Synthesis Of Heterocycles Research Articles

The Tetrafluoroethylene-Mediated Ring-Closing Metathesis: Enabling Unfavored Reactions.

While ring-closing metathesis (RCM) is a powerful method for constructing medium and large cyclic alkenes, its application to the synthesis of heterocycles faces considerable limitations. For instance, RCM of divinyloxyalkanes does not proceed under the conventional conditions of RCM. The challenge lies in the formation of stable Fischer-type carbene intermediates with heteroatom(s) bound to the carbene carbon, impeding subsequent metathesis. In the present research, we develop a novel reaction system termed "tetrafluoroethylene (TFE)-mediated RCM", which enables the RCM of divinyloxyalkanes. In this system, a divinyloxyalkane and a TFE molecule are converted to the corresponding ring-closing product (cyclic 1,2-dioxyethene) and two molecules of 1,1-difluoroethylene. This method facilitates the construction of six- to eight-membered rings with various functional groups. The addition of TFE has two key effects: thermodynamically, it renders the entire reaction exergonic, while kinetically, it ensures that all ruthenium-carbene intermediates in the catalytic cycle are Fischer-type.

Asymmetric Synthesis of Polycyclic Heterocyclic Compounds via Friedel-Crafts Reaction/Cyclization Reaction Catalyzed by Nickel Catalyst.

The first highly enantioselective asymmetric Friedel-Crafts reaction/cyclization reaction of 5-aminopyrazoles with 3-alkenyloxindoles to afford polycyclic heterocyclic compounds bearing an all-carbon quaternary stereocenter catalyzed by a complex of NiII with the C2-symmetric bipyridine-N,N'-dioxide ligand L12 has been developed. The relevant products with a wide range of substrates and good functional tolerance were obtained in 89-98% yield with 56-99% ee in the presence of 10 mol % Ni(OTf)2 and 11 mol % L12 in DCM at 25 °C. Moreover, an experiment on scaling up the process along with the transformations of the cycloadducts further emphasized the practical application of the synthesis.

Recent Advances in Sequentially Pd-Catalyzed One-Pot Syntheses of Heterocycles

Recent Advances in Sequentially Pd-Catalyzed One-Pot Syntheses of Heterocycles

Cholesterol-Based B-Ring 2H-Pyran: Synthesis and Reaction Mechanism by Using Density Functional Theoretical Study

Abstract: The steroidal B-ring 2H-pyran 2 is synthesized by reacting steroidal B-ring α,β- unsaturated ketone 1 and 2-cyano-N-methylacetamide by refluxing for 18 h in methanol in the presence of a catalyst, i.e., chitosan. The product is obtained with a yield of 67%. The structure of the final product 2 is confirmed by utilizing IR, Mass, 13C and 1H NMR spectra. The reaction mechanism of the steroidal pyran ring formation is explored in this paper. The reaction pathway is described by using FMO analysis and relative energies of starting material, intermediate, and transition states, calculated by using the theoretical method, i.e., DFT with B3LYP/6-31G(d). It is found that two intermediates are formed throughout the reaction, which undergo a respective transition state (TS1 and TS2). The energy barrier of each step of the reaction is also calculated. It is also concluded that the reaction is endothermic. The green synthetic method reported in this study would be very useful for the synthetic and medicinal chemists involved in the synthesis of biologically important pyran ring-containing heterocyclic compounds.

Synthesis, Structure elucidation and characterization of new heterocyclic compound: 2-aminobenzimidazolium-4-carboxybutanoate

Synthesis, Structure elucidation and characterization of new heterocyclic compound: 2-aminobenzimidazolium-4-carboxybutanoate

Ionic Liquids as a Non-conventional Catalyst for the Synthesis of N-heterocycles

Abstract: Ionic liquids (ILs) have emerged as one of the potential alternates of organic solvents in chemistry. Nitrogen-containing heterocyclic compounds are the important structural motifs of some bioactive compounds. A variety of ILs, such as first-generation, second-generation, and thirdgeneration ILs have been used in the synthesis of various types of nitrogen-containing heterocyclic compounds, such as aziridine, indole, pyrrazole, imidazole, oxazole, thiazole, triazole, pyridine, pyrimidine, quinolones, benzodiazapiene and their derivatives. Due to their unique chemical and physical properties, ILs can act as both solvent and catalyst and have contributed towards high efficiency, improved yield and recyclability for the synthesis of heterocyclic skeleton. In this review, the application of ILs in the synthesis of different nitrogen-containing heterocyclic compounds has been discussed.

Candida antarctica lipase B catalyzed condensation reactions: Water mediated chemo-enzymatic synthesis of different heterocycles

Candida antarctica lipase B catalyzed condensation reactions: Water mediated chemo-enzymatic synthesis of different heterocycles

Mechanochemical Synthesis of Carbazole Isomer Phosphors.

The 1H-benzo[f]indole (Bd[f]), a carbazole (Cz) isomer is first reported as the source of Cz-based phosphors in 2020. In this work, the novel carbazole isomers, 1H-benzo[g]indole (Bd[g]) based derivatives, are synthesized by a one-step solvent-free mechanical ball milling reaction, establishing a facile, efficient, and environmentally friendly method for the synthesis of new Cz isomer phosphorescent derivatives with high yields compared to previously reported multi-step solvent-based thermochemical synthesis routes of Bd[f] derivatives with low yields. Six Bd[g] derivatives with different substituents, namely OCH3-Bd, In-Bd, Bn-Bd, F-Bd, Cl-Bd, and Br-Bd, are synthesized, which exhibit distinctly different single-crystal structures and phosphorescent properties. After irradiation with 365nm UV light, Bd[g] derivatives-doped poly (methyl methacrylate) (PMMA) films exhibit photoactivated green room-temperature phosphorescence with ultra-long lifetimes up to 1.65s. Interestingly, the phosphorescence is stable in seawater along with good bactericidal properties, which also provide new candidates for indole-based marine antifoulants. This study demonstrates that mechanical ball milling is an efficient method for the synthesis of benzoindole heterocycles. Bd[g], as new members of the benzoindole family, are new building units to construct carbazole isomer phosphorescent molecules besides Bd[f].

Photoinduced Intramolecular C−N Coupling For The Synthesis Of Azolo[1,2,4]Benzothiadiazines Derivatives

AbstractThis paper explores an original synthesis of novel heterocyclic compounds derived from photoinduced intramolecular coupling reactions, involving the formation of C−N and C−C bonds. Specifically, two classes of compounds were targeted: 4H‐benzo[e]pyrazolo[1,5‐b][1,2,4]thiadiazines and 5‐amino‐6‐thia‐4,5a‐diazaacephenanthrylenes. The synthetic strategy involved nucleophilic substitution reactions to prepare key sulfonamide starting substrates, followed by photoinduced cyclization (via the Substitution Radical Nucleophilic Unimolecular, SRN1) under mild conditions using visible light. The scope of the reaction was explored with different substituent groups on the starting materials, which demonstrated moderate to very good product yields, with 13 examples and yields of up to 78 %. Moreover, this strategy represents the first synthetic approach to obtain 5‐amino‐6‐thia‐4,5a‐diazaphenanthrylenes.

Sodium Copper Chlorophyllin: A Sustainable Bioinspired Catalyst for the Aerobic Oxidative Synthesis of Nitrogen Heterocycles and the Oxidative Cyanation of Tertiary Amines

AbstractA remarkably simple and straightforward protocol has been reported showcasing sodium copper chlorophyllin (SCC) as an eco‐friendly, bioinspired catalyst for the aerobic oxidative synthesis of pharmaceutically prevalent nitrogen‐containing heterocycles, such as benzimidazoles and quinoxalines. This reaction was performed in green solvent water, using the green oxidant, molecular oxygen. SCC displayed exceptional efficiency, congruent with the prevailing metal/non‐metal‐based catalyst regime without requiring additives. The SCC catalyst exhibited excellent recyclability upto three cycles for the benzimidazole synthesis reaction. This benign strategy was successfully applied in synthesizing a bioactive quinoxaline i. e., Tyrphostin AG1296, a promising candidate for melanoma treatment. The catalytic activity of SCC was explored for the synthesis of another privileged moiety i. e., α‐aminonitriles, via the α‐cyanation of tertiary amines under oxidative conditions. This reaction progressed with a mild, easy‐to‐use, convenient cyanide source, such as ethyl cyanoformate, and a green and attractive solvent, such as methanol, precluding acidic media. SCC catalyst was efficiently recycled upto three cycles for the α‐aminonitriles synthesis. Overall, the utility of a biodegradable, robust catalyst such as SCC, eco‐friendly solvents such as water and methanol, green oxidants such as O2, and mild reaction conditions, devoid of acidic additives, renders the present work viable for academic and industrial research.

Regio-, Site- and Stereo-Selective Aziridination of Conjugated Dienes Enabled by Palladium/Copper/Iodide/Oxygen Cooperation.

Vinylaziridines are important building blocks in organic chemistry, especially in the synthesis of nitrogen-containing heterocycles. The direct and efficient transfer of an appropriate nitrogen source to readily accessible conjugated dienes is a notable methodology. The Pd-catalyzed oxidative 1,2-difunctionalization of conjugated dienes through a π-allyl-palladium species should be an ideal method for the selective synthesis of vinylaziridines. However, this method faces the challenge of regioselectivity, often resulting in 1,4-difunctionalization instead. In this study, we developed a Pd-catalyzed aerobic 1,2-difunctionalization of conjugated dienes via a π-allyl-palladium species to achieve regio-, site- and stereo-selective aziridination under the synergistic effects of Pd(II), Cu(I), I-, and O2. The π-allyl palladium species formed in the system undergoes an unusual iodination process, leading to the formation of an allyl iodide intermediate. Subsequently, the vinylaziridine is obtained through intramolecular SN2' substitution of the allyl iodide.

The applications of nanocatalysts in the synthesis of heterocyclic compounds

Nanocatalysts in heterocyclic synthesis are a very important direction in producing eco-friendly compounds. These catalysts can be reused up to six times without losing their quantity and efficiency. Most of these nanocatalysts are cheap, available, economical and safe for the environment. In this review, I focused on the synthesis of furans, pyrans, chromenes and thiazoles from nanocatalysts. For example, pyranopyrazoles 8a-c were synthesized by the multicomponent reactions between aldehydes 4a-c, malononitrile (5), ethyl acetoacetate (6) and hydrazine hydrate (7) using titanium dioxide as a nanocatalyst. KEY WORDS: Heterocyclic, Chromenes, Nanocatalysts, Eco-friendly compounds Bull. Chem. Soc. Ethiop. 2025, 39(1), 123-129. DOI: https://dx.doi.org/10.4314/bcse.v39i1.10

Substituent-Dependent, Switchable Synthesis of Nonaromatic and Aromatic Heterocyclic Sulfones Using Visible Light.

In this Letter, we described a visible-light-induced switchable synthesis of nonaromatic and aromatic sulfonyl heterocycles. The product selectivity between 2,5-dihydropyrrole and pyrrole can be tuned by altering the substituent on the N atom of 1,6-diyne. We highlight the intricacy and efficiency of this approach in constructing molecular frameworks under mild conditions with a high functional group tolerance. This study elucidates the mechanism underlying product selectivity, highlighting its potential as a compelling alternative to traditional synthetic techniques.

1,2‐Diaza‐1,3‐Dienes as a Multifaceted Synthons for the Synthesis of Heterocycles: A Fifteen‐Years Update

AbstractThe discovery of structurally unique scaffolds entities with increased complexity and balanced physicochemical properties has the potential to allow synthetic chemists to exploit areas of chemical space that were previously inaccessible. Among the different strategies employed for generating N‐heterocycles, cyclization and cycloaddition reactions represent a valuable synthetic tool. The purpose of this minireview is to summarize the recent advances (2009‐present) from our laboratory on the generation of intriguing five‐, six‐ and seven‐membered mono‐ or poly‐heterocyclic architectures (linear, fused and spiro) employing 1,2‐diaza‐1,3‐dienes (DDs) as key synthons.

Stereocontrolled Synthesis of 1,4-Dicarbonyls via [3,3]-Sulfonium Rearrangement and Application to the Synthesis of Heterocycles

Due to an inherent polarity mismatch of the corresponding retrosynthetic synthons, 1,4-dicarbonyl synthesis through polar pathways requires a retrosynthetic rethink. While Umpolung-based approaches exist, efficient control of both the absolute and relative configuration of newly formed stereogenic centres within this motif has long proven particularly challenging. In this Synpacts, we highlight our work on the stereodivergent synthesis of 1,4-dicarbonyl compounds through an unusual transformation that relies on vinyl sulfoxides and ynamides as reactants. This method allows stereoselective access to each and every one out of the four possible stereoisomers of a generic 1,4-dicarbonyl target in a process where enantio- and diastereoselectivity are “dialled into” the vinyl sulfoxide partner. Recent studies show that the thus formed 1,4-dicarbonyls serve as excellent linchpins for structural diversification into highly substituted heterocycles, including those found in natural products. 1. Introduction 2. Synthesis of 1,4-dicarbonyl compounds under acid catalysis 3. Cyclisation towards γ-lactones and γ-lactams 4. Application in total synthesis 5. Conclusion

Strategic 1,9-Proton-Transfer-Driven Cycloaddition: Synthesis and Stereoselective Contraction of Nine-Membered Heterocycles

Strategic 1,9-Proton-Transfer-Driven Cycloaddition: Synthesis and Stereoselective Contraction of Nine-Membered Heterocycles

Quinoline Synthesis: Nanocatalyzed Green Protocols-An Overview.

Heterocyclic compounds are of great interest in our daily lives. They are widely distributed in nature and are synthesized in laboratories. Heterocycles play an important role in the metabolism of all living cells, including vitamins and coenzyme precursors like thiamine and riboflavin. Furthermore, heterocyclic systems are essential building blocks for creating innovative materials with intriguing electrical, mechanical, and biological properties. Also, more than 85% of all biologically active chemical entities comprise a heterocycle. As a result, heterocycle synthesis piqued researchers' curiosity, and in recent decades, chemists have concentrated more on nitrogen-containing cyclic nuclei in structures. Quinoline and its derivatives exhibit several biological functions, including antimicrobial, anticancer, antimalarial, anti-inflammatory, antihypertensive, and antiasthmatic effects. In addition, over a hundred quinoline-based drugs are available to treat a variety of disorders. Because of its biological importance, researchers developed one-pot synthetic methods employing effective acid/base catalysts (Lewis acids, Brønsted acids, and ionic liquids), reagents, and transition-metal-based catalysts. These methods have some downsides, including longer reaction times, harsher reaction conditions, creation of byproducts, costly catalysts, use of hazardous solvents, an unacceptable economic yield, and catalyst recovery. Researchers' focus has switched to creating environmentally friendly and effective methods for the synthesis of quinoline derivatives as a result of these methodologic shortcomings. Because of its special qualities, the use of nanocatalysts or nanocomposites offers an option for the effective synthesis of quinolines. This review focuses on the published research articles on nanocatalysts to synthesize substituted quinoline derivatives. This review covers all contributions until May 2024, focusing on quinoline ring building and mechanistic issues. With the aid of this review, we anticipate that synthetic chemists will be able to develop more effective methods of synthesizing quinolines.

Anion-driven C[sbnd]F bond cleavage of trifluoromethyl N-aryl hydrazones toward the assembly of N-heterocycles

Herein we report an efficient and convenient method for synthesizing 1H-benzo[d]imidazoles via a base-promoted reaction of readily available α-CF3 ketone-derived hydrazones with o-phenylenediamines. The key innovation is the anion-driven triple-cleavage of the CF bond in the CF3 group, which acts as a C1 synthon at the 2-position of the 1H-benzo[d]imidazole. This novel approach simplifies the synthesis and can be extended to the preparation of benzo[d]oxazoles and benzo[d]thiazoles. Our method offers a versatile and robust platform for the synthesis of important heterocyclic compounds, with potential applications in medicinal chemistry and drug discovery.

Novel Organosulfur Building Blocks for Heterocycle Synthesis

AbstractThe present article provides a personalized account of our recent work on the synthesis of substituted and fused five-membered heterocycles using various organosulfur building blocks, derived primarily through base-mediated condensation of active methylene compounds with (het)aryl/alkyl dithioesters, which have not been previously explored. We initially describe the ring-opening transformations of 4-[(methylthio)-(het)aryl-methylene]-2-phenyl-5-oxazolones, leading to the synthesis of functionalized oxazoles, thiazoles, and bisoxazoles. We then go on to focus on the synthesis of substituted benzothiophenes, indoles, and benzofurans, as well as their hetero-fused analogs. These compounds are synthesized via transition-metal-catalyzed intramolecular C–heteroatom (C–S, C–N, C–O) bond formation (via cross-coupling or C–H bond functionalization) of various reactive organosulfur intermediates, derived from base-mediated condensation of 2-bromo(het)arylacetonitriles, acetates, or desoxybenzoins or the corresponding 2-unsubstituted precursors. Finally, we highlight the synthetic applications of a new class of previously unexplored organosulfur building blocks, namely, unsymmetrically substituted 1,3-bis(het)aryl-1,3-monothioketones, derived via base-mediated condensation of ketones with (het)aryl/alkyl dithioesters, for the regioselective synthesis of substituted pyrazoles, isoxazoles, thiophenes, imidazoles, and benzothiophenes.1 Introduction2 4-[(Methylthio)-het(aryl)-methylene]-2-phenyl/2-(2-thienyl)-5-oxazolones: Versatile Templates for the Synthesis of Oxazoles, Thiazoles, and Bisoxazoles3 Synthesis of Benzothiophenes, Indoles, and Benzofurans via Transition-Metal-Catalyzed Intramolecular C–Heteroatom Bond Formation4 1,3-Bis(het)arylmonothio-1,3-diketones and 1,3-Bis(Het)aryl-3-(methylthio)-2-propenones: Versatile Intermediates for the Regioselective Synthesis of Five-Membered Heterocycles5 Conclusion

Diastereoselective Addition of Lithiated Allenyl Sulfones to Nonracemic Sulfinimines: Asymmetric Synthesis of Diverse Heterocycles.

The addition of lithiated allenyl sulfones to nonracemic sulfinimines furnished sulfinamides possessing the allenyl sulfonyl moiety with excellent diastereoselectivity. The formed products are transformed into different heterocycles, including the synthesis of pyrroline, pyran, and functionalized benzopyran.