Oxidative Cyclization Reaction Research Articles

Selective synthesis of 2‐substituted 2,3‐dihydroquinazolin‐4(1H)‐ones and quinazolin‐4(3H)‐ones catalyzed by Schiff base dioxomolybdenum(VI) complex

AbstractSchiff base dioxomolybdenum(VI) complex is found to be a novel and efficient catalyst for the selective synthesis of 2‐substituted 2,3‐dihydroquinazolin‐4(1H)‐ones via condensation of 2‐aminobenzamide with aldehydes or ketones. Also, this catalyst is also found to be efficient for the construction of quinazolin‐4(3H)‐ones while in the presence of hydrogen peroxide as oxidant. At higher temperature the aldehydes undergo an oxidative cyclization reaction affording the quinazolin‐4(3H)‐ones. Herein we report a novel protocol with practical simplicity, broad substrate scope, good selectivity, moderate to excellent yields, and low catalyst loading (0.5% mol).

Synthesis and Biological Evaluation of a Fused Structure of Indolizine and Pyrrolo[1,2-c]pyrimidine: Identification of Its Potent Anticancer Activity against Liver Cancer Cells

A highly efficient approach to a new indolizine scaffold fused with pyrrolo[1,2-c]pyrimidine was achieved via one-pot three-component coupling followed by an oxidative cyclization reaction. The simple two-step sequence allowed rapid access to various tetracyclic compounds from commercially available starting materials with the formation of five new bonds. Here, we observed the effects of these compounds on cell viability in HepG2, H1299, HT29, AGS, and A549 cancer cell lines. Interestingly, this fused scaffold had more potent anticancer activity in hepatocellular carcinoma HepG2 and Huh7 cells than other cancer cells. In particular, 5r strongly decreased cell viability in HepG2 and Huh7 cells with an IC50 value of 0.22 ± 0.08 and 0.10 ± 0.11 µM, respectively, but had a very weak inhibitory effect on the cell viability of other cancer cell lines. In addition, 5r significantly inhibited cell migration and induced apoptosis in HepG2 and Huh7 cells via the activation of caspase-3 and cleavage of PARP in a dose-dependent manner. Notably, the co-treatment of 5r with gemcitabine resulted in the significant additional inhibition of cell viability in HepG2 and Huh7 cells. Our results suggest that 5r could be used to develop new chemotype anticancer agents against liver cancers.

Cu/TBHP mediated tetrahydroquinoline synthesis in water via oxidative cyclization reaction

Cu/TBHP mediated tetrahydroquinoline synthesis in water via oxidative cyclization reaction

Palladium‐Catalyzed Oxidative Cyclization of Azulene‐2‐Carboxylic Acids with 1,3‐Dienes for the Synthesis of Alkenyl Azulenolactones

AbstractWe have developed Pd‐catalyzed oxidative cyclization reactions of a wide range of azulene‐2‐carboxylic acids with a large number of activated as well as unactivated 1,3‐dienes, consequently allowing a streamlined synthetic method for the selective preparation of monosubstituted alkenyl dihydroazulenolactones and their derivatives.magnified image

Synthesis of dihydrofuran-3-one and 9,10-phenanthrenequinone hybrid molecules and biological evaluation against colon cancer cells as selective Akt kinase inhibitors.

A series of dihydrofuran-3-one and 9,10-phenanthrenequinone hybrid compounds were synthetized through a one-pot gold-catalyzed oxidative cyclization and Aldol-type addition cascade reaction of homopropargylic alcohols with 9,10-phenanthrenequinone. The cytotoxicity of newly synthesized compounds was evaluated in CCK8 assay against different human cancer cells, showing significantly antiproliferative activity against tested tumor cell lines with a lowest IC50 value of 0.92μM over HCT-116. Further investigation revealed that the treatment of HCT-116 cell line with the promising compound 4c induced cell death as a selective Akt inhibitor. In addition, controlled experiments and molecular docking study suggested that the significant antitumor activity might be attributed to the unique hybrid structure, which implied the promising potential of this dual heterocycle hybrid method in the discovery of novel bioactive molecules with structural diversity.

Highly Efficient Zn(L‐Pro)2 Catalyst for the Synthesis of 2‐Phenyl Benzimidazoles and 2‐Phenyl Benzothiazoles via Aerobic Oxygenation

AbstractThe synthesis of biologically active 2‐substituted benzimidazoles and benzothiazoles was developed using Zn(L‐Pro)2 as catalyst in ethanol at room temperature in an aerobic oxidative cyclization reaction involving o‐phenylenediamine and 2‐aminothiophenol with various substituted aldehydes. This process offers a quick and eco‐friendly way to synthesize a variety of pharmacologically important benzothiazoles and benzimidazoles.

Versatile Electrochemical Synthesis of Selenylbenzo[b]Furan Derivatives Through the Cyclization of 2-Alkynylphenols.

We report an electrochemical oxidative intramolecular cyclization reaction between 2-alkynylphenol derivatives and different diselenides species to generate a wide variety of substituted-benzo[b]furans. Driven by the galvanostatic electrolysis assembled in an undivided cell, it provided efficient transformation into oxidant-, base-, and metal-free conditions in an open system at room temperature. With satisfactory functional group compatibility, the products were obtained in good to excellent yields.

PIDA‐Mediated Intramolecular N‐N Bond Formation to Access 2‐Aminoindazoles and 2,2′‐Biindazoles**

AbstractA synthesis of 2‐aminoindazole and 2,2′‐biindazole derivatives from corresponding hydrazones using phenyliodine(III) diacetate (PIDA) as oxidant is reported at ambient temperature. This oxidative intramolecular cyclization reaction proceeds through the formation of the N−N bond. This protocol is metal‐free, operationally simple, has a short reaction time, and proceeds in ethyl acetate (preferred green solvent). Indazole core moieties are well established for their biological activity similarly 2‐aminoindazoles may also possess biological significance. A plausible reaction pathway has been reported based on a few control experiments.

Utility of iodine catalyzed tandem oxidation, cross-coupling and cyclisation reactions in organic synthesis

Molecular iodine is an eco-friendly, powerful catalyst and plays an important role in pharmaceutical, medicinal and organic chemistry. For a long time, molecular iodine has been hugely applied in carbohydrate chemistry. Due to the huge application of molecular iodine in oxidation, cross coupling and cyclisation reactions, it has emerged as an elegant tool in organic synthesis. Earlier I discussed (Biswas, 2021) on iodine mediated cascade oxidative functionalisation, cyclisation and annulation reactions. In this review, I describe the utility of iodine catalysed tandem oxidation, cross coupling, and cyclisation reactions in organic synthesis. Molecular iodine catalysed mild oxidative conditions yielding desired products, and oxidising techniques applied to the efficient synthesis tolerate a wide range of starting materials with aryl or alkyl replacements. These reactions were carried out as a one-pot or multi-step eco-friendly process that could be used for a wide range of drug and pharmaceutical product synthesis.

The Apparently Unreactive Substrate Facilitates the Electron Transfer for Dioxygen Activation in Rieske Dioxygenases.

Rieske dioxygenases belong to the non‐heme iron family of oxygenases and catalyze important cis‐dihydroxylation as well as O‐/N‐dealkylation and oxidative cyclization reactions for a wide range of substrates. The lack of substrate coordination at the non‐heme ferrous iron center, however, makes it particularly challenging to delineate the role of the substrate for productive O2 activation. Here, we studied the role of the substrate in the key elementary reaction leading to O2 activation from a theoretical perspective by systematically considering (i) the 6‐coordinate to 5‐coordinate conversion of the non‐heme FeII upon abstraction of a water ligand, (ii) binding of O2 , and (iii) transfer of an electron from the Rieske cluster. We systematically evaluated the spin‐state‐dependent reaction energies and structural effects at the active site for all combinations of the three elementary processes in the presence and absence of substrate using naphthalene dioxygenase as a prototypical Rieske dioxygenase. We find that reaction energies for the generation of a coordination vacancy at the non‐heme FeII center through thermoneutral H2O reorientation and exothermic O2 binding prior to Rieske cluster oxidation are largely insensitive to the presence of naphthalene and do not lead to formation of any of the known reactive Fe‐oxygen species. By contrast, the role of the substrate becomes evident after Rieske cluster oxidation and exclusively for the 6‐coordinate non‐heme FeII sites in that the additional electron is found at the substrate instead of at the iron and oxygen atoms. Our results imply an allosteric control of the substrate on Rieske dioxygenase reactivity to happen prior to changes at the non‐heme FeII in agreement with a strategy that avoids unproductive O2 activation.

Synthesis of 2‐Benzyl‐3,4‐dihydronaphthalenes via Oxidative Radical Opening/Cyclization of Methylenecyclopropanes with Potassium Benzyltrifluoroborates

AbstractA Copper‐catalyzed benzylation of methylenecyclopropanes with potassium benzyltrifluoroborate salts has been developed to produce 2‐benzyl‐3,4‐dihydronaphthalenes in moderate to good yields. This oxidative cyclization reaction proceeds well via a sequence of radical addition, ring‐opening, and cyclization. This protocol represents a new example of methylenecyclopropane oxidative cyclization and tolerates a diverse range of substrate.

An easy access to 2,3-dihydrofuran derivatives by oxidative cyclization reactions

An easy and simple access to 2,3-dihydrofuran derivatives from 1,3-dicarbonyl compounds and methyl cinnamate is reported here. The reaction was facilitated by the CAN mediated oxidative free radical cyclisation reaction. Moderate to good yields of products were obtained and preliminary studies of these showed potential medicinal activities. These compounds also find application in material chemistry and in dyes.

DMSO-assisted environmentally benign synthesis of benzo[c]-chromeno[4,3,2-gh]phenanthridines by remote oxidative hetero cross-coupling cyclization and aromatization reaction.

An unprecedented metal-free and catalyst-free synthesis of benzo[c]chromeno[4,3,2-gh]phenanthridine derivatives, a class of 1,6-diheterophenalenoid heterocycle, is reported for the first time. The oxidative cross-coupling reaction for the remote cyclization is achieved through the in situ generated o-quinone methide intermediate followed by an electrocyclic ring closure reaction. The aromatization of the cyclohexane ring is achieved by sequential H shift, hydroxylation, and elimination reaction. DMSO-assisted concomitant cyclization and aromatization reactions are also disclosed for the first time.

Electrochemical synthesis of dipyrazolo/dipyrimidine-fused pyridines via oxidative domino cyclization of C(sp3)–H bonds

An electrochemically oxidative domino cyclization reaction of methyl azaarenes/ketones with pyrazol-5-amines and 6-amino-pyrimidine-2,4-diones was developed, providing a variety of dipyrazolo/dipyrimidine-fused pyridines with moderate to good yields.

Recent synthetic methodologies for imidazo[1,5-a]pyridines and related heterocycles.

Imidazo[1,5-a]pyridine is a significant structural component of a large number of agrochemicals and pharmaceuticals. The synthesis of imidazo[1,5-a]pyridine has been a subject of intense research for numerous decades. A large number of transformations are now available to conveniently access imidazo[1,5-a]pyridine from readily available starting materials. This review details the recent development in imidazo[1,5-a]pyridine construction involving cyclocondensation, cycloaddition, oxidative cyclization, and transannulation reactions.

Copper-Catalyzed Cyclization/Dimerization of Tryptamines with O2/Air as the Sole Oxidant: Direct Access to Complex Bispyrrolidino[2,3-b]indoline.

The first transition metal catalytic one-step synthesis of the 3a, 3a'-bispyrrolidino [2,3-b] indoline scaffold via tandem cyclization/dimerization of tryptamines has been realized with the environmentally friendly O2/air as the sole oxidant. Different from the traditional direct oxidation of indole "N-H" group by excess amount of metal salts, a copper-catalyzed oxidative cyclization reaction is developed for the formation of the radical pyrrolidinoindoline intermediate in the current strategy. The robustness and practicality of this methodology is demonstrated by the step-economic, divergent total synthesis of natural products (±)-folicanthine and meso-folicanthine.

Oxidative cyclo-rearrangement of helicenes into chiral nanographenes

Nanographenes are emerging as a distinctive class of functional materials for electronic and optical devices. It is of remarkable significance to enrich the precise synthetic chemistry for these molecules. Herein, we develop a facile strategy to recompose helicenes into chiral nanographenes through a unique oxidative cyclo-rearrangement reaction. Helicenes with 7~9 ortho-fused aromatic rings are firstly oxidized and cyclized, and subsequently rearranged into nanographenes with an unsymmetrical helicoid shape through sequential 1,2-migrations. Such skeletal reconstruction is virtually driven by the gradual release of the strain of the highly distorted helicene skeleton. Importantly, the chirality of the helicene precursor can be integrally inherited by the resulting nanographene. Thus, a series of chiral nanographenes are prepared from a variety of carbohelicenes and heterohelicenes. Moreover, such cyclo-rearrangement reaction can be sequentially or simultaneously associated with conventional oxidative cyclization reactions to ulteriorly enrich the geometry diversity of nanographenes, aiming at innovative properties.

EVALUATION OF POTENTIAL ANTIMICROBIAL ACTIVITY OF SYNTHETIC FLAVONOIDS

Introduction: In recent times, most of the currently available antimicrobial agents have developed resistance. Extensive pharmacological activities including bactericidal and bacteriostatic nature of flavonoids, made them as priority agents in this aspect of research study. Synthetic flavonoids such as hydroxy thiophen derivatives were considered to evaluate for antimicrobial activity in this study. 
 Objective: The present study involves the analysis for antimicrobial activity of thiophen substituted synthetic flavonoids.
 Methods: Claisen-Schmidt method of condensation fallowed by oxidative cyclization reactions from substituted hydroxyacetophenone with aromatic aldehydes were used to synthesize the various analogues of flavonoid compounds. Then these compounds after their FTIR, 1H NMR, MS spectral characterization and elemental analysis, were screened for in vitro antibacterial and antifungal activity by using disc diffusion method followed by determining their respective zone of inhibitions.
 Results: All the synthesized test flavonoid compounds exhibited the good antibacterial and antifungal spectrum activity over B. subtilis, S. aureus, E. coli and P. aeurugenosa bacteria and Candida albicans and Aspergillus niger fungal microbes. However compounds such as F1, F2 and F4 showed moderately significant antibacterial activity against P. aerugenosa organism than the other test compounds and the same F1 and F2 test compounds exhibited significant antifungal activity at100µg concentration.
 Conclusion: The present study demonstrated that the novel thiophen substituted flavonoids (F1, F2, F3 and F4 ) found to have promising antimicrobial and antifungal activity which needs to be confirmed by in vivo studies.

Synthesis of imidazo[1,2-f]phenanthridine derivatives under a metal- and base-free condition and their anticancer activity

A series of imidazo[1,2-f]phenanthridine derivatives were synthesized from phenanthridin-6-amine and aldehydes through sulfur endorsed oxidative cyclization reaction under a metal- and base-free condition with atom economy strategy and evaluated their anticancer activity. Among all the synthesized derivatives, the compound 3d and 3f exhibited IC50 values of 2.18 ± 0.08 and 2.24 μM ± 0.71 μM, respectively. Compound 3d had the strongest inhibitory activity against HT-29 cells with an IC50 value being 1.25 μM ± 0.22 μM, which was even stronger than that of paclitaxel.

Pt(II)-Decorated Covalent Organic Framework for Photocatalytic Difluoroalkylation and Oxidative Cyclization Reactions.

A new covalent organic framework (COF) based on imine bonds was assembled from 2-(4-formylphenyl)-5-formylpyridine and 1,3,6,8-tetrakis(4-aminophenyl)pyrene, which showed an interesting dual-pore structure with high crystallinity. Postmetallation of the COF with Pt occurred selectively at the N donor (imine and pyridyl) in the larger pores. The metallated COF served as an excellent recyclable heterogeneous photocatalyst for decarboxylative difluoroalkylation and oxidative cyclization reactions.