Suzuki–Miyaura coupling of quinazolines containing an unprotected NH2 group: Synthesis and biological testing of quinazoline derivatives

A robust approach to 4-amino quinazoline bi-aryl compounds was developed through Suzuki–Miyaura coupling reaction of quinazoline containing an unprotected NH₂ group and arylboronic acids. Pd(dcpf)Cl₂ was found to be an efficient catalyst for the reaction. All the compounds were evaluated for antimicrobial activity against gram-positive and gram-negative bacteria and fungi. One of the compounds, 3l, found to be more active against Candida albicans than the standard Miconazole.     

One‐pot three‐component synthesis of novel 2‐(3‐nitro‐phenyl)‐quinazoline‐4‐carboxylic acid derivatives

A simple and easy synthesis of 2‐(3‐nitro‐phenyl)‐quinazoline‐4‐carboxylic acid ( 3 ) has been successfully developed through a one‐pot three‐component condensation reaction of (2‐amino‐phenyl)‐oxo‐acetic acid sodium salt ( 1 ) obtained from the hydrolysis of isatin with ammonium acetate and 3‐nitrobenzaldehyde. Some novel quinazoline‐ester derivatives 4‐7 were then obtained by the reaction between the new compound 3 and various alcohols. Then, quinazoline‐amide derivatives 10‐14 were synthesized from the reaction of various amines and 2‐(3‐nitro‐phenyl)‐quinazoline‐4‐carbonyl chloride ( 8 ), obtained by the reaction of compound 3 with SOCl₂. Finally, some novel quinazoline‐azo derivatives 17‐19 were synthesized by the coupling reaction between β‐dicarbonyl compounds and the novel amino‐quinazoline derivative compound 15 , obtained by reduction of nitro‐quinazoline derivative compound 11 . Thus, a new series of quinazoline‐4‐carboxylic acid, ester, amide, and azo derivatives was synthesized and fully characterized by ¹H NMR, ¹³C NMR, IR, and mass spectrometry analysis.     

Microwave assisted synthesis of N-arylheterocyclic substituted-4-aminoquinazoline derivatives

A simple, efficient, and general method has been developed for the synthesis of various N-aryl heterocylic substituted-4-aminoquinazoline compounds from 4-chloro- quinazoline and aryl heterocyclic amines under microwave irradiation using 2-propanol as solvent. The advantages of the use of microwave irradiation in relation to the classical method were demonstrated.     

Ionic liquid supported on magnetic nanoparticles as a novel reusable nanocatalyst for the efficient synthesis of tetracyclic quinazoline compounds

A magnetic ionic liquid supported on γ-Fe₂O₃ nanocatalyst was synthesized successfully and characterized by Fourier transform infrared spectroscopy, vibrating sample magnetometry, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. The resulting nano-Fe₃O₄-supported, ionic liquid was an efficient catalyst for preparation of a series of tetracyclic quinazoline compounds by three components reaction of a mixture of isatoic anhydride and amine with ninhydrin in PEG and the desired products were obtained in good to excellent yields. High efficiency, waste-free, mild reaction conditions, effortless magnetic recovery and reusability up to four continuous cycles are the noteworthy features of the currently employed heterogeneous catalytic system.     

Microwave-enhanced synthesis of aryl nitriles using dimeric orthopalladated complex of tribenzylamine and K4[Fe(CN)6]

The activity of palladacycle [Pd{C₆H₄(CH₂N(CH₂Ph)₂)} (μ-Br)]₂ complex was investigated in the synthesis of benzonitriles under both conventional and microwave irradiation conditions and their results were compared together. This complex is an efficient, stable, and non-sensitive to air and moisture catalyst for the cyanation reaction. The substituted benzonitriles were produced of various aryl halides in excellent yields and short reaction times using a catalytic amount of [Pd{C₆H₄(CH₂N(CH₂Ph)₂)} (μ-Br)]₂ complex and K₄[Fe(CN)₆] in DMF at 130 °C. In comparison to conventional heating conditions, the reactions under microwave irradiation gave higher yields in shorter reaction times.     

Regioselective addition of Grignard reagents to 2,6-dicyanoanilines and cyclization to new quinazoline derivatives under thermal/microwave irradiation conditions

Two strategies have been developed for the synthesis of novel quinazoline derivatives. 2,6-Dicyanoanilines were reacted with Grignard reagents followed by cyclization to give two quinazoline regioisomers 2 and 3. Alternately 2,6-dicyanoanilines on reaction with Grignard reagents gave imine regioisomers 4 and 5. Each imine regioisomer was separated and independently cyclized to give new quinazoline derivatives 6, 7 and 8, 9, respectively, under different microwave irradiation conditions.     

微波辐射下2-氨基苯并[h]喹唑啉衍生物的合成

2-芳亚甲基-3，4-二氢-2H-1（2H）-萘酮和碳酸胍在以乙二醇为溶剂、微波辐 射下反应，生成一系列新的2-氨基-4-芳基-5，6-二氢化苯并[h]喹啉衍生物，产物 的结构通过单晶X射线衍射分析确证。     

An efficient Stille cross‐coupling reaction catalyzed by ortho‐palladated complex of tribenzylamine under microwave irradiation

The catalytic activity of [Pd{C₆H₄(CH₂N(CH₂Ph)₂)}(μ‐Br)]₂ complex as an efficient, stable and catalyst that is non‐sensitive to air and moisture was investigated in the Stille cross‐coupling reaction of various aryl halides with phenyltributyltins under microwave irradiation. The substituted biaryls were produced in excellent yield in short reaction times using a catalytic amount of this complex in DMF at 100 C. The combination of dimeric complex as homogeneous catalyst and microwave irradiation and also DMF as microwave‐active polar solvent gave higher yields in shorter reaction times. Copyright © 2011 John Wiley & Sons, Ltd.     

(5RS)‐6H‐Spiro[pyrazolo[1,5‐c]quinazoline‐5,4′‐thiochroman]: efficient synthesis under mild conditions,molecular structure and supramolecular assembly

Pyrazolo[1,5‐c]quinazolines are fused‐quinazoline derivatives which have been reported as potential agents against neurological disorders. The normal synthesis routes to these compounds require harsh reaction conditions, long reaction times or multistep sequences. The title compound, C₁₈H₁₅N₃S, has been prepared under very mild conditions by condensation of thiochroman‐4‐one with 5‐(2‐aminophenyl)‐1H‐pyrazole, which had itself been prepared by the reaction of hydrazine hydrate with 4‐hydroxyquinoline mediated by a brief period of microwave heating. Within the molecule in the crystal structure, the reduced pyrimidine ring adopts an envelope conformation, whereas the thiane ring adopts a half‐chair conformation. Molecules are linked into sheets by a combination of one N—H...S hydrogen bond and two independent C—H...π(arene) hydrogen bonds, which utilize the same aryl ring as the acceptor, with one C—H bond donating to each face of the ring. Comparisons are made with some related compounds.     

Rapid Ti(Oi-Pr)4 facilitated synthesis of α,α,α-trisubstituted primary amines by the addition of Grignard reagents to nitriles under microwave heating conditions

A series of carbinamines (α,α,α-trisubstituted amines) have been prepared in a simple and efficient one-pot procedure by the addition of Grignard reagents to a series of aliphatic, aromatic and heteroaromatic nitriles. The resulting magnesium imines are subsequently converted to the desired amine after treatment with Ti(Oi-Pr)₄ and additional microwave heating. Key to this procedure is the use of microwave heating for both steps of the reaction protocol, which significantly improves both reaction yields and reduces reaction times. In general, the Grignard addition reaction is complete within 5-10 min at 100 °C followed by conversion with Ti(Oi-Pr)₄ and additional microwave heating to give the target amines in good yields.     

“On-Water” Palladium-Catalyzed Tandem Cyclization Reaction for the Synthesis of Biologically Relevant 4-Arylquinazolines

The quinazoline scaffold is prevalent in pharmaceutically relevant molecules that show diverse biological activities. Herein, we report an efficient “on-water” palladium-catalyzed tandem cyclization reaction from commercially available arylboronic acids and benzonitriles that enable the rapid access to 4-arylquinazoline scaffolds in good to excellent yields (45 examples, up to 98 % yield). This protocol has shown good functional group tolerance and broad substrate scope. The reaction was also performed on a gram scale and successfully applied to the synthesis of the highly potent and selective PI3Kδ inhibitor N11, showing the practicability and synthetic utility of the protocol. In this reaction, the quinazoline scaffold is efficiently constructed with the simultaneous formation of one C−C bond and one C−N bond. Collectively, the protocol could serve as an alternative strategy to synthesize biologically important quinazoline scaffolds.     

Direct synthesis of 2-aryl-1,3-benzoselenazoles by reaction of bis(2-aminophenyl) diselenides with aryl aldehydes using sodium metabisulfite

We present here a general and easy method for the synthesis of several 2-aryl-1,3-benzoselenazoles from the reaction of bis(2-aminophenyl) diselenides with different aryl aldehydes, promoted by the non-toxic inorganic reducing agent sodium metabisulfite (Na₂S₂O₅) in DMSO at 120 °C. This efficient method furnishes in high yields the corresponding 2-aryl substituted 1,3-benzoselenazoles and tolerates a range of substituents at the aryl ring of aldehydes. The use of focused microwave irradiation decreases drastically the reaction time from 48 to 2 h.     

Nanomagnetically modified vitamin B3 (Fe3O4@Niacin): An efficient and reusable green biocatalyst for microwave‐assisted rapid synthesis of 2‐amino‐3‐cyanopyridines in aqueous medium

Superparamagnetic nanoparticles of modified vitamin B₃ (Fe₃O₄@Niacin) represent a new, efficient and green biocatalyst for the one‐pot synthesis of 2‐amino‐3‐cyanopyridine derivatives via four‐component condensation reaction between aldehydes, ketones, malononitrile, and ammonium acetate under microwave irradiation in water. This new magnetic organocatalyst was easily isolated from the reaction mixture by magnetic decantation using an external magnet and reused at least six times without significant degradation in the activity. The catalyst was fully characterized by FT‐IR, XRD, SEM, VSM, UV–Vis, DLS and EDS. Excellent yield, very short reaction time (7–10 min), operational simplicity, easy work‐up procedure, avoidance of hazardous or toxic catalysts and organic solvents are the main advantages of this green methodology which makes it more economic than the other conventional methods.     

Green synthesis of Ni‐Cu‐Zn ferrite nanoparticles using tragacanth gum and their use as an efficient catalyst for the synthesis of polyhydroquinoline derivatives

Ni_0.35Cu_0.25Zn_0.4Fe₂O₄ MNPs were synthesized using tragacanth gum as biotemplate and Metals nitrate as the metal source by the sol–gel method. The sample was characterized by powder X‐ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), vibrating sample magnetometer (VSM), scanning electron microscopy (SEM) and energy dispersive X‐ray analysis (EDX). The nanoparticles exhibit ferromagnetic behaviour at room temperature, with a saturation magnetization of 52.76 emu/g and a coercivity of 80.14 Oe. Thereupon, Ni‐Cu‐Zn ferrite nanoparticles as an efficient catalyst was used for the synthesis of polyhydroquinoline derivatives via multi‐component reactions under microwave irradiation. Simple work‐up, mild reaction conditions, short reaction times, use of an economically convenient catalyst, and excellent product yields are the advantageous features of this method. The catalyst could easily be recycled and reused few times without noticeable decrease in catalytic activity.     

(BeDABCO)2Pd2Cl6 (1‐benzyl‐4‐aza‐1‐azoniabicyclo[2.2.2]octane chloride) as a highly active catalytic system for the Stille cross‐coupling reaction under microwave irradiation

An efficient catalytic system using (BeDABCO)₂Pd₂Cl₆ was developed for the Stille cross‐coupling reaction. The substituted biaryls were produced in excellent yields in short reaction times using a catalytic amount of this catalyst in DMF at 120 °C. The ionic character of homogeneous catalyst and microwave irradiation and also DMF as microwave‐active polar solvent gave higher yields and shorter reaction times than conventional heating. Benzyl DABCO as an efficient ligand and also a quaternary ammonium salt had an efficient stabilizing effect on the Pd(0) species. Copyright © 2013 John Wiley & Sons, Ltd.     

Fe3O4@SiO2@propyl‐ANDSA: A new catalyst for the synthesis of tetrazoloquinazolines

In this paper, a mild and green protocol has been developed for the synthesis of quinazoline derivatives. The catalytic activity of 7‐aminonaphthalene‐1,3‐disulfonic acid‐functionalized magnetic Fe₃O₄ nanoparticles (Fe₃O₄@SiO₂@Propyl–ANDSA) was investigated in the one‐pot synthesis of new derivatives of tetrahydrotetrazolo[1,5‐a]quinazolines and tetrahydrobenzo[h]tetrazolo[5,1‐b]quinazolines from the reaction of aldehydes, 5‐aminotetrazole, and dimedone or 6‐methoxy‐3,4‐dihyronaphtalen‐1(2H)‐one at 100 °C in H₂O/EtOH as the solvent. The catalyst was characterized before and after the organic reaction. Fe₃O₄@SiO₂@Propyl–ANDSA showed remarkable advantages in comparison with previous methods. Advantages of the method presented here include easy purification, reusability of the catalyst, green and mild procedure, and synthesis of new derivatives in high yields within short reaction time.     

Application of a dimeric ortho‐palladated complex of tribenzylamine as an efficient catalyst in microwave‐assisted Hiyama coupling reactions

The activity of [Pd{C₆H₄(CH₂N(CH₂Ph)₂)}(μ‐Br)]₂ complex was investigated in cross‐coupling reactions of triethoxy(phenyl)silane with various aryl halides under microwave irradiation. This complex is an efficient and stable catalyst for the synthesis of substituted biphenyls that is non‐sensitive to air and moisture. The combination of dimeric complex as homogenous catalyst, microwave irradiation, DMF as microwave‐active polar solvent and TBAF as microwave‐active additive led to excellent yields in short reaction times. Copyright © 2012 John Wiley & Sons, Ltd.     

A Facile Synthesis of New L‐Proline‐Based Trifluoromethyl Oxazole Derivatives Using Microwave Irradiation and Conventional Method

Cyclization reaction of l ‐proline with trifluoroacetimidoyl chlorides has been developed as an efficient strategy for the synthesis of trifluoromethyl oxazole derivatives by two methods: (a) in the presence of K₂CO₃ as a base in acetonitrile at room temperature and (b) in the presence of K₂CO₃ as a base in acetonitrile using microwave irradiation, in one pot reaction. The microwave irradiation has been found to be the most efficient method. High yields and short reaction times were obtained for both electron‐releasing and electron‐withdrawing substituted N‐aryltrifluoroacetimidoyl chloride derivatives by microwave irradiation.     

An efficient palladium catalytic system for microwave assisted cyanation of aryl halides

Application of a new catalytic system for cyanation reaction of various aryl halides using K₄[Fe(CN)₆] as cyanating source was examined. The reactions were performed under microwave irradiation and results showed that application of this catalytic system and DMF at 130 °C minimized the reaction times from hours to minutes in good to excellent yields.     

Microwave‐Assisted Solid‐Phase Synthesis of a 1,2‐Disubstituted Benzimidazole Library by Using a Phosphonium Linker

An efficient and rapid microwave‐assisted solid‐phase method for the synthesis of 5‐methyl‐1,2‐disubstituted benzimidazoles derivatives has been developed. The phosphonium linker, obtained by reaction between polymer‐supported triphenylphosphine and 4‐fluoro‐3‐nitrobenzyl iodide, underwent aromatic substitution with primary amines, followed by one‐pot reaction with aldehydes in the presence of SnCl₂·2H₂O, yielded the benzimidazole system under microwave irradiation. The final products were released from the resin with NaOH under microwave irradiation and were obtained in high purity and good overall yield.