Oxygen-containing Heterocycles Research Articles

Trifluoroacetic Acid-Mediated Oxidative Self-Condensation of Acetophenones in the Presence of SeO2: A Serendipitous Approach for the Synthesis of Fused [1,3]Dioxolo[4,5-d][1,3]dioxoles.

A method for the synthesis of fused 1,3-dioxolanes was developed by self-condensation of glyoxal generated in situ by oxidation of acetophenones with SeO2 in the presence of trifluoroacetic acid. Three molecules of the glyoxal generated by oxidation of ketone with SeO2 condensed to form architecturally novel oxygen-containing heterocycles (3a-aryldihydro-[1,3]dioxolo[4,5-d][1,3] dioxole-2,5-diyl)bis(phenylmethanones). This reaction provides a unique methodology for the construction of four C–O bonds in a concerted fashion, generating highly embedded oxygen heterocycles from readily available ketones using affordable shelf reagents and simple reaction conditions.

Synthesis, Structural Characterization, Catalytic, Biological and α-Glucosidase Inhibitory Studies of Metal Complexes with Flavone Derivatives

Heterocyclic compounds, in particular oxygen-containing heterocyclic compounds, are of special interest to medicinal chemists because of their unusual biological properties. In the present study, the highly conjugated nitrogen heterocyclic scaffold comprised of flavone derivative with metal acetates to form metal chelates of the type [MIIL(OAc)2], flavone analogues (L); M=Co2+, Zn2+, Cu2+ and Ni2+. The above title compounds were characterized using composition analysis o fCHN and spectroscopic techniques. Based on spectroscopic and analytical measurements confirmed that square planar arrangements for the Co2+, Zn2+, Cu2+ and Ni2+ complexes. Antimicrobial efficacy of prepared complexes were assessed against A.flavus, A.niger, B.subtilis, E. coli, C. albicans and S.aureus. The anti-mycobacterial (H37Rv) efficacy of flavone analogues and its complexes were screened using MABA approach and compared with standard. The acetylcholinesterase (AChE) inhibitory effect of the ligand was examined to find out the therapeutic efficiency of compound in the treatment of neurodegenerative disorders. The synthesized ligand exhibited selective inhibition (AChE & BuChe) values (IC50:0.20(flavone analogue), 2.41 (Rivastigmine) and 3.01 µM (Galantamine), respectively. Further, the in vitro ant-inflammatory efficiency of metal chelates were performed with the help of egg albumin method. The α-glucosidase inhibition activity was also carried out for the prepared metal complexes.

DFT Calculations and Molecular Docking Studies on a Chromene Derivative

Chromenes and their derivatives have been considered as an important class of oxygen-containing heterocycles. There has been an increasing interest in the study of chromenes due to their biological activity. Herein, the structural, electronic, and vibrational properties of a chromene derivative, entitled 2‐amino‐5‐oxo‐4‐phenyl‐4,5‐dihydropyrano[3,2‐c]chromene‐3‐carbonitrile and abbreviated as Chrom-D, have been reported. The FT-IR, UV-vis, and 1H-NMR and 13C-NMR chemical shifts’ measurements were recorded. The molecular geometry and the vibrational frequencies are computed in the frame of density functional theory at the B3LYP/6-311++G(d,p) level of theory. The noncovalent interactions in the crystal lattice which are responsible to the 3D crystal structure of Chrom-D are investigated based on Hirshfeld surfaces and topological reduced density gradient (RDG) analysis. Molecular electrostatic potential surface, Mulliken charges, and Fukui functions are computed in order to find out the electrophilic and nucleophilic sites. The electronic properties of the title compound have been studied based on the TD-DFT calculations. Finally, Chrom-D has been evaluated as a multifunctional agent against Alzheimer’s disease (AD).

Biowaste-Derived Heterogeneous Catalyst for the One-Pot Multicomponent Synthesis of Diverse and Densely Functionalized 2-Amino-4H-Chromenes

Chromene skeletons are crucial structural motifs existing in abundant natural products and drug molecules.1 These oxygen-containing heterocyclic compounds have a broad range of biological propertie...

Catalyst-Free Synthesis of O-Heteroacenes by Ladderization of Fluorinated Oligophenylenes.

A novel catalyst‐free approach to benzoannulated oxygen‐containing heterocycles from fluorinated oligophenylenes is reported. Unlike existing methods, the presented reaction does not require an oxygen‐containing precursor and relies on an external oxygen source, potassium tert‐butoxide, which serves as an O2− synthon. The radical nature of the reaction facilitates nucleophilic substitution even in the presence of strong electron‐donating groups and enables de‐tert‐butylation required for the complete annulation. Also demonstrated is the applicability of the method to introduce five‐, six‐, and seven‐membered rings containing oxygen, whereas multiple annulations also open up a short synthetic path to ladder‐type O‐heteroacenes and oligodibenzofurans.

Facile and Efficient Synthesis of 9-Aryl-1,8-Dioxo-Octahydroxanthenes Catalyzed by Sulfacetamide

In this study, the domino Knoevenagel-Michael and cyclization reaction between 5,5-dimethyl-1,3-cyclohexanedione (dimedone) and aryl aldehydes was performed in the presence of sulfacetamide as an organocatalyst in refluxing ethanol for the synthesis of 3,3,6,6-tetramethyl-9-aryl-1,8-dioxo-octahydroxanthene derivatives. This organocatalyzed reaction proceeds through the formation of 2,2′-[(4-(aryl)phenyl)methylene]bis[3-hydroxy-5,5-dimethylcyclohex-2-en-1-one] intermediates, leading to the construction of final oxygen-containing heterocyclic compounds. Considering the loading of the organocatalyst and the study of the effects of the solvent, it can be concluded that 2 mol% of catalyst and ethanol are the best choice to run the pseudo-three-component reaction. Furthermore, the pot-economy, atom-economy, and step-economy reaction follows some principles of green chemistry, such as cost-effectiveness, benign catalyst, and using nontoxic solvent.

Catalyst-free visible-light induced synthesis of nitrogen- and oxygen-containing heterocycles from 1,3-diketones

The synthesis of nitrogen- and oxygen-containing heterocycles has found many applications in the preparation of biomedical intermediates, yet actual synthetic procedures display limitations such as high-loading catalysts, harsh reaction conditions and tedious preparation of heterogeneous catalysts. Alternatively, photocatalysis allows to access functional products with minimum synthetic procedures and waste generation. Here, we present an efficient, simple, green protocol for the synthesis of N- and O-containing six-membered-ring compounds under mild conditions under visible blue light. Various aldehydes and 1,3-diketones can be reacted to afford eight series of corresponding 1,4-dihydropyridines and 4H-benzo[b]pyrans. This protocol has some merits such as the use of abundant and sustainable aqueous ethanol as solvent, short reaction time (within 60 min), no need of catalyst and broad functional group tolerance to afford 81 different series of target molecules in 75–96% yield under mild conditions.

The oxa-Michael reaction in the synthesis of 5- and 6-membered oxygen-containing heterocycles

In this review, we provide an updated account on the recent advances and applications of oxa-Michael reaction in the synthesis 5- and 6-membered monocyclic oxygen-containing heterocyclic compounds published in the literature since 2013 to date.

Styrylchromones: Biological Activities and Structure-Activity Relationship.

Styrylchromones (SC) are a group of oxygen-containing heterocyclic compounds, which are characterized by the attachment of a styryl group to the chromone core. SC can be found in nature or can be chemically synthesized in the laboratory. As their presence in nature is scarce, the synthetic origin is the most common. Two types of SC are known: 2-styrylchromones and 3-styrylchromones. However, 2-styrylchromones are the most common, being more commonly found in nature and which chemical synthesis is more commonly described. A wide variety of SC has been described in the literature, with different substituents in different positions, the majority of which are distributed on the A- and/or B-rings. Over the years, several biological activities have been attributed to SC. This work presents a comprehensive review of the biological activities attributed to SC and their structure-activity relationship, based on a published literature search, since 1989. The following biological activities are thoroughly revised and discussed in this review: antioxidant, antiallergic, antiviral, antibacterial, antifungal, anti-inflammatory, and antitumoral, affinity and selectivity for A3 adenosine receptors, neuroprotective, and α-glucosidase inhibition. In general, SC are composed by a promising scaffold with great potential for the development of new drugs.

Current developments in the synthesis of 4-chromanone-derived compounds

The chroman-4-one framework is a significant structural entity that belongs to the class of oxygen-containing heterocycles. It acts as a major building block in a large class of medicinal compounds, and synthetic compounds exhibit a broad variety of remarkable biological and pharmaceutical activities. Several studies have been performed to improve the methodologies of 4-chromanone-derived compounds. This review focuses on the major synthetic methods of preparation reported on chroman-4-one derivatives from 2016 to 2021.

Synthesis of Nitrogen- and Oxygen-Containing Heterocycles by Prins Cyclization in Continuous Flow

AbstractAza-silyl-Prins and oxa-Prins cyclization reactions in continuous-flow chemistry are described for the synthesis of the corresponding tetrahydropyridines and pyran derivatives, respectively. In particular, the use of pyridine-carboxaldehydes for aza-silyl-Prins reaction led to either a symmetrical triarylmethane or two new bicyclic compounds. 4-Fluorinated-2-substituted tetrahydropyran derivatives were also obtained in the oxa-Prins cyclization with good selectivity in favor of the anti-isomer.

Recent Achievement in the Synthesis of Benzo[b]furans.

Benzo[b]furan derivatives are oxygen-containing heterocyclic compounds consisting of fused benzene and furan rings and are present in a large number of natural and non-natural compounds. This class of compounds has a wide spectrum of biological activities, such as antiarrhythmic, anticancer, inflammatory, antioxidant, antimicrobial, and antiviral. Furthermore, benzo[b]furan derivatives have also been applied in various areas, such as organic electroluminescence device materials and organic dyes, photosensitizing material, organic synthesis as building blocks or intermediates. Because of a broad range of applicability, the synthesis of benzo[b]furan derivative has drawn great attention of chemists and many studies on the synthesis of this class of compounds have been reported recently. This review will give an overview of benzo[b]furan preparation based on studies dating back to the year 2012. In this review, recent development in the synthesis of benzo[b]furans are discussed. There has been increasingly new methodologies for the construction of benzo[b]furans skeleton to improve efficiency or develop environmentally friendly procedures. In some studies, reaction mechanisms were also outlined. Many methods for the synthesis of benzo[b]furans have been reported recently. Most of them involve cyclization or cycloisomerization processes. Unquestionably, more imaginative strategies for the construction of benzo[b]furan skeleton will be established in the near future. Application of known methods to natural products or drug synthesis, on industrial scale for the synthesis of economically or medicinally important benzo[ b]furans will probably be paid attention to.

Syntheses of 3,3-Disubstituted Dihydrobenzofurans, Indolines, Indolinones and Isochromanes by Palladium-Catalyzed Tandem Reaction Using Pd(PPh3)2Cl2/(±)-BINAP as a Catalytic System

A general procedure for the tandem arylation reaction of arylbromide with heteroaryl compounds was developed by using Pd(PPh3)2Cl2/(±)-BINAP (1,1′-Binaphthalene-2,2′-diylbis (diphenylphosphane)) as catalytic system. Both sulphur- and oxygen-containing heterocycles were also employed as an efficient reagent for arylation, which gave moderate to excellent yields with moderate to good regioselectivities (5:1 to > 20:1 ir (isomer ratio)). Except for dihydrobenzofurans, indolines and indolinones, this type of tandem reaction was also expanded to synthesize isochromanes. The synthesized new compounds were well characterized through different spectroscopic techniques, such as 1H and 13C NMR (nuclear magnetic resonance), and mass spectral analysis.

Synthesis of Oxygen-Containing Heterocyclic Compounds by Iron-Catalyzed Alkylative Cyclization of Unsaturated Carboxylic Acids and Alcohols.

Iron-catalyzed alkylative cyclization of alkenes bearing oxygen nucleophiles with secondary and tertiary alkyl bromides through carbon-carbon and carbon-oxygen bond formations has been developed. A broad substrate scope is an attractive feature of this synthetic method, providing a variety of potentially bioactive five- and six-membered oxygen-containing heterocycles. The reaction pathway is proposed to involve a radical addition of the in situ-formed alkyl radical to an alkene followed by carbon-oxygen bond-forming intramolecular cyclization.

Ultrasound Promoted Green Synthesis of Spiro Indoline-3,4′-pyrano[2,3-c]pyrazoles

Pyranopyrazoles make up one of the interesting classes of oxygen-containing heterocycles 1 known to have valuable medicinal properties such as anti-dysplasia, hypoglycaemic, 2 anti-microbial, 3 ant...

Synthesis of chimeric amides of 2-arilaminopyrimidine series

Methodological approaches to the synthesis of 2-arylpyrimidine amides with predicted antitumor activity using the design of chimeric molecules by combining pharmacophore fragments of known antitumor drugs are considered. The results of the synthesis of chimeric amides containing, along with the 2-amino-pyrimidine fragment, fragments of other nitrogen and oxygen-containing heterocycles (piperazine, morpholine, isoxazole, etc.), aromatic cycles (benzene, methylnitroaniline, phenylenediamine) and functional (methyl-, amino-, carboxy-, etc.) groups in different positions of the molecule, are presented.

Synthesis of enantiomerically pure oxygen-containing helical heterocycles via stereospecific rearrangement of benzofused-2,2′-diphenoquinone derivatives

Three different enantiomerically pure poly-condensed oxygen-containing heterocyclic compounds were synthesized by the rearrangement of enantiomerically pure (P)- and (M)-benzofused-2,2′-diphenoquinones. The three products were: a spiro compound bearing a γ-lactone ring, and two derivatives with a helical structure, one containing a δ-lactone ring and the other oxepin and furan rings. When the helical quinone derivative was heated in solution, the rearrangement proceeded with retention of configuration. Thus, (P)-quinone derivatives gave the corresponding (S)-spiro and (P)-helicene-like derivatives without compromising their enantiomeric purity, and vice versa.

Cocatalyst-controlled divergent cascade cycloaddition reaction of arylalkynols and dioxopyrrolidienes: access to spiroketals and oxa-bridged eight-membered cyclic ethers

A cocatalyst-controlled divergent cascade cycloaddition reaction was developed for the synthesis of two different complex oxygen-containing heterocyclic compounds from arylalkynols and dioxopyrrolidienes in the presence of Au(i) catalyst.

Base-Mediated One-pot Synthesis of Oxygen-Based Heterocycles from 2-Hydroxyphenyl-Substituted para-Quinone Methides.

One-pot synthesis of oxygen-containing heterocycles has been achieved through alkylation/acylation of 2-hydroxyphenyl-substituted para-quinone methides followed by an intramolecular 1,6-conjugate addition/cyclization and oxidation sequence. This protocol provides access to a wide range of oxygen-based heterocycles, such as 2,3-disubstituted benzo[b]furans, 2,3-dihydrobenzofurans and diaryl-substituted coumarin derivatives in moderate to good yields.

An Overview of Saturated Cyclic Ethers: Biological Profiles and Synthetic Strategies.

Saturated oxygen heterocycles are widely found in a broad array of natural products and other biologically active molecules. In medicinal chemistry, small and medium rings are also important synthetic intermediates since they can undergo ring-opening and -expansion reactions. These applications have driven numerous studies on the synthesis of oxygen-containing heterocycles and considerable effort has been devoted toward the development of methods for the construction of saturated oxygen heterocycles. This paper provides an overview of the biological roles and synthetic strategies of saturated cyclic ethers, covering some of the most studied and newly discovered related natural products in recent years. This paper also reports several promising and newly developed synthetic methods, emphasizing 3–7 membered rings.