Five-membered Heterocyclic Ring Research Articles

A mechanistic study of the activation of small molecules (H2 and C2H2) by group 14 analogues of selenophene

In this study, the reactivity influenced by group 14 elements (E = C, Si, Ge, Sn, and Pb), which are used as substituents in heterocyclic five-membered rings, was theoretically examined by using density functional theory (B3PW91/def2-SVP).

A Mini-Review 5-Amino-N-Substituted Pyrazoles as Building Blocks for Bioactive Molecules

In this review a five-membered heterocyclic ring having two adjacent nitrogen atoms known as Pyrazole, we have framed 5-amino-N-substituted pyrazoles in particular focusing on its substantial role as a building block and starting materials for producing enormous heterocyclic skeletons. The existence of this moiety in larger compounds renders them to expose medicinal, pharmacological and biological therapeutic activities. Enormous drugs contain 5-amino-N-substituted pyrazoles such as celecoxib anti-inflammatory, antipsychotic, anti-obesity, analgesic, and antidepressant. We reported various routes of synthesis and the use of these compounds.

Synthesis of Pyrimidine-Annulated Five-Membered Heterocycles: An Overview

This review describes the non-exhaustive scenery of the synthesis of various biologically interesting pyrimidine annulated five-membered heterocyclic ring systems that have been appeared in the literature during the last two decades. During this period, different synthetic routes and various methodologies have been developed for the functionalization of pyrimidine ring towards the construction of five-membered heterocyclic rings. The aim of this review is to give an overview of the assorted methodologies that have been reported about the chemistry of construction of pyrimidines annulated nitrogen, oxygen and sulphur containing five-membered heterocycles.

Overview of recent developments of pyrazole derivatives as an anticancer agent in different cell line.

Pyrazole is a five-membered aromatic heterocyclic ring with two adjacent nitrogen atoms C3H3N2H.The presence of this nucleus in pharmacological agents of various therapeutic categories gifts a broad spectrum of biological activities and pharmaceuticals that contain pyrazole like celecoxib (anti-inflammatory), CDPPB (antipsychotic), Rimonabant (anti-obesity), Difenamizole, (Analgesic), Betazole (H2 receptor agonist), Fezolamide (Antidepressant), etc… The pharmacological potential of the pyrazole fraction is proved in many publication where they synthesized and evaluated pyrazoles against several biological agents. The aim of this article review is to survey recent works linking pyrazole structures to anticancer activities corresponding to 9 different type of cancer.

Interface-Hybridization-Enhanced Photothermal Performance of Polypyrrole/Polydopamine Heterojunctions on Porous Nanoparticles.

Photothermal conversion agents (PTCAs) based on π-conjugated polymers are promising for cancer therapy, but the alteration of bandgap energies toward boosted photothermal properties remains challenging. Herein, polymer PTCAs with heterojunctions of a binary optical component are developed by interface hybridization on porous particles. Specifically, polypyrrole (PPy) nanodomains are successfully hosted on the wet-adhesive surface of mesoporous polydopamine nanoparticles through the loading and polymerization of pyrrole in the confined pore space (≈5.0 nm). The near-infrared absorbing polymers in the heterojunctions possess similar five-membered heterocyclic rings and can interact mutually to generate photoinduced electron transfer (PET). Such a large-area optoelectronic interaction progressively reduces the bandgap energy (down to 0.56 eV) by increasing the doped amount of PPy, which consequently enhances the extinction coefficient and photothermal conversion efficiency by 4.6- and 2.2-fold, respectively. Notably, the hybrid PTCA exhibits good biocompatibility, photocytotoxicity, and great potential for cancer therapy.

Resonance electron interaction with five-membered heterocyclic compounds: Vibrational Feshbach resonances and hydrogen-atom stripping

Low-energy (0--15 eV) resonance electron attachment to a series of five-membered heterocyclic rings (isoxazole, imidazole, pyrazole, pyrrole, 1-methyl-, and 2-methylimidazole) is studied under gas-phase conditions by means of electron transmission spectroscopy and dissociative electron attachment spectroscopy (DEAS). Experimental spectral features are assigned on the basis of Hartree-Fock and density functional theory calculations. Sharp features, with a width of less than 0.1 eV, observed in the electron transmission spectra of imidazole, pyrazole, and pyrrole close to 0.45 eV, i.e., well below the energy of their lowest-lying ${\ensuremath{\pi}}^{*}$ shape resonances detected at 1.90, 1.87, and 2.33 eV, respectively, are associated with formation of negative ion states bound by long-range electron-molecule interactions. Effective range theory calculations which include both dipolar and polarization interactions support this interpretation. In addition to the general observation of cleavage of the N--H bond at incident electron energies close to 2 eV, elimination of as many as three hydrogen atoms from the molecular negative ions is detected at higher energies by DEAS with the only exception of methylated imidazoles. This complex process is associated with ring opening and formation of diatomic hydrogen as one of the neutral fragments, as indicated by the calculations to satisfy the energetic requirements. The present results are of importance for understanding the basic mechanisms of damages caused in living tissues by high-energy radiations.

Sulfate radical-based oxidation of the antibiotics sulfamethoxazole, sulfisoxazole, sulfathiazole, and sulfamethizole: The role of five-membered heterocyclic rings.

The widespread occurrence of sulfonamides (SAs) in natural waters, wastewater, soil and sediment has raised increasing concerns about their potential risks to human health and ecological systems. Sulfate radical (SO4-)-based advanced oxidation processes (SR-AOPs) have become promising technologies to remove such contaminants in the environment. The present study systematically investigated the degradation of four selected SAs with different five-membered heterocyclic rings, namely, sulfamethoxazole (SMX), sulfisoxazole (SIX), sulfathiazole (STZ), and sulfamethizole (SMT), by thermo-activated persulfate (PS) process, and the role of heterocyclic rings was assessed particularly. The results revealed that all the selected SAs could be degraded efficiently by thermo-activated PS process and their decay rates were appreciably increased with increasing temperature. For instance, degradation rates of STZ increased from 0.3 × 10-3 to 19.5 × 10-3 min-1 as the temperature was increased from 30 to 60 °C. Under the same experimental conditions, the degradation rates of SAs followed the order of SIX > SMX ≈ STZ > SMT, which was in accordance with decay rates of their R-NH2 moieties. Kinetic results indicated that five-membered heterocyclic rings could serve as reactive moieties toward SO4- attack, which were confirmed by frontier electron density (FED) calculations. Based on the transformation products identified by high-resolution mass spectrometry (HR-MS), five different oxidation pathways, including hydroxylation, aniline moiety oxidation, dimerization, sulfonamide bond cleavage, and heterocyclic ring oxidation/cleavage were proposed. Moreover, the degradation efficiency in real surface water (RSW) was found to be slightly slower than that in artificial surface water (ASW), suggesting that SR-AOPs could be an efficient approach for remediation of soil and water contaminated by these SAs.

SYNTHESIS AND BIOLOGICAL EVALUATION OF 1-SUBSTITUTED-2-THIENYL- 5-(4-CHLOROPHENYL) PYRAZOLINE DERIVATIVES AS ANTIPROLIFERATIVE AGENTS

Cancer is not a single disease, but a large group of diseases characterized by uncontrolled, rapid and pathological proliferation of abnormally transformed cells. Pyrazoline is a five-membered heterocyclic ring having two adjacent nitrogen atoms within the ring. It has only one endocyclic double bond and is basic in nature. The present study involves synthesis of 1-substituted-2-thienyl-5-(4-chlorophenyl) pyrazoline derivatives. The synthesized compounds were subjected to anticancer screening against SK-OV-3 cells line to determine the growth inhibitory effects of the compounds. Amongst all the derivatives in series (6a-j), the pyrazoline derivatives exhibited potent anticancer activity. All synthesized compounds possessed good to moderate anticancer activity. Compounds 6b and 6c at concentration 80 μg/mL possessed % control growth inhibition comparable to standard drug andriamycin. The order for the % control growth inhibition of SK-OV-3 was found to be 6h> 6j> 6f> 6i> 6e> 6g> 6d> 6a. All the compounds inhibited 50 % of the cell growth at the conc.

De Novo Synthesis of Highly Functionalized Benzimidazolones and Benzoxazolones through an Electrochemical Dehydrogenative Cyclization Cascade.

Benzimidazolone and benzoxazolone moieties are important scaffolds in a variety of pharmaceutical molecules. These bicyclic heterocycles are usually prepared from a benzene derivative through the construction of an additional five-membered heterocyclic ring. We report herein a method that enables the efficient synthesis of highly substituted benzimidazolone and benzoxazolone derivatives by building both the benzene and the heterocyclic rings through a dehydrogenative cyclization cascade. Readily available arylamine-tethered 1,5-enynes undergo a biscyclization/dehydrogenation cascade to afford functionalized benzanellated heterocycles in a single step with complete control of regioselectivity. These electricity-powered oxidative transformations proceed with H2 evolution, thus obviating the need for transition-metal-based catalysts and oxidizing reagents.

Effect of chalcogen atoms on the electronic band gaps of donor-acceptor-donor type semiconducting polymers: a systematic DFT investigation.

We systematically investigated and compared the electronic band gaps of 16 different donor-acceptor-donor type semiconducting polymer systems that included different chalcogen atoms in their donor and acceptor units. The five-membered heterocyclic rings furan, thiophene, selenophene, and tellurophene were considered as electron donor units, whereas benzochalcogenadiazole groups, i.e., benzoxadiazole, benzothiadiazole, benzoselenadiazole, and benzotelluradiazole, were used as electron acceptor units. Our findings from B3LYP/6-31G(d) and B3LYP/LANL2DZ calculations performed with and without the polarizable continuum model indicated that the size of the chalcogen atom used as a heteroatom in the donor units plays a more important role than the size of the chalcogen atom in the benzochalcogenadiazole acceptor unit does. On the other hand, our results also suggest that the best way to modify and narrow the electronic band gap is to use heavy chalcogen atoms in both donor and acceptor units.

(R,R/S,S)-9-Benzyl-3-methyl-7-phenyl-1,6-dioxa-3,9-diazaspiro[4.4]nonane-2,8-dione

The title compound, C19H18N2O4, a rare example of a spirocyclic orthoamide, was synthesized by a double cyclization of a N-Boc protected sarcosine derivative. The crystal structure of the racemic (R,R/S,S) modification reveals two near-orthogonal five-membered heterocyclic ring systems, each in an envelope configuration.

The impact of the heteroatom in a five-membered ring on the photophysical properties of difluoroborates

A series of novel BF2 complexes, bearing a five-membered heterocyclic ring (with X = NMe, O, and S), were synthesized and characterized with a focus on the influence of atom exchange on the photophysical properties of both unsubstituted and dimethylamino derivatives. The experimental results show that the optical spectra substantially differ in both sets of dyes. In particular, the dimethylamino series are more strongly affected by heteroatom substitution, i.e., the insertion of X = O or X = S in lieu of X = NMe causes substantial bathochromic shifts of the absorption and emission bands, as well as marked changes in their topologies. In contrast, the optical spectra of the unsubstituted compounds undergo only relatively small red-shifts, and no variation of band shapes is observed. Moreover, the measured absorption spectra of the unsubstituted compounds bearing X = NMe and X = O are almost identical. Interestingly, the fluorescence yields of the dimethylamino derivatives are much larger (up to one order of magnitude) than those of the corresponding unsubstituted compounds. The experimental analyses are supported by state-of-the-art quantum chemistry calculations, which satisfactorily reproduced the experimental trends and provided further insights into the observed optical signatures.

Triazole derivatives and their antiplasmodial and antimalarial activities

Malaria, caused by protozoan parasites of the genus Plasmodium especially by the most prevalent parasite Plasmodium falciparum, represents one of the most devastating and common infectious disease globally. Nearly half of the world population is under the risk of being infected, and more than 200 million new clinical cases with around half a million deaths occur annually. Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance, so it's imperative to develop new antimalarials with great potency against both drug-susceptible and drug-resistant malaria. Triazoles, bearing a five-membered heterocyclic ring with three nitrogen atoms, exhibit promising in vitro antiplasmodial and in vivo antimalarial activities. Moreover, several triazole-based drugs have already used in clinics for the treatment of various diseases, demonstrating the excellent pharmaceutical profiles. Therefore, triazole derivatives have the potential for clinical deployment in the control and eradication of malaria. This review covers the recent advances of triazole derivatives especially triazole hybrids as potential antimalarials. The structure-activity relationship is also discussed to provide an insight for rational designs of more efficient antimalarial candidates.

Energetic furazan-triazole hybrid with dinitromethyl and nitramino groups: decreasing sensitivity via the formation of a planar anion.

Energetic salts (4, 5 and 7-11) of 3-(3-dinitromethanide-1H-1,2,4-triazol-5-yl)-4-nitraminofurazanate and the azo compound (15) as well as its ammonium (14), hydrazinium (16) and hydroxylammonium (17) salts were synthesized and fully characterized. The structures of 5 and 15 were confirmed by single crystal X-ray diffraction analysis. The hydroxylammonium salt (5) has a high measured density (1.85 g cm-3) and shows promising properties as a replacement for the traditional explosive (RDX). The anion is planar which suggests that a combination of two heterocyclic five-membered rings with nitramino and dinitromethyl groups could open a new avenue to advanced energetic materials with high detonation performance and good sensitivities.

Copper Catalysts in the Synthesis of Five-membered N-polyheterocycles

Background: Due to significant biological activity associated with N-, O- and S-heterocycles, a number of reports for their synthesis have appeared in recent decades. Traditional approaches require expensive or highly specialized equipment or would be of limited use to the synthetic organic chemist due to their highly inconvenient approaches. This review summarizes the applications of copper catalysts with the emphasis on their synthetic applications for nitrogen bearing polyheterocylces. In summary, this review article describes the synthesis of a number of five-membered poly heterocyclic rings. Objective: Nowadays new approaches that employ atom-economical and efficient pathway have been developed. The researchers are following natural models to design and synthesize heterocycles. The transition metal catalyzed protocols have attracted the attention as compared to other synthetic methodologies because they use easily available substrates to build multiple substituted complicated molecules directly under mild conditions. In organic synthesis, constituted by transition metal catalyzed coupling transformations are one of the most powerful and useful protocols. The N-heterocycles are synthesized by this convenient and useful tool. Conclusion: The efficient and chemoselective synthesis of heterocycles by this technique has appeared as an important tool. This review shows a highly dynamic research field and the employment of copper catalysts in organic synthesis. Several strategies have been pointed out in the past few years, to meet more sustainable, efficient and environmentally benign chemical products and procedures. The catalytic strategies have been the focus of intense research because they avoid the use of toxic reagents. Among these catalytic strategies, highly rewarding and an important method in heterocycles synthesis is metal catalyzed synthesis.

Photoinduced Heterocyclic Ring Opening of Furfural: Distinct Open-Chain Product Identification by Ultrafast X-ray Transient Absorption Spectroscopy.

The ultraviolet-induced photochemistry of five-membered heterocyclic rings often involves ring opening as a prominent excited-state relaxation pathway. The identification of this particular photoinduced mechanism, however, presents a challenge for many experimental methods. We show that femtosecond X-ray transient absorption spectroscopy at the carbon K-edge (∼284 eV) provides core-to-valence spectral fingerprints that enable the unambiguous identification of ring-opened isomers of organic heterocycles. The unique differences in the electronic structure between a carbon atom bonded to the oxygen in the ring versus a carbon atom set free of the oxygen in the ring-opened product are readily apparent in the X-ray spectra. Ultrafast ring opening via C-O bond fission occurs within ∼350 fs in 266-nm photoexcited furfural, as evidenced by fingerprint core (carbon 1s) electronic transitions into a nonbonding orbital of the open-chain carbene intermediate at 283.3 eV. The lack of recovery of the 1sπ* ground-state depletion in furfural at 286.4 eV indicates that internal conversion to the ground state is a minor channel. These experimental results, augmented by recent advances in the generation of isolated attosecond pulses at the carbon K-edge, will pave the way for probing ring-opened conical intersection dynamics in the future.

Novel desferrioxamine derivatives synthesized using the secondary metabolism-specific nitrous acid biosynthetic pathway in Streptomyces davawensis.

Recently, a novel nitrous acid biosynthetic pathway composed of two enzymes was discovered to be involved in the biosynthesis of cremeomycin for the formation of its diazo group. In this pathway, CreE oxidizes L-aspartic acid to nitrosuccinic acid and CreD liberates nitrous acid from nitrosuccinic acid. Bioinformatic analysis showed that various actinobacteria have putative secondary metabolite biosynthesis gene clusters containing creE and creD homologs, suggesting that this pathway is widely used for the biosynthesis of various natural products. Here, we focused on creE and creD homologs (BN159_4422 and BN159_4421) in Streptomyces davawensis. In vitro analysis of recombinant BN159_4422 and BN159_4421 proteins showed that these enzymes synthesized nitrous acid from L-aspartic acid. Secondary metabolites produced by this gene cluster were investigated by comparing the metabolic profiles of the wild-type and ΔBN159_4422 strains. When these strains were co-cultured with Tsukamurella pulmonis TP-B0596, three compounds were specifically produced by the wild-type strain. These compounds were identified as novel desferrioxamine derivatives containing either of two unique five-membered heterocyclic ring structures and shown to have iron-binding properties. A putative desferrioxamine biosynthetic gene cluster was found in the S. davawensis genome, and inactivation of a desD homolog (BN159_5485) also abolished the production of these compounds. We propose that these compounds should be synthesized by the modification of desferrioxamine B and a shorter chain analog using nitrous acid produced by the CreE and CreD homologs. This study provides an important insight into the diverse usage of the secondary metabolism-specific nitrous acid biosynthetic pathway in actinomycetes.

π-Electron delocalization in 2-benzoyl-5-phenylpyrazolidin-3-one

Abstract The crystal and molecular structures of 2-benzoyl-5-phenylpyrazolidin-3-one have been characterized by X-ray diffraction along with density functional theory studies. Cinnamic acid chloride was reacted with benzhydrazide, yielding 2-benzoyl-5-phenylpyrazolidin-3-one. This product was formed in the transformation comprising the nucleophilic addition of benzhydrazide to the styryl fragment of the α,β-unsaturated arrangement and subsequent cyclization. The molecule contains two benzene rings and one five-membered heterocyclic ring with an N–N single bond. The five-membered ring is composed of three atoms of sp 3 hybridization and two atoms of sp 2 hybridization, which cause the flattening of the heterocyclic ring. The Harmonic Oscillator Model of Aromaticity and Nucleus-Independent Chemical Shift indexes, calculated for the benzene rings, demonstrate that there are no substantial interactions between the regions of π-electron delocalization in the molecule. In the crystal structure, there are N–H···O hydrogen bonds that link the molecules along the crystallographic c axis and weak intermolecular C–H···O hydrogen bonds.

Investigation on the Effects of Antimicrobial imidazo[2,1-b]thiazole Derivatives on the Genitourinary Microflora.

Fused five-membered heterocyclic rings containing bridgehead nitrogen atom are particularly versatile in the field of medicinal chemistry because of their different biological activities. Among them, the imidazo[2,1-b]thiazole is an attractive fused heterocyclic core that has been extensively studied. The aim of the current study was to study the therapeutic applications of imidazo[2,1- b]thiazole derivatives as antimicrobial agents for the treatment of genitourinary infections. A traditional synthetic methodology was involved to obtain a small series of imidazothiazole derivatives. Herein, we report the antimicrobial activity of the imidazo[2,1-b]thiazole or imidazo[2,1- b]thiazolidine derivatives against selected fungi, Gram-positive and Gram-negative bacteria. Moreover, experiments were carried out to investigate the interference towards the endogenous microbiota. The most interesting of the series are the thiocyano derivatives (19, 23) showing a good profile for the treatment of genitourinary infections: a spectrum of activity covering both bacteria and fungi together with a reduced impact versus critical lines of Lactobacillus exerting defense against pathogens.

Charge distribution and conformational stability effects of organic structure-directing agents on zeolite synthesis.

While the use of the so-called organic structure-directing agents (OSDAs) is no stranger to zeolite synthesis at all, the effects of their charge distribution and conformational stability on the phase selectivity of the crystallization remain elusive. To systematically investigate these effects, we have prepared a series of imidazolium and pyrazolium derivatives with the same geometric shape but different positions of nitrogen atoms in the five-membered heterocyclic aromatic ring and used them as OSDAs for the synthesis of zeolites with pure-silica composition. Meaningful differences in the zeolite product were observed.