Synthesis Of Quinazolinones Research Articles

Ruthenium-Catalyzed Carbonylative Synthesis of Quinazolinones

Ruthenium-Catalyzed Carbonylative Synthesis of Quinazolinones

One-Pot Magnetic Iron Oxide-Carbon Nanodot Composite-Catalyzed Cyclooxidative Aqueous Tandem Synthesis of Quinazolinones in the Presence of tert-Butyl Hydroperoxide.

The development of synthetic protocols for biologically important molecules using biocompatible catalysts in aqueous medium holds the key in green and sustainable chemistry. Herein, a magnetically recoverable iron oxide–carbon dot nanocomposite has been demonstrated as an effective catalyst for cyclooxidative tandem synthesis of quinazolinones in aqueous medium using alcohols as starting materials. Fluorescent carbon dots, the newest entrant in the nanocarbon family, were used as the stabilizing agent for the iron oxide nanoparticles, and a continuous layer of carbon dots decorates the iron oxide nanoparticle surface as observed by transmission electron microscopy. The fluorescence studies demonstrated the effective electron transfer from carbon dots to the iron oxide nanoparticles resulting in complete quenching of emission owing to carbon dots, once it binds with iron oxide nanoparticles. The nanocatalyst showed high activity with significant reusability for the syntheses of quinazolinones in the presence of tert-butyl hydroperoxide (TBHP) in an aqueous medium. Controlled experiments revealed the synergistic effect of carbon dots in enhancing the catalytic activity of iron oxide, as they might influence the decomposition of TBHP into radicals owing to their peroxidase activity. These radicals stabilized over the nanoparticle surface are known to have increased lifetime compared to solution-based radicals. These surface-stabilized radicals then could catalyze the tandem reaction resulting in the formation of the quinazolinone derivatives in high yields.

Cu(II)–Glucose: Sustainable Catalyst for the Synthesis of Quinazolinones in a Biomass-Derived Solvent 2-MethylTHF and Application for the Synthesis of Diproqualone

An efficient method for the synthesis of quinazolinones by a domino cross-coupling reaction of 2-halobenzoic acids and amidines is demonstrated for the first time using a copper–glucose combination as an inexpensive catalytic system in a biomass-derived green solvent 2-methylTHF. Here, glucose plays a dual role, both as a reducing agent generating the low-valent copper ions from cupric precursors and as a chelating agent of the generated low-valent copper species, thereby impeding their deactivation. A wide variety of quinazolinones were synthesized in good to excellent yields. Notably, the activation of less reactive 2-bromo/chlorobenzoic acids by the catalyst not only advocates the efficiency of the developed protocol but also the broad substrate scope. Moreover, the developed methodology was successfully applied to the synthesis of the drug molecule diproqualone. The UV–vis spectrophotometric titration study of cupric and cuprous salts with glucose showed evidence of glucose playing the role as a ligan...

"On-Water" Synthesis of Quinazolinones and Dihydroquinazolinones Starting from o-Bromobenzonitrile.

A versatile and practical “on-water” protocol was newly developed to synthesize quinazolinones using o-bromobenzonitrile as a novel starting material. Studies have found that air as well as water plays an important role in synthesis of quinazolinones. Further investigation indicated that dihydroquinazolinones can be prepared with this protocol under the protection of N2. The protocol can be extended to other substrates and various quinazolinones and dihydroquinazolinones were obtained. o-Bromobenzamide, o-aminobenzonitrile, and o-aminobenzamide were also evaluated as starting materials, and the results further proved the versatility of this protocol, especially towards dihydroquinazolinones.

The Synthesis of Quinazolinones from Olefins, CO, and Amines over a Heterogeneous Ru-clusters/Ceria Catalyst.

Quinazolinones, an important class of heterocyclic compounds, have been widely used in pharmaceuticals because of their biological activity. However, the efficient and economical synthesis of quinazolinones has remained a challenge. A novel synthetic approach has now been developed to produce quinazolinones from olefins, CO, and amines over heterogeneous Ru-clusters/ceria catalyst in the absence of acids, bases, and oxidants. Furthermore, H2 O is generated as the only by-product. A series of quinazolinones with aromatic or non-aromatic substituents can be obtained in yields of up to 99 %. The Ru-clusters/ceria can be reused at least four times. The analysis of the E-factor (environmental impact factor) for the synthesis of 2-ethyl quinazolinone suggests that this system is more environmentally friendly than other processes reported previously.

The Synthesis of Quinazolinones from Olefins, CO, and Amines over a Heterogeneous Ru‐clusters/Ceria Catalyst

AbstractQuinazolinones, an important class of heterocyclic compounds, have been widely used in pharmaceuticals because of their biological activity. However, the efficient and economical synthesis of quinazolinones has remained a challenge. A novel synthetic approach has now been developed to produce quinazolinones from olefins, CO, and amines over heterogeneous Ru‐clusters/ceria catalyst in the absence of acids, bases, and oxidants. Furthermore, H2O is generated as the only by‐product. A series of quinazolinones with aromatic or non‐aromatic substituents can be obtained in yields of up to 99 %. The Ru‐clusters/ceria can be reused at least four times. The analysis of the E‐factor (environmental impact factor) for the synthesis of 2‐ethyl quinazolinone suggests that this system is more environmentally friendly than other processes reported previously.

Kosmotropes Perturbation and Ambiphilic Dual Activation: Responsible Features for the Construction of C‐N Bond towards the Synthesis of Quinazolin‐4(3H)‐ones in Water

AbstractA novel water assisted strategy has been developed for the synthesis of quinazolinones by the reaction of o‐aminobenzamides 1 with benzyl alcohols 2 using NaCl in regioselective manner under microwave radiation (MW). NaCl and water plays an unprecedented and vital role in the reaction. NaCl create more space for the reactants in aqueous media and bring them in very close proximity for C−N bond formation through “kosmotropes perturbation”. There is no need of any metal, ligand and base for further activation of the reactants in the reaction because water trigger the reaction via “ambiphilic dual activation” of reactants through hydrogen bond accepter and donor ability in the pertinent C−N bond forming steps in the reaction. This “kosmotropes perturbation” and “ambiphilic dual activation” is the accountable attribute for making a new water‐assisted strategy. Several controlled experiments have been carried out to establish the suitable mechanism and stipulation of the reactions. The process illustrated significant selectivity for quinazolinones over dihydrogenated quinazolinones.

Metal-free oxidative cyclization of 2-amino-benzamides, 2-aminobenzenesulfonamide or 2-(aminomethyl)anilines with primary alcohols for the synthesis of quinazolinones and their analogues

A general metal-free oxidative cyclization process has been developed for the synthesis of quinazolinones, benzothiadiazines and quinazolines. By this protocol, a range of substituted 2-aminobenzamides, 2-aminobenzenesulfonamide and 2-(aminomethyl)anilines react with various alcohols, leading to the desired annulated products smoothly. This protocol features many advantages as broad substrate scope, mild reaction conditions, low environmental pollution, high atom-economy and good to excellent yields.

Synthesis of quinazolinones and benzazoles utilizing recyclable sulfated metal-organic framework-808 catalyst in glycerol as green solvent

Zirconium-based metal-organic framework MOF-808 was synthesized, and sulfated with aqueous sulfuric acid. Sulfated MOF-808 was utilized as a recyclable heterogeneous catalyst for the synthesis of quinazolinones from β-ketoesters and benzamides, and for the synthesis of benzimidazoles from β-ketoesters and o-phenylenediamines in glycerol as a green solvent. The sulfated MOF-808 catalyst was more active than many heterogeneous and homogeneous catalysts. The combination of the sulfated MOF-808 and glycerol was also effective for the reaction of o-aminothiophenols with β-diketones or cyclic β-diketones to produce benzothiazoles. To our best knowledge, MOF-based catalysts were not previously utilized as heterogeneous catalyst in glycerol as green solvent.

Heterogeneous AlPO4(SO3H) nanosheets: novel catalyst for the multi-component synthesis of quinazolinones and highly functionalized piperidines

Nanosheets AlPO4(SO3H) as a highly active solid acid catalyst were prepared and characterized. The morphology of obtained catalyst exhibited nanosheets with ∼ 25–35 nm thickness. The heterogeneous nanocatalyst was characterized by FT-IR, EDX, and FE-SEM analysis. The nanosulfonated-AlPO4 were found useful for cyclization synthesis of highly functionalized piperidines and quinazolinones derivatives in good to excellent yields. Notable features include easy and quick isolation of products, ease of handling of the catalyst at low cost, no need to purify with column chromatography, and mild reaction conditions. In addition, according to the literature, another significant feature of our method for quinazolinone synthesis is that structurally diverse molecules were synthesized. Finally, the newly developed catalytic systems avoid the use of toxic metal catalysts and were reused up to 5 times without a noticeable their catalytic activity.

A silver catalyzed domino reaction of N-cyanamide alkenes and 1,3-dicarbonyls for the synthesis of quinazolinones.

A silver catalyzed domino reaction of N-cyanamide alkenes and 1,3-dicarbonyls including 1,3-diketones and ethyl acetoacetate has been developed for the facile synthesis of quinazolinones. In the presence of AgNO3/K2S2O8, the diketones could be converted to radicals and coupled with N-cyanamide alkenes to undergo a cyclization cascade for accessing quinazolinones. This method features mild reaction conditions, readily available starting materials, and valuable synthetic utility. Moreover, the products could be further transformed into various heterocycles.

Basic ionic liquid as catalyst and surfactant: green synthesis of quinazolinone in aqueous media.

Basic imidazolium-based ionic liquids not only possess the extraordinary physicochemical properties of ionic liquids, but also have excellent basicity and surfactivity. 1-Propyl-3-alkylimidazole hydroxide ionic liquids ([PRIm][OH]) were synthesized and their catalytic and surfactant behavior were studied in this work. [PRIm][OH] owned excellent surfactivity, and their alkyl chains and ion pairs benefit hydrophobicity and hydrophilicity respectively. The surfactivity of [PRIm][OH] increased with increasing alkyl chain length. [PRIm][OH] showed better catalytic performance than NaOH in the condensation of 2-aminobenzonitrile with cyclohexanone in aqueous medium, and the catalytic performance was well coincident with their surfactant behavior. [PRIm][OH] could decrease the interfacial tension of solvent effectively and form micelles in water. The formed micelles could solubilise more reactants into water and effectively increase the chance of contact between reactants and catalytic active sites. The catalyst dosage obviously affected catalytic performance. The catalytic system is a promising recyclable system.

Palladium-catalyzed oxidative CC bond cleavage with molecular oxygen: one-pot synthesis of quinazolinones from 2-amino benzamides and alkenes

Palladium-catalyzed oxidative cleavage/cyclization has been disclosed for the concise synthesis of various quinazolinone derivatives from readily available 2-aminobenzamides and terminal alkenes with excellent functional group tolerance.

Zirconia‐Supported Cu(I)‐Stabilized Copper Oxide Mesoporous Catalyst for the Synthesis of Quinazolinones Under Ambient Conditions

AbstractAlthough there are many reports on the synthesis of quinazolinones, the use of high boiling solvents and high temperature restricts their scale‐up to the industrial level. The current research reveals a simple protocol for the catalytic synthesis of quinazolines in the presence of a cost‐effective and reusable mesoporous ZrO2‐supported Cu2O (Cu2ZrO3) catalyst. The catalyst was prepared by simple co‐precipitation and characterized using techniques like XRD, TGA, BET, SEM and TEM. The catalyst was reused for five cycles without significant loss in the activity and the catalyst was truly heterogeneous. The present synthesis utilizes environmentally benign H2O2 as an oxidant. The present protocol showed good tolerance for various substituted aldehydes and good yields for quinazolinone derivatives. The method followed a simple workup procedure and no column chromatography was needed.

Direct synthesis of quinazolinones by heterogeneous Cu(OH)X/OMS-2 catalyst under oxygen

Copper hydroxide supported on manganese oxide octahedral molecular sieves (Cu(OH)X/OMS-2) was prepared and was found to be highly active for the oxidative cyclization of benzyl alcohols or methylarenes solely with anthranilamides using oxygen as oxidant. The low loading copper hydroxide was used as a catalytic metal. The hydroxyl of catalyst with spherical agglomeration led to higher performance of catalytic activity for the synthesis of quinazolinones. Moreover, Cu(OH)X/OMS-2 could be reused 5 times without any significant loss of activity.

Design and synthesis of quinazolinones as EGFR inhibitors to overcome EGFR resistance obstacle

The epidermal growth factor receptor (EGFR) T790M mutant is found in about 50% of clinically acquired resistance to gefitinib among patients with non-small cell lung cancer (NSCLC). New derivatives of 4(3H)-quinazolinones were synthesized and evaluated for their inhibitory activity against NSCLC. The results of the study demonstrated that compound 79, 7-chloro-3-(5-(4-methoxyphenyl)-1,3,4-thiadiazol-2-yl)-2-phenylquinazolin-4(3H)-one was found to be the most potent compounds of the series with IC50 value of 0.031μM against mutant T790M/L858R EGFR. Compounds 15, 51, 73, 75, 78, 79 and 96 were less potent against A549 (WT EGFR and k-Ras mutation) and HT-29 (non-special gene type) cells, showing a high safety index. The obtained results showed that compounds 15, 51, 73, 75, 78, 79 and 96 could be the promising template to overcome drug resistance mediated by the EGFR T790 Mutant.

Magnetic nanoparticle-supported DABCO tribromide: a versatile nanocatalyst for the synthesis of quinazolinones and benzimidazoles and protection/deprotection of hydroxyl groups

MNPs-DABCO tribromide as a magnetically reusable tribromide type nanocatalyst couples the advantages of heterogeneous and homogeneous tribromide-based systems.

Synthesis of Quinazolinones, Imidazo[1,2‐c]quinazolines and Imidazo[4,5‐c]quinolines through Tandem Reductive Amination of Aryl Halides and Oxidative Amination of C(sp3)–H Bonds

A tandem multicomponent approach has been described for the synthesis of quinazolinones, imidazo[1,2‐c]quinazolines and imidazo[4,5‐c]quinolines. The reaction involves a copper‐catalyzed reductive amination through azidation followed by reduction and oxidative amination of C(sp3)–H bonds of N,N‐dimethylacetamide in the presence of TBHP (tert‐butylhydroperoxide) as oxidant. The method uses the easily available sodium azide as a nitrogen source and DMA (N,N‐dimethylacetamide) as a one‐carbon source for the synthesis of these N‐fused heterocycles in good to excellent yields. The reaction can also be used for gram‐scale synthesis.

ChemInform Abstract: Iron Nitrate/TEMPO‐Catalyzed Aerobic Oxidative Synthesis of Quinazolinones from Alcohols and 2‐Aminobenzamides with Air as the Oxidant.

A highly efficient, iron nitrate/TEMPO-catalyzed approach for the synthesis of quinazolinones has been achieved via a one-pot, tandem aerobic oxidative cyclization of primary alcohols with 2-aminobenzamides. This practical reaction tolerates a broad scope of substrates and could afford a variety of desirable products in good to excellent yields with air as the terminal green oxidant. Thus, the present synthetic protocol provides an efficient and concise strategy for the synthesis of quinazolinones.

A facile vanadium-catalyzed aerobic oxidative synthesis of quinazolinones from 2-aminobenzamides with aldehydes or alcohols

An efficient and simple VO(acac)2-catalyzed approach to the synthesis of quinazolinones has been developed. Various substituted quinazolinones have been synthesized from 2-aminobenzamides with alcohols or aldehydes in good to excellent yields with molecular oxygen as the oxidant. The process can also be scaled up.