Synthesis Of Quinazolines Research Articles

Solvent/oxidant-switchable synthesis of multisubstituted quinazolines and benzimidazoles via metal-free selective oxidative annulation of arylamidines.

A fast and simple divergent synthesis of multisubstituted quinazolines and benzimidazoles was developed from readily available amidines, via iodine(III)-promoted oxidative C(sp(3))-C(sp(2)) and C(sp(2))-N bond formation in nonpolar and polar solvents, respectively. Further selective synthesis of quinazolines in polar solvent was realized by TEMPO-catalyzed sp(3)C-H/sp(2)C-H direct coupling of the amidine with K2S2O8 as the oxidant. No metal, base, or other additives were needed.

Copper-catalyzed domino reaction between 1-(2-halophenyl)methanamines and amidines or imidates for the synthesis of 2-substituted quinazolines

The CuI-catalyzed domino reaction between 1-(2-bromophenyl)methanamines and amidines using K3PO4 as the base, pivalic acid as the additive, and aerial oxygen as the oxidant gives access to substituted quinazolines in a single step with yields in the range between 43 and 90%. It is assumed that the reaction proceeds as a Cu(I)-catalyzed intermolecular N-arylation followed by an intramolecular nucleophilic substitution and a Cu(II)-catalyzed oxidation. The amidines can be replaced with imidates and the reaction can also be run with 1-(2-iodophenyl)methanamine.

Recent advances in the structural library of functionalized quinazoline and quinazolinone scaffolds: Synthetic approaches and multifarious applications

Drug development has been a principal driving force in the rapid maturation of the field of medicinal chemistry during the past several decades. During this period, the intriguing and challenging molecular architectures of nitrogen-containing heterocycles with potential bioactive properties have received significant attention from researchers engaged in the areas of natural product synthesis and heterocyclic methodology, and constituted a continuous stimulus for development in bio(organic) chemistry. In this perspective, the current review article is an effort to summarize recent developments in the environmentally benign synthetic methods providing access to quinazoline and quinazolinone scaffolds with promising biological potential. This article also aims to discuss potential future directions on the development of more potent and specific analogues for various biological targets.

Synthesis of quinazolines via CuO nanoparticles catalyzed aerobic oxidative coupling of aromatic alcohols and amidines.

CuO nanoparticles were found to be efficient catalysts for the synthesis of quinazoline derivatives; twenty-four products were obtained with good to excellent yields via reaction of N-arylamidines and aromatic aldehydes or benzyl alcohol in air. Neither a base nor an organic oxidant was necessary, and CuO nanoparticles can be recycled without a significant decrease in catalytic activity.

H3PW12O40 catalyzed synthesis of benzoxazine and quinazoline in aqueous media

A heteropolyacid efficiently catalyzed the cyclocondensation reaction of 2-aminobenzamide and salicylamide with aldehydes and ketones to afford good yields of benzoxazine and quinazoline ring systems in an aqueous medium. The method gives clean reactions, has simple workup procedure, and uses environment friendly conditions.

A convenient palladium-catalyzed carbonylative synthesis of quinazolines from 2-aminobenzylamine and aryl bromides

An interesting approach for the synthesis of 2-functionalized quinazolines has been developed. Various quinazolines have been produced in moderate to excellent yields.

Design and synthesis of quinazoline carboxylates against Gram-positive, Gram-negative, fungal pathogenic strains, and Mycobacterium tuberculosis.

Aim:A novel series of ethyl 5-(4-substituted phenyl)-3-methyl-6,7,8,9-tetrahydro-5H-thiazolo[2,3-b] quinazoline-2-carboxylate 3a-3j, were synthesized, characterized by spectral, elemental analyses and screened for their in vitro antibacterial and Mycobacterium tuberculosis (MTB) activities.Materials and Methods:The in vitro antibacterial and antifungal activities were determined by agar well-diffusion and cup-plate agar diffusion methods and the anti-tuberculosis (TB) screening for test compounds were evaluated against MTB H37Rv strain by Resazurin assay.Results:Among the derivatives tested, most of the compounds were found to have potent activity against microbial strains. The structure-activity relationship point of view, introduced group that enhance the lipophilicity as well ester, substituted aromatic ring at thiazole quinazoline nucleus showed increasing antimicrobial and anti TB activity. The high level of activity shown by the compounds with electron withdrawing groups in the para position on the benzene ring (3 g) suggests that these compounds could serve as leads for development of novel synthetic compounds with enhanced antibacterial and anti TB activities.Conclusion:These results provide a further insight into the structural requirements for targeting thiazolo quinazoline carboxylate to develop potential new agents to combat TB treatment.

Synthesis of Quinazolines and Tetrahydroquinazolines: Copper‐Catalyzed Tandem Reactions of 2‐Bromobenzyl Bromides with Aldehydes and Aqueous Ammonia or Amines

An efficient synthesis of diversely substituted quinazolines and 1,2,3,4-tetrahydroquinazolines through copper-catalyzed tandem reactions of the readily available 2-bromobenzyl bromides, aldehydes, and aqueous ammonia or amines has been developed. By using ammonia and simple aliphatic amines as the nitrogen source, the present method provides a versatile and practical protocol for the synthesis of quinazolines and 1,2,3,4-tetrahydroquinazolines.

ChemInform Abstract: Copper‐Catalyzed Annulation of Amidines for Quinazoline Synthesis.

An efficient Cu-catalyzed synthesis of quinazolines via the C–N bond formation reactions between N–H bonds of amidines and C(sp3)–H bonds adjacent to sulfur or nitrogen atoms in the commonly used solvents, such as DMSO, DMF, DMA, NMP or TMEDA, followed by intramolecular C–C bond formation reactions was developed for the first time.

Visible light-mediated synthesis of quinazolines from 1,2-dihydroquinazoline 3-oxides

A series of quinazolines were synthesized in good to excellent yields by exposing 1,2-dihydroquinazoline 3-oxides to visible light in acetonitrile without the presence of any external sensitizers. The only exception was the 2-(p-nitrophenyl)-substituted substrate, which is insensitive to visible light. This compound could be first oxidized to quinazoline 3-oxide via ruthenium-catalyzed visible light photoredox catalysis, and followed by treating with PCl3 to yield the corresponding quinazoline. The mechanisms of these visible light-mediated reactions were proposed.

An efficient synthesis of quinazoline and xanthene derivatives using starch sulfate as a biodegradable solid acid catalyst

Starch sulfate as bio-supported solid acid catalyst was applied to synthesis of heterocyclic compounds such as 2,3-dihydroquinazolin-4(1H)-one, 2-substituted-1,2,3,4-tetrahydro-4-quinazolinones, 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one, 1,8-dioxo-octahydroxanthenes, and 5H-dibenzo[b,i]xanthene-5,7,12,14(13H)-tetraone derivatives under thermal solvent-free conditions. In all these synthetic methods, the work-up is simple and the catalyst can be easily separated from the product and reused for several times without any loss of its activity. The present protocol with starch sulfate as an effective catalyst is convincingly superior to the recently reported catalytic methods with respect to reaction times and yields of the obtained products.

ChemInform Abstract: A Cooperative Catalytic System of Platinum/Iridium Alloyed Nanoclusters and a Dimeric Catechol Derivative: An Efficient Synthesis of Quinazolines Through a Sequential Aerobic Oxidative Process.

AbstractA new polymer‐supported catalyst system consisting of platinum/iridium alloyed nanoclusters and spiro‐bisindane ligand THSI is used for the facile preparation of fused quinazoline derivatives under mild aerobic oxidative conditions.

Spectral Characterization of Novel 3-Phenyl-2-Substituted Quinazoline and Fused Quinazoline Derivatives

3-phenyl-2-thioxo-quinazolin-4(3H)one 1 was utilized for the construction of some novel 2-substituted quinazolin-4(3H)one derivatives through the formation of 2-hydrazinyl quinazolinone, which was used as the key starting material for the synthesis of 2-heteryl quinazolines via the reaction with one carbon donors, β-diketones and β-ketoester. Infrared, 1H NMR, and mass spectra of the synthesized compounds were discussed. Some of them showed promising anti-inflammatory activity. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

Synthesis of 2-substituted quinazolinesvia iridium catalysis

An iridium-catalyzed hydrogen transfer reaction was successfully applied in the synthesis of 2-substituted quinazolines in moderate yields starting from aldehydes or alcohols with 2-aminobenzylamines.

Copper-catalyzed annulation of amidines for quinazoline synthesis

An efficient Cu-catalyzed synthesis of quinazolines via the C-N bond formation reactions between N-H bonds of amidines and C(sp(3))-H bonds adjacent to sulfur or nitrogen atoms in the commonly used solvents, such as DMSO, DMF, DMA, NMP or TMEDA, followed by intramolecular C-C bond formation reactions was developed for the first time.

ChemInform Abstract: Copper‐Catalyzed Synthesis of Quinazolines in Water Starting from o‐Bromobenzylbromides and Benzamidines.

Water makes it possible: The Cu(2)O-catalyzed reaction between easily available o-bromobenzylbromides and benzamidines by using Cs(2)CO(3) as the base and N,N'-dimethylethylenediamine (DMEDA) as the additive in water as the solvent gives access to substituted quinazolines in a single step with yields ranging from 57 to 85 % (see scheme).

Mimicking the Intramolecular Hydrogen Bond: Synthesis, Biological Evaluation, and Molecular Modeling of Benzoxazines and Quinazolines as Potential Antimalarial Agents

The intramolecular hydrogen bond formed between a protonated amine and a neighboring H-bond acceptor group in the side chain of amodiaquine and isoquine is thought to play an important role in their antimalarial activities. Here we describe isoquine-based compounds in which the intramolecular H-bond is mimicked by a methylene linker. The antimalarial activities of the resulting benzoxazines, their isosteric tetrahydroquinazoline derivatives, and febrifugine-based 1,3-quinazolin-4-ones were examined in vitro (against Plasmodium falciparum ) and in vivo (against Plasmodium berghei ). Compounds 6b,c caused modest inhibition of chloroquine transport via the parasite's "chloroquine resistance transporter" (PfCRT) in a Xenopus laevis oocyte expression system. In silico predictions and experimental evaluation of selected drug-like properties were also performed on compounds 6b,c. Compound 6c emerged from this work as the most promising analogue of the series; it possessed low toxicity and good antimalarial activity when administered orally to P. berghei -infected mice.

ChemInform Abstract: Intrinsic Catalytic Activity of an Acidic Ionic Liquid as a Solvent for Quinazoline Synthesis.

AbstractQuinazoline derivatives are synthesized using the ionic liquid as solvent and catalyst which can be recycled and reused for further conversions.

A Cooperative Catalytic System of Platinum/Iridium Alloyed Nanoclusters and a Dimeric Catechol Derivative: An Efficient Synthesis of Quinazolines Through a Sequential Aerobic Oxidative Process

AbstractA cooperative catalytic system of heterogeneous polymer‐supported bi‐metallic platinum/iridium (Pt/Ir) alloyed nanoclusters and 5,5′,6,6′‐tetrahydroxy‐3,3,3′,3′‐tetramethyl‐1,1′‐spiro‐bisindane (TTSBI) enabled the facile preparation of quinazoline derivatives with low catalyst loadings and broad substrate scope under mild aerobic oxidative conditions. The ability to perform the reaction in gram‐scale and under open‐air conditions highlights the synthetic application of this cooperative catalytic system.

Copper-catalyzed three-component one-pot synthesis of quinazolines

Two efficient approaches to multi-substituted quinazolines by the three-component one-pot reaction of o-bromo aromatic ketones/aldehydes, ammonia water and aromatic aldehydes, or primary alcohols catalyzed by CuCl have been developed.