Family Of Heterocycles Research Articles

The Structure of N‐phenyl‐pyrazoles and Indazoles: Mononitro, Dinitro, and Trinitro Derivatives

This review explores the heterocyclic family of N‐nitrophenyl pyrazoles and indazoles covering mainly their structural aspects, with special emphasis on the X‐ray diffraction data. NMR spectroscopy and the theoretical calculations will also be briefly summarized. The synthesis and reactivity aspects will be reported when they are specific to these compounds.

Convenient two-step synthesis of highly functionalized benzo-fused 1,4-diazepin-3-ones and 1,5-diazocin-4-ones by sequential Ugi and intramolecular SNAr reactions

Benzodiazepinones are an important family of heterocycles with very attractive pharmacological properties and peptidomimetic abilities. We report herein a rapid and efficient two-step synthesis of polysubstituted 1,4-benzodiazepin-3-ones and 1,5-benzodiazocin-4-ones using a multicomponent condensation/cyclization strategy. The approach uses an Ugi four-component reaction to condense readily available Nα-Fmoc-amino acids, amines and isocyanides with a 2-fluorobenzaldehyde derivative followed by a one-pot Fmoc-group removal, intramolecular aromatic nucleophilic substitution for ring closure and side chain deprotection. The described method gives access to benzo-fused 7- and 8-membered rings bearing a wide variety of functionalized substituents and was applied to efficiently prepare tri- and tetrasubstituted 1,4-benzodiazepin-3-ones and 1,5-benzodiazocin-4-ones in high yields in two straightforward steps.

Influence of anchoring of a pyrazoline dye 3-naphthyl-1-phenyl-5 (4-amino phenyl)-2-pyrazoline (NPAP) in manipulating the electronic and chemical properties of a graphene oxide via amidation: Synthesis, characterization and photophysics

Owing to the unique opto-electronic properties, pyrazoline derivatives are considered to be one of the most elegant member in heterocyclic family. In this work we have utilized a pyrazoline dye 3-naphthyl-1-phenyl-5-(4-amino phenyl)-2-pyrazoline (NPAP) for functionalizing graphene oxide (GO) through amide linkage, as the progress of graphene based materials are quicker than other comparable materials. All the employed characterization techniques support the bridging of –NH bond between the two segments. Moreover, the enhanced photophysical properties of the resulting hybrid (GO-NPAP) reflect an efficient charge delocalization, allowing an electronic interaction at the interface of GO and NPAP partners as they are electronically separated. Very simple, economic and an effective reagent for making GO fluorescent, it is expected that the pyrazoline functionalized GO will hold a prominent position in developing high-performance graphene based devices.

Structurally Diverse Boron-Nitrogen Heterocycles from an N2 O23- Formazanate Ligand.

Five new compounds comprised of unprecedented boron-nitrogen heterocycles have been isolated from a single reaction of a potentially tetradentate N2 O23- formazanate ligand with BF3 ⋅OEt2 and NEt3 . Optimized yields for each product were obtained through variation of experimental conditions and rationalized in terms of relative Gibbs free energies of the products as determined by electronic structure calculations. Chemical reduction of two of these compounds resulted in the formation of a stable anion, radical anion, and diradical dianion. Structural and electronic properties of this new family of redox-active heterocycles were characterized using UV/vis absorption spectroscopy, cyclic voltammetry and X-ray crystallography.

Unified Synthesis of 1,2-Oxy-aminoarenes via a Bio-inspired Phenol-Amine Coupling

Summary 1,2-Aminophenols and their related nitrogen-containing heterocycles are ubiquitous in medicine, agriculture, and materials science. Here, we describe a bio-inspired and unified approach for their synthesis through a direct, catalytic aerobic coupling of phenols and amines. Key to the formation of the aromatic C–N bond is a facile condensation between the amine and an ortho -quinone, which triggers redox isomerization to an ortho -iminophenol before a series of downstream events. We discuss the factors that govern regioselectivity during aerobic ortho -oxygenation of the phenol and condensation of the amine, and we demonstrate synthetic utility by preparing a structurally diverse family of immunosuppressive heterocycles and the indole alkaloid cephalandole A. Our conditions involve a wide range of simple, un-activated substrates, occur at room temperature with an earth-abundant copper-catalyst and a commercially available diamine ligand, and produce water as the only stoichiometric by-product.

ChemInform Abstract: Hydrazones as Singular Reagents in Asymmetric Organocatalysis

AbstractReview: [55 refs.

1H‐1,2,3‐Triazole: From Structure to Function and Catalysis

The heterocyclic family of azoles have recently become one of the most widely used members of the N‐heterocycles; the most prominent one being 1H‐1,2,3‐triazole and its derivatives. The sudden growth of interest in this structural motif was sparked by the advent of click chemistry, first described in the early 2000s. From the early days of click chemistry, when the accessibility of triazoles made them into one of the most versatile linkers, interest has slowly turned to the use of triazoles as functional building blocks. The presence of multiple N‐coordination sites and a highly polarized carbon atom allows for metal coordination and the complexation of anions by both hydrogen and halogen bonding. Exploitation of these multiple binding sites makes it possible for triazoles to be used in various functional materials, such as metallic and anionic sensors. More recently, triazoles have also shown their potential in catalytic systems, thus increasing their impact far beyond the initial purpose of click chemistry. This report gives an overview of the structure, functionalities, and use of triazoles with a focus on their use in catalytic systems.

How a Small Structural Difference Can Turn Optical Properties of π-Extended Coumarins Upside Down: The Role of Non-Innocent Saturated Rings.

The fluorescence properties of two new families of heterocycles possessing either a seven- or five-membered ring attached at the core molecule are entirely different in solution and in the solid state. Crystallization has the effect of inhibiting non-radiative excited-state deactivation pathways, operative in solution for the seven-membered ring compounds, thus leading to significant fluorescence efficiency in the solid state, with quantum yields ranging from 0.10 to 0.36. Conversely, the five-membered ring derivatives, which display notable emission properties in solution, are almost non-emissive in the crystalline state, characterized by a long-range π-stacked arrangement. When embedded in polymeric films, both series show fluorescence features similar to the solution case, with remarkable fluorescence quantum yields ranging from 0.09 to 0.41. According to quantum chemical calculations, 3H-chromeno[3,4-c]pyridine-4,5-diones show the specific mechanism of fluorescence quenching. The derivatives bearing the seven-membered ring undergo, in solution, a significant structural deformation in the excited state, resulting in a large decrease of the energy gap between S1 and S0 and hence to a substantial contribution of the internal conversion in the relaxation process. The fluorescence quenching of the five-membered ring derivatives is in turn related to the intermolecular interaction between adjacent molecules prevailing to a greater extent in the crystal lattice.

Hydrazones as Singular Reagents in Asymmetric Organocatalysis.

This Minireview summarizes strategies and developments regarding the use of hydrazones as reagents in asymmetric organocatalysis, their distinct roles in nucleophile-electrophile, cycloaddition, and cyclization reactions. The key structural elements governing the reactivity of these reagents in a preferred pathway will be discussed, as well as their different interactions with organocatalysts, leading to diverse activation modes. Along these studies, the synthetic equivalence of N-monoalkyl, N,N-dialkyl, and N-acyl hydrazones with several synthons is also highlighted. Emphasis is also put on the mechanistic studies performed to understand the observed reactivities. Finally, the functional group transformations performed from the available products has also been analyzed, highlighting the synthetic value of these methodologies, which served to access numerous families of valuable multifunctional compounds and nitrogen-containing heterocycles.

Synthesis of Kappa Opioid Antagonists Based On Pyrrolo[1,2-α]quinoxalinones Using an N-Arylation/Condensation/Oxidation Reaction Sequence.

The quinoxaline and quinoxalinone family of nitrogen heterocycles is present in molecules of therapeutic relevance for diverse applications ranging from infectious diseases to neuroscience targets. Here, we describe a general synthetic sequence to afford pyrrolo[1,2-α]quinoxalinones from commercially available starting materials and their use in preparing potential kappa opioid receptor antagonists. The biological data obtained from the latter set of compounds is briefly presented and discussed.

Polyfunctional 4-quinolinones. Synthesis of 2-substituted 3-hydroxy-4-oxo-1,4-dihydroquinolines

We present here two new methods based on rearrangement reactions to obtain novel 2-substituted 3-hydroxy-4-oxo-1,4-dihydroquinolines, an important family of heterocycles with potential applications. Alkyl 3-hydroxy-4-oxo-1,4-dihydroquinoline-2-carboxylates were obtained by alkoxide promoted rearrangement of alkyl isatinacetates. A second synthetic route involves the alkoxide promoted reaction of both isatin and N-methylisatin, with alkylating agents having acidic methylenes. This reaction leads to the formation of spiroepoxyoxindoles via Darzens’ condensation. When phenacyl bromides are used, the initially obtained benzoyl substituted spiroepoxyoxindoles were smoothly transformed into the corresponding 2-benzoyl-3-hydroxy-4-quinolinones with good to excellent yields.

ChemInform Abstract: Rh(III)‐Catalyzed [5 + 1] Oxidative Cycloaddition of Arylguanidines with Alkynes: A Novel Access to C4‐Disubstituted 1,4‐Dihydroquinazolin‐2‐amines.

A novel and mild RhIII-catalyzed [5+1] oxidative cycloaddition between arylguanidines and alkynes efficiently affords C4-disubstituted 1,4-dihydroquinazolin-2-amines. Members of this family of heterocycles, which contain the relevant cyclic guanidine units, have shown interesting pharmacological properties. The mechanism probably involves the formation of an eight-membered rhodacycle in which the imine unit of guanidine is coordinated to the Rh center. This rhodacycle would evolve to give the C-4 disubstituted 1,4-dihydroquinazolin-2-amine skeleton.

Systematic Evaluation of the Metabolism and Toxicity of Thiazolidinone and Imidazolidinone Heterocycles.

The thiazolidine and imidazolidine heterocyclic scaffolds, i.e., the rhodanines, 2,4-thiazolidinediones, 2-thiohydantoins, and hydantoins have been the subject of debate on their suitability as starting points in drug discovery. This attention arose from the wide variety of biological activities exhibited by these scaffolds and their frequent occurrence as hits in screening campaigns. Studies have been conducted to evaluate their value in drug discovery in terms of their biological activity, chemical reactivity, aggregation-based promiscuity, and electronic properties. However, the metabolic profiles and toxicities have not been systematically assessed. In this study, a series of five-membered multiheterocyclic (FMMH) compounds were selected for a systematic evaluation of their metabolic profiles and toxicities on TAMH cells, a metabolically competent rodent liver cell line and HepG2 cells, a model of human hepatocytes. Our studies showed that generally the rhodanines are the most toxic, followed by the thiazolidinediones, thiohydantoins, and hydantoins. However, not all compounds within the family of heterocycles were toxic. In terms of metabolic stability, 5-substituted rhodanines and 5-benzylidene thiohydantoins were found to have short half-lives in the presence of human liver microsomes (t1/2 < 30 min) suggesting that the presence of the endocyclic sulfur and thiocarbonyl group or a combination of C5 benzylidene substituent and thiocarbonyl group in these heterocycles could be recognition motifs for P450 metabolism. However, the stability of these compounds could be improved by installing hydrophilic functional groups. Therefore, the toxicities and metabolic profiles of FMMH derivatives will ultimately depend on the overall chemical entity, and a blanket statement on the effect of the FMMH scaffold on toxicity or metabolic stability cannot and should not be made.

ChemInform Abstract: Imidazothiazole and Related Heterocyclic Systems. Synthesis, Chemical and Biological Properties

AbstractReview: 90 refs.

Synthesis Characterization and Antimicrobial Activity of N-nitroso-2, 6-Diphenylpiperidin-4-One Semicarbazone

Among the family of heterocyclic compounds, The nitrogen containing six membered heterocyle, the piperidine structural was the most dominant and very prevalent element in nature and often found to be naturally occurring bioactive compounds such as alkaloids. Piperidin-3-one derivatives are used as precursors for the synthesis of antimalarial agents febrifugine and Isofebrifugine. Piperidin-4-ones mostly display varied and potent biological properties such as antiviral, antitumour, analgesic, antimicrobial, fungicidal, herbicidal, insecticidal, antihistaminic, anti-inflammatory and anticancer. CNS stimulant and recent reports suggest that compounds containing piperidin-4-one moiety elicit excellent activity when aromatic substitutions are present at 2- and/or 6-positions. In this work, the compound N-nitroso-2,6- diphenylpiperidin-4-one semicarbazone has been prepared and analyzed. The product showed positive nitrogen test (Lassign test), a single spot in TLC and sharp melting point for the purity of the compound. The structure of the compound was further confirmed from the CHN analysis FT-IR, and 1H NMR Spectral data and the compound have being screened for its antimicrobial activity against gram positive bacteria Bacillus subtilis, Staphylococcus aureus and Gram-negative bacteria Escherichia coli by using ciprofloxacin as standard and fungi Candida albicans by using cetramazole as standard. The compound exhibited significant activities against all the tested bacterial and fungal strains.

A series of temperature-dependent CdII-complexes containing an important family of N-rich heterocycles from in situ conversion of pyridine-type Schiff base

An efficient method for the synthesis of N-rich heterocycles has been systematically explored through solvothermal in situ generation from ligand (L) mediated by Cd2+. Their in situ formation mechanisms and coordination chemistry are investigated.

Imidazothiazole and related heterocyclic systems. Synthesis, chemical and biological properties.

Fused heterobicyclic systems have gained much importance in the field of medicinal chemistry because of their broad spectrum of physiological activities. Among the heterocyclic rings containing bridgehead nitrogen atom, imidazothiazoles derivatives are especially attractive because of their different biological activities. Since many imidazothiazoles derivatives are effective for treating several diseases, is interesting to analyze the behavior of some isosteric related heterocycles, such as pirrolothiazoles, imidazothiadiazoles and imidazotriazoles. In this context, this review summarizes the current knowledge about the syntheses and biological behavior of these families of heterocycles. Traditional synthetic methodologies as well as alternative synthetic procedures are described. Among these last methodologies, the use of multicomponent reaction, novel and efficient coupling reagents, and environmental friendly strategies, like microwave assistance and solvent-free condition in ionic liquids are also summarized. This review includes the biological assessments, docking research and studies of mechanism of action performed in order to obtain the compounds leading to the development of new drugs.

ChemInform Abstract: MCRs Reshaped into a Switchable Microwave‐Assisted Protocol Toward 5‐Aminoimidazoles and Dihydrotriazines.

A tunable microwave-assisted protocol for the synthesis of two biologically relevant families of heterocycles has been designed. Via a simple switch of reaction conditions, the same starting materials can be engaged in either an improved synthesis of the dihydrotriazine scaffold or a novel, first-in-class MCR to render the challenging 5-aminoimidazole nucleus in a single step. An additional first-in-class MCR is also reported utilizing guanidines to afford 2,5-aminoimidazoles.

Tetrazolation of Side Chains and Anhydrous Conductivity in a Hydrophobic Polymer

1H-Tetrazoles possess the lowest pKa within the azole family of nitrogen-containing heterocycles, making them attractive amphoteric moieties for anhydrous proton conduction. The synthesis of a styrenic, random coil polymer with pendent C-substituted 1H-tetrazoles is described in detail. This facile route results in a polymer containing free proton-bearing tetrazoles, limits side reactions, and proceeds using low polarity, halogenated solvents (e.g., 1,2-dichlorobenzene or chlorobenzene), which improve solubility during tetrazole cyclization. The resulting polymer, when probed by NMR spectroscopy and elemental analysis, had no measurable salt content, ensuring accurate proton conductivity measurements. Utilizing interdigitated electrodes (IDEs) in conjunction with electrochemical impedance spectroscopy (EIS), undoped anhydrous proton conductivities were measured to be as high as 10–5 S cm–1 at 120 °C. This weakly acidic, 1H-tetrazole-bearing polymer is thermally stable to 210 °C, possesses two distinct gla...

Pyrazoline: A Promising Scaffold for the Inhibition of Monoamine Oxidase

In the five membered nitrogen containing heterocyclic family, pyrazoline could be recognized as a promising scaffold for the inhibition of Monoamine oxidase. Substitution at 1, 3 and 5-position of the pyrazoline nucleus displayed a significant activity towards MAO in the past 15 years. Our study identified the detailed structure activity relationship, the structural requirement for enzyme interaction and the effect of chirality on the pyrazoline nucleus towards MAO-A and MAO-B. We propose that the selectivity of pyrazoline nucleus towards MAO isoenzyme depends up on the bulkiness of the ring in the 1 and 3 position of the scaffold. The current review revealed that the derivatives of pyrazolines have proven to be versatile pharmacophores for the inhibition of MAO on the basis of existing literatures between (1998-2013).