Synthesis Of Quinazolinones Research Articles

Copper nitrate as a powerful and eco-friendly natural catalyst for mediator-free aerobic oxidation of 2,3-dihydroquinazolinones and 1,4-dihydropyridines under mild conditions

For the first time, copper (II) nitrate trihydrate was used as an efficient, eco-friendly, operational ease, inexpensive, and commercially available catalyst for the biomimetic aerobic oxidation synthesis of quinazolinones and Hantzsch pyridines from their corresponding 2,3-dihydroquinazolinones and 1,4-dihydropyridines, respectively. The products were achieved in satisfactory to excellent yields using acetonitrile as the solvent. These methods are considered to be more eco-friendly, efficient, uncomplicated, and useful compared to existing ones as they align with various principles of green chemistry. Hence, these techniques can be utilized in pharmaceuticals and other delicate synthesis processes.

Dimethyl Sulfoxide Promoted Quinazolinone Synthesis

AbstractAn efficient and one‐step synthesis of quinazolinones using 2‐aminobenzamide and benzylamine in DMSO under external catalyst‐ and base‐free conditions is reported. A broad substrate scope and environment‐benign mild reaction conditions are the major attributes of this straightforward synthesis. Moreover, the synthesized quinazolinone derivatives were used to produce pharmaceutically active rutaecarpine analogues using a two‐step reaction: N‐alkylation followed by intramolecular cyclization.

Acceptorless Dehydrogenation under Neat Reaction Conditions: Synthesis of 2-Aryl/Alkyl Quinazolinones Using Supported Ni NPs as Catalyst

AbstractWe report here a Ni-NPs-catalyzed one-pot synthesis of 2-alkyl/aryl quinazolinone motifs via acceptorless dehydrogenation of alcohol, condensation of an aldehyde intermediate with 2-aminobenzamide, followed by a second dehydrogenation of the cyclized intermediate. The protocol is atom-economical and require earth-abundant Ni as the catalyst. The present report involves the annulation of 2-aminobenzamide with various types of primary alcohols, including aryl/heteroaryl methanol, and aliphatic alcohols, and produces high yields of the desired products under neat conditions. The catalyst was synthesized via a high-temperature pyrolysis strategy, using ZIF-8 as the sacrificial template. The Ni NPs@N-C catalyst was characterized by XPS, HR-TEM, HAADF-STEM, XRD, and ICP-MS. The catalyst is stable even in air at room temperature and displayed excellent activity in the acceptorless dehydrogenative coupling synthesis of quinazolinones and could be recycled five times without appreciable loss of its activity.

Green Synthesis of Quinazolinones via Selective Electro‐oxidation Using Iron Electrode and NaCl Electrolyte as an Eco‐friendly Electrolyte

AbstractPrimary alcohols 2(a–h) and o‐aminobenzamides 1(a–h) can be selectively oxidized electrochemically to yield dihydroquinazolinone 4(a–h) and quinazolinones 5(a–h) in an efficient and chemoselective manner. This methodology employs sodium chloride (NaCl) 3(a) as a co‐catalyst and electricity as the oxidizing agent, utilizing cost‐effective and commercially available materials such as Graphite anode, Iron (Fe) cathode, and isopropyl alcohol (iPrOH) as a solvent and weak base. The synthesis yields various quinazolinone derivatives with diverse structural characteristics in good quantities, showcasing the method‘s broad applicability. This approach facilitates the production of a range of dihydroquinazolinones and quinazolinones (24 examples), highlighting its versatility and compatibility with different functional groups. Characterization of the synthesized derivatives included CHN analysis, 1HNMR spectroscopy, and determination of melting points.

Magnetic metal–organic framework (MOF) as an effective photocatalyst for synthesis of quinazolinones under oxidation and visible-light conditions

Magnetic metal–organic framework (MOF) as an effective photocatalyst for synthesis of quinazolinones under oxidation and visible-light conditions

Vanadium-Silsesquioxane Nanocages as Heterogeneous Catalysts for Synthesis of Quinazolinones.

The functionalization of polyoxovanadate clusters is promising but of great challenge due to the versatile coordination geometry and oxidation state of vanadium. Here, two unprecedented silsesquioxane ligand-protected "fully reduced" polyoxovanadate clusters were fabricated via a facial solvothermal methodology. The initial mixture of the two polyoxovanadate clusters with different colors and morphologies (green plate V14 and blue block V6) was successfully separated as pure phases by meticulously controlling the assembly conditions. Therein, the V14 cluster is the highest-nuclearity V-silsesquioxane cluster to date. Moreover, the transformation from a dimeric silsesquioxane ligand-protected V14 cluster to a cyclic hexameric silsesquioxane ligand-protected V6 cluster was also achieved, and the possible mechanism termed "ligand-condensation-involved dissociation reassembly" was proposed to explain this intricate conversion process. In addition, the robust V6 cluster was served as a heterogeneous catalyst for the synthesis of important heterocyclic compounds, quinazolinones, starting from 2-aminobenzamide and aldehydes. The V6 cluster exhibits high activity and selectivity to access pure quinazolinones under mild conditions, where the high selectivity was attributed to the confinement effect of the macrocyclic silsesquioxane ligand constraining the molecular freedom of the reaction species. The stability and recyclability as well as the tolerance of a wide scope of aldehyde substrates endow the V6 cluster with a superior performance and appreciable potential in catalytic applications.

Unveiling the Untapped Potential of Bertagnini's Salts in Microwave-Assisted Synthesis of Quinazolinones.

Microwave-assisted organic synthesis (MAOS) has emerged as a transformative technique in organic chemistry, significantly enhancing the speed, efficiency, and selectivity of chemical reactions. In our research, we have employed microwave irradiation to expedite the synthesis of quinazolinones, using water as an eco-friendly solvent and thereby adhering to the principles of green chemistry. Notably, the purification of the product was achieved without the need for column chromatography, thus streamlining the process. A key innovation in our approach is using aldehyde bisulfite adducts (Bertagnini's salts) as solid surrogates of aldehydes. Bertagnini's salts offer several advantages over free aldehydes, including enhanced stability, easier purification, and improved reactivity. Green metrics and Eco-Scale score calculations confirmed the sustainability of this approach, indicating a reduction in waste generation and enhanced sustainability outcomes. This methodology facilitates the synthesis of a diverse array of compounds, offering substantial contributions to the field, with potential for widespread applications in pharmaceutical research and beyond.

Synthesis of Quinazolinones and Benzothiazoles Using α-Keto Acids under Ball Milling.

Mechanochemistry refers to the initiation of chemical reactions via mechanical forces such as milling, grinding, or shearing to achieve the chemical transformations. As a manifestation of mechanocatalysis, herein, an oxidant-free and solvent-free approach for the synthesis of quinazolinones (23 derivatives) and benzothiazoles (23 derivatives) has been developed through stainless-steel-driven decarboxylative acyl radical generation from α-keto acids. A library of 2-arylquinazolinones and 2-arylbenzothiazoles has been prepared in moderate to good yields at room temperature. Moreover, control experiments and XPS studies supported the reduction (by zerovalent iron) of molecular oxygen through the moderate abrasion of balls, which promoted the generation of a superoxide radical anion via a SET process.

"One pot" synthesis of quinazolinone-[2,3]-fused polycyclic scaffolds in a three-step reaction sequence.

Diverse quinazolinone-[2,3]-fused polycyclic skeletons occupy a prominent position in drug discovery. Even with currently available methods there still remain unmet needs for flexible access to such structures. Herein, we have explored a mild "one pot" procedure for the construction of various quinazolinone-[2,3]-fused polycycles. The procedure involves Pd-catalyzed carbonylation of N-(2-iodophenyl)acetamides, release of the masked terminal amine, and two sequential and spontaneous cyclizations. This generally applicable approach features easy assembly of precursors from readily available starting materials, mild reaction conditions, non-cumbersome operation, and polycyclic diversity.

Visible light-mediated synthesis of quinazolinones from benzyl bromides and 2-aminobenzamides without using any photocatalyst or additive.

This paper reports a novel method for the visible-light-mediated synthesis of quinazolinones from the reaction of benzyl bromides with 2-aminobenzamides. The reaction proceeded efficiently at room temperature upon irradiation with an 18 W blue light-emitting diode in air without photocatalysts or additives. By varying the solvent type, substrate molar ratio, and reaction time, the optimal reaction conditions, including the use of methanol solvent, room temperature, and reaction time of 28 h, were identified. Under these conditions, various quinazolinones were obtained using 18 substrates, with the highest yield of 93%. To determine the industrial value of the proposed method, a scale-up reaction was performed and 80% product yield was achieved. Mechanistic studies revealed that the reaction likely proceeded via a radical pathway and that the hydrogen bromide by-product generated during the first step of the reaction of benzyl bromide with 2-aminobenzamide promoted the subsequent step.

Biomass derived Cu2O nanoparticles for N-atom insertion reactions: a base-free synthesis of quinazolinones with a green approach

This work describes the use of an eco-friendly biogenic approach for the synthesis of Cu2O NPs utilizing Cucumis melo peel extract for the first time and employed for the one-pot multicomponent synthesis of quinazolinones in a green solvent.

A microwave assisted tandem synthesis of quinazolinones using ionic liquid supported copper(II) catalyst with mechanistic insights.

Quinazolinone is a preferred structural motif with notable pharmacological activity that is present in a wide range of naturally occurring compounds. A microwave assisted tandem cyclooxidative method has been developed to afford quinazolinones via a recyclable ionic liquid supported copper catalyst. This sustainable method exhibits operational simplicity through a rapid, clean, and energy-efficient route and a variety of 2-substituted quinazolinones are obtained in excellent yields. In addition, this innovative approach enables us to develop a library of nitriles in an environment-friendly synthetic protocol. Moreover, the catalyst can be recycled and reused up to three consecutive cycles without any significant loss of catalytic activity. Further organic transformation of the synthesized quinazolinones was carried out to afford reported as well as novel bioactive heterocyclic compounds.

Photogenerated chlorine radicals activate C(sp3)-H bonds of alkylbenzenes to access quinazolinones.

An Fe-catalyzed visible-light induced condensation of alkylbenzenes with anthranilamides has been developed. Upon irradiation, the trivalent iron complex could generate chlorine radicals, which successfully abstracted the hydrogen of benzylic C-H bonds to form benzyl radicals. And these benzyl radicals were converted into oxygenated products under air conditions, which subsequently reacted with anthranilamides for the synthesis of quinazolinones.

Visible light-mediated synthesis of quinazolinones and benzothiadiazine-1,1-dioxides utilizing aliphatic alcohols.

The activation and utilization of challenging aliphatic alcohols like methanol and ethanol is a very appealing approach to synthesize valuable organic molecules. Utilization of methanol and ethanol as a coupling partner has emerged as a valuable alternative to synthesize industrially relevant N-heterocycles because they can be easily procured from renewable sources unlike other activated coupling partners which are expensive and also unstable. Herein, a mild and metal-free photocatalytic protocol to synthesize quinazolinones and more challenging benzothiadiazine-1,1-dioxides, which is unprecedented at room temperature, is demonstrated. This methodology showcased broad substrate scope and provided important N-heterocycles more efficiently than the transition metal-based high temperature protocols. An unexplored reactivity with allyl alcohol is observed following the developed protocol. A series of control experiments were carried out to understand the mechanism.

Highly-stable Silverton-type UIV-containing polyoxomolybdate frameworks for the heterogeneous catalytic synthesis of quinazolinones

The first series of Silverton {UMo12O40}-based polyoxomolybdates linked by FeII, CoII, and NiII were synthesized and characterized. They exhibited excellent stabilities and were used as heterogeneous catalysts for the synthesis of quinazolinones.

Visible‐Light‐Initiated Dehydrogenative Cyclization of o‐Aminobenzamide and Alcohols for Coproduction of Quinazolinones and Hydrogen over PtS/ZnIn2S4

PtS/ZnIn2S4 nanocomposites are obtained via a microwave‐assisted synthesis followed by a photoreduction. The resultant PtS/ZnIn2S4 nanocomposites are used as an effective multifunctional photocatalyst for the reaction between alcohols and o‐aminobenzamide to coproduce quinazolinones and hydrogen under visible light, via a cascade alcohols/aldehydes transformation, condensation between aldehydes and o‐aminobenzamide, as well as the dehydrogenation/cyclization to produce quinazolinones. PtS acts as an efficient cocatalyst to promote the dehydrogenation of both the alcohols and the condensation intermediates for the production of quinazolinones. An almost complete conversion of o‐aminobenzamide was achieved in 24 h, with a yield of 98.8% to 2‐phenyl‐quinazline‐4(3H)‐one and quantitative hydrogen produced over PtS/ZnIn2S4 after irradiated for 24 h. The apparent quantum yield at 450 nm is determined to 15.2%. The superior activity observed over PtS/ZnIn2S4 nanocomposite as compared with that over either NiS/ZnIn2S4 or MoS2/ZnIn2S4 can be ascribed to a moderate binding between PtS and the surface adsorbed H*. This study supplies an effective, green, and atom‐economic strategy for the synthesis of quinazolinones with coproduction of hydrogen under visible light. This work also demonstrates the high potential of fabrication of metal sulfide‐based multifunctional catalysts for light‐driven one‐pot tandem/cascade reactions.

One pot facile visible-light promoted synthesis of quinazolinones via Csp3-H oxidation in aqueous media

The utilization of biocompatible catalysts for the synthesis of biologically significant molecules in aqueous environments represents a pivotal and challenging aspect within the realm of green and sustainable chemistry. Herein, a KI-mediated Csp3-H oxidation reaction to synthesis heterogeneously of quinazolinones is reported in this study. Aldehydes, formed from the oxidation of alcohols, undergo amide attacks and subsequent cyclization, efficiently producing a variety of quinazolinones under sunlight and in aqueous media. The utilization of solar energy significantly reduces experimental costs and minimizes the occurrence of toxic effects. This approach proceeded smoothly to afford quniazolinones in high to excellent yields with a wide substrate scope.

Synthesis of Quinazolinone Based Spirocyclopropanes via [3 + 2] Cycloaddition Reaction: In Silico Anti-Tubercular Molecular Docking Studies and ADME Prediction

A highly efficient cascade annulation approach is developed for the synthesis of novel quinazolinone-based spirocyclopropanes via three-component [3 + 2] cycloaddition reaction with aldehydes, tosylhydrazide and quinazolinyl chalcones. The reaction features the formation of two C–C bonds and three stereogenic centers. A variety of highly functionalized spirocyclopropyl quinazolinones were obtained in good yields under mild reaction conditions. Furthermore, in silico anti-tubercular (anti-TB) molecular docking studies were performed for the generated compounds against three Mycobacterium tuberculosis proteins with PDBID: 1DF7, 1P44 and 4TZK. ADME prediction were evaluated for the drug like properties of the synthesized compounds.

One-pot electrochemical synthesis of quinazolinones by Fe(III)-catalyzed indirect anodic oxidation

An operationally simple electrochemical approach for the one-pot synthesis of quinazolinones employing low-cost and relatively environmentally friendly FeCl3 as electrocatalysts has been established. By use of readily available o-aminobenzamides and alcohols as starting materials, the Fe/acid electrocatalytic system was conducted under mild conditions to provide quinazolinones via indirect anodic oxidation/cyclization/dehydrogenation cascade in moderate to good yields. This protocol provides a practical and environmentally benign route for the preparation of quinazolinone derivatives under mild conditions.

Selective synthesis of quinazolinones by using fluorescein catalyst under mild conditions

A fast and highly efficient method for the synthesis of functionalized dihydroquinazolinone and quinazolinone via photocatalysis has been reported. Fluorescein has respectively participated in the cyclization and dehydrogenation reactions, and different products were obtained in the presence and absence of light. 2-Phenyl-2,3-dihydroquinazolin-4(1H)-one was synthesized by fluorescein without visible light. Subsequently, quinazolinone was further obtained with the dehydrogenation of dihydroquinazolinone by fluorescein induce. The reaction process was highly efficient, and a wide range of quinazolinones could be synthesized with a highest yield of 98% in just 1 h under visible light conditions. Furthermore, the reaction could be extended to the gram level by up to 88%. This protocol provides an alternative route for preparing quinazolinone derivatives by employing photocatalytic methods for synthesizing quinazolinones without additional oxidants, acids and metals.