Heterocyclic Structures Research Articles

Construction of Isoquinolone Scaffolds on DNA via Rhodium(III)-Catalyzed C-H Activation.

Isoquinolone is one of the most common heterocyclic core structures in countless natural products and many bioactive compounds. Here, a highly efficient approach to synthesize isoquinolone scaffolds on DNA via rhodium(III)-catalyzed C-H activation has been described. This chemistry transformation is robust and has shown good compatibility with DNA, which is suitable for DNA-encoded library synthesis.

Synthesis of novel 1,2,4-oxadiazine derivatives and the substituent effect study on 13C NMR spectra

In this study, eight mostly new 6-Methyl-4-phenyl-3-(substituted-phenyl)-4H-1,2,4-oxadiazin-5(6H)-one (OXA-ON) and eight new 6-Methyl-4-phenyl-3-(substituted-phenyl)-4H-1,2,4-oxadiazine-5(6H)-thione (OXA-TY) were synthesized. The synthesized heterocycle structures were characterized by IR, 1H NMR, 13C NMR and HRMS analyses. The carbons of interest in the OXA-ON and OXA-TY compounds are CH3, CH, C=N and C=O (C=S). The 13C NMR experimental chemical shifts (ppm) (SCS) of the CH3, CH, C=N, C=O (C=S) carbons of these OXA-ON and OXA-TY derivatives were correlated with the Hammett substitution constants and Swain-Lupton parameters, using the single substituent parameter (SSP) and dual substituent parameter (DSP) methods. Negative ρ values were detected for C=N and C=O carbons in OXA-ON derivatives and for C=N and C=S carbons in OXA-TY derivatives (reverse substituent effect). Positive ρ values were detected for CH carbon in OXA-ON derivatives and for CH3 and CH carbons in OXA-TY derivatives (normal substituent effect). According to the results of all statistical analyses, SCS (ppm) values of C=N, C=O carbons of OXA-ON derivatives, and C=N, C=S carbons of OXA-TY derivatives showed excellent correlation. The SCS (ppm) of CH carbon of OXA-ON and the CH3 and CH carbons of OXA-TY showed good correlation. The excellent and good correlations implied that the substituent effects are electronic in nature.

Analysis of the microstructure of high viscosity components in Tahe ultra heavy oil based on the combination of ESI (±) FT-ICR/MS

In addressing the challenge of high viscosity in Xinjiang Tahe heavy oil, crucial for optimizing extraction processes, this study focuses on identifying and analyzing the microstructure of key components influencing oil viscosity. The aim is to uncover the underlying reasons for its high viscosity and guide research towards effective viscosity reduction techniques. Electrospray ionization (ESI) combined with fourier transform ion cyclotron resonance mass spectrometry (FT-ICR/MS) characterizes the molecular-level constituents contributing to oil viscosity. The investigation covers the composition and distribution of oxygen-containing, nitrogen-containing, and organometallic compounds, developing a molecular structure model for these critical viscosity-inducing components. Findings reveal Xinjiang Tahe extra heavy oil as a solid mass at room temperature, with significant viscosity reduction observed post-deasphalting, highlighting asphaltenes' pivotal role in viscosity. Analysis indicates a higher content of metal elements (such as V and Ni) in asphaltenes compared to the crude oil itself, with an abundance of porphyrin structures in asphaltenes markedly influencing oil viscosity. Cyclic, aromatic, and unsaturated compound structures are predominantly found in the asphaltenes of heavy oil. Through combined ESI (±) FT-ICR/MS analysis, the crude oil is determined to mainly comprise acidic compounds, non-basic nitrogen compounds, and basic nitrogen compounds, offering significant insight into heavy oil's complex chemical composition. Specifically, non-basic nitrogen compounds in Tahe crude oil, including alkylcarbazoles, alkylbenzocarbazoles, and alkylpolybenzocarbazoles, are identified as key components, with molecular carbon numbers ranging from C12 to C56 and a predominance near C27. Additionally, asphaltenes in Tahe heavy oil exhibit a higher double bond equivalence (DBE) than the crude oil, indicating a greater degree of condensation with an increased number of double bonds and heterocyclic structures. The significant difference in DBE values between asphaltenes and crude oil underscores their impact on viscosity. A detailed molecular structure model of the asphaltenes in Tahe extra heavy oil has been constructed based on FT-ICR/MS analysis, providing a foundational understanding for developing viscosity reduction strategies.

Rhodium-Catalyzed Enantioselective Cyclization of 2-Allenylbenzoxazoles.

The enantioselective rhodium-catalyzed cyclization of 2-allenylbenzoxazoles to the corresponding vinyl-functionalized, fused heterocyclic structures is reported. The presented method offers several advantages, including the use of low catalyst loadings, commercially available catalyst precursors, and mild reaction conditions. Due to its broad scope, scalability, and valuable products, we consider this methodology to be a useful tool for the construction of benzoxazole-containing building blocks.

Intramolecular Friedel-Crafts Reaction with Trifluoroacetic Acid: Synthesizing Some New Functionalized 9-Aryl/Alkyl Thioxanthenes.

In this study, a series of halogen-substituted thioxanthenes were synthesized because the most important and biologically active derivatives of xanthenes are thioxanthenes. In order to obtain new thioxanthene derivatives, first, the starting molecules were synthesized by the appropriate reaction methods in two steps. The intramolecular Friedel-Crafts alkylation (FCA) method was used to convert the prepared three aromatic substituted starting alcohol compounds to their corresponding thioxanthenes by cyclization. For the intramolecular FCA reaction of secondary alcohols, which are the starting compounds (1a-1t), organic Bro̷nsted acids, which require more innovative, easier, and suitable reaction conditions, were used instead of halide reagents with corrosive effects as classical FCA catalysts. Trifluoroacetic acid was determined to be the organocatalyst with the best yield. Therefore, some original 9-aryl/alkyl thioxanthene derivatives (2a-2t) were synthesized using the optimized FCA method. In addition, a new sulfone derivative of thioxanthene 3i was prepared by performing the oxidation reaction with one of the obtained new thioxanthene 2i. Thioxanthenes and their derivatives are important heterocyclic structures that contain pharmacologically valuable sulfur and are used in the treatment of psychotic diseases such as Alzheimer's or schizophrenia, as well as a number of potent biological activities.

Synthesis and Characterization of Novel Heteroarylacrylonitrile Derivatives Containing Pyrazole Scaffold

2,3-disubstituted acrylonitriles derivatives are among the most important molecules in medicinal chemistry due to their bioactivity and their role as starting compounds for many bioactive molecules. Many heterocyclic structures have been investigated as AChE enzyme inhibitors. Nowadays, E/Z acrylonitrile derivatives are being studied as new AChE inhibitors. This study aimed to synthesis new heteroaryl-acrylonitrile compounds using Knoevenagel condensation. In this context, acrylonitrile compounds with aryl and heteroaryl structures at positions 2 and 3 (respectively )were synthesized from the reactions of pyrazole aldehyde derivative (4) with various acetonitrile compounds. Synthesized novel heteroarylacrylonitrile derivatives (5a-d) containing pyrazole ring are potential AChE inhibitors. The structures of the synthesized compounds were elucidated by FTIR, 1H-NMR and 13C-NMR spectroscopic techniques.

Comparison of conventional hydrothermal and microwave‐assisted synthesized g‐C3N4/MoS2 nanocomposite coated steel substrate by tribological measurement

AbstractMolybdenum disulfide is an effective solid lubricant, but it suffers from oxidation and moisture absorption issues, resulting in insufficient wear resistance and a shortened lifespan. This study introduces an innovative approach, integrating graphitic carbon nitride with molybdenum disulfide via advanced microwave‐assisted synthesis, offering precise control over synthesis parameters. The research assesses the tribological performance, comparing it with conventional hydrothermal synthesis. The study extensively investigates the morphology, microstructure, and tribology of a g‐C3N4/MoS2 nanocomposite created through novel microwave (g‐C3N4/MoS2‐MW) and hydrothermal techniques (g‐C3N4/MoS2‐HT). MoS2 exhibits a flower‐like structure, while graphitic carbon nitride has a layered structure, as confirmed by elemental analysis via energy‐dispersive X‐ray spectroscopy. X‐ray diffraction identifies g‐C3N4 peaks at 13.0° (100) and 27.5° (002) and hexagonal MoS2 peaks at 14° (002), 32.7° (100), 35.8° (102), and 58.3° (110). The Fourier‐transform infrared spectrum reveals peaks at 1237.4 and 808 cm−1 (aromatic and triazine ring breathing modes in g‐C3N4), 1407.1 and 1638.9 cm−1 (C=N and C−C heterocyclic structures), and 3432 cm−1 (vibrations due to −NH and −OH). The coefficients of friction for microwave‐assisted and traditional hydrothermal synthesized nanocomposites are 0.22 and 0.34, respectively. The wear depths are 98 microns and 141 microns, with a wear scar diameter of 2.87 mm for g‐C3N4/MoS2‐MW and 3.45 mm for g‐C3N4/MoS2‐HT, indicating superior lubrication with the microwave‐assisted coating.

Effect of Maillard reaction based on catechol polymerization on the conversion of food waste to humus

The pollution and harm of food waste (FW) are increasingly concerned, which has the dual attributes of pollutants and resources. This study aimed to improve the synthesis efficiency of FW humic substances (HS), and investigating the effect of catechol on the formation mechanism and structure of humic acid (HA) and fulvic acid (FA). Results indicated that catechol incorporation could enable to exhibit higher HS yield and more complex structure, especially the maximum particle size of FA reached 4800 nm. This was due to the combination of catechol with multiple nitrogenous compounds, which accelerated molecular condensation. Spectroscopic scans analysis revealed that Maillard reaction occurs first. Subsequently, Maillard reaction products and amino acids were combined with different sites of catechol, which leads to the difference of molecular structure of HS. The structure of FA is characterized by an abundance of carboxyl and hydroxyl groups, whereas HA is rich in benzene and heterocyclic structures. The structural difference was responsible for the disparity in the functional properties of FA and HA. Specifically, the presence of amino, hydroxyl, pyridine, and carboxyl groups in FA contributes significantly to its chelating activity. This research provides an efficient and sustainable unique solution for the high-value of FW conversion, and provides evidence for understanding the structural evolution of HA and FA.

N‐Heterocyclic Carbene Organocatalyzed [3+3] Annulation for the Enantioselective Synthesis of Benzopyranothiazinones

AbstractThe design, inspired by the core‐structure of oxicam has allowed the enantioselective synthesis of benzopyranothiazinone motifs employing N‐heterocyclic carbene (NHC) catalysis. The NHC‐mediated transformation involves the reaction of α,β‐unsaturated aldehydes with suitable substituted benzothiazinone derivatives. This process encompasses the initial formation of α,β‐unsaturated acylazoliums from ynals and concurrent generation of enolates from benzothiazinone. The culmination of these reactions results in an efficient annulation, yielding the desired products with reasonable yields and high stereoselectivities. This study underscores the potential of NHC catalysis in the streamlined synthesis of complex heterocyclic structures.

P4O10/TfOH-mediated metal-free synthesis of 4-hydroxycoumarins and a one-pot strategy to build their hybrids

4-Hydroxycoumarins are among the most versatile heterocyclic scaffolds, and they are extensively used in the synthesis of a wide range of chemical molecules. Because of their biological and pharmacological effects, 4-hydroxycoumarin-based compounds are important among heterocyclic structures. In this study, a new method is developed to synthesize 4-hydroxycoumarins using a phosphoric anhydride and trifluromethanesulfonic acid (P4O10/TfOH) reagent system without the employment of either a catalyst or solvent. The direct condensation of phenols with malonic acid at ambient conditions provided 4-hydroxycoumrins in 85–90% yield. In medicinal chemistry, the 4-hydroxycoumarin motif is often used to make new hybrid heterocyclic scaffolds that can be used to find new molecules. The method was then successfully extended to synthesize hybrids of 4-hydroxycoumarin, such as biscoumarylphenylmethane, dioxinocoumarin, and tetracoumarylpehylenebismethane, in a one-pot method from phenol, avoiding the intermediate step of isolating and purifying 4-hydroxycoumarin.

Recent Advances in the Multicomponent Synthesis of Heterocycles Using 5-Aminotetrazole

AbstractThe unique reactivity and beneficial features of the 5-aminotetrazole synthon (1H-tetrazol-5-amine) have made it a versatile and effective building block in the synthesis of heterocyclic compounds. In addition, several drugs containing this scaffold with a wide array of biological properties have been already introduced. Heterocyclic structures are the backbone of many biologically active and industrially important compounds. 5-Aminotetrazole is one of the favored synthons used in the preparation of heterocycle-bearing compounds, especially in multicomponent synthesis. This review highlights a comprehensive overview of the emerging applications of 5-aminotetrazole as a key component in the synthesis of heterocyclic frameworks through multicomponent reactions, reported between 2017 and July 2023.1 Introduction2 5-Aminotetrazole3 Tetrazolopyrimidine Compounds4 Spiro Compounds5 Miscellaneous6 Conclusion

Proton exchange membrane deriving from sulfonated N-heterocyclic poly(aryl ether ketone)s containing ether-free proton conducting units and performing enhanced physicochemical stability and conduction properties

Sulfonated aromatic polymer proton exchange membranes suffer from the trade-off relationship between physicochemical stability and proton conductivity hampering the membrane application in fuel cells. To bridge the effect, the high-performance membranes exhibiting excellent proton conduction behavior and good stability are constructed from sulfonated N-heterocyclic poly(aryl ether)s designed elaborately, in which the hydrophilic units are constructed by combining the high-density pendant benzenesulfonic groups and biphthalazindione structures without the introduction of weak linkage units like ether bonds. The twisted heterocyclic structures and the multiple interactions between heterocyclic structures and sulfonic groups enhance the physical stability and proton-conduction behavior with the highest conductivity of 256 mS cm−1 for the membranes. The membranes perform rupture time between 3.9 and 7.1 h in high temperature Fenton's oxidation test, exhibiting good chemical stability. The cells loading the membranes perform the maximum power density between 1.08 and 2.30 W cm−2. The above results verify the benefits of constructing ether-free heterocyclic hydrophilic units with high-density proton-conducting groups for the improvement of comprehensive membrane performance.

Integrating amino acids into Bcr-Abl inhibitors: design, synthesis, biological evaluation, and in silico studies.

Bcr-Abl is successfully applied to drug discovery as a CML therapeutic target, but point mutation resistance has become a major challenge in the clinical treatment of CML. Our previous studies have shown that the introduction of amino acids as flexible linkers and heterocyclic structures as HBMs can achieve potent inhibition of Bcr-AblT315I. In continuation of these studies, we further enriched the linker types by developing a library of compounds with tert-leucine or serine as a linker. Biological results showed that these compounds exhibited enhanced inhibition against Bcr-AblWT and Bcr-AblT315I kinases as well as improved antiproliferative activity in leukemia cell assays compared to previously disclosed compounds. In particular, compounds TL8, TL10, BS4, BS10, SR5 and SR11 exhibited potent inhibitory activities against Ba/F3 cells bearing a T315I mutant. Additionally, compounds TL8, BS4 and SR5 effectively induced K562 cell apoptosis, arrested the cell cycle at the S or G2/M phase, and inhibited the phosphorylation of Bcr-Abl and STAT5 in a dose-dependent manner. Docking studies verified the rationality of tert-leucine or serine as a flexible linker and indicated that phenylpyridine with an amide side chain favored the potency of these inhibitors. Moreover, ADME prediction suggested that the tested compounds had a favorable safety profile. Thus, tert-leucine or serine can be used as a promising class of flexible linkers for Bcr-Abl inhibitors with heterocyclic structures as HBMs, and compounds BS4, SR5, and especially TL8, can be used as starting points for further optimization.

Eco-friendly, in-water, and catalyst-free assembly of acylethenylpyrroloimidazoindoles from 3H-indoles and acylpyrrolylacetylenes

A new approach to prepare of dihydropyrrolo[1′,2′:3,4]imidazo[1,2-a]indoles through [2+3] cyclization of 3H-indoles with acylpyrrolylacetylenes was developed.

Rational design and comparison of three curcumin-based fluorescent probes for viscosity detection in living cells and zebrafish.

Viscosity is a crucial indicator of the cellular microenvironment, which can affect the normal level of cellular metabolism. Aberrant levels of viscosity can result in the emergence of a variety of physiological problems including diabetes, Parkinson's disease, inflammation, etc. Therefore, it is crucial to exploit effective assays that can detect viscosity levels in living cells and organisms. Three new nitrogen-containing heterocyclic fluorescent probes, CNO, CNN and CNNB, were designed and prepared by coupling curcumin with isoxazole, pyrazole, and phenylpyrazole rings, respectively. The fluorescence response properties of these probes to the viscosity level were analyzed in parallel. All the probes, CNO, CNN and CNNB, exhibited a significantly enhanced fluorescence response to viscosity in a broad pH range with excellent photostability, sensitivity and anti-interference ability. The sensing mechanisms of these probes for viscosity were verified by DFT calculations. In addition, these probes were successfully employed for detecting viscosity levels in living HeLa cells and zebrafish. This research compares the viscosity-responsive capabilities of curcumin-based fluorescent probes containing different nitrogen-containing heterocyclic structures, and provides a new design strategy and guidance for developing curcumin-based fluorescent probes for viscosity analysis.

Recent Advances in the Cascade Cyclization Reactions of 1,7‐Enynes

AbstractElaborated molecular architectures, especially carbocyclic, heterocyclic, endocyclic, and polycyclic molecular structures, serve as an important class of organic complexes because they are frequently occurring core structural units in a variety of biologically and pharmacologically relevant natural products, drug molecules, agrochemicals, and functional materials. A main challenge of current synthetic approaches is the development of strategically efficient and selective formation of these compounds from easy‐to‐handle starting materials. The cascade cyclizations of 1,7‐enynes have afforded an indispensable method for accessing molecular complexity and diversity, thus highlighting their potential significance in both academic and industrial communities. In the last decades, tremendous efforts have been devoted to discovering convenient routes to access sophisticated annulation derivatives, and a wide range of powerful and straightforward synthetic strategies have been reported. In this review, the latest achievements in the cascade cyclization reactions of 1,7‐enynes are summarized, which could be separated into three categories: (1) Visible‐light‐induced reactions of 1,7‐enynes; (2) Metal‐free catalyzed reactions of 1,7‐enynes; (3) Transition‐metal‐catalyzed reactions of 1,7‐enynes.

The Synthesis of Nitrogen- and Oxygen-Containing Heterocyclic Scaffolds Assisted by Ionic Liquids: A 2022 Literature Survey

AbstractHeterocycles have gained recognition as vital components in approved drugs, drawing substantial attention from the scientific community. Ionic liquids (ILs) have been utilized for their transformative roles in heterocycle synthesis, showcasing distinctive properties that are pivotal in diverse chemical transformations, while also acting as effective catalysts and offering safer alternatives to volatile organic solvents. This account delves into the synthesis of nitrogen- and oxygen-containing heterocyclic structures, employing various ILs such as ammonium, cholinium, DABCO-based, DBU-based, guanidinium-based, imidazolium, phosphonium, pyridinium, and other miscellaneous examples. They have proven indispensable in facilitating reactions like the Fischer indole synthesis, the Biginelli reaction, Knoevenagel condensations and many more. Notably, the recyclability of ILs serves as a valuable asset, aiding in the completion of intricate synthetic pathways, multicomponent reactions, and one-pot syntheses, ultimately enhancing yields. This account, covering the literature published in 2022, seeks to guide researchers in selecting suitable ILs for specific chemical reactions that enable the synthesis of aza- and/or oxa-heterocycles. The described advancements represent promising prospects for drug development and other applications within the domain of heterocyclic chemistry.

Catalytic Domino Three-Component Synthesis of Functionalized Heterocycles from Carbon Dioxide.

A catalytic domino, three-component reaction has been developed for the transformation of carbon dioxide into functionalized six-membered cyclic carbonates. The catalytic process combines an initial carboxylative cyclization of β-epoxy alcohols followed by an oxa-Michael reaction affording an unparalleled scope of heterocyclic structures. The wide range of functional groups, including free-alcohols, empowers the access to a range of products including C11-oxo-based bicyclic heterocycles. The versatility of these functionalized carbonates is further complemented by a series of synthetic diversifications. Control experiments are consistent with the first step of this domino process being promoted by a binary Lewis acid/base catalyst, while the second stage only requires catalytic base.

Acetylenic and allenic carbanions in the reaction with heterocumulenes: a simple way to fundamental heterocycles

The synthetic potential of adducts of acetylenic and allenic carbanions with isothiocyanates and azatrienic systems based on them - precursors of fundamental aza- and thiaheterocycles - pyrroles, 2,3-dihydropyridines, pyridines, quinolines, 3 H -azepines, 4,5-dihydro-3 H -azepines, 2-azabicyclo[3.2.0]hept-2-енов, thietanes, thiophenes, thiophene-2(5 H )-imines, 1,3-thiazoles, 4,5-dihydro-1,3-thiazoles, and other heterocyclic structures with rare and/or difficult-to-build functional and pharmacophore substituents is briefly described.

Directed C−H Allylation of Aromatic Carboxamides with Allyl Aryl Ethers under Cp*Co(III)‐Catalysis

AbstractThe Cp*Co(III) C−H allylation of (hetero)arenes with allyl aryl ethers has been developed using an amide as directing group (24 examples). DFT calculations have shed light on the mechanistic course and reactivity pattern, showing that strong electron releasing groups favour the reaction by reducing the activation barrier of the rate‐determining C−H activation step. However, the steric strain can increase the energy of the migratory insertion step to the point of completely preventing the reaction, as in the case of the 3,5‐dimethylbenzamide. The obtained allylated compounds have been transformed into a variety of interesting heterocyclic and carbocyclic structures, such as isoquinolones and isochromanones.