the field.

An Overview of Preparation for Different Azo Compounds

Azo compounds are a class of organic materials that have the group R-N=N-R' where the substitution group R and R' are aromatic or heterocyclic sides. The azo compounds have a variety of applications including dyes, pigments, and pharmaceuticals. The preparation and characterization of different azo compounds is an important area of research in organic synthesis. The azo compound synthesis typically involves the diazotization process for coupling between an aromatic amine and another aromatic compound containing an activating group such as -OH, -NH2, or -NR2. The reaction conditions must be carefully controlled to prevent side reactions, such as the formation of unwanted byproducts. Once synthesized, azo compounds can be characterized using a variety of techniques including UV-Vis spectroscopy, NMR spectroscopy, and mass spectrometry. UV-Vis spectroscopy is a commonly used technique for characterizing azo compounds. The absorption spectrum of an azo compound typically exhibits a strong absorption band in the visible region due to the delocalized π-electrons in the azo group. While in FTIR, the loss of the amine peak and showing a weak peak at about 1550 cm−1forthe (N=N) group, indicates the presence of Azo. The preparation and characterization of different azo compounds is a significant field of research in organic chemistry, which are applied as acid and base indicators, food coloring, optical switches, liquid crystal and in medicine. By carefully controlling the synthesis conditions and using a variety of characterization techniques, researchers can gain a better understanding of the properties and applications of these compounds.

Contribution to Pharmacy/pharmacist Education through Writing

The Education Award of the Pharmaceutical Society of Japan (PSJ) was conferred for "Contribution to pharmacy/pharmacist education through writing on organic chemistry." The award-winning activities were described in three parts section 1-3. Section 1 Importance of Research and Education in Organic Chemistry: In this section, it is explained that organic chemistry serves as the fundamental basis for a wide range of natural science disciplines studied in pharmaceutical departments. It emphasizes that having a solid foundation in organic chemistry is essential for pharmacists to understand pharmaceuticals. This knowledge contributes significantly in healthcare settings such as team-based medical care (interprofessional cooperation) with physicians and nurses, as well as in interactions with patients, providing a unique contribution that other professions cannot achieve. Section 2 Two Serial Articles Written on Organic Chemistry: This part mentions two serial articles that are beneficial for pharmacists and pharmaceutical researchers. These articles aimed to broaden specialized knowledge and provide practical information, contributing to pharmaceutical education and professional training for pharmacists. Section 3 Publication of New Organic Chemistry Textbooks: In this section, the introduction of textbooks and reference books in the field of organic chemistry for pharmaceutical education is highlighted. These educational materials were published to offer valuable information to pharmaceutical students and aspiring pharmacists, enhancing their expertise. These three writing activities significantly contributed to pharmaceutical education and the improvement of the professional work of pharmacists.

Reaction Space Charting as a Tool in Organic Chemistry Research and Development

AbstractThe chemical and reaction spaces are incredibly vast and special procedures are required to study them. Their complex and multiparametric nature encompass myriads of compounds and interactions and endless modifications involving the distinct impact of relevant variables (temperature, solvent, stoichiometry, etc.). This often calls for the design, collection, and analysis/interpretation of large datasets. Reaction charting, the systematic scanning, description, analysis, and guided modifications of a given process, stands as the most promising approach. It offers fast and accurate solutions as well as expanding the knowledge about the systems. This deeper understanding enables reliable predictions, improvement of the productivity (yields, scope), eventually leading to sustainable, economic, and safe applications. The present review introduces the topic, analyzing selected examples and recent advancements in different organic chemistry‐related fields. The covered methodologies range from classical experimentation modifying one factor at a time, to Design of Experiments and more modern computational approaches involving Machine Learning and Artificial Intelligence. In this way, the impact of charting in process development, biological and medicinal chemistry, catalysis, reaction discovery and computational methods is accounted. Finally, the conclusion/outlook section gives a general appraisal and a prospect on the future implementation of the methodology.

(Invited) Electrocatalytic Radical-Polar Crossover Hydrofunctionalization of Alkenes

Due to the unique reactivity of open-shell intermediates, the development of catalytic transformations driven by single-electron transfer (SET) has been an area of intense research in organic chemistry. In particular, the employment of unconventional means of activation, including photoredox catalysis and electrocatalysis, has provided unique entry to single-electron reactivities and led to new solutions to challenging synthetic problems that are not readily addressed using existing tools.We disclose a general electrocatalytic hydrofunctionalization by utilizing a wide range of alkenes. The integration of the two involves an electrochemically instigated cobalt-hydride-catalyzed radical-polar crossover of alkenes that enable the generation of key cationic intermediates, which could readily be entrapped by challenging nucleophiles. We highlight the importance of precise control of the reaction potential by electrochemistry in conjunction with the decisive role of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as the co-solvent to obtain optimal and exclusive chemoselectivity.In addition, we develope an electrocatalytic method for intramolecular hydroamination of allylic sulfonamides to access azetidines. The merger of cobalt catalysis and electricity enables regioselective generation of key carbocationic intermediates, which could directly undergo intramolecular C-N bond formation. The mechanistic investigations including electrochemical kinetic analysis suggest that the catalyst regeneration by nucleophilic cyclization is involved in the rate-determining step (RDS) of our electrochemical protocol and highlight the ability of electrochemistry in providing ideal means to mediate catalyst oxidation.

Ultrasonic Assisted Three Component Synthesis of 3-Cyano-pyridine-2(1H)-ones

The requirements of sustainability and the green chemistry principles have prompted organic chemistry researchers to come up with novel methods for the synthesis of organic compounds that require minimum energy consumption and pose lesser environment harm. Ultrasonication of reaction mixtures is one such methodology. High frequency sound waves are known to emit energy that is utilized in product generation. Attempts were made to synthesize 2-pyridone derivatives using ultrasonication assisted method of synthesizing 3-cyano-pyridine-2(1H)-one starting from a three component one pot reaction. The reaction between cyanoacetamide, aromatic ketones and substituted aromatic aldehydes in the presence of NaOH as base yielded 4,6-diaryl-2-oxo-1,2-dihydropyridine-3-carbonitrile derivatives as a result of one-pot multicomponent reaction. The synthesized 4,6-diaryl-2-oxo-1,2-dihydropyridine-3-carbonitrile derivatives were characterized by 1H NMR, 13C NMR, HRMS and FTIR spectra. Ultrasonication has been found to significantly reduce reaction time, enhance reaction rate and yield compared to conventional heating methods.

Selective Functionalizations of Cycloalkene‐Fused β‐Lactams and their Transformations into Densely‐Substituted Three‐Dimensional Molecular Entities

AbstractHighly‐functionalized, three‐dimensional molecules have had an increasing impact in synthetic organic chemistry and pharmaceutical research over the past decades. Their syntheses and the development of novel synthetic approaches towards versatile, small molecules with chemical and structural diversity have generated great interest. We have designed various selective and stereocontrolled methodologies for the functionalization of cycloalkene‐fused β‐lactams with a common C−C bond, as three‐dimensional, functionalized scaffolds, involving the transformation of their ring olefin bond. The synthetic methodologies developed to access various pharmacologically interesting derivatives with multiple chiral centers might be valuable protocols for the preparation of other classes of organic compounds as well.

Quinolone Tethered 1,2,3-triazole Conjugates: Design, Synthesis, and Computational Docking Studies on New Heterocycles as Potent Antimicrobial Targets

Abstract: The synthesis and biological properties of molecules simultaneously comprising various heterocycles, such as fused 2-quinolones and 1,2,3-triazoles, have been evaluated as a part of our ongoing research in medicinal and organic chemistry. We were successful in developing a synthetic procedure for 1,2,3-triazole substituted quinolone derivatives. Infrared, proton, and carbon nuclear magnetic resonance, mass spectroscopy and elemental analysis were used to characterise the structures of the recently synthesised triazole derivatives. From screening results, all the compounds demonstrated increased antibacterial action against both Gram-positive and Gram-negative bacteria. Moreover, 1,2,3-triazoles linked to tert-butyl benzyl (3a), trifluoromethyl benzyl (3b), 3-chlorobenzyl (3c), 4- hydroxy-3-nitrobenzyl (6b), 4-hydroxy-4-trifluoromethylbenzyl (6d), and 4-hydroxy-2,4- difluorobenzyl (6e) compounds showed promising antibacterial and antifungal activities with MICs values of 1.07-4.33 μg/mL. The prepared ligand 4-hydroxy-2,4-difluoro benzyl-1,2,3-triazole (6e) exhibited the highest docking score of -6.34 kcal/mol and showed interacting amino acid residues ArgB:1122, MetB:1121, AspB:1083, TryB:1087, AlaB:1118, AlaB:1120, GluB:1088, GlyB:1117, SerB:1084, and AlaB:1119 within the active site of 2XCT. Final scaffolds were further evaluated for their ADMET and physicochemical properties by using ADMETlab2.0 and SwissADME web servers as good oral bioavailability drugs.

Transforming organic chemistry research paradigms: Moving from manual efforts to the intersection of automation and artificial intelligence

Transforming organic chemistry research paradigms: Moving from manual efforts to the intersection of automation and artificial intelligence

Recent Advances in the Synthesis and Antioxidant Activity of Low Molecular Mass Organoselenium Molecules.

Selenium is an essential trace element in living organisms, and is present in selenoenzymes with antioxidant activity, like glutathione peroxidase (GPx) and thioredoxin reductase (TrxR). The search for small selenium-containing molecules that mimic selenoenzymes is a strong field of research in organic and medicinal chemistry. In this review, we review the synthesis and bioassays of new and known organoselenium compounds with antioxidant activity, covering the last five years. A detailed description of the synthetic procedures and the performed in vitro and in vivo bioassays is presented, highlighting the most active compounds in each series.

The Ring‐Opening Reaction of Benzofuran Involving the Cleavage of C−O Bond

AbstractRing‐opening of (di)benzofurans is a significant area of research in organic chemistry, offering versatile and direct synthetic strategies to access valuable functional phenol derivatives. Transition metal catalysis, particularly nickel‐catalyzed reactions, has been extensively explored for the selective cleavage of the C−O bond in (di)benzofuran. Metal‐free methods, such as acid catalysis and strong base‐mediated process, have also emerged as important alternatives. Organometallic reagents, including Grignard and organolithium reagents, play a pivotal role in promoting efficient C−O bond activation. The field of (di)benzofuran ring opening holds great promise for the synthesis of complex molecules with diverse applications in pharmaceuticals, materials science, and fine chemical synthesis. Continued research efforts will pave the way for innovative strategies and broaden the utility of (di)benzofuran derivatives in various fields.