Conditions In Excellent Yields Research Articles

Discovery of C-3 Tethered 2-oxo-benzo[1,4]oxazines as Potent Antioxidants: Bio-Inspired Based Design, Synthesis, Biological Evaluation, Cytotoxic, and in Silico Molecular Docking Studies

The discovery of C-3 tethered 2-oxo-benzo[1,4]oxazines as potent antioxidants is disclosed. All the analogs 20a-20ab have been synthesized via “on water” ultrasound-assisted irradiation conditions in excellent yields (upto 98%). All the compounds have been evaluated for their in vitro antioxidant activities using DPPH free radical scavenging assay as well as FRAP assay. The result showed promising antioxidant activities having IC50 values in the range of 4.74 ± 0.08 to 92.20 ± 1.54 μg/mL taking ascorbic acid (IC50 = 4.57 μg/mL) as standard reference. In this study, compounds 20b and 20t, the most active compound of the series, showed IC50 values of 6.89 ± 0.07 μg/mL and 4.74 ± 0.08 μg/mL, respectively in comparison with ascorbic acid. In addition, the detailed SAR study shows that electron-withdrawing group increases antioxidant activity and vice versa. Furthermore, in the FRAP assay, eight compounds (20c, 20j, 20m, 20n, 20r, 20u, 20z, and 20aa) were found more potent than standard reference BHT (C0.5FRAP = 546.0 ± 13.6 μM). The preliminary cytotoxic study reveals the non-toxic nature of active compounds 20b and 20t in non-cancerous 3T3 fibroblast cell lines in MTT assay up to 250 μg/mL concentration. The results were validated via carrying out in silico molecular docking studies of promising compounds 20a, 20b, and 20t in comparison with standard reference. To the best of our knowledge, this is the first detailed study of C-3 tethered 2-oxo-benzo[1,4]oxazines as potential antioxidant agents.

Non-peptide-based new class of platelet aggregation inhibitors: Design, synthesis, bioevaluation, SAR, and in silico studies.

A series of 2-oxo-2-phenylethylidene linked 2-oxo-benzo[1,4]oxazine analogues 17a-x and 18a-o, incorporated with a variety of electron-withdrawing as well as electron-donating groups at ring A and ring C, were synthesized under greener conditions in excellent yields (up to 98%). These analogues 17a-x and 18a-o were evaluated for their arachidonic acid (AA)-induced platelet aggregation inhibitory activities in comparison with the standard reference aspirin (IC50 = 21.34 ± 1.09 µg/mL). Among all the screened compounds, eight analogues, 17i, 17x, 18f, 18g, 18h, 18i, 18l, and 18o, were identified as promising platelet aggregation inhibitors as compared to aspirin. In addition, cytotoxic studies in 3T3 fibroblast cell lines by MTT assay of the promising compounds (17i, 17x, 18f-18i, 18l, and 18o) were also performed and the compounds were found to be non-toxic in nature. Furthermore, the results on the AA-induced platelet aggregation inhibitory activities of these compounds (17i, 17x, 18f-18i, 18l, and 18o) were validated via in silico molecular docking simulation studies. To the best of our knowledge, this is the first report of the identification of non-peptide-based functionalized 2-oxo-benzo[1,4]oxazines as platelet aggregation inhibitors.

An Efficient Synthesis of Pyrido[3, 2‐c]coumarins under Microwave Irradiation in Solvent‐Free Conditions

AbstractSynthesized some novel functionalized pyrido[3, 2‐c] coumarins from the reaction of 4‐chloro‐3‐formylcoumarins obtained from 4‐hydroxycoumarins, and aryl methyl ketones/ethyl acetoacetate/ethyl cyanoacetate in the presence of ammonium acetate under microwave irradiation in solvent‐free condition in excellent yields.

Nano Fe3O4 as Green Catalyst for Beckmann Rearrangement under Ultrasound Irradiation

Nano-Fe3O4 particles were used as a green and heterogeneous catalyst for Beckmann rearrangement under ultrasound irradiation and protic solvent condition in excellent yields. The advantage of this method was simple, inexpensive, easy work-up procedure, suppression of any side product.

Synthesis, crystal structure and 3D-QSAR studies of antifungal (bis-)1,2,4-triazole Mannich bases containing furyl and substituted piperazine moieties

A series of novel title compounds 6a-6r and 7a-7c have been synthesized by Mannich reaction of the new triazole Schiff base intermidiates, substituted piperazine and formaldehyde under mild conditions in excellent yields. The crystal structure of compound 6i was determined to show a chair conformation of the piperazine ring and an (E)-configuration of the CN double bond. The bioassay results indicated that most of the newly synthesized compounds exhibited excellent in vitro inhibitory activities and broader spectrum against several plant fungi, and were more effective than the control Triadimefon. Several compounds also displayed favourable in vivo antifungal activities. The relationships between the compound structures and various biological activities were discussed. Furthermore, the CoMFA calculation based on the antifungal activity data of compounds 6 against R. cerealis was carried out to establish a 3D-QSAR model, which revealed that steric and electrostatic fields were two most important factors for contributing the bioactivity of the compounds. The present work will provide significant information for guiding optimization of such new structures to develop novel agrochemicals with higher antifungal activities.

Synthesis of Spiro[indazole-3,3'-indolin]-2'-ones via [3 + 2] Dipolar Cycloaddition of Arynes with 3-Diazoindolin-2-ones and Indazolo[2,3-c]quinazolin-6(5H)-ones by Subsequent Thermal Isomerization.

An efficient protocol for facile construction of spiro[indazole-3,3'-indolin]-2'-ones was developed via [3 + 2] dipolar cycloaddition of arynes with 3-diazoindolin-2-ones under mild conditions in excellent yields. Subsequent thermal isomerization of the spiro[indazole-3,3'-indolin]-2'-ones readily afforded indazolo[2,3-c]quinazolin-6(5H)-ones.

Preparation of Solid Polyfunctional Alkynylzinc Pivalates with Enhanced Air and Moisture Stability for Organic Synthesis.

We report the preparation of solid and air-stable polyfunctionalized alkynylzinc pivalates from the corresponding alkynes using TMPZnOPiv (TMP=2,2,6,6-tetramethylpiperidyl) as base. These organozinc pivalates are obtained as powders under mild conditions in excellent yields and can be manipulated in air for several hours without significant decomposition. These zinc reagents show an excellent reactivity in various carbon-carbon bond- forming reactions and 1,3-dipolar cycloadditions. An alkynylzinc pivalate has been used to prepare a carboxyamidotriazole with potential antineoplastic activity in eight steps and 38 % overall yield.

An efficient one-pot synthesis of highly substituted [1,8]naphthyridin-1-phenyl-1-ethanone derivatives via a four-component reaction

An operationally simple one-pot protocol for the synthesis of highly substituted [1,8]naphthyridin-1-phenyl-1-ethanones dealing with 2-chloroquinoline-3-carbaldehyde and 1-phenyl-2-(1,1,1-triphenyl-λ 5-phosphanylidene)ethan-1-one, 1,1-bis(methylthio)-2-nitroethylene or ketene N,S-acetals, and aromatic/aliphatic amine or diamines under mild and catalyst-free conditions in excellent yields is described. The structures of products were corroborated spectroscopically (IR, 1H- and 13C-NMR, and EI-MS) and by X-ray analysis. An efficient, useful and general procedure for the synthesis of [1,8]naphthyridin-1-phenyl-1-ethanones via a one-pot four-component reaction of 2-chloroquinoline-3-carbaldehyde and 1-phenyl-2-(1,1,1-triphenyl-λ 5-phosphanylidene)ethan-1-one, 1,1-bis(methylthio)-2-nitroethylene or ketene N,S-acetals, and aromatic/aliphatic amine or diamines under mild and catalyst-free conditions in excellent yields is described. The major advantages of this protocol are high yields, mild and catalyst-free conditions, short reaction times, and application of green solvent.

Facile and simple synthesis of pyrimido[4,5-d]pyrimidinones and pyrano[2,3-d]pyrimidinones catalyzed by nano-sized NS-C4(DABCO-SO3H)2·4Cl

In this work, 4,4′-(butane-1,4-diyl)bis(1-sulfo-1,4-diazabicyclo[2.2.2]octane-1,4-diium)tetrachloride (NS-C4(DABCO-SO3H)2·4Cl), a newly reported nano-sized Bronsted acid catalyst is used for the effective synthesis of pyrimido[4,5-d]pyrimidinones and pyrano[2,3-d]pyrimidinones derivatives. The products were formed under mild and environmentally friendly conditions in excellent yields over very short reaction times. Using green solvent and simple methodologies, no side reactions and use of inexpensive catalyst with lower loading are other advantages of this work.

Photocatalytic Hydrogen-Evolution Cross-Couplings: Benzene C-H Amination and Hydroxylation.

We present a blueprint for aromatic C-H functionalization via a combination of photocatalysis and cobalt catalysis and describe the utility of this strategy for benzene amination and hydroxylation. Without any sacrificial oxidant, we could use the dual catalyst system to produce aniline directly from benzene and ammonia, and phenol from benzene and water, both with evolution of hydrogen gas under unusually mild conditions in excellent yields and selectivities.

An efficient method for the preparation of dialkoxymethanes from dichloromethane with alcohols catalyzed by a Cu-NHC complex

A facile, rapid and efficient method for the preparation of dialkoxymethanes from dichloromethane with alcohols catalyzed by a Cu-NHC complex is reported. A variety of symmetrical dialkoxymethanes can be prepared under mild condition in excellent yields (up to 98%). The unsymmetrical ether is also obtained in 89% yield from the etherification of p-tolylmethanol and n-butyl chloride catalyzed by ICyCuCl complex at 80°C. The reaction provides a new method for the preparation of dialkoxymethanes under mild conditions in excellent yields.

ChemInform Abstract: Silver Catalyzed Domino Aza‐Annulation/Diels—Alder Cyclization of 2‐Ene‐Yne Anilines: A Facile One‐Pot Access to Carbazole, Dihydrocarbazole and Tetrahydrocarbazole Frameworks.

AbstractThe domino aza‐annulation/Diels—Alder cyclization of 2‐ene‐yne anilines (I) with acetylenedicarboxylate leads to desired carbazoles (III).

ChemInform Abstract: Solvent‐Free Green Synthesis of Azines and Their Conversion to 2,5‐Disubstituted‐1,3,4‐thiadiazoles.

Abstract1,3,4‐Thiadiazole derivatives (III) are synthesized via azines (II) by a solvent‐free, clean and efficient method under eco‐friendly benign reaction conditions in excellent yields.

Imidazo[4,5-a]quinindolines as highly effective antibacterial agents

Resistance to antimicrobial agents is a concern that exists globally and has a considerable impact on human and animal health, so that the discovery of new antibacterial compounds has become increasingly more important in combating infectious disease. In this paper, imidazo[4,5-a]quinindolines are introduced as new antibacterial agents against Gram-positive and Gram-negative bacteria. These pentacyclic compounds are synthesized by the reaction of N-alkyl-5-nitrobenzimidazoles with 2-(1-alkyl-1H-3-indolyl)acetonitrile under basic conditions in excellent yields. The structures of newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, and mass spectral data. The antibacterial activities of the synthesized compounds were screened against standard strains of two Gram-positive and two Gram-negative bacteria using the broth microdilution method. Most of the compounds studied showed promising activities against both types of bacteria.

Microwave Assisted Rapid Synthesis of (Arylselanyl)phenyl-1H-1,2,3-triazoles by Copper Catalyzed 1,3-Dipolar Cycloaddition

We describe here a simple and rapid protocol for the synthesis of (arylselanyl)phenyl-1H- 1,2,3-triazoles by copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions using Microwave Irradiation. The products were obtained under mild conditions in excellent yields in a short reaction time by reacting azidophenyl arylselenides with a range of terminal alkynes using catalytic amount of Cu(OAc)2.H2O/sodium ascorbate. This Click Chemistry protocol is an efficient method to synthesize new selenium compounds with potential application in biological studies and materials sciences. Keywords: Alkynes, azides, catalysis, 1, 3-dipolar, click chemistry, copper, cycloaddition, green chemistry, heterocycles, microwave, 1, 2, 3-triazoles, nitrogen compounds, selanyltriazoles, selenium compounds.

ChemInform Abstract: Atom Economical Synthesis of Oxindoles by Metal‐Catalyzed Intramolecular C—C Bond Formation under Solvent‐Free and Aerobic Conditions.

Diversely substituted oxindoles were obtained from atom economical direct C–C bond formation reactions of various substituted anilides and pyridinylamides with metal salts and oxides. The catalysts include CuO, Cu2O, FeCl3, Fe2O3, TiO2, ZnO, and Ag2O and their nanoparticles. The reaction proceeds under solvent-free and aerobic conditions in excellent yields. The reaction mechanism was proved to be a single electron transfer pathway with oxygen as the re-oxidant of the metal catalysts.

P-Sulfonic acid calix[4]arene as an efficient and reusable catalyst for the synthesis of acridinediones and xanthenes

p-Sulfonic acid calix[4]arene has been found to be an efficient catalyst for the synthesis of acridinediones and xanthenes under mild conditions in excellent yields. The present approach offers the advantages of simple methodology, short reaction time, and high yield.

Practical Iron‐ and Cobalt‐Catalyzed Cross‐Coupling Reactions between N‐Heterocyclic Halides and Aryl or Heteroaryl Magnesium Reagents

The reaction scope of iron- and cobalt-catalyzed cross-coupling reactions in the presence of isoquinoline (quinoline) in the solvent mixture tBuOMe/THF has been further investigated. Various 2-halogenated pyridine, pyrimidine, and triazine derivatives were arylated under these mild conditions in excellent yields. The presence of isoquinoline allows us to perform Fe-catalyzed cross-coupling reactions between 6-chloroquinoline and aryl magnesium reagents. Furthermore, it was found that the use of 10% N,N-dimethylquinoline-8-amine increases the yields of some Co-catalyzed cross-coupling reactions with chloropyridines bearing electron-withdrawing substituents.

ChemInform Abstract: Enantioselective Chlorination of β‐Keto Esters and Amides Catalyzed by Chiral Copper(II) Complexes of Squaramide‐Linked Bisoxazoline Ligand.

AbstractThe chlorinated products are obtained under optimized reaction conditions in excellent yields but only moderate enantioselectivities.

Vitamin B1 supported on alumina as an efficient heterogeneous catalyst for synthesis of tetrahydro-2,6-dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione derivatives

The efficient synthesis of tetrahydro-2,6-dioxopyrimidin-4-yl)-2,3-dihydrophthalazine-1,4-dione derivatives via four-component reaction of hydrazine hydrate, phthalic anhydride, aromatic aldehydes and barbituric acid using vitamin B1 supported on alumina (VB1-Al2O3) as a heterogeneous catalyst under thermal solvent-free conditions in excellent yields is described.